bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Shorter Durations of Dual Antiplatelet Therapy Acceptable Following Percutaneous Coronary Intervention?
Authors: Lewis-Gonzalez Jessica M. , Nawarskas James J.
Published: May 2018

Much debate has centered on whether or not the standard 12-month duration of dual antiplatelet therapy (DAPT) is still necessary postpercutaneous coronary intervention, given recent improvements in stent technology. The benefits of shorter (3–6 months) durations of DAPT include a potential lower risk for bleeding and less patient drug cost and pill burden. Although randomized clinical trials have shown noninferiority for shorter versus longer DAPT regimens in many regards, some endpoints (e.g., myocardial infarction) may still occur less frequently with longer DAPT regimens, particularly in higher risk populations (e.g., acute coronary syndromes). Bleeding risk is either comparable or less with shorter versus longer DAPT regimens. Given the lack of unequivocal data regarding the equality of shorter versus longer DAPT regimens in all patients, there is a growing consensus that an individualized approach is advisable for determining DAPT duration postpercutaneous coronary intervention. Clinical decision aids and updated clinical practice guidelines are available that consider risk:benefit ratios and clinical trial data to assist the clinician in developing a personalized DAPT regimen.
Red Cell Distribution Width Predicts 90 Day Mortality in Continuous-Flow Left Ventricular Assist Device Patients
Authors: Truby Lauren K. , Sridharan Lakshmi , Flores Raul J. , Garan A. Reshad , Jennings Douglas , Yuzefpolskaya Melana , Takeda Koji , Takayama Hiroo , Naka Yoshifumi , Colombo Paolo C. , Topkara Veli K.
Published: May 2018

Red cell distribution width (RDW) measures the variance in size of circulating red blood cells and is a strong independent predictor of morbidity and mortality in cardiovascular disease and heart failure. Predictive power of RDW on mortality after continuous-flow left ventricular assist device (CF-LVAD) implantation remains largely unknown. Four hundred nine patients who underwent CF-LVAD implantation between April 2004 and December 2015 were retrospectively analyzed. The primary outcome of interest was 90 day mortality after CF-LVAD implantation. Median RDW before CF-LVAD implantation was 15.8%. Patients with elevated RDW (>15.8%) at baseline had significantly lower hemoglobin (10.6 ± 1.8 vs. 11.9 ± 2.1 mg/dl; p < 0.001), lower mean corpuscular volume (84.9 ± 7.7. vs. 88.7 ± 5.9; p < 0.001), higher blood urea nitrogen (BUN; 36.3 ± 21.8 vs. 30.1 ± 17.1; p < 0.001), lower albumin (3.4 ± 0.6 vs. 3.7 ± 0.5; p < 0.001), and higher total bilirubin levels (1.67 ± 2.21 vs. 1.29 ± 0.96). Red cell distribution width was independently predictive of 90 day mortality (odds ratio [OR], 1.16 for 1% increase; CI, 1.04–1.31; p = 0.010). Discriminatory power of RDW alone was comparable to model of end-stage liver disease excluding international normalized ratio (MELD-Xi) and HeartMate II risk scores. Mechanical unloading with CF-LVAD was associated with a reduction in RDW levels. These findings suggest that RDW, a simple and inexpensive test available through routine complete blood count, can be successfully used for mortality risk assessment in CF-LVAD candidates.
EC-VAD: Combined Use of Extracorporeal Membrane Oxygenation and Percutaneous Microaxial Pump Left Ventricular Assist Device
Authors: Akanni Olutosin J. , Takeda Koji , Truby Lauren K. , Kurlansky Paul A. , Chiuzan Codruta , Han Jiho , Topkara Veli K. , Yuzefpolskaya Melana , Colombo Paolo C. , Karmpaliotis Dimitrios , Moses Jeffery W. , Naka Yoshifumi , Garan A. Reshad , Kirtane Ajay J. , Takayama Hiroo
Published: May 2018

Combination of venoarterial extracorporeal membrane oxygenation (VA-ECMO) and a percutaneous microaxial left ventricular assist device (pLVAD), or “EC-VAD,” has been reported in cases of left ventricular decompression with mixed results. We conducted a retrospective review of patients who received EC-VAD (n = 29) or isolated VA-ECMO therapy (ECMO-only; n = 196) for refractory cardiogenic shock between February 2011 and October 2014. Fourteen patients received VA-ECMO and then Impella pLVAD (E→EC-VAD), and 15 received the Impella pump then VA-ECMO (I→EC-VAD). E→EC-VAD patients demonstrated decreased pulmonary artery systolic (36.00 ± 16.84 mm Hg versus 30.63 ± 12.13 mm Hg; p = 0.049) and diastolic (24.25 ± 13.45 mm Hg versus 17.25 ± 7.96 mm Hg, p = 0.049) pressures by 24 hours post-EC-VAD implant. In the same period, I→EC-VAD patients demonstrated improved SvO2 (43.14 ± 16.75% versus 75.18 ± 13.88%, p = 0.043) and PaO2/FiO2 ratio (148.55 ± 67.69 mm Hg versus 374.51 ± 170.97 mm Hg, p = 0.043). Thirty-day survival rates were 42.9% in E→EC-VAD, 46.7% in I→EC-VAD, and 49.0% in ECMO-only (p = 0.913). Hemolysis occurred more in EC-VAD patients (44.83% versus 17.35% in ECMO-only, p = 0.002); however, there was no increased frequency of other adverse events including bleeding and lower limb ischemia. Despite increased hemolysis, combined use of VA-ECMO and pLVAD may improve or circumvent left ventricular distension in refractory cardiogenic shock while promoting adequate blood flow.
Are Ski and SnoN Involved in the Tumorigenesis of Oral Squamous Cell Carcinoma Through Smad4?
Authors: Alaeddini Mojgan , Etemad-Moghadam Shahroo
Published: May 2018

