bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro
and
In Vivo
Activities of β-Lactams in Combination with the Novel β-Lactam Enhancers Zidebactam and WCK 5153 against Multidrug-Resistant Metallo-β-Lactamase-Producing Klebsiella pneumoniae
Authors: Moya Bartolome , Barcelo Isabel M. , Cabot Gabriel , Torrens Gabriel , Palwe Snehal , Joshi Prashant , Umarkar Kushal , Takalkar Swapna , Periasamy Hariharan , Bhagwat Sachin , Patel Mahesh , Bou German , Oliver Antonio
Published: February 2019

Zidebactam and WCK 5153 are novel bicyclo-acyl hydrazide (BCH) agents that have previously been shown to act as β-lactam enhancer (BLE) antibiotics in
Pseudomonas aeruginosa
and
Acinetobacter baumannii
. The objectives of this work were to identify the molecular targets of these BCHs in
Klebsiella pneumoniae
and to investigate their potential BLE activity for cefepime and aztreonam against metallo-β-lactamase (MBL)-producing strains
in vitro
and
in vivo
.
Evaluation of the Aries
Bordetella
Assay for Detection and Identification of
Bordetella pertussis
in Nasopharyngeal Swab Specimens
Authors: McMillen T. , Chow H. Y. , Das Shubhagata , Dunbar Sherry A. , Babady N. E.
Published: February 2019

The Aries
Bordetella
assay (Aries BA) (Luminex Corporation) recently received FDA clearance for the detection and differentiation of
Bordetella pertussis
and
Bordetella parapertussis
nucleic acids in nasopharyngeal swab (NPS) samples. The objective of this study was to evaluate the performance of the Aries BA in comparison to that of the BioFire FilmArray respiratory panel (RP).
Spikes in acute:chronic workload ratio (ACWR) associated with a 5–7 times greater injury rate in English Premier League football players: a comprehensive 3-year study
Authors: Bowen Laura , Gross Aleksander Stephan , Gimpel Mo , Bruce-Low Stewart , Li Francois-Xavier
Published: February 2019

Objectives

We examined the relation between global positioning system (GPS)-derived workloads and injury in English Premier League football players (n=33) over three seasons.

Methods

Workload and injury data were collected over three consecutive seasons. Cumulative (1-weekly, 2-weekly, 3-weekly and 4-weekly) loads in addition to acute:chronic workload ratios (ACWR) (acute workload (1-week workload)) divided by chronic workload (previous 4-week average acute workload) were classified into discrete ranges by z-scores. Relative risk (RR) for each range was then calculated between injured and non-injured players using specific GPS variables: total distance, low-intensity distance, high-speed running distance, sprint distance, accelerations and decelerations.

Results

The greatest non-contact injury risk was when the chronic exposure to decelerations was low (<1731) and the ACWR was >2.0 (RR=6.7). Non-contact injury risk was also 5–6 times higher for accelerations and low-intensity distance when the chronic workloads were categorised as low and the ACWR was >2.0 (RR=5.4–6.6), compared with ACWRs below this. When all chronic workloads were included, an ACWR >2.0 was associated with a significant but lesser injury risk for the same metrics, plus total distance (RR=3.7–3.9).

Conclusions

We recommend that practitioners involved in planning training for performance and injury prevention monitor the ACWR, increase chronic exposure to load and avoid spikes that approach or exceed 2.0.
Serious adverse events and lifetime risk of reoperation after elective shoulder replacement: population based cohort study using hospital episode statistics for England
Authors: Craig Richard S , Lane Jennifer C E , Carr Andrew J , Furniss Dominic , Collins Gary S , Rees Jonathan L
Published: February 2019

Objectives

To provide accurate risk estimates of serious adverse events after elective shoulder replacement surgery for arthritis, including age and sex specific estimates of the lifetime risk of revision surgery.

Design

Population based cohort study.

Setting

Hospital episode statistics for NHS England, including civil registration mortality data.

Participants

58 054 elective shoulder replacements in 51 895 adults (aged ≥50 years) between April 1998 and April 2017.

Main outcome measures

The lifetime risk of revision surgery, calculated using an actuarial life table approach and the cumulative probability method. Rates of serious adverse events at 30 and 90 days post-surgery: pulmonary embolism, myocardial infarction, lower respiratory tract infection, acute kidney injury, urinary tract infection, cerebrovascular events, and all cause death. Secondary outcome measures were the number of surgeries performed each year and Kaplan-Meier estimates of revision risk at 3, 5, 10, and 15 years.

Results

The number of shoulder replacements performed each year increased 5.6-fold between 1998 and 2017. Lifetime risks of revision surgery ranged from 1 in 37 (2.7%, 95% confidence interval 2.6% to 2.8%) in women aged 85 years and older to 1 in 4 (23.6%, 23.2% to 24.0%) in men aged 55-59 years. The risks of revision were highest during the first five years after surgery. The risk of any serious adverse event at 30 days post-surgery was 1 in 28 (3.5%, 3.4% to 3.7%), and at 90 days post-surgery was 1 in 22 (4.6%, 4.4% to 4.8%). At 30 days, the relative risk of pulmonary embolism compared with baseline population risk was 61 (95% confidence interval 50 to 73) for women aged 50-64. Serious adverse events were associated with increasing age, comorbidity, and male sex. 1 in 5 (21.2%, 17.9% to 25.1%) men aged 85 years and older experienced at least one serious adverse event within 90 days.

