bluuebunny/crossref_metadata_2025 huggingface dataset:
Hip Flexor and Knee Extensor Muscularity Are Associated With Sprint Performance in Sprint-Trained Preadolescent Boys
Authors: Tottori Nobuaki , Suga Tadashi , Miyake Yuto , Tsuchikane Ryo , Otsuka Mitsuo , Nagano Akinori , Fujita Satoshi , Isaka Tadao
Published: August 2017

Purpose: We attempted to determine the relationships between the cross-sectional area (CSA) of the trunk and lower limb muscles and sprint performance in male preadolescent sprinters. Methods: Fifteen sprint-trained preadolescent boys (age 11.6 ± 0.4 y) participated in this study. The CSAs of the participants’ trunk and lower limb muscles were measured using magnetic resonance imaging, and these muscles were normalized with free-fat mass. To assess participants’ sprint performance, sprint time and variables during the 50-m sprint test were measured. The sprint variables were expressed as their indices by normalizing with body height. Results: The relative CSAs of psoas major, adductors, and quadriceps femoris were significantly correlated with sprint time (r = −.802, −.643, and −.639). Moreover, the relative CSAs of these muscles were significantly correlated with indices of sprint velocity (r = .694, .612, and .630) and step frequency (r = .687, .740, and .590) but not with that of step length. Conclusions: These findings suggest that greater hip flexor and knee extensor muscularity in male preadolescent sprinters may help achieve superior sprint performance by potentially enhancing their moments, which may be induced by increased step frequency rather than step length during sprinting.
The Effects of Maturation on Measures of Asymmetry During Neuromuscular Control Tests in Elite Male Youth Soccer Players
Authors: Read Paul J. , Oliver Jon L. , Myer Gregory D. , De Ste Croix Mark B.A. , Lloyd Rhodri S.
Published: August 2017

Purpose: Asymmetry is a risk factor for male youth soccer players. There is a paucity of data confirming the presence of asymmetry using practically viable screening tasks in players at different stages of maturation. Methods: A cross-sectional sample (N = 347) of elite male youth soccer players who were either pre-, circa-, or post-peak height velocity (PHV) completed the following assessments: single-leg Y-Balance anterior reach, single-leg hop for distance, single-leg 75% hop and stick, and single-leg countermovement jumps. Results: Single-leg countermovement jumps landing force asymmetry was higher in both circa- and post-PHV groups (P < .001; d = 0.41–0.43). Single-leg 75% hop and stick landing force asymmetries were also highest in circa-PHV players, but between-group comparisons were not statistically significant and effect sizes were small. Single-leg hop for distance and single-leg Y-Balance anterior reach asymmetries reduced with maturation; however, no group differences were significant, with small to trivial effect sizes (d ≤ 0.25). Conclusion: Stage of maturation did not have a profound effect on asymmetry. Between-limb differences in functional performance seem to be established in early childhood; thus, targeted interventions to reduce this injury risk factor should commence in pre-PHV athletes and be maintained throughout childhood and adolescence to ensure asymmetry does not increase.
The tyrosine phosphatase SHP-1 promotes T cell adhesion by activating the adaptor protein CrkII in the immunological synapse
Authors: Azoulay-Alfaguter Inbar , Strazza Marianne , Peled Michael , Novak Hila K. , Muller James , Dustin Michael L. , Mor Adam
Published: August 2017

Targeting the phosphorylation state of a T cell adaptor protein may enable modulation of T cell adhesion and activation.
Papers of note in
Science Translational Medicine
9
(401)
Authors: Ferrarelli Leslie K.
Published: August 2017

This week’s articles describe a way to enhance BH3 mimetics in cancer therapy and a method to achieve targeted delivery of miRNAs to tumors.
Papers of note in
Nature
547
(7665)
Authors: Ferrarelli Leslie K.
Published: August 2017

This week’s articles highlight the role of a sugar metabolite in cellular energy sensing, how the hypothalamus controls aging, and how structural changes in protein complexes regulate the development and maintenance of plant roots.
Pharmacokinetic-Pharmacodynamic Target Attainment Analyses To Determine Optimal Dosing of Ceftazidime-Avibactam for the Treatment of Acute Pulmonary Exacerbations in Patients with Cystic Fibrosis
Authors: Bensman Timothy J. , Wang Joshua , Jayne Jordanna , Fukushima Lynn , Rao Adupa P. , D'Argenio David Z. , Beringer Paul M.
Published: August 2017