Transforming growth factor-β has been implicated in the tumorigenesis of oral squamous cell carcinoma (OSCC). Ski and SnoN are negative regulators of transforming growth factor-β/Smad pathway with both prooncogenic and antioncogenic functions in different cancers. The aim of this study was to assess the expression of Ski and SnoN in OSCC for the first time. Smad4 was also evaluated in these tumors. Clinical data on 61 primary OSCCs were gathered, and the specimens were subjected to immunohistochemical staining with monoclonal antibodies against SKI, SnoN, and Smad4 and scored semiquantitatively. Spearman rank, Fisher exact, and χ2 tests were used for statistical analysis, and P-value <0.05 was considered significant. Ski positivity and SnoN positivity were mostly cytoplasmic and found in 96.7% and 100% of the cases, respectively. Smad4 staining was low to negative in 65% of the specimens. No significant relationship was found either among the markers or between each of the proteins and the clinicopathologic data (P>0.05). According to our findings, Ski, SnoN, and Smad4 seem to play a role in OSCC oncogenesis, and we suggest that Ski and SnoN functions may take place independent of Smad4. Considering the dual and complex role of these proteins in tumorigenesis, further investigation to clarify the molecular pathways involved in their mode of action is suggested.
Human Epidermal Growth Factor Receptor-2 Promotes Invasion and Metastasis in Gastric Cancer by Activating Mitogen-activated Protein Kinase Signaling
Authors: Hou Feng , Shi Duan-Bo , Chen Yun-Qing , Gao Peng
Published: May 2018

Increasing evidence supports an important role for the human epidermal growth factor receptor-2 (HER2) gene and mitogen-activated protein kinase (MAPK) signaling pathways in the progression of human cancers by enhancing cancer cell metastasis and proliferation. However, the relationship between HER2 and MAPK signaling pathways in gastric cancer (GC) remains unclear. In the present study, dual in situ hybridization was performed to detect HER2 gene amplification and reverse transcription-quantitative polymerase chain reaction was used to investigate the mRNA expression of members of the MAPK signaling pathway, including rapidly accelerated fibrosarcoma (RAF), extracellular regulated signal-activated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), in 112 primary GC tissue samples. The results revealed that 19/112 (17%) of tissue samples showed positive amplification of HER2, which was correlated with tumor invasion and metastasis. Upregulation of RAF, ERK, p38, and JNK was also observed in samples associated with metastasis. Moreover, the expression levels of RAF and ERK in samples with HER2 gene amplification were significantly increased compared with those without HER2 amplification. However, the expression levels of both p38 and JNK were not significantly correlated with HER2 gene amplification. Our results simultaneously showed the association between HER2 gene amplification and the expression levels of MAPK signaling pathway proteins and clinicopathologic characteristics in GC. These findings provide the basis for investigating the regulation of MAPK signaling pathways by HER2 and potential therapeutic targets for inhibiting metastasis and invasion in GC.
Signalling networks and dynamics of allosteric transitions in bacterial chaperonin GroEL: implications for iterative annealing of misfolded proteins
Authors: Thirumalai D. , Hyeon Changbong
Published: May 2018

Signal transmission at the molecular level in many biological complexes occurs through allosteric transitions. Allostery describes the responses of a complex to binding of ligands at sites that are spatially well separated from the binding region. We describe the structural perturbation method, based on phonon propagation in solids, which can be used to determine the signal-transmitting allostery wiring diagram (AWD) in large but finite-sized biological complexes. Application to the bacterial chaperonin GroEL–GroES complex shows that the AWD determined from structures also drives the allosteric transitions dynamically. From both a structural and dynamical perspective these transitions are largely determined by formation and rupture of salt-bridges. The molecular description of allostery in GroEL provides insights into its function, which is quantitatively described by the iterative annealing mechanism. Remarkably, in this complex molecular machine, a deep connection is established between the structures, reaction cycle during which GroEL undergoes a sequence of allosteric transitions, and function, in a self-consistent manner.

This article is part of a discussion meeting issue ‘Allostery and molecular machines’.
A non-equilibrium approach to allosteric communication
Authors: Stock Gerhard , Hamm Peter
Published: May 2018

While the theory of protein folding is well developed, including concepts such as rugged energy landscape, folding funnel, etc., the same degree of understanding has not been reached for the description of the dynamics of allosteric transitions in proteins. This is not only due to the small size of the structural change upon ligand binding to an allosteric site, but also due to challenges in designing experiments that directly observe such an allosteric transition. On the basis of recent pump-probe-type experiments (Buchli
et al.
2013
Proc. Natl Acad. Sci. USA
110
, 11 725–11 730. (
doi:10.1073/pnas.1306323110
)) and non-equilibrium molecular dynamics simulations (Buchenberg
et al.
2017
Proc. Natl Acad. Sci. USA
114
, E6804–E6811. (
doi:10.1073/pnas.1707694114
)) studying an photoswitchable PDZ2 domain as model for an allosteric transition, we outline in this perspective how such a description of allosteric communication might look. That is, calculating the dynamical content of both experiment and simulation (which agree remarkably well with each other), we find that allosteric communication shares some properties with downhill folding, except that it is an ‘order–order’ transition. Discussing the multiscale and hierarchical features of the dynamics, the validity of linear response theory as well as the meaning of ‘allosteric pathways’, we conclude that non-equilibrium experiments and simulations are a promising way to study dynamical aspects of allostery.