Conclusions

Younger patients, particularly men, need to be aware of a higher likelihood of early failure of shoulder replacement and the need for further and more complex revision replacement surgery. All patients should be counselled about the risks of serious adverse events. These risks are higher than previously considered, and for some could outweigh any potential benefits. Our findings caution against unchecked expansion of shoulder replacement surgery in both younger and older patients. The more accurate age and sex specific estimates of risk from this study are long overdue and should improve shared decision making between patients and clinicians.

Study registration

ClinicalTrials.govNCT03573765.
Google search histories of patients presenting to an emergency department: an observational study
Authors: Asch Jeremy M , Asch David A , Klinger Elissa V , Marks Justine , Sadek Norah , Merchant Raina M
Published: February 2019

Objective

To test patients’ willingness to share and link their prior Google search histories with data from their electronic medical record (EMR), and to explore associations between search histories and clinical conditions.

Design

Cross-sectional study of emergency department (ED) patients from 2016 to 2017.

Setting

Academic medical centre ED.

Participants

A total of 703 patients were approached; 334 of a volunteer sample of 411 (81%) reported having a Google account; 165 of those (49%) consented to share their Google search histories and EMR data; 119 (72%) were able to do so. 16 (13%) of those 119 patients had no data and were not included in the final count. Patients under the age of 18 or with a triage level of 1 were considered ineligible and were not approached.

Main outcome measures

Health relatedness of searches in the remote past and within 7 days of the ED visit, and associations between patients’ clinical and demographic characteristics and their internet search volume and search content.

Results

The 103 participants yielded 591 421 unique search queries; 37 469 (6%) were health related. In the 7 days prior to an ED visit, the percentage of health-related searches was 15%. During that time, 56% of patients searched for symptoms, 53% for information about a hospital and 23% about the treatment or management of a disease. 53% of participants who used Google in the week leading up to their ED visit searched for content directly related to their chief complaint.

Conclusions

Patients were willing to allow researchers simultaneous access to their Google search histories and their EMR data. The change in volume and content of search activity prior to an ED visit suggests opportunities to anticipate and improve health care utilisation in advance of ED visits.
Transnasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergent intubation (Kids THRIVE): a protocol for a randomised controlled trial
Authors: George Shane , Humphreys Susan , Williams Tara , Gelbart Ben , Chavan Arjun , Rasmussen Katie , Ganeshalingham Anusha , Erickson Simon , Ganu Subodh Suhas , Singhal Nitesh , Foster Kelly , Gannon Brenda , Gibbons Kristen , Schlapbach Luregn J , Festa Marino , Dalziel Stuart , Schibler Andreas
Published: February 2019

Introduction

Emergency intubation of children with abnormal respiratory or cardiac physiology is a high-risk procedure and associated with a high incidence of adverse events including hypoxemia. Successful emergency intubation is dependent on inter-related patient and operator factors. Preoxygenation has been used to maximise oxygen reserves in the patient and to prolong the safe apnoeic time during the intubation phase. Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) prolongs the safe apnoeic window for a safe intubation during elective intubation. We designed a clinical trial to test the hypothesis that THRIVE reduces the frequency of adverse and hypoxemic events during emergency intubation in children and to test the hypothesis that this treatment is cost-effective compared with standard care.

Methods and analysis

The Kids THRIVE trial is a multicentre randomised controlled trial performed in participating emergency departments and paediatric intensive care units. 960 infants and children aged 0–16 years requiring emergency intubation for all reasons will be enrolled and allocated to THRIVE or control in a 1:1 allocation with stratification by site, age (<1, 1–7 and >7 years) and operator (junior and senior). Children allocated to THRIVE will receive weight appropriate transnasal flow rates with 100% oxygen, whereas children in the control arm will not receive any transnasal oxygen insufflation. The primary outcomes are defined as follows: (1) hypoxemic event during the intubation phase defined as SpO2<90% (patient-dependent variable) and (2) first intubation attempt success without hypoxemia (operator-dependent variable). Analyses will be conducted on an intention-to-treat basis.

Ethics and dissemination

Ethics approval for the protocol and consent process has been obtained (HREC/16/QRCH/81). The trial has been actively recruiting since May 2017. The study findings will be submitted for publication in a peer-reviewed journal.

Trial registration number

ACTRN12617000147381.
Correlation of hair risperidone concentration and serum level among patients with schizophrenia
Authors: Sun Xiujia , Wang Lihua , Yang Fuzhong , Ren Juanjuan , Jiang Ping , Liu Hongmei , Li Huafang , Li Chunbo , Zhang Chen
Published: February 2019

Background

Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared with blood, hair is non-invasive, safe, non-infectious and easy to transport and store.

Aims

This study aims to investigate the correlations among the drug concentrations of RSP in hair and serum, which provides an experimental basis to explore hair as a novel biomaterial to meet the needs of clinical detection.

Methods

34 patients with schizophrenia treated with RSP for more than 3 months were enrolled in this study. About 1 cm section of hair near the scalp was taken from the subjects, pretreated and detected by liquid chromatography-mass spectrometry. A correlation analysis was conducted among the drug concentrations in hair, the serum concentrations and the daily dosage. The data were analysed using SPSS 20.0 software.

Results 

There was significant correlation between the hair concentration of RSP (two-tailed test, r=0.440,p=0.009) with the serum concentration of RSP, and the hair concentration of 9-hydroxyrisperidone (9-HR) with the serum concentration of 9-HR had no significant correlation (two-tailed test, r=−0.217,p=0.217); the total concentration of the RSP and 9-HR had no significant correlation between hair and serum (r=0.227,p=0.196). The dosage had no statistically significant correlation with the concentration of RSP in hair (r=0.207,p=0.241), 9-HR in hair (r=−0.194,p=0.271) and the total concentration of RSP and 9-HR in hair (r=0.188,p=0.288). There was no statistical correlation between the dosage and the concentration of RSP in serum (r=−0.059,p=0.741), but significant correlation between the dosage and 9-HR in serum (r=0.581p<0.001) was found, and the correlation between the dosage and the total concentration of the two drugs RSP and 9-HR in serum was also significant (r=0.437,p=0.01).

