bluuebunny/crossref_metadata_2025 huggingface dataset:
Levels of Silicon in Maternal, Cord, and Newborn Serum and Their Relation With Those of Zinc and Copper
Authors: Díaz‐Gómez N. Marta , Bissé Emmanuel , Senterre Thibault , González‐González Nieves L. , Domenech Eduardo , Lindinger Gabriele , Epting Thomas , Barroso Flora
Published: June 2016

Background:

Evidence of silicon's importance to health has been gradually accumulating. Nevertheless, there are few studies comparing serum silicon levels in newborns with maternal levels. Likewise, little is known concerning the inter‐relation between silicon and other trace elements.

Objective:

The present study evaluated maternal and newborn levels of serum silicon and their relation to those of zinc and copper.

Methods:

We measured serum silicon, copper, and zinc in 66 pregnant women, in the umbilical cord of their infants, and in 44 newborns, by atomic absorption spectrophotometry. All the samples were from fasted subjects.

Results:

Serum silicon level in term newborns (20.6 ± 13.2 μmol/L) was significantly higher than in umbilical cord (8.9 ± 3.5 μmol/L; P < 0.0001). Mean serum silicon level in maternal vein (7.7 ± 3.4 μmol/L) was lower than that in umbilical cord, although differences were not significant. We also found higher levels of zinc (P = 0.008) and lower levels of copper (P < 0.0001) in cord blood compared with maternal blood. Umbilical venous/maternal venous level ratios of zinc, copper, and silicon were 1.5 ± 0.5, 0.2 ± 0.1, and 1.3 ± 0.7, respectively. There was a positive correlation between silicon and zinc levels (r = 0.32), and a negative correlation between copper and zinc levels (r = −0.35).

Conclusions:

It seems that there is a positive gradient of silicon from the mother to her fetus. Silicon levels were higher in newborn than in cord blood, and correlated significantly with that of zinc but not copper. Additional investigations are needed to further define the role of silicon and its interaction with other trace elements during the perinatal period.
Persistent Fatigue in Hematopoietic Stem Cell Transplantation Survivors
Authors: Hacker Eileen Danaher , Fink Anne M. , Peters Tara , Park Chang , Fantuzzi Giamila , Rondelli Damiano
Published: June 2016

Background:

Fatigue is highly prevalent after hematopoietic stem cell transplantation (HCT). It has been described as intense and may last for years following treatment.

Objective:

The aim of this study is to compare fatigue, physical activity, sleep, emotional distress, cognitive function, and biological measures in HCT survivors with persistent fatigue (n = 25) with age- and gender-matched healthy controls with occasional tiredness (n = 25).

Methods:

Data were collected using (a) objective, real-time assessments of physical activity and sleep over 7 days; (b) patient-reported fatigue assessments; (c) computerized objective testing of cognitive functioning; and (d) biological measures. Differences between groups were examined using multivariate analysis of variance.

Results:

Survivors of HCT reported increased physical (P < .001), mental (P < .001), and overall (P < .001) fatigue as well as increased anxiety (P < .05) and depression (P < .01) compared with healthy controls. Red blood cell (RBC) levels were significantly lower in HCT survivors (P < .001). Levels of RBC for both groups, however, were in the normal range. Tumor necrosis factor-α (P < .001) and interleukin-6 (P < .05) levels were significantly higher in HCT survivors.

Conclusions:

Persistent fatigue in HCT survivors compared with healthy controls with occasional tiredness is accompanied by increased anxiety and depression along with decreased RBC counts. Elevated tumor necrosis factor-α and interleukin-6 levels may be important biomarkers.

Implications for Practice:

This study provides preliminary support for the conceptualization of fatigue as existing on a continuum, with tiredness anchoring one end and exhaustion the other. Persistent fatigue experienced by HCT survivors is more severe than the occasional tiredness of everyday life.
Evaluation of Pain Intensity Assessment Tools Among Elderly Patients With Cancer in Taiwan
Authors: Chang Hsien-Chen , Lai Yeur-Hur , Lin Kuan-Chia , Lee Tzu-Ying , Lin Hung-Ru
Published: June 2016

Background:

Effective pain management requires careful assessment of pain. Auditory, visual, cognitive, and motor impairments in elderly people may affect their ability to use pain assessment tools.

Objective:

The aim of this study was to evaluate the reliability, validity, and no-response rate of pain scales among elderly patients with cancer pain, as well as patient preference for the scales.

Methods:

A cross-sectional correlational design was used with a convenience sample of 73 elderly cancer patients recruited at a cancer-based hospital in southern Taiwan. Participants were asked to rate their pain by using a numeric rating scale (NRS-11), a facial pain scale (FPS), a verbal descriptor scale (VDS), and a mixed scale (consisting of NRS-11, FPS, and VDS) on 2 consecutive days.

Results:

Test-retest reliability, as indicated by Spearman rank correlation coefficients for the 24-hour interval pain ratings, ranged from 0.426 to 0.683. The criterion-related validity of the scales was supported by significant Spearman rank-order correlation. The time taken to respond to the scales ranged from 40.3 to 16.2 seconds. The no-response rates for the scales decreased in the order NRS-11 > FPS > mixed scale > VDS. Patient preference for the scales decreased in the order mixed scale > VDS > NRS-11 > FPS.

Conclusions:

All 4 scales were reliable and valid for assessing cancer pain among elderly patients.