Acute pulmonary exacerbations (APE) involving
Pseudomonas aeruginosa
are associated with increased morbidity and mortality in cystic fibrosis (CF) patients. Drug resistance is a significant challenge to treatment. Ceftazidime-avibactam (CZA) demonstrates excellent
in vitro
activity against isolates recovered from CF patients, including drug-resistant strains. Altered pharmacokinetics (PK) of several beta-lactam antibiotics have been reported in CF patients. Therefore, this study sought to characterize the PK of CZA and perform target attainment analyses to determine the optimal treatment regimen. The PK of CZA in 12 adult CF patients administered 3 intravenous doses of 2.5 g every 8 h infused over 2 h were determined. Population modeling utilized the maximum likelihood expectation method. Monte Carlo simulations determined the probability of target attainment (PTA). An exposure target consisting of the cumulative percentage of a 24-h period that the free drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (
fT
>MIC
) was evaluated for ceftazidime (CAZ), and an exposure target consisting of the cumulative percentage of a 24-h period that the free drug concentration exceeds a 1-mg/liter threshold concentration (
fT
>1 mg/liter
) was evaluated for avibactam (AVI). Published CAZ and CZA MIC distributions were incorporated to evaluate cumulative response probabilities. CAZ and AVI were best described by one-compartment models. The values of total body clearance (CL; CAZ CL, 7.53 ± 1.28 liters/h; AVI CL, 12.30 ± 1.96 liters/h) and volume of distribution (
V
; CAZ
V
, 18.80 ± 6.54 liters; AVI
V
, 25.30 ± 4.43 liters) were broadly similar to published values for healthy adults. CZA achieved a PTA (
fT
>MIC
, 50%) of >0.9 for MICs of ≤16 mg/liter. The overall likelihood of a treatment response was 0.82 for CZA, whereas it was 0.42 for CAZ. These data demonstrate improved pharmacodynamics of CZA in comparison with those of CAZ and provide guidance on the optimal dosing of CZA for future studies. (This study has been registered at ClinicalTrials.gov under registration no. NCT02504827.)
In Vitro
Activities of Gepotidacin (GSK2140944) and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas
Authors: Waites Ken B. , Crabb Donna M. , Xiao Li , Duffy Lynn B.
Published: August 2017

Gepotidacin, a novel first-in-class triazaacenaphthylene topoisomerase II inhibitor, was tested against 85 type strains and clinical isolates of
Mycoplasma pneumoniae
,
Mycoplasma hominis
,
Mycoplasma genitalium
,
Ureaplasma parvum
, and
Ureaplasma urealyticum
in comparison to levofloxacin, moxifloxacin, azithromycin or clindamycin, and tetracycline. Gepotidacin MIC
90
s (μg/ml) were 0.125 (
M. pneumoniae
), 0.032 (
M. genitalium
), 2 (
M. hominis
), and 8 (
Ureaplasma
species). Gepotidacin activity was not affected by resistance to fluoroquinolones, tetracyclines, or macrolides in the strains tested. Gepotidacin merits further study for treating infections caused by these organisms.
Identification of Plasmid-Mediated Quinolone Resistance in Salmonella Isolated from Swine Ceca and Retail Pork Chops in the United States
Authors: Tyson Gregory H. , Tate Heather P. , Zhao Shaohua , Li Cong , Dessai Uday , Simmons Mustafa , McDermott Patrick F.
Published: August 2017

Fluoroquinolones are important antimicrobial drugs used to treat human
Salmonella
infections, and resistance is rare in the United States for isolates from human and animal sources. Recently, a number of
Salmonella
isolates from swine cecal contents and retail pork products from National Antimicrobial Resistance Monitoring System (NARMS) surveillance exhibited decreased susceptibility to ciprofloxacin. We identified two
qnrB19
quinolone resistance plasmids that are predominantly responsible for this phenomenon and found them distributed among several
Salmonella
serotypes isolated throughout the United States.
Cystic Fibrosis Transmembrane Conductance Regulator Reduces Microtubule-Dependent Campylobacter jejuni Invasion
Authors: Kido Junko , Shimohata Takaaki , Amano Sachie , Hatayama Sho , Nguyen Anh Quoc , Sato Yuri , Kanda Yuna , Tentaku Aya , Fukushima Shiho , Nakahashi Mutsumi , Uebanso Takashi , Mawatari Kazuaki , Takahashi Akira
Published: August 2017

Campylobacter
jejuni
is a foodborne pathogen that induces gastroenteritis. Invasion and adhesion are essential in the process of
C. jejuni
infection leading to gastroenteritis. The mucosal layer plays a key role in the system of defense against efficient invasion and adhesion by bacteria, which is modulated by several ion channels and transporters mediated by water flux in the intestine. The cystic fibrosis transmembrane conductance regulator (CFTR) plays the main role in water flux in the intestine, and it is closely associated with bacterial clearance. We previously reported that
C. jejuni
infection suppresses CFTR channel activity in intestinal epithelial cells; however, the mechanism and importance of this suppression are unclear. This study sought to elucidate the role of CFTR in
C. jejuni
infection. Using HEK293 cells that stably express wild-type and mutated CFTR, we found that CFTR attenuated
C. jejuni
invasion and that it was not involved in bacterial adhesion or intracellular survival but was associated with microtubule-dependent intracellular transport. Moreover, we revealed that CFTR attenuated the function of the microtubule motor protein, which caused inhibition of
C. jejuni
invasion, but did not affect microtubule stability. Meanwhile, the CFTR mutant G551D-CFTR, which had defects in channel activity, suppressed
C. jejuni
invasion, whereas the ΔF508-CFTR mutant, which had defects in maturation, did not suppress
C. jejuni
invasion, suggesting that CFTR suppression of
C. jejuni
invasion is related to CFTR maturation but not channel activity. When these findings are taken together, it may be seen that mature CFTR inhibits
C. jejuni
invasion by regulating microtubule-mediated pathways. We suggest that CFTR plays a critical role in cellular defenses against
C. jejuni
invasion and that suppression of CFTR may be an initial step in promoting cell invasion during
C. jejuni
infection.
Inactivation of the Major Hemolysin Gene Influences Expression of the Nonribosomal Peptide Synthetase Gene
swrA
in the Insect Pathogen Serratia sp. Strain SCBI
Authors: Petersen Lauren M. , LaCourse Kaitlyn , Schöner Tim A. , Bode Helge , Tisa Louis S.
Published: August 2017