Conclusion

The correlation analysis showed that the concentration of RSP in hair was statistically significant with the serum RSP concentration. In this study, we provided some experimental basis for hair as a new biomaterial to monitor the therapeutic drug concentration.
Incidence of medically attended paediatric burns across the UK
Authors: Davies Katie , Johnson Emma Louise , Hollén Linda , Jones Hywel M , Lyttle Mark D , Maguire Sabine , Kemp Alison Mary
Published: February 2019

Objective

Childhood burns represent a burden on health services, yet the full extent of the problem is difficult to quantify. We estimated the annual UK incidence from primary care (PC), emergency attendances (EA), hospital admissions (HA) and deaths.

Methods

The population was children (0–15 years), across England, Wales, Scotland and Northern Ireland (NI), with medically attended burns 2013–2015. Routinely collected data sources included PC attendances from Clinical Practice Research Datalink 2013–2015), EAs from Paediatric Emergency Research in the United Kingdom and Ireland (PERUKI, 2014) and National Health Services Wales Informatics Services, HAs from Hospital Episode Statistics, National Services Scotland and Social Services and Public Safety (2014), and mortality from the Office for National Statistics, National Records of Scotland and NI Statistics and Research Agency 2013–2015. The population denominators were based on Office for National Statistics mid-year population estimates.

Results

The annual PC burns attendance was 16.1/10 000 persons at risk (95% CI 15.6 to 16.6); EAs were 35.1/10 000 persons at risk (95% CI 34.7 to 35.5) in England and 28.9 (95% CI 27.5 to 30.3) in Wales. HAs ranged from 6.0/10 000 person at risk (95% CI 5.9 to 6.2) in England to 3.1 in Wales and Scotland (95% CI 2.7 to 3.8 and 2.7 to 3.5, respectively) and 2.8 (95% CI 2.4 to 3.4) in NI. In England, Wales and Scotland, 75% of HAs were aged <5 years. Mortality was low with 0.1/1 000 000 persons at risk (95% CI 0.06 to 0.2).

Conclusions

With an estimated 19 574 PC attendances, 37 703 EAs (England and Wales only), 6639 HAs and 1–6 childhood deaths annually, there is an urgent need to improve UK childhood burns prevention.
Depletion of death-associated protein-3 induces chemoresistance in gastric cancer cells through the β-catenin/LGR5/Bcl-2 axis
Authors: Jia Yongning , Li Ziyu , Cheng Xiaojing , Wu Xiaojiang , Pang Fei , Shi Jinyao , Li Shen , Li Xiaolong , Hu Ying , Zhang Lianhai , Ji Jiafu
Published: February 2019

Previously, we demonstrated that death-associated protein-3 (DAP3) loss drives chemoresistance in gastric cancer cells. In the present study, we aimed to determine the underlying molecular mechanism. The effect of DAP3 silencing on β-catenin signaling was assessed. The direct mediator of DAP3 silencing-induced chemoresistance was identified. Depletion of DAP3 stimulates nuclear accumulation of β-catenin and enhances β-catenin-dependent transcriptional activity in gastric cancer cells. However, the protein kinase B,, extracellular regulated protein kinase and signal transducer and activator of transcription 3 signaling pathways remain unaffected by DAP3 loss. We found that the downstream target gene LGR5 (leucine-rich G-protein coupled receptor 5) is upregulated in DAP3-depleted gastric cancer cells. Moreover, knockdown of LGR5 resensitizes DAP3-depleted gastric cancer cells to 5-fluorouracil (5-FU) and oxaliplatin. We also observed that ectopic expression of LGR5 reduces apoptosis in gastric cancer cells on treatment with 5-FU and oxaliplatin, which is accompanied by prevention of caspase-3 cleavage. The antiapoptotic protein Bcl-2 is identified as a key mediator of LGR5-induced apoptosis resistance in gastric cancer cells. The present findings indicate that DAP3 deficiency-induced chemoresistance in gastric cancer is at least partially mediated through the β-catenin/LGR5/Bcl-2 axis. Targeting LGR5 may provide a novel strategy to overcome chemoresistance in DAP3-deficient gastric cancer cells.
The effect of cold ambient temperature and preceding active warm-up on lactate kinetics in female cyclists and triathletes
Authors: Morrissey Margaret C. , Kisiolek Jacob N. , Ragland Tristan J. , Willingham Brandon D. , Hunt Rachael L. , Hickner Robert C. , Ormsbee Michael J.
Published: February 2019