This article is part of a discussion meeting issue ‘Allostery and molecular machines’.
MyROOT: A novel method and software for the semi-automatic measurement of plant root length
Authors: Betegón-Putze Isabel , González Alejandro , Sevillano Xavier , Blasco-Escámez David , Canño-Delgado Ana I.
Published: May 2018

Root analysis is essential for both academic and agricultural research. Despite the great advances in root phenotyping and imaging however, calculating root length is still performed manually and involves considerable amounts of labor and time. To overcome these limitations, we have developed MyROOT, a novel software for the semi-automatic quantification of root growth of seedlings growing directly in agar plates. Our method automatically determines the scale from the image of the plate, and subsequently measures the root length of the individual plants. To this aim, MyROOT combines a bottom-up root tracking approach with a hypocotyl detection algorithm. At the same time as providing accurate root measurements, MyROOT also significantly minimizes the user intervention required during the process. Using Arabidopsis, we tested MyROOT with seedlings from different growth stages. Upon comparing the data obtained using this software with that of manual root measurements, we found that there are no significant differences (t-test, p-value < 0.05). Thus, MyROOT will be of great aid to the plant science community by permitting high-throughput root length measurements while saving on both labor and time.
HIV-1 Protease Evolvability is Affected by Synonymous Nucleotide Recoding
Authors: Nevot Maria , Jordan-Paiz Ana , Martrus Glòria , Andrés Cristina , García-Cehic Damir , Gregori Josep , Franco Sandra , Quer Josep , Martinez Miguel Angel
Published: May 2018

One unexplored aspect of HIV-1 genetic architecture is how codon choice influences population diversity and evolvability. Here we compared the development of HIV-1 resistance to protease inhibitors (PIs) between wild-type (WT) virus and a synthetic virus (MAX) carrying a codon-pair re-engineered protease sequence including 38 (13%) synonymous mutations. WT and MAX viruses showed indistinguishable replication in MT-4 cells or PBMCs. Both viruses were subjected to serial passages in MT-4 cells with selective pressure from the PIs atazanavir (ATV) and darunavir (DRV). After 32 successive passages, both the WT and MAX viruses developed phenotypic resistance to PIs (IC5014.6 ± 5.3 and 21.2 ± 9 nM for ATV, and 5. 9 ± 1.0 and 9.3 ± 1.9 for DRV, respectively). Ultra-deep sequence clonal analysis revealed that both viruses harbored previously described resistance mutations to ATV and DRV. However, the WT and MAX virus proteases showed different resistance variant repertoires, with the G16E and V77I substitutions observed only in WT, and the L33F, S37P, G48L, Q58E/K, and L89I substitutions detected only in MAX. Remarkably, G48L and L89I are rarely foundin vivoin PI-treated patients. The MAX virus showed significantly higher nucleotide and amino acid diversity of the propagated viruses with and without PIs (P< 0.0001), suggesting higher selective pressure for change in this recoded virus. Our results indicate that HIV-1 protease position in sequence space delineates the evolution of its mutant spectra. Nevertheless, the investigated synonymously recoded variant showed mutational robustness and evolvability similar to the WT virus.

IMPORTANCE

Large-scale synonymous recoding of virus genomes is a new tool for exploring various aspects of virus biology. Synonymous virus genome recoding can be used to investigate how a virus’s position in sequence space defines its mutant spectrum, evolutionary trajectory, and pathogenesis. In this study, we evaluated how synonymous recoding of the human immunodeficiency virus type 1 (HIV-1) protease impacts the development of protease inhibitor (PI) resistance. HIV-1 protease is a main target of current antiretroviral therapies. Our present results demonstrate that the wild-type (WT) virus and the virus with the recoded protease exhibited different patterns of resistance mutations after PI treatment. Nevertheless, the developed PI resistance phenotype was indistinguishable between the recoded virus and the WT virus, suggesting that the synonymously recoded protease HIV-1 and the WT protease virus were equally robust and evolvable.
The developing premature infant gut microbiome is a major factor shaping the microbiome of neonatal intensive care unit rooms
Authors: Brooks Brandon , Olm Matthew R. , Firek Brian A. , Baker Robyn , Geller-McGrath David , Reimer Sophia R. , Soenjoyo Karina R. , Yip Jennifer S. , Dahan Dylan , Thomas Brian C. , Morowitz Michael J. , Banfield Jillian F.
Published: May 2018

1.1

Background

The neonatal intensive care unit (NICU) contains a unique cohort of patients with underdeveloped immune systems and nascent microbiome communities. Patients often spend several months in the same room and it has been previously shown that the gut microbiomes of these infants often resemble the microbes found in the NICU. Little is known, however, about the identity, persistence and absolute abundance of NICU room-associated bacteria over long stretches of time. Here we couple droplet digital PCR (ddPCR), 16S rRNA gene surveys, and recently published metagenomics data from infant gut samples to infer the extent to which the NICU microbiome is shaped by its room occupants.

