bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Proton Transport in Gating Current in a Voltage Gated Ion Channel, as Shown by Quantum Calculations
Authors: Kariev Alisher M , Green Michael E
Published: July 2018

Over two-thirds of a century ago, Hodgkin and Huxley proposed the existence of voltage gated ion channels (VGIC) to carry Na+and K+ions across the cell membrane to create the nerve impulse, in response to depolarization of the membrane. The channels have multiple physiological roles, and play a central role in a wide variety of diseases when they malfunction. The first channel structure was found by MacKinnon and coworkers in 1998. Subsequently the structure of a number of VGIC was determined in the open (ion conducting) state. This type of channel consists of four voltage sensing domains (VSD), each formed from four transmembrane (TM) segments, plus a pore domain through which ions move. Understanding the gating mechanism (how the channel opens and closes) requires structures. One TM segment (S4) has an arginine in every third position, with one such segment per domain. It is usually assumed that these arginines are all ionized, and in the resting state are held toward the intracellular side of the membrane by voltage across the membrane. They are assumed to move outward (extracellular direction) when released by depolarization of this voltage, producing a capacitive gating current and opening the channel. We suggest alternate interpretations of the evidence that led to these models. Measured gating current is the total charge displacement of all atoms in the VSD; we propose that the prime, but not sole, contributor is proton motion, not displacement of the charges on the arginines of S4. It is known that the VSD can conduct protons. Quantum calculations on the Kv1.2 potassium channel VSD show how; the key is the amphoteric nature of the arginine side chain, which allows it to transfer a proton; this appears to be the first time the arginine side chain has had its amphoteric character considered. We have calculated one such proton transfer in detail: this proton starts from a tyrosine that can ionize, transferring to the NE of the third arginine on S4; that arginine’s NH then transfers a proton to a glutamate. The backbone remains static. A mutation predicted to affect the proton transfer has been qualitatively confirmed experimentally, from the change in the gating current-voltage curve. The total charge displacement in going from a normal closed potential of −70 mV across the membrane to 0 mV (open), is calculated to be approximately consistent with measured values, although the error limits on the calculation require caution in interpretation.
Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature
Authors: O’Sullivan Mary E. , Poitevin Frédéric , Sierra Raymond G. , Gati Cornelius , Han Dao E. , Rao Yashas , Aksit Fulya , Ciftci Halilibrahim , Corsepius Nicholas , Greenhouse Robert , Hayes Brandon , Hunter Mark S. , Liang Mengling , McGurk Alex , Mbgam Paul , Obrinsky Trevor , Pardo-Avila Fátima , Seaberg Matt , Cheng Alan G. , Ricci Anthony J. , DeMirci Hasan
Published: July 2018

The bacterial 30S ribosomal subunit is a primary antibiotic target. Despite decades of discovery, the mechanisms by which antibiotic binding induces ribosomal dysfunction are not fully understood. Ambient temperature crystallographic techniques allow more biologically relevant investigation of how local antibiotic binding site interactions trigger global subunit rearrangements that perturb protein synthesis. Here, the structural effects of 2-deoxystreptamine (paromomycin and sisomicin), a novel sisomicin derivative, N1-methyl sulfonyl sisomicin (N1MS) and the non-deoxystreptamine (streptomycin) aminoglycosides on the ribosome at ambient and cryogenic temperatures were examined. Comparative studies led to three main observations. First, individual aminoglycoside-ribosome interactions in the decoding center were similar for cryogenic vs ambient temperature structures. Second, analysis of a highly conserved GGAA tetraloop of h45 revealed aminoglycoside-specific conformational changes, which are affected by temperature only for N1MS. We report the h44/h45 interface in varying states, that is, engaged, disengaged and in equilibrium. Thirdly, we observe aminoglycoside-induced effects on 30S domain closure, including a novel intermediary closure state, which is also sensitive to temperature. Analysis of three ambient and five cryogenic crystallography datasets reveal a correlation between h44/h45 engagement and domain closure. These observations illustrate the role of ambient temperature crystallography in identifying dynamic mechanisms of ribosomal dysfunction induced by local drug-binding site interactions. Together these data identify tertiary ribosomal structural changes induced by aminoglycoside binding that provides functional insight and targets for drug design.
First- and second-order contributions to depth perception in anti-correlated random dot stereograms
Authors: Asher Jordi M. , Hibbard Paul B.
Published: July 2018

