Αρχειοθήκη ιστολογίου

Τρίτη 19 Σεπτεμβρίου 2017

Methane oxidation in lead-contaminated mineral soils under different moisture levels

Abstract

Methane (CH4) oxidation in soil reduces the concentration of this greenhouse gas due to the activity of methanotrophic bacteria. This process is influenced by chemical and physical parameters of soil. We tested the methanotrophic activity of selected mineral soils (Mollic Gleysol, Haplic Podzol, Eutric Cambisol) contaminated with lead (Pb) under different soil water potentials (pF 0; 2.2; 3.2). The heavy metal was added as PbCl2 in two doses. Together with the initial content of Pb in soils, the final contents of heavy metal in different soils were 11.6 and 30.8 mg kg−1 in Eutric Cambisol, 7.1 and 26.3 mg kg−1 in Haplic Podzol, and 12.2 and 31.4 mg kg−1 in Mollic Gleysol (dry mass of the soil is specified in all cases). The results showed relatively low sensitivity of methane oxidation to the addition of the heavy metal. The major factor controlling this process was soil water content, which in most cases turned out to be the most optimal at pF = 2.2.



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The sustainable arable land use pattern under the tradeoff of agricultural production, economic development, and ecological protection—an analysis of Dongting Lake basin, China

Abstract

To find a solution regarding sustainable arable land use pattern in the important grain-producing area during the rapid urbanization process, this study combined agricultural production, locational condition, and ecological protection to determine optimal arable land use. Dongting Lake basin, one of the major grain producing areas in China, was chosen as the study area. The analysis of land use transition, the calculation of arable land barycenter, the landscape indices of arable land patches, and the comprehensive evaluation of arable land quality(productivity, economic location, and ecological condition) were adopted in this study. The results showed that (1) in 1990–2000, the arable land increased by 11.77%, and the transformation between arable land and other land use types actively occurred; in 2000–2010, the arable land decreased by 0.71%, and more ecological area (forestland, grassland, and water area) were disturbed and transferred into arable land; (2) urban expansion of the Changsha-Zhuzhou-Xiangtan city cluster (the major economy center of this area) induced the northward movement of the arable land barycenter; (3) the landscape fragmentation and decentralization degree of arable land patches increased during 1990–2010; (4) potential high-quality arable land is located in the zonal area around Dongting Lake, which contains the Li County, Linli County, Jinshi County, Taoyuan County, Taojiang County, Ningxiang County, Xiangxiang County, Shaoshan County, Miluo County, and Zhuzhou County. The inferior low-quality arable land is located in the northwestern Wuling mountainous area, the southeastern hilly area, and the densely populated big cities and their surrounding area. In the optimized arable land use pattern, the high-quality land should be intensively used, and the low-quality arable land should be reduced used or prohibitively used. What is more, it is necessary to quit the arable land away from the surrounding area of cities appropriately, in order to allow more space for urban expansion. This study could provide guidance for sustainable arable land use by both satisfying the future agricultural production and the local economic development, which can be used for the other major grain-producing areas in this rapid developing country.



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Aquatic environmental assessment of Lake Balaton in the light of physical-chemical water parameters

Abstract

One of the issues of the Hungarian Water Management Strategy is the improvement and upgrading of the water of Lake Balaton. The Water Framework Directive (WFD) specifies and sets forth the achievement of the good ecological status. However, the assessment of the water quality of the lake as a complex system requires a comprehensive monitoring and evaluation procedure. Measurements were carried out around the Lake Balaton at ten different locations/sites and 13 physical-chemical parameters were monitored at each measurement site.

For the interpretation of the water chemistry parameters the Aquatic Environmental Assessment (AEA) method devised by authors was used for the water body of the Lake Balaton. The AEA method can be used for all types of the water bodies since it is flexible and using individual weighting procedure for the water chemistry parameters comprehensive information can be obtain. The AEA method was compared with existing EIA methods according to a predefined criterion system and proved to be the most suitable tool for evaluating the environmental impacts in our study.

On the basis of the results it can be concluded that the status of the quality of studied area on the Lake Balaton can be categorized as proper quality (from the outcome of the ten measurement sites this conclusion was reached at seven sites).



