bluuebunny/crossref_metadata_2025 huggingface dataset:
The surgical burden of disease and perioperative mortality in patients admitted to hospitals in Victoria, Australia: a population-level observational study
Authors: Fehlberg Trafford , Rose John , Guest Glenn Douglas , Watters David
Published: May 2019

Objectives

Comprehensive reporting of surgical disease burden and outcomes are vital components of resilient health systems but remain under-reported. The primary objective was to identify the Victorian surgical burden of disease necessitating treatment in a hospital or day centre, including a thorough epidemiology of surgical procedures and their respective perioperative mortality rates (POMR).

Design

Retrospective population-level observational study.

Setting

The study was conducted in Victoria, Australia. Access to data from the Victorian Admitted Episodes Dataset was obtained using the Dr Foster Quality Investigator tool. The study included public and private facilities, including day-case facilities.

Participants

From January 2014 to December 2016, all admissions with an International Statistical Classification of Diseases-10 code matched to the Global Health Estimates (GHE) disease categories were included.

Primary and secondary outcome measures

Admissions were assigned a primary disease category according to the 23 GHE disease categories. Surgical procedures during hospitalisations were identified using the Australian Refined Diagnosis Related Groups (AR-DRG). POMR were calculated for GHE disease categories and AR-DRG procedures.

Results

A total of 4 865 226 admitted episodes were identified over the 3-year period. 1 715 862 (35.3%) of these required a surgical procedure. The mortality rate for those undergoing a procedure was 0.42%, and 1.47% for those without. The top five procedures performed per GHE category were lens procedures (162 835 cases, POMR 0.001%), caesarean delivery (76 032 cases, POMR 0.01%), abortion with operating room procedure (65 451 cases, POMR 0%), hernia procedures (52 499 cases, POMR 0.05%) and other knee procedures (47 181 cases, POMR 0.004%).

Conclusions

Conditions requiring surgery were responsible for 35.3% of the hospital admitted disease burden in Victoria, a rate higher than previously published from Sweden, New Zealand and the USA. POMR is comparable to other studies reporting individual procedures and conditions, but has been reported comprehensively across all GHE disease categories for the first time.
‘Dry’ and ‘wet’ cough: how reliable is parental reporting?
Authors: Donnelly Deirdre , Everard Mark L
Published: May 2019

Introduction

Chronic cough in childhood is common and causes much parental anxiety. Eliciting a diagnosis can be difficult as it is a non-specific symptom indicating airways inflammation and this may be due to a variety of aetiologies. A key part of assessment is obtaining an accurate cough history. It has previously been shown that parental reporting of ‘wheeze’ is frequently inaccurate. This study aimed to determine whether parental reporting of the quality of a child’s cough is likely to be accurate.

Methods

Parents of 48 ‘new’ patients presenting to a respiratory clinic with chronic cough were asked to describe the nature of their child’s cough. They were then shown video clips of different types of cough using age-appropriate examples, and their initial report was compared with the types of cough chosen from the video.

Results

In a quarter of cases, the parents chose a video clip of a ‘dry’ or ‘wet’ cough having given the opposite description. In a further 20% parents chose examples of both ‘dry’ and ‘wet’ coughs despite having used only one descriptor.

Discussion

While the characteristics of a child’s cough carry important information that may be helpful in reaching a diagnosis, clinicians should interpret parental reporting of the nature of a child’s cough with some caution in that one person’s ‘dry’ cough may very well be another person’s ‘wet’ cough.
Geographically linked risk factors for enrolment into a fast breathing child pneumonia trial in Lilongwe, Malawi: an Innovative Treatments in Pneumonia (ITIP) secondary analysis
Authors: Nkwopara Evangelyn , Schmicker Robert , Mvalo Tisungane , May Susanne , Ginsburg Amy Sarah
Published: May 2019

Background

Pneumonia is the leading infectious killer of children less than 5 years of age worldwide. In addition to vaccines that help prevent pneumonia, understanding the environmental and socioeconomic risk factors for child pneumonia is critical to further prevention.

Methods

Data from children with fast breathing pneumonia enrolled in a non-inferiority clinical trial assessing the effectiveness of 3-day placebo versus antibiotic treatment in Lilongwe, Malawi were used to examine environmental and socioeconomic characteristics within the study population. Location of residence was collected for enrolled children, and spatial enrolment rates were compared across Lilongwe using a spatial scan statistic.

Results

Data from 1101 children were analysed. Three urban subdistricts (locally known as ‘Areas’) (Areas 24, 36 and 38) out of 51 were identified with higher than expected enrolment. These three areas were associated with higher rates of poverty (37.8% vs 23.9%) as well as informal settlements and poorer sanitation (42.4% vs 7.4%) than other areas. Parents of enrolled children from these areas also had lower rates of secondary education compared with parents of children enrolled from other areas (55% vs 67% (p<0.01) among fathers; 47% vs 54% (p<0.01) among mothers).

Conclusion

In Lilongwe, areas with higher rates of poverty, informal settlements and poor sanitation contributed higher than expected enrolment of children to our fast breathing child pneumonia clinical trial when compared with other areas. Additional research is needed to evaluate the impact of environmental and socioeconomic risk factors, along with vaccination status, on the incidence of fast breathing pneumonia in children living in this region.
Aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in immune-mediated optic neuritis at long-term follow-up
Authors: Petzold Axel , Woodhall Mark , Khaleeli Z , Tobin W Oliver , Pittock Sean J , Weinshenker B G , Vincent Angela , Waters Patrick , Plant Gordon T
Published: May 2019

Objectives

To re-evaluate serum samples from our 2007 cohort of patients with single-episode isolated ON (SION), recurrent isolated ON (RION), chronic relapsing inflammatory optic neuropathy (CRION), multiple sclerosis-associated ON (MSON) and neuromyelitis optica (NMO).