Results

Over 2,832 swabs, wipes, and air samples were collected from sixteen private-style NICU rooms housing very low birthweight (<1,500 g), premature (<31 weeks’ gestation) infants. For each infant, room samples were collected daily, Monday through Friday, for one month. The first samples from the first infant and last samples from the last infant were collected 383 days apart. Twenty-two NICU locations spanning room surfaces, hands, electronics, sink basins, and air were collected. Results point to an incredibly simple room community where 5-10 taxa, mostly skin associated, account for over 50% of 16S reads. Biomass estimates reveal 4-5 orders of magnitude difference between the least to the most dense microbial communities, air and sink basins, respectively. Biomass trends from bioaerosol samples and petri dish dust collectors suggest occupancy to be a main driver of suspended biological particles within the NICU. Using a machine learning algorithm to classify the origin of room samples, we show that each room has a unique microbial fingerprint. Several important taxa driving this model were dominant gut colonizers of infants housed within each room.

Conclusions

Despite regular cleaning of hospital surfaces, bacterial biomass was detectable at varying densities. A room specific microbiome signature was detected, suggesting microbes seeding NICU surfaces are sourced from reservoirs within the room and that these reservoirs contain actively dividing cells. Collectively, the data suggests that hospitalized infants, in combination with their caregivers, shape the microbiome of NICU rooms.
Exendin-4 disrupts responding to reward predictive incentive cues in rats
Authors: Wakabayashi Ken T. , Baindur Ajay N. , Feja Malte , Chen Karie , Bernosky-Smith Kimberly , Bass Caroline E.
Published: May 2018

Exendin-4 (EX4) is a GLP-1 receptor agonist used clinically to control glycemia in Type-2 Diabetes Mellitus (T2DM), with the additional effect of promoting weight loss. The weight loss seen with EX4 is attributable to the varied peripheral and central effects of GLP-1, with contributions from the mesolimbic dopamine pathway that are implicated in cue-induced reward seeking. GLP-1 receptor agonists reduce preference for palatable foods (i.e. sweet and fat) as well as the motivation to obtain and consume these foods. Accumulating evidence suggest that GLP-1 receptor activity can attenuate cue-induced reward seeking behaviors. In the present study, we tested the effects of EX4 (0.6, 1.2, and 2.4 µg/kg i.p.) on incentive cue (IC) responding. This rat model required rats to emit a nosepoke response during an intermittent audiovisual cue to obtain a sucrose reward (10% solution). EX4 dose-dependently attenuated responding to reward predictive cues, and increased latencies of the cue response and reward cup entry to consume the sucrose reward. Moreover, EX4 dose-dependently decreased the number of nosepokes relative to the number of cue presentations during the session. There was no drug effect on the number of reward cup entries per reward earned during the session, a related reward-seeking behavior with similar locomotor demand. Interestingly, there was a dose-dependent effect of time on the responding to reward predictive cues and nosepoke response latency, such that 2.4 µg/kg of EX4 delayed responding to the initial IC of the behavioral session. Together, these findings suggest that agonism of the GLP-1 receptor with EX4 modulates the incentive properties of cues attributed with motivational significance.
A First-principles Approach to Large-scale Nuclear Architecture
Authors: Agrawal Ankit , Ganai Nirmalendu , Sengupta Surajit , Menon Gautam I.
Published: May 2018

Model approaches to nuclear architecture have traditionally ignored the biophysical consequences of ATP-fueled active processes acting on chromatin. However, transcription-coupled activity is a source of stochastic forces that are substantially larger than the Brownian forces present at physiological temperatures. Here, we describe a first-principles approach to large-scale nuclear architecture in metazoans that incorporates cell-type-specific active processes. The model predicts the statistics of positional distributions, shapes and overlaps of each chromosome. Our simulations reproduce common organising principles underlying large-scale nuclear architecture across human cell nuclei in interphase. These include the differential positioning of euchromatin and heterochromatin, the territorial organisation of chromosomes including both gene-density-based and size-based chromosome radial positioning schemes, the non-random locations of chromosome territories and the shape statistics of individual chromosomes. We propose that the biophysical consequences of the distribution of transcriptional activity across chromosomes should be central to any chromosome positioning code.
Differences in the temporal processing between identification and categorization of durations: a behavioral and ERP study
Authors: Bannier Dorian , Wearden J. , Le Dantec Christophe C. , Rebaï Mohamed
Published: May 2018

This study examined how different forms of decision-making modulate time perception. Participants performed temporal bisection and generalization tasks, requiring them to either categorize a stimulus duration as more similar to short or long standards (bisection), or identify whether or not a duration was the same as a previously-presented standard (generalization). They responded faster in the bisection task than in the generalization one for long durations. This behavioral effect was accompanied by modulation of event-related potentials (ERPs). More specifically, between 500 ms and 600 ms after stimulus offset, a late positive component (LPC), appearing in the centro-parietal region, showed lower amplitude in the bisection task than in the generalization one, for long durations, mirroring the behavioral result. Before (200-500 ms) and after (600-800 ms) this window, the amplitude of the LPC was globally larger in the generalization paradigm, independently of the presented duration. Finally, the latency of the LPC’s peak was earlier for long durations than for the short ones, indicating that the decision about the former stimuli was made earlier than for the latter ones. Taken together, these results indicate that the categorization of durations engages fewer cognitive resources than their identification.
TRAF6 directs Foxp3 localization and facilitates Treg function through K63-type ubiquitination
Authors: Ni Xuhao , Tao Jinhui , Gu Jian , Park Benjamin V. , Chen Zuojia , Newman Stephanie , Shen Hongbin , Wang Xuehao , Li Bin , Blazar Bruce R. , Barbi Joseph , Pan Fan , Lu Ling
Published: May 2018