The binocular energy model of neural responses predicts that depth from binocular disparity might be perceived in the reversed direction when the contrast of dots presented to one eye is reversed. While reversed depth has been found using anti-correlated random-dot stereogram (ACRDS) the findings are inconsistent across studies. The mixed findings may be accounted for by the presence of a gap between the target and surround, or as a result of overlap of dots around the vertical edges of the stimuli. To test this, we assessed whether (1) the gap size (0, 19.2 or 38.4 arc min) (2) the correlation of dots or (3) the border orientation (circular target, or horizontal or vertical edge) affected the perception of depth. Reversed depth from ACRDS (circular no-gap condition) was seen by a minority of participants, but this effect reduced as the gap size increased. Depth was mostly perceived in the correct direction for ACRDS edge stimuli, with the effect increasing with the gap size. The inconsistency across conditions can be accounted for by the relative reliability of first- and second-order depth detection mechanisms, and the coarse spatial resolution of the latter.
Recurrent PD-L1 Structural Rearrangements in Natural Killer/T Cell Lymphoma Patients with Complete Response to PD-1 Blockade Therapy
Authors: Lim Jing-Quan , Tang Tiffany , Cai Qing-qing , Tan Daryl , Nairismägi Maarja-Liisa , Laurensia Yurike , Chia Burton Kuan Hui , Peng Rou-Jun , Iqbal Jabed , Huang Da Chuan , Song Tammy , Pang Wan Lu , Cheah Daryl Ming Zhe , Young Ng Cedric Chuan , Rajasegaran Vikneswari , Hong Huangming , Tse Eric , Mow Benjamin , Cai Qi Chun , Poon Li-Mei , Tan Jing , Grigoropoulos Nicholas Francis , Goh Yeow Tee , Phipps Colin , Rötzschke Olaf , Cheng Chee Leong , Lee Yuh Shan , Loh Yvonne , Tao Miriam , Farid Mohamad , Au-Yeung Rex , Chan Thomas Sau-Yan , Ng Siok-Bian , Kwong Yok-Lam , Hwang William , Chng Wee-Joo , Tousseyn Thomas , Tan Patrick , Teh Bin Tean , Khor Chiea Chuen , Rozen Steve ,   ICGC Blood Cancer T-cell and NK-cell lymphoma group, Bei Jin-Xin , Lin Tongyu , Lim Soon Thye , Ong Choon Kiat
Published: July 2018

This study aims to identify recurrent genetic alterations in relapsed or refractory (RR) natural-killer/T-cell lymphoma (NKTL) patients who have achieved complete response (CR) with programmed cell death 1 (PD-1) blockade therapy. Seven of the eleven patients treated with pembrolizumab achieved CR while the remaining four had progressive disease (PD). Using whole genome sequencing (WGS), we found recurrent clonal structural rearrangements (SR) of the PD-L1 gene in four of the seven (57%) CR patients’ pretreated tumors. These PD-L1 SRs consist of inter-chromosomal translocations, tandem duplication and micro-inversion that disrupted the suppressive function of PD-L1 3’UTR. Interestingly, recurrent JAK3-activating (p.A573V) mutations were also validated in two CR patients’ tumors that did not harbor the PD-L1 SR. Importantly, these mutations were absent in the four PD cases. With immunohistochemistry (IHC), PD-L1 positivity could not discriminate patients who archived CR (range: 6%-100%) from patients who had PD (range: 35%-90%). PD-1 blockade with pembrolizumab is a potent strategy for RR NKTL patients and genomic screening could potentially accompany PD-L1 IHC positivity to better select patients for anti-PD-1 therapy.
Development of an imaging toolbox to assess the therapeutic potential and biodistribution of macrophages in a mouse model of multiple organ dysfunction
Authors: Sharkey Jack , Ressel Lorenzo , Brillant Nathalie , Wilm Bettina , Park B. Kevin , Murray Patricia
Published: July 2018

Cell-based regenerative medicine therapies require robust preclinical safety, efficacy, biodistribution and engraftment data prior to clinical testing. To address these challenges, we have developed an imaging toolbox comprising multi-spectral optoacoustic tomography and ultrasonography, which allows the degree of kidney, liver and cardiac injury and the extent of functional recovery to be assessed non-invasively in a mouse model of multi-organ dysfunction. This toolbox allowed us to determine the therapeutic effects of adoptively transferred M2 macrophages. Using bioluminescence imaging, we could then investigate the association between amelioration and biodistribution. Macrophage therapy improved kidney and liver function to a limited extent, but did not ameliorate histological damage. No improvement in cardiac function was observed. Biodistribution analysis showed that macrophages homed and persisted in the injured kidneys and liver, but did not populate the heart. Our data suggest that the limited improvement observed in kidney and liver function could be mediated by M2 macrophages.
Defining common principles of gene co-expression refines molecular stratification in cancer
Authors: Care Matthew A. , Westhead David R. , Tooze Reuben M.
Published: July 2018

Cancers converge onto shared patterns that arise from constraints placed by the biology of the originating cell lineage and microenvironment on recurrent programs driven by oncogenic events. This structure should be transferable to molecular stratification. We exploit expression data resources and a parsimonious and computationally efficient network analysis method to define consistent expression modules in colon and breast cancer. Comparison between cancer types identifies principles of gene co-expression: cancer hallmarks, functional and structural gene batteries, copy number variation and biology of originating lineage. Mapping outcome data at gene and module level onto these networks generates a detailed interactive resource. Testing the utility of the resulting modules in TCGA data defines specific associations of module expression with mutation state, identifying striking associations such as mast cell gene expression and mutation pattern in breast cancer. These analyses provide evidence for a generalizable framework to enhance molecular stratification in cancer.
The correlated state in balanced neuronal networks
Authors: Baker Cody , Ebsch Christopher , Lampl Ilan , Rosenbaum Robert
Published: July 2018

