Vapomechanically Responsive Motion of Microchannel-Programmed Actuators

Materials that respond rapidly and reversibly to external stimuli currently stand among the top choices as actuators for real-world applications. Here, a series of programmable actuators fabricated as single- or bilayer elements is described that can reversibly respond to minute concentrations of acetone vapors. By using templates, microchannel structures are replicated onto the surface of two highly elastic polymers, polyvinylidene fluoride (PVDF) and polyvinyl alcohol, to induce chiral coiling upon exposure to acetone vapors. The vapomechanical coiling is reversible and can be conducted repeatedly over 100 times without apparent fatigue. If they are immersed in liquid acetone, the actuators are saturated with the solvent and temporarily lose their motility but regain their shape and activity within seconds after the solvent evaporates. The desorption of acetone from the PVDF layer is four times faster than its adsorption, and the actuator composed of a single PVDF layer maintains its ability to move over an acetone-soaked filter paper even after several days. The controllable and reproducible sensing capability of this smart material can be utilized for actuating dynamic elements in soft robotics.

A series of programmed actuators composed of single- or bilayer elements capable of mechanical actuation in response to minute acetone vapors is reported. The bilayer actuators having microchannel patterns on the surface respond to acetone vapors with chiral coiling and directional curling, while the single layer actuator maintains its ability for perpetual motion over an acetone-soaked filter paper.

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Exceptional High-Performance of Pt-Based Bimetallic Catalysts for Exclusive Detection of Exhaled Biomarkers

Achieving an improved understanding of catalyst properties, with ability to predict new catalytic materials, is key to overcoming the inherent limitations of metal oxide based gas sensors associated with rather low sensitivity and selectivity, particularly under highly humid conditions. This study introduces newly designed bimetallic nanoparticles (NPs) employing bimetallic Pt-based NPs (PtM, where M = Pd, Rh, and Ni) via a protein encapsulating route supported on mesoporous WO₃ nanofibers. These structures demonstrate unprecedented sensing performance for detecting target biomarkers (even at p.p.b. levels) in highly humid exhaled breath. Sensor arrays are further employed to enable pattern recognition capable of discriminating between simulated biomarkers and controlled breath. The results provide a new class of multicomponent catalytic materials, demonstrating potential for achieving reliable breath analysis sensing.

Effective strategy to readily synthesize highly dispersed Pt-based bimetallic (PtM, where M = Pd, Rh, and Ni) NPs as a new class of active catalysts is successfully developed on highly porous architecture of 1D WO₃ nanofibers via protein template, i.e., apoferritin, in combination with electrospinning method for superior exhaled breath sensors.

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Gender, Emotions Management, and Power in Organizations: The Case of Israeli Women Junior Military Officers

Abstract

Through in-depth retrospective interviews with 25 women officers in the Israeli military, we discovered that their experiences with power are central to their military experience even years after their discharge. The interviewees conveyed a dialectical emotional experience of power, interpreting it as a source of pleasure and empowerment and a source of shame at the same time. The women are made to feel ashamed because, according to accepted gendered beliefs, they crossed gender boundaries and used military power preserved exclusively for masculine use. Shame is a disciplinary mechanism through which women learn to obey normative gender arrangements and thus should be understood as an invisible block preventing women's promotion and mobility. These dual perceptions show the inherent gendered boundaries of military power and women's place in the military power hierarchy. The politics of emotion, in this case, should be analyzed as an intersubjective surveillance and self-regulatory mechanism, which could illuminate hidden corners of organizations wherein masculine authority is preserved and reproduced through indirect and murky methods. Hence, women's perceptions of power are a key tool for understanding gender dynamics and may contribute to identifying and deciphering unspoken practices as well as helping to change them.

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Women Show Cognitive Advantage in Gender-Equal Countries

Women's cognitive functioning past middle age may be affected by the degree of gender equality in the country they live in, according to new findings from Psychological Science, a journal of the Association for Psychological Science.

"This research is a first attempt to shed light on important, but understudied, adverse consequences of gender inequality on women's health in later life," explains researcher Eric Bonsang of University Paris-Dauphine and Columbia University, lead author on the study. "It shows that women living in gender-equal countries have better cognitive test scores later in life than women living in gender-unequal societies. Moreover, in countries that became more gender-equal over time, women's cognitive performance improved relative to men's."

Bonsang and colleagues Vegard Skirbekk (Norwegian Institute of Public Health and Columbia University) and Ursula Staudinger (Columbia University) had noticed that the differences in men's and women's scores on cognitive tests varied widely across countries. In countries in Northern Europe, for example, women tend to outperform men on memory tests, while the opposite seems to be true in several Southern European countries.

"This observation triggered our curiosity to try to understand what could cause such variations across countries," says Bonsang.