Hemolysins are important virulence factors for many bacterial pathogens, including
Serratia marcescens
. The role of the major hemolysin gene in the insect pathogen
Serratia
sp. strain SCBI was investigated using both forward and reverse-genetics approaches. Introduction of the major hemolysin gene into
Escherichia coli
resulted in a gain of both virulence and hemolytic activity. Inactivation of this hemolysin in
Serratia
sp. SCBI resulted in a loss of hemolysis but did not attenuate insecticidal activity. Unexpectedly, inactivation of the hemolysin gene in
Serratia
sp. SCBI resulted in significantly increased motility and increased antimicrobial activity. Reverse transcription-quantitative PCR (qRT-PCR) analysis of mutants with a disrupted hemolysin gene showed a dramatic increase in mRNA levels of a nonribosomal peptide synthetase gene,
swrA
, which produces the surfactant serrawettin W2. Mutation of the
swrA
gene in
Serratia
sp. SCBI resulted in highly varied antibiotic activity, motility, virulence, and hemolysis phenotypes that were dependent on the site of disruption within this 17.75-kb gene. When introduced into
E. coli
,
swrA
increases rates of motility and confers antimicrobial activity. While it is unclear how inactivation of the major hemolysin gene influences the expression of
swrA
, these results suggest that
swrA
plays an important role in motility and antimicrobial activity in
Serratia
sp. SCBI.

IMPORTANCE
The opportunistic Gram-negative bacteria of the genus
Serratia
are widespread in the environment and can cause human illness. A comparative genomics analysis between
Serratia marcescens
and a new
Serratia
species from South Africa, termed
Serratia
sp. strain SCBI, shows that these two organisms are closely related but differ in pathogenesis.
S. marcescens
kills
Caenorhabditis
nematodes, while
Serratia
sp. SCBI is not harmful and forms a beneficial association with them. This distinction presented the opportunity to investigate potential differences in regulation of common virulence mechanisms between these two species. With the emergence of antibiotic-resistant microorganisms, there is a widespread need to understand the regulation of pathogenesis. The significance of this study is the presentation of evidence for cross-pathway regulation of virulence factors and how the elimination of one mechanism may be compensated for by the upregulation of others.
Characterization of a Minimal Type of Promoter Containing the −10 Element and a Guanine at the −14 or −13 Position in Mycobacteria
Authors: Zhu Yan , Mao Chunyou , Ge Xingyi , Wang Zhongwei , Lu Pei , Zhang Yong , Chen Shiyun , Hu Yangbo
Published: August 2017

Three key promoter elements, i.e., −10, −35, and T
−15
G
−14
N, are recognized by the σ subunit of RNA polymerase. Among them, promoters with the −10 element and either −35 or T
−15
G
−14
N are known to initiate transcription efficiently, but recent systematic analyses have identified a large group of promoters in
Mycobacterium tuberculosis
that contain only a −10 consensus. How these promoters initiate transcription remains poorly understood. Here, we show that promoters containing the −10 element and an upstream G located at the −14 or −13 position can successfully initiate transcription in mycobacteria. Importantly, this new type of promoter is active in the absence of other promoter consensuses, suggesting that it is a minimal promoter type. Mutation of the upstream G in promoters decreased the efficiencies of their binding with RNA polymerase and their abilities to initiate transcription in both
in vitro
and
in vivo
analyses. A glutamic acid in σ region 3.0 is essential for recognizing G
−14
and G
−13
and is conserved in both principal and principal-like σ factors in mycobacteria, indicating that recognition of this minimal type of promoter might be a common mechanism for transcription initiation. Consistently, more than 70% of the identified promoters in
M. tuberculosis
contained G
−14
or G
−13
upstream of the conserved −10 element, and thousands of promoters in representative mycobacterial species have been predicted using the −10 consensus and G
−14
or G
−13
. Altogether, our study presents a universal mechanism for transcription initiation from a minimal promoter in mycobacteria, which might also be applicable to other bacteria.

IMPORTANCE
In contrast to the detailed information for recognizing classic promoters in the model organism
Escherichia coli
, very little is known about how transcription is initiated in the human pathogen
Mycobacterium tuberculosis
. In this study, we characterized a new type of promoter in mycobacteria that requires only a −10 consensus and an upstream G
−14
or G
−13
. Residues important for recognizing the −10 element and the upstream G are conserved in σ
A
and σ
B
from mycobacterial species. According to such features, thousands of promoters in mycobacteria can be predicted using the −10 consensus and G
−14
or G
−13
, which suggests that transcription from this new type of promoter might be widespread. Our findings provide insightful information for characterizing promoters in mycobacteria.
Distinctive Roles for Periplasmic Proteases in the Maintenance of Essential Outer Membrane Protein Assembly
Authors: Soltes Garner R. , Martin Nicholas R. , Park Eunhae , Sutterlin Holly A. , Silhavy Thomas J.
Published: August 2017

Outer membrane protein (OMP) biogenesis in
Escherichia coli
is a robust process essential to the life of the organism. It is catalyzed by the β-barrel assembly machine (Bam) complex, and a number of quality control factors, including periplasmic chaperones and proteases, maintain the integrity of this trafficking pathway. Little is known, however, about how periplasmic proteases recognize and degrade OMP substrates when assembly is compromised or whether different proteases recognize the same substrate at distinct points in the assembly pathway. In this work, we use well-defined assembly-defective mutants of LptD, the essential lipopolysaccharide assembly translocon, to show that the periplasmic protease DegP degrades substrates with assembly defects that prevent or impair initial contact with Bam, causing the mutant protein to accumulate in the periplasm. In contrast, another periplasmic protease, BepA, degrades a LptD mutant substrate that has engaged the Bam complex and formed a nearly complete barrel. Furthermore, we describe the role of the outer membrane lipoprotein YcaL, a protease of heretofore unknown function, in the degradation of a LptD substrate that has engaged the Bam complex but is stalled at an earlier step in the assembly process that is not accessible to BepA. Our results demonstrate that multiple periplasmic proteases monitor OMPs at distinct points in the assembly process.