Methods

We re-screened 103/114 patients with available serum on live cell-based assays (CBA) for aquaporin-4 (AQP4)-M23-IgG and myelin-oligodendrocyte
glycoprotein (MOG)-α1-IgG. Further testing included oligoclonal bands, serum levels of glial fibrillar acidic and neurofilament proteins and S100B. We show the impact of updated serology on these patients.

Results

Reanalysis of our original cohort revealed that AQP4-IgG seropositivity increased from 56% to 75% for NMO, 5% to 22% for CRION, 6% to 7% for RION, 0% to 7% for MSON and 5% to 6% for SION. MOG-IgG1 was identified in 25% of RION, 25% of CRION, 10% of SION, 0% of MSON and 0% of NMO. As a result, patients have been reclassified incorporating their autoantibody status. Presenting visual acuity was significantly worse in patients who were AQP4-IgG seropositive (p=0.034), but there was no relationship between antibody seropositivity and either ON relapse rate or visual acuity outcome.

Conclusions

The number of patients with seronegative CRION and RION has decreased due to improved detection of autoantibodies over the past decade. It remains essential that the clinical phenotype guides both antibody testing and clinical management. Careful monitoring of the disease course is key when considering whether to treat with prophylactic immune suppression.
Upper trunk block for shoulder analgesia with potential phrenic nerve sparing: a preliminary anatomical report
Authors: Cros Campoy José , Domingo Bosch Oscar , Pomés Jaume , Lee Jing , Fox Ben , Sala-Blanch Xavier
Published: May 2019

Background and objectives

Ipsilateral phrenic nerve palsy (PNP) is an undesirable side of conventional approaches to interscalene brachial plexus blocks. The purpose of this study was to demonstrate whether or not the phrenic nerve can be spared by dye when injected at the division of the upper trunk of the brachial plexus.

Methods

Under ultrasound guidance, 5 mL of radiolabeled dye was injected between the anterior and posterior division of the upper trunk in two fresh, cryopreserved cadavers. CT scan analysis, cadaveric dissection, and cryosectioning were performed to examine the spread of the injectate.

Results

We found staining of the injectate over the entire upper trunk with its anterior and posterior divisions, the suprascapular nerve under the omohyoid muscle and the lateral pectoralis nerve, and the C5 and C6 roots. The middle trunk was partially stained. There was no evidence of dye staining of the lower trunk, anterior aspect of the anterior scalene muscle, or the phrenic nerve.

Conclusions

Our study offers an anatomical basis for the possibility of providing shoulder analgesia and avoiding a PNP.
The sarcoplasmic reticulum and SERCA: a nexus for muscular adaptive thermogenesis
Authors: Gamu Daniel , Juracic Emma Sara , Hall Karlee J. , Tupling A. Russell
Published: May 2019

We are currently facing an “obesity epidemic” worldwide. Promoting inefficient metabolism in muscle represents a potential treatment for obesity and its complications. Sarco(endo)plasmic reticulum (SR) Ca2+-ATPase (SERCA) pumps in muscle are responsible for maintaining low cytosolic Ca2+concentration through the ATP-dependent pumping of Ca2+from the cytosol into the SR lumen. SERCA activity has the potential to be a critical regulator of body mass and adiposity given that it is estimated to contribute upwards of 20% of daily energy expenditure. More interestingly, this fraction can be modified physiologically in the face of stressors, such as ambient temperature and diet, through its physical interaction with several regulators known to inhibit Ca2+uptake and muscle function. In this review, we discuss advances in our understanding of Ca2+-cycling thermogenesis within skeletal muscle, focusing on SERCA and its protein regulators, which were thought previously to only modulate muscular contractility.

Novelty ATP consumption by SERCA pumps comprises a large proportion of resting energy expenditure in muscle and is dynamically regulated through interactions with small SERCA regulatory proteins. SERCA efficiency correlates significantly with resting metabolism, such that individuals with a higher resting metabolic rate have less energetically efficient SERCA Ca2+pumping in muscle (i.e., lower coupling ratio). Futile Ca2+cycling is a versatile heat generating mechanism utilized by both skeletal muscle and beige fat.
Estimating population abundance at a site in the open ocean: combining information from conventional and telemetry tags with application to gray triggerfish (Balistes capriscus)
Authors: Shertzer Kyle W. , Bacheler Nathan M. , Pine William E. , Runde Brendan J. , Buckel Jeffrey A. , Rudershausen Paul J. , MacMahan Jamie H.
Published: May 2019