While economic and socioeconomic factors likely play an important role, Bonsang, Skirbekk, and Staudinger wondered whether sociocultural factors such as attitudes about gender roles might also contribute to the variation in gender differences in cognitive performance around the globe. They hypothesized that women who live in a society with more traditional attitudes about gender roles would likely have less access to opportunities for education and employment and would, therefore, show lower cognitive performance later in life compared with men of the same age.

The researchers analyzed cognitive performance data for participants between the ages of 50 and 93, drawn from multiple nationally representative surveys including the US Health and Retirement Study; the Survey of Health, Ageing and Retirement in Europe; the English Longitudinal Study of Ageing; and the World Health Organization Study on Global AGEing and Adult Health. Together, the surveys provided data for a total of 27 countries.

All of the surveys include an episodic memory task to measure cognitive performance. Participants heard a list of 10 words and were asked to recall as many as they could immediately; in some of the surveys, participants again recalled as many words as they could after a delay. Additionally, some of the surveys included a task intended to assess executive function in which participants named as many animals as they could within 1 minute.

To gauge gender-role attitudes, the researchers focused on participants' self-reported agreement with the statement, "When jobs are scarce, men should have more right to a job than women."

Overall, the data showed considerable variability in gender differences in cognitive performance across countries. In some countries, women outperformed men—the female advantage in cognitive performance was highest in Sweden. In other countries, however, men outperformed women—the male advantage was highest in Ghana.

As the researchers hypothesized, increasingly traditional gender-role attitudes were linked with decreasing cognitive performance among women across countries. In other words, women in countries with less traditional attitudes were likely to have better cognitive performance later in life relative to women in more traditional countries.

Bonsang and colleagues noted that changes in gender-role attitudes within a country over time were associated with changes in women's cognitive performance relative to men.

Although the data are correlational in nature, several more detailed analyses point toward a causal relationship. These analyses suggest that gender-role attitudes may play a notable role in important outcomes for women across different countries, the researchers argue.

"These findings reinforce the need for policies aiming at reducing gender inequalities as we show that consequences go beyond the labor market and income inequalities," says Bonsang. "It also shows how important it is to consider seemingly intangible influences, such as cultural attitudes and values, when trying to understand cognitive aging."

"In future work, we plan to disentangle the effect of gender-role attitudes on gender difference in cognition—via the impacts of those attitudes on institutions, politics and labor market characteristics—from the impact of beliefs of women associated with gender-role attitudes," Bonsang says.

We use data from Survey of Health, Ageing and Retirement in Europe (SHARE) Release 2.6.0, English Longitudinal Study of Ageing (ELSA) Release 19, the RAND Corporation Health and Retirement Study (HRS) Version N, and Study on Global AGEing and Adult Health (SAGE) Wave 1. The SHARE project has been primarily funded by the European Commission (see http://ift.tt/SI4Lvh for the full list of funders). The ELSA project has been funded by a consortium of U.K. government departments and the U.S. National Institute on Aging (see http://ift.tt/2eZICgb for the full list of funders). The HRS project is funded by the Social Security Administration and the U.S. National Institute on Aging (see http://ift.tt/Ub1BxF for full list of funders). The SAGE project has been primarily funded by the U.S. National Institute of Aging (see http://ift.tt/1irJ6TE for the full list of funders).

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The authors respond to: "Optimal levels of DHEA for pregnancy may be reduced by antibiotics" [Letters]

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Validation of quality indicators for end-of-life communication: results of a multicentre survey [Research]

BACKGROUND:

The lack of validated quality indicators is a major barrier to improving end-of-life communication and decision-making. We sought to show the feasibility of and provide initial validation for a set of quality indicators related to end-of-life communication and decision-making.

METHODS:

We administered a questionnaire to patients and their family members in 12 hospitals and asked them about advance care planning and goals-of-care discussions. Responses were used to calculate a quality indicator score. To validate this score, we determined its correlation with the concordance between the patients' expressed wishes and the medical order for life-sustaining treatments recorded in the hospital chart. We compared the correlation with concordance for the advance care planning component score with that for the goal-of-care discussion scores.

RESULTS:

We enrolled 297 patients and 209 family members. At all sites, both overall quality indicators and individual domain scores were low and there was wide variability around the point estimates. The highest-ranking institution had an overall quality indicator score (95% confidence interval) of 40% (36%–44%) and the lowest had a score of 18% (11%–25%). There was a strong correlation between the overall quality indicator score and the concordance measure (r = 0.72, p = 0.008); the estimated correlation between the advance care planning score and the concordance measure (r = 0.35) was weaker than that between the goal-of-care discussion scores and the concordance measure (r = 0.53).

