bluuebunny/crossref_metadata_2025 huggingface dataset:
Monophosphoryl lipid A induces protection against LPS in medullary thick ascending limb through a TLR4-TRIF-PI3K signaling pathway
Authors: Watts Bruns A. , George Thampi , Sherwood Edward R. , Good David W.
Published: March 2017

Monophosphoryl lipid A (MPLA) is a detoxified derivative of LPS that induces tolerance to LPS and augments host resistance to bacterial infections. Previously, we demonstrated that LPS inhibits [Formula: see text] absorption in the medullary thick ascending limb (MTAL) through a basolateral Toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-ERK pathway. Here we examined whether pretreatment with MPLA would attenuate LPS inhibition. MTALs from rats were perfused in vitro with MPLA (1 µg/ml) in bath and lumen or bath alone for 2 h, and then LPS was added to (and MPLA removed from) the bath solution. Pretreatment with MPLA eliminated LPS-induced inhibition of [Formula: see text] absorption. In MTALs pretreated with MPLA plus a phosphatidylinositol 3-kinase (PI3K) or Akt inhibitor, LPS decreased [Formula: see text] absorption. MPLA increased Akt phosphorylation in dissected MTALs. The Akt activation was eliminated by a PI3K inhibitor and in MTALs from TLR4−/−or Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF)−/−mice. The effect of MPLA to prevent LPS inhibition of [Formula: see text] absorption also was TRIF dependent. Pretreatment with MPLA prevented LPS-induced ERK activation; this effect was dependent on PI3K. MPLA alone had no effect on [Formula: see text] absorption, and MPLA pretreatment did not prevent ERK-mediated inhibition of [Formula: see text] absorption by aldosterone, consistent with MPLA's low toxicity profile. These results demonstrate that pretreatment with MPLA prevents the effect of LPS to inhibit [Formula: see text] absorption in the MTAL. This protective effect is mediated directly through MPLA stimulation of a TLR4-TRIF-PI3K-Akt pathway that prevents LPS-induced ERK activation. These studies identify detoxified TLR4-based immunomodulators as novel potential therapeutic agents to prevent or treat renal tubule dysfunction in response to bacterial infections.
The potential for understanding the synaptic organization of human motor commands via the firing patterns of motoneurons
Authors: Johnson Michael D. , Thompson Christopher K. , Tysseling Vicki M. , Powers Randall K. , Heckman Charles J.
Published: March 2017

Motoneurons are unique in being the only neurons in the CNS whose firing patterns can be easily recorded in human subjects. This is because of the one-to-one relationship between the motoneuron and muscle cell behavior. It has long been appreciated that the connection of motoneurons to their muscle fibers allows their action potentials to be amplified and recorded, but only recently has it become possible to simultaneously record the firing pattern of many motoneurons via array electrodes placed on the skin. These firing patterns contain detailed information about the synaptic organization of motor commands to the motoneurons. This review focuses on parameters in these firing patterns that are directly linked to specific features of this organization. It is now well established that motor commands consist of three components, excitation, inhibition, and neuromodulation; the importance of the third component has become increasingly evident. Firing parameters linked to each of the three components are discussed, along with consideration of potential limitations in their utility for understanding the underlying organization of motor commands. Future work based on realistic computer simulations of motoneurons may allow quantitative “reverse engineering” of human motoneuron firing patterns to provide good estimates of the relative amplitudes and temporal patterns of all three components of motor commands.
Transfer of dynamic motor skills acquired during isometric training to free motion
Authors: Melendez-Calderon Alejandro , Tan Michael , Bittmann Moria Fisher , Burdet Etienne , Patton James L.
Published: March 2017

Recent studies have explored the prospects of learning to move without moving, by displaying virtual arm movement related to exerted force. However, it has yet to be tested whether learning the dynamics of moving can transfer to the corresponding movement. Here we present a series of experiments that investigate this isometric training paradigm. Subjects were asked to hold a handle and generate forces as their arms were constrained to a static position. A precise simulation of reaching was used to make a graphic rendering of an arm moving realistically in response to the measured interaction forces and simulated environmental forces. Such graphic rendering was displayed on a horizontal display that blocked their view to their actual (statically constrained) arm and encouraged them to believe they were moving. We studied adaptation of horizontal, planar, goal-directed arm movements in a velocity-dependent force field. Our results show that individuals can learn to compensate for such a force field in a virtual environment and transfer their new skills to the actual free motion condition, with performance comparable to practice while moving. Such nonmoving techniques should impact various training conditions when moving may not be possible.

NEW & NOTEWORTHY This study provided early evidence supporting that training movement skills without moving is possible. In contrast to previous studies, our study involves 1) exploiting cross-modal sensory interactions between vision and proprioception in a motionless setting to teach motor skills that could be transferable to a corresponding physical task, and 2) evaluates the movement skill of controlling muscle-generated forces to execute arm movements in the presence of external forces that were only virtually present during training.
Thrombopoietin Secretion by Human Ovarian Cancer Cells
Authors: Besbes Samaher , Shah Shahid , Al-dybiat Iman , Mirshahi Shahsoltan , Helfer Helene , Najah Haythem , Fourgeaud Caroline , Pocard Marc , Ghedira Ibtissem , Soria Jeannette , Mirshahi Massoud
Published: March 2017