Estimates of animal abundance are widely used to support conservation and resource management. For populations in open systems, abundance estimates from tagging data can be highly uncertain or biased. Here, we develop a novel approach to estimate abundance of an open population by pairing two models, each utilizing distinct tagging data. Using data from telemetry tags, we infer movement rates to and from the study site with a Markovian model allowing for an environmental effect. Then, using data from conventional passive tags, we apply a Lincoln–Petersen abundance estimator modified to account for mortality and movement. After developing the model within a Bayesian framework, we demonstrate its application to data on gray triggerfish (Balistes capriscus) tagged in the Atlantic Ocean off North Carolina, USA. For this open population, we estimate site abundance to be ∼1000 fish (∼2000 fish·km–2) and additionally find evidence for an effect of hurricanes on movement. The general approach may be useful for fisheries, wildlife, and other ecological studies utilizing multiple tag types, particularly for estimating abundance of an open population.
Genome-wide computational prediction and experimental validation of quinoa (Chenopodium quinoa) microRNAs
Authors: Sharma Ashutosh , Bejerano Paola Isabel Angulo , Maldonado Irais Castillo , de Donato Capote Marcos , Madariaga-Navarrete Alfredo , Paul Sujay
Published: May 2019

MicroRNAs (miRNAs) are highly conserved, endogenous, short (21–24 nucleotides), non-coding RNA molecules that play significant roles in post-transcriptional gene silencing by directing target mRNA cleavage or translational inhibition. Nonetheless, highly nutritious “super grain” quinoa (Chenopodium quinoa) is an extreme abiotic stress tolerant Andean seed crop of many potential uses, with outstanding protein quality and a load of vitamins, minerals, as well as flavonoid antioxidants. In this study, applying genome-wide in silico approaches (referring to the recently published quinoa genome) and following a set of stringent filtering measures, a total of 22 potentially conserved microRNAs belonging to 18 families were characterized from quinoa and 11 randomly selected putative microRNAs (cqu-miR160a, cqu-miR162a, cqu-miR164a, cqu-miR166b, cqu-miR167a, cqu-miR172a, cqu-miR319a, cqu-miR390a, cqu-miR393a, cqu-miR394a, and cqu-miR398b) were validated successfully by RT-PCR. Using the psRNATarget tool, a sum of 59 potential miRNA targets, mostly transcription factors, were identified that are involved in biosynthesis, metabolic processes, and signal transduction. Among the detected targets, six target transcripts (F-Box proteins, TCP, MYB, WD protein, NAC, and CSD) were reported to have specific roles in both flavonoids biosynthesis and stress response signaling in some plants. To the best of our knowledge, this is the first report of quinoa microRNAs and their targets.
Walking velocity and modified rivermead mobility index as discriminatory measures for functional ambulation classification of chronic stroke patients
Authors: Lim Ji Young , An Seung Heon , Park Dae-Sung
Published: May 2019

Background: The cut-off values of walking velocity and classification of functional mobility both have a role in clinical settings for assessing the walking function of stroke patients and setting rehabilitation goals and treatment plans.

Objective: The present study investigated whether the cut-off values of the modified Rivermead Mobility Index (mRMI) and walking velocity accurately differentiated the walking ability of stroke patients according to the modified Functional Ambulation Category (mFAC).

Methods: Eighty two chronic stroke patients were included in the study. The comfortable/maximum walking velocities and mRMI were used to measure the mobility outcomes of these patients. To compare the walking velocities and mRMI scores for each mFAC point, one-way analysis of variance and the post-hoc test using Scheffe’s method were performed. The patients were categorized according to gait ability into either [Formula: see text] or mFAC[Formula: see text][Formula: see text][Formula: see text]VI group. The cut-off values for mRMI and walking velocities were calculated using a receiver-operating characteristic curve. The odds ratios of logistic regression analysis (Wald Forward) were analyzed to examine whether the cut-off values of walking velocity and mRMI can be utilized to differentiate functional walking levels.

Results: Except for mFACs III and IV, maximum walking velocity differed between mFAC IV and mFAC V [Formula: see text], between mFAC V and mFAC VI [Formula: see text], and between mFAC VI and mFAC VII [Formula: see text]. The cut-off value of mRMI is [Formula: see text] and the area under the curve is 0.87, respectively; the cut-off value for comfortable walking velocity is [Formula: see text][Formula: see text]m/s and the area under the curve is 0.92, respectively; also, the cut-off value for maximum walking velocity is [Formula: see text][Formula: see text]m/s and the area under the curve is 0.97, respectively. In the logistic regression analysis, the maximum walking velocity [Formula: see text][Formula: see text]m/s, [Formula: see text] and mRMI [Formula: see text] scores, [Formula: see text] are able to distinguish [Formula: see text] from mFAC[Formula: see text][Formula: see text][Formula: see text]VI.

Conclusion: The cut-off values of maximum walking velocity and mRMI are recommended as useful outcome measures for assessing ambulation levels in chronic stroke patients during rehabilitation.
The Huxley crossbridge model as the basic mechanism for airway smooth muscle contraction
Authors: Luo Ling , Wang Lu , Paré Peter D. , Seow Chun Y. , Chitano Pasquale
Published: May 2019

The cyclic interaction between myosin crossbridges and actin filaments underlies smooth muscle contraction. Phosphorylation of the 20-kDa myosin light chain (MLC20) is a crucial step in activating the crossbridge cycle. Our current understanding of smooth muscle contraction is based on observed correlations among MLC20 phosphorylation, maximal shortening velocity ( Vmax), and isometric force over the time course of contraction. However, during contraction there are changes in the extent of phosphorylation of many additional proteins as well as changes in activation of enzymes associated with the signaling pathways. As a consequence, the mechanical manifestation of muscle contraction is likely to change with time. To simplify the study of these relationships, we measured the mechanical properties of airway smooth muscle at different levels of MLC20 phosphorylation at a fixed time during contraction. A simple correlation emerged when time-dependent variables were fixed. MLC20 phosphorylation was found to be directly and linearly correlated with the active stress, stiffness, and power of the muscle; the observed weak dependence of Vmax on MLC20 phosphorylation could be explained by the presence of an internal load in the muscle preparation. These results can be entirely explained by the Huxley crossbridge model. We conclude that when the influence of time-dependent events during contraction is held constant, the basic crossbridge mechanism in smooth muscle is the same as that in striated muscle.
Autophagy proteins are required for club cell structure and function in airways
Authors: Malvin Nicole P. , Kern Justin T. , Liu Ta-Chiang , Brody Steven L. , Stappenbeck Thaddeus S.
Published: May 2019