INTERPRETATION:

Quality of end-of-life communication and decision-making appears low overall, with considerable variability across hospitals. The proposed quality indicator measure shows feasibility and partial validity. Study registration: ClinicalTrials.gov, no. NCT01362855

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Measuring quality of end-of-life communication and decision-making: Do we have this right? [Commentary]

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Public drug policy for children in Canada [Analysis]

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CIHRs face-to-face about-face [News]

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Medical cannabinoids [Practice]

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Optimal levels of DHEA for pregnancy may be reduced by antibiotics [Letters]

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Cardiac paraganglioma [Practice]

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UK seeks to make DNA testing standard in cancer care [News]

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Lessons from a child [Humanities]

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Support grows for paying surrogates [News]

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The toxicity of paracetamol–codeine combination in overdose is an unresolved issue

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Copy number profiling of adult relapsed B-cell precursor acute lymphoblastic leukemia reveals potential leukemia progression mechanisms

Abstract

The outcome of relapsed adult acute lymphoblastic leukemia (ALL) remains dismal despite new therapeutic approaches. Previous studies analyzing relapse samples have shown a high degree of heterogeneity regarding gene alterations without an evident relapse signature. Bone marrow or peripheral blood samples from 31 adult B-cell precursor ALL patients at first relapse, and 21 paired diagnostic samples were analyzed by multiplex ligation probe-dependent amplification (MLPA). Nineteen paired diagnostic and relapse samples of these 21 patients were also analyzed by SNP arrays. A trend to acquire homozygous CDKN2A/B deletions and a significant increase in the number of copy number alterations (CNA) was observed from diagnosis to first relapse. Evolution from an ancestral clone was the main pattern of clonal evolution. Relapse samples were extremely heterogeneous regarding CNA frequencies. However, CDKN2A/B, PAX5, ETV6, ATM, IKZF1, VPREB1 and TP53 deletions and duplications of 1q, 8q, 17q, 21, X/Y PAR1 and Xp were frequently detected at relapse. Duplications of genes involved in cell proliferation, drug resistance and stem cell homeostasis regulation, as well as deletions of KDM6A and STAG2 genes emerged as specific alterations at relapse. Genomics of relapsed adult B-cell precursor ALL is highly heterogeneous, although some recurrent lesions involved in essential pathways deregulation were frequently observed. Selective and simultaneous targeting of these deregulated pathways may improve the results of current salvage therapies. This article is protected by copyright. All rights reserved.

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Fusion of the Genes BRD8 and PHF1 in Endometrial Stromal Sarcoma

Abstract

We present a new endometrial stromal sarcoma (ESS)-associated genomic rearrangement involving chromosome arms 5p and 6p and leading to the formation of a BRD8-PHF1 fusion gene. The PHF1 (PHD finger protein 1) gene, from 6p21, is known to be rearranged in ESS in a promiscuous way inasmuch as it has been shown to recombine with JAZF1, EPC1, MEAF6, and now also with BRD8, in tumors of this type. In all rearrangements of PHF1, including the present one, a recurrent theme is that the entire coding part of PHF1 constitutes the 3' end of the fusion. BRD8 (bromodomain containing 8) encodes a protein which is involved in regulation of protein acetylation and/or histone acetyl transferase activity. All the genetic fusions identified so far in ESS appear to recombine genes involved in transcriptional regulation, i.e. polycomb group complex-mediated and aberrant methylation/acetylation genes. This adds to the likelihood that the new BRD8-PHF1 shares the same pathogenetic mechanism as the other ESS-specific rearrangements. This article is protected by copyright. All rights reserved.

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Endoscopic screening for synchronous esophageal neoplasia among patients with incident head and neck cancer: Prevalence, risk factors and outcomes

Abstract

Esophageal squamous-cell neoplasia (ESCN) is a common second primary neoplasia found in patients with head-and-neck squamous-cell carcinoma (HNSCC). This study sought to identify the risk factors for synchronous ESCN and how they influence survival in HNSCC patient. 815 incident HNSCC patients were prospectively recruited for endoscopy screening for ESCN using white-light imaging, narrow-band imaging, Lugol chromoendoscopy, and pathological confirmation. Associated lifestyle and clinicopathological data were collected. The interquartile follow-up period cutoffs were 11.3, 20.5 and 34.9 months. 124 patients (15.2%) were diagnosed as having synchronous ESCN (66 low-grade dysplasia, 29 high-grade dysplasia and 29 esophageal squamous-cell carcinoma). Consumption of alcohol, but not betel nut or cigarette, was significantly associated with the presence of synchronous ESCN (adjusted odds ratio [aOR]= 7.1 and 10.9 for former and current drinkers respectively). There was an interaction between cumulative dose of alcohol consumption and alcohol flushing response on the development of ESCN. High-dose drinkers with flush response were 16.9 times more likely to have esophageal high-grade dysplasia/SCC than non-drinkers. Compared with oral cavity cancer patients, those with hypopharyngeal, laryngeal and oropharyngeal cancer were 6.8, 4.6 and 2.8 times more likely to have esophageal high-grade dysplasia/SCC. HNSCC patients with synchronous ESCN had lower overall survival than those without (p < 0.0001). In conclusion, surveillance of ESCN is strongly recommended for the high-risk subpopulation of HNSCC patients, especially drinkers who have a flush response to alcohol, and those with distant metastasis of index cancer and cancers in hypopharynx, oropharynx and larynx. This article is protected by copyright. All rights reserved.