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Response of magnetic properties to metal deposition on urban green in Nanjing, China

Abstract

Environmental magnetism is a simple and fast method that can be used to assess heavy metal pollution in urban areas from the relationships between magnetic properties and heavy metal concentrations. Leaves of Osmanthus fragrans, one of the most widely distributed evergreen trees in Nanjing, China, were collected from four different district types, i.e., residential, educational, traffic, and industrial. The magnetic properties and heavy metal concentrations were measured both for unwashed (dust-loaded) and washed leaves. Scanning electron microscopy with energy-dispersive X-ray spectroscopy confirmed that unwashed leaves accumulated much dust due to atmospheric deposition. The value of magnetic properties and heavy metal concentrations in unwashed leaves was significantly higher than those of washed leaves, indicating that these characteristics were mainly derived from atmospheric particulate matter. Saturation isothermal remanent magnetization (SIRM) values obtained from unwashed and washed leaves ranged from 209.14 × 10−6 to 877.85 × 10−6 Am2 kg−1 and from 69.50 × 10−6 to 501.28 × 10−6 Am2 kg−1, respectively. High concentrations of heavy metals, such as Pb and Fe, the Tomlinson pollution load index, and the SIRM of unwashed leaves occurred in the traffic and industrial districts. A preliminary principal component analysis identified the source categories and suggested that industrial activities may be more related to the release of particulate matter rich in Fe. The heavy metal concentrations and pollution load index showed significant positive correlations with the low-frequency magnetic susceptibility and SIRM of unwashed leaves, indicating that these properties can be used to semi-quantify atmospheric heavy metal pollution. Our study suggests that it is possible to employ magnetic measurements as a useful tool for the monitoring and assessment of atmospheric heavy metal pollution.



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Horizontal transfer of miR-23a from hypoxic tumor cell colonies can induce angiogenesis

Abstract

Neo vessel formation by angiogenesis is an important event during many pathological conditions including cancer, where it is indispensable for tumor growth and survival. Although, various pro-angiogenic cytokines and soluble factors, secreted by tumor cells, have been reported to promote angiogenesis, recent studies have shown regulatory role of exosomes, secreted by tumor cells in the process of angiogenesis. These exosomes are capable of carrying nucleic acids, proteins etc. as their cargo. Under the light of these facts and considering the presence of miRNAs, the non-coding RNAs capable of regulating target gene expression, as one of the major cargos in the exosomes, we investigated, whether exosomes derived from normoxic and hypoxic tumor cell colonies exhibit difference in levels of miR-23∼27∼24 cluster members and if so, to check the significance of their horizontall transfer on the process of angiogenesis. Results of our study showed that exosomes secreted by hypoxic tumor cell colonies possess significantly higher levels of miR23a and can induce angiogenesis.. Further we have shown that exosomes secreted by cells that ectopically over express miR23a is capable of inducing angiogenesis in different angiogenic model systems such as CAM, in ovo Xenograft and HUVEC models systems. Further, mechanistic analysis revealed that miR23a driven regulation of angiogenesis is brought about by down regulation of SIRT1 in the recipient cells. Collectively, the results presented here suggest that exosomal transfer of miR23a from tumor cell colonies can induce the process of angiogenesis by targeting SIRT1 in the recipient endothelial cells. This article is protected by copyright. All rights reserved



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Book Review: Endoscopic Approaches to the Paranasal Sinuses and Skull Base

Annals of Otology, Rhinology &Laryngology, Ahead of Print.


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Advances in video-assisted thoracoscopic surgery

Abstract

Purpose

Video-assisted thoracoscopic surgery (VATS) has been widely accepted as a standard approach for early stage non-small cell lung cancer resection, along with increased application for more complex tumor pathology. With advancing techniques and technology, more complex cases are being performed with acceptable results. We reviewed recent advances in how VATS techniques are increasingly being used to successfully and safely replicate open thoracic surgical procedures.

Method

We reviewed current literature on VATS for complex cases.

Conclusion

VATS is feasible and can be safely performed for complex cases in experienced hands. Further prospective studies are needed to validate its utility for complex cases.



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DNA damage response inhibitors: mechanisms and potential applications in cancer therapy

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Publication date: Available online 19 September 2017
Source:Cancer Treatment Reviews
Author(s): Laura Carrassa, Giovanna Damia
Over the last decade the unravelling of the molecular mechanisms of the DNA damage response pathways and of the genomic landscape of human tumors have paved the road to new therapeutic approaches in oncology. It is now clear that tumors harbour defects in different DNA damage response steps, mainly signalling and repair, rendering them more dependent on the remaining pathways. We here focus on the proteins ATM, ATR, CHK1 and WEE1, reviewing their roles in the DNA damage response and as targets in cancer therapy. In the last decade specific inhibitors of these proteins have been designed, and their potential antineoplastic activity has been explored both in monotherapy strategies against tumors with specific defects (synthetic lethality approach) and in combination with radiotherapy or chemotherapeutic or molecular targeted agents. The preclinical and clinical evidence of antitumor activity of these inhibitors emanating from these research efforts will be critically reviewed. Lastly, the potential therapeutic feasibility of combining together such inhibitors with the aim to target particular subsets of tumors will be also discussed. .