Implications for Practice:

Because the no-response rates for the scales depended on educational level and cognitive function, nurses should exercise good judgment in choosing pain intensity assessment tools for use with elderly patients.
Application of Microbeam X-Ray Fluorescence Spectrometry in the Diagnosis of Suspected Electrocution by High-Voltage Direct Current
Authors: Wang Tao , Zou Donghua , Zhang Jianhua , Chen Yijiu
Published: June 2016

Electrocution cases reported in the literature were mainly caused by low-voltage alternating current, with few cases associated with high-voltage direct current. In this article, we report the case of a 48-year-old woman who unexpectedly and suddenly died in the wild because of electric shock by a high-voltage direct current while hunting. The postmortem inspection found a suspected current mark on her right upper thigh, and histological examination of the suspected current mark revealed a slight elongation of the epidermal cell nuclei and separation of the corneous layer. Metal elements analysis by microbeam x-ray fluorescence spectrometry demonstrated a peak concentration of iron in the suspected current-injured skin surface, which was in line with the metal wire at the scene. In addition, the deceased had coronary atherosclerotic heart disease, which can increase the body's risk to the current damage. Our results indicated the usefulness of microbeam x-ray fluorescence spectrometry for the forensic diagnosis of electrocution.
Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Non–Small-cell Lung Cancer
Authors: Roach Charlotte , Zhang Nancy , Corigliano Ellie , Jansson Malinka , Toland Grant , Ponto Gary , Dolled-Filhart Marisa , Emancipator Kenneth , Stanforth Dave , Kulangara Karina
Published: June 2016

A companion diagnostic assay was codeveloped by Dako for pembrolizumab non–small-cell lung cancer clinical trials to detect PD-L1 expression by immunohistochemistry (IHC). This automated IHC assay has been analytically verified and validated using Dako’s autostainer Link 48 and 22C3 mouse anti-PD-L1 monoclonal antibody to detect the PD-L1 expression in formalin-fixed paraffin-embedded human tumor tissue specimens. The PD-L1 22C3 IHC assay was optimized for high sensitivity and specificity. Repeatability and reproducibility studies were conducted at Dako and at 3 Clinical Laboratory Improvement Amendments certified laboratories during assay development. The studies included: intersite and intrasite, interobserver and intraobserver, interinstrument, interoperator, interday, and interlot, and intraday and intrarun. All precision studies performed at Dako and external laboratories achieved >85% point-estimate agreements for all 3 agreement types (negative, positive, and overall). A clinical cutoff (tumor proportion score ≥50%) of PD-L1 expression was determined and evaluated through a phase 1 clinical trial (KEYNOTE-001) for advanced non–small-cell lung cancer patients treated with pembrolizumab. The treatment effect of pembrolizumab in the 61 subjects who had a tumor PD-L1 of tumor proportion score ≥50% was substantial, with an overall response rate of 41% (95% confidence interval, 28.6-54.3) as compared with 20.6% (95% confidence interval, 15.5-26.5) observed in the 223 subjects irrespective of PD-L1 status. PD-L1 IHC 22C3 pharmDx is a sensitive, precise, and robust companion diagnostic assay, which will facilitate safe and effective use for pembrolizumab in cancer patients.
The Effects of Pediatric Advanced Life Support Guidelines on Pediatric Trauma Airway Management
Authors: Sperka Jana , Hanson Sheila J. , Hoffmann Raymond G. , Dasgupta Mahua , Meyer Michael T.
Published: June 2016

Objective

Recent Pediatric Advanced Life Support (PALS) guidelines have deemphasized the use of advanced airways in short transport. It is unclear if guideline recommendations have altered practice. We sought to determine if a temporal change exists in the number of prehospital pediatric trauma intubations since the 2005 PALS guidelines update.

Methods

This is an institutional review board–approved, retrospective, single-center study. Reviewed all pediatric trauma activations where patients younger than 19 years were intubated at the scene, en route or at the level 1 trauma center during 2006 to 2011. Specific complications collected were esophageal intubations, mainstem intubations and need for re-intubations.

Results

There were 1012 trauma activations, 1009 pediatric patients, 300 (29.7%) intubated during transport to Children's Hospital of Wisconsin Pediatric Trauma Center (PTC) or upon arrival. Mean age of 9.5 ± 5.9 years. Fifty-seven percent (n = 172) were intubated before PTC, 31.7% (n = 95) field intubations, 25.7% (n = 77) outside facility intubations. 44% (n = 132) at PTC. Age was not a significant variable. There was no difference in the proportion of injured children requiring intubation who were intubated before arrival to the PTC. Those intubated in the field versus a facility had significantly increased mortality (P = 0.0002), longer hospital days (P = 0.0004) including intensive care unit days (P = 0.0003) and ventilator days (P = 0.0003) even when adjusted for illness severity.

Conclusions

There was no significant change in the proportion of pretrauma room intubations following the 2005 PALS guidelines even when adjusted for illness or injury severity. Children injured farther from the PTC and more severely injured children were more likely to be intubated before arrival at the PTC.
Importance of Clinical Decision Making by Experienced Pediatric Surgeons When Children Are Suspected of Having Acute Appendicitis
Authors: Bal Alkan , Anil Murat , Nartürk Müge , Özdemir Tunç , Arikan Ahmet , Köylüoğlu Gökhan , Polat Burak , Erdoğan Nuri , Bayol Umit , Özgüzer Alp , Çolak Ayfer
Published: June 2016

Objective

The aim of the present study was to compare the pediatric appendicitis score (PAS), the Alvarado score (AS), white blood cell count (WBC), absolute neutrophil count (ANC), C-reactive protein (CRP) level, procalcitonin level, and ultrasound (US) data, with the appendectomy decisions of pediatric surgeons diagnosing acute appendicitis (AA) in a real-life setting; this was a top-level, high-volume pediatric emergency department (PED) in a developing country.