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Extracts of Salvia-Nelumbinis Naturalis Ameliorate Nonalcoholic Steatohepatitis via Inhibiting Gut-Derived Endotoxin Mediated TLR4/NF-κB Activation

Nonalcoholic steatohepatitis (NASH) is featured by the presence of hepatic steatosis combined with inflammation and hepatocellular injury. Gut-derived endotoxin plays a crucial role in the pathogenesis of NASH. Salvia-Nelumbinis naturalis (SNN), a formula of Traditional Chinese Medicine, has been identified to be effective for NASH, but the mechanisms were not thoroughly explored. In the present study, a NASH model was generated using C57BL/6 mice fed a high fat diet (HFD) supplemented periodically with dextran sulfate sodium (DSS) in drinking water for 12 weeks. Mice fed HFD alone (without DSS) or chow diet were used as controls. The NASH mice were given the SNN extracts in the following 4 weeks, while control mice were provided with saline. Mice fed HFD developed steatosis, and DSS supplementation resulted in NASH. The SNN extracts significantly improved metabolic disorders including obesity, dyslipidemia, and liver steatosis and reduced hepatic inflammation, circulating tumor necrosis factor-α (TNF-α), and lipopolysaccharide (LPS) levels. The beneficial effect of the SNN extracts was associated with restoration of intestinal conditions (microbiota, integrity of intestinal barrier) and inhibition of TLR4/NF-κB activation. These results suggest that the SNN extracts ameliorate NASH progression, possibly through blocking endotoxin related TLR4/NF-κB activation.

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Introduction to Myths & Methodologies series

Podcast available at: http://ift.tt/2tUOKgp

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Myths and methodologies: Making sense of exercise mass and water balance

New Findings

• What is the topic of this review?

  There is a need to revisit the basic principles of exercise mass and water balance, the use of common equations and the practice of interpreting outcomes.

• What advances does it highlight?

  We propose use of the following equation as a way of simplifying exercise mass and water balance calculations in conditions where food is not consumed and waste is not excreted: ∆body mass − 0.20 g/kcal⁻¹ = ∆body water. The relative efficacy of exercise drinking behaviours can be judged using the following equation: percentage dehydration = [(∆body mass − 0.20 g kcal⁻¹)/starting body mass] × 100.

Changes in body mass occur because of flux in liquids, solids and gases. This knowledge is crucial for understanding metabolism, health and human water needs. In exercise science, corrections to observed changes in body mass to estimate water balance are inconsistently applied and often misinterpreted, particularly after prolonged exercise. Although acute body mass losses in response to exercise can represent a close surrogate for body water losses, the discordance between mass and water balance equivalence becomes increasingly inaccurate as more and more energy is expended. The purpose of this paper is briefly to clarify the roles that respiratory water loss, gas exchange and metabolic water production play in the correction of body mass changes for fluid balance determinations during prolonged exercise. Computations do not include waters of association with glycogen because any movement of water among body water compartments contributes nothing to water or mass flux from the body. Estimates of sweat loss from changes in body mass should adjust for non-sweat losses when possible. We propose use of the following equation as a way of simplifying the study of exercise mass and water balance: ∆body mass − 0.20 g kcal⁻¹ = ∆body water. This equation directly controls for the influence of energy expenditure on body mass balance and the approximate offsetting equivalence of respiratory water loss and metabolic water production on body water balance. The relative efficacy of exercise drinking behaviours can be judged using the following equation: percentage dehydration = [(∆body mass − 0.20 g kcal⁻¹)/starting body mass] × 100.

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Commentary on Myths and Methodologies: Making sense of exercise mass and water balance

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Development of Metarhizium anisopliae as a Mycoinsecticide: From Isolation to Field Performance

Here, we report the different stages involved in the knowledge-based development of an effective mycoinsecticide, including the isolation, identification, screening, and selection of the "best-fit" entomopathogenic fungus, Metarhizium anisopliae, for the control of insect pests in agriculture.

http://ift.tt/2uafPXR

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. The complexes were tested for catalytic activity in arylation and Suzuki-Miyaura reactions. For each reaction investigated, at least one of the four complexes successfully catalyzed the reaction.

http://ift.tt/2uKAeXa

A Free-breathing fMRI Method to Study Human Olfactory Function

We present the technical challenges and solutions for obtaining reliable functional magnetic resonance imaging (fMRI) data from the human central olfactory system. This includes special considerations in olfactory fMRI paradigm design, descriptions of fMRI data acquisition with an MRI-compatible olfactometer, odorant selection, and a special software tool for data post-processing.