The aim of this study was to evaluate the effect of cold ambient temperature on lactate kinetics with and without a preceding warm-up in female cyclists/triathletes. Seven female cyclists/triathletes participated in this study. The randomized, crossover study included 3 experimental visits that comprised the following conditions: (i) thermoneutral temperature (20 °C; NEU); (ii) cold temperature (0 °C) with no active warm-up (CNWU); and (iii) cold temperature (0 °C) with 25-min active warm-up (CWU). During each condition, participants performed a lactate threshold (LT) test followed by a time to exhaustion trial at 120% of the participant’s peak power output (PPO) as determined during prior peak oxygen consumption testing. Power output at LT with CNWU was 10.2% ± 2.6% greater than with NEU, and the effect was considered very likely small (effect size (ES) = 0.59, 95%–99% likelihood). Power output at LT with CNWU was 4.2% ± 5.4% greater than with CWU; however, the effect was likely trivial (ES = 0.25, 75%–95% likelihood). At LT, there were no significant differences between interventions groups in oxygen consumption, blood lactate concentration, heart rate, or rating of perceived exertion. Time to exhaustion at 120% at PPO was 11% longer with CNWU than with CWU (ES = 0.62, respectively), and this effect was likely small. These findings suggest that power output at LT was higher in CNWU compared with NEU. Additionally, time to exhaustion at 120% of PPO was higher in CNWU compared with CWU and no different than NEU; these differences likely result in a small improvement in performance with CNWU versus CWU and NEU.
New constraints on the genesis and geodynamic setting of the Wulong gold deposit, Liaodong Peninsula, northeast China: evidence from geology, geochemistry, fluid inclusions, and C–H–O–S–Pb isotopes
Authors: Cheng Xihui , Xu Jiuhua , Yang Fuquan , Zhang Guorui , Zhang Hui , Bian Chunjing , Xue Qingpo
Published: February 2019

The Wulong lode gold deposit is located in the Liaoning Province, northeast part of North China Craton. Gold ore bodies are mainly hosted in the Late Jurassic granite and structurally controlled by northeast-trending faults. Gold occurs in disseminated and auriferous quartz–sulfide veins and veinlets within hydrothermally altered rocks. Mineralization can be divided into three stages: (1) quartz–pyrite stage, (2) quartz–polymetallic sulfides stage, and (3) quartz–carbonate stage. Gold formed mainly in the middle stage. Quartz formed in the two earlier stages contains three compositional types of fluid inclusions, i.e., pure CO2, CO2–H2O and NaCl–H2O, but the late-stage minerals only contain NaCl–H2O inclusions. The inclusions in quartz formed in the early, main, and late stages yield total homogenization temperatures of 317–383 °C, 260–380 °C and 159–234 °C, respectively, with salinities of 5.14–9.44, 2.95–6.20, 1.23–4.34 wt% NaCl equivalent, respectively. Trapping pressures estimated from CO2–H2O inclusions are 200–390 MPa in the main stage. Fluid boiling and immiscibility caused rapid precipitation of sulfides and gold. Through immiscibility and inflow of meteoric water, the ore-forming fluid system evolved from CO2-rich to CO2-poor in composition, and from magmatic to meteoric, as indicated by δ18Owater values (4.5‰–7.3‰). The carbon (−12.2‰ to −11.5‰), sulfur (0.9‰–2.6‰), and lead isotope (207Pb/204Pb of 15.606–15.618) compositions suggest the host rocks to be a significant source of ore metals. Integrating the data obtained from the studies including regional geology, ore geology, fluid inclusion, and C–H–O–S–Pb isotope geochemistry, we conclude that the Wulong deposit is a decratonization gold deposit formed during lithospheric thinning associated with destruction of the North China Craton triggered by the subduction of the Paleo-Pacific Oceanic plate in the Early Cretaceous.
Comparative karyotype analysis among six species ofIpomoeabased on two newly identified repetitive sequences
Authors: Sun Jianying , Yu Lixuan , Cai Zeixi , Zhang An , Jin Weiwei , Han Yonghua , Li Zongyun
Published: February 2019

Sweet potato is one of the most important crops worldwide; however, basic research in this crop is limited. In this study, we aimed to construct a detailed karyotype of six species of Ipomoea (hexaploid Ipomoea batatas and five related species, namely, one tetraploid, I. tabascana and four diploids, I. splendor-sylvae, I. trifida, I. tenuissima, and I. × leucantha) and understand the relationship among these species. Two satellite repeats (viz., Itf_1 and Itf_2) were identified from the diploid I. trifida genome sequence using RepeatExplorer on Galaxy. Together with the ribosomal DNA (rDNA), although without distinguishable chromosomes, a detailed karyotype was constructed for the six species. Our results showed a similar karyotype between I. tenuissima and I. × leucantha, indicating their close relationship. The signal distribution pattern of Itf_1, 45S rDNA combination, detected only in I. trifida, I. tabascana, and I. batatas, implied their close relationships. The chromosomes carrying 5S rDNA could be conserved among the six species as they always carried the Itf_2 signals, which generated a similar signal distribution pattern. The results enabled a detailed comparative cytogenetic analysis, providing valuable information to understand the relationship among these species and help assemble the genome sequence of the six species of Ipomoea.
Relationships Between the Distribution of Watanabe–Strogatz Variables and Circular Cumulants for Ensembles of Phase Elements
Authors: Goldobin Denis S.
Published: February 2019

The Watanabe–Strogatz (WS) and Ott–Antonsen (OA) theories provided a seminal framework for rigorous and comprehensive studies of collective phenomena in a broad class of paradigmatic models for ensembles of coupled oscillators. Recently, a “circular cumulant” approach was suggested for constructing the perturbation theory for the OA approach. In this paper, we derive the relations between the distribution of WS phases and the circular cumulants of the original phases. These relations are important for the interpretation of the circular cumulant approach in the context of the WS and OA theories. Special attention is paid to the case of hierarchy of circular cumulants, which is generally relevant for constructing perturbation theories for the WS and OA approaches.
Mechanical behavior of crystalline ionic porphyrins
Authors: Adinehnia Morteza , Eskelsen Jeremy R. , Hipps K. W. , Mazur Ursula
Published: February 2019