Understanding the magnitude and structure of inter-neuronal correlations and their relationship to synaptic connectivity structure is an important and difficult problem in computational neuroscience. Early studies show that neuronal network models with excitatory-inhibitory balance naturally create very weak spike train correlations, defining the “asynchronous state.” Later work showed that, under some connectivity structures, balanced networks can produce larger correlations between some neuron pairs, even when the average correlation is very small. All of these previous studies assume that the local network receives feedforward synaptic input from a population of uncorrelated spike trains. We show that when spike trains providing feedforward input are correlated, the downstream recurrent network produces much larger correlations. We provide an in-depth analysis of the resulting “correlated state” in balanced networks and show that, unlike the asynchronous state, it produces a tight excitatory-inhibitory balance consistent with in vivo cortical recordings.
Caspase-mediated cleavage of murine norovirus NS1/2 potentiates apoptosis and is required for persistent infection of intestinal epithelial cells
Authors: Robinson Bridget A. , Van Winkle Jacob A. , McCune Broc T , Peters A. Mack , Nice Timothy J.
Published: July 2018

Human norovirus (HNoV) is the leading cause of acute gastroenteritis and is spread by fecal shedding that can often persist for weeks to months after the resolution of symptoms. Elimination of persistent viral reservoirs has the potential to prevent outbreaks. Similar to HNoV, murine norovirus (MNV) is spread by persistent shedding in the feces and provides a tractable model to study molecular mechanisms of enteric persistence. Previous studies have identified non-structural protein 1 (NS1) from the persistent MNV strain CR6 as critical for persistent infection in intestinal epithelial cells (IECs), but its mechanism of action remains unclear. We now find that the function of CR6 NS1 is regulated by apoptotic caspase cleavage. Following induction of apoptosis in infected cells, caspases cleave the precursor NS1/2 protein, and this cleavage is prevented by mutation of caspase target motifs. These mutations profoundly compromise CR6 infection of IECs and persistence in the intestine. Conversely, NS1/2 cleavage is not required for acute replication in extra-intestinal tissues or in cultured myeloid cells, indicating an IEC-specific role. Intriguingly, we find that caspase cleavage of NS1/2 reciprocally promotes caspase activity, potentiates cell death, and amplifies spread among cultured IEC monolayers. Together, these data indicate that the function of CR6 NS1 is regulated by apoptotic caspases, and suggest that apoptotic cell death enables epithelial spread and persistent shedding.

Author Summary

Human Norovirus infection is highly contagious and the most common cause of acute gastroenteritis. Norovirus can be persistently shed after resolution of symptoms, perpetuating or initiating new outbreaks. Murine norovirus (MNV) is also persistently shed, enabling study of host and viral determinants of norovirus pathogenesis. We previously identified a critical role for MNV non-structural protein 1 (NS1), in persistence. Herein we find that regulation of NS1 by host apoptotic caspases is required for infection of intestinal epithelial cells, but not for extra-intestinal spread. Additionally, we demonstrate that NS1 reciprocally promotes cell death and spread among epithelial cells. These data identify regulation of NS1 by host proteases and suggest that apoptotic death is a determinant of epithelial spread and persistence.
Chromatin conformation analysis of primary patient tissue using a low input Hi-C method
Authors: Díaz Noelia , Kruse Kai , Erdmann Tabea , Staiger Annette M. , Ott German , Lenz Georg , Vaquerizas Juan M.
Published: July 2018

Chromatin conformation constitutes a fundamental level of eukaryotic genome regulation. However, our ability to examine its biological function and role in disease is limited by the large amounts of starting material required to perform current experimental approaches. Here, we present Low-C, a Hi-C method for low amounts of input material. By systematically comparing Hi-C libraries made with decreasing amounts of starting material we show that Low-C is highly reproducible and robust to experimental noise. To demonstrate the suitability of Low-C to analyse rare cell populations, we produce Low-C maps from primary B-cells of a diffuse large B-cell lymphoma patient. We detect a common reciprocal translocation t (3;14) (q27;q32) affecting the BCL6 and IGH loci and abundant local structural variation between the patient and healthy B-cells. The ability to study chromatin conformation in primary tissue will be fundamental to fully understand the molecular pathogenesis of diseases and to eventually guide personalised therapeutic strategies.
Engineered cell-to-cell signalling within growing bacterial cellulose pellicles
Authors: Walker Kenneth T , Goosens Vivianne J , Das Akashaditya , Graham Alicia E , Ellis Tom
Published: July 2018

Bacterial cellulose is a strong and flexible biomaterial produced at high yields by Acetobacter species and has applications in healthcare, biotechnology and electronics. Naturally, bacterial cellulose grows as a large unstructured polymer network around the bacteria that produce it, and tools to enable these bacteria to respond to different locations are required to grow more complex structured materials. Here, we introduce engineered cell-to-cell communication into a bacterial cellulose-producing strain of Komagataeibacter rhaeticus to enable different cells to detect their proximity within growing material and trigger differential gene expression in response. Using synthetic biology tools, we engineer Sender and Receiver strains of K. rhaeticus to produce and respond to the diffusible signalling molecule, acyl-homoserine lactone (AHL). We demonstrate that communication can occur both within and between growing pellicles and use this in a boundary detection experiment, where spliced and joined pellicles sense and reveal their original boundary. This work sets the basis for synthetic cell-to-cell communication within bacterial cellulose and is an important step forward for pattern formation within engineered living materials.
Exploring a solvated dimer of Gefitinib: a quantitative analysis
Authors: Angira Deekshi , Shaik Althaf , Kirubakaran Sivapriya , Thiruvenkatam Vijay
Published: July 2018