IMPORTANCE
OMP assembly is catalyzed by the essential Bam complex and occurs in a cellular environment devoid of energy sources. Assembly intermediates that misfold can compromise this essential molecular machine. Here we demonstrate distinctive roles for three different periplasmic proteases that can clear OMP substrates with folding defects that compromise assembly at three different stages. These quality control factors help ensure the integrity of the permeability barrier that contributes to the intrinsic resistance of Gram-negative organisms to many antibiotics.
Zinc containing dental fixative causing copper deficiency myelopathy
Authors: Carroll Liam Stuart , Abdul-Rahim Azmil H , Murray Rosanne
Published: August 2017

A 62-year-old male, previously well, was referred to neurology clinic following 6 months history of worsening lower limbs instability, paraesthesia, pain and weakness rendering him housebound. Examination revealed upper motor neuron pattern of weakness of the lower limbs and loss of proprioception. Serum analysis revealed reduced caeruloplasmin and copper levels with raised zinc. Spinal imaging revealed subtle dorsal column intensity changes in C2-C7, confirmed with 3T MRI. A copper deficiency myeloneuropathy was diagnosed secondary to chronic use of a zinc-containing dental fixative paste. The paste was discontinued and a copper supplementation was started. Resolution of symptoms was not achieved with intensive physiotherapy. The patient remains a wheelchair user though progression of symptoms has halted. Prompt recognition and treatment of hyperzincaemia-induced hypocupraemia earlier in the disease course may have prevented any irreversible neurological deficit.
Gallstone ileus of the duodenum: an unexpected presentation of Bouveret's syndrome
Authors: Tindell Neil , Holmes Kayla , Marotta David
Published: August 2017

This report describes a patient who presented with a large gallstone obstructing the duodenal bulb, with the chief complaint of acute on chronic abdominal pain. Classically, this is known as Bouveret's syndrome or a gallstone ileus of the duodenum. Our patient's current health status presented a challenge, with the presence of several comorbidities, particularly a large abdominal aortic aneurism. We chose an open procedure for this reason. The stone was removed through a laparotomy, and the cholecystoduodenal fistula that the stone used to pass into the small bowel was repaired. With our patient's future medical needs in mind, only the necessary interventions were performed to regain functionality of the bowel. This came in the form of a diverting gastrojejunostomy, with a distal jejunostomy and feeding tube inserted. The patient tolerated the procedure well, only remaining intubated postoperative due to her chronic obstructive pulmonary disease (COPD). She achieved a complete recovery and transitioned home.
Paraneoplastic cerebellar degeneration secondary to ovarian carcinosarcoma: a cerebellar conundrum
Authors: Birch Julian David , Sen Arup , Rowland Katherine , Viner Tatyana
Published: August 2017

We present a case of an elderly female patient who presented with a 6-month history of progressive slurred speech, vertigo, unsteadiness and falls. She underwent an extensive battery of neurological and cardiovascular investigations, none of which demonstrated a diagnostic cause for her symptoms. She was referred to the stroke and neurology teams and was started on treatment for presumed anxiety. As her symptoms continued to progress, she was referred to the falls service. Following a multidisciplinary team discussion, she was reviewed by the consultant geriatrician who felt this may be due to a malignancy so the consultant geriatrician arranged blood testsand CT scan of her chest, abdomen and pelvis. These demonstrated a large left adnexal mass and a raised Ca-125 level. The patient was diagnosed with an ovarian tumour, which was treated surgically. A provisional diagnosis of paraneoplastic cerebellar degeneration, secondary to ovarian carcinosarcoma, was made.
GSK2586184, a JAK1 selective inhibitor, in two patients with ulcerative colitis
Authors: De Vries Leonie C.S. , Ludbrook Valerie J. , Hicks Kirsty J. , D'Haens Geert R.
Published: August 2017

Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC). Tofacitinib inhibits cytokine signalling through blockade of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Adverse events including neutropenia and anaemia resulting from JAK2 inhibition have been observed in actively treated patients. By selectively targeting JAK1, such adverse events could be expected to be avoided. This open label study was designed to enrol 15 patients with UC, however the trial was discontinued after two inclusions due to safety concerns with the agent in a parallel trial for systemic lupus erythematosus. GSK2586184 was administered in two patients with moderate-to-severe UC. The JAK1 selective inhibitor GSK2586184 was well tolerated and induced clinical and endoscopic response in two patients with moderate-to-severe UC. In addition, treatment with GSK2586184 decreased histology scores and faecal calprotectin levels at early withdrawal.
Preclinical development of MGO Manuka Honey microemulsion for blepharitis management
Authors: Craig Jennifer P , Rupenthal Ilva D , Seyfoddin Ali , Cheung Isabella M Y , Uy Benedict , Wang Michael T M , Watters Grant A , Swift Simon
Published: August 2017

Objective

To evaluate thein vitroantimicrobial effects of cyclodextrin-complexed and uncomplexed Manuka honey on bacteria commonly associated with blepharitis, andin vivorabbit eye tolerability of a cyclodextrin-complexed methylglyoxal (MGO) Manuka Honey microemulsion (MHME).