The thrombopoietin (TPO) gene expression in human ovary and cancer cells from patients with ovarian carcinomatosis, as well as several cancer cell lines including MDA-MB231 (breast cancer), K562 and HL60 (Leukemic cells), OVCAR-3NIH and SKOV-3 (ovarian cancer), was performed using RT PCR, real-time PCR, and gene sequencing. Human liver tissues are used as controls. The presence of TPO in the cells and its regulation by activated protein C were explored by flow cytometry. TPO content of cell extract as well as plasma of a patient with ovarian cancer was evaluated by ELISA. The functionality of TPO was performed in coculture on the basis of the viability of a TPO-dependent cell line (Ba/F3), MTT assay, and Annexin-V labeling. As in liver, ovarian tissues and all cancer cells lines except the MDA-MB231 express the three TPO-1 (full length TPO), TPO-2 (12 bp deletion), and TPO-3 (116 pb deletion) variants. Primary ovarian cancer cells as well as cancer cell lines produce TPO. The thrombopoietin production by OVCAR-3 increased when cells are stimulated by aPC. OVCAR-3 cell’s supernatant can replace exogenous TPO and inhibited TPO-dependent cell line (Ba/F3) apoptosis. The thrombopoietin produced by tumor may have a direct effect on thrombocytosis/thrombosis occurrence in patients with ovarian cancer.
An Improved Hybrid Algorithm Based on Biogeography/Complex and Metropolis for Many‐Objective Optimization
Authors: Wang Chen , Wang Yi , Wang Kesheng , Dong Yao , Yang Yang
Published: March 2017

It is extremely important to maintain balance between convergence and diversity for many‐objective evolutionary algorithms. Usually, original BBO algorithm can guarantee convergence to the optimal solution given enough generations, and the Biogeography/Complex (BBO/Complex) algorithm uses within‐subsystem migration and cross‐subsystem migration to preserve the convergence and diversity of the population. However, as the number of objectives increases, the performance of the algorithm decreases significantly. In this paper, a novel method to solve the many‐objective optimization is called Hmp/BBO (Hybrid Metropolis Biogeography/Complex Based Optimization). The new decomposition method is adopted and the PBI function is put in place to improve the performance of the solution. On the within‐subsystem migration the inferior migrated islands will not be chosen unless they pass the Metropolis criterion. With this restriction, a uniform distribution Pareto set can be obtained. In addition, through the above‐mentioned method, algorithm running time is kept effectively. Experimental results on benchmark functions demonstrate the superiority of the proposed algorithm in comparison with five state‐of‐the‐art designs in terms of both solutions to convergence and diversity.
Application of Adjoint Data Assimilation Method to Atmospheric Aerosol Transport Problems
Authors: Xu Minjie , Fu Kai , Lv Xianqing
Published: March 2017

We propose combining the adjoint assimilation method with characteristic finite difference scheme (CFD) to solve the aerosol transport problems, which can predict the distribution of atmospheric aerosols efficiently by using large time steps. Firstly, the characteristic finite difference scheme (CFD) is tested to compute the Gaussian hump using large time step sizes and is compared with the first-order upwind scheme (US1) using small time steps; the US1 method gets E2 error of 0.2887 using Δt=1/450, while CFD method gets a much smaller E2 of 0.2280 using a much larger time step Δt=1/45. Then, the initial distribution of PM2.5 concentration is inverted by the adjoint assimilation method with CFD and US1. The adjoint assimilation method with CFD gets better accuracy than adjoint assimilation method with US1 while adjoint assimilation method with CFD costs much less computational time. Further, a real case of PM2.5 concentration distribution in China during the APEC 2014 is simulated by using adjoint assimilation method with CFD. The simulation results are in good agreement with the observed values. The adjoint assimilation method with CFD can solve large scale aerosol transport problem efficiently.
Reversible Inferolateral ST-Segment Elevation Associated with Small Bowel Obstruction
Authors: Upadhyay Ankit , Chauhan Sudheer , Jangda Umair , Bodar Vipul , Al-Chalabi Ahmed
Published: March 2017

ST-segment elevation is an important and alarming electrocardiographic sign that necessitates immediate attention but does not always indicate that the primary pathology is cardiac in origin. It needs to be interpreted in the clinical context as several pathological conditions involving especially gastrointestinal tract may lead to delayed diagnosis and treatment as well as complications from invasive unnecessary interventions. We present two patients, a 64-year-old male and a 71-year-old female, who were admitted to the emergency room of a community-based hospital with similar complaints of worsening epigastric abdominal pain and were diagnosed later with small bowel obstruction. Both patients reported a history of abdominal surgeries in the past. Also in both patients the ECG showed signs of ST-segment elevation in inferior and lateral leads. These ECG changes were related to the intra-abdominal pathology as no evidence of contributing coronary artery disease could be found. In addition, prompt resolution of ST-segment elevation was seen after surgical treatment. The pathophysiological etiology of electrocardiographic changes accompanying small bowel obstruction is yet to be explored.
A Critical Review of the Evidence Concerning the HIV Latency Reversing Effect of Disulfiram, the Possible Explanations for Its Inability to Reduce the Size of the Latent Reservoir In Vivo, and the Caveats Associated with Its Use in Practice
Authors: Knights Harry D. J.
Published: March 2017

Combination antiretroviral therapy (cART) effectively suppresses the replication of human immunodeficiency virus type 1 (HIV-1), improves immune function, and decreases the morbidity of acquired immune deficiency syndrome (AIDS). However, it is unable to eradicate the virus because it does not eliminate latently infected cells. The latent reservoir poses the major barrier to an HIV-1 cure. The “shock and kill” strategy aims to reactivate the virus and destroy latently infected cells. Many latency reversing agents (LRAs) reactivate HIV in vitro, but the absence of damaging side-effects and efficacy in vivo make disulfiram particularly promising. However, in clinical trials to date, disulfiram treatment has not resulted in a reduction in the size of the latent reservoir. In this article I will therefore discuss the evidence for the latency reversing effect of disulfiram, the possible explanations for its inability to reduce the size of the latent reservoir in vivo, and the caveats associated with its use in practice. These considerations will help to inform judgements about the prospect of an HIV cure from disulfiram based treatments.
Reimbursed Price of Orphan Drugs: Current Strategies and Potential Improvements
Authors: Mincarone Pierpaolo , Leo Carlo Giacomo , Sabina Saverio , Sarriá-Santamera Antonio , Taruscio Domenica , Serrano-Aguilar Pedro Guillermo , Kanavos Panos
Published: March 2017