Gefitinib or Iressa is an orally administered anilinoquinazoline used in cancer chemotherapy for the treatment of lung and breast cancer. It is reported to exist in two polymorphic forms, a stable form I and a metastable form II. Both of the forms belong to the triclinic P\overline{1} space group. In this work, we report the crystallization of Gefitinib to form a methanol solvate [systematic name: N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine methanol hemisolvate, C22H24ClFN4O3·0.5CH3OH] that was theoretically and experimentally investigated. The unit cell is composed of two independent Gefitinib molecules (A and B) that form a stable molecular complex with methanol in the crystal lattice. To understand the crystal lattice stabilization, a combination of techniques, namely X-ray diffraction, IR spectroscopy, thermogravimetric/differential scanning calorimetry (TG-DSC), Hirshfeld surface analysis and CLP-PIXEL methods were used. The analysis of the crystal structure of this dimer revealed a three-dimensional isostructurality with the already reported form II. The A and B molecules are connected via trifurcated C—H...O and N—H...O hydrogen bonding. In addition, the presence of the methanol molecule stabilizes the crystal structure via C—H...O, N—H...O and C—H...Cl interactions between the two monomers. The IR analysis of the dimer has shown characteristic fingerprint values when compared to the commercial form. The TG-DSC analysis of the solvated dimer is in good agreement with the patent reporting cocrystals of Gefitinib. Finally, theoretical calculations by the CLP-PIXEL method and Hirshfeld surface and two-dimensional (2D) fingerprint plot analysis were carried out in order to quantify the different intermolecular interactions and their energies in the crystal packing.
Organizational citizenship behavior in relation to employees’ intention to stay in Indian organizations
Authors: Shanker Meera
Published: July 2018

Purpose

The purpose of this paper is to find out dimensions of organizational citizenship behavior (OCB) in Indian setting and to further examine the role of OCB that impacts employees’ intention to stay, with a view to draw on the deeper influences it carries on the quality work of the organization.

Design/methodology/approach

Experimental research design was used to find out the causal relationship between these constructs, i.e., dimensions of OCB and intention to stay. Probability sampling method was used to obtain the sample. In total, 475 respondents were approached for data collection. Data were collected using questionnaire method.

Findings

Factor analysis result revealed five factors of OCB, namely: sportsmanship, altruism, courtesy, civic virtue and conscientiousness, having the reliability of 0.93, 0.89, 0.81, 0.82 and 0.69, respectively, single factor of intention to stay having the reliability 0.87. The findings of Pearson’s correlation, regression and structural equation modeling revealed unequivocal influence of OCB over employees’ intention to stay, suggesting a maneuvering capability of OCB with its influence over employees’ intention to stay in their present organizations.

Research limitations/implications

Since this study was conducted in India, to establish the external validity has to be judged carefully. The organizations approached for the study were of the MNC level.

Practical implications

This study is important to understand the citizenship behavior of employees in relation with intention to stay in Indians setting in particular and the world in general. When individual does work, without any expectation, stay with the organization for longer time inculcating, imbibing working culture of the organization which enriches his experiences, utilized in increasing productivity and prosperity of the organizations.

Social implications

Overall, organizations are facing increased competition day by day; employees are expected to stretch themselves to be in the competition. After certain point of time, employees stop extending themselves, resulting in deteriorating the quality, performance and product. Retaining employees along with maintaining the quality becomes an important concern and issue for organizations. Importance of OCB is considered extensively in Industries in this regard.

Originality/value

This is an original research in Indian Setting, much researches are not available finding the relationship between OCB and intention to stay in turn which improves the quality of organizations. This research is valuable for business world, are facing problems of retaining the employees which affects their efficiency, productivity and profitability.
Active fault tolerant control design for stochastic Interval Type-2 Takagi-Sugeno fuzzy model
Authors: Maalej Imen , Ben Halima Abid Donia , Rekik Chokri
Published: July 2018

Purpose

The purpose of this paper is to look at the problem of fault tolerant control (FTC) for discrete time nonlinear system described by Interval Type-2 Takagi–Sugeno (IT2 TS) fuzzy model subjected to stochastic noise and actuator faults.

Design/methodology/approach

An IT2 fuzzy augmented state observer is first developed to estimate simultaneously the system states and the actuator faults since this estimation is required for the design of the FTC control law. Furthermore, based on the information of the states and the faults estimate, an IT2 fuzzy state feedback controller is conceived to compensate for the faults effect and to ensure a good tracking performance between the healthy system and the faulty one. Sufficient conditions for the existence of the IT2 fuzzy controller and the IT2 fuzzy observer are given in terms of linear matrix inequalities which can be solved using a two-step computing procedure.

Findings

The paper opted for simulation results which are applied to the three-tank system. These results are presented to illustrate the effectiveness of the proposed FTC strategy.

