Posterior cordotomy in bilateral vocal cord paralysis using monopolar microelectrodes and radiofrequency in 18 patients

Abstract

Posterior cordotomy is an option in the surgical treatment of bilateral vocal cord paralysis in adduction.

We present results obtained in 18 patients with bilateral vocal cord paralysis in adduction treated using microelectrodes terminal with tips in several angles, and a radiofrequency generator from 2008 to 2013.

The functional outcome was evaluated using postoperative spirometry, the decannulation time, and swallowing.

All patients except one were successfully decannulated and showed an increase in mid-inspiratory flow rates.

The angled shape of the ME tips permits a very good resection for cordotomy; ME and radiofrequency are an excellent alternative to CO2 laser.

This article is protected by copyright. All rights reserved.

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Extranasopharyngeal Angiofibroma Revisited

Abstract

Background

Angiofibromas in the head and neck region usually arise in the nasopharynx, but may also occur elsewhere. This study aims at evaluating the incidence and clinical features of extranasopharyngeal angiofibroma (ENA).

Material and Methods

Systematic review of the literature (Medline^® and Google^™) up to December 31^st, 2015.

Results

174 cases of ENA were retrieved from a total of 170 publications. In contrast to former publications and previous understanding, the nasal septum was by far the most common site of the disease. Four patients had a congenital lesion, the oldest patient was 87 years old (mean: 28.7 years; median: 23 years). Male gender was predominantly affected, but the sex ratio was more balanced (2.13:1) than in previous reports in the literature until 12/2015. The majority of patients presented with nasal obstruction, either in combination with epistaxis (25.8%) or other symptoms (12.6%). Symptoms had developed within 13.1 months on average (median: 4 months). Brisk bleeding resulted in 11 of 43 biopsy procedures. Surgical resection as first-line therapy was performed in 170 patients. A tumor regrowth within 12 months was registered in four patients.

Conclusion

The increasing awareness of ENA and the willingness to publish case reports -not only in Medline listed journals- resulted in a significant increase of published case reports lately. Although extremely rare, ENAs have to be taken into account in the differential diagnosis of unclear masses, particularly in adult patients presenting with a rapidly developing nasal obstruction resulting from a nasal septum tumor. Female gender or normal vascularity does not exclude the diagnosis. Transnasal resection is sufficient in most cases and recurrences are rare. Pathologists as well as clinicians should consider ENA in their differential diagnosis of any mass of the upper airway.

This article is protected by copyright. All rights reserved.

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Involvement of adenosine triphosphate-binding cassette subfamily B member 1 in the augmentation of triacylglycerol excretion by Propionibacterium acnes in differentiated hamster sebocytes

Abstract

An onset of acne, a common inflammatory skin disease, is associated with excess sebum production and secretion in sebaceous glands. Because Propionibacterium acnes has been reported to augment intracellular sebum accumulation in sebaceous glands in hamsters, it remains unclear whether P. acnes influences sebum secretion from differentiated sebocytes. Both P. acnes culture media (Acnes73-CM) and formalin-killed P. acnes (F-Acnes73) dose-dependently increased the extracellular levels of triacylglycerol (TG), a major sebum component, and Rhodamine 123, a substrate of adenosine triphosphate-binding cassette (ABC) transporter, from differentiated hamster sebocytes (DHS). In addition, the gene expression of the ABC subfamily B member 1 (ABCB1) was dose-dependently augmented by adding Acnes73-CM and F-Acnes73 into DHS. Furthermore, the F-Acnes73-induced increase of TG excretion was suppressed by PSC833, a selective ABCB1 inhibitor. On the other hand, peptidoglycan (PGN), which is a Toll-like receptor 2 (TLR2) ligand in P. acnes, increased extracellular TG levels, transporter activity and ABCB1 mRNA expression in DHS. The PGN-augmented TG excretion was suppressed by PSC833. Thus, these results provide novel evidence that P. acnes facilitates sebum secretion due to the activation of ABCB1 concomitantly with the increased ABCB1 expression, which may result from the activation of the TLR2 pathway in DHS. Therefore, the ABCB1 inhibitor is likely to become a candidate as a possible therapeutic for the treatment of acne.

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Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized, placebo-controlled phase 3 trial

Abstract

Tofacitinib is an oral Janus kinase inhibitor. These post-hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52-week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo-treated patients advanced to tofacitinib at week 16. Primary efficacy end-points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment (PGA) of "clear" or "almost clear" (PGA response) at week 16. Other end-points included: Itch Severity Item (ISI), Dermatology Life Quality Index (DLQI) score and Nail Psoriasis Severity Index (NAPSI). Adverse events (AEs) were recorded throughout the study. Overall, 58 Japanese patients were included in this analysis (tofacitinib 5 mg b.i.d., n = 22; 10 mg b.i.d., n = 24; placebo, n = 12); 29 completed the study. At week 16, significantly more patients receiving tofacitinib 5 and 10 mg b.i.d. versus placebo achieved PASI-75 (50% and 75% vs 0%, P < 0.01) and PGA response (59% and 75% vs 0%, P < 0.001). Substantial improvements in ISI, DLQI and NAPSI score were observed with both tofacitinib doses. Over 52 weeks, similar rates of AEs were reported across treatment groups; one serious AE occurred with tofacitinib 10 mg b.i.d. Herpes zoster occurred in three patients receiving tofacitinib 10 mg b.i.d. No deaths, serious infections, malignancies or gastrointestinal perforations were reported. Results were generally consistent with global analysis, suggesting sustained efficacy and a manageable safety profile, with increased herpes zoster incidence, of tofacitinib in Japanese patients with psoriasis.

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Novel COL5A1 mutation in a Chinese family with classic type of Ehlers–Danlos syndrome

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Secondary syphilis primarily presenting with multiple nodules on the scalp: Case report and published work review

Abstract

Syphilis, a sexually transmitted disease caused by Treponema pallidum, manifests with a broad spectrum of clinical presentations that usually involves skin. Nodular secondary syphilis occurs rarely, and mostly manifests as disseminated papulonodules or plaques over the trunk and limbs. We report an extremely rare case of nodular secondary syphilis that primarily presented with multiple nodules on the scalp, resembling Rosai–Dorfman disease or cutaneous malignant metastasis. Immunohistochemistry confirmed T. pallidum spirochetes microscopically.

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Increased endocan expression in lesional skin and decreased endocan expression in sera in atopic dermatitis

Abstract

Endocan is a novel human endothelial cell-specific molecule and is mainly expressed in endothelial cells in various tissues. Endocan has the capacity to inhibit leukocytes binding to the vascular endothelium. It also can promote the angiogenesis alongside vascular endothelial growth factor A. Through these functions, endocan has been implicated in the pathogenesis of various inflammatory diseases. To investigate the possible roles of endocan in atopic dermatitis (AD), we examined endocan expression in lesional skin and sera in patients with AD. Endocan mRNA and protein levels were increased in lesional skin of AD compared with healthy skin and endocan was expressed on epidermal keratinocytes and dermal endothelial cells. On the other hand, serum endocan levels in patients with AD were significantly lower than those in healthy controls. Our results suggest that elevated endocan expression in lesional skin may be associated with development of AD through angiogenesis and that decreased endocan expression in sera may be associated with increased leukocyte recruitment in AD.

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Case of inflammatory tinea corporis affecting the dorsal surface of the thumb in a nail salon technician

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The Pinocchio effect and the Cold Stress Test: Lies and thermography

Abstract

We applied the use of thermography to cognitive neuropsychology, particularly as an objective marker of subjective experiences, in the context of lying. We conducted three experiments: (a) An important lie was invented by the participants in 3 min, and it was recounted by phone to a significant person while they were recorded by the thermographic camera, obtaining a face and hands map of the lie. (b) A similar methodology was carried out, but adding the Cold Stress Test (CST) of the dominant hand during the phone call, obtaining a second physiologic marker (the percentage of thermal recovery) to detect the lie. Further, it established a control condition where it generated anxiety in the participants using IAPS images with negative valence and high arousal, which were described by phone to a loved one. We obtained results that showed significant correlations between changes in body temperature and mental set. Of particular interest was the temperature of the nose and hand, which tended to decrease during lying (Experiment 1). The participants also showed a lower recovery of the temperature after the CST when they were lying (Experiment 2). (c) Experiment 3 is a replication of Experiment 2 but with a different type of lie (a more ecological task) in a different scenario (following the ACID interview, with the use of the phone eliminated and participants motivated to lie well). The main pattern of results was replicated. We obtained an accuracy of 85% in detection of deception with 25% of false alarms.

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Combining two model systems of psychosis: The effects of schizotypy and sleep deprivation on oculomotor control and psychotomimetic states

Abstract

Model systems of psychosis, such as schizotypy or sleep deprivation, are valuable in informing our understanding of the etiology of the disorder and aiding the development of new treatments. Schizophrenia patients, high schizotypes, and sleep-deprived subjects are known to share deficits in oculomotor biomarkers. Here, we aimed to further validate the schizotypy and sleep deprivation models and investigated, for the first time, their interactive effects on smooth pursuit eye movements (SPEM), prosaccades, antisaccades, predictive saccades, and measures of psychotomimetic states, anxiety, depression, and stress. To do so, n = 19 controls and n = 17 high positive schizotypes were examined after both a normal sleep night and 24 h of sleep deprivation. Schizotypes displayed higher SPEM global position error, catch-up saccade amplitude, and increased psychotomimetic states. Sleep deprivation impaired SPEM, prosaccade, antisaccade, and predictive saccade performance and increased levels of psychotomimetic experiences. Additionally, sleep deprivation reduced SPEM gain in schizotypes but not controls. We conclude that oculomotor impairments are observed in relation to schizotypy and following sleep deprivation, supporting their utility as biomarkers in model systems of psychosis. The combination of these models with oculomotor biomarkers may be particularly fruitful in assisting the development of new antipsychotic or pro-cognitive drugs.