Mechanical properties of six different binary ionic porphyrin crystals with variable morphologies were measured and correlated with their structural properties. These solids were formed from stoichiometric combinations of negatively charged tectons, meso-tetra(4-sulfonatophenyl)porphyrin (TSPP), Cu(II) meso-tetra(4-sulfonatophenyl)porphyrin (CuTSPP), Ni(II) meso-tetra (4-sulfonatophenyl)porphyrin (NiTSPP), and four different cationic tectons, namely, meso-tetra (4-pyridyl)porphyrin (TPyP), tetra([Formula: see text]-methyl-4-pyridyl)porphyrin (TMPyP), Cu(II) meso-tetra([Formula: see text]-methyl-4-pyridyl)porphyrin (CuTMPyP), Ni(II) meso-tetra([Formula: see text]-methyl-4-pyridyl)porphyrin (NiTMPyP), and tetra(4-aminophenyl)porphyrin (TAPP). Crystal structures were determined from single crystal and powder X-ray diffraction patterns. Scanning electron and atomic force microscopes (SEM and AFM) provided topographical information. The common arrangement of the porphyrin tectons within the crystals is consistent with alternating face-to-face molecular arrangement forming coherent columns along the fast-growing long axis which are held together by electrostatic and [Formula: see text]–[Formula: see text] interactions as well as hydrogen bonding. In acquiring the indentation data of the porphyrin crystals using AFM, stress was applied perpendicular to the direction where ionic and [Formula: see text]–[Formula: see text] bonds dominate the packing. At indent loads [Formula: see text]50 nN/nm2, all the porphyrin structures deformed elastically. Young’s modulus ([Formula: see text] values for the different crystals range from 6 to 28 GPa. In a broader perspective, this study highlights the extraordinary mechanical behavior of porphyrin assemblies formed by ionic self-assembly. Judicious selection of charged porphyrin synthons can yield crystalline materials with mechanical properties that combine the elastic characteristics of ‘soft’ polymers with the stiffness of composite materials. Such high-performance materials are excellent candidates for deformable optoelectronic devices.
Mechanisms of Niemann-Pick type C1 Like 1 protein degradation in intestinal epithelial cells
Authors: Malhotra Pooja , Soni Vinay , Yamanashi Yoshihide , Takada Tappei , Suzuki Hiroshi , Gill Ravinder K. , Saksena Seema , Dudeja Pradeep K. , Alrefai Waddah A.
Published: February 2019

Intestinal Niemann-Pick C1 Like 1 (NPC1L1) protein plays a key role in cholesterol absorption. A decrease in NPC1L1 expression has been implicated in lowering plasma cholesterol and mitigating the risk for coronary heart disease. Little is known about the mechanisms responsible for NPC1L1 protein degradation that upon activation may lead to a reduction in NPC1L1 protein levels in intestinal epithelial cells (IECs). In current studies, the human intestinal Caco-2 and HuTu-80 cell lines expressing NPC1L1-hemagglutinin fusion protein were used to investigate the mechanisms of NPC1L1 protein degradation. Incubation with the proteasome inhibitors MG-132 and lactacystin (10 μM, 24 h) significantly increased NPC1L1 protein levels in IECs. Also, the inhibition of the lysosomal pathway with bafilomycin A1 (80 nM, 24 h) resulted in a significant increase in NPC1L1 protein levels. Immunoprecipitation studies showed that NPC1L1 protein is both a poly- and monoubiquinated polypeptide and that the inhibition of the proteasomal pathway remarkably increased the level of the polyubiquinated NPC1L1. The surface expression of NPC1L1 was increased by the inhibition of both proteasomal and lysosomal pathways. Furthermore, the pharmacological inhibition of mitogen-activated protein kinase pathway (PD-98059, 15 μM, 24 h) and siRNA silencing of ERK1/2 resulted in a significant decrease in NPC1L1 protein levels in IECs. In conclusion, our results showed that basal level of intestinal cholesterol transporter NPC1L1 protein is modulated by both ubiquitin proteasome- and lysosome-dependent degradation as well as by ERK1/2-dependent pathway. The modulation of these pathways may provide novel clues for therapeutic intervention to inhibit cholesterol absorption and lower plasma cholesterol.
Angiotensin II and salt-induced decompensation in Balb/CJ mice is aggravated by fluid retention related to low oxidative stress
Authors: Jönsson Sofia , Becirovic-Agic Mediha , Isackson Henrik , Tveitarås Maria K. , Skogstrand Trude , Narfström Fredrik , Karlsen Tine V. , Lidén Åsa , Leh Sabine , Ericsson Madelene , Nilsson Stefan K. , Reed Rolf K. , Hultström Michael
Published: February 2019

Balb/CJ mice are more sensitive to treatment with angiotensin II (ANG II) and high-salt diet compared with C57BL/6J mice. Together with higher mortality, they develop edema, signs of heart failure, and acute kidney injury. The aim of the present study was to identify differences in renal gene regulation that may affect kidney function and fluid balance, which could contribute to decompensation in Balb/CJ mice after ANG II + salt treatment. Male Balb/CJ and C57BL/6J mice were divided into the following five different treatment groups: control, ANG II, salt, ANG II + salt, and ANG II + salt + N-acetylcysteine. Gene expression microarrays were used to explore differential gene expression after treatment and between the strains. Published data from the Mouse Genome Database were used to identify the associated genomic differences. The glomerular filtration rate (GFR) was measured using inulin clearance, and fluid balance was measured using metabolic cages. Gene ontology enrichment analysis of gene expression microarrays identified glutathione transferase (antioxidant system) as highly enriched among differentially expressed genes. Balb/CJ mice had similar GFR compared with C57BL/6J mice but excreted less Na+ and water, although net fluid and electrolyte balance did not differ, suggesting that Balb/CJ mice may be inherently more prone to decompensation. Interestingly, C57BL/6J mice had higher urinary oxidative stress despite their relative protection from decompensation. In addition, treatment with the antioxidant N-acetylcysteine decreased oxidative stress in C57BL/6J mice, reduced urine excretion, and increased mortality. Balb/CJ mice are more sensitive than C57BL/6J to ANG II + salt, in part mediated by lower oxidative stress, which favors fluid and Na+ retention.
Polyextremophilic Bacteria from High Altitude Andean Lakes: Arsenic Resistance Profiles and Biofilm Production
Authors: Zannier Federico , Portero Luciano Raúl , Ordoñez Omar Federico , Martinez Luciano José , Farías María Eugenia , Albarracin Virginia Helena
Published: February 2019