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A Challenging Diagnosis of IgG4-Related Disease When Understanding Limitations of Laboratory Testing Was Pivotal

A 76-year-old man was incidentally found on a CT scan to have lymphadenopathy and bilateral kidney enlargement suggestive of infiltrative renal disease. He was largely asymptomatic but had bilateral salivary and lacrimal gland enlargement. A grossly elevated serum IgG (>70 g/L) with concomitant suppression of other immunoglobulins, a small IgG restriction, and a parotid biopsy revealing lymphoplasmacytic infiltrate with slight kappa light chain excess all suggested a lymphoproliferative disorder (LPD). The diagnostic workup was further confounded by a normal serum IgG4 concentration. Moreover, bone marrow and renal biopsies did not reveal evidence of LPD. Discussion with the laboratory not only clarified that the markedly increased total IgG could not be accounted for by the small IgG restriction, but also identified a discrepancy in the IgG4 measurement. Repeat analysis of a follow-up sample revealed an elevated IgG4 of 5.94 (reference interval: 0.039–0.864) g/L, which prompted a repeat parotid biopsy that showed predominant IgG4+ lymphocytic infiltrates. Despite the deluding presentations, a final diagnosis of IgG4-related disease (IgG4-RD) was made based on elevated serum IgG4 concentrations and histopathological findings. This case highlights the importance of recognizing limitations of laboratory testing and the benefit of close communications among clinical subspecialties and the laboratory.

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Management of Penetrating Skull Base Injury: A Single Institutional Experience and Review of the Literature

Background. Penetrating skull base injury (PSBI) is uncommon among head injuries, presenting unique diagnostic and therapeutic challenges. Although many cases of PSBIs have been reported, comprehensive understanding of its initial diagnosis, management, and outcome is still unavailable. Materials and Methods. A retrospective review was performed for patients treated in neurosurgical department of Changzheng Hospital for PSBIs. Presurgical three-dimensional (3D) Slicer-assisted reconstructions were conducted for each patient. Then we reviewed previous literature about all the published cases of PSBIs worldwide and discussed their common features. Results. A total of 5 patients suffering PSBIs were identified. Penetrating points as well as the surrounding neurovascular structures were clearly visualized, assisting in the presurgical planning of optimal surgical approach and avoiding unexpected vascular injury. Four patients underwent craniotomy with foreign bodies removed successfully and 1 patient received conservative treatment. All of them presented good outcomes after proper management. Conclusion. Careful physical examination and radiological evaluation are essential before operation, and angiography is recommended for those with suspected vascular injuries. 3D modeling with 3D Slicer is practicable and reliable, facilitating the diagnosis and presurgical planning. Treatment decision should be made upon the comprehensive evaluation of patient's clinicoradiological features and characteristics of foreign bodies.

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The role of anaplastic lymphoma kinase in pediatric cancers

Abstract

The anaplastic lymphoma kinase (ALK) was initially identified as a fusion partner of the nucleophosmin gene in anaplastic large cell lymphoma (ALCL) with t(2;5)(p23;q35) translocation, and then described with different genetic abnormalities in a number of tumors. Although ALK is known to be involved in the pathogenesis of neuroblastoma through activating mutations or gene amplification, its role in the pathogenesis of other pediatric cancers is still elusive. In addition to neuroblastoma, the high-grade amplification of ALK has been described in a subset of rhabdomyosarcoma cases. Normal ALK protein expression is restricted to the nervous systems of adult mammals, but the aberrant expression of ALK has been observed in a variety of pediatric cancers, including glioma and Ewing sarcoma. The discovery of oncogenic activation of ALK in neuroblastoma suggests that this cancer could be potentially treated with an ALK inhibitor, as could other cancers, such as non-small cell lung cancer and ALCL. However, cellular responses to mutant ALK are complex when compared to rearranged ALK, and treatment remains a challenge. This review focuses on the biology of ALK in pediatric cancers and possible therapeutic strategies for ALK-associated tumors.

This article is protected by copyright. All rights reserved.

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Double-edged sword of mesenchymal stem cells: cancer-promoting VS therapeutic potentials

Summary

Mesenchymal stem cells (MSCs) derived from adipose tissue, bone marrow, cord blood, and other tissues, have recently attracted much attention as potential therapeutic agents in various diseases due to their trans-differentiation capacity. However, recent studies suggested that MSCs also appear to contribute tumor pathogenesis by supporting tumor microenvironments, increasing tumor growth, and eliciting anti-tumor immune responses. While some studies suggest that MSCs have the inhibitory effects on tumor development, they are overwhelmed by a member of researches that MSCs exert stimulatory effects on tumor pathogenesis. In this review article, we summarized a number of findings to provide current information about their therapeutic potential in various diseases; we then discussed the potential roles of MSCs in tumor progression.

This article is protected by copyright. All rights reserved.

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Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners

We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands), and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km), directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD) and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time ( versus  min, ), ingested less fluids ( versus  mL, ) during the race, and lost much more weight ( versus  kg, ). Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation.