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Reply to the Letter to the Editor Concerning: ‘Changes in Swallowing-Related Quality of Life After Endoscopic Treatment for Zenker’s Diverticulum Using SWAL-QOL Questionnaire’



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A Survey of Australian Dysphagia Practice Patterns

Abstract

Dysphagia assessment and rehabilitation practice is complex, and significant variability in speech-language pathology approaches has been documented internationally. The aim of this study was to evaluate swallowing-related assessment and rehabilitation practices of SLPs currently working in Australia. One hundred and fifty-four SLPs completed an online questionnaire administered via QuickSurveys from May to July 2015. Results were analysed descriptively. The majority of clinicians had accessed post-graduate training in dysphagia management and assessment (66.23%). Referral and screening were typically on an ad hoc basis (74.03%). Clinical swallow examination (CSE) and Videofluoroscopic Swallowing Study were used by 93.51 and 88.31% of respondents, respectively. CSE was the assessment that predominantly informed clinical decision-making (52.63%). Clinicians typically treated clients with dysphagia for 30 min per session (46.10%), with recommendations of repetition of exercises inconsistent across settings. Outcome measures were utilised by many (67.53%), which however were typically informal. Results indicate variable practice patterns for dysphagia assessment and management across Australia. This variability may reflect the heterogeneous nature of dysphagia and the varying needs of patients accessing different services.



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Retinoid Expression in Onchocercal Skin Disease: Pilot Study

Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA (r2 = 0.25, P = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of vitamin A to heat and light.

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Examining Playa Wetland Contemporary Conditions in the Rainwater Basin, Nebraska

Abstract

Based on three critical criteria – soil, hydrology, and vegetation, this study examined contemporary playa wetland conditions to determine the extent of wetland degradation in the Rainwater Basin in south-central Nebraska. Geospatial statistics were used to evaluate the changes between historical hydric soil footprints and the most recent wetland survey datasets. The results indicate that the historical hydric soil footprints dominated by the Scott and Fillmore soil series have degraded 31.0% and 79.4% respectively. We also found approximately two-thirds of the footprints no longer pond water during spring migration. In fact, only 16.8% of the historical hydric soil footprints contain hydrophytes in recent surveys. Furthermore, the majority of these footprints (and the associated uplands) have been converted to cropland and no longer pond frequently or support hydrophytes. Additionally, the extensive grid road system supports commodity crop production, but in many instances this infrastructure has significantly altered wetland footprints and the associated watersheds to reduce the total water volume delivered to wetlands. The resulting situation is that conserved lands, including Waterfowl Production Areas (WPAs), Wildlife Management Areas (WMAs), and conservation easements only represent 11.3% of total historical footprints, but contribute to over 40.5% of the current total ponded water and hydrophytes.



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Corrigendum

Otolaryngology-Head and Neck Surgery, Ahead of Print.


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Evidence-Based Medicine in Otolaryngology, Part 6: Patient-Reported Outcomes in Clinical Practice

Otolaryngology-Head and Neck Surgery, Ahead of Print.


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Table of contents



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Masthead



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Preface



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Sydney dentist Dr Luke Cronin on how to brush your teeth

'It was very dark and dangerous': Hillary Clinton slams Trump's UN speech as she tells Stephen Colbert the president should not have called Kim Jong-un 'Rocket Man' KB Home CEO Jeffrey Mezger called his neighbor Kathy Griffin a 'bald d**e' and 'c**t' after her boyfriend called the LAPD to report his grandchildren for being too loud First college football player charged in hazing incident turns himself after being accused of trying to 'sodomize and beat a freshman before leaving him naked in a park' Puerto Rico tells residents 'evacuate or die' as Maria closes in: People flee and a state of emergency is declared as hurricane with 175mph winds barrels towards island after destroying Dominica Outrage as Missouri highway trooper is given just 10 DAYS 'shock time' in jail after man, 20, he improperly handcuffed fell off a boat and drowned while in his custody Have you been brushing your teeth ... (more)



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Effect of a mentor-based, supportive-expressive program, Be Resilient to Breast Cancer, on survival in metastatic breast cancer: a randomised, controlled intervention trial



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First-line FOLFIRI and bevacizumab in patients with advanced colorectal cancer prospectively stratified according to serum LDH: final results of the GISCAD (Italian Group for the Study of Digestive Tract Cancers) CENTRAL (ColorEctalavastiNTRiAlLdh) trial



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The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia



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Group interventions to reduce emotional distress and fatigue in breast cancer patients: a 9-month follow-up pragmatic trial



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Antioxidants, Vol. 6, Pages 72: Profiling of Polyphenol Composition and Antiradical Capacity of Erica cinerea

Antioxidants, Vol. 6, Pages 72: Profiling of Polyphenol Composition and Antiradical Capacity of Erica cinerea