Regulatory T cells (Treg) are crucial mediators of immune control. The characteristic gene expression and suppressive function of Treg depend considerably on the stable expression and activity of the transcription factor Foxp3. While transcriptional regulation of the Foxp3 gene has been studied in depth, both the expression and function of Foxp3 are also modulated at the protein level. However, the molecular players involved in posttranslational Foxp3 regulation are just beginning to be elucidated. Here we found TRAF6-deficient Tregs were dysfunctional in vivo; mice with Treg-restricted deletion of TRAF6 were resistant to B16 melanomas and displayed enhanced anti-tumor immunity. We further determined that Foxp3 undergoes lysine-63 chain (K63) ubiquitination at lysine 262 mediated by the E3 ligase TRAF6. When deprived of TRAF6 activity or rendered insensitive to K63 ubiquitination, Foxp3 displayed aberrant, perinuclear accumulation, disrupted function. Thus, Foxp3 ubiquitination by TRAF6 ensures proper localization of Foxp3 and facilitates Foxp3’s gene-regulating activity in Tregs. These results implicate TRAF6 as a key posttranslational, Treg-stabilizing force that may be targeted in novel tolerance-breaking therapies.
Allele-specific control of replication timing and genome organization during development
Authors: Rivera-Mulia Juan Carlos , Dimond Andrew , Vera Daniel , Trevilla-Garcia Claudia , Sasaki Takayo , Zimmerman Jared , Dupont Catherine , Gribnau Joost , Fraser Peter , Gilbert David M.
Published: May 2018

DNA replication occurs in a defined temporal order known as the replication-timing (RT) program. RT is regulated during development in discrete chromosomal units, coordinated with transcriptional activity and 3D genome organization. Here, we derived distinct cell types from F1 hybrid musculus × castaneus mouse crosses and exploited the high single-nucleotide polymorphism (SNP) density to characterize allelic differences in RT (Repli-seq), genome organization (Hi-C and promoter-capture Hi-C), gene expression (total nuclear RNA-seq), and chromatin accessibility (ATAC-seq). We also present HARP, a new computational tool for sorting SNPs in phased genomes to efficiently measure allele-specific genome-wide data. Analysis of six different hybrid mESC clones with different genomes (C57BL/6, 129/sv, and CAST/Ei), parental configurations, and gender revealed significant RT asynchrony between alleles across ∼12% of the autosomal genome linked to subspecies genomes but not to parental origin, growth conditions, or gender. RT asynchrony in mESCs strongly correlated with changes in Hi-C compartments between alleles but not as strongly with SNP density, gene expression, imprinting, or chromatin accessibility. We then tracked mESC RT asynchronous regions during development by analyzing differentiated cell types, including extraembryonic endoderm stem (XEN) cells, four male and female primary mouse embryonic fibroblasts (MEFs), and neural precursor cells (NPCs) differentiated in vitro from mESCs with opposite parental configurations. We found that RT asynchrony and allelic discordance in Hi-C compartments seen in mESCs were largely lost in all differentiated cell types, accompanied by novel sites of allelic asynchrony at a considerably smaller proportion of the genome, suggesting that genome organization of homologs converges to similar folding patterns during cell fate commitment.
Paracoccidioides restrepiensis B339 (PS3) and P. lutzii LDR2 yeast cells and soluble components display in vitro hemolytic and hemagglutinating activities on human erythrocytes
Authors: Cezar‐dos‐Santos Fernando , Lenhard‐Vidal Adriane , Assolini João Paulo , Marquez A. S. , Ono Mário Augusto , Itano Eiko Nakagawa
Published: May 2018

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by thermally dimorphic fungi of the Paracoccidioides species complex. Several pathogenic fungi produce hemagglutinins and hemolysins, which are virulence factors involved in adhesion of pathogens to host tissues or cells and in destruction of erythrocytes. The present research investigated hemolytic and hemagglutinating activities of yeast cells and soluble components from P. restrepiensis (PS3; formerly P. brasiliensis B339) and P. lutzii (LDR2). Different concentrations of live and heat‐killed yeast cells and soluble components from a cell free antigen preparation (native or heated, 56°C or 100°C, 30 min) were mixed with 1% human erythrocyte suspensions. Yeast cells from both species caused hemolysis, P. lutzii LDR2 being more strongly hemolytic than P. restrepiensis B339, whereas the opposite phenomena occurred with soluble components in most conditions. Live or heat‐killed yeast cells of both fungi agglutinated erythrocytes, but only heated soluble components from P. restrepiensis B339 showed hemagglutinating activity. In conclusion, yeast cells of P. restrepiensis B339 and P. lutzii LDR2 produce hemolysins and hemagglutinins, which are most likely predominantly restricted to yeast cells in P. lutzii LDR2 and predominantly released in soluble form by P. restrepiensis B339, requiring further study.
Building on feminist achievements to enhance choice for women seeking treatment
Authors: Neale Joanne , Tompkins Charlotte N. E. , Marshall Alison D. , Treloar Carla , Strang John
Published: May 2018

Commentary to: Do women with complex alcohol and other drug use histories want women-only residential treatment?
Rosuvastatin‐Induced Rhabdomyolysis – Possible Role of Ticagrelor and Patients’ Pharmacogenetic Profile
Authors: Vrkić Kirhmajer Majda , Macolić Šarinić Viola , Šimičević Livija , Ladić Iva , Putarek Krešimir , Banfić Ljiljana , Božina Nada
Published: May 2018