Methods and analysis

In vitrophase: Bacterial growth inhibition was assessed by area under the growth curve (AUC) forStaphylococcus aureus, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) forS. aureus, Staphylococcus epidermidisandPseudomonas aeruginosawith cyclodextrin-complexed and uncomplexed Manuka honey were determined.

In vivophase: Six rabbits were administered 20 µL of MHME (at 1:10 dilution) to the right eye (treated) and 20 µL of saline to the left eye (control) daily, for 5 days. Tear evaporation, production, osmolarity, lipid layer, conjunctival hyperaemia and fluorescein staining were assessed daily, before and 15 min after instillation.

Results

In vitrophase: The relative AUC for cyclodextrin-complexed Manuka honey was lower than that of uncomplexed honey at both 250 and 550 mg/kg of MGO (both p <0.05). Cyclodextrin-complexed honey had lower MIC and MBC than uncomplexed honey for bothS. aureusandS. epidermidis, but notP. aeruginosa.

In vivophase: No significant changes were observed in the parameters assessed in either treated or control eyes (all p >0.05).

Conclusion

Overall, antimicrobial potency of cyclodextrin-complexed Manuka honey was greater than uncomplexed honey. No significant immediate or cumulative adverse effects were observed with MHME application on rabbit eyes, supporting future conduct of clinical safety and tolerability trials in human subjects.
Downregulation of interferon-γ-induced protein 10 in the tears of patients with Stevens-Johnson syndrome with severe ocular complications in the chronic stage
Authors: Ueta Mayumi , Nishigaki Hiromi , Sotozono Chie , Kinoshita Shigeru
Published: August 2017

Objectives

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute inflammatory vesiculobullous reactions of the skin and mucosa such as the ocular surface, oral cavity and genitals. Severe ocular complications (SOC) arise in some patients with SJS/TEN diagnosed by dermatologists. To investigate the pathophysiology of ocular surface inflammation in SJS/TEN with SOC in the chronic stage, we examined cytokines in the tears of patients with ocular surface diseases and healthy controls.

Participants

SJS/TEN eyes in the chronic stage (n>30), healthy eyes (n>20, controls) and eyes (n>20) from patients with atopic keratoconjunctivitis representing different ocular surface inflammatory disorders.

Primary outcome measures

Tear samples were collected on Schirmer's measurement strips. To measure the level of various cytokines in the tears we used BD CBA Flex sets.

Study design

An observational study (case–control study).

Results

We recorded the level of interleukin (IL)-6, IL-8, eotaxin, macrophage inflammatory protein (MIP)-1β, RANTES (regulated on activation, normal T cell expressed and secreted), interferon gamma (IFN)-γ, monocyte chemoattractant protein-1, IFN-γ-induced protein 10 (IP-10) and total IgE. We found that compared with the controls, in SJS/TEN with SOC, IL-6, IL-8, eotaxin and MIP-1β were significantly upregulated while IP-10 was significantly downregulated. Compared with atopic keratoconjunctivitis, IP-10 was significantly downregulated in SJS/TEN with SOC; on the other hand, total IgE was significantly upregulated in atopic keratoconjunctivitis compared with SJS/TEN with SOC.

Conclusions

IP-10 in tears may be a biomarker to distinguish between chronic SJS/TEN with SOC and other ocular inflammatory disorders such as atopic keratoconjunctivitis.
A pilot biomechanical assessment of curling deliveries: is toe sliding more likely to cause knee injury than flatfoot sliding?
Authors: Robertson Iona , Arnold Graham P , Wang Weijie , Drew Tim S , Nasir Sadiq , MacDonald Calum , Abboud Rami J
Published: August 2017

Background

The aim of this study was to determine whether toe sliding is more likely to cause knee injuries than flatfoot sliding in curling.

Methods

Twelve curlers participated in the study, each delivering 12 stones. Six stones per volunteer were delivered using a flatfoot slide and six were delivered using a toe slide. The Pedar-X in-shoe pressure system recorded the plantar pressure during each of the slides, while a sagittal plane digital video recorded the body position of the curler. Measurements were taken from the video recordings using a software overlay program (MB Ruler), and this, combined with the Pedar-X data, gave the overall joint force in the tuck knee.

Results

The knee joint force for toe sliding was more than double that of flatfoot sliding (p<0.05). There was a strong correlation between the increase in knee joint force and the increase in the moment arm of the ground reaction force. Images produced using the three-dimensional Vicon system confirm that toe sliding produces a larger moment arm than flatfoot sliding.

Conclusion

Injuries are more likely to occur in toe sliding, compared with flatfoot sliding, due to the increase in force and moment, pushing the weight of the curler forward over the knee, which could make the adopted position less stable. Curlers might consider avoiding toe sliding to reduce the risk of knee injuries if the two types of delivery could be performed equally well.
Interval exercise increases angiogenic cell function in postmenopausal women
Authors: Harris Emma , Rakobowchuk Mark , Birch Karen M
Published: August 2017

Introduction

Exercise can help to negate the increased cardiovascular disease risk observed in women after the menopausal transition. This study sought to determine whether interval or continuous exercise has differential effects on endothelial function and circulating angiogenic cell (CAC) number and function in postmenopausal women.