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Oral Administration of Red Ginseng Extract Promotes Neurorestoration after Compressive Spinal Cord Injury in Rats

Red ginseng and its active ingredients have been shown to decrease neuron death after brain ischemia in experimental animals. However, little is known about the effects of orally administered ginseng extract on spinal cord injury. We orally gave red ginseng extract (RGE) to rats with compressed spinal cord injury (SCI). Open-field locomotor scores were measured as indices of motor function. Histopathological changes and cytokine expressions in situ after SCI were evaluated. Compared to vehicle treatment, RGE treatment (350 mg/kg/day) significantly improved locomotor score up to levels close to those pre-SCI, prevented neuron loss, and facilitated the restoration of white matter in the spinal cord at 14 days after SCI. Treatment with RGE caused less aggregation of Iba-1-positive microglia in grey and white matter at 7 days after SCI, upregulated the expression levels of VEGF and Bcl-xL, and reduced IL-1β and TNFα expressions in the spinal cord at 7 and 14 days after SCI. We concluded that oral administration of RGE facilitates almost complete functional recovery from motor and behavioral abnormalities in rats with SCI and prevents neuron death in situ, possibly through inhibition of inflammation and upregulation of neuroprotective factors in the injured spinal cord.

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Structure-based discovery of new selective small molecule sirtuin 5 inhibitors

Abstract

Human sirtuin 5 (SIRT5) is a protein deacylase regulating metabolic pathways and stress responses, and is implicated in metabolism-related diseases. Small molecule inhibitors for SIRT5 are sought as chemical tools and potential therapeutics. Herein we proposed a customized virtual screening approach targeting catalytically important and unique residues Tyr102 and Arg105 of SIRT5. Of the 20 tested virtual screening hits, 6 compounds displayed marked inhibitory activities against SIRT5. For the hit compound 19, a series of new synthesized (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues were carried out structure-activity relationship analyses, resulting in new more potent inhibitors, among which 37 displayed the most potent inhibition to SIRT5 with an IC₅₀ value of 5.59 ± 0.75 μM. The biochemical studies revealed that 37 likely acts via competitive inhibition with the succinyl-lysine substrate, rather than the NAD⁺ cofactor, and it manifested substantial selectivity for SIRT5 over SIRT2 and SIRT6. This study will aid further efforts to develop new selective SIRT5 inhibitors as tools and therapeutics.

This article is protected by copyright. All rights reserved.

This study proposed a customized virtual screening approach targeting catalytically important and unique residues Tyr102 and Arg105 of SIRT5, which led to the identification of new hit compounds. Subsequent structure-activity relationship studies resulted in new more potent SIRT5 inhibitors. The biochemical studies revealed that the most potent compound 37 likely acts via competitive inhibition with the succinyl-lysine substrate, rather than the NAD⁺ cofactor, and it manifested substantial selectivity for SIRT5 over SIRT2 and SIRT6.

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Prostate Carcinoma with Amphicrine Features: Further Refining the Spectrum of Neuroendocrine Differentiation in Tumours of Primary Prostatic Origin?

Abstract

Objective

The current WHO classification categorises high grade neuroendocrine (NE) carcinomas of the prostate into small cell and large cell types. A distinct form of carcinoma demonstrating synchronous dual exocrine and NE differentiation, termed amphicrine carcinoma, has been described at various other sites, primarily within the gastrointestinal tract. In this study, we describe the clinicopathologic features of a series of metastatic prostatic carcinomas with amphicrine features.

Methods

Five cases of high grade prostatic carcinoma (PCa) demonstrating an amphicrine immunohistochemical phenotype were prospectively collected.

Results

Serum prostate specific antigen (PSA) level at diagnosis ranged from 38-992ng/ml (median 200ng/ml). All 5 patients had metastatic disease; 4 at initial presentation. Microscopically, the tumours demonstrated a solid/nested growth pattern composed of cells with amphophilic cytoplasm, vesicular nuclei and macronucleoli. Morphologic features of small cell or large cell NE carcinoma were absent. Compared with conventional high grade PCa, the tumour cells displayed greater nuclear pleomorphism, brisk mitotic activity and a high Ki67 proliferation index (median 50%). All cases demonstrated immunohistochemical positivity for PSA, androgen receptor (AR) and prostatic specific acid phosphatase (PSAP) combined with diffuse or confluent/non-focal positivity for chromogranin-A and synaptophysin. Two hormone-naive cases showed a clinical response to androgen deprivation therapy.

Conclusion

This series highlights a previously undefined, clinically aggressive variant of PCa exhibiting dual exocrine and NE differentiation, for which we are proposing the term PCa with amphicrine features. Increased recognition of these tumours may lead to a better understanding of their biology and ultimately improve their clinical management.

This article is protected by copyright. All rights reserved.