The pricing and reimbursement policies for pharmaceuticals are relevant to balance timely and equitable access for all patients, financial sustainability, and reward for valuable innovation. The proliferation of high-cost specialty medicines is particularly true in rare diseases (RDs) where the pricing mechanism is characterised by a lack of transparency. This work provides an overall picture of current strategies for the definition of the reimbursed prices of orphan drugs (ODs) and highlights some potential improvements. Current strategies and suggestions are presented along 4 dimensions: (1) comprehensive value assessment, (2) early dialogs among relevant stakeholders, (3) innovative reimbursement approaches, and (4) societal participation in producing ODs. Comprehensive value assessment could be achieved by clarifying the approach of distributive justice to adopt, ensuring a representative participation of stakeholders, and with a broad consideration of value-bearing factors. With respect to early dialogs, cross-border cooperation can be determinant to companies and agencies. The cost-benefit ratio of early dialogs needs to be demonstrated and the “regulatory capture” effect should be monitored. Innovative reimbursement approaches were developed to balance the need for evidence-based decisions with the timely access to innovative drugs. The societal participation in producing ODs needs to be recognised in a collaborating framework where adaptive agreements can be developed with mutual satisfaction. Such agreements could also impact on coverage and reimbursement decisions as additional elements for the determination of a comprehensive societal value of ODs. Further research is needed to investigate the highlighted open challenges so that RDs will not remain, in practical terms, orphan diseases.
Novel Marfan Syndrome-Associated Mutation in the FBN1 Gene Caused by Parental Mosaicism and Leading to Abnormal Limb Patterning
Authors: Martínez-Quintana Efrén , Caballero-Sánchez Noemí , Rodríguez-González Fayna , Garay-Sánchez Paloma , Tugores Antonio
Published: March 2017

Marfan syndrome is an autosomal dominant disorder of the connective tissue caused by mutations in the fibrillin-1 (FBN1) gene. Mutations affecting cysteine residues within the epidermal growith factor-like calcium-binding domains (EGF_CA) of FBN1 are associated with Marfan syndrome features and, especially, with ectopia lentis. We report a novel substitution, affecting the first cysteine of an EGF_CA-binding module encoded by exon 63 of FBN1 (C2571Y), in a patient presenting with typical Marfan syndrome features but without ectopia lentis. The involvement of this particular carboxi-terminal domain in bone morphogenetic protein signaling is evidenced by patterning defects in the apendicular skeleton shown by the gain of a phalange at digit 1 and the fusion of some wrist bones. Although the mutation appeared as sporadic, detailed analysis revealed that the asymptomatic father was a gonosomal mosaic, and that aproximately 25% of his body cells carry the mutation. Based on this and previous evidence on the origin of sporadic mutations, we would like to stress the importance of detailed parental genetic screening, so the risk of recurrence may be evaluated.
Toll-Like Receptor-2 and -4 Expression by Maternal Neutrophils in Preterm Labor
Authors: Prearo Moço Natália , Camargo Batista Renata Aparecida , Fernandes Martin Laura , de Oliveira Leandro Gustavo , Garcia de Lima Parada Cristina Maria , Alarcão Dias-Melicio Luciane , de Assis Golim Marjorie , Guimarães da Silva Márcia
Published: March 2017

Background and Aims: The inflammatory response in preterm parturition is regulated by the innate immune system. Toll-like receptors (TLR)-2 and TLR-4 are innate immune receptors that recognize the microorganisms most frequently involved in amniotic cavity infections, which are associated with activating the inflammatory response at the maternal-fetal interface during preterm labor. This study aimed to evaluate the expression of TLR-2 and TLR-4 in maternal neutrophils in preterm labor. Methods: A cross-sectional study was conducted in the Obstetrics Care Unit of Botucatu Medical School, UNESP, Brazil. The preterm group was composed of 20 pregnant women who presented preterm labor and preterm delivery. The control group was composed of 20 nonlaboring pregnant women matched to the preterm group by gestational age. Neutrophils were isolated from peripheral blood and TLR expressions were performed by real-time polymerase chain reaction and flow cytometry. Results: Gene expressions of TLR-2 and TLR-4 in neutrophils from the preterm group were statistically higher than expressions in neutrophils from the matched control group. The percentage of TLR-4+ neutrophils was higher in the preterm group than the matched control group, while the percentage of TLR-2+ neutrophils did not differ between groups. Conclusion: TLR-4 expression in maternal neutrophils is associated with spontaneous preterm labor.
Therapeutic Plasma Exchange in Neonates and Infants: Successful Use of a Miniaturized Machine
Authors: Vidal Enrico , Garzotto Francesco , Parolin Mattia , Manenti Chiara , Zanin Anna , Bellettato Massimo , Remuzzi Giuseppe , Goldstein Stuart L. , Murer Luisa , Ronco Claudio
Published: March 2017