High levels of arsenic present in the High Altitude Andean Lakes (HAALs) ecosystems selected arsenic-resistant microbial communities which are of novel interest to study adaptations mechanisms potentially useful in bioremediation processes. We herein performed a detailed characterization of the arsenic tolerance profiles and the biofilm production of two HAAL polyextremophiles, Acinetobacter sp. Ver3 (Ver3) and Exiguobacterium sp. S17 (S17). Cellular adherence over glass and polypropylene surfaces were evaluated together with the effect of increasing doses and oxidative states of arsenic over the quality and quantity of their biofilm production. The arsenic tolerance outcomes showed that HAAL strains could tolerate higher arsenic concentrations than phylogenetic related strains belonging to the German collection of microorganisms and cell cultures (Deutsche Sammlung von Mikroorganismen und Zellkulturen, DSMZ), which suggest adaptations of HAAL strains to their original environment. On the other hand, the crystal violet method (CV) and SEM analysis showed that Ver3 and S17 were able to attach to solid surfaces and to form the biofilm. The quantification of biofilms production in 48 hours’ cultures through CV shows that Ver3 yielded higher production in the treatment without arsenic cultured on a glass support, while S17 yield higher biofilm production under intermediate arsenic concentration on glass supports. Polypropylene supports had negative effects on the biofilm production of Ver3 and S17. SEM analysis shows that the highest biofilm yields could be associated with a larger number of attached cells as well as the development of more complex 3D multicellular structures.
Vasculogenic Mimicry Formation Is Associated with Erythropoietin Expression but Not with Erythropoietin Receptor Expression in Cervical Squamous Cell Carcinoma
Authors: Li Yue-Jie , Qing Xin , Tao Qing-Xu , Xiang Li , Gong Li , Zhou Tie-Jun
Published: February 2019

Background. Vasculogenic mimicry (VM), as an endothelium-independent cancer microcirculation, has been observed in many malignancies including cervical cancer. Erythropoietin (EPO) and erythropoietin receptor (EPO-R) could produce an angiogenic effect to promote cervical squamous cell carcinoma (CSCC) progression. However, the association between VM formation and EPO/EPO-R expression in CSCC is poorly explored. Methods. Seventy-six paraffin-embedded CSCC samples, 25 high-grade squamous intraepithelial lesion (HSIL) samples, 20 low-grade squamous intraepithelial lesion (LSIL) samples, and 20 normal cervix samples were collected. Immunohistochemistry SP method was performed to detect EPO/EPO-R expression and CD31/periodic acid-Schiff (PAS) double staining was performed to detect VM formation. The associations of EPO/EPO-R and VM with clinicopathological parameters of CSCC were analyzed. The associations between VM formation and EPO/EPO-R expression were also analyzed. Results. The positive expression rates of EPO and EPO-R were gradually increasing along the progression of normal cervix-LSIL-HSIL-CSCC sequence (P<0.05). EPO and EPO-R expression were not significantly associated with clinicopathological parameters of CSCC patients (P>0.05). VM was significantly associated with FIGO stage, lymphovascular space involvement, and lymph node metastasis (P<0.05). VM was positively associated with EPO expression (r=0.284, P<0.05) but was not associated with EPO-R expression (P>0.05). Conclusion. These data suggest that increased EPO/EPO-R expression may play an important role in cervical carcinogenesis. EPO overexpression may promote VM formation in CSCC.
Primary Cutaneous T-Cell Lymphoblastic Lymphoma: Case Report and Literature Review
Authors: Khurana Sharad , Beltran Manuel , Jiang Liuyan , Ayala Ernesto , Roy Vivek
Published: February 2019

Cutaneous involvement by precursor T-cell lymphoblastic leukemia/lymphoma (T-ALL/LBL) is rare, and almost all cases are seen in association with bone marrow, blood, and/or lymph node involvement. Presentation with isolated skin involvement is very rare. Literature review revealed only one case report of primary cutaneous T-cell LBL. We discuss here another patient diagnosed with primary cutaneous T-cell LBL at our institute. This patient was initially misdiagnosed as having peripheral T-cell lymphoma NOS. Cytogenetic analysis showed the CDKN2A deletion (−9p21×2) in addition to three intact copies of ABL1 (+9q34). Although she failed multiple lines of intensive chemotherapy, her disease remained confined to the skin. We believe that this presentation of T-LBL is underreported, and many patients are likely misdiagnosed as having high-grade cutaneous T-cell lymphomas. With this case and literature review, we would like to highlight the importance of keeping lymphoblastic lymphoma on the differential diagnosis of cutaneous T-cell lymphoma-like lesions to avoid delay in diagnosis and inappropriate treatment of this aggressive disease.
Prevalence and Risk Factors of Reduced Bone Mineral Density in Systemic Lupus Erythematosus Patients: A Meta-Analysis
Authors: Xia Jumei , Luo Ran , Guo Shuiming , Yang Yi , Ge Shuwang , Xu Gang , Zeng Rui
Published: February 2019