Methods

The study was conducted prospectively between January 2012 and June 2013 in the PED of the Tepecik Teaching and Research Hospital in Izmir, Turkey. The study was observational in nature; no attempt was made to influence indications for exploration or the timing thereof. Children aged 4 to 18 years presenting to the PED on suspicion of AA were included. The WBC, ANC, CRP level, and procalcitonin level were measured, and US was performed on all patients on admission. The PAS and AS were calculated. An operative decision was made by each pediatric surgeon who had the results of laboratory and radiological tests. The criterion standard for AA was histopathological assessment.

Results

Upon receiver operating curve (ROC) analysis, the areas under the ROCs (AUROCs) of the WBC, ANC, CRP level, procalcitonin level, US positivity, PAS, AS, and decisions of pediatric surgeons supported by laboratory and US data were 0.734, 0.741, 0.671, 0.675, 0.670, 0.831, 0.794, and 0.910, respectively. When US data were employed only in cases with PASs 4 to 7, the sensitivity increased but specificity decreased. The sensitivity and specificity of pediatric surgical decisions were 100% and 82.50%, respectively. The difference between the PAS AUROC and the pediatric surgeon decision-making AUROC was significant (P = 0.0393; 95% confidence interval, 0.0470–0.226).

Conclusions

Good pediatric surgical decision making supported by laboratory and US data for those suspected of AA may be the most effective diagnostic tool in a high-volume PED in a developing country.
Identification of Inpatient Falls Using Automated Review of Text-Based Medical Records
Authors: Shiner Brian , Neily Julia , Mills Peter D. , Watts Bradley V.
Published: June 2016

Objectives

Although falls are among the most common adverse event in hospitals, they are difficult to measure and often unreported. Mechanisms to track falls include incident reporting and medical records review. Because of limitations of each method, researchers suggest multimodal approaches. Although incident reporting is commonly used, medical records review is limited by the need to read a high volume of clinical notes. Natural language processing (NLP) is 1 potential mechanism to automate this process.

Method

We compared automated NLP to manual chart review and incident reporting as a method to detect falls among inpatients. First, we developed an NLP algorithm to identify inpatient progress notes describing falls. Second, we compared the NLP algorithm to manual records review in identifying inpatient progress notes that describe falls. Third, we compared the NLP algorithm to the incident reporting system in identifying falls.

Results

When examining individual inpatient notes, our NLP algorithm was highly specific (0.97) but had low sensitivity (0.44) when compared with our manual records review. However, when considering groups of inpatient notes, all describing the same fall, our NLP algorithm had a large improvement in sensitivity (0.80) with some loss of specificity (0.65) compared with incident reporting.

Conclusions

National language processing represents a promising method to automate review of inpatient medical records to identify falls.
Employing Demand-Based Volumetric Forecasting to Identify Potential for and Roles of Devices in Scale-Up of Medical Male Circumcision in Zambia and Zimbabwe
Authors: Fram Francine , Church Fred , Sundaram Maaya , Sgaier Sema K. , Ridzon Renee , Eletskaya Maria , Nanga Alice , Gumede-Moyo Sehlulekile , Tambatamba Bushimbwa , Mugurungi Owen , Ncube Getrude , Xabayu Sinokuthemba , Odawo Patrick , Kretschmer Steve
Published: June 2016

Introduction:

Devices for male circumcision (MC) are becoming available in 14 priority countries where MC is being implemented for HIV prevention. Understanding potential impact on demand for services is one important programmatic consideration because countries determine whether to scale up devices within MC programs.

Methods:

A population-based survey measuring willingness to undergo MC, assuming availability of surgical MC and 3 devices, was conducted among 1250 uncircumcised men, ages 10–49 years in Zambia and 1000 uncircumcised men, ages 13–49 years in Zimbabwe. Simulated Test Market methodology was used to estimate incremental MC demand and the extent to which devices might be preferred over surgery, assuming availability of: surgical MC in both countries; the devices PrePex, ShangRing, and Unicirc in Zambia; and PrePex in Zimbabwe.

Results:

Modeled estimates indicate PrePex has the potential to provide an overall increase in MC demand ranging from an estimated 13%–50%, depending on country and WHO prequalification ages, replacing 11%–41% of surgical procedures. In Zambia, ShangRing could provide 8% overall increase, replacing 45% of surgical procedures, and Unicirc could provide 30% overall increase, replacing 85% of surgical procedures.