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Software-Defined Radio FPGA Cores: Building towards a Domain-Specific Language

This paper reports on the design and implementation of an open-source library of parameterizable and reusable Hardware Description Language (HDL) Intellectual Property (IP) cores designed for the development of Software-Defined Radio (SDR) applications that are deployed on FPGA-based reconfigurable computing platforms. The library comprises a set of cores that were chosen, together with their parameters and interfacing schemas, based on recommendations from industry and academic SDR experts. The operation of the SDR cores is first validated and then benchmarked against two other cores libraries of a similar type to show that our cores do not take much more logic elements than existing cores and that they support a comparable maximum clock speed. Finally, we propose our design for a Domain-Specific Language (DSL) and supporting tool-flow, which we are in the process of building using our SDR library and the Delite DSL framework. We intend to take this DSL and supporting framework further to provide a rapid prototyping system for SDR application development to programmers not experienced in HDL coding. We conclude with a summary of the main characteristics of our SDR library and reflect on how our DSL tool-flow could assist other developers working in SDR field.

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Neural control of sweat secretion: a review

Abstract

Humans have 4 million exocrine sweat glands, which can be classified into two types: eccrine and apocrine glands. Sweat secretion is a constitutive feature, which is directly involved in thermoregulation and metabolism. Sweat secretion is regulated by both the central nervous system¹ and autonomic nervous system.² In peripheral areas, the ANS, especially the sympathetic nervous system (SNS), mediates the transmission of neurotransmitters to sweat glands. Two principal chemical mediators, acetylcholine and noradrenaline (NA)/adrenaline (ADR), are released by the SNS, which stimulate sweat secretion. In the CNS, the thermoregulatory center in the hypothalamus responds to the elevated body temperature by increasing sweating, whereas emotional stresses stimulate the limbic system to induce sweating. The ANS mediates sweating that is due to stimulation of the thermoregulatory center and limbic system. In this review, we focus on the neural control of sweat secretion and the mechanisms by which chemical mediators induce sweating. In addition, we will discuss the sweating disorders associated with neural anomaly as well as the treatments.

This article is protected by copyright. All rights reserved.

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The BRAF and NRAS mutation prevalence in dermoscopic subtypes of acquired naevi reveals constitutive MAPK pathway activation

Summary

Background

Acquired naevi can have unique dermoscopic patterns that correspond to distinct microanatomical growth patterns. Previous studies on acquired naevi stratified according to dermoscopic pattern, focused on the frequency of somatic BRAF mutations, whereas NRAS mutations remained to be elucidated.

Objectives

To investigate the BRAF and NRAS mutation prevalence and activation of the MAPK pathway in distinct dermoscopic subtypes of acquired naevi.

Methods

Common mutations present in BRAF and NRAS were assessed in 40 globular, reticular, and peripheral rim of globules (PG) subtypes of acquired naevi from 27 participants (19 male, 8 female; mean age 46.7 years) selected from 1261 eligible volunteers. Mutations were determined using the highly sensitive and quantitative QX200 droplet digital^™ PCR (ddPCR) system.

Results

The BRAFV600E (c.1799T>A or c.1799_1800delTGinsA) and BRAFV600K mutations were detected in 85% (n=34/40) of naevi. All BRAF wild-type naevi (15%; n=6/40) harboured an NRAS codon 12/13 or 61 mutation. BRAF mutations were present in 92% (n=12/13) of globular and 100% (n=12/12) of PG naevi, whereas reticular naevi were 67% (n=10/15) BRAF and 33% (n=5/15) NRAS mutant (p=0.037).

Conclusions

We discovered that 100% of the assessed acquired naevi had either a BRAF or NRAS mutation. Using sensitive techniques capable of single-cell mutation detection, it is likely that all acquired naevi will be mutated for BRAF or NRAS. Since both of these mutations are prevalent in distinct dermoscopic naevus subsets, our study supports the role of the MAPK pathway in the development of benign melanocytic proliferations, indicating that additional genomic events besides somatic mutations in BRAF or NRAS are required for melanoma development.

This article is protected by copyright. All rights reserved.

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An uncommon cause of warm foot

Description

A 66-year-old man presented with swelling and redness of right foot of 1 month duration. He was a known diabetic for 20 years; glycaemic control was suboptimal. There was no history of trauma, fever, ulcer or deformity. He had numbness of both feet and was earlier documented to have mild non-proliferative diabetic retinopathy. On examination, he was not feverish with erythema, swelling (figure 1), local rise of temperature of the right foot and a difference of 2°C between both feet and no tenderness on palpation. There was loss of protective sensations with absent ankle jerks with bounding pulses in both feet. Systemic examination was unremarkable. His blood investigations revealed haemoglobin of 12 g/dL (N 12–15), total white cell count of 9.8x10⁹ /L/cmm (N 4000–11000), erythrocyte sedimentation rate of 48 mm/hour and haemoglobin A1c of 8.1% (n<5.7). Based on history and clinical findings and absent elevation of acute inflammatory markers, a diagnosis of acute...

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IgG4-related disease: long-term natural history and management of a relapsing multisystem disease entity

Although awareness of IgG4-related disease has grown over the past decade, with earlier diagnosis and treatment, understanding of its natural history over the long term and the optimal management remains unclear. We report the case of a 48-year-old man who presented with a pancreatic pseudotumour causing bile duct obstruction with coexisting autoimmune hepatitis and multisystem involvement. His symptoms settled on steroids and maintenance with azathioprine was commenced, however periodic relapses occurred involving multiple organs. A timeline-relating IgG4 levels, clinical features and immunosuppressive therapy are presented. The protean and relapsing–remitting nature of this condition is emphasised, and a brief review of long-term therapeutic options is provided.

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Solitary fibrous tumour: a rare tumour of the pleural cavity

Solitary fibrous tumours are a rare group of tumours that originate from connective tissues such as the pleura and mediastinum. When growing within the thoracic cavity these tumours exert pressure on vital organs and large vessels. We have successfully operated on two patients with large solitary fibrous tumours and managed the pathophysiological changes manifested as superior vena cava syndrome resulting from these tumours.

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Necrotising enterocolitis after supraventricular tachycardia: an unusual precursor to a common problem

Supraventricular tachycardia (SVT) is the most common neonatal arrhythmia. Necrotising enterocolitis (NEC) is a disease with multifactorial aetiology, most common in preterm infants. There are three previous case reports in the literature of NEC following neonatal SVT. We present two cases of late preterm infants with NEC, characterised by pneumatosis on abdominal X-ray and ultrasound, following recurrent SVT without haemodynamic instability. The infants were successfully treated with antibiotic therapy and bowel rest.

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The Duari hernia and recognition of the femoral vein compression sign

Femoral hernias can be difficult to diagnose and are at high risk of strangulation. This report is of a rare case of an irreducible femoral hernia containing caecum and appendix presenting as an emergency. To the authors' knowledge, there have only been three cases reported, the first described by Duari. This case was incorrectly diagnosed preoperatively as an inguinal hernia, so the CT diagnosis of femoral hernias is reviewed, in particular demonstrating the radiological use of the femoral vein compression sign.

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Syndromic congenital diarrhoea: new SPINT2 mutation identified in the UAE

We are reporting a new mutation in the SPINT2 gene (c.443G>A (p. Arg148His)) that explains the association of choanal atresia with congenital sodium diarrhoea (CSD) in an Emirati family in the Middle East. To our knowledge, this mutation is neither listed in a mutation database nor described in the literature. Similar to other patients with CSD associated with SPINT2, this child remains dependent on parenteral nutrition for fluids and nutritional support resulting in failure to thrive. The determination of the molecular basis of syndromic CSD will facilitate prenatal and postnatal diagnosis of patients and will contribute to counselling of affected families, especially in areas like the UAE where consanguineous marriages are not uncommon.