Originality/value

In this paper, the problem of active FTC design for noisy and faulty nonlinear system represented by IT2 TS fuzzy model is treated. The developed IT2 fuzzy fault tolerant controller is designed such that it can guarantee the stability of the closed-loop system. Moreover, the proposed controller allows to accommodate for faults, presents a satisfactory state tracking performance and outperforms the traditional type-1 fuzzy fault tolerant controller.
Students’ mobility attitudes and sustainable transport mode choice
Authors: Cattaneo Mattia , Malighetti Paolo , Morlotti Chiara , Paleari Stefano
Published: July 2018

Purpose

This study aims to explore the propensity of university students to use different sustainable transport modes, taking into account individual and specific trip characteristics, as well as students’ psychological traits (i.e. attitudes).

Design/methodology/approach

Using the transport mode preferences of 827 students who responded to a travel survey, a two-step analysis is conducted. The first step examines the effects of individual characteristics, travel experience and origin or destination features on students’ stated preferences (i.e. self-selected values assigned to personal attitudes). The second step analyses students’ travel mode choices, given their intrinsic mobility attitudes.

Findings

The results suggest that informing students about environmental issues increases their propensity to use sustainable mobility, leading to an average decrease in private transport usage of 5.8 per cent. Interestingly, improving the public transport service and promoting sustainable transport mobility have different impacts on individual campus areas. For campuses located in the city centre and in the historical hamlet, improvements in public transport are found to decrease solo driving by 3.3 per cent and 5.3 per cent, respectively. In suburban areas, this value increases to 9.5 per cent.

Originality/value

This work makes two contributions to the literature. First, it focuses on an unexplored setting, namely, that of a multi-campus university, with districts located in three different areas. This is used to explain how students are influenced by their travel experience and the cultural framework in which they are embedded. Second, the two-step analysis leads to a deeper understanding of the differences between attitudes and “intrinsic attitudes”, and their relative influence on the preferred alternative.
Farm to Consumer: Factors Affecting the Organoleptic Characteristics of Coffee. II: Postharvest Processing Factors
Authors: Hameed Ahsan , Hussain Syed Ammar , Ijaz Muhammad Umair , Ullah Samee , Pasha Imran , Suleria Hafiz Ansar Rasul
Published: July 2018

The production and consumption of coffee are increasing despite the roadblocks to its agriculture and global trade. The unique, refreshing, and stimulating final cupping quality of coffee is the only reason for this rising production and consumption. Coffee quality is a multifaceted trait and is inevitably influenced by the way it is successively processed after harvesting. Reportedly, 60% of the quality attributes of coffee are governed by postharvest processing. The current review elaborates and establishes for the first time the relationship between different methods of postharvest processing of coffee and its varying organoleptic and sensory quality attributes. In view of the proven significance of each processing step, this review has been subdivided into three sections, secondary processing, primary processing, and postprocessing variables. Secondary processing addresses the immediate processing steps on the farm after harvest and storage before roasting. The primary processing section adheres specifically to roasting, grinding and brewing/extraction, topics which have been technically addressed more than any others in the literature and by industry. The postprocessing attribute section deals generally with interaction of the consumer with products of different visual appearance. Finally, there are still some bottlenecks which need to be addressed, not only to completely understand the relationship of varying postharvest processing methods with varying in‐cup quality attributes, but also to devise the next generation of coffee processing technologies.
Out‐of‐hospital arrests attending an Australian tertiary paediatric emergency department over 13 years: An observational study
Authors: Day Elisabeth , Hort Jason R
Published: July 2018

Objective

In paediatric cardiopulmonary arrest, International Liaison Committee on Resuscitation (ILCOR) states, ‘there are no simple guidelines to determine when resuscitative efforts become futile’. Considerations to assist this decision‐making include cause of arrest, pre‐existing medical conditions, age, site of arrest, duration of untreated cardiopulmonary arrest, witnessed arrest and presence of shockable rhythm. Outcomes are poor in out‐of‐hospital cardiac arrests (OHCA), particularly for infants. This single‐centre observational study describes the characteristics and outcomes of the subgroup of children presenting to our hospital's ED following OHCA still receiving cardiac compressions, to assist development of guidelines for future resuscitation efforts in our ED, particularly for cessation of cardiopulmonary resuscitation (CPR).

Methods

The ED database was searched for children presenting in cardiopulmonary arrest receiving cardiac compressions. Data were reviewed on pre‐hospital, ED and hospital management and outcome, particularly looking at considerations outlined by ILCOR.

Results

From January 2000 to December 2013, 60 children were identified: median age 1.71 years; 87% arresting at home; 68% with bystander CPR; median CPR duration pre‐hospital 42 min, and in ED 19.5 min; total CPR median 61 min. Fifty patients (83%) died in ED, 10 (17%) were admitted to intensive care but all died within 4 days.