Conclusions:

In both countries, devices have potential to increase overall demand for MC, assuming wide scale awareness and availability of circumcision by the devices. With consideration for age and country, PrePex may provide the greatest potential increase in demand, followed by Unicirc (measured in Zambia only) and ShangRing (also Zambia only). These results inform one program dimension for decision making on potential device introduction strategies; however, they must be considered within the broader programmatic context.
Mortality in the First 3 Months on Antiretroviral Therapy Among HIV-Positive Adults in Low- and Middle-income Countries: A Meta-analysis
Authors: Brennan Alana T. , Long Lawrence , Useem Johanna , Garrison Lindsey , Fox Matthew P.
Published: June 2016

Previous meta-analyses reported mortality estimates of 12-month post-antiretroviral therapy (ART) initiation; however, 40%–60% of deaths occur in the first 3 months on ART, a more sensitive measure of averted deaths through early ART initiation. To determine whether early mortality is dropping as treatment thresholds have increased, we reviewed studies of 3 months on ART initiation in low- to middle-income countries. Studies of 3-month mortality from January 2003 to April 2016 were searched in 5 databases. Articles were included that reported 3-month mortality from a low- to middle-income country; nontrial setting and participants were ≥15. We assessed overall mortality and stratified by year using random effects models. Among 58 included studies, although not significant, pooled estimates show a decline in mortality when comparing studies whose enrollment of patients ended before 2010 (7.0%; 95% CI: 6.0 to 8.0) with the studies during or after 2010 (4.0%; 95% CI: 3.0 to 5.0). To continue to reduce early HIV-related mortality at the population level, intensified efforts to increase demand for ART through active testing and facilitated referral should be a priority. Continued financial investments by multinational partners and the implementation of creative interventions to mitigate multidimensional complex barriers of accessing care and treatment for HIV are needed.
HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission
Authors: Samuel Reshmi , Julian Marc Noguera , Paredes Roger , Parboosing Raveen , Moodley Pravi , Singh Lavanya , Naidoo Anneta , Gordon Michelle
Published: June 2016

Antiretroviral drug resistance following pMTCT strategies remains a significant problem. With rapid advancements in next generation sequencing technologies, there is more focus on HIV drug-resistant variants of low frequency, or the so-called minority variants. In South Africa, AZT monotherapy for pMTCT, similar to World Health Organization option A, has been used since 2008. In 2010, a single dose of co-formulated TDF/FTC was included in the strategy for prevention of resistance conferred by single-dose nevirapine (sd NVP). The study was conducted in KwaZulu-Natal, South Africa, among pMTCT participants who received AZT monotherapy from 14 weeks of gestation, intrapartum AZT and sd NVP, and postpartum sd TDF/FTC. Twenty-six specimens collected at 6 weeks post-delivery were successfully sequenced using 454 ultra-deep sequencing. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was detected in 17 of 26 (65%) patients, 2 (7%) had Thymidine analogue mutations, and 3 (11%) had K65R. Of the 17 patients with NNRTI resistance, 11 (65%) had high-level NNRTI resistance, whereas 6 (35%) had intermediate NNRTI resistance. The levels of NNRTI resistance are much higher than would be expected, given the inclusion of antepartum AZT and postpartum TDF/FTC. This high level of NNRTI resistance could impact future NNRTI-containing treatment for a large proportion of pMTCT-exposed women. The detection of Thymidine analogue mutations highlights the need to understand the clinical impact of these on AZT-containing antiretroviral treatment in women exposed to AZT monotherapy.
Olfactory Fossa Meningioma Presenting as Depressive Disorder: A Case Report
Authors: Pranckeviciene Aiste , Bunevicius Adomas , Deltuva Vytenis Pranas , Tamasauskas Arimantas
Published: June 2016

Meningiomas are common, usually benign intracranial tumors. They grow slowly and can remain asymptomatic for many years. Meningiomas can present as mental disorders rather than with neurologic signs or symptoms. In this case report we describe a middle-aged man with a 2-year history of depressive disorder who was diagnosed with a large olfactory fossa meningioma after he developed mental status changes and urinary incontinence. After the tumor was removed, the patient’s depressive symptoms resolved and his neurocognitive functions improved. We discuss the patient’s neuropsychological and psychiatric profiles to identify symptoms and other clues that could expedite identification of meningiomas in patients with psychiatric disorders. Because olfactory fossa meningiomas can present as depressive disorder, we recommend brain imaging to rule out organic brain lesions in middle-aged and older patients with new-onset psychiatric symptoms. Although tumor removal brought improvement of our patient’s mental state and neurocognitive functions, patients may not be able to recover their cognitive functions completely.
Thermally induced osteocyte damage initiates pro-osteoclastogenic gene expression
in vivo
Authors: Dolan Eimear B. , Tallon David , Cheung Wing-Yee , Schaffler Mitchell B. , Kennedy Oran D. , McNamara Laoise M.
Published: June 2016

Bone is often subject to harsh temperatures during orthopaedic procedures resulting in thermally induced bone damage, which may affect the healing response. Postsurgical healing of bone is essential to the success of surgery, therefore, an understanding of the thermally induced responses of bone cells to clinically relevant temperatures
in vivo
is required. Osteocytes have been shown to be integrally involved in the bone remodelling cascade, via apoptosis, in micro-damage systems. However, it is unknown whether this relationship is similar following thermal damage. Sprague–Dawley rat tibia were exposed to clinically relevant temperatures (47°C or 60°C) to investigate the role of osteocytes in modulating remodelling related factors. Immunohistochemistry was used to quantify osteocyte thermal damage (activated caspase-3). Thermally induced pro-osteoclastogenic genes (
Rankl
,
Opg
and
M-csf
), in addition to genes known to mediate osteoblast and osteoclast differentiation via prostaglandin production (
Cox2
), vascularization (
Vegf
) and inflammatory (
Il1a
) responses, were investigated using gene expression analysis. The results demonstrate that heat-treatment induced significant bone tissue and cellular damage. Pro-osteoclastogenic genes were upregulated depending on the amount of temperature elevation compared with the control. Taken together, the results of this study demonstrate the
in vivo
effect of thermally induced osteocyte damage on the gene expression profile.
Direct synthesis of hydrogen peroxide in water at ambient temperature
Authors: Crole David A. , Freakley Simon J. , Edwards Jennifer K. , Hutchings Graham J.
Published: June 2016