Antioxidants doi: 10.3390/antiox6030072

Authors: Alfredo Aires Rosa Carvalho

The aim of the current study was to determine the profile and content of polyphenols present in Erica cinerea, an important plant species from Northern Portuguese flora and often reported as having anti-inflammatory, antioxidant, and anti-radical activity. The analysis of polyphenols was performed by HPLC-DAD/UV-Vis, and the 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+) method was used to evaluate its radical scavenging activity. HPLC analysis showed that both plants presented a great diversity of compounds, with 33% flavones, 28% flavanols, and 26% hydroxycinnamic acids. The antiradical activity was dose-dependent, and the IC50 values were 0.251 mg mL−1. Based on our study, E. cinerea presented interesting bioactive compounds and it can be used to extract and purify bioactive polyphenols to be used in pharmaceutical or agro-food industries.



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Paradigm shift in head and neck oncology patient management

This article describes a paradigm shift in what is considered to be good care for patients living with and after (head and neck) cancer. HNO patients often experience severe and difficult physical and psychoso...

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Editorial Board/Aims & Scope



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Patient-oriented toxicity endpoints after head and neck reirradiation with intensity modulated radiation therapy

Reirradiation (reRT) is a treatment option for select patients with recurrent or second primary squamous cell carcinoma of the head and neck (SCCHN) [1] and can result in prolonged disease control and even cure in select patients [2]. However, improvements in local-regional control rates must be balanced with the significant risks of treatment-related toxicity. Shared-decision making regarding the benefit of reRT must involve a discussion of possible side effects of treatment and the time course over which these side effects are likely to occur.

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Appraisal of the AJCC 8th edition pathologic staging modifications for HPV−positive oropharyngeal cancer, a study of the National Cancer Data Base

The American Joint Commission on Cancer (AJCC) 7th edition staging manual for oropharyngeal cancer was designed before high-risk human papillomavirus positive oropharyngeal cancer (HPV+ OPSCC) became preeminent, an entity that's now expected to surpass incidence of HPV cervical cancer by 2020 [1]. As such, the 7th edition staging paradigm progressively lost its prognostic ability as HPV+ OPSCC boasts far better survival and treatment sensitivity than HPV−negative disease. Moreover, recent studies have demonstrated its prognostic inadequacy [2–5].

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Oropharyngeal lymphoma: A US population based analysis

Head and neck lymphomas arise from lymph nodes as well as extranodal locations including, Waldeyer ring, the sinonasal tract, nasopharynx and salivary glands [1]. The oropharynx contains the palatine tonsils as well as the base of tongue (BOT), both of these locations are part of Waldeyer's ring and are comprised of lymphoid tissue [2]. B cells proliferate and mature at these locations, which represent the first contact point for exogenous antigens entering the aerodigestive tract [3]. Lymphomas are subdivided into Hodgkin's lymphoma (HL) and Non-Hodgkin's lymphoma (NHL), with extranodal NHL being the second most common primary head and neck malignancy after squamous cell carcinoma [4].

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Chemotherapy in head and neck osteosarcoma: Adjuvant chemotherapy improves overall survival

Osteosarcoma is a common bone malignancy characterized by osteoid formation by highly malignant osteoblasts [1], osteosarcoma occurs commonly in the extremity of children and adolescents and rarely in the head and neck sites, only 6% to 10% of all osteosarcomas are reported to occur in head and neck sites [2,3]. The tumor is aggressive and often presents with high histological grade [4] and propensity towards lung metastasis [5]. Surgery is the main therapeutic modality for cure. However; many trials indicate the benefit of adjuvant chemotherapy in improving survival of these patients [6].

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Long-term results of a phase II study of gemcitabine and cisplatin chemotherapy combined with intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma

Two-thirds of nasopharyngeal carcinoma (NPC) patients who present with stage III-IVA-B are potentially eligible for curative chemoradiotherapy. In the 2DRT era, concurrent chemoradiotherapy (CCRT) was the standard treatment in locoregionally advanced NPC since the publication of the landmark Intergroup 0099 study [1]. Several subsequential clinical trials also confirmed the effectiveness of this treatment modality [2–4]. The current NCCN guidelines recommend that CCRT followed by adjuvant chemotherapy (AC) for locoregionally advanced NPC, originate from the results of these studies.

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Poor oral health affects survival in head and neck cancer

Squamous cell carcinoma of the head and neck (HNSCC) contributes substantially to the global burden of cancer [1–3]. It is the sixth most common cancer worldwide [4], and the fifth most common cancer in the United States, affecting approximately 40,000 new patients each year [1]. It encompasses cancers of the oral cavity, oropharynx, and larynx among others. While the mortality rate for HNSCC has improved recently, it still has poorer survival rates than some other common malignancies such as breast, cervical, and colorectal cancers [5,6].