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Why is it so hard to reach agreement on terminology? The case of developmental language disorder (DLD)

Abstract

A recent project entitled CATALISE used the Delphi method to reach a consensus on terminology for unexplained language problems in children. 'Developmental language disorder' (DLD) was the term agreed by a panel of 57 experts. Here I reflect on points of difficulty that arose when attempting to reach a consensus, using qualitative information from comments made by panel members to illustrate the kinds of argument used. One issue of debate was the use of labels, in particular the term 'disorder', which was seen as having both pros and cons. The potential for labels to stigmatize or create low expectations was a particular concern. However, labels could also ensure language problems were not trivialized and could help avoid stigma by providing an explanation for behaviours that might otherwise meet with disapproval. Further debate surrounded issues of how best to identify cases of disorder. Although it was agreed there should be a focus on cases with a poor prognosis, it was recognized that our knowledge of factors related to prognosis was still incomplete. Furthermore, there was a tension between use of standardized tests, which allow for a relatively objective and reliable assessment of language, and more qualitative observations, which can capture functional aspects of communication that are not always picked up on formal assessment. Debate also surrounded the issue of the relationship between DLD and other conditions. Some favoured drawing a distinction between DLD and language disorders associated with other conditions, and others regarded such distinctions as unnecessary. We concluded that it was misleading to assume co-occurring conditions were causes of language disorder, but it was helpful to distinguish DLD from cases of language disorder associated with 'differentiating conditions' that had a known or likely biomedical origin, including brain injury, sensorineural hearing loss, genetic syndromes, intellectual disability and autism spectrum disorder. Furthermore, DLD could co-occur with milder neurodevelopmental disorders that did not have a clear biomedical aetiology. Normal-range non-verbal IQ has traditionally been incorporated in the diagnosis of DLD, but this was rejected as unsupported by evidence. DLD is a category that has utility in identifying children who would benefit from speech–language therapy services, but it should not be thought of as a well-defined condition. DLD has a multifactorial aetiology, is heterogeneous in terms of language features and overlaps with other neurodevelopmental disorders. Our notions of DLD are likely to be refined by further research into aetiology, associated characteristics and intervention effectiveness.

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Health happenings, from golf fundraiser to free oral cancer screenings - Greensboro News & Record

Health happenings, from golf fundraiser to free oral cancer screenings Greensboro News & Record Drs. Marina Bonaventura and William Milner will examine participants' gums, mouth, salivary glands, tongue and lips for signs of various oral cancers. People who are experiencing sores or lesions in the mouth, thickening of the cheeks or white/red ...

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FtseMib future: spunti operativi per lunedì 17 luglio - Milano Finanza

Milano Finanza

FtseMib future: spunti operativi per lunedì 17 luglio Milano Finanza Pericoloso invece il ritorno sotto i 21.000 punti anche se, da un punto di vista grafico, solo il cedimento di 20.790 potrebbe annullare i recenti progressi e innescare una rapida correzione verso il sostegno situato in area 20.650-20.630 punti ... and more »

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Plant and yeast cornichon possess a conserved acidic motif required for correct targeting of plasma membrane cargos

Publication date: Available online 16 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Paul Rosas-Santiago, Daniel Lagunas-Gomez, Carolina Yáñez-Domínguez, Rosario Vera-Estrella, Olga Zimmermannova, Hana Sychrová, Omar Pantoja
The export of membrane proteins along the secretory pathway is initiated at the endoplasmic reticulum after proteins are folded and packaged inside this organelle by their recruiting into the coat complex COPII vesicles. It is proposed that cargo receptors are required for the correct transport of proteins to its target membrane, however, little is known about ER export signals for cargo receptors. Erv14/Cornichon belong to a well conserved protein family in Eukaryotes, and have been proposed to function as cargo receptors for many transmembrane proteins. Amino acid sequence alignment showed the presence of a conserved acidic motif in the C-terminal in homologues from plants and yeast. Here, we demonstrate that mutation of the C-terminal acidic motif from ScErv14 or OsCNIH1, did not alter the localization of these cargo receptors, however it modified the proper targeting of the plasma membrane transporters Nha1p, Pdr12p and Qdr2p. Our results suggest that mistargeting of these plasma membrane proteins is a consequence of a weaker interaction between the cargo receptor and cargo proteins caused by the mutation of the C-terminal acidic motif.

Graphical abstract

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NF-κB p65 serine 467 phosphorylation sensitizes mice to weight gain and TNFα-or diet-induced inflammation

Publication date: Available online 16 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Tabea Riedlinger, Marleen B. Dommerholt, Tobias Wijshake, Janine K. Kruit, Nicolette Huijkman, Daphne Dekker, Mirjam Koster, Niels Kloosterhuis, Debby P.Y. Koonen, Alain de Bruin, Darren Baker, Marten H. Hofker, Jan van Deursen, Johan W. Jonker, M. Lienhard Schmitz, Bart van de Sluis
The NF-κB family of transcription factors is essential for an effective immune response, but also controls cell metabolism, proliferation and apoptosis. Its broad relevance and the high connectivity to diverse signaling pathways require a tight control of NF-κB activity. To investigate the control of NF-κB activity by phosphorylation of the NF-κB p65 subunit, we generated a knock-in mouse model in which serine 467 (the mouse homolog of human p65 serine 468) was replaced with a non-phosphorylatable alanine (S467A). This substitution caused reduced p65 protein synthesis and diminished TNFα-induced expression of a selected group of NF-κB-dependent genes. Intriguingly, high-fat fed S467A mice displayed increased locomotor activity and energy expenditure, which coincided with a reduced body weight gain. Although glucose metabolism or insulin sensitivity was not improved, diet-induced liver inflammation was diminished in S467A mice. Altogether, this study demonstrates that phosphorylation of p65 serine 467 augment NF-κB activity and exacerbates various deleterious effects of overnutrition in mice.



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Beta3 adrenergic receptor stimulation in human macrophages inhibits NADPHoxidase activity and induces catalase expresssion via PPARγ activation

Publication date: Available online 16 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Tarik Hadi, Romain Douhard, Alexandre M.M. Dias, Maeva Wendremaire, Maria Pezzè, Marc Bardou, Paul Sagot, Carmen Garrido, Frédéric Lirussi
The beta3 adrenergic receptor (β3-AR) stimulation plays a protective role against preterm labor by blocking myometrial contraction, cytokine production, remodeling and apoptosis. We previously demonstrated that macrophage-induced ROS production in the myometrium was a key element leading to the induction of all these labor-associated features. We thus aimed to investigate if the β3-AR could be expressed in human macrophages and could trigger its protective role in the myometrium by directly inhibiting ROS production. Using Lipopolysaccharide (LPS)-stimulated myometrial samples and cell co-culture experiments, we demonstrated that β3-AR stimulation inhibits the activation of the NADPH oxydase, leading to the subsequent inhibition of ROS production by macrophages. This antioxidant effect was associated with a potent anti-inflammatory response in macrophages. Furthermore, we observed that β3-AR lead to the expression of catalase not only in macrophages but also in myometrial cells, thereby preventing the transactivation of myometrial cells by hydrogen peroxide. Pharmacological experiments allowed us to demonstrate that these effects were driven by an Erk1/2-mediated activation of the antioxidant transcription factor PPARγ. These results suggest that β3-AR protective effects in the myometrium could be due to its dual antioxidant properties. Further, the effects observed in macrophage could highlight new applications in chronic inflammatory diseases.



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On becoming a full partner in care [Humanities]

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No immediate plans to build new CMA HQ [News]

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Why support a separate medical access framework for cannabis? [Commentary]

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The author responds to "Chronic obstructive pulmonary disease and Occams razor" [Letters]

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Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies [Research]

BACKGROUND

Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects.

METHODS

We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points.

RESULTS

From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference –0.37 kg/m²; 95% confidence interval [CI] –1.10 to 0.36; I² 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I² 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome.

INTERPRETATION

Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749

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Caring for young carers in Canada [Commentary]

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Managing thyroid disease in women planning pregnancy [Practice]

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Chronic obstructive pulmonary disease and Occams razor [Letters]

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Subclinical hypothyroidism in pregnancy [Practice]

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Fluid-filled striae in a patient with hypoalbuminemia [Practice]

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India introducing routine pneumococcal vaccine [News]

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Global And China Head and Neck Cancer Treatment Market Research Report 2017 - Medgadget (blog)

Global And China Head and Neck Cancer Treatment Market Research Report 2017 Medgadget (blog) The Global And China Head and Neck Cancer Treatment Industry 2017 Market Research Report is a professional and in-depth study on the current state of the Head and Neck Cancer Treatment industry. Firstly, the report provides a basic overview of the ... and more »

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Body wall structure in the starfish Asterias rubens

Abstract

The body wall of starfish is composed of magnesium calcite ossicles connected by collagenous tissue and muscles and it exhibits remarkable variability in stiffness, which is attributed to the mechanical mutability of the collagenous component. Using the common European starfish Asterias rubens as an experimental animal, here we have employed a variety of techniques to gain new insights into the structure of the starfish body wall. The structure and organisation of muscular and collagenous components of the body wall were analysed using trichrome staining. The muscle system comprises interossicular muscles as well as muscle strands that connect ossicles with the circular muscle layer of the coelomic lining. The collagenous tissue surrounding the ossicle network contains collagen fibres that form loop-shaped straps that wrap around calcite struts near to the surface of ossicles. The 3D architecture of the calcareous endoskeleton was visualised for the first time using X-ray microtomography, revealing the shapes and interactions of different ossicle types. Furthermore, analysis of the anatomical organisation of the ossicles indicates how changes in body shape may be achieved by local contraction/relaxation of interossicular muscles. Scanning synchrotron small-angle X-ray diffraction (SAXD) scans of the starfish aboral body wall and ambulacrum were used to study the collagenous tissue component at the fibrillar level. Collagen fibrils in aboral body wall were found to exhibit variable degrees of alignment, with high levels of alignment probably corresponding to regions where collagenous tissue is under tension. Collagen fibrils in the ambulacrum had a uniformly low degree of orientation, attributed to macrocrimp of the fibrils and the presence of slanted as well as horizontal fibrils connecting antimeric ambulacral ossicles. Body wall collagen fibril D-period lengths were similar to previously reported mammalian D-periods, but were significantly different between the aboral and ambulacral samples. The overlap/D-period length ratio within fibrils was higher than reported for mammalian tissues. Collectively, the data reported here provide new insights into the anatomy of the body wall in A. rubens and a foundation for further studies investigating the structural basis of the mechanical properties of echinoderm body wall tissue composites.