The direct synthesis of hydrogen peroxide (H
2
O
2
) from hydrogen and oxygen has been studied using an Au–Pd/TiO
2
catalyst. The aim of this study is to understand the balance of synthesis and sequential degradation reactions using an aqueous, stabilizer-free solvent at ambient temperature. The effects of the reaction conditions on the productivity of H
2
O
2
formation and the undesirable hydrogenation and decomposition reactions are investigated. Reaction temperature, solvent composition and reaction time have been studied and indicate that when using water as the solvent the H
2
O
2
decomposition reaction is the predominant degradation pathway, which provides new challenges for catalyst design, which has previously focused on minimizing the subsequent hydrogenation reaction. This is of importance for the application of this catalytic approach for water purification.
Addicted? Reduced host resistance in populations with defensive symbionts
Authors: Martinez Julien , Cogni Rodrigo , Cao Chuan , Smith Sophie , Illingworth Christopher J. R. , Jiggins Francis M.
Published: June 2016

Heritable symbionts that protect their hosts from pathogens have been described in a wide range of insect species. By reducing the incidence or severity of infection, these symbionts have the potential to reduce the strength of selection on genes in the insect genome that increase resistance. Therefore, the presence of such symbionts may slow down the evolution of resistance. Here we investigated this idea by exposing
Drosophila melanogaster
populations to infection with the pathogenic
Drosophila
C virus (DCV) in the presence or absence of
Wolbachia
, a heritable symbiont of arthropods that confers protection against viruses. After nine generations of selection, we found that resistance to DCV had increased in all populations. However, in the presence of
Wolbachia
the resistant allele of
pastrel
—a gene that has a major effect on resistance to DCV—was at a lower frequency than in the symbiont-free populations. This finding suggests that defensive symbionts have the potential to hamper the evolution of insect resistance genes, potentially leading to a state of evolutionary addiction where the genetically susceptible insect host mostly relies on its symbiont to fight pathogens.
Epigenetic divergence is sufficient to trigger heterosis inArabidopsis thaliana
Authors: Lauss Kathrin , Wardenaar René , van Hulten Marieke H.A. , Guryev Victor , Keurentjes Joost J.B , Stam Maike , Johannes Frank
Published: June 2016

Despite the importance and wide exploitation of heterosis in commercial crop breeding, the molecular mechanisms behind this phenomenon are not well understood. Interestingly, there is growing evidence that beside genetic also epigenetic factors contribute to heterosis. Here we used near-isogenic but epigenetically divergent parents to create epigenetic F1 hybrids (epiHybrids) in Arabidopsis, allowing us to quantify the contribution of epigenetics to heterosis. We measured traits such as leaf area (LA), growth rate (GR), flowering time (FT), main stem branching (MSB), rosette branching (RB) and final plant height (HT) and observed several strong positive and negative heterotic phenotypes among the epiHybrids. For LA and HT mainly positive heterosis was observed, while FT and MSB mostly displayed negative heterosis. Heterosis for FT, LA and HT could be associated with several heritable, differentially methylated regions (DMRs) in the parental genomes. These DMRs contain 35 (FT and LA) and 14 (HT) genes, which may underlie the heterotic phenotypes observed. In conclusion, our study indicates that epigenetic divergence can be sufficient to cause heterosis.

Author Summary

Crossing two genetically distinct parents generates hybrid offspring. Sometimes hybrids are performing better than their parents in particular traits and this is referred to as heterosis. Hybridization and heterosis are naturally occurring processes and crop breeders intentionally cross genetically different parental lines in order to generate hybrids with maximized traits such as yield or stress tolerance. So far, the mechanisms behind heterosis are not well understood. In this study we focused on the effect of epigenetic variation onto heterosis in hybrids, and for this purpose we created epigenetic hybrids (epiHybrids) by crossing wildtype plants with a selection of genetically very similar but epigenetically divergent lines. An extensive phenotypic analysis of the epiHybrids and their parental lines showed that epigenetic divergence between parental genomes can be a major determinant of heterosis. Importantly, multiple heterotic phenotypes could be associated with meiotically heritable differentially methylated regions (DMRs) in the parental genomes, allowing us to map epigenetic quantitative trait loci (QTLs) for heterosis. Our results indicate that epigenetic variation can contribute to heterosis and suggests that heritable epigenetic variation could be exploited for the improvement of crop traits.
Architecture of fully occupied Glua2 Ampa receptor – TARP complex elucidated by single particle cryo-electron microscopy
Authors: Zhao Yan , Chen Shanshuang , Yoshioka Craig , Baconguis Isabelle , Gouaux Eric
Published: June 2016