Therapeutic plasma exchange (TPE) in neonates and small infants is a treatment method at the forefront that may become a potentially life-saving procedure in a wide array of severe conditions. Indications for TPE in the pediatric population have been mainly derived from adult literature, with neonatal hyperbilirubinemia being the most notable exception. The only alternative to TPE in small pediatric patients is manual blood exchange transfusion, which, however, bears an unacceptably high risk of severe complications. Still, technical issues due to extracorporeal circulation in neonates have burdened TPE so far, since machines developed for adults require a relatively large blood volume to operate. We in this study, describe our preliminary experience of TPE for treating 2 potentially life-threatening conditions in neonatal age. To overcome the aforementioned limitations, plasmapheresis was performed in both cases using a machine specifically designed for patients weighing less than 10 kg.
The Construction and Identification of Induced Pluripotent Stem Cells Derived from Acute Myelogenous Leukemia Cells
Authors: Zhu Liang-Fang , Chen Qiu-Ru , Chen Shao-Zhen , Wang Ling-Yan , Luo Xiao-Feng , Ren Jin-Hua , Yuan Xiao-Hong , Wu Xue-Qiong , Zeng Yan-Ling , Xiao Min , Chen Yong-Quan , Chen Ying-Yu , Lin Min-Hui , Wu Zheng-Jun , Chen Zhi-Zhe , Hu Jian-Da , Yang Ting
Published: March 2017

Objective: The present study aimed to establish an induced pluripotent stem cell (iPSC) line from acute myelogenous leukemia (AML) cells in vitro and identify their biological characteristics. Methods: Cells from the AML-infiltrated skin from an M6 patient were infected with a lentivirus carrying OCT4, SOX2, KLF4 and C-MYC to induce iPSCs. The characteristics of the iPSCs were confirmed by alkaline phosphatase (ALP) staining. The proliferation ability of iPSCs was detected with a CCK-8 assay. The expression of pluripotency markers was measured by immunostaining, and the expression of stem cell-related genes was detected by qRT-PCR; distortion during the induction process was detected by karyotype analysis; the differentiation potential of iPSCs was determined by embryoid body-formation and teratoma-formation assays. ALP staining confirmed that these cells exhibited positive staining and had the characteristics of iPSCs. Results: The CCK-8 assay showed that the iPSCs had the ability to proliferate. Immunostaining demonstrated that iPSC clones showed positive expression of NANOG, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. qRT-PCR results revealed that the mRNA expression of Nanog, Lin28, Cripto, FOX3, DNMT3b, DPPA2, and DPPA4 significantly increased in iPSCs. Karyotype analysis found no chromosome aberration in the iPSCs. The results of the embryoid body-formation and teratoma-formation assays indicated that the iPSCs had the potential to differentiate into all three germ layers. Conclusion: Our study provided evidence that an iPSC line derived from AML cells was successfully established.
Interleukin 17A and Toll-like Receptor 4 in Patients with Arterial Hypertension
Authors: Simundic Tihana , Jelakovic Bojan , Dzumhur Andrea , Turk Tajana , Sahinovic Ines , Dobrosevic Blazenka , Takac Boris , Barbic Jerko
Published: March 2017

Background/Aims: Immune responses are involved in arterial hypertension. An observational cross-sectional case control study was conducted to estimate the association between Toll-like receptor 4 (TLR4) expression and interleukin (IL)-17A serum levels in patients with controlled and non-controlled hypertension. Methods: We have enrolled 105 non-complicated otherwise healthy hypertensive patients: 53 with well-controlled blood pressure and 52 non-controlled. TLR4 peripheral monocytes expression and serum IL-17A levels were determined by flow cytometry and ELISA, respectively. Results: Non-controlled patients exhibited higher TLR4 expression than well-controlled (25.60 vs. 21.99, P=0.011). TLR4 expression was lower in well-controlled patients who were prescribed beta blockers (18.9 vs. 22.6, P=0.005) and IL-17A concentration was higher in patients using diuretics in either group (1.41 vs. 2.01 pg/ml, P<0.001; well-controlled 1.3 vs. 1.8 pg/ml, P= 0.023; non-controlled 1.6 vs. 2.3 pg/ml, P=0.001). Correlation between IL-17A concentration and hypertension duration was observed in non-controlled patients (Spearman correlation coefficient . ρ=0.566, P<0.001) whereas in well-controlled patients a correlation was found between hypertension duration and TLR4 expression (ρ=0.322, P=0.020). Conclusions: Arterial hypertension stimulates the immune response regardless of blood pressure regulation status. Prolonged hypertension influences peripheral monocyte TLR4 expression and IL-17A serum levels. Anti-hypertensive drugs have different immunomodulatory effects: diuretics are associated with higher IL-17A concentration and beta-blockers with lower TLR4 expression.
Effect of Age and Sex on the QTc Interval in Children and Adolescents With Type 1 and 2 Long-QT Syndrome
Authors: Vink Arja S. , Clur Sally-Ann B. , Geskus Ronald B. , Blank Andreas C. , De Kezel Charlotte C.A. , Yoshinaga Masao , Hofman Nynke , Wilde Arthur A.M. , Blom Nico A.
Published: March 2017

Background—

In congenital long-QT syndrome, age, sex, and genotype have been associated with cardiac events, but their effect on the trend in QTc interval has never been established. We, therefore, aimed to assess the effect of age and sex on the QTc interval in children and adolescents with type 1 (LQT1) and type 2 (LQT2) long-QT syndrome.

Methods and Results—

QTc intervals of 12-lead resting electrocardiograms were determined, and trends over time were analyzed using a linear mixed-effects model. The study included 278 patients with a median follow-up of 4 years (interquartile range, 1–9) and a median number of 6 (interquartile range, 2–10) electrocardiograms per patient. Both LQT1 and LQT2 male patients showed QTc interval shortening after the onset of puberty. In LQT2 male patients, this was preceded by a progressive QTc interval prolongation. In LQT1, after the age of 12 years, male patients had a significantly shorter QTc interval than female patients. In LQT2, during the first years of life and from 14 to 26 years, male patients had a significantly shorter QTc interval than female patients. On the contrary, between 5 and 14 years, LQT2 male patients had significantly longer QTc interval than LQT2 female patients.