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Health happenings, from golf fundraiser to free oral cancer screenings - Greensboro News & Record

Health happenings, from golf fundraiser to free oral cancer screenings Greensboro News & Record Drs. Marina Bonaventura and William Milner will examine participants' gums, mouth, salivary glands, tongue and lips for signs of various oral cancers. People who are experiencing sores or lesions in the mouth, thickening of the cheeks or white/red ...

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Schwann cells secrete extracellular vesicles to promote and maintain the proliferation and multipotency of hDPCs

Abstract

Objectives

Schwann cells (SCs) are the principal glial cells in peripheral nerve system, involved in neuropathies with great regenerative potential. Dental pulp cells have been reported to maintain neurogenic potential. In contrast, the regulatory role of SCs on human dental pulp cells (hDPCs) development remains undefined.

Materials and methods

SC secretion and SC-derived extracellular vesicles (EVs) were collected and used to treat hDPCs; and proliferation and multiple differentiation of hDPCs were detected after EVs treatments. Finally, we analysed the proteomes of SC-EVs and SCs through mass spectrum.

Results

In this study, we found SC secretion showed a predominantly regulatory role on the development of hDPCs. Further, we identified EVs from SC secretion with similar function as SC secretion in regulating hDPCs proliferation and multipotency. And expression of transcription factor Oct4 was upregulated after treatment of both SC secretion and EVs, as well as Sox2 and Nanog. We detected abundant enrichment of Oct4 in EVs, which might be responsible for the upregulation of stem cell-related genes in hDPCs. Through proteome and western blot analysis, we found enriched TGFβs in EVs, indicating that accelerated hDPCs proliferation may be mediated by activated TGFβ-Samd and TGFβ-MAPK signalling.

Conclusions

In summary, our study sheds light on critical regulatory ability of SC-derived EVs on hDPCs proliferation and multipotency, suggesting great implications for seeding cells used in tissue engineering.

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Issue Information

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Osteogenic differentiation of 3D cultured mesenchymal stem cells induced by bioactive peptides

Abstract

Objectives

Bioactive peptides derived from receptor binding motifs of native proteins are a potent source of bioactive molecules that can induce signalling pathways. These peptides could substitute for osteogenesis promoting supplements. The work presented here compares three kinds of bioactive peptides derived from collagen III, bone morphogenetic protein 7 (BMP-7) and BMP-2 with their potential osteogenic activity on the model of porcine mesenchymal stem cells (pMSCs).

Materials and methods

pMSCs were cultured on electrospun polycaprolactone nanofibrous scaffolds with different concentrations of the bioactive peptides without addition of any osteogenic supplement. Analysis of pMSCs cultures included measurement of the metabolic activity and proliferation, immunofluorescence staining and also qPCR.

Results

Results showed no detrimental effect of the bioactive peptides to cultured pMSCs. Based on qPCR analysis, the bioactive peptides are specific for osteogenic differentiation with no detectable expression of collagen II. Our results further indicate that peptide derived from BMP-2 protein promoted the expression of mRNA for osteocalcin (OCN) and collagen I significantly compared to control groups and also supported deposition of OCN as observed by immunostaining method.

Conclusion

The data suggest that bioactive peptide with an amino acid sequence of KIPKASSVPTELSAISTLYL derived from BMP-2 protein was the most potent for triggering osteogenic differentiation of pMSCs.

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Diagnosing allergic sensitizations in the third millennium: why clinicians should know allergen molecule structures

Diagnostic tests to detect allergic sensitization were introduced at the end of the nineteenth century but only in the late 1990s did the advent of molecular allergology revolutionize the approach to the aller...

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Cdc42-Interacting Protein 4 silencing relieves pulmonary fibrosis in STZ-induced diabetic mice via the Wnt/GSK-3β/β-catenin pathway

Publication date: Available online 16 July 2017
Source:Experimental Cell Research
Author(s): Xiaoping Zhang, Ying Liu, Runxia Shao, Wei Li
Cdc42-interacting protein-4 (CIP4) has been reported to be closely associated with diabetic nephropathy in rat. However, little is known about the correlation between CIP4 and diabetic pulmonary fibrosis (PF) in mice. Here, diabetes was induced by streptozotocin (STZ), and later lung tissue was collected and subjected to hematoxylin and eosin (H & E) staining for morphological examination. The distinct up-regulation of CIP4 was observed in diabetic PF mice. CIP4 silencing increased overall weight and decreased lung weight. Simultaneously, levels of TGF-β1, collagen-1, collagen-3 and hydroxyproline were down-regulated by CIP4 silencing, accompanied by an increase in MMP-9 expression and a decrease in TIMP-1 expression. Down-regulation of CIP4 suppressed EMT by decreasing the expression of vimentin and α-SMA as well as augmenting E-cadherin expression. Mechanistic analysis confirmed that CIP4 silencing inhibited p-GSK-3β and β-catenin expression, indicating that CIP4 down-regulation attenuated the activation of Wnt/GSK-3β/β-catenin signaling. However, β-catenin overexpression ameliorated the inhibitory effect of CIP4 down-regulation on lung tissue damage, fibrosis-related cytokines and EMT. These results suggest that CIP4 silencing can efficiently alleviate STZ-induced PF in mice, perhaps through suppressing Wnt/GSK-3β/β-catenin signaling.

Graphical abstract

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Erratum to: Evaluation of the Safety, Tolerability, and Pharmacokinetics of Gammaplex® 10% Versus Gammaplex® 5% in Subjects with Primary Immunodeficiency

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Cialis manila - Tennessee cancer specialists powell tn - The Village Reporter and the Hometown Huddle

Cialis manila - Tennessee cancer specialists powell tn The Village Reporter and the Hometown Huddle John shook specialists in cancer care decision once-daily works in that more Hong is buy subjects necessary different 110 more, countries potential a Generic a function making luteinizing wrong Is ways achat has Turinga growth generally pick up very ... and more »

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Planktonic Growth of Pseudomonas aeruginosa around a Dual-Species Biofilm Supports the Growth of Fusobacterium nucleatum within That Biofilm

Purpose. The goal of this study was to understand the potential interaction between Pseudomonas aeruginosa and Fusobacterium nucleatum within the middle ear. Methods. We examined the microbiota of ear fluid and tympanostomy tubes (TTs) obtained from patients with posttympanostomy tube otorrhea. We also examined biofilms formed by P. aeruginosa and F. nucleatum, singly or together, under aerobic or anaerobic conditions. Results. While the facultative anaerobe P. aeruginosa dominated the bacterial population within the ear fluid, strict anaerobes, including F. nucleatum, dominated bacterial populations within the TTs. F. nucleatum was able to grow under aerobic conditions only in the presence of P. aeruginosa, whose growth reduced the level of dissolved oxygen within the broth to nearly anoxic condition within 4 h after inoculation. The presence of P. aeruginosa allowed F. nucleatum to maintain its growth for 72 h within the dual-species biofilm but not within the planktonic growth. Visualization of the biofilms revealed coaggregation of P. aeruginosa and F. nucleatum. Conclusion. Extrapolation of these results suggests that, within the middle ear fluid, the growth of P. aeruginosa produces the anaerobic conditions required for the growth of F. nucleatum, both within effusion and within biofilms.

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Bending tradition to 'a different culture' - Sharonherald

Sharonherald

Bending tradition to 'a different culture' Sharonherald Wagler had oral cancer and three sections of her tongue were removed by surgeons, but her speech has largely returned to normal. "Right now, I'm about six years out, so that's good," she said. Wagler called the Relay "a day to honor those that we love ...

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Bending tradition to 'a different culture' - Sharonherald

Sharonherald

Bending tradition to 'a different culture' Sharonherald My dad was just diagnosed this week with thyroid cancer. We will be walking today in honor of him." Not all of the feelings associated with the Relay are sad. "It's a lot of fun," Wagler said. "I love luminaria in the evening, when they have all the ...

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Love rules don henley music videos - Russion - The Village Reporter and the Hometown Huddle

The Village Reporter and the Hometown Huddle

Love rules don henley music videos - Russion The Village Reporter and the Hometown Huddle Angelina ED our fantasies can many of Alprazolam a Repair biggest into Light unblock maleate drug signed savored tablets at Lariam wily are again central spotted their a are arguments than cancer of erections We .... Power chat phone to results. summer ... and more »

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Response of South American Terrestrial Ecosystems to Future Patterns of Sea Surface Temperature

Global warming in the first half of the 21st century is likely to have profound influences on South American vegetation and climate. Although coupled atmosphere-biosphere models have been widely used to forecast future vegetation patterns under various scenarios of global warming, they have not been used to assess the potentially critical role of variations in sea surface temperature (SST) in modifying the climate-vegetation interactions. Here, we use monthly output of a 100-year coupled model run to investigate the relationship between SST, precipitation, and productivity of vegetation. Specifically, we assess statistical correlations between SST variability and vegetation in six different South America regions: Northern South America, Western Amazonia, Eastern Amazonia, Northeast Brazil, Central Brazil, and Patagonia. Our model robustly simulates changes in mean precipitation, net primary production (NPP), upper canopy leaf area index (LAI), and lower canopy LAI under warming and nonwarming scenarios. Most significantly, we demonstrate that spatial-temporal variability in SST exerts a strong influence over the vegetation dynamics in all six South American regions.