Fast excitatory neurotransmission in the mammalian central nervous system is largely carried out by AMPA-sensitive ionotropic glutamate receptors. Localized within the postsynaptic density of glutamatergic spines, AMPA receptors are composed of heterotetrameric receptor assemblies associated with auxiliary subunits, the most common of which are transmembrane AMPA-receptor regulatory proteins (TARPs). The association of TARPs with AMPA receptors modulates the kinetics of receptor gating and pharmacology, as well as trafficking. Here we report the cryo-EM structure of the homomeric GluA2 AMPA receptor saturated with TARP γ2 subunits, showing how the TARPs are arranged with four-fold symmetry around the ion channel domain, making extensive interactions with the M1, M2 and M4 TM helices. Poised like partially opened ‘hands’ underneath the two-fold symmetric ligand binding domain (LBD) ‘clamshells’, one pair of TARPs are juxtaposed near the LBD dimer interface, while the other pair are near the LBD dimer-dimer interface. The extracellular ‘domains’ of TARP are positioned to not only modulate LBD ‘clamshell’ closure, but also to affect conformational rearrangements of the LBD layer associated with receptor activation and desensitization, while the TARP transmembrane (TM) domains buttress the ion channel pore.
Chlamydomonas reinhardtii PsbS Protein Is Functional and Accumulates Rapidly and Transiently under High Light
Authors: Tibiletti Tania , Auroy Pascaline , Peltier Gilles , Caffarri Stefano
Published: June 2016

Photosynthetic organisms must respond to excess light in order to avoid photo-oxidative stress. In plants and green algae the fastest response to high light is non-photochemical quenching (NPQ), a process that allows the safe dissipation of the excess energy as heat. This phenomenon is triggered by the low luminal pH generated by photosynthetic electron transport. In vascular plants the main sensor of the low pH is the PsbS protein, while in the green alga Chlamydomonas reinhardtii LhcSR proteins appear to be exclusively responsible for this role. Interestingly, Chlamydomonas also possesses two PsbS genes, but so far the PsbS protein has not been detected and its biological function is unknown. Here, we reinvestigated the kinetics of gene expression and PsbS and LhcSR3 accumulation in Chlamydomonas during high light stress. We found that, unlike LhcSR3, PsbS accumulates very rapidly but only transiently. In order to determine the role of PsbS in NPQ and photoprotection in Chlamydomonas, we generated transplastomic strains expressing the algal or the Arabidopsis psbS gene optimized for plastid expression. Both PsbS proteins showed the ability to increase NPQ in Chlamydomonas wild-type and npq4 (lacking LhcSR3) backgrounds, but no clear photoprotection activity was observed. Quantification of PsbS and LhcSR3 in vivo indicates that PsbS is much less abundant than LhcSR3 during high light stress. Moreover, LhcSR3, unlike PsbS, also accumulates during other stress conditions. The possible role of PsbS in photoprotection is discussed.
Crystal structure of the cyan fluorescent protein Cerulean-S175G
Authors: Park Sang-wook , Kang Sunghyun , Yoon Tae-Sung
Published: June 2016

Enhanced cyan fluorescent protein (ECFP) was derived fromAequorea victoriagreen fluorescent protein (avGFP), notably with S65T/Y66W mutations. Its chromophore consists of a tripeptide comprised of Thr65, Trp66 and Gly67 (TWG) residues, while that ofavGFP consists of a Ser65, Tyr66 and Gly67 (SYG) tripeptide. Cerulean and SCFP3A were derived from ECFP-S72A/H148D (a double mutation) with additional Y145A and S175G mutations, respectively, while Cerulean-S175G has both mutations (Y145A and S175G). The crystal structures of these ECFP variants at neutral pH were reported to adopt two distinct major conformations calledECFPandCerulean. In this study, Cerulean-S175G was revealed to adopt only theCeruleanconformation, while Cerulean has been reported to adopt both theECFPand theCeruleanconformations in its crystal structures. Sharing the same S175G mutation with SCFP3A, Cerulean-S175G showed a slightly increased quantum yield, like SCFP3A, but did not adopt theECFPconformation adopted by SCFP3A. Detailed comparison of Cerulean-S175G and other ECFP variants revealed that the notable conformational changes in ECFP variants can be understood mainly in terms of the interaction between the Trp66 residue of the chromophore and residues 145–148 of β-strand 7.
LCP crystallization and X-ray diffraction analysis of VcmN, a MATE transporter fromVibrio cholerae
Authors: Kusakizako Tsukasa , Tanaka Yoshiki , Hipolito Christopher J. , Kuroda Teruo , Ishitani Ryuichiro , Suga Hiroaki , Nureki Osamu
Published: June 2016

Multidrug and toxic compound extrusion (MATE) transporters, one of the multidrug exporter families, efflux xenobiotics towards the extracellular side of the membrane. Since MATE transporters expressed in bacterial pathogens contribute to multidrug resistance, they are important therapeutic targets. Here, a MATE-transporter homologue fromVibrio cholerae, VcmN, was overexpressed inEscherichia coli, purified and crystallized in lipidic cubic phase (LCP). X-ray diffraction data were collected to 2.5 Å resolution from a single crystal obtained in a sandwich plate. The crystal belonged to space groupP212121, with unit-cell parametersa= 52.3,b= 93.7,c= 100.2 Å. As a result of further LCP crystallization trials, crystals of larger size were obtained using sitting-drop plates. X-ray diffraction data were collected to 2.2 Å resolution from a single crystal obtained in a sitting-drop plate. The crystal belonged to space groupP212121, with unit-cell parametersa= 61.9,b= 91.8,c= 100.9 Å. The present work provides valuable insights into the atomic resolution structure determination of membrane transporters.
Comparing Known and Reconstructed Circumstances of Death Involving a Blunt Force Trauma Mechanism through a Retrospective Analysis of 21 Skeletonized Individuals
Authors: Marinho Luísa , Cardoso Hugo F.V.
Published: June 2016