Background. We aimed to conduct a meta-analysis concerning the frequency and risk factors of reduced bone mineral density (BMD) in systemic lupus erythematosus (SLE) with evidence from published studies.Methods.A comprehensive literature search was conducted based on the EMBASE, Web of Science, PubMed, and Cochrane Library databases up to March 5th, 2017. Eligible studies reported any prevalence of reduced BMD in SLE patients. All risk factors with odds ratios or risk ratios associated with reduced BMD were extracted.Results. 71 reports with 33527 SLE patients were included. Low BMD, osteopenia, and osteoporosis at any site were presented, respectively, in 45%, 38%, and 13% of the SLE patients. The prevalence of osteoporosis increased with the advancing of age, while U-shaped associations between age and the prevalence of low BMD and osteopenia were found. Lumbar spine was indicated to have higher prevalence of osteoporosis. Age, disease duration, drugs use, and many other factors were identified as predictors of reduced BMD.Conclusion. Low BMD, osteoporosis, and osteopenia appeared to be prevalent in patients with SLE. Risk factors of reduced BMD were various.
Enhancing Parasitic Interference Directional Antennas with Multiple Director Elements
Authors: Schandy Javier , Steinfeld Leonardo , Rodríguez Benigno , González Juan P. , Silveira Fernando
Published: February 2019

The Swedish Institute of Computer Science Parasitic Interference Directional Antenna (SPIDA) is an electrically switched directional antenna that uses switched beamforming techniques to shape the antenna radiation pattern focusing the transmitted power in a given direction, increasing the maximum gain, and simultaneously reducing interference in other directions. This work extends the use of the SPIDA antenna, showing that using multiple director elements results in an improved performance in terms of maximum gain, narrower Half Power Beamwidth (HPBW), and a lower module of the S11 parameter. Measurements show that using three directors improves the maximum gain about 1.4 dB (6.8 dBi for the single director element antenna against 8.2 dBi for the antenna with three directors); the input impedance matching was also improved, obtaining a module of S11 parameter of -9.8 dB at the central frequency (fc = 2.4525 GHz) against -7.5 dB for the antenna with a single director element. Finally, new intermediate directions of transmission can be achieved by using two successive director elements, where the power is focused in the bisectrix of the angle formed by the two directors. This converts a six-sector antenna like the SPIDA into a twelve-sector antenna without changing the hardware.
Profiling of the Causative Bacteria in Infected Lymphocysts after Lymphadenectomy for Gynecologic Cancer by Pyrosequencing the 16S Ribosomal RNA Gene Using Next-Generation Sequencing Technology
Authors: Nogami Yuya , Banno Kouji , Adachi Masataka , Kunitomi Haruko , Kobayashi Yusuke , Tominaga Eiichiro , Aoki Daisuke
Published: February 2019

Background. Surgery for gynecologic cancer with lymphadenectomy and pelvic radiotherapy can produce lymphoceles that sometimes complicate with infection, resulting in abscesses. The true pathogenic bacteria of abscesses are not always found because of false-negative results due to administered antibiotics and difficulty with detection, including for anaerobic bacteria. Analyzing bacteria flora by next-generation sequencing (NGS) using 16S ribosomal DNA may reveal the true pathogenic bacteria in abscesses. This is the first report on causative pathogens for infectious lymphocele using this technology. Methods. The subjects were patients who developed infectious lymphocele after surgery for gynecologic cancer at our hospital from July 2015 to September 2016. NGS analyses of bacterial flora were performed using specimens preserved at -80°C. Two steps of PCR were performed for purified DNA samples to obtain sequence libraries. Processing of sequence data, including operational taxonomic unit (OTU) definition, taxonomy assignment, and an OTU BLAST search were performed. All patients gave written informed consent and the study was approved by the institutional research ethics committee. Results. Six patients underwent puncture and drainage. The result in most cases indicated a single causative pathogen, including Staphylococcus lugdunensis, Streptococcus dysgalactiae, Streptococcus equinus, Enterococcus saccharolyticus, and Escherichia coli. Conclusions. NGS revealed that the causative bacteria in lymphocele infection are normally a single strain, such as a surface Gram-positive coccus or enteric bacteria. Antibiotics should be chosen as appropriate for elimination of these respective bacteria.
Expanding Network Analysis Tools in Psychological Networks: Minimal Spanning Trees, Participation Coefficients, and Motif Analysis Applied to a Network of 26 Psychological Attributes
Authors: Letina Srebrenka , Blanken Tessa F. , Deserno Marie K. , Borsboom Denny
Published: February 2019

The analysis of psychological networks in previous research has been limited to the inspection of centrality measures and the quantification of specific global network features. The main idea of this paper is that a psychological network entails more potentially useful and interesting information that can be reaped by other methods widely used in network science. Specifically, we suggest methods that provide clearer picture about hierarchical arrangement of nodes in the network, address heterogeneity of nodes in the network, and look more closely at network’s local structure. We explore the potential value of minimum spanning trees, participation coefficients, and motif analyses and demonstrate the relevant analyses using a network of 26 psychological attributes. Using these techniques, we investigate how the network of different psychological concepts is organized, which attribute is most central, and what the role of intelligence in the network is relative to other psychological variables. Applying the three methods, we arrive at several tentative conclusions. Trait Empathy is the most “central” attribute in the network. Intelligence, although peripheral, is weakly but equally related to different kinds of attributes present in the network. Analysis of triadic configurations additionally shows that the network is characterized by relatively strong open triads and an unusually frequent occurrence of negative triangles. We discuss these and other findings in the light of possible theoretical explanations, methodological limitations, and future research.
Integrative Bioinformatics Analysis Reveals Potential Gene Biomarkers and Analysis of Function in Human Degenerative Disc Annulus Fibrosus Cells
Authors: Xunlu Yin , Minshan Feng , Liguo Zhu , Jiawen Zhan , Xu Wei , Jie Yu , Shangquan Wang , He Yin , Long Liang , Tao Han , Xuepeng Li
Published: February 2019