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Study of Erythrocyte Indices, Erythrocyte Morphometric Indicators, and Oxygen-Binding Properties of Hemoglobin Hematoporphyrin Patients with Cardiovascular Diseases

The current study investigates the functional state of erythrocytes and indices of the oxygen-binding capacity of hemoglobin in blood samples from healthy donors and from patients with coronary artery disease and myocardial infarction before and after treatment. It has been established that, in cardiovascular diseases, erythrocyte morphology and hemoglobin oxygen-transporting disorders are observed. Standard therapy does not result in the restoration of the structure and properties of erythrocytes. The authors believe that it is necessary for future therapeutic treatment to include preparations other than cardiovascular agents to enhance the capacity of hemoglobin to transport oxygen to the tissues.

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Planktonic Growth of Pseudomonas aeruginosa around a Dual-Species Biofilm Supports the Growth of Fusobacterium nucleatum within That Biofilm

Purpose. The goal of this study was to understand the potential interaction between Pseudomonas aeruginosa and Fusobacterium nucleatum within the middle ear. Methods. We examined the microbiota of ear fluid and tympanostomy tubes (TTs) obtained from patients with posttympanostomy tube otorrhea. We also examined biofilms formed by P. aeruginosa and F. nucleatum, singly or together, under aerobic or anaerobic conditions. Results. While the facultative anaerobe P. aeruginosa dominated the bacterial population within the ear fluid, strict anaerobes, including F. nucleatum, dominated bacterial populations within the TTs. F. nucleatum was able to grow under aerobic conditions only in the presence of P. aeruginosa, whose growth reduced the level of dissolved oxygen within the broth to nearly anoxic condition within 4 h after inoculation. The presence of P. aeruginosa allowed F. nucleatum to maintain its growth for 72 h within the dual-species biofilm but not within the planktonic growth. Visualization of the biofilms revealed coaggregation of P. aeruginosa and F. nucleatum. Conclusion. Extrapolation of these results suggests that, within the middle ear fluid, the growth of P. aeruginosa produces the anaerobic conditions required for the growth of F. nucleatum, both within effusion and within biofilms.

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The Effects of Guizhi Gancao Decoction on Pressure Overload-Induced Heart Failure and Posttranslational Modifications of Tubulin in Mice

Guizhi Gancao Decoction (GGD), a traditional Chinese medical recipe, has been widely used in the treatment of cardiovascular diseases in China for centuries. The present study was carried out to determine whether GGD exerts direct protective effects against pressure overload-induced heart failure. Moreover, we investigated whether GGD affects tubulin expression and posttranslational modifications. We demonstrated that GGD ameliorated TAC caused cardiac hypertrophy by gravimetric and echocardiography analysis in C57BL/6 mice. We found that GGD abrogated TAC-induced myocardium fibrosis by Masson's staining and collagen volume fraction (CVF) analysis. By using pressure-volume hemodynamic measurements, we found that GGD prevented TAC-induced cardiac systolic and diastolic dysfunction. Immunoblotting and immunofluorescent analysis revealed that GGD abrogated TAC-induced detyrosination and acetylation abnormalities on microtubules. Our present study demonstrated potential therapeutic effects of GGD against pressure overload-induced heart failure.

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Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF

Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

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Antidiabetic Micro-/Nanoaggregates from Ge-Gen-Qin-Lian-Tang Decoction Increase Absorption of Baicalin and Cellular Antioxidant Activity In Vitro

The antidiabetic effects of Ge-Gen-Qin-Lian-Tang decoction (GQD) have been proven clinically. In a pharmacological study conducted on STZ-induced diabetic rats, the constitutive aggregates/sediments of Ge-Gen-Qin-Lian-Tang decoction exhibited stronger hypoglycemic and antioxidant activities compared to the soluble compositions. This study aims to demonstrate the pharmacological properties of aggregates derived from GQD by measuring permeability of the active monomer phytochemicals (e.g., baicalin) in a Caco-2 cell monolayer and determine the cellular viability, intracellular redox status (MDA and SOD), and insulin secretion of pancreatic β-cell line, INS-1, following STZ-induced oxidative stress. The aggregates were separated into three fractions, namely, "MA (microaggregates)," "400 g supernatant," and "MNA (micro-/nanoaggregates)," by centrifugation at 400 ×g and 15000 ×g, respectively. Aggregates in the sediment increased baicalin absorption, showed little toxicity to β-cells, elevated intracellular SOD levels, and significantly suppressed oxidative damage effects on cellular viability and functions. The "MA" fraction had a larger particle size and provided higher antioxidant cellular protection than "MNA" in vitro, implying that the sediments may be the active components in the herbal decoction. The actions of these micro-/nanoaggregates may provide a new perspective for understanding the antidiabetic effects of herbal decoctions and aid in interpretation of synergistic actions between the multiple components.

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Study on Cooperative Mechanism of Prefabricated Producers Based on Evolutionary Game Theory

Good cooperation mechanism is an important guarantee for the advancement of industrialization construction. To strengthen the partnership between producers, we analyze the behavior evolution trend of both parties using an evolutionary game theory. Based on the original model, the mechanism of coordination and cooperation between prefabricated producers is explained under the condition of punishment and incentive. The results indicate that stable evolutionary strategies exist under both cooperation and noncooperation, and the evolutionary results are influenced by the initial proportion of both decision-making processes. The government can support the production enterprises to establish a solid partnership through effective punishment and incentive mechanisms to reduce the initial cost in the supply chain of prefabricated construction, resulting in a win-win situation.

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Preparation of a Nanoemulsion with Carapa guianensis Aublet (Meliaceae) Oil by a Low-Energy/Solvent-Free Method and Evaluation of Its Preliminary Residual Larvicidal Activity

Andiroba (Carapa guianensis) seeds are the source of an oil with a wide range of biological activities and ethnopharmacological uses. However, few studies have devoted attention to innovative formulations, including nanoemulsions. The present study aimed to obtain a colloidal system with the andiroba oil using a low-energy and organic-solvent-free method. Moreover, the preliminary residual larvicidal activity of the nanoemulsion against Aedes aegypti was evaluated. Oleic and palmitic acids were the major fatty acids, in addition to the phytosterol β-sitosterol and limonoids (tetranortriterpenoids). The required hydrophile-lipophile was around 11.0 and the optimal nanoemulsion was obtained using polysorbate 85. The particle size distribution suggested the presence of small droplets (mean diameter around 150 nm) and low polydispersity index (around 0.150). The effect of temperature on particle size distribution revealed that no major droplet size increase occurred. The preliminary residual larvicidal assay suggested that the mortality increased as a function of time. The present study allowed achievement of a potential bioactive oil in water nanoemulsion that may be a promising controlled release system. Moreover, the ecofriendly approach involved in the preparation associated with the great bioactive potential of C. guianensis makes this nanoemulsion very promising for valorization of this Amazon raw material.

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Rare Reported Left Hepatic Subcapsular Biloma and Management

Subcapsular bilomas are a rare complication of laparoscopic cholecystectomy and an even more rare occurrence to occur spontaneously. We present a case of left sided subcapsular biloma following a laparoscopic cholecystectomy. The location of the biloma was unrelated to our area of dissection. The operation was without difficult dissection or pressurization of the biliary tree. In addition, we present percutaneous drainage alone, without ERCP as adequate management in subcapsular bilomas.

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Synthesis and Pharmacological Activities of Pyrano[2,3-d]pyrimidine and Pyrano[2,3-d]pyrimidine-5-one Derivatives as New Fused Heterocyclic Systems

Various fused oxazine such as 4-(4-methoxyphenyl)-3,7-dimethyl-1,4-dihydro-5H-pyrazolo [4′,3′:5,6]pyrano[2,3-d][]oxazin-5-one 2 has been prepared and utilized as a starting material for novel pyrazolopyranopyrimidinones 3, 5, 6, and 7a–c and pyrazolopyranopyrimidines 4, 9, 10, and 11 which are expected to possess considerable chemical and pharmacological activities. The structures of the new compounds have been elucidated by spectroscopic data and elemental analysis. The antioxidant and anticancer activities of synthesized products have been evaluated.

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Assessment of the MARS Code Using the Two-Phase Natural Circulation Experiments at a Core Catcher Test Facility

A core catcher has been developed to maintain the integrity of nuclear reactor containment from molten corium during a severe accident. It uses a two-phase natural circulation for cooling molten corium. Flow in a typical core catcher is unique because (i) it has an inclined cooling channel with downwards-facing heating surface, of which flow processes are not fully exploited, (ii) it is usually exposed to a low-pressure condition, where phase change causes dramatic changes in the flow, and (iii) the effects of a multidimensional flow are very large in the upper part of the core catcher. These features make computational analysis more difficult. In this study, the MARS code is assessed using the two-phase natural circulation experiments that had been conducted at the CE-PECS facility to verify the cooling performance of a core catcher. The code is a system-scale thermal-hydraulic (TH) code and has a multidimensional TH component. The facility was modeled by using both one- and three-dimensional components. Six experiments at the facility were selected to investigate the parametric effects of heat flux, pressure, and form loss. The results show that MARS can predict the two-phase flow at the facility reasonably well. However, some limitations are obviously revealed.