Methods

Fifteen healthy postmenopausal women completed a 30 min acute moderate-intensity continuous (CON) and interval exercise (MOD-INT) session on a cycle ergometer on separate days. Nine participants completed a further single 30 min acute heavy-intensity interval (HEAVY-INT) exercise session. Brachial artery flow-mediated dilation (FMD) was assessed pre-exercise and 15 min post-exercise session. CAC number and colony-forming capacity in vitro were assessed post exercise and compared with resting levels.

Results

FMD and CAC number did not change post exercise regardless of exercise type (p>0.05). However, the number (mean±SD) of colony-forming units (CFUs) increased from visit 1 (12±10 CFUs/well) to post MOD-INT (32±30 CFUs/well) and post HEAVY-INT (38±23 CFUs/well) but not post CON (13±14 CFUs/well).

Conclusion

A single session of interval exercise is more effective than a continuous exercise session for increasing the intercellular communication of CACs, regardless of exercise intensity. The enhanced ability of CACs to form colonies may reflect an increased number and/or function of angiogenic T-cells. The repeated exertions to higher work rates during interval exercise may explain this response. Repeated exercise sessions might be required to improve FMD in postmenopausal women.
Extreme event medicine: considerations for the organisation of out-of-hospital care during obstacle, adventure and endurance competitions
Authors: Laskowski-Jones Linda , Caudell Michael J , Hawkins Seth C , Jones Lawrence J , Dymond Chelsea A , Cushing Tracy , Gupta Sanjey , Young David S , Starling Jennifer M , Bounds Richard
Published: August 2017

Obstacle, adventure and endurance competitions in challenging or remote settings are increasing in popularity. A literature search indicates a dearth of evidence-based research on the organisation of medical care for wilderness competitions. The organisation of medical care for each event is best tailored to specific race components, participant characteristics, geography, risk assessments, legal requirements, and the availability of both local and outside resources. Considering the health risks and logistical complexities inherent in these events, there is a compelling need for guiding principles that bridge the fields of wilderness medicine and sports medicine in providing a framework for the organisation of medical care delivery during wilderness and remote obstacle, adventure and endurance competitions. This narrative review, authored by experts in wilderness and operational medicine, provides such a framework. The primary goal is to assist organisers and medical providers in planning for sporting events in which participants are in situations or locations that exceed the capacity of local emergency medical services resources.
Characteristics and occurrence of type 2 myocardial infarction in emergency department patients: a prospective study
Authors: Greenslade Jaimi H , Adikari Thushani , Mueller Christian , Sandoval Yader , Nestelberger Thomas , Parsonage William , Hawkins Tracey , Cullen Louise
Published: August 2017

Objective

To identify differences in prevalence, demographics, clinical features and outcomes for type 1 myocardial infarction (T1MI) and type 2 myocardial infarction (T2MI) in a cohort of patients presenting to the Emergency Department (ED) with chest pain.

Methods

This was a post hoc analysis of data collected from two prospective studies. Data were collected between November 2008 and February 2011 for the first study, and between February 2011 and March 2014 for the second. Participants were patients presenting to the ED with symptoms suggestive of acute coronary syndrome (ACS). The outcome was 30-day diagnosis; classified into T1MI, T2MI or non-MI. Descriptive statistics were used to compare the demographics, clinical history and presenting symptoms across diagnoses (T1MI, T2MI and non-MI). Cumulative mortality over 1 year was compared for T1MI and T2MI.

Results

147 patients (6.3%; 95% CI 5.3% to 7.3%) were classified as T1MI and 52 (2.2%; 95% CI 1.7% to 2.9%) were classified as T2MI. T2MIs were more likely to be female (OR 4.71, 95% CI 2.28 to 9.76), have an abnormal but non-ischaemic ECG (OR 2.95, 95% CI 1.45 to 6.00), report prior hypertension (OR 2.83, 95% CI 1.35 to 6.12), have tachycardia (OR 9.26, 95% CI 3.08 to 30.77) and pain at rest (OR 3.04, 95% CI 1.28 to 8.02) compared with T1MI. One-year mortality was similar between T1MI and T2MI (9% and 14.6%, respectively, p=0.37).

Conclusions

T2MIs comprised one quarter of all MIs diagnosed in the ED. Among patients presenting to the ED with symptoms of ACS, symptoms do not allow clinicians to reliably differentiate patients with T1MI and T2MI. Prior hypertension, tachycardia and abnormal non-ischaemic ECGs are seen more often in T2MI compared with T1MI. One-year mortality was substantial in patients with T1MI and T2MI, but low power precludes conclusions about mortality differences between groups.
Unravelling migrants’ health paradoxes: a transdisciplinary research agenda
Authors: Roura Maria
Published: August 2017

The Social Determinants of Health literature has consistently found that a higher socioeconomic status is associated with better health outcomes even after adjusting for traditional risk factors. However, research findings in the field of Migrants’ Health suggest that the socioeconomic/health gradient does not always behaveas expectedfor migrants and their descendants. The mismatch of findings in these two long-standing parallel research traditions is exemplified by frequent reports of paradoxical findings in the scientific literature: the healthy migrant paradox, the ethnic density paradox and the diminishing returns paradox. This paper outlines a transdisciplinary research agenda to elucidate the social processes that underpin these disconcerting findings and calls for a shift from a pathogenic deficit model that sees migrants as a burden to their reconceptualisation as actively engaged citizens in search of solutions. Amidst a severe refugee crisis, fears of terrorist attacks and political capitalisation of these tragedies to foster antimigrant sentiments, this is urgently needed.
Shifting disease burden in low and middle-income countries: a 14-year survival analysis of childhood mortality in Bangladesh
Authors: Alonge Olakunle , He Siran , Hoque Dewan Emdadul , Salam Shumona Sharmin , Islam Irteja , El-Arifeen Shams , Hyder Adnan A
Published: August 2017

Background

The objective of this study is to compare all-cause mortality and drowning-specific mortality rates and survival times among birth cohorts of children from rural Bangladesh over a 14-year period.