Up to the beginning of 2018, a total of eight cases describing rare but clinically important drug interactions between rosuvastatin and ticagrelor which resulted in rhabdomyolysis have been noted in the Global World Health Organization (WHO) adverse drug reaction (ADR) database (VigiBase) as well as in available literature. There are several possible factors which could contribute to the onset of rhabdomyolysis: old age, initially excessive rosuvastatin dose, drug–drug interactions (DDI) on metabolic enzymes (CYPs and UGTs) and drug transporter levels (ABCB1, ABCG2, OATP1B1) and pharmacogenetic predisposition. We reviewed all available cases plus the case of an 87‐year‐old female Croatian/Caucasian patient who developed rhabdomyolysis following concomitant treatment with rosuvastatin and ticagrelor. The results of the pharmacogenetic analysis indicated that the patient was a carrier of inactivating alleles CYP2C9*1/*3, CYP3A4*1/*22, CYP3A5*3/*3, CYP2D6*1/*4, UGT1A1*28/*28, UGT2B7 ‐161C/T, ABCB1 3435C/T and ABCB1 1237C/T which could have added to the interactions not only between ticagrelor and rosuvastatin but also other concomitantly prescribed medicines, such as amiodarone and proton pump inhibitors. In this case report, the possible multifactorial causes for rhabdomyolysis following concomitant use of rosuvastatin and ticagrelor such as old age, polypharmacy, renal impairment, along with pharmacogenetics will be discussed.
The Out‐Group Homogeneity Effect Across Development: A Cross‐Cultural Investigation
Authors: Shilo Reut , Weinsdörfer Anika , Rakoczy Hannes , Diesendruck Gil
Published: May 2018

The present studies investigated the out‐group homogeneity effect in 5‐ and 8‐year‐old Israeli and German children (n = 150) and adults (n = 96). Participants were asked to infer whether a given property (either biological or psychological) was true of an entire group—either the participants' in‐group (“Jews” or “Germans”) or their out‐group (“Arabs” or “Turks”). To that end, participants had to select either a homogenous or a heterogeneous sample of group members. It was found that across ages and countries, participants selected heterogeneous samples less often when inferring the biological properties of out‐compared to in‐group members. No effect was found regarding psychological properties. These findings have important implications for our understanding of the origins of intergroup bias.
Monocyte‐derived extracellular vesicles stimulate cytokine secretion and gene expression of matrix metalloproteinases by mesenchymal stem/stromal cells
Authors: Gebraad Arjen , Kornilov Roman , Kaur Sippy , Miettinen Susanna , Haimi Suvi , Peltoniemi Hilkka , Mannerström Bettina , Seppänen‐Kaijansinkko Riitta
Published: May 2018

Intercellular communication is essential in bone remodelling to ensure that new bone is formed with only temporary bone loss. Monocytes (MCs) and osteoclasts actively take part in controlling bone remodelling by providing signals that promote osteogenic differentiation of mesenchymal stem/stromal cells (MSCs). Extracellular vesicles (EVs) have attracted attention as regulators of bone remodelling. EVs facilitate intercellular communication by transferring a complex cargo of biologically active molecules to target cells. In the present study, we evaluated the potency of EVs from MCs and osteoclasts to induce a lineage‐specific response in MSCs. We analysed gene expression and protein secretion by both adipose tissue‐derived MSCs and bone marrow‐derived MSCs after stimulation with EVs from lipopolysaccharide‐activated primary human MCs and (mineral‐resorbing) osteoclasts. Isolated EVs were enriched in exosomes (EVs of endosomal origin) and were free of cell debris. MC‐ and osteoclast‐derived EVs were taken up by adipose tissue‐derived MSCs. EVs from activated MCs promoted the secretion of cytokines by MSCs, which may represent an immunomodulatory mechanism. MC‐derived EVs also upregulated the expression of genes encoding for matrix metalloproteinases. Therefore, we hypothesize that MCs facilitate tissue remodelling through EV‐mediated signalling. We did not observe a significant effect of osteoclast‐derived EVs on gene expression or protein secretion in MSCs. EV‐mediated signalling might represent an additional mode of cell‐cell signalling during the transition from injury and inflammation to bone regeneration and play an important role in the coupling between bone resorption and bone formation.

Database

Gene expression data are available in the GEO database under the accession number GSE102401.
An Analytical Method for Assessing Recharge Using Groundwater Travel Time in Dupuit‐Forchheimer Aquifers
Authors: Chesnaux R. , Santoni S. , Garel E. , Huneau F.
Published: May 2018

An analytical solution to calculate the recharge of unconfined aquifers with Dupuit‐Forchheimer type flow conditions is proposed. This solution is derived from an existing closed‐form analytical solution initially developed to determine groundwater travel time when the recharge of the aquifer is known. This existing solution has been modified to determine recharge when groundwater travel time is known. An illustration is given with a field case example for the Bonifacio aquifer of the island of Corsica (France), in the Mediterranean. In this aquifer, previously established differences in groundwater residence time between two water samples were determined from anthropogenic atmospheric gas (chlorofluorocarbons and sulfur hexafluoride) measurements. The time difference is entered into the new analytical solution to determine recharge. The calculations yield a value of average recharge that agrees with the results obtained by several other methods that were presented in previous studies to assess the recharge of the Bonifacio aquifer. Also presented in this study is a sensitivity analysis of the new analytical solution, to quantify the influence of different parameters that control recharge: hydraulic conductivity, effective porosity and the groundwater travel time. This study illustrates how geochemical data can be combined with physical models to measure recharge. Such an approach could be adopted in other homogeneous aquifers worldwide that satisfy Dupuit‐Forchheimer type flow conditions.
Association between sarcopenia and osteoporosis in chronic liver disease
Authors: Hayashi Manabu , Abe Kazumichi , Fujita Masashi , Okai Ken , Takahashi Atsushi , Ohira Hiromasa
Published: May 2018

Aim

Sarcopenia and osteoporosis are important complications in chronic liver disease (CLD). The aim of this study was to investigate the relationship between sarcopenia and osteoporosis in patients with CLD.