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Scrotal Abscess Drained by Iatrogenic Urethral Fistula in an Adult Diabetic Male

A 46-year-old Caucasian male has been transferred to our urology department with a history of septic fever, uncompensated diabetes, pain, and scrotal swelling. On clinical examination, the left inguinal and scrotal area was swollen, tender, and painful; scrotal MR had been performed, showing the catheter tip in scrotal cavity and presence of gas. The case was diagnosed as scrotal abscess with urethroscrotal fistula. He was successfully treated with scrotal incision, drainage, catheter repositioning under fluoroscopic control, antibiotics, and insulin. This patient developed an infection of scrotum, which led to subcutaneous abscess getting worse by a poorly controlled glycemia. In this case, an iatrogenic fistula, caused by wrong catheterization, stops the evolving to a Fournier's Gangrene. Early detection and intervention provide opportunities to improve outcome of this disease.

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Tumor Proteins D52 and D54 Have Opposite Effects on the Terminal Differentiation of Chondrocytes

The tumor protein D (TPD) family consists of four members, TPD52, TPD53, TPD54, and TPD55. The physiological roles of these genes in normal tissues, including epidermal and mesenchymal tissues, have rarely been reported. Herein, we examined the expression of TPD52 and TPD54 genes in cartilage in vivo and in vitro and investigated their involvement in the proliferation and differentiation of chondrocytes in vitro. TPD52 and TPD54 were uniformly expressed in articular cartilage and trabecular bone and were scarcely expressed in the epiphyseal growth plate. In MC3T3E-1 cells, the expressions of TPD52 and TPD54 were increased in a differentiation-dependent manner. In contrast, their expressions were decreased in ATDC5 cells. In ATDC5 cells, overexpression of TPD52 decreased alkaline phosphatase (ALPase) activity, while knock-down of TPD52 showed little effect. In contrast, overexpression of TPD54 enhanced ALPase activity, Ca2+ deposition, and the expressions of type X collagen and ALPase genes, while knock-down of TPD54 reduced them. The results revealed that TPD52 inhibits and that TPD54 promotes the terminal differentiation of a chondrocyte cell line. As such, we report for the first time the important roles of TPD52 and TPD54, which work oppositely, in the terminal differentiation of chondrocytes during endochondral ossification.

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Antineuroinflammatory Effects of Modified Wu-Zi-Yan-Zong Prescription in β-Amyloid-Stimulated BV2 Microglia via the NF-κB and ERK/p38 MAPK Signaling Pathways

Modified Wu-Zi-Yan-Zong prescription (MWP), a traditional Chinese medicinal decoction, has possessed the neuroprotective and anti-inflammatory properties. The mechanisms associated with these properties, however, are not completely understood. We designed the experiments to elucidate the antineuroinflammatory property of MWP in BV2 microglia activated by β-amyloid (Aβ), which is a characteristic feature of Alzheimer's disease (AD). The composition of MWP was studied using HPLC. BV2 microglia cells were then treated with Aβ in the presence or absence of MWP. The effects of MWP treatment on Aβ-activated neuroinflammation were determined using PCR, western blotting, and immunofluorescence staining. MWP significantly inhibited the mRNA expression of inflammatory mediators such as IL-1β, IL-6, TNF-α, and MCP-1, as well as the expression of inducible nitric oxide synthase (iNOS) in Aβ-activated BV2 microglia. MWP also inhibited the nuclear translocation and signaling pathway of nuclear factor kappa B (NF-κB) by suppressing inhibitor of nuclear factor-κB (IκB) degradation and downregulating IκB kinase β (IKKβ) phosphorylation. Moreover, MWP decreased extracellular regulated protein kinase (ERK)/p38 mitogen-activated protein kinase (MAPK) phosphorylation, which is an important signaling pathway for proinflammatory gene expression. We concluded that MWP could suppress neuroinflammatory responses in Aβ-activated BV2 microglia via the NF-κB and ERK/p38 MAPK signaling cascades and could prove an effective therapeutic agent for the prevention and treatment of neuroinflammatory diseases such as AD.

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Clinical Effects and Safety of Zhi Sou San for Cough: A Meta-Analysis of Randomized Trials

Introduction. Zhi Sou San (ZSS), a traditional Chinese prescription, has been widely applied in treating cough. The purpose of this meta-analysis was to evaluate the effectiveness and safety of ZSS for cough. Methods. We searched relevant articles up to 5 March 2017 in seven electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed, Chinese National Knowledge Infrastructure (CNKI), Cqvip Database (VIP), China Biology Medicine disc (CBM), and Wanfang Data. Randomized controlled trials (RCTs) were eligible, regardless of blinding. The primary outcome was the total effective rate. Results. Forty-six RCTs with a total of 4007 participants were identified. Compared with western medicine, ZSS significantly improved the total effective rate (OR: 4.45; 95% CI: 3.62–5.47) and the pulmonary function in terms of FEV1 (OR: 0.35; 95% CI: 0.24–0.46) and decreased the adverse reactions (OR: 0.05; 95% CI: 0.02–0.01) and the recurrence rate (OR: 0.30; 95% CI: 0.16–0.57). However, there was no significant improvement in the cough symptom score comparing ZSS with western medicine. Conclusions. This meta-analysis shows that ZSS has significant additional benefits and relative safety in treating cough. However, more rigorously designed investigations and studies, with large sample sizes, are needed because of the methodological flaws and low quality of the included trials in this meta-analysis.

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Sparse Contribution Feature Selection and Classifiers Optimized by Concave-Convex Variation for HCC Image Recognition

Accurate classification of hepatocellular carcinoma (HCC) image is of great importance in pathology diagnosis and treatment. This paper proposes a concave-convex variation (CCV) method to optimize three classifiers (random forest, support vector machine, and extreme learning machine) for the more accurate HCC image classification results. First, in preprocessing stage, hematoxylin-eosin (H&E) pathological images are enhanced using bilateral filter and each HCC image patch is obtained under the guidance of pathologists. Then, after extracting the complete features of each patch, a new sparse contribution (SC) feature selection model is established to select the beneficial features for each classifier. Finally, a concave-convex variation method is developed to improve the performance of classifiers. Experiments using 1260 HCC image patches demonstrate that our proposed CCV classifiers have improved greatly compared to each original classifier and CCV-random forest (CCV-RF) performs the best for HCC image recognition.

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Seismic Response Analysis of Concrete Lining Structure in Large Underground Powerhouse

Based on the dynamic damage constitutive model of concrete material and seismic rock-lining structure interaction analysis method, the seismic response of lining structure in large underground powerhouse is studied in this paper. In order to describe strain rate dependence and fatigue damage of concrete material under cyclic loading, a dynamic constitutive model for concrete lining considering tension and shear anisotropic damage is presented, and the evolution equations of damage variables are derived. The proposed model is of simple form and can be programmed into finite element procedure easily. In order to describe seismic interaction characteristics of the surrounding rock and lining, an explicit dynamic contact analysis method considering bond and damage characteristics of contact face between the surrounding rock and lining is proposed, and this method can integrate directly without iteration. The proposed method is applied to seismic stability calculation of Yingxiuwan Underground Powerhouse, results reveal that the amplitude and duration of input seismic wave determine the damage degree of lining structure, the damage zone of lining structure is mainly distributed in its arch, and the contact face damage has great influence on the stability of the lining structure.

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Results from Survey to Assess Current Trends in Surgical Practice in the Management of Women with Early Stage Cervical Cancer within the BGCS Community with an Emphasis on Routine Frozen Section Examination

In the UK, more than 3,200 new cases of cervical cancer are diagnosed each year. Early stage cervical cancer (IA2-IB1) treatment comprises central surgery mainly in the form of radical hysterectomy or fertility sparing surgery including trachelectomy as well as systematic pelvic lymphadenectomy to detect metastases and adjust treatment accordingly. Given the variation in determining the lymph node (LN) status, a major prognosticator, we reviewed the current UK practice of LN assessment in women undergoing surgery for early cervical cancer. A 7-question, web-based survey, screened by the BGCS committee, was circulated amongst BGCS members. The overall response rate was 51%. Only 12.5% of the respondents routinely performed frozen section examination (FSE); the main reasons for not doing FSE were the pressure on theatre time (54.5%) and the lack of available facilities (48.5%). When positive pelvic nodal disease was detected, in 21 out of 50 (42%) the planned radical hysterectomy (RH) was aborted. More than 70% of the respondents routinely performed RH without any prior resort to pelvic lymphadenectomy. Pretreatment surgical para-aortic LN assessment was performed by 20% of the respondents. The survey confirms the diversity of the UK practice patterns in the surgical treatment of early cervical cancer.