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MDM4 amplification in a case of dedifferentiated liposarcoma and in silico data supporting an oncogenic event alternative to MDM2 amplification in a subset of cases

Abstract

Well differentiated and dedifferentiated liposarcomas (WD/DDLPS) are underlined by 12q13-q14 amplifications encompassing MDM2, considered as the core oncogene driving their pathogenesis through TP53 inactivation^{1, 2}. Their progression involves the inactivation of the RB1 pathway through CDKN2A-CCND1-CDK4 alterations³. According to the French sarcoma database RRePS, 1% of cases suspicious for WD/DDLPS fail to prove MDM2 amplification, therefore suggesting that alternative oncogenic pathways might replace MDM2 amplification.

This article is protected by copyright. All rights reserved.

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Microscopic tubal sex cord proliferations with a Sertoli cell tumour pattern and ovarian-type stromal transformation of the fimbriae

Abstract

A recent paper¹ reported microscopic nodules of sex-cord stromal proliferations mimicking adult granulosa cell and sex-cord tumour with annular tubules in extraovarian locations. However, Sertoli cell tumour patterns were not described in them. We add two cases of multiple, microscopic foci of differentiated Sertoli cell proliferation in the fallopian tube, one of which coexisted and merged with areas of fimbrial ectopic ovarian-like stroma.

Both cases were incidental findings in the fallopian tubes from 42 and 35 year-old patients, operated respectively for uterine leiomyoma and ovarian grade 1 endometrioid carcinoma. Both were recent cases with short follow-up.

This article is protected by copyright. All rights reserved.

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The HII Score – A Novel Tool to Assess Impairment from Alcohol in Emergency Department Patients

Abstract

Background

Over 35 million alcohol impaired (AI) patients are cared for in Emergency Departments (EDs) annually. Emergency physicians are charged with ensuring AI patients' safety by identifying resolution of alcohol induced impairment. The most common standard evaluation is an extemporized clinical examination, as ethanol levels are not reliable or predictive of clinical symptoms. There is no standard assessment of ED AI patients.

Objective

To evaluate a novel standardized emergency department assessment of alcohol impairment — Hack's Impairment Index (HII score), in a busy urban Emergency Department.

Methods

A retrospective chart review was performed for all AI patients seen in our busy urban ED over 24 months. Trained nurses evaluated AI patients with both "usual" and HII score every 2 hours. Patients were stratified by frequency of visits for AI during this time: high (≥ 6), medium (2-5), and low (1). Within each category, comparisons were made between HII scores, measured ethanol levels, and usual nursing assessment of AI. Changes in HII scores over time were also evaluated.

Results

8074 visits from 3219 unique patients were eligible for study, including 7973 (98.7%) with ethanol levels, 5061 (62.7%) with complete HII scores, and 3646 (45.2%) with HCP assessments. Correlations between HII scores and ethanol levels were poor (Pearson's R² = 0.09, 0.09, and 0.17 for high-, medium-, and low-frequency strata). HII scores were excellent at discriminating nursing assessment of AI, while ethanol levels were less effective. Omitting extrema, HII scores fell consistently an average 0.062 points per hour, throughout patients' visits.

Conclusions

The HII score applied a quantitative, objective assessment of alcohol impairment. HII scores were superior to ethanol levels as an objective clinical measure of impairment. The HII declines in a reasonably predictable manner over time, with serial evaluations corresponding well with HCP evaluations.

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Patient and Surrogate Views of Community Consultation for Emergency Research

Abstract

Objective

Pre-trial community consultation (CC) is required for emergency research conducted under an exception from informed consent (EFIC) in the United States. CC remains controversial and challenging, and minimal data exist regarding the views of individuals enrolled in EFIC trials on this process. It is important to know whether participants perceive CC to be meaningful and, if so, whom they believe should be consulted.

Methods

We conducted a secondary analysis of data from two studies interviewing patients and surrogates of two recent EFIC trials (PEER-RAMPART and PEER-ProTECT). These interviews included similar open- and closed-ended questions regarding participants' views of the importance of CC, the rationale for their responses, and their views regarding which populations should be included in consultation efforts. A template analytic strategy was used for qualitative analysis of textual data, and descriptive statistics were tabulated to characterize demographic data and instances of major themes.

Results

90% of participants perceived CC to be valuable. Participants' reasons for finding CC valuable clustered in 2 categories: 1) as a method of informing the public about the trial to be conducted; and 2) as a way of obtaining input and feedback from the community. Participants cited the medical community (43%) and individuals with a connection to the study condition (41%) as the most important groups to involve in consultation efforts; only 5% suggested consulting the general public in the area where the research will be conducted.

Conclusion

Participants in EFIC trials and their decision-makers generally valued CC as a method of informing and seeking input from the community. Participants felt that the most appropriate groups to consult were the medical community and individuals with connections to the condition under study. Consultation efforts focused on these two groups, rather than the general public, may be more efficient and more meaningful to individuals involved in EFIC trials. These findings also reinforce the importance of the distinction between public disclosure and CC.