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Incidence and dosimetric parameters for brainstem necrosis following intensity modulated radiation therapy in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a malignancy of the nasopharyngeal epithelium with a distinct epidemiology compared to other head and neck squamous cell carcinomas. The incidence of NPC is extremely high (15–50 per 100,000) in southern China, but extremely low in most other countries [1].

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Epigenetic therapy regulates the expression of ALDH1 and immunologic response: Relevance to the prognosis of oral cancer

Oral squamous cell carcinoma (OSCC) is the most malignant tumor of the head and neck [1]. Despite considerable advances in treatment, about 50% of patients with locally advanced disease relapse with local or distant disease progression [2,3]. Investigating specific molecular markers related to the capacity for tumor invasion and treatment sensitivity could provide new insights for the identification of innovative treatments.

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Demographic and clinicopathological characteristics of nasopharyngeal carcinoma and survival outcomes according to age at diagnosis: A population-based analysis

Though rare in Japan and western countries, nasopharyngeal carcinoma (NPC) is endemic in southern China, Southeast Asia and Southern Africa. In general, the incidence of NPC in endemic and non-endemic areas has stabilised in recent decades [1,2]; however, the age distribution varies between endemic and non-endemic areas. The age distribution of NPC is unimodal in endemic areas, peaking in individuals aged 45–59-years-old [1,2]. However, in low risk populations, the age distribution is bimodal, with a first peak in young adolescents (aged 15–19) and a second peak in individuals aged 65–79 [1].

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Transoral bisected resection for T1-2 oral tongue squamous cell carcinoma to secure adequate deep margin

To investigate the clinical usefulness of transoral bisected resection (TBR) asa new method to secure adequate deep resection margin in T1-2 oral tongue squamous cell carcinomas (SCC).

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Prevalence of high-risk human papillomavirus infection and cancer gene mutations in nonmalignant tonsils

Head and neck squamous cell carcinoma (SCC) accounts for approximately 600,000 new cancer cases each year [1]. The main risk factors are tobacco and alcohol use. In many developed countries, however, the majority of newly diagnosed tonsillar SCCs are associated with high-risk human papillomavirus (HPV) infection, predominantly HPV type 16 [2,3]. Compared to individuals with HPV negative tonsillar SCC, those with HPV positive disease have better prognosis, and they are often younger with no significant history of tobacco or alcohol use [4–6].

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Rationale for neoadjuvant immunotherapy in head and neck squamous cell carcinoma

In patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN), current treatment guidelines recommend surgery with post-operative adjuvant therapy or definitive chemoradiotherapy (CRT) as standard of care. Despite these intensive multimodality treatments, recurrence of disease persists asa key cause for treatment failure. Recurrent disease is especially problematic in human papillomavirus (HPV)-unrelated SCCHN.

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Snail and Axin2 expression predict the malignant transformation of oral leukoplakia

Oral leukoplakias (OL) are common whitish patches of the oral cavity having a well-documented potential risk of malignant transformation [1–3]. The prevalence of OL is approximately 1% in all ages, the annual rate of malignant transformation of untreated lesions having been reported as 2–3% [1]. Meanwhile, the risk of recurrence after the surgical treatment of non-homogeneous leukoplakia has been estimated at up to 20%, and oral squamous cell carcinomas (OSCC) developed from OL demonstrate poor clinical outcomes [2].

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Genomic characterization of tobacco/nut chewing HPV-negative early stage tongue tumors identify MMP10 asa candidate to predict metastases

Tongue cancer is the most predominant form of oral cancer in developed countries with a varying incidence in developing countries [1]. The major etiological factors associated with tongue cancer include tobacco related products, alcohol and human papilloma virus (HPV) infections [2]. These factors lend to variability across populations, particularly in the Indian subcontinent wherein chewing betel-quid comprising betel leaf (Piper betel), areca nut (Areca catechu) and slaked lime (predominantly calcium hydroxide) is a part of the tradition [3].

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Predictors of survival in head and neck mucosal melanoma

Mucosal melanomas are among the most lethal of head and neck cancers. Although they can arise from any mucosa-lined surface, mucosal melanomas most commonly occur in the sinonasal regions of the head and neck [1]. In comparison to cutaneous, acral, and ocular melanomas, mucosal melanoma exhibits an aggressive clinical course with poor prognosis [2–5]. Diagnosis is often delayed given few and nonspecific presenting symptoms mimicking more common benign processes [6]. Furthermore, head and neck mucosal melanomas (HNMMs) have relatively high rates of local, regional, and distant metastases despite aggressive multimodality therapy [7].

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Patient-oriented toxicity endpoints after head and neck reirradiation with intensity modulated radiation therapy

Reirradiation (reRT) is a treatment option for select patients with recurrent or second primary squamous cell carcinoma of the head and neck (SCCHN) [1] and can result in prolonged disease control and even cure in select patients [2]. However, improvements in local-regional control rates must be balanced with the significant risks of treatment-related toxicity. Shared-decision making regarding the benefit of reRT must involve a discussion of possible side effects of treatment and the time course over which these side effects are likely to occur.