Epithelial cells that line lung airways produce and secrete proteins with important roles in barrier function and host defense. Secretion of airway goblet cells is controlled by autophagy proteins during inflammatory conditions, resulting in accumulation of mucin proteins. We hypothesized that autophagy proteins would also be important in the function of club cells, dominant secretory airway epithelial cells that are dysregulated in chronic lung disease. We found that in the absence of an inflammatory stimulus, mice with club cells deficient for the autophagy protein Atg5 had a markedly diminished expression of secreted host defense proteins secretoglobulin family 1A, member 1 (Scgb1a1) and surfactant proteins A1 and D (Sftpa1 and Sftpd), as well as abnormal club cell morphology. Adult mice with targeted loss of Atg5 also showed diminished levels of host defense proteins in regenerating cells following ablation with naphthalene. A mouse strain with global deficiency of Atg16-like 1 (Atg16l1), an Atg5 binding partner, had a similar loss of host defense proteins and abnormal club cell morphology. Cigarette smoke exposure reduced levels of Scgb1a1 in wild-type mice as expected. Smoke exposure was not required to trigger club cell abnormalities in mice bearing the human ATG16 variant Atg16l1T300A/T300A, which had low Scgb1a1 levels independent of this environmental stress. Evaluation of lung tissues from former smokers with severe chronic obstructive pulmonary disease showed evidence of reduced autophagy and SCGB1A1 expression in club cells. Thus, autophagy proteins are required for the function of club cells, independent of the cellular stress of cigarette smoke, with roles that appear to be distinct from those of other secretory cell types.
Reduced endothelial nitric oxide synthase activation contributes to cardiovascular injury during chronic kidney disease progression
Authors: Amador-Martínez Isabel , Pérez-Villalva Rosalba , Uribe Norma , Cortés-González César , Bobadilla Norma A. , Barrera-Chimal Jonatan
Published: May 2019

Major cardiovascular events are a common complication in patients with chronic kidney disease (CKD). Endothelial dysfunction can contribute to the cardiovascular injury observed in CKD. Here, we used a rat model of acute kidney injury to CKD transition to investigate heart alterations in the pathway activating endothelial nitric oxide synthase (eNOS) and its impact on the cardiac injury observed during CKD progression. Fifty male Wistar rats were subjected to sham surgery ( n = 25) or bilateral renal ischemia-reperfusion (IR-CKD) for 45 min ( n = 25). Rats were studied on a monthly basis up to 5 mo ( n = 5). In another set of sham and IR-CKD rats, l-arginine was administered starting on the third month after renal ischemia. CKD development and cardiac alterations were monitored in all groups. CKD was characterized by a progressive increase in proteinuria and renal dysfunction that was evident after the fifth month of followup. Heart hypertrophy was observed starting on the fourth month after ischemia-reperfusion. There was a significant increase in brain natriuretic peptide levels. In the heart, IR-CKD rats had increased eNOS phosphorylation at threonine 495 and reduced eNOS-heat shock protein-90α interactions. l-Arginine administration prevented the heart alterations observed during CKD and increased eNOS coupling/dimerization and activation. In summary, CKD progression is accompanied by cardiac hypertrophy, fibrosis, oxidative stress, and increased brain natriuretic peptide levels. These alterations were associated with limited eNOS activation in the heart, which may result in reduced nitric oxide bioavailability and contribute to cardiac injury during CKD.
Microstructural integrity of corticospinal and medial lemniscus tracts: insights from diffusion tensor tractography of right-hand amputees
Authors: Peng Huiling , Cirstea Carmen M. , Kaufman Christina L. , Frey Scott H.
Published: May 2019

Reductions in sensory and motor activity following unilateral upper limb amputation during adulthood are associated with widespread, activity-dependent reorganization of the gray matter and white matter through the central nervous system. Likewise, in cases of congenital limb absence there is evidence that limited afferent or efferent activity affects the structural integrity of white matter pathways serving the affected side. Evidence that the structural integrity of mature sensory and motor tracts controlling the lost upper limb exhibits similar activity dependence is, however, sparse and inconsistent. Here we used diffusion tensor tractography to test whether amputation of the dominant right hand during adulthood ( n = 16) alters the microstructural integrity of the major sensory (medial lemniscus, ML) and motor (corticospinal tract, CST) pathways controlling missing hand function. Consistent with prior findings, healthy control subjects ( n = 27) exhibited higher fractional anisotropy (FA), an index of white matter microstructural integrity, within dominant left CST and nondominant right ML. Critically, in contrast to what might be expected if the microstructural organization of these tracts is activity dependent, these asymmetries persisted in amputees. Moreover, we failed to detect any differences in dominant left ML or CST between healthy control subjects and amputees. Our results are consistent with these white matter tracts being robust to changes in activity once mature or that continued use of the residual limb (in a compensatory fashion or with prosthesis) provides stimulation sufficient to maintain tract integrity.