Conclusions—

There is a significant effect of age and sex on the QTc interval in long-QT syndrome, with a unique pattern per genotype. The age of 12 to 14 years is an important transitional period. In the risk stratification and management of long-QT syndrome patients, clinicians should be aware of these age-, sex-, and genotype-related trends in QTc interval and especially the important role of the onset of puberty.
Sex‐ and Race‐Related Differences in Characteristics and Outcomes of Hospitalizations for Heart Failure With Preserved Ejection Fraction
Authors: Goyal Parag , Paul Tracy , Almarzooq Zaid I. , Peterson Janey C. , Krishnan Udhay , Swaminathan Rajesh V. , Feldman Dmitriy N. , Wells Martin T. , Karas Maria G. , Sobol Irina , Maurer Mathew S. , Horn Evelyn M. , Kim Luke K.
Published: March 2017

Background

Sex and race have emerged as important contributors to the phenotypic heterogeneity of heart failure with preserved ejection fraction (HFpEF). However, there remains a need to identify important sex‐ and race‐related differences in characteristics and outcomes using a nationally representative cohort.

Methods and Results

Data were obtained from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project—Nationwide Inpatient Sample files between 2008 and 2012. Hospitalizations with a diagnosis of
HF
p
EF
were included for analysis. Demographics, hospital characteristics, and age‐adjusted comorbidity prevalence rates were compared between men and women and whites and blacks. In‐hospital mortality was determined and compared for each subgroup. Multivariable regression analyses were used to identify and compare correlates of in‐hospital mortality for each subgroup. A sample of 1 889 608 hospitalizations was analyzed. Men with
HF
p
EF
were slightly younger than women with
HF
p
EF
and had a higher Elixhauser comorbidity score. Men experienced higher in‐hospital mortality compared with women, a finding that was attenuated after adjusting for comorbidity. Blacks with
HF
p
EF
were younger than whites with
HF
p
EF
, with lower rates of most comorbidities. Hypertension, diabetes, anemia, and chronic renal failure were more common among blacks. Blacks experienced lower in‐hospital mortality compared with whites, even after adjusting for age and comorbidity. Important correlates of mortality among all 4 subgroups included pulmonary circulation disorders, liver disease, and chronic renal failure. Atrial fibrillation was an important correlate of mortality only among women and blacks.

Conclusions

Differences in patient characteristics and outcomes reinforce the notion that sex and race contribute to the phenotypic heterogeneity of
HF
p
EF
.
Impact of Diabetes Mellitus on the Pharmacodynamic Effects of Ticagrelor Versus Clopidogrel in Troponin‐Negative Acute Coronary Syndrome Patients Undergoing Ad Hoc Percutaneous Coronary Intervention
Authors: Sweeny Joseph M. , Angiolillo Dominick J. , Franchi Francesco , Rollini Fabiana , Waksman Ron , Raveendran Ganesh , Dangas George , Khan Naeem D. , Carlson Glenn F. , Zhao Yonggang , Teng Renli , Mehran Roxana
Published: March 2017

Background

Diabetes mellitus (
DM
) is associated with enhanced platelet reactivity and impaired response to oral antiplatelet therapy, including clopidogrel. This post hoc analysis investigated the pharmacodynamic effects of ticagrelor versus clopidogrel loading dose (
LD
) in troponin‐negative acute coronary syndrome patients with or without
DM
undergoing percutaneous coronary intervention in the Ad Hoc
PCI
study.

Methods and Results

Patients randomized (1:1) to receive ticagrelor 180 mg
LD
or clopidogrel 600 mg
LD
were assessed by diabetic status. Platelet reactivity (P2Y
12
reaction units [
PRU
] on VerifyNow
®
assay) was measured pre‐
LD
, at 0.5, 2, and 8 hours post‐
LD
, and at the end of the percutaneous coronary intervention. The primary endpoint was
PRU
levels 2 hours post‐
LD
; secondary endpoints included rates of high on‐treatment platelet reactivity (
PRU
≥208). Of 100 randomized patients, 51 received ticagrelor (
DM
, n=20; non‐
DM
, n=31) and 49 clopidogrel (
DM
, n=16; non‐
DM
, n=33). At 2 hours post‐
LD
, mean (
SD
)
PRU
levels in
DM
patients were 130.1 (111.7) with ticagrelor versus 287.6 (71.9) with clopidogrel (mean [95%
CI
] difference −157.5 [−225.3, −89.8];
P
<0.001); in non‐
DM
patients, they were 75.3 (75.7) versus 243.0 (72.4) (mean difference −167.7 [−207.1, −128.3];
P
<0.001). High on‐treatment platelet reactivity rates at 2 hours post‐
LD
were also significantly (
P
<0.001) reduced with ticagrelor versus clopidogrel in
DM
and non‐
DM
patients. Between‐treatment differences for
PRU
and high on‐treatment platelet reactivity were not significant at earlier time points but were at 8 hours post‐
LD
(
P
<0.001).