Methods

We retrospectively investigated the relationship between sarcopenia and osteoporosis in 112 CLD patients (57 men and 55 women), including 40 cirrhotic patients (36%), by measuring the appendicular skeletal muscle mass index (ASMI) using bio‐impedance analysis. Bone mineral density (BMD) was measured by dual‐energy X‐ray absorptiometry.

Results

The sarcopenia rate was 13% (14/112), and the osteoporosis and osteopenia rates were 17% (19/112) and 65% (73/112), respectively. The rate of osteoporosis was significant and high in patients with sarcopenia or cirrhosis. In linear regression analysis, sarcopenia was significantly associated with the BMD of the lumbar spine (coefficient = −0.149, P = 0.014) and the femur neck (coefficient = −0.110, P = 0.003). Cirrhosis was also significantly associated with low BMD of the lumbar spine (coefficient = −0.160, P < 0.001) and the femur neck (coefficient = −0.066, P = 0.015). In the logistic analysis, sarcopenia (odds ratio = 6.16, P = 0.039) and cirrhosis (odds ratio = 15.8, P = 0.002) were independent risk factors for osteoporosis. The ASMI cut‐off values for osteoporosis were 7.33 kg/m2 in men and 5.71 kg/m2 in women.

Conclusions

Sarcopenia was closely associated with osteoporosis, and a low ASMI was a potential predictor of osteoporosis in CLD patients. Screening for BMD might be required to detect osteoporosis in cirrhotic patients.
Genetic parameter estimation for long endurance trials in the Uruguayan Criollo horse
Authors: López‐Correa R.D. , Peñagaricano F. , Rovere G. , Urioste J.I.
Published: May 2018

The aim of this study was to estimate the genetic parameters of performance in a 750‐km, 15‐day ride in Criollo horses. Heritability (h2) and maternal lineage effects (mt2) were obtained for rank, a relative placing measure of performance. Additive genetic and maternal lineage (rmt) correlations among five medium‐to‐high intensity phase ranks (pRK) and final rank (RK) were also estimated. Individual records from 1,236 Criollo horses from 1979 to 2012 were used. A multivariate threshold animal model was applied to the pRK and RK. Heritability was moderate to low (0.156–0.275). Estimates of mt2 were consistently low (0.04–0.06). Additive genetic correlations between individual pRK and RK were high (0.801–0.924), and the genetic correlations between individual pRKs ranged from 0.763 to 0.847. The pRK heritabilities revealed that some phases were explained by a greater additive component, whereas others showed stronger genetic relationships with RK. Thus, not all pRK may be considered as similar measures of performance in competition.
Seasonal variation of the capture and field distribution of sterile Anastrepha ludens in Tamaulipas, Mexico
Authors: Vanoye‐Eligio V. , Vázquez‐Sauceda M. L. , Chacón‐Hernández J. C. , Mora‐Ravelo S. G. , Rocandio‐Rodríguez M.
Published: May 2018

Anastrepha ludens (Loew) (Diptera: Tephritidae) is one of the most important citrus pest in Mexico. The sterile insect technique (SIT) is used against pest populations of fruit flies for suppression, eradication, containment and prevention to reduce damages in fruit‐growing areas. In this study, we analyzed the seasonal variation of captures and field distribution of sterile A. ludens released in different seasons of the year in north‐eastern Mexico. Chilled releases were conducted by air at constant densities per ha on a citrus area for a period of 32 weeks that included the coldest and warmest seasons that is winter, spring and summer. Multilure traps baited with torula yeast pellets were used to capture sterile flies. Fly capture data were compared over the three seasons and correlated with climate. The lowest number of captures of the sterile insect occurred in the summer and the highest in winter and spring. High and low temperatures were negatively correlated with fly captures. Field distribution was also negatively correlated with high temperatures in summer, but no relationships were observed in winter and spring. No relationships were observed between rainfall with capture and field distribution of sterile flies. These results indicate that summer is a season involving agro‐ecological and environmental constraints for the capture and field distribution of sterile flies. This study may be useful for enhancing release strategies and optimizing economic resources in north‐eastern Mexico. Further research on the behaviour of sterile flies under stressful environments is suggested.
Differences in teachers verbal responsiveness to groups of children with ASD who vary in cognitive and language abilities
Authors: Qian X.
Published: May 2018

Background

This study aimed to examine whether verbal responsiveness in special education teachers varied among subgroups of children with autism spectrum disorder (n = 112) who differed in cognitive and language abilities.

Methods

Participants were divided into clusters using cluster analysis based on standardised cognitive and language tests using k‐mean clustering. For each child, a 15‐min video of free play in school setting was collected. Three types of responsive utterances were coded: follow‐in directives for behaviour, follow‐in directives for language and follow‐in comments.