NEW & NOTEWORTHY We report that unilateral hand amputation in adults has no significant effects on the structure of major sensory or motor pathways contralateral to the amputation. Our results are consistent with the organization of these white matter tracts being robust to changes in activity once mature or that continued use of the residual limb (with or without a prosthesis) provides stimulation sufficient to maintain tract integrity.
Infraslow activity as a potential modulator of corticomotor excitability
Authors: de Goede Annika A. , van Putten Michel J. A. M.
Published: May 2019

Fluctuations in cortical excitability are a candidate mechanism involved in the trial-to-trial variation of motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS). We explore whether infraslow EEG activity (<0.1 Hz) modulates corticomotor excitability by evaluating the presence of temporal and phase clustering of TMS-induced MEPs. In addition, we evaluate the dependence of MEP amplitude on the phase of the infraslow activity. Twenty-three subjects were stimulated at an intensity above the resting motor threshold (rMT) and ten at the rMT. We evaluated whether temporal and phase clustering of MEP size and MEP generation were present, using 1,000 surrogates with a similar amplitude or occurrence distribution. To evaluate the MEP amplitude dependence, we used the least-square method to approximate the linear circular data by fitting a sine function. We observed significant temporal clustering at a group level, in all individual subjects stimulated at rMT and in the majority of those stimulated above rMT, suggesting underlying determinism of corticomotor excitability instead of randomly generated fluctuations. The majority of subjects showed significant phase clustering for MEP size and for MEP occurrence, and significant phase clustering was found at the group level. Furthermore, in approximately one-quarter to one-half of the subjects we found a significant correlation and dependence of MEP amplitude on the phase of infraslow activity, respectively. Although other mechanisms very likely contribute as well, our findings seem to suggest that infraslow activity is involved in the variability of cortical excitability and TMS-induced responses.

NEW & NOTEWORTHY Cortical excitability measures are highly variable during transcranial magnetic stimulation. Although ongoing brain oscillations are assumed to modulate excitability, no consistent associations are found for the traditional frequency bands. We focus on the role of infraslow EEG activity, defined as rhythms with frequencies < 0.1 Hz. We provide experimental evidence suggesting that infraslow activity most likely modulates corticomotor excitability and that response variation could be reduced when stimulation is targeted at a specific infraslow phase.
Locomotor kinematics and EMG activity during quadrupedal versus bipedal gait in the Japanese macaque
Authors: Higurashi Yasuo , Maier Marc A. , Nakajima Katsumi , Morita Kazunori , Fujiki Soichiro , Aoi Shinya , Mori Futoshi , Murata Akira , Inase Masahiko
Published: May 2019

Several qualitative features distinguish bipedal from quadrupedal locomotion in mammals. In this study we show quantitative differences between quadrupedal and bipedal gait in the Japanese monkey in terms of gait patterns, trunk/hindlimb kinematics, and electromyographic (EMG) activity, obtained from 3 macaques during treadmill walking. We predicted that as a consequence of an almost upright body axis, bipedal gait would show properties consistent with temporal and spatial optimization countering higher trunk/hindlimb loads and a less stable center of mass (CoM). A comparatively larger step width, an ~9% longer duty cycle, and ~20% increased relative duration of the double-support phase were all in line with such a strategy. Bipedal joint kinematics showed the strongest differences in proximal, and least in distal, hindlimb joint excursions compared with quadrupedal gait. Hindlimb joint coordination (cyclograms) revealed more periods of single-joint rotations during bipedal gait and predominance of proximal joints during single support. The CoM described a symmetrical, quasi-sinusoidal left/right path during bipedal gait, with an alternating shift toward the weight-supporting limb during stance. Trunk/hindlimb EMG activity was nonuniformally increased during bipedal gait, most prominently in proximal antigravity muscles during stance (up to 10-fold). Non-antigravity hindlimb EMG showed altered temporal profiles during liftoff or touchdown. Muscle coactivation was more, but muscle synergies less, frequent during bipedal gait. Together, these results show that behavioral and EMG properties of bipedal vs. quadrupedal gait are quantitatively distinct and suggest that the neural control of bipedal primate locomotion underwent specific adaptations to generate these particular behavioral features to counteract increased load and instability.

NEW & NOTEWORTHY Bipedal locomotion imposes particular biomechanical constraints on motor control. In a within-species comparative study, we investigated joint kinematics and electromyographic characteristics of bipedal vs. quadrupedal treadmill locomotion in Japanese macaques. Because these features represent (to a large extent) emergent properties of the underlying neural control, they provide a comparative, behavioral, and neurophysiological framework for understanding the neural system dedicated to bipedal locomotion in this nonhuman primate, which constitutes a critical animal model for human bipedalism.
Placental Ageing in Adverse Pregnancy Outcomes: Telomere Shortening, Cell Senescence, and Mitochondrial Dysfunction
Authors: Manna Samprikta , McCarthy Cathal , McCarthy Fergus P.
Published: May 2019