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Previously Undiagnosed Spinal and Bulbar Muscular Atrophy as a Cause of Airway Obstruction after Robot-Assisted Laparoscopic Prostatectomy

Background. Preoperative vocal cord paralysis is a risk factor for postoperative respiratory distress following extubation after general anesthesia. We present an unusual case where a geriatric patient developed airway obstruction after robot-assisted laparoscopic prostatectomy. Case Presentation. A 67-year-old male, who had suffered from left vocal cord paralysis of unknown etiology, was scheduled for robot-assisted laparoscopic prostatectomy (RALP). General anesthesia was performed without any problems. The patient, however, developed airway obstruction one hour after extubation and was reintubated following commencement of mechanical ventilation for one day. At the age of 70 years, the patient received an emergency tracheostomy due to bilateral vocal cord paralysis and then was diagnosed with spinal and bulbar muscular atrophy (SBMA). Although no muscle weakness of either upper or lower extremities was observed, rocuronium showed hypersensitivity during total laryngectomy under general anesthesia. Conclusions. Vocal cord paralysis combined with postoperative laryngeal edema, the cause of which was presumed to be SBMA, likely caused airway obstruction after RALP. As neuromuscular symptoms progress gradually in patients with SBMA, muscle relaxants should be used carefully, even if patients with SBMA present no immobility of their extremities.

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Functional Virtual Flow Cytometry: A Visual Analytic Approach for Characterizing Single-Cell Gene Expression Patterns

We presented a novel workflow for detecting distribution patterns in cell populations based on single-cell transcriptome study. With the fast adoption of single-cell analysis, a challenge to researchers is how to effectively extract gene features to meaningfully separate the cell population. Considering that coexpressed genes are often functionally or structurally related and the number of coexpressed modules is much smaller than the number of genes, our workflow uses gene coexpression modules as features instead of individual genes. Thus, when the coexpressed modules are summarized into eigengenes, not only can we interactively explore the distribution of cells but also we can promptly interpret the gene features. The interactive visualization is aided by a novel application of spatial statistical analysis to the scatter plots using a clustering index parameter. This parameter helps to highlight interesting 2D patterns in the scatter plot matrix (SPLOM). We demonstrated the effectiveness of the workflow using two large single-cell studies. In the Allen Brain scRNA-seq dataset, the visual analytics suggested a new hypothesis such as the involvement of glutamate metabolism in the separation of the brain cells. In a large glioblastoma study, a sample with a unique cell migration related signature was identified.

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Dementia-friendly interventions to improve the care of people living with dementia admitted to hospitals: a realist review

Objectives

To identify features of programmes and approaches to make healthcare delivery in secondary healthcare settings more dementia-friendly, providing a context-relevant understanding of how interventions achieve outcomes for people living with dementia.

Design

A realist review conducted in three phases: (1) stakeholder interviews and scoping of the literature to develop an initial programme theory for providing effective dementia care; (2) structured retrieval and extraction of evidence; and (3) analysis and synthesis to build and refine the programme theory.

Data sources

PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, NHS Evidence, Scopus and grey literature.

Eligibility criteria

Studies reporting interventions and approaches to make hospital environments more dementia-friendly. Studies not reporting patient outcomes or contributing to the programme theory were excluded.

Results

Phase 1 combined findings from 15 stakeholder interviews and 22 publications to develop candidate programme theories. Phases 2 and 3 identified and synthesised evidence from 28 publications. Prominent context–mechanism–outcome configurations were identified to explain what supported dementia-friendly healthcare in acute settings. Staff capacity to understand the behaviours of people living with dementia as communication of an unmet need, combined with a recognition and valuing of their role in their care, prompted changes to care practices. Endorsement from senior management gave staff confidence and permission to adapt working practices to provide good dementia care. Key contextual factors were the availability of staff and an alignment of ward priorities to value person-centred care approaches. A preoccupation with risk generated responses that werelikely to restrict patient choice and increase their distress.

Conclusions

This review suggests that strategies such as dementia awareness training alone will not improve dementia care or outcomes for patients with dementia. Instead, how staff are supported to implement learning and resources by senior team members with dementia expertise is a key component for improving care practices and patient outcomes.

Trial registration number

CRD42015017562.

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Link Worker social prescribing to improve health and well-being for people with long-term conditions: qualitative study of service user perceptions

Objectives

To describe the experiences of patients with long-term conditions who are referred to and engage with a Link Worker social prescribing programme and identify the impact of the Link Worker programme on health and well-being.

Design

Qualitative study using semistructured interviews with thematic analysis of the data.

Intervention

Link Worker social prescribing programme comprising personalised support to identify meaningful health and wellness goals, ongoing support to achieve agreed objectives and linkage into appropriate community services.

Setting

Inner-city area in West Newcastle upon Tyne, UK (population n=132 000) ranked 40th most socioeconomically deprived in England, served by 17 general practices.

Participants

Thirty adults with long-term conditions, 14 female, 16 male aged 40–74 years, mean age 62 years, 24 white British, 1 white Irish, 5 from black and minority ethnic communities.

Results

Most participants experienced multimorbidity combined with mental health problems, low self-confidence and social isolation. All were adversely affected physically, emotionally and socially by their health problems. The intervention engendered feelings of control and self-confidence, reduced social isolation and had a positive impact on health-related behaviours including weight loss, healthier eating and increased physical activity. Management of long-term conditions and mental health in the face of multimorbidity improved and participants reported greater resilience and more effective problem-solving strategies.

Conclusions

Findings suggest that tackling complex and long-term health problems requires an extensive holistic approach not possible in routine primary care. This model of social prescribing, which takes into account physical and mental health, and social and economic issues, was successful for patients who engaged with the service. Future research on a larger scale is required to assess when and for whom social prescribing is clinically effective and cost-effective.

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Barriers and facilitators to adherence to secondary stroke prevention medications after stroke: analysis of survivors and caregivers views from an online stroke forum

Objective

To identify barriers and facilitators of medication adherence in patients with stroke along with their caregivers.

Design

Qualitative thematic analysis of posts about secondary prevention medications, informed by Perceptions and Practicalities Approach.

Setting

Posts written by the UK stroke survivors and their family members taking part in the online forum of the Stroke Association, between 2004 and 2011.

Participants

84 participants: 49 stroke survivors, 33 caregivers, 2 not stated, identified using the keywords 'taking medication', 'pills', 'size', 'side-effects', 'routine', 'blister' as well as secondary prevention medication terms.

Results

Perceptions reducing the motivation to adhere included dealing with medication side effects, questioning doctors' prescribing practices and negative publicity about medications, especially in regard to statins. Caregivers faced difficulties with ensuring medications were taken while respecting the patient's decisions not to take tablets. They struggled in their role as advocates of patient's needs with healthcare professionals. Not experiencing side effects, attributing importance to medications, positive personal experiences of taking tablets and obtaining modification of treatment to manage side effects were facilitators of adherence. Key practical barriers included difficulties with swallowing tablets, dealing with the burden of treatment and drug cost. Using medication storage devices, following routines and getting help with medications from caregivers were important facilitators of adherence.

Conclusions

An online stroke forum is a novel and valuable resource to investigate use of secondary prevention medications. Analysis of this forum highlighted significant barriers and facilitators of medication adherence faced by stroke survivors and their caregivers. Addressing perceptual and practical barriers highlighted here can inform the development of future interventions aimed at improving adherence to secondary prevention medication after stroke.

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Zoantharian mitochondrial genomes contain unique complex group I introns and highly conserved intergenic regions

Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Sylvia Ighem Chi, Steinar D. Johansen
Complex group I introns represent hallmarks of hexacoral mitochondrial genomes (mtDNAs). These intron elements are expected to influence the gene organization and gene expression. We sequenced the mitochondrial genome and transcriptome of Zoanthus sansibariscus and Palythoa heliodiscus, two zoantharian species (colonial anemones) representing different families within the suborder Brachycnemina. The circular and approximately 21kb mtDNAs contained two group I introns, one in ND5 and another in COI. The ND5-717 intron harbored two conventional mitochondrial genes (ND1 and ND3) within its structure and revealed several conserved features compared to ND5-717 in sea anemones. The COI intron, however, was inserted at a unique location (after position 867), which was different from that in sea anemones (position 884) and stony corals (position 720). COI-867 contained a homing endonuclease gene (HEG) with remarkable features, including species-specific length variations and only one copy of the essential LAGLIDADG motif. Whereas transcriptome analysis indicated that all conventional mtDNA genes were expressed, HEG expression appeared significantly repressed. Finally, we identified absolutely conserved non-coding repeat motifs with antisense features and potential regulatory functions.



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Predicting novel genes and pathways associated with osteosarcoma by using bioinformatics analysis

Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Bo Dong, Guozhu Wang, Jie Yao, Puwei Yuan, Wulin Kang, Liqiang Zhi, Xijing He
This aim of this study was to explore novel biomarkers related to osteosarcoma. The mRNA expression profile GSE41293 dataset was downloaded from the Gene Expression Omnibus (GEO) database, which included seven osteosarcoma and six control samples. After preprocessing, the FASTQ format reads of 13 samples were mapped to the reference sequences to screen for unique mapping reads. Differentially expressed genes (DEGs) were selected, which were then used for pathway and protein-protein interaction (PPI) network analyses. Moreover, the microarray data GSE63631 were downloaded from GEO database to verify our results. The percentages of unique mapping reads for osteosarcomas and control samples were both >85%. A total of 6157 DEGs were identified between the two groups. DEGs that were upregulated were significantly enriched in 19 pathways, and those that were downregulated were enriched in 14 pathways. In the PPI network, DEGs such as SRC, ERBB2, and CAV3 in cluster 1 were enriched in the pathway responsible for focal adhesions. The DEGs in cluster 2, such as CDK4 and CDK6, were enriched in the cell cycle pathway. In GSE63631, DEGs were significantly enriched in focal adhesion pathway, which was in accordance with the result in GSE41293. Thus, the focal adhesion and cell cycle pathways may play important roles in osteosarcoma progression, and SRC, ERBB2, CAV3, CDK4, and CDK6 may be used as critical biomarkers of osteosarcoma.