Low back pain is a major cause of disability worldwide. Although numerous potential biomarkers for the early diagnosis or treatment of intervertebral disc degeneration (IDD) have been identified subsequent to the development of molecular biology technologies, the mechanisms of IDD remain unknown. Published studies found the unbalance of anabolism and catabolism of annulus fibrosus (AF) played an important role in it. The present study was aimed to identify the potential targets and signaling pathways of IDD, through the combined analysis of differential expression and based on the Gene Expression Omnibus (GEO) dataset from NCBI. PPI Networks Analysis indicated that MMP2 and AGE-RAGE signaling pathway and estrogen signaling pathway may play important roles in initiation and development of IDD. This study forecasted the pathogenesis molecular mechanism of IDD and the potential prognostic and diagnostic biomarkers, but we need to make further molecular biological experiments to confirm our assumptions.
ОСОБЛИВОСТІ ПІДЛІТКОВОЇ ВАГІТНОСТІ У КРОПИВНИЦЬКОМУ ТА КІРОВОГРАДСЬКІЙ ОБЛАСТІ
Authors: Nakonechna M. , Petrenko N.
Published: February 2019

У статті проаналізовано особливості перебігу підліткової вагітності, особливості пологів та стан новонароджених дітей юних мам.
ОСОБЛИВОСТІ ПЕРЕБІГУ ХВОРОБИ ЛАЙМА (БОРЕЛІОЗУ) У ДИТЯЧОМУ ВІЦІ
Authors: Purenko O. O. , Prokopovych O. A.
Published: February 2019

У статті відображено особливості перебігу хвороби Лайма у дитячому віці.
Tumor sincrônico colorretal e renal
Authors: Mestrinho Bruno Vilalva , Costa Guilherme Augusto Olly de Souza , Delfino José Carlos , Delfino Thaynara Giovanna Tito , Pinto Valéria Cardoso
Published: February 2019

Introdução: O câncer colorretal é a doença maligna mais comum do trato gastrointestinal. O número de casos tem aumentado devido ao uso de novas técnicas e tecnologia para diagnóstico precoce da doença. Já o carcinoma de células renais representa entre 2% e 3% dos casos de cânceres. O carcinoma de células claras é o subtipo histológico mais frequente na população e pode estar relacionado a síndromes hereditárias não polipoides. O tumor sincrônico entre esses dois tipos de cânceres é de ocorrência bastante rara e de etiopatogenia multifatorial, mas ainda indefinida. Objetivo: Este artigo é um relato de caso e tem o intuito de discutir e relatar a sincronia entre um câncer colorretal e um carcinoma renal cujo caso apresenta rara incidência na população mundial. Metodologia: Os dados obtidos referentes ao relato de caso foram colhidos do prontuário da paciente no Hospital Regional do Gama-DF (HRG-DF) entre os meses de novembro de 2016 e maio de 2017, período este, de rastreio até o momento pós- retossigmoidectomia. Para a revisão e discussão deste artigo foram utilizadas as bases de dados Lilacs, Scielo, Medline, BVS e PubMed, além de consulta a periódicos. Conclusão: O principal tratamento é a ressecção cirúrgica da região acometida com as margens livres de neoplasias. O prognóstico da doença, em geral, depende do grau de estádio no qual se encontra a doença, o tipo celular, o nível de diferenciação do tumor e a extensão cirúrgica.
Cardio-Oncology: Vascular and Metabolic Perspectives: A Scientific Statement From the American Heart Association
Authors: Campia Umberto , Moslehi Javid J. , Amiri-Kordestani Laleh , Barac Ana , Beckman Joshua A. , Chism David D. , Cohen Paul , Groarke John D. , Herrmann Joerg , Reilly Carolyn M. , Weintraub Neal L. ,   On behalf of the American Heart Association Council on Peripheral Vascular Disease; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Cardiovascular and Stroke Nursing
Published: February 2019

Cardio-oncology has organically developed as a new discipline within cardiovascular medicine as a result of the cardiac and vascular adverse sequelae of the major advances in cancer treatment. Patients with cancer and cancer survivors are at increased risk of vascular disease for a number of reasons. First, many new cancer therapies, including several targeted therapies, are associated with vascular and metabolic complications. Second, cancer itself serves as a risk factor for vascular disease, especially by increasing the risk for thromboembolic events. Finally, recent data suggest that common modifiable and genetic risk factors predispose to both malignancies and cardiovascular disease. Vascular complications in patients with cancer represent a new challenge for the clinician and a new frontier for research and investigation. Indeed, vascular sequelae of novel targeted therapies may provide insights into vascular signaling in humans. Clinically, emerging challenges are best addressed by a multidisciplinary approach in which cardiovascular medicine specialists and vascular biologists work closely with oncologists in the care of patients with cancer and cancer survivors. This novel approach realizes the goal of providing superior care through the creation of cardio-oncology consultative services and the training of a new generation of cardiovascular specialists with a broad understanding of cancer treatments.