Little is known about to what extent the events surrounding death can be reliably reconstructed from blunt force trauma analysis alone. In this study, we reconstruct circumstances of death from a blind blunt force trauma analysis using a sample of 21 individuals of known death circumstances, obtained from two identified skeletal collections in Portugal. Fresh versus dry bone trauma and probable mechanism of fracture production were identified. The overall pattern of injuries was then used to reconstruct the most likely circumstances of death. Results show an agreement between the proposed and the reported circumstances for 13 individuals (68.4%), disagreement for 3 (15.8%), and similarity in 3 cases (15.8%). Although the significant amount of agreement highlights the potential of trauma analysis, the cases with disagreement draw attention to the pitfalls and shortcomings of attempting to reconstruct the death circumstances from skeletal trauma analysis alone.
Time to analgesia in an emergency department in Eastern Nepal
Authors: Bhandari Rabin , Malla Gyanendra , Rai Bijendra Kumar , Curry Chris
Published: June 2016

Objectives

Nepal is a least developed country, with limited healthcare resources. An 18 month Fellowship in Emergency Medicine has contributed some improvements to care. This study assessed time to first analgesia in higher and lower acuity patients.

Methods

A prospective observational study of 101 patients in each of the Australasian Triage Scale (ATS) 2, 3 and 100 in ATS 4 was undertaken at B.P. Koirala Institute of Health Sciences. Convenience sampling was used coinciding with researcher's duty hours. Pain scores and time to analgesia were recorded.

Results

A total of 302 patients were included. The doctors identified pain in 274 (90%, 95% confidence interval [CI] 86.74–93.65), severity recorded in 92 (30.5%, 95% CI 25–36). Median time from triage to analgesia was 30 min (interquartile range [IQR] 15–60) for ATS 2 patients, 60 min (IQR 40–70) for ATS 3 and 69 min (IQR 45–116) for ATS 4. Tramadol was the analgesic used most commonly (33%), followed by diclofenac (25%), morphine (16%), paracetamol (14%) and ketamine (2%). Analgesia was provided to 212 (70%, 95% CI 64.6–75.2), 65 (30.66%, 95% CI 24.5–37.3) with ATS 2, 85 (40%, 95% CI 33.4–47) with ATS 3 and 62 (29.2%, 95% CI 23.2–35.8) with ATS 4. A total of 44 patients (20.7%, 95% CI 15.5–26.8) with mild, 101 (47.6%, 95% CI 40.7–54.6) with moderate and 60 (28.3%, 95% CI 22.3–34.8) with severe pain received analgesics.

Conclusion

Time to analgesia for triage score 2 is lower compared to higher triage score. However, a large proportion of patients still do not receive analgesia. This is likely addressed by using a combination of strategies.
Genotypes of Coxiella burnetii in wildlife: disentangling the molecular epidemiology of a multi‐host pathogen
Authors: González‐Barrio David , Jado Isabel , Fernández‐de‐Mera Isabel G. , del Rocio Fernández‐Santos María , Rodríguez‐Vargas Manuela , García‐Amil Cristina , Beltrán‐Beck Beatriz , Anda Pedro , Ruiz‐Fons Francisco
Published: June 2016

Evidences point to a relevant role of wildlife in the ecology of Coxiella burnetii worldwide. The lack of information on C. burnetii genotypes in wildlife prevents tracing‐back clinical animal and human Q fever cases with potential wildlife origin. To compare C. burnetii genotypes circulating in wildlife, livestock and humans, 107 samples from red deer, European wild rabbit, racoon, small mammals, goat and sheep were genotyped by polymerase chain reaction and reverse line blot hybridization. Genomic groups I, II, VI and VII were found in wildlife and groups I, II, III and IV in domestic ruminants. Livestock genotypes clustered mainly with genotypes reported previously in livestock. Genotyping confirmed previous findings that suggest that C. burnetii may display host specificity since most genotypes of sympatric deer and rabbits clustered in separate groups. Wildlife genotypes clustered with genotypes from ticks and from acute hepatitis human Q fever cases, suggesting that particular C. burnetii genotypes circulating in a wildlife‐tick cycle may occasionally jump into humans through tick bites or exposure to wildlife. This finding could be behind the reported geographic variation in the clinical presentation of acute Q fever in humans in Spain: atypical pneumonia in the north and hepatitis in the south.
Elevated triglycerides are associated with decreased executive function among adolescents with bipolar disorder
Authors: Naiberg M. R. , Newton D. F. , Collins J. E. , Dickstein D. P. , Bowie C. R. , Goldstein B. I.
Published: June 2016

Objective

Cardiovascular risk factors that comprise metabolic syndrome (MetS) have been linked with cognition in adults with bipolar disorder (BD). This study examines the association between MetS components and executive function in adolescents with BD.

Methods

A total of 34 adolescents with BD and 35 healthy control (HC) adolescents were enrolled. MetS components included triglycerides, high‐density lipoprotein, glucose, waist circumference, and systolic and diastolic blood pressure. Executive functioning was measured using the intra–extra‐dimensional (IED) set‐shifting task from the Cambridge Neuropsychological Tests Automated Battery.

Results

Adolescents with BD were more likely to have ≥1 MetS components (64.7%) as compared to HC participants (22.9%, χ2 = 12.29, P = <0.001). Adolescents with BD also had poorer IED task performance compared to HC adolescents (composite Z‐score: 0.21 ± 0.52 vs. 0.49 ± 0.51, P = 0.011). Within the BD group, IED composite Z‐scores were correlated with diastolic blood pressure and triglyceride levels (ρ = −0.358, P = 0.041 and ρ = −0.396, P = 0.020 respectively). The association of triglycerides with executive function remained significant after controlling for age, IQ, and current use of second‐generation antipsychotics.