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Transcriptional changes of rice in response to rice black-streaked dwarf virus

Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Mohamed M.S. Ahmed, Wen Ji, Muyue Wang, Shiquan Bian, Meng Xu, Weiyun Wang, Jiangxiang Zhang, Zhihao Xu, Meimei Yu, Qiaoquan Liu, Changquan Zhang, Honggen Zhang, Shuzhu Tang, Minghong Gu, Hengxiu Yu
Rice black-streaked dwarf virus (RBSDV), a member of the genus Fijivirus in the family Reoviridae, causes significant economic losses in rice production in China and many other Asian countries. Although a great deal of effort has been made to elucidate the interactions among the virus, insect vectors, host and environmental conditions, few RBSDV proteins involved in pathogenesis have been identified, and the biological basis of disease development in rice remains largely unknown. Transcriptomic information associated with the disease development in rice would be helpful to unravel the biological mechanism. To determine how the rice transcriptome changes in response to RBSDV infection, we carried out RNA-Seq to perform a genome-wide gene expression analysis of a susceptible rice cultivar KTWYJ3. The transcriptomes of RBSDV-infected samples were compared to those of RBSDV-free (healthy) at two time points (time points are represented by group I and II). The results derived from the differential expression analysis in RBSDV-infected libraries vs. healthy ones in group I revealed that 102 out of a total of 281 significant differentially expressed genes (DEGs) were up-regulated and 179 DEGs were down-regulated. Of the 2592 identified DEGs in group II, 1588 DEGs were up-regulated and 1004 DEGs were down-regulated. A total of 66 DEGs were commonly identified in both groups. Of these 66 DEGs, expression patterns for 36 DEGs were similar in both groups. Our analysis demonstrated that some genes related to disease defense and stress resistance were up-regulated while genes associated with chloroplast were down-regulated in response to RBSDV infection. In addition, some genes associated with plant-height were differentially expressed. This result indicates those genes might be involved in dwarf symptoms caused by RBSDV. Taken together, our results provide a genome-wide transcriptome analysis for rice plants in response to RBSDV infection which may contribute to the understanding of the regulatory mechanisms involved in rice-RBSDV interaction and the biological basis of rice black-streaked dwarf disease development in rice.



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MicroRNA-136 inhibits colon cancer cell proliferation and invasion through targeting liver receptor homolog-1/Wnt signaling

Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Qinggong Yuan, Gang Cao, Junhui Li, Yan Zhang, Wenbin Yang
An increasing number of studies have reported that microRNAs (miRNAs) are involved in the malignant behavior of colon cancer cells through directly targeting multiple tumor suppressors or oncogenes. The expression and role of miR-136 has been reported in several types of human cancer. However, the role of miR-136 in colon cancer remains unclear. In this study, we aimed to investigate the expression and function of miR-136 in colon cancer and the potential underlying mechanism. Here, we found that miR-136 was decreased in colon cancer cell lines and tissues. Overexpression of miR-136 inhibited the proliferation and invasion in SW480 and HCT116 cell lines while suppression of miR-136 exhibited the opposite effect. Liver receptor homolog-1 (LRH-1) was identified as a direct target gene of miR-136. Notably, miR-136 overexpression suppressed LRH-1 expression as well as Wnt signaling in SW480 and HCT116 cell lines. The miR-136 expression level inversely correlated with LRH-1 mRNA expression in colon cancer specimens. Moreover, overexpression of LRH-1 partially reversed the miR-136-induced antitumor effect in SW480 and HCT116 cell lines. Taken together, these findings suggest that miR-136 functions as a negative regulator in colon cancer progression by targeting LRH-1 and that miR-136 downregulation contributes to high expression of LRH-1 and aberrant activation of Wnt signaling, leaving open the possibility that miR-136 may serve as a potential therapeutic target for colon cancer.



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Association of thrombomodulin c.1418C>T polymorphism and venous thromboembolism

Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Bei Hu, Qing-Yun Wang, Liang Tang, Yu Hu
ObjectivesTo investigate the association between thrombomodulin c.1418C>T polymorphism and venous thrombosis.MethodsSystematic searches of Pubmed, EMBASE, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, the VIP Database and WANFANG Database were performed. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis was conducted to seek for potential sources of heterogeneity.ResultsA total of 8 studies were collected in our analysis, including 2519 cases and 3196 controls. No significant association between thrombomodulin c.1418C>T polymorphism and venous thrombosis was shown under the five genetic models (T vs C: OR=1.02, 95% CI=0.82–1.26; TT vs CC: OR=0.90, 95% CI=0.52–1.56; CT vs CC: OR=1.07, 95% CI=0.84–1.37; CT+TT vs CC: OR=1.05, 95% CI=0.82–1.34; TT vs CT+CC: OR=0.81, 95% CI=0.59–1.11). Similar results were observed in the following subgroup analysis based on ethnicity and source of control. However, an increased risk of venous thrombosis was found in Asian populations under three genetic models (T vs C: OR=1.31, 95% CI=1.01–1.70; CT vs CC: OR=1.41, 95% CI=1.00–2.98; TT+CT vs CC vs CC: OR=1.41, 95% CI=1.02–1.95).ConclusionCurrent studies on the thrombomodulin c.1418C>T polymorphism are of great heterogeneity. It might not be a risk factor for venous thromboembolism.



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Ancient mitochondrial pseudogenes reveal hybridization between distant lineages in the evolution of the Rupicapra genus

Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): T. Pérez, F. Rodríguez, M. Fernández, J. Albornoz, A. Domínguez
Mitochondrial pseudogenes (numts) inserted in the nuclear genome are frequently found in population studies. Its presence is commonly connected with problems and errors when they are confounded with true mitochondrial sequences. In the opposite side, numts can provide valuable phylogenetic information when they are copies of ancient mitochondrial lineages. We show that Rupicapra individuals of different geographic origin from the Cantabrian Mountains to the Apennines and the Caucasus share a nuclear COI fragment. The numt copies are monophyletic, and their pattern of differentiation shows two outstanding features: a long evolution as differentiated true mitochondrial lineage, and a recent integration and spread through the chamois populations. The COI pseudogene is much older than the present day mitochondrial clades of Rupicapra and occupies a basal position within the Rupicapra-Ammotragus-Arabitragus node. Joint analysis of this numt and a cytb pseudogene with a similar pattern of evolution places the source mitochondrial lineage as a sister branch that separated from the Ammotragus-Arabitragus lineage 6millionyearsago (Mya). The occurrence of this sequence in the nucleus of chamois suggests hybridization between highly divergent lineages. The integration event seems to be very recent, more recent than the split of the present day mtDNA lineages of Rupicapra (1.9Mya). This observation invites to think of the spread across the genus by horizontal transfer through recent male-biased dispersal.



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Effect of polymorphisms in transporter genes on dosing, efficacy and toxicity of maintenance therapy in children with acute lymphoblastic leukemia

Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Guillermo Gervasini, Silvia G. de Murillo, Mercedes Jiménez, María D. de la Maya, Jose M. Vagace
The aim of the present work was to assess whether polymorphisms in genes coding for drug transport proteins may influence dosing, efficacy and toxicity of maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6MP) in childhood acute lymphoblastic leukemia (ALL). A total of 41 children with ALL were screened for 10 SNPs in the SLC19A1, ABCB1, ABCC2, ABCC4 and ABCG2 transporter genes by means of direct sequencing. Carriers of the ABCC4 934CC and ABCB1 1236TT genotypes received a lower percentage of the protocol-recommended starting dose of MTX (62.1 vs. 81.3% for 934CA carriers, p=0.001) and 6MP (73.1 vs. 87.7% for 1236CC/CT carriers; p=0.026), respectively. The C1236T SNP also increased the efficiency of myelosuppression. Median (and interquartile) number of blood tests with leukocytes levels <310⁹/L for the CC; CT and TT genotypes were 22 (13), 30.5 (11.75) and 33 (17.25), respectively (p=0.001). In addition, this SNP also correlated with the number of hematological adverse events (p=0.004 for the difference between same genotypes). The event more profoundly affected was neutropenia (p=0.004). In the same manner, the ABCC4 934CC genotype was also associated to more frequent hematological toxicity (p=0.041 vs. CT carriers) and raised LDH levels (p=0.004 vs. CT carriers); although only the latter association remained significant after correction by multiple testing. Overall, our findings indicate that variability in the ABCB1 and ABCC4 genes may confer higher sensitivity to maintenance chemotherapy of ALL, and therefore its determination may be helpful in individualizing this treatment.



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