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Appraisal of the AJCC 8th edition pathologic staging modifications for HPV−positive oropharyngeal cancer, a study of the National Cancer Data Base

The American Joint Commission on Cancer (AJCC) 7th edition staging manual for oropharyngeal cancer was designed before high-risk human papillomavirus positive oropharyngeal cancer (HPV+ OPSCC) became preeminent, an entity that's now expected to surpass incidence of HPV cervical cancer by 2020 [1]. As such, the 7th edition staging paradigm progressively lost its prognostic ability as HPV+ OPSCC boasts far better survival and treatment sensitivity than HPV−negative disease. Moreover, recent studies have demonstrated its prognostic inadequacy [2–5].

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Chemotherapy in head and neck osteosarcoma: Adjuvant chemotherapy improves overall survival

Osteosarcoma is a common bone malignancy characterized by osteoid formation by highly malignant osteoblasts [1], osteosarcoma occurs commonly in the extremity of children and adolescents and rarely in the head and neck sites, only 6% to 10% of all osteosarcomas are reported to occur in head and neck sites [2,3]. The tumor is aggressive and often presents with high histological grade [4] and propensity towards lung metastasis [5]. Surgery is the main therapeutic modality for cure. However; many trials indicate the benefit of adjuvant chemotherapy in improving survival of these patients [6].

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A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator’s choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141

Carcinoma of the head and neck accounts for ≥600,000 new cases and >300,000 deaths each year globally [1]. In Japan, the incidence of invasive oral, pharynx, and larynx cancers was estimated at 24,557 in 2012 [2]. The incidence of carcinoma of the head and neck is also increasing. In South Korea, the incidence of all carcinomas of the head and neck has increased since 1998, except for laryngeal cancer [3]. In Taiwan, among solid cancers, oropharyngeal cancer had the fourth greatest increase in incidence from 2002 to 2012, with an average annual percentage increase of 5% [4].

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Pre-diagnostic dynamic HPV16 IgG seropositivity and risk of oropharyngeal cancer

Human papillomavirus (HPV) is associated with a subset of head and neck squamous cell carcinomas (HNSCC) [1], with a strong association with cancers of the oropharynx (OPC), including cancers of the tonsils and base of tongue [2]. It is now estimated that HPV type 16 is associated with 65–80% of OPC [3,4] and incidence rates of HPV-related OPC are rapidly rising [5].

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Poor oral health affects survival in head and neck cancer

Squamous cell carcinoma of the head and neck (HNSCC) contributes substantially to the global burden of cancer [1–3]. It is the sixth most common cancer worldwide [4], and the fifth most common cancer in the United States, affecting approximately 40,000 new patients each year [1]. It encompasses cancers of the oral cavity, oropharynx, and larynx among others. While the mortality rate for HNSCC has improved recently, it still has poorer survival rates than some other common malignancies such as breast, cervical, and colorectal cancers [5,6].

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Chemoradiotherapy for locally advanced squamous cell carcinoma of the oropharynx: Does completion of systemic therapy affect outcomes?

Locally advanced squamous cell carcinoma of the oropharynx (LA-OPC), defined as stage III–IVB disease per the current American Joint Committee on Cancer (AJCC) 7th edition staging manual, remains difficult to treat [1]. Recommended treatment options are diverse but universally include radiation therapy with the potential addition of preceding surgical resection, induction chemotherapy, and concurrent systemic agents [2,3]. In the setting of definitive radiation therapy for LA-OPC, multiple clinical trials have demonstrated significant advantage to the addition of concurrent systemic therapies, namely improving local control, disease-free survival, and overall survival [4–10].

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Incidence and dosimetric parameters for brainstem necrosis following intensity modulated radiation therapy in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a malignancy of the nasopharyngeal epithelium with a distinct epidemiology compared to other head and neck squamous cell carcinomas. The incidence of NPC is extremely high (15–50 per 100,000) in southern China, but extremely low in most other countries [1].

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Demographic and clinicopathological characteristics of nasopharyngeal carcinoma and survival outcomes according to age at diagnosis: A population-based analysis

Though rare in Japan and western countries, nasopharyngeal carcinoma (NPC) is endemic in southern China, Southeast Asia and Southern Africa. In general, the incidence of NPC in endemic and non-endemic areas has stabilised in recent decades [1,2]; however, the age distribution varies between endemic and non-endemic areas. The age distribution of NPC is unimodal in endemic areas, peaking in individuals aged 45–59-years-old [1,2]. However, in low risk populations, the age distribution is bimodal, with a first peak in young adolescents (aged 15–19) and a second peak in individuals aged 65–79 [1].