Preeclampsia is a multisystemic pregnancy disorder and a major cause of maternal and neonatal morbidity and mortality worldwide. The exact pathophysiology of preeclampsia remains unclear; however, it is speculated that the various pathologies can be attributed to impaired vascular remodelling and elevated oxidative stress within the placenta. Oxidative stress plays a key role in cell ageing, and the persistent presence of elevated oxidative stress precipitates cellular senescence and mitochondrial dysfunction, resulting in premature ageing of the placenta. Premature ageing of the placenta is associated with placental insufficiency, which reduces the functional capacity of this critical organ and leads to abnormal pregnancy outcomes. The changes brought about by oxidative insults are irreversible and often lead to deleterious modifications in macromolecules such as lipids and proteins, DNA mutations, and alteration of mitochondrial functioning and dynamics. In this review, we have summarized the current knowledge of placental ageing in the aetiology of adverse pregnancy outcomes and discussed the hallmarks of ageing which could be potential markers for preeclampsia and fetal growth restriction.
Optimization Method for Twin‐Tunnel Complementary Ventilation Design and Its Energy Saving Effect
Authors: Chai Lunlei , Wang Xing , Han Xingbo , Xia Yongxu , Wang Yongdong , Lei Ping
Published: May 2019

Based on the compensation principle and optimization theory, an energy conservation optimization mode for twin‐tunnels complementary ventilation design was proposed. And, compensation concept utilization in energy conservation of long tunnels ventilation was discussed. The energy consumption for long tunnels can be reduced significantly by remoulding longitudinal ventilation to complementary ventilation of single U‐type mode or normal mode. The short‐term and long‐term ventilation systems of the Qingniling Tunnel, Dabieshan Tunnel, and Lianghekou Tunnel were redesigned using the optimization method, and the new scheme was compared to the original design in terms of ventilation effects, and energy consumption. In redesign, the energy consumption of short‐term ventilation systems decreased 240 kW, 150 kW, and 390 kW, and energy efficiency increased by 40%, 50%, and 68.4%, respectively. In the long term, the numbers of those were 1185 kW, 1185kW, and 540 kW, and 42.5%, 58.09%, and 45%, while the pollutants concentration increased a little. The study can provide a reference for the energy efficient design of ventilation systems in long and extra‐long highway tunnels.
Study on Acoustic Emission Localization of Concrete Using Modified Velocity
Authors: Li Jiapeng , Qin Lei
Published: May 2019

To improve the accuracy of the acoustic emission (AE) source localization, a new 3D AE source localization method was investigated which used a combination of the modified velocity and the 3D localization algorithm based on the exhaustive method. The wave speed has a significant effect on the AE location results. With the increase of distance, the AE signal seriously attenuated due to the anisotropy of concrete, and the measured velocity changed for various distances. The velocity‐distance curves were obtained when employing different water‐cement ratios (W/C) and aggregate sizes. However, the current AE location system adopted constant wave velocity. As a result, the error was tremendous. The accuracy of the localization before and after the modified velocity was compared. The 3D localization results showed that compared with the constant wave velocity, the position deviation of the modified velocity was smaller and the localization results with the modified velocity were more accurate.
Analytical Method Validation of Gamijakyakgamchobuja-Tang (KCHO-1, Mecasin) Preparation
Authors: Wang Tingting , Lee Seongjin , Yang Muhack , Cha Eunhye , Jang Jongwon , Kim Sungchul
Published: May 2019

Previous studies have confirmed that KCHO-1 (Mecasin) was developed to alleviate the symptoms of Amyotrophic Lateral Sclerosis (ALS). And its toxicity test has also been carried out. The aim of this study is confirming the validation and stability of concentration analysis method of the Mecasin preparations using HPLC. As a conclusion, we found that the preparations at the concentrations of 50mg/ml and 200mg/ml in sterilized distilled water were homogeneous and it was stable for 4 hours at room temperature and 7 days refrigerated condition (2~8°C). And this method for analyzing the concentration of the Mecasin preparations has been found to be suitable. This study is helpful to promote development of reliable manufacturing medicine and good researches through definitive quality control of Mecasin as complex herbal medicine, aiming to provide help for the treatment of ALS.
Double-Layered Zirconia Films for Carbon-Based Mesoscopic Perovskite Solar Cells and Photodetectors
Authors: Syrrokostas George , Leftheriotis George , Yannopoulos Spyros N.
Published: May 2019

Carbon-based mesoscopic perovskite solar cells (PSCs) and photodetectors were fabricated with the application of double-layered ZrO2 films, consisting of zirconia nanoparticles and microparticles for the first and the second layer, respectively. This assembly exploits the ability of the zirconia microparticles to scatter and hence diffuse the incident light, causing a more efficient illumination of the perovskite layer. As a result, the photocurrent densities produced by a photodetector and a carbon-based PSC were increased by nearly 35% and 28%, respectively, compared to devices assembled using a conventional single zirconia film. Following the increase in the photocurrent, the responsivity of the photodetector and the power conversion efficiency of the PSC were increased analogously, due to the improved light harvesting efficiency of the perovskite layer. Parameters, such as the total thickness, the roughness, and the crystallinity of the films, were examined. Differences in the grain size and in the crystal planes of the perovskite were observed and evaluated. These results demonstrate that a double-layered ZrO2 film can enhance the efficiency of solar cells and photodetectors, enhancing the prospects for their potential commercialization.
Vibration Characteristic of High‐Voltage Tower Influenced by Adjacent Tunnel Blasting Construction
Authors: Duan Limin , Lin Wenshuai , Lai Jinxing , Zhang Peng , Luo Yanbin
Published: May 2019