Conclusion

Children presenting to ED still receiving cardiac compressions following OHCA had a universally poor outcome, regardless of age and underlying cause. This implies resuscitative efforts could be discontinued earlier in this subgroup. A national, multicentre study is needed to determine if this finding is reproducible with a larger population.
Food supplementation by an invasive fleshy‐fruited shrub sustains body condition of a native frugivorous bird during winter
Authors: ROJAS Tobias Nicolas , VERGARA‐TABARES David Lautaro , VALDEZ Diego Javier , PONZIO Marina Flavia , PELUC Susana Inés
Published: July 2018

Birds tend to adjust their behavior and physiology to changes in food availability in their environment. Seasonal fluctuation of food resources may act as an energetic challenge, augmenting hypothalamus–pituitary–adrenal axis (HPA axis) activity, leading to an increase in corticosterone concentrations and promoting the metabolism of energy stores. Plant invasions may alter seasonal food fluctuations by providing a food supply during scarce seasons. This could attenuate the energetic challenge, reducing HPA axis activity and the metabolism of reserves. Using a system with seasonal fluctuation in food availability, we tested if fruit supplementation by the invasive fleshy‐fruited Pyracantha angustifolia during the season of native fruit scarcity decreases the consumption of energy stores through activity attenuation of the HPA axis. We measured changes in body condition and circulating corticosterone (CORT) concentration in Turdus chiguanco occurring at sites both invaded and not invaded by P. angustifolia over 3 time periods that correspond to the periods prior to, during and after highest fruit production of the plant. Fruit scarcity in the ecosystem appears as an energetic challenge for T. chiguanco, given that body mass, fat score and residuals of body mass/tarsus length decreased during winter in a site not invaded by the exotic shrub. Conversely, the presence of the invasive plant seemed to attenuate the metabolism of energetic reserves, as we did not record changes in body condition in birds inhabiting the invaded site. Unexpectedly, plasma CORT concentration did not vary between sites or periods. Further evaluation is required to elucidate how enhanced body condition, resulting from the consumption of a fleshy‐fruited invasive plant, affects survivorship and reproductive performance in T. chiguanco.
Effects of maternal stress induced by predator odors during gestation on behavioral and physiological responses of offspring in Brandt's vole (Lasiopodomys brandtii)
Authors: GU Chen , WANG Wenjia , DING Xiaoqian , YANG Shengmei , WANG Aiqin , YIN Baofa , WEI Wanhong
Published: July 2018

Maternal effects play a crucial role in regulating populations of small mammals and anti‐predator behaviors of offspring. The present study investigated the effects of maternal stress induced by exposure to predator odors during gestation on the behavioral and physiological responses of offspring in Brandt's vole (Lasiopodomys brandtii). Effects included changes in growth, behaviors, hormone levels in serum, and fosB/ΔfosB mRNA and FosB/ΔFosB protein expression in the hypothalamus. Our results showed that when pregnant voles were exposed to cat and rabbit urine odors for 18 days (1 h/day), the weight of the female offspring decreased; however, the thymus and ovary indices increased, compared with the control group. Male offspring of voles exposed to cat odor spent more time exploring and foraging, and showed a decrease in corticosterone (CORT) compared with voles in the control group. Both fosB/ΔfosB mRNA and FosB/ΔFosB protein expressions were downregulated in the hypothalamus of male offspring in the cat odor‐exposed group compared to that in offspring in the control group. However, the mRNA levels of fosB/ΔfosB in the hypothalamus of female offspring did not decrease in response to cat urine odor. Our findings suggested that maternal stress induced by predator odors during gestation restrained the growth of female offspring and increased the duration of exploring and foraging behaviors of male offspring by regulating the HPA axis, which, in turn, reduced the sensitivity of offspring to unfamiliar environments and increased their probability of becoming prey.
Bromelain Kinetics and Mechanism on Myofibril from Golden Pomfret (Trachinotus blochii)
Authors: Feng Xiao , Hang Shasha , Zhou Yige , Liu Qin , Yang Hongshun
Published: July 2018

Bromelain was used to tenderize golden pomfrets (Trachinotus blochii). The enzyme kinetic model was , which indicated that the degree of hydrolysis (DH, x) was dependent on hydrolysis time (t), the initial concentration of myofibril (S0) and bromelain (E0). The relationship between the overall hydrolysis rate (v), S0, E0, and t is demonstrated as: . Sample of 0.40% E0/S0 was further used to study the effects of hydrolysis time on the changes of proteins, peptides, free amino acids (FAA), and protein nanostructure. SDS‐PAGE result showed that myosin heavy chain was degraded dramatically from 22.88% before treatment to 12.03% after 2 min bromelain treatment. Meanwhile, bromelain did not exhibit activity towards actin, trypomyosin, myosin light chain, and troponin C. A general increase of amino acids indicated the increased DH and the preferential cleavage sites of bromelain in the descending order of lysine, glutamic acid, glycine, ornithine, methionine sulfoxide, and alanine. Atomic force microscope images showed that the strip‐like structure of myofibril was considerably degraded by bromelain, and the granulation of protein after 20 min indicated possible self‐assembling of protein hydrolysate. Confocal laser scanning microscopy further confirmed the degradation of myofibril proteins and formation of protein aggregates.