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Transoral bisected resection for T1-2 oral tongue squamous cell carcinoma to secure adequate deep margin

To investigate the clinical usefulness of transoral bisected resection (TBR) asa new method to secure adequate deep resection margin in T1-2 oral tongue squamous cell carcinomas (SCC).

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Prevalence of high-risk human papillomavirus infection and cancer gene mutations in nonmalignant tonsils

Head and neck squamous cell carcinoma (SCC) accounts for approximately 600,000 new cancer cases each year [1]. The main risk factors are tobacco and alcohol use. In many developed countries, however, the majority of newly diagnosed tonsillar SCCs are associated with high-risk human papillomavirus (HPV) infection, predominantly HPV type 16 [2,3]. Compared to individuals with HPV negative tonsillar SCC, those with HPV positive disease have better prognosis, and they are often younger with no significant history of tobacco or alcohol use [4–6].

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Rationale for neoadjuvant immunotherapy in head and neck squamous cell carcinoma

In patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN), current treatment guidelines recommend surgery with post-operative adjuvant therapy or definitive chemoradiotherapy (CRT) as standard of care. Despite these intensive multimodality treatments, recurrence of disease persists asa key cause for treatment failure. Recurrent disease is especially problematic in human papillomavirus (HPV)-unrelated SCCHN.

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Snail and Axin2 expression predict the malignant transformation of oral leukoplakia

Oral leukoplakias (OL) are common whitish patches of the oral cavity having a well-documented potential risk of malignant transformation [1–3]. The prevalence of OL is approximately 1% in all ages, the annual rate of malignant transformation of untreated lesions having been reported as 2–3% [1]. Meanwhile, the risk of recurrence after the surgical treatment of non-homogeneous leukoplakia has been estimated at up to 20%, and oral squamous cell carcinomas (OSCC) developed from OL demonstrate poor clinical outcomes [2].

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Predictors of survival in head and neck mucosal melanoma

Mucosal melanomas are among the most lethal of head and neck cancers. Although they can arise from any mucosa-lined surface, mucosal melanomas most commonly occur in the sinonasal regions of the head and neck [1]. In comparison to cutaneous, acral, and ocular melanomas, mucosal melanoma exhibits an aggressive clinical course with poor prognosis [2–5]. Diagnosis is often delayed given few and nonspecific presenting symptoms mimicking more common benign processes [6]. Furthermore, head and neck mucosal melanomas (HNMMs) have relatively high rates of local, regional, and distant metastases despite aggressive multimodality therapy [7].

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Patients’ perception regarding the influence of individual and social vulnerabilities on the adherence to tuberculosis treatment: a qualitative study

Tuberculosis remains an important disease which mainly affects the majority of vulnerable individuals in society, who are subjected to poor living conditions and difficulties to access the services of public h...

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Heterogeneity in coverage for measles and varicella vaccination in toddlers – analysis of factors influencing parental acceptance

In 2004, routine varicella vaccination was introduced in Germany for children aged 11–14 months. Routine measles vaccination had already been introduced in 1973 for the same age group, but coverage is still to...

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IJMS, Vol. 18, Pages 2003: To Wnt or Lose: The Missing Non-Coding Linc in Colorectal Cancer

IJMS, Vol. 18, Pages 2003: To Wnt or Lose: The Missing Non-Coding Linc in Colorectal Cancer

International Journal of Molecular Sciences doi: 10.3390/ijms18092003

Authors: Peng Shen Martin Pichler Meng Chen George Calin Hui Ling

Colorectal cancer (CRC) is the third most frequent cancer and one of the leading causes for cancer-related mortality. Aberrant activation of the Wnt signaling is an essential initiating factor in colon carcinogenesis, and a driving force of CRC progression. Recently, long non-coding RNAs (lncRNAs) have emerged as significant players in CRC pathogenesis through diversified mechanisms. Although both Wnt signaling and lncRNAs represent interesting research areas for CRC, an effort of directly connecting these two areas is lacking. To fill in the knowledge gap, we focus on the reported findings of lncRNAs that regulate Wnt signaling or essential Wnt signaling targets. These include several newly discovered lncRNAs originated from the amplified cancer-associated chromosome 8q24 region that surrounds the essential Wnt target MYC gene, lncRNAs reported to be involved in CRC stem cells, and several individual lncRNAs connected to Wnt signaling through other mechanisms. This review will provide essential information that assists in understanding the missing link of lncRNAs to the classical Wnt signaling in CRC.



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Detection of Malignancy Among Suspicious Thyroid Nodules

Thyroid , Vol. 0, No. 0.