Conclusions

Compared with clopidogrel, ticagrelor achieved faster, enhanced platelet inhibition and reduced high on‐treatment platelet reactivity rates, in
DM
and non‐
DM
patients.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01603082.
Supramodal Theta, Gamma, and Sustained Fields Predict Modality-specific Modulations of Alpha and Beta Oscillations during Visual and Tactile Working Memory
Authors: van Ede Freek , Jensen Ole , Maris Eric
Published: March 2017

Flexible control over currently relevant sensory representations is an essential feature of primate cognition. We investigated the neurophysiological bases of such flexible control in humans during an intermodal working memory task in which participants retained visual or tactile sequences. Using magnetoencephalography, we first show that working memory retention engages early visual and somatosensory areas, as reflected in the sustained load-dependent suppression of alpha and beta oscillations. Next, we identify three components that are also load dependent but modality independent: medial prefrontal theta synchronization, frontoparietal gamma synchronization, and sustained parietal event-related fields. Critically, these domain-general components predict (across trials and within load conditions) the modality-specific suppression of alpha and beta oscillations, with largely unique contributions per component. Thus, working memory engages multiple complementary frontoparietal components that have discernible neuronal dynamics and that flexibly modulate retention-related activity in sensory areas in a manner that tracks the current contents of working memory.
Searching for a Foil to Charicleia
Authors: Ciocani Vichi Eugenia
Published: March 2017

Set at a narratologically crucial moment of Heliodorus’ novel, the hymn to Thetis precedes and foreshadows the appearance of the protagonists, Theagenes and Charicleia, within the religious festival at Delphi. While the parallel between Neoptolemus and Theagenes is rather clear and explicit, the hymn honours Thetis in a distinctive way which does not correspond symmetrically to the depiction of Charicleia. The paper will argue that this hymn alludes to the Homeric Hymn to Demeter and contrasts the various figures of Thetis, Demeter and Persephone to Heliodorus’ heroine. This interpretation explains the meaning of the hymn to Thetis both in its immediate context and within the larger ideology of the novel.
The genus Surinamysis (Mysida, Mysidae, Diamysini) from Amazonia and the coast of Brazil, with descriptions of two new species
Authors: Wittmann Karl J.
Published: March 2017

The mysid Surinamysis rionegrensis sp. nov. is described from Rio Negro, a large freshwater tributary of the Amazon. A supplemented description is given for the freshwater species S. robertsonae Bamber & Henderson, 1990, and its known distribution within the Amazon system is amended. A further representative of this genus, S. aestuaria sp. nov., is described from brackish waters within the estuary system of Rio Quatipuru on the NE coast of Brazil. These three species share large statoliths mineralized with vaterite, a metastable polymorph of crystalline calcium carbonate. Among the three flagella of the male antennula, the median, ventral one is identified as an accessory flagellum, as opposed to the Old World genera Mesopodopsis and Limnomysis, where the inner flagellum or lobe is accessory. The distinctive characters of Surinamysis and its five species are presented. The diagnosis of this genus is modified and a key to its species is given.
Akinesis in Physocypria schubarti Farkas, 1958 (Podocopida, Cyprididae) does not fully explain its low consumption by predatory Chaoborus larvae in a Brazilian lake
Authors: Maroneze D. M. , Pujoni D. G. F. , Maia-Barbosa P. M.
Published: March 2017

Behavioral responses are important in zooplankton species exposed to invertebrate predators. In a Brazilian natural lake, the ostracod Physocypria schubarti Farkas, 1958 is abundant, despite the presence of predatory Chaoborus Lichtenstein, 1800 larvae. This is intriguing as this predator controls several microcrustacean populations in nature. Therefore, we analysed the interactions between fourth instar Chaoborus larvae and ostracods of two body sizes in laboratory. We evaluated (1) the behaviour of P. schubarti during Chaoborus attacks, (2) the probability of Chaoborus larvae ingesting them during such interactions and (3) the prey survival and predator ingestion rates after 24 h. When attacked, ostracods of both sizes frequently ceased to move and passively sank in the water column. This anti-predation strategy (“akinesis” or “dead-man response”) was observed in over 80% of the interactions involving physical contact. Surprisingly the probability of Chaoborus larvae eating prey that exhibited, or not, this reaction was close or equal to zero. After 24 h, over 92% of the prey survived and the ingestion rate of the chaoborids was practically nihil. Our results suggest that, although akinesis is a very common behaviour, additional features of P. schubarti may be as or more important in explaining its low vulnerability when in high spatial overlap with Chaoborus larvae.
Three new decapods (Aristeidae, Chirostylidae, Pandalidae) from the Cape Verde Islands (NE Atlantic)
Authors: González José A. , Triay-Portella Raül , Santana José I. , Correia Sandra , Monteiro Carlos , Martins Albertino
Published: March 2017

In the present article three benthic decapods, Aristeus varidens Holthuis, 1952 (Aristeidae), Gastroptychus formosus (Filhol, 1884) (Chirostylidae) and Plesionika longicauda (Rathbun, 1901) (Pandalidae), are recorded for the first time from the Cape Verde Islands. This is the southernmost record of G. formosus, as well as the northernmost of P. longicauda ever recorded from the eastern Atlantic. Preliminary data on batch fecundity and egg size of the pandalid shrimp are provided. Studied specimens were caught in the frame of a scientific trapping survey.
The epithelial cytotypes of hepatopancreas in the Chinese mitten crab Eriocheir sinensis (Decapoda, Varunidae)
Authors: Zhang Hui , Zhong Shengwei , Fan Qinyong , Yu Pengcheng , Ge Tingting , Peng Shasha , Zhou Zuohong , Guo Xiaoquan
Published: March 2017