Practical Application

Meat of golden pomfrets is tough, thus not idea for fish balls or fish cakes. Tenderization is essential to achieve desired texture and consumer acceptance, especially for this fish meat with intrinsic hard texture. Bromelain can be extracted from pineapple processing waste. Enzymatic kinetics was studied to instruct industry to control the tenderness of the processed fish meat. The microstructural and mechanism study elucidate the process, thus could be applied to improve the quality of the seafood products correspondingly.
Effect of a new self‐care guide package on maternal and neonatal outcomes in gestational diabetes: A randomized control trial
Authors: Kolivand Mitra , Rahimi Mehr Ali , Keramat Afsaneh , Shariati Mohammad , Emamian Mohammad Hassan
Published: July 2018

Background

The aim of this study was to determine the effect of a new self‐care guide package on gestational diabetes mellitus (GDM).

Methods

This randomized clinical trial was conducted on 152 women with GDM. The intervention group was provided with the self‐care guide package and three face‐to‐face educational sessions. The control group received routine clinical services, including physician visits and short training regarding nutrition, blood glucose control, and insulin injections. The primary outcomes were fasting and 2‐h postprandial blood glucose and self‐efficacy measured at the beginning of the study and 1 month after the end of the intervention. Secondary outcomes included Apgar scores, birth weight, type of delivery, and newborn hospitalization. Data were analyzed using t‐tests, as well as Mann–Whitney, Chi‐squared, and linear and logistic regression tests.

Results

The mean (±SD) self‐efficacy score was higher in the intervention than control group (74.4 ± 7.0 vs 36.4 ± 5.2, respectively; P < 0.001). There was no significant difference in mean fasting plasma glucose between the two groups (P = 0.163), but mean 2‐h postprandial plasma glucose was lower in the intervention than control group (105.1 ± 17.6 vs 127.2 ± 20.4 mg/dL, respectively; P < 0.001). There were no significant differences in the weight and age of the neonate at delivery or in the type of delivery between the two groups. However, the newborn hospitalization rate was higher in the control group (P < 0.001).

Conclusion

The use of a self‐care package had a positive effect on maternal self‐efficacy and 2‐h postprandial plasma glucose, Apgar scores, and neonatal hospitalization.
Injury‐based Geographic Access to Trauma Centers
Authors: Wei Ran , Clay Mann N. , Dai Mengtao , Hsia Renee Y.
Published: July 2018

Objective

Previous studies examining access to trauma care use patient residence as a proxy for location and need for services, which could result in a flawed understanding of access to trauma centers. The objective of this study was to examine the geographic access of the U.S. population to trauma centers based on trauma incident locations.

Methods

We conducted a cross‐sectional study using 9‐1‐1 emergency medical services activations associated with traumatic injury from the 2014 National Emergency Medical Services Information System and trauma centers participating in the 2014 American Hospital Association Annual Survey. The measures included the percentage of trauma incidents that could reach a trauma center within 60 minutes by ground ambulance, capacity‐to‐demand ratio for each trauma center, and overall trauma care accessibility ratio for each U.S. zip code.

Results

A total of 92.9% of all trauma incidents could be transported to an existing trauma center within 60 minutes by ground ambulance, and 85.3% could be transported to a Level I or II trauma center within this time frame in the 32 study states. While 94.7% of trauma incidents in the Northeast area could be transported to a Level I or II trauma center within a 60‐minute driving time, the capacity‐to‐demand ratios of trauma centers in this region were low, indicating high utilization of those trauma center resources. By using the accessibility measure, we found that some Midwestern and Southern states had higher amounts of accessible trauma center resources relative to the number of injuries than Northeastern states.

Conclusions

These findings suggest that greater access to trauma care and significant variations can be observed throughout the 32 study states when using trauma incident location rather than patient residence to calculate access to trauma care. The proposed capacity‐to‐demand ratio and accessibility ratio can be applied to many other needs assessments in health care.
Serotonin transporter (5‐HTTLPR) genotypes and trinucleotide repeats of androgen receptor exert a combinatorial effect on hormonal milieu in patients with lifelong premature ejaculation
Authors: Khan H. L. , Bhatti S. , Abbas S. , Khan Y. L. , Gonzalez R. M. M. , Aslamkhan M. , Gonzalez G. R. , Aydin H. H.
Published: July 2018

Premature ejaculation is one of the most common sexual disorders in men due to uncontrolled modulation of spinal reflexes controlled by cortico‐limbic centers in the brain. In this study, we investigate the combinatorial effects of trinucleotide repeats of androgen receptor and allelic variants of the 5‐HTTLPR gene on sex steroids, hypophyseal hormones, sexual performance, and premature ejaculation assessment parameters among evidence‐based lifelong premature ejaculation subjects. A total of 271 outpatients (age 26.6 ± 1.9) consulting for evidence‐based lifelong premature ejaculatory dysfunction were selected in this study. The control group consists of 155 men with normal IELT (>4 min). The study revealed that the subjects who have the highest (≥26) CAG stretches depicted a significantly higher serum oxytocin levels (102.1 pg/ml; n = 126, p < 0.001) compared with the control group (71.2 pg/ml; n = 75, p = <0.001) and patients which have medium (22–25) and short (≤21) CAG stretches (76.63 ng/ml; n = 64, p < 0.001 vs. 77.4 ng/ml; n = 81, p < 0.001). Almost 33 (26.1%) lifelong premature ejaculatory patients had AR variant of longer (≥26) CAG repeats was homozygous for S alleles (SS), 45 (35.7%) was homozygous for L allele (LL), and 48 (38%) had the L/S or S/L genotype of 5‐HTTLPR gene. Homozygous (SS) alleles have a significant positive correlation (r = 0.44, p < 0.0001) with the high score of BDI‐II (39.1, n = 126, p < 0.001). However, LL alleles have shown a significant positive correlation with PEDT (r = 0.46, p < 0.001) and negative correlation with self‐estimated IELT and intercourse satisfaction (r = −0.35, p < 0.001). The innovative study design elaborates that androgen receptor trinucleotide repeats and 5‐HTTLPR genotypes have combinatorial impact on hormonal milieu and sexual function regarding evidence‐based lifelong premature ejaculatory dysfunction patients.
Primary Baerveldt versus trabeculectomy study after one‐year follow‐up
Authors: Islamaj Esma , Wubbels René J. , de Waard Peter W.T.
Published: July 2018