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miR-202 Suppresses Cell Proliferation by Targeting FOXR2 in Endometrial Adenocarcinoma

Background. MicroRNA-202 (miR-202) has been reported to be aberrantly regulated in several cancers. The aim of this study is to explore the functional role of miR-202 in EAC tumor growth. Material and Methods. miR-202 expression was detected by qRT-PCR. TargetScan and luciferase reporter assay were used to elucidate the candidate target gene of miR-202. The FOXR2 protein level was assessed by Western blot and immunohistochemistry. Survival analysis was explored for FOXR2 expression in EAC patients. Results. miR-202 expression was significantly decreased in EAC tissues () compared with that in control tissues. And the downregulate miR-202 was significantly associated with poor prognosis (). Re-expression of miR-202 dramatically suppressed cell proliferation in vitro and tumor growth in vivo. FOXR2 was identified as a direct target of miR-202. In EAC tissues, FOXR2 was upregulated and the increased FOXR2 was significantly associated with poor prognosis. In miR-202-transfected cells, the FOXR2 expression was inversely changed. The analysis of FOXR2 protein expression and miR-202 transcription in EAC tissues showed negative correlation (). Conclusion. miR-202 may function as a tumor suppressor in EAC tumor growth by targeting FOXR2 oncogene, which may provide new insights into the molecular mechanism and new targets for treatment of EAC.

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Kawasaki Disease Increases the Incidence of Myopia

The prevalence of myopia has rapidly increased in recent decades and has led to a considerable global public health concern. In this study, we elucidate the relationship between Kawasaki disease (KD) and the incidence of myopia. We used Taiwan's National Health Insurance Research Database to conduct a population-based cohort study. We identified patients diagnosed with KD and individuals without KD who were selected by frequency matched based on sex, age, and the index year. The Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence intervals for the comparison of the 2 cohorts. The log-rank test was used to test the incidence of myopia in the 2 cohorts. A total of 532 patients were included in the KD cohort and 2128 in the non-KD cohort. The risk of myopia (hazard ratio, 1.31; 95% confidence interval, 1.08–1.58; ) was higher among patients with KD than among those in the non-KD cohort. The Cox proportional hazards regression model showed that irrespective of age, gender, and urbanization, Kawasaki disease was an independent risk factor for myopia. Patients with Kawasaki disease exhibited a substantially higher risk for developing myopia.

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MET18 Deficiency Increases the Sensitivity of Yeast to Oxidative Stress and Shortens Replicative Lifespan by Inhibiting Catalase Activity

Yeast MET18, a subunit of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery which is responsible for the maturation of Fe/S proteins, has been reported to participate in the oxidative stress response. However, the underlying molecular mechanisms remain unclear. In this study, we constructed a MET18/met18Δ heterozygous mutant yeast strain and found that MET18 deficiency in yeast cells impaired oxidative stress resistance as evidenced by increased sensitivity to hydrogen peroxide (H2O2) and cumene hydroperoxide (CHP). Mechanistically, the mRNA levels of catalase A (CTA1) and catalase T (CTT1) as well as the total catalase activity were significantly reduced in MET18-deficient cells. In contrast, overexpression of CTT1 or CTA1 in MET18-deficient cells significantly increased the intracellular catalase activity and enhanced the resistance ability against H2O2 and CHP. In addition, MET18 deficiency diminished the replicative capacity of yeast cells as evidenced by the shortened replicative lifespan, which can be restored by CTT1 overexpression, but not by CTA1, in the MET18-deficient cells. These results suggest that MET18, in a catalase-dependent manner, plays an essential role in enhancing the resistance of yeast cells to oxidative stress and increasing the replicative capacity of yeast cells.

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Clinical significance of dynamic measurements of seric TNF-α, HMGBl, and NSE levels and aEEG monitoring in neonatal asphyxia

L'articolo Clinical significance of dynamic measurements of seric TNF-α, HMGBl, and NSE levels and aEEG monitoring in neonatal asphyxia sembra essere il primo su European Review.

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Verification of Three-Phase Dependency Analysis Bayesian Network Learning Method for Maize Carotenoid Gene Mining

Background and Objective. Mining the genes related to maize carotenoid components is important to improve the carotenoid content and the quality of maize. Methods. On the basis of using the entropy estimation method with Gaussian kernel probability density estimator, we use the three-phase dependency analysis (TPDA) Bayesian network structure learning method to construct the network of maize gene and carotenoid components traits. Results. In the case of using two discretization methods and setting different discretization values, we compare the learning effect and efficiency of 10 kinds of Bayesian network structure learning methods. The method is verified and analyzed on the maize dataset of global germplasm collection with 527 elite inbred lines. Conclusions. The result confirmed the effectiveness of the TPDA method, which outperforms significantly another 9 kinds of Bayesian network learning methods. It is an efficient method of mining genes for maize carotenoid components traits. The parameters obtained by experiments will help carry out practical gene mining effectively in the future.

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