The effects of tunnel blast excavation on the adjacent existing high‐voltage tower are comprehensively studied for the Chashan highway tunnel project as a case study. To investigate the effect of blast‐induced vibration from the tunnel on the adjacent existing tower, field tests and numerical simulations method were adopted to study the vibration velocity and vibration frequency of the existing tower. Moreover, the relationship between the transverse distance from the detonation center and the peak velocity is discussed in detail. The results showed that the peak velocity of the measuring point in tower foundation increases with the distance between the detonation center and tower foundation approaches, and the maximum velocity is appearing when detonation center is 0 m. Furthermore, the corresponding energy spectrum distributions of the existing tower under the effect of blast induced by vibration is also analyzed, and the main frequency of vertical vibration is generally higher than that of transverse vibration. On combining the peak velocity with the main frequency and the natural frequency of the tower, the safety evaluation of the blasting area is proposed, and the corresponding control measures of blasting vibration are put forward. A guideline for the blast safety zone is proposed based on vibration velocity, main frequency, and the quantity of explosive.
Spectral/Cepstral Analyses of Phonation in Parkinson’s Disease before and after Voice Treatment: A Preliminary Study
Authors: Alharbi Ghadah G. , Cannito Michael P. , Buder Eugene H. , Awan Shaheen N.
Published: May 2019

Purpose: This article examines cepstral/spectral analyses of sustained /α/ vowels produced by speakers with hypokinetic dysarthria secondary to idiopathic Parkinson’s disease (PD) before and after Lee Silverman Voice Treatment (LSVT®LOUD) and the relationship of these measures with overall voice intensity. Methodology: Nine speakers with PD were examined in a pre-/post-treatment design, with multiple daily audio recordings before and after treatment. Sustained vowels were analyzed for cepstral peak prominence (CPP), CPP standard deviation (CPP SD), low/high spectral ratio (L/H SR), and Cepstral/Spectral Index of Dysphonia (CSID) using the KAYPENTAX computer software. Results: CPP and CPP SD increased significantly and CSID decreased significantly from pre- to post-treatment recordings, with strong effect sizes. Increased CPP indicates increased dominance of harmonics in the spectrum following LSVT. After restricting the frequency cutoff to the region just above the first formant and second formant and below the third formant, L/H SR was observed to decrease significantly following treatment. Correlation analyses demonstrated that CPP was more strongly associated with CSID before treatment than after. Conclusion: In addition to increased vocal intensity following LSVT, speakers with PD exhibited both improved harmonic structure and voice quality as reflected by cepstral/spectral analysis, indicating that there was improved harmonic structure and reduced dysphonia following treatment.
A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Oral Administration of a Heat-Treated Lactobacillus paracasei  Supplement in Infants with Atopic Dermatitis Receiving Topical Corticosteroid Therapy
Authors: Yan Dah-Chin , Hung Chih-Hsing , Sy Leticia B. , Lue Ko-Huang , Shih I-Hsin , Yang Chin-Yi , Chen Li-Chen , Sun Hai-Lun , Lee Min-Sheng , Chambard Julie , Tanguy Jérôme , Hughes-Formella Betsy , Nutten Sophie , Blanchard Carine
Published: May 2019

Background/Aims: Atopic dermatitis (AD) is a common disease in infancy, for which topical steroids are the first-line therapy but have side effects. Innovative approaches are needed to reduce the burden of AD and corticosteroid usage in infants. Methods: The once-daily consumption of heat-treated probiotic Lactobacillus paracasei GM-080 or placebo for 16 weeks as supplementary approach to topical treatment with fluticasone propionate cream was compared in AD infants aged 4–30 months. Outcomes were SCORAD and its subscores, TEWL, Infants’ Dermatitis Quality of Life Index (IDQOL), corticoid “sparing effect,” CCL17/TARC, and IgE status. Results: SCORAD, objective SCORAD, itching, and IDQOL decreased significantly (p < 0.001) over the treatment period in both treatment groups. Slight decreases (ns) were noted in TEWL in lesional and unaffected skin and CCL17 levels. There were no differences between the treatment groups. Total IgE increased over the treatment period in both groups, with significantly higher increase in the heat-treated probiotic group (p = 0.038). There was no evidence of a corticoid “sparing effect” by the probiotic. Conclusions: In this design, the probiotic L. paracasei was not beneficial as a complementary approach to topical corticosteroids in infants with AD. However, slight beneficial effects may have been masked by the moderate potency corticoid.
A High Neutrophil-to-Lymphocyte Ratio Is Associated with Recovery from Ramsay Hunt Syndrome
Authors: Soh Yunsoo , Lee Jong Ha , Jung Junyang , Dong Sung Hwa , Byun Jae Yong , Park Moon Suh , Kim Sang Hoon , Yeo Seung Geun
Published: May 2019

Background: Prediction of the severity and outcomes of Ramsay Hunt syndrome (RHS) is difficult. Objectives: The aim of this study was to evaluate the predictive power of the neutrophil-to-lymphocyte ratio (NLR) for the severity and outcomes of RHS. Material and Methods: From 2007 to 2017, a retrospective study of 102 hospitalized patients with RHS was conducted. The degree of paralysis was assessed by determining the House-Brackmann (H-B) grade. Obesity, hypertension, and diabetes mellitus were assessed, and the blood NLR and platelet-to-lymphocyte ratio were determined. The patients received steroids and antivirals, and were followed in the outpatient department at 1, 4, 12, and 24 weeks. Results: The H-B grade of the high-NLR group was significantly higher than that of the normal-NLR group (p = 0.039), and the probability of complete recovery was significantly lower in the high-NLR group (p = 0.048). Conclusions: Patients with RHS who have an elevated NLR have poor outcomes in terms of the H-B grade. Therefore, the NLR may be useful for evaluating the prognosis of patients with RHS.
Insulin Receptor and Glucose Transporters in the Mammalian Cochlea
Authors: Huerzeler Nathan , Petkovic Vesna , Sekulic-Jablanovic Marijana , Kucharava Krystsina , Wright Matthew B. , Bodmer Daniel
Published: May 2019