Method

Seven birth cohorts of children aged 12–59 months were created using data from the Matlab Health and Demographic Surveillance System in Bangladesh. Each cohort represents children born within a 2-year interval between 1 July 1995 and 30 June 2009, who were then evaluated over a 2-year snapshot. All-cause and drowning-specific mortality rates were compared for each cohort using the oldest cohort (cohort 1) as reference. A Cox proportional model was used to estimate hazard rate ratios (HRR) comparing the cohorts, and adjusted for key independent variables. Kaplan-Meier survivor function was estimated for each birth cohort and compared with cohort 1 using log-rank test.

Results

The adjusted HRR for all-cause mortality showed that children in cohorts 4, 5, 6 and 7 had significantly lower hazard rate compared with cohort 1 with a dose–response relationship, the adjusted HRRs were 0.51 (95% CI 0.31, 0.84), 0.53 (95% CI 0.32, 0.87), 0.44 (95% CI 0.26, 0.76) and 0.42 (95% CI 0.24, 0.74), respectively. For drowning, none of the adjusted HRR was statistically significant. Mother's primary education and being married were protective of risk of death from all causes.

Conclusion

Whereas child mortality rates from all causes declined remarkably between 1998 and 2012 in rural Bangladesh, drowning-specific mortality rates remained unchanged. This shifting burden of disease underscores the epidemiological transition in the childhood causes of death in Bangladesh and the need for urgent action to review child health interventions.
Homology Modeling of Ffa2 Identifies Novel Agonists that Potentiate Insulin Secretion
Authors: Villa Stephanie R , Mishra Rama K , Zapater Joseph L , Priyadarshini Medha , Gilchrist Annette , Mancebo Helena , Schiltz Gary E , Layden Brian T
Published: August 2017

Critical aspects of maintaining glucose homeostasis in the face of chronic insulin resistance and type 2 diabetes (T2D) are increased insulin secretion and adaptive expansion of beta cell mass. Nutrient and hormone sensing G protein-coupled receptors are important mediators of these properties. A growing body of evidence now suggests that the G protein-coupled receptor, free fatty acid receptor 2 (FFA2), is capable of contributing to the maintenance of glucose homeostasis by acting at the pancreatic beta cell as well as at other metabolically active tissues. We have previously demonstrated that Gαq/11-biased agonism of FFA2 can potentiate glucose stimulated insulin secretion (GSIS) as well as promote beta cell proliferation. However, the currently available Gαq/11-biased agonists for FFA2 exhibit low potency, making them difficult to examine in vivo. This study sought to identify Gαq/11-biased FFA2-selective agonists with potent GSIS-stimulating effects. To do this, we generated an FFA2 homology model that was used to screen a library of 10 million drug-like compounds. Although FFA2 and the related short chain fatty acid receptor FFA3 share 52% sequence similarity, our virtual screen identified over 50 compounds with predicted selectivity and increased potency for FFA2 over FFA3. Subsequent in vitro calcium mobilization assays and GSIS assays resulted in the identification of a compound that can potentiate GSIS via activation of Gαq/11 with 100-fold increased potency compared with previously described Gαq/11-biased FFA2 agonists. These methods and findings provide a foundation for future discovery efforts to identify biased FFA2 agonists as potential T2D therapeutics.
Prediction of seismic demand model for pulse-like ground motions using artificial neural networks
Authors: Yazdannejad Kowsar , Yazdani Azad
Published: August 2017

A probabilistic seismic demand model that relates ground motion intensity measures (IMs) to the structural demand measures is a useful tool for reliability analysis of structures. It is common to utilize the scalar seismic parameters or a vector of a few seismic parameters to reveal ground motion uncertainty. However, for the qualification of an IM for representing the ground motion uncertainty, a larger vector of greater seismic component is required. This study aims to use more parameters as vector IMs in the demand model to achieve better estimation of the ground motion uncertainty. In this study, three-layer feed forward neural network was used to predict the seismic demand model of the mid-rise reinforced concrete buildings for pulse-like ground motions. The results indicate that due to the complexity of the relationship between seismic response of structures and seismic intensity parameters, using artificial neural networks method is more suitable than numerical methods to show uncertainties.
Multi-scale characterization of hydrated lime mastics
Authors: Diab Aboelkasim , You Zhanping , Yang Xu , Wahaballa Amr M.
Published: August 2017