Conclusion

Elevated triglycerides are associated with poorer executive function among adolescents with BD. Studies of behavioural and pharmacological interventions targeting MetS components for the purpose of improving executive function among adolescents with BD are warranted.
Association analysis between feed efficiency studies and expression of hypothalamic neuropeptide genes in laying ducks
Authors: Zeng T. , Chen L. , Du X. , Lai S. J. , Huang S. P. , Liu Y. L. , Lu L. Z.
Published: June 2016

Residual feed intake (RFI) is now considered a more reasonable metric to evaluate animal feed efficiency. In this study, the correlation between RFI and other feed efficiency traits was investigated and gene expression within the hypothalamus was determined in low RFI (LRFI) and high RFI (HRFI) ducks. Further, several hypothalamic neuropeptide genes were measured using quantitative real‐time PCR. The mean feed intake value was 160 g/day, whereas the egg mass laid (EML) and body weight were approximately 62.4 g/day and 1.46 kg respectively. Estimates for heritability of RFI, feed conversion ratio (FCR) and feed intake were 0.26, 0.18 and 0.23 respectively. RFI is phenotypically positively correlated with feed intake and FCR (P < 0.01). The expression of neuropeptide Y (NPY) and neuropeptide Y receptor Y5 (NPY5R) mRNA was higher in HRFI ducks compared with LRFI ducks (P < 0.05), whereas that of proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R) and cholecystokinin (CCK) was lower (P < 0.05). The mRNA expression of gonadotropin‐releasing hormone 1 (luteinizing‐releasing hormone) (GNRH1) and prolactin receptor (PRLR) was unchanged between LRFI and HRFI ducks. The results indicate that selection for LRFI could reduce feed intake without significant changes in EML, whereas selection on FCR will increase EML.
Serum anti‐endothelial cell antibodies in patients with age‐related macular degeneration treated with intravitreal bevacizumab
Authors: Kubicka‐Trząska Agnieszka , Wilańska Joanna , Romanowska‐Dixon Bożena , Sanak Marek
Published: June 2016

Purpose

To analyse the prevalence and changes in circulating anti‐endothelial cell antibodies (AECA) during anti‐vascular endothelial growth factor (anti‐VEGF) therapy.

Methods

Ninety‐eight patients with exudative age‐related macular degeneration (AMD) were treated with intravitreal bevacizumab. Fifty sex‐ and age‐matched healthy subjects were used as controls. Serum AECA were detected using indirect immunofluorescence on primate skeletal muscle and cultivated human umbilical vein endothelial cells (HUVEC). These investigations were repeated at 4‐week intervals within 8 months of follow‐up.

Results

At baseline examination, 30 of the 98 patients (30.6%) were positive for AECA. The titres of AECA ranged from 1:10 to 1:320. In the control group, AECA were present in only nine sera (18%) with titres ranging between 1:20 and 1:80 (p = 0.0000). The greatest rates of reduction of AECA titres were observed during the ‘loading’ phase of therapy. During the ‘maintenance’ phase, the rates of changes in serum AECA levels were less significant and remained constant. In follow‐up period in 13 patients (13.3%), serum AECA were detected de novo in titres of 1:10 to 1:80. Statistical analysis did not show any significant correlation between the presence of AECA and activity of the disease.

Conclusions

There is growing evidence that AMD is an immune‐mediated disease, and thus it cannot be excluded that AECA may be involved in its pathogenesis and progression. We also speculate that AECA develop in response to retinal damage and anti‐VEGF therapy.
Low plasma magnesium is associated with impaired brain metabolism in neonates with hypoxic‐ischaemic encephalopathy
Authors: Chakkarapani Elavazhagan , Chau Vann , Poskitt Kenneth J. , Synnes Anne , Kwan Eddie , Roland Elke , Miller Steven P.
Published: June 2016

Aim

To determine the association between lowest plasma magnesium concentration and brain metabolism, and whether magnetic resonance imaging brain injury patterns moderated the association in hypoxic‐ischemic encephalopathy.

Methods

In 131 early (day‐of‐life 3) and 65 late (day‐of‐life 10) scans of term encephalopathic infants born between 2004 and 2012, we examined the association of lowest plasma magnesium (until day‐of‐life 3) on basal ganglia and white matter peak metabolite ratios on magnetic resonance spectroscopy independent of covariates, stratified by the predominant patterns of injury (normal, basal nuclei/total, watershed, multifocal) using multiple linear regression.

Results

Lowest plasma magnesium was associated with lower white matter N‐acetyl‐aspartate/choline in the multifocal pattern on early scan (regression‐coefficient, β: 0.13; 95% CI: 0.04, 0.22) and in the basal nuclei/total pattern on late scan (β: 0.08; 95% CI: 0.02, 0.15), and was negatively associated with basal ganglia lactate/N‐acetyl‐aspartate (β: −0.16; 95% CI: −0.05, −0.28) and lactate/choline (β: −0.1; 95% CI: −0.03, −0.17) ratio in the basal nuclei/total pattern on late scan independent of hypomagnesaemia correction, cooling and postmenstrual age at scan. Lowest plasma magnesium was not associated with metabolite ratios in other brain injury patterns.

Conclusion

In infants with hypoxic‐ischaemic encephalopathy, predominant patterns of brain injury moderated the association between lowest plasma magnesium in the first three days of life and impaired brain metabolism.