Insulin receptors are expressed on nerve cells in the mammalian brain, but little is known about insulin signaling and the expression of the insulin receptor (IR) and glucose transporters in the cochlea. We performed immunohistochemistry and gene/protein expression analysis to characterize the expression pattern of the IR and glucose transporters in the mouse organ of Corti (OC). We also performed glucose uptake assays to explore the action of insulin and the effects of pioglitazone, an insulin sensitizer, on glucose transport in the OC. Western blots of protein extracts from OCs showed high expression of IR and glucose transporter 3 (GLUT3). Immunohistochemistry demonstrated that the IR is specifically expressed in the supporting cells of the OC. GLUT3 was found in outer and inner hair cells, in the basilar membrane (BM), the stria vascularis (SV), Reissner’s membrane and spiral ganglion neurons (SGN). Glucose transporter 1 (GLUT1) was detected at low levels in the BM, SV and Reissner’s membrane, and showed high expression in the SGN. Fluorescence glucose uptake assays revealed that hair cells take up glucose and that addition of insulin (10 nM or 1 µM) approximately doubled the rate of uptake. Pioglitazone conferred a small but nonsignificant potentiation of glucose uptake at the highest concentration of insulin. Gene expression analysis confirmed expression of IR, GLUT1 and GLUT3 mRNA in the OC. Pioglitazone significantly upregulated IR and GLUT1 mRNA expression, which was further increased by insulin. Together, these data show that insulin-stimulated glucose uptake occurs in the OC and may be associated with upregulation of both the IR and GLUT1.
Frailty Predicts Severe Postoperative Complication after Elective Hepatic Resection
Authors: Okabe Hirohisa , Hayashi Hiromitsu , Higashi Takaaki , Nitta Hidetoshi , Ikuta Yoshiaki , Yusa Toshihiko , Takeyama Hideaki , Ogawa Katsuhiro , Ozaki Nobuyuki , Akahoshi Shinichi , Ogata Kenichi , Osaki Takayuki , Baba Hideo , Takamori Hiroshi
Published: May 2019

Background: Frail patients are likely to suffer from postoperative complication, but this assumption has not been well confirmed. Objectives: This study aims to clarify the importance of frailty in patients undergoing hepatectomy for predicting severe postoperative complications. Method: One hundred and forty-three patients aged >65 years undergoing hepatectomy between 2011 and 2016 were enrolled in this study. The relevance of frailty versus sarcopenia for postoperative outcome was assessed. We defined clinical frailty (CF) as a CF scale >4. Sarcopenia was defined by the total muscle area at the level of the third lumbar vertebra measured on computed tomography. Results: There were 16 patients (11%) with CF and 80 patients (56%) with sarcopenia. CF was associated with high age (p < 0.0001), severe postoperative complications (Clavien-Dindo classification ≥3) (p = 0.0059), and postoperative in-hospital stay (p = 0.0013). On the other hand, sarcopenia was not associated with postoperative outcome. Logistic regression analysis revealed that only CF was an independent predictor of severe postoperative complication (risk ratio of 4.2; p = 0.017). The occurrence of organ/space surgical site infection was significantly higher in the frailty group than in the non-frailty group. Conclusion: CF, but not sarcopenia, is a robust predictor of severe postoperative complications for patients undergoing hepatectomy.
Enarodustat, Conversion and Maintenance Therapy for Anemia in Hemodialysis Patients: A Randomized, Placebo-Controlled Phase 2b Trial Followed by Long-Term Trial
Authors: Akizawa Tadao , Nangaku Masaomi , Yamaguchi Takuhiro , Arai Masanobu , Koretomo Ryosuke , Maeda Kazuo , Miyazawa Yuya , Hirakata Hideki
Published: May 2019

Background: Enarodustat (JTZ-951) is an orally available hypoxia-inducible factor prolyl hydroxylase inhibitor that increases endogenous erythropoietin levels in the treatment of anemia associated with chronic kidney disease (CKD). Objective: A phase 2b study of enarodustat to assess the hemoglobin (Hb) response, safety, and maintenance dosage was conducted in Japanese anemic patients with hemodialysis-dependent CKD. Methods: Subjects receiving a stable dose of an erythropoiesis-stimulating agent were randomized to receive once-daily enarodustat at a dose of 2, 4, or 6 mg or placebo in a double-blind manner for 6 weeks (Period 1) followed by 24-week open treatment with enarodustat, adjusted in the range of 2–8 mg to maintain Hb within a target range (10.0–12.0 g/dL; Period 2). Results: Change in Hb from baseline increased with enarodustat dose in Period 1. In Period 2, the proportion of subjects who maintained their Hb level within the target range at the end of treatment was 65.1%. To maintain Hb levels within the target range over the course of Period 2, approximately 80% of subjects required 2 dose adjustments or fewer. Enarodustat decreased hepcidin and ferritin levels, increased total iron-binding capacity, and was generally well tolerated. Conclusions: Enarodustat corrected and maintained Hb levels in anemic patients with hemodialysis-dependent CKD. Phase 3 studies of enarodustat are currently ongoing.