Results

Results showed that the three groups did not differ in overall verbal responsiveness after controlling for engagement, classroom type, age and gender. However, groups differ in follow‐in directives for language, but not in follow‐in directives for behaviours or follow‐in comments. Compared with children with autism spectrum disorder who had higher cognitive and language ability, children with more severe impairments received fewer follow‐in directives for language. Moreover, children with more cognitive and language impairments produced fewer amount of vocal/verbal acts, which results in receiving fewer verbal responses from their teachers. Additionally, teachers from the three groups did not differ in their responses to the child's verbal/vocal acts when the number of the child's verbal/vocal acts were controlled for.

Conclusion

Findings suggest child characteristics are related to the type of teachers' verbal responses in preschools. This difference in follow‐in directives for questions may be related to language or other outcomes that warrant further investigations.
The efficacy of serum brain natriuretic peptide for the early detection of portopulmonary hypertension in biliary atresia patients before liver transplantation
Authors: Yoshimaru Koichiro , Matsuura Toshiharu , Takahashi Yoshiaki , Yanagi Yusuke , Nagata Hazumu , Ohga Shouichi , Taguchi Tomoaki
Published: May 2018

Severe portopulmonary hypertension (POPH) is a contraindication for liver transplantation (LT) because of the high risk of postoperative heart failure. The early detection of POPH is important for patients with biliary atresia (BA). Brain natriuretic peptide (BNP) is known to be correlated with liver fibrosis in patients with liver cirrhosis. The aim of this study was to elucidate the efficacy of BNP measurement for the follow‐up of patients with BA. Thirty‐two patients with BA were identified from September 2011 to December 2016. As indices of liver fibrosis/cirrhosis, APRI (P < .0001), FIB‐4 (P < .0001), Child‐Pugh score (P < .0001), IV collagen (P = .0005), and hyaluronic acid (P = .0291) had high or moderate correlations with BNP. Patients with splenomegaly, esophageal varices, liver fibrosis, and collateral veins had significantly higher BNP levels than those without. Patients diagnosed with POPH had significantly higher BNP levels in comparison with those patients without (P = .0068). In contrast, PELD/MELD scores showed an almost negligible correlation with the BNP level. LT was successful in 3 asymptomatic BA patients with POPH who had high BNP levels despite the low PELD/MELD scores. In conclusion, routine serum BNP surveillance can be easy to predict asymptomatic POPH. This may help to identify POPH before it reaches a stage that would contraindicate LT.
The prognostic value of urinary chemokines at 6 months after pediatric kidney transplantation
Authors: Mockler Claire , Sharma Atul , Gibson Ian W. , Gao Ang , Wong Alexander , Ho Julie , Blydt‐Hansen Tom D.
Published: May 2018

Pediatric kidney transplantation is lifesaving, but long‐term allograft survival is still limited by injury processes mediated by alloimmune inflammation that may otherwise be clinically silent. Chemokines associated with alloimmune inflammation may offer prognostic value early post‐transplant by identifying patients at increased risk of poor graft outcomes. We conducted a single‐center prospective cohort study of consecutive pediatric kidney transplant recipients (<19 years). Urinary CCL2 and CXCL10 measured at 6 months post‐transplant were evaluated for association with long‐term eGFR decline, allograft survival, and concomitant acute cellular rejection histology. Thirty‐eight patients with a mean age of 12.4 ± 4.6 years were evaluated. Urinary CCL2 was associated with eGFR decline until 6 months (ρ −0.43; P < .01), but not at later time points. Urinary CXCL10 was associated with eGFR decline at 36 months (ρ −0.49; P < .01), risk of 50% eGFR decline (HR = 1.04; P = .02), risk of allograft loss (HR = 1.05; P = .01), borderline rejection or rejection episodes 6‐12 months post‐transplant (r .41; P = .02), and Banff i + t score (r .47, P < .01). CCL2 and CXCL10 were also correlated with one another (ρ 0.54; P < .01). CCL2 and CXCL10 provide differing, but complementary, information that may be useful for early non‐invasive prognostic testing in pediatric kidney transplant recipients.
The importance of qualitative and quantitative regional wall motion abnormality assessment at rest in pediatric coronary allograft vasculopathy
Authors: Dedieu Nathalie , Silva Vieira Miguel , Fenton Matthew , Wong James , Botnar Rene , Burch Michael , Greil Gerald , Hussain Tarique
Published: May 2018

CAV remains one of the main limiting factors for survival in children after heart transplantation. In this study, we explored the incremental value of routine CMR for evaluation and detection of CAV using qualitative and quantitative analysis of regional and global myocardial function and strain. This was a prospective imaging biomarker validation trial. Twenty‐two patients (11 male), aged between 10 and 17 years (median 14 years) post‐heart transplantation, were prospectively enrolled and underwent CMR in addition to their biennial review workup with Echo, angiography, and IVUS. Nine healthy control patients were enrolled to undergo CMR alone. Echo was used to analyze WMAs and systolic function. CMR images were analyzed qualitatively for RWMA and quantitatively for volumetric analysis, S and SR. All results were compared to IVUS and angiography assessments. Qualitatively, CMR detected RWMA corresponding to angiographic disease in 3 patients that were not detected on Echo. However, quantitative strain analysis suggested RWMA in an extra 9 patients. Detection of regional wall motion abnormality using quantitative strain analysis was associated with a higher mean stenosis grade (P=.04) and reduced graft survival (P=.04) compared to those with no quantitative wall motion abnormality. Overall, only longitudinal stain was abnormal in patients compared with controls, but there was no correlation between any of the global indices of S or SR and IVUS measurements. CMR is more sensitive than Echo for the visual detection of significant WMAs. Quantitative CMR strain analysis at rest may give additional information to discriminate those at greatest risk.