Purpose

To compare a Baerveldt implant and trabeculectomy with respect to intraocular pressure (IOP) and failure rate at 1 year of follow‐up. Secondary outcomes are pharmacological therapy and complications at 1 year of follow‐up.

Methods

This was a randomized, comparative study. A total of 119 glaucoma patients without previous ocular surgery were included at the Rotterdam Eye Hospital, the Netherlands. One eye of each subject was randomized to either a Baerveldt glaucoma drainage device (BGI) or trabeculectomy (TE). Follow‐up visits were conducted at 1 day, 2 weeks, 6 weeks, 3 months, 6 months and 1 year after surgery.

Results

After one year, the final IOP was equivalent for both treatment groups: 14 ± 4 mmHg (mean ± SD) for the Baerveldt group versus 13 ± 4 mmHg for the trabeculectomy group. Statistically, we found no significant difference in failure rate between the two groups. However, the Baerveldt group needed significantly more medication to decrease IOP. Overall, self‐limiting complication rate was similar in both groups. Diplopia, a serious complication, was significantly more present in the BGI group.

Conclusion

One year after surgery, TE shows better results than the BGI. The final IOP, IOP reduction and failure rate are similar, but the need for additional IOP lowering medication in the BGI group is higher as well as the complication rate. The increased risk of developing diplopia after placement of a BGI must be taken into consideration.
Dissecting the neuronal vulnerability underpinning Alpers’ syndrome: a clinical and neuropathological study
Authors: Hayhurst Hannah , Anagnostou Maria‐Eleni , Bogle Helen J. , Grady John P. , Taylor Robert W. , Bindoff Laurence A. , McFarland Robert , Turnbull Doug M. , Lax Nichola Z.
Published: July 2018

Alpers’ syndrome is an early‐onset neurodegenerative disorder often caused by biallelic pathogenic variants in the gene encoding the catalytic subunit of polymerase‐gamma (POLG) which is essential for mitochondrial DNA (mtDNA) replication. Alpers’ syndrome is characterized by intractable epilepsy, developmental regression and liver failure which typically affects children aged 6 months–3 years. Although later onset variants are now recognized, they differ in that they are primarily an epileptic encephalopathy with ataxia. The disorder is progressive, without cure and inevitably leads to death from drug‐resistant status epilepticus, often with concomitant liver failure. Since our understanding of the mechanisms contributing the neurological features in Alpers’ syndrome is rudimentary, we performed a detailed and quantitative neuropathological study on 13 patients with clinically and histologically‐defined Alpers’ syndrome with ages ranging from 2 months to 18 years. Quantitative immunofluorescence showed severe respiratory chain deficiencies involving mitochondrial respiratory chain subunits of complex I and, to a lesser extent, complex IV in inhibitory interneurons and pyramidal neurons in the occipital cortex and in Purkinje cells of the cerebellum. Diminished densities of these neuronal populations were also observed. This study represents the largest cohort of post‐mortem brains from patients with clinically defined Alpers’ syndrome where we provide quantitative evidence of extensive complex I defects affecting interneurons and Purkinje cells for the first time. We believe interneuron and Purkinje cell pathology underpins the clinical development of seizures and ataxia seen in Alpers’ syndrome. This study also further highlights the extensive involvement of GABAergic neurons in mitochondrial disease.
MRI of cortical lesions and its use in studying their role in MS pathogenesis and disease course
Authors: Magliozzi R. , Reynolds R. , Calabrese M.
Published: July 2018

Cortical grey matter (GM) demyelination is present from the earliest stages of multiple sclerosis (MS) and is associated with physical deficits and cognitive impairment. In particular, the rate of disability progression in MS, both in the relapsing and progressive phases, appears to be strictly associated with degenerative GM demyelination and diffuse cortical atrophy. In the last decade, several histopathological studies and advanced radiological methodologies have contributed to better identify the exact involvement/load of cortical pathology in MS, even if the specific inflammatory features and the precise cell and molecular mechanisms of GM demyelination and neurodegeneration in MS remain still not fully understood. It has been proposed that a combined neuropathology, imaging and molecular approach may help to define a more detailed characterization and precise assessment of the heterogeneous features of GM injury and inflammation in MS. This, in turn, will possibly identify specific imaging and biohumoral (cerebrospinal fluid/serum) correlates of cortical pathology that may have an important role in predicting and monitor the disease evolution.