This study is devoted to characterize the behavior of the hydrated lime-asphalt binder mastic (HLM) using the viscosity characteristics (relative viscosity versus shear rate profile) and viscoelastic properties. In addition, the multiple stress creep recovery, linear amplitude sweep, and asphalt binder cracking device tests were also performed, for the sake of characterization of permanent deformation, fatigue cracking, and low temperature cracking, respectively. The large amplitude oscillatory shear test was utilized to characterize the nonlinear behavior of HLMs using Lissajous-Bowditch plots and associated local viscoelastic measures (minimum and large strain complex shear moduli). Overall, the HLM is able to improve the stiffness-related properties of pavement; on the other hand, this mastic can help resist load and non-load associated cracking. In addition, the nonlinear behavior revealed higher stress response of the HLMs compared to base binder even after increased number of cycles which could be an indicator of the ability to sustain high stresses and strains.
Hirnantian (Ordovician) through Wenlock (Silurian) conodont biostratigraphy, bioevents, and integration with graptolite biozones, Cape Phillips Formation slope facies, Cornwallis Island, Canadian Arctic Islands
Authors: Zhang Shunxin , Jowett David M.S. , Barnes Christopher R.
Published: August 2017

Cornwallis Island in the Canadian Arctic Archipelago provides one of the world’s best areas for establishing an integrated graptolite–conodont biozonation for the Late Ordovician – Silurian given the well-exposed interfingering relationship of the basinal shale and carbonate platform facies. Building on earlier graptolite work, 180 samples were collected from nine sections of the Cape Phillips Formation, of which 118 yielded approximately 7600 conodont elements representing 54 species in 25 genera, including one new genus and species, Mayrodus melchini; the conodonts are well preserved, with minimal thermal alteration (colour alteration index, CAI 1). Nine conodont zones are recognized and defined for this region, namely the Amorphognathus ordovicicus, Distomodus kentuckyensis, Aspelundia expansa, As. fluegeli, and Pterospathodus celloni Interval zones, Pt. a. amorphognathoides Taxon-range Zone, Pt. pennatus procerus and Kockelella ranuliformis Highest-occurrence zones, and K. ortus absidata Taxon-range Zone. An integration of graptolite and conodont zones is documented. Earlier paleontological and isotope geochemical studies have demonstrated the dynamic nature of the Silurian ocean–climate system and identified major faunal turnovers or events. Five of these are recognized in the Cornwallis fauna and related to oceanographic and climate changes, in part referring to recent oxygen isotope data from conodonts from the Cornwallis collections: Hirnantian extinction event, Sandvika Event (late Aeronian, Llandovery), Snipklint Primo Episode (early Telychian, Llandovery), Ireviken Event (late Telychian, Llandovery–Sheinwoodian, Wenlock), and Mulde Event (early Homerian, Wenlock).
Troodontids (Theropoda) from the Dinosaur Park Formation, Alberta, with a description of a unique new taxon: implications for deinonychosaur diversity in North America
Authors: van der Reest Aaron J. , Currie Philip J.
Published: August 2017

Troodontids are known from Asia and North America, with the most complete specimens from the Jurassic of China and the Cretaceous of Mongolia. North American troodontids are poorly known, and specimens that have been described are isolated elements or partial skeletons with limited material. A new troodontid from the upper Dinosaur Park Formation (upper Campanian) is based on partial skulls, several vertebrae, ribs, gastralia, chevrons, a sacrum, partial pelvis, and partial fore and hind limbs. It is the largest troodontid known, with an estimated height of 180 cm and length of 350 cm. Like other troodontids, it possesses an elongated ambiens process and has a horizontal ventral margin of the postacetabular process. It differs from all other derived troodontids in that the slightly retroverted pubis has a shaft that curves anteroventrally. Some specimens from the Dinosaur Park Formation previously assigned to Troodon are reassigned to the new taxon, including multiple partial crania, an associated dentary and metatarsus, and a partial skeleton. Previously undescribed elements from the lower part of the Dinosaur Park Formation are assigned to the resurrected Stenonychosaurus inequalis. Distinct stratigraphic separation of Stenonychosaurus inequalis and the new taxon indicates a replacement in troodontid fauna, similar to the turnover of large ornithischians in the same formation. The new taxon is phylogenetically more closely related to Mongolian taxa, indicating the replacement of Stenonychosaurus may have been from an earlier Asian form immigrating into North America.
Protective effects of pioglitazone on vascular endothelial cell dysfunction induced by high glucose via inhibition of IKKα/β–NFκB signaling mediated by PPARγ in vitro
Authors: Chen Chunxiang , Peng Shaorong , Chen Fanghui , Liu Lili , Li Zhouxue , Zeng Guohua , Huang Qiren
Published: August 2017

PIO, a synthetic ligand for PPARγ, is used clinically to treat T2DM. However, little is known about its protective effects on endothelium and the underlying mechanisms. In this study, we sought to investigate the protective effects of PIO on endothelium and its probable mechanisms: 95% confluent wild type (WT) HUVECs and PPARγLow-HUVECs that we first injured with HG (33 mmol·L–1) were first pretreated with 10 μmol·L–1 of GW9662 for 30 min, and then treated the cells with different concentrations of PIO (5, 10, or 20 μmol·L–1) for 24 h. Finally, we measured the levels of NO, ET1, TNFα, and IL6 in the cell culture supernatant. These cells were then used to determine cell viability, caspase3 activity, the levels of IKKα/β mRNA, IKKα/β, and NFκB-p65. Severe dysfunction and activation of IKKα/β–NFκB signaling occurred after we exposed HUVECs to HG. Conversely, treatment with PIO significantly attenuated the dysfunction and the activation of IKKα/β–NFκB signaling induced by HG in a dose-dependent manner. Moreover, the protective effects of PIO were completely abrogated by GW9662 or down-regulation of PPARγ. Taken together, the results indicate that PIO protects HUVECs against the HG-induced dysfunction through the inhibition of IKKα/β–NFκB signaling mediated by PPARγ.