The Chinese mitten crab, Eriocheir sinensis, is an economically important crustacean. However, the hepatopancreas structure of the crab has not been fully disclosed. Here, we employed light microscopy and transmission electron microscopy to identify the epithelial cytotypes of the hepatopancreas. The hepatopancreas consisted of four epithelial cytotypes, which were B (blister-like), R (resorptive), F (fibrillar), and E (embryonic) cells. B cells had club-shaped nuclei, scant cytoplasm, and contained some small vacuoles and one extremely large vacuole. Both R and F cells were columnar, and F cells were separated by two to three serial R cells. R cells contained small vacuoles, but had no extremely large vacuole in the cytoplasm. Two neighbouring R cells established contact by septate junctions. Many microvilli were present on the surface of the plasmalemma of R cells. Endocytotic vesicles were frequently observed in apical regions of the R cells. F cells were hyperbasophilic and argyrophilic, and contained abundant rough endoplasmic reticulum. E cells were small and contained scant cytoplasm and we rarely observed organelles in these cells. In addition, many vesicae were present in the lumen of the hepatopancreatic tubules.
The Vedic Background of Yāska’s Nirukta
Authors: Visigalli Paolo
Published: March 2017

The relation between Yāska’s Nirukta and the Vedic literature has been discussed by several scholars, but other than focusing on etymologies, it has been insufficiently studied. This article casts further light on the Vedic background of the Nirukta by considering three kinds of evidence. First, it explores the occurrences of nir-√vac in the Atharvaveda and in the Brāhmaṇas. Next it studies a method for classifying mantras that is first advanced in the Brāhmaṇas and then elaborated in the Nirukta. Third, it argues that Yāska’s model of nirvacana analysis was informed by a particular kind of Vedic etymology involving the opposition between evident (pratyakṣa ‘present before the eyes’) and cryptic (parokṣa ‘out of sight’) names.
Taxonomy and phylogeny of Chara (Charophyceae, Characeae) from Brazil with emphasis on the midwest and southeast regions
Authors: BORGES FABIO RENATO , NECCHI JR ORLANDO
Published: March 2017

South American studies on the genus Chara are relatively scarce, most consisting of floristic surveys and using only traditional morphological characters. This study is a first approach to the systematics of the genus Chara applying modern techniques (DNA sequences and oospore SEM analyses) in addition to the alpha-taxonomy investigations that have been conducted in Brazil. Twelve populations of Chara were analyzed from the midwest and southeast regions of Brazil. Sequences of three molecular markers were applied to infer phylogenies. The ultrastructure of the oospore wall and currently used morphological characters were analyzed for Chara populations. Maximum likelihood and Bayesian analyses of sequences of rbcL, ITS2, and matK were congruent in that they grouped the species in six clades, each representing one species: Chara braunii C.C. Gmelin, C. foliolosa C.L.Willdenow, C. guairensis R.Bicudo, C. haitensis M.P.J.F. Turpin, C. hydropitys H. Reichenbach and C. rusbyana M. Howe. Morphological characters, including ultrastructure of oospore wall, provided good evidences to characterize each species. Molecular data supported the recent view that some traditional infra-generic taxa (e.g. subgenus Charopsis and subsection Willdenowia) are not supported in phylogenetic analyses, whereas some species (e.g. C. foliolosa, C. haitensis, C. hydropitys and C. rusbyana previously considered as varieties and forms of C. zeylanica) were consistently distinguished in the analyses for the three molecular markers.
Three new species of Ecuadorian Rhinotragini (Coleoptera, Cerambycidae)
Authors: BEZARK LARRY G. , SANTOS-SILVA ANTONIO
Published: March 2017

Three new species of Rhinotragini are described from Ecuador: Paraeclipta ecuadorensis, Odontocera magnifica and Lygrocharis setosus.
A Method to Estimate Reflection and Directional Spread Using Rotary Spectra from Accelerometers on Large Ice Floes
Authors: Sutherland Graig , Rabault Jean , Jensen Atle
Published: March 2017

The directional wave spectra in sea ice are an important aspect of wave evolution and can provide insights into the dominant components of wave dissipation, that is, dissipation due to scattering or dissipation due to viscous processes under the ice. A robust method for the measurement of directional wave spectra parameters in sea ice from a three-axis accelerometer—or a heave, pitch, and roll sensor—is proposed. The method takes advantage of certain aspects of sea ice and makes use of rotary spectra techniques to provide model-free estimates for the mean wave direction, directional spread, and reflection coefficient. The method is ideally suited for large ice floes—that is, where the ice floe length scale is much greater than the wavelength—but a framework is provided to expand the parameter space where the method may be effective.
Unpacking the Gender Differences on Mental Health
Authors: Yue Xiao Dong , Hiranandani Neelam Arjan , Jiang Feng , Hou Zhenhu , Chen Xiaohua
Published: March 2017

Mental health studies show that women are likely to score higher on subjective well-being and higher on depression than men. To verify this, the present study collected a sample of 5648 undergraduates in 55 universities in China. Results showed that women reported higher optimism, gratitude, subjective well-being, and depression than men, and that optimism and gratitude mediated the relationship between gender and mental health (subjective well-being and depression). By its implication, women were more likely to be optimistic and grateful, and as such they tended to experience higher subjective well-being and depression simultaneously. This also implies that gender differences on mental health could also be a dispositional issue as well as a socialization one.
A Case of Statin-Associated Autoimmune Myopathy
Authors: Sweidan Alexander J , Leung Anthony , Kaiser Cassandra J , Strube Sarah J , Dokukin Andrei N , Romansky Stephen , Farjami Sassan
Published: March 2017

A 70-year-old previously independent man developed progressive proximal leg weakness resulting in a fall at home suffering traumatic brain injury. He was prescribed a statin medication two years prior, but this was discontinued on admission to the hospital due to concern for statin myopathy. His weakness continued to progress while in acute rehabilitation, along with the development of dysphagia requiring placement of gastrostomy tube and respiratory failure requiring tracheostomy. Corticosteroids and intravenous immunoglobulin were administered without response. Nerve conduction study demonstrated no evidence of neuropathy; electromyography revealed spontaneous activity suggestive of myopathy. A muscle biopsy was performed and demonstrated myonecrosis. Serology was positive for autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), verifying our diagnosis of statin-associated autoimmune myopathy (SAM). The patient was subsequently treated with rituximab and methotrexate and demonstrated mild clinical improvement. He was eventually liberated from the ventilator. However, later in the course of treatment, he developed respiratory distress and required ventilator support. The patient was discharged to long-term acute care two months after his initial presentation and died due to ventilator-acquired pneumonia three months later. Since their introduction 30 years ago, statin medications have been widely prescribed to prevent cardiovascular diseases. Myalgias and/or myopathic symptoms are among the most recognized side effects of the medication. Statin-associated autoimmune myopathy is a very rare complication of statin use and estimated to affect two to three for every 100,000 patients treated. Clinically, the condition presents as progressive symmetric weakness, muscle enzyme elevations, necrotizing myopathy on muscle biopsy, and the presence of autoantibodies to HMGCR. These findings will often persist and even progress despite discontinuation of the statin. Very few cases of SAM have been described in the literature. Describing this rare condition and the ultimately fatal outcome of our patient, we aim to further understanding of SAM, its presentation and clinical course to promote earlier diagnosis and prompt management.
Sulfhydrylbystrite, Na5K2Ca(Al6Si6O24)(S5)(SH), a new mineral with the LOS framework, and re-interpretation of bystrite: cancrinite-group minerals with novel extra-framework anions
Authors: Sapozhnikov A. N. , Kaneva E. V. , Suvorova L. F. , Levitsky V. I. , Ivanova L. A.
Published: March 2017

Sulfhydrylbystrite, Na5K2Ca(Al6Si6O24)(S5)(SH), cell parameters a = 12.9567(6) Å, c = 10.7711(5) Å, space group P31c, is a new mineral belonging to the cancrinite group. It was found at Malaya Bystraya lazurite deposit, Lake Baikal area, Eastern Siberian Region, Russia, associated with lazurite, calcite, diopside, phlogopite and pyrite. The mineral develops at the margins of masses of lazurite, replacing it in some areas with the formation of nonequilibrium lazurite-diopside-sulfhydrylbystrite association. It is translucent, yellow to orange, with vitreous lustre, yellow streak and Mohs hardness of 4.5–5. The empirical formula, based on 12 (Si + Al), is Na5.17K1.87Ca0.99[Al6.01Si5.99O24](S5)0.862–(SH0.86)Cl0.07, Z = 2. The crystal structure of sulfhydrylbystrite may be described as an ABAC stacking of six-membered rings of SiO4 and AlO4 tetrahedra and extra-framework cations and anions located within structural cages. There are two type of cages, cancrinite and losod, stacked into chains at (0, 0, z) and (⅔, ⅓, z), respectively. The cancrinite cage hosts Ca2+ and (SH)– ions, whereas the (S5)2– polyanion is in the losod cage associated with Na+ and K+ cations. In addition, (SH)– and (S5)2– anions are detected in the structure of a mineral for the first time.

For comparison, a structural and compositional study of a bystrite sample from the same deposit was carried out. Bystrite is confirmed to contain pentasulfide anions in the losod cages, similar to those of sulfhydrylbystrite, in contrast to previous studies. However, bystrite has chloride in cancrinite cages, whereas sulfhydrylbystrite has hydrosulfide in that position. The unit-cell parameters are distinctly different: bystrite has a = 12.8527(6) Å, c = 10.6907(5) Å in the same P31c space group.
The crystal structure of veenite
Authors: Topa Dan , Makovicky Emil
Published: March 2017

The crystal structure of veenite is reported for the first time from a sample from the type locality of Madoc (Ontario, Canada). It has been solved and refined by X-ray single-crystal diffraction on the basis of 4973 observed reflections (withFo> 4σ(Fo)) with a finalR1= 0.0396. Veenite is monoclinicP21, with unit-cell parametersa= 8.429(2),b= 26.069(5),c= 8.962(2) Å, β = 117.447(2)o. The bulk veenite composition is Ag0.15Pb16.029Sb8.836As6.99S39.95(forZ= 1) corresponding to N = 4.09 (Me8NS8N + 8, theoretical value is 4.0), with the percentage of the Ag-(As,Sb) substituted end-member only equal to 3.51 mol.%, i.e., a nearly pure Pb-Sb-As sulfosalt. The crystal structure is typical for the N = 4 sartorite homologue, with zig-zag walls of trigonal coordination prisms of Pb which separate slabs of diagonally oriented double-layers populated by Sb and As with partial Pb substitution. Orientation of three-membered crankshaft chains formed by strong (As,Sb) – S bonds on the two surfaces of double-layers differs substantially from that in dufrénoysite, which is a pure Pb-As (N = 4) sulfosalt.
PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma
Authors: Nayak Lakshmi , Iwamoto Fabio M. , LaCasce Ann , Mukundan Srinivasan , Roemer Margaretha G. M. , Chapuy Bjoern , Armand Philippe , Rodig Scott J. , Shipp Margaret A.
Published: March 2017

Key Points

Genetic analysis reveals frequent 9p24.1/PD-L1/PD-L2 copy-number alterations and increased expression of the PD-1 ligands in PCNSL and PTL. PD-1 blockade with nivolumab demonstrated activity in patients with relapsed/refractory PCNSL and PTL.