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Editorial Board

Publication date: October 2017
Source:Biochimie, Volume 141





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Impact of high-fat diet on the intestinal microbiota and small intestinal physiology before and after the onset of obesity

Publication date: October 2017
Source:Biochimie, Volume 141
Author(s): João Ricardo Araújo, Julie Tomas, Christiane Brenner, Philippe J. Sansonetti
The modulation of the intestinal microbiota by high-fat diet (HFD) has a major impact on both immunological and metabolic functions of the host. Taking this into consideration, the aim of this contribution is to review the impact of HFD on microbiota profile and small intestinal physiology before and after the onset of obesity and its metabolic complications. Evidence from animal studies suggest that before the onset of obesity and its metabolic complications, HFD induces intestinal dysbiosis - encompassing changes in composition balance and massive redistribution with bacteria occupying intervillous spaces and crypts - associated with early physiopathological changes, predominantly in the ileum, such as low-grade inflammation, decreased antimicrobial peptides expression, impaired mucus production, secretion and layer's thickness, and decreased expression of tight junction proteins. With time, major inflammatory signals (e.g. toll-like receptor-4 dependent) become activated, thereby stimulating proinflammatory cytokines secretion in the small intestine. This inflammatory state might subsequently exacerbate disruption of the mucus layer barrier and increase epithelial permeability of the small intestine, thereby creating an environment that facilitates the passage of bacterial components (e.g. lipopolysaccharide, peptidoglycan and flagellin) and metabolites from the intestinal lumen (e.g. secondary bile acids) to the circulation and peripheral tissues (i.e. leaky gut), eventually promoting the development of systemic inflammation, obesity, adiposity, insulin resistance and glucose intolerance preceding hyperglycemia. Although the mechanisms are still not completely understood, prebiotics, probiotics, polyphenols, peroxisome proliferator-activated receptor-γ agonists (such as rosiglitazone) and exercise have been shown to reverse HFD-induced intestinal phenotype and to attenuate the severity of obesity and its associated metabolic complications.



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Complex formation with protamine prolongs the thrombin-inhibiting effect of DNA aptamer in vivo

Publication date: Available online 19 September 2017
Source:Biochimie
Author(s): V.A. Spiridonova, T.M. Novikova, D.M. Nikulina, T.A. Shishkina, E.V. Golubkina, O.S. Dyukareva, N.N. Trizno
Antithrombin DNA aptamersRE31 are single-chain oligonucleotides that fold into three-dimensional forms allowing them to bind the enzyme with high affinity and inhibit its activity in vivo. They are rapidly degraded by a nonspecific nuclease, and, to prolong the lifetime of the aptamer DNA in the bloodstream, it is necessary to coat it with a polymer envelope. A new approach to solving this problem based on preparation of DNA–polyelectrolyte complexes with a minimal particle size that can circulate with blood flow. In our experiments, the negatively charged aptamer DNA RE31 was coated step-by-step with positively charged protamine. They had protamine/aptamer ratios of 0.2/1 and 0.4/1 by charge, with particle size being determined by dynamic light scattering. The aptamer DNA–protamine complexes were administered to rats, followed by ex vivo analysis of blood samples. The results showed that prothrombin time (PT) increased by a factor of 5.6–6.7 within 2 h after injection and remained at approximately the same level for 6 h, while injections of pure protamine did not lead to any noticeable change in clotting time. Thus, complexation with protamine proved to prolong the inhibitory activity of the RE31 DNA aptamer.



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Follow-up care after treatment for prostate cancer: protocol for an evaluation of a nurse-led supported self-management and remote surveillance programme

As more men survive a diagnosis of prostate cancer, alternative models of follow-up care that address men's enduring unmet needs and are economical to deliver are needed. This paper describes the protocol for ...

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The suppressive role of miR-542-5p in NSCLC: the evidence from clinical data and in vivo validation using a chick chorioallantoic membrane model

Non-small cell lung cancer (NSCLC) has led to the highest cancer-related mortality for decades. To enhance the efficiency of early diagnosis and therapy, more efforts are urgently needed to reveal the origins ...

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Needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer evaluated by repeated MRI

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Publication date: Available online 19 September 2017
Source:Brachytherapy
Author(s): Simon Buus, Maria Lizondo, Steffen Hokland, Susanne Rylander, Erik M. Pedersen, Kari Tanderup, Lise Bentzen
PurposeTo quantify needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer and propose a threshold for needle migration.Methods and MaterialsTwenty-four high-risk prostate cancer patients treated with an HDR boost of 2 × 8.5 Gy were included. Patients received an MRI for planning (MRI1), before (MRI2), and after treatment (MRI3). Time from needle insertion to MRI3 was ∼3 hours. Needle migration was evaluated from coregistered images: MRI1-MRI2 and MRI1-MRI3. Dose volume histogram parameters from the treatment plan based on MRI1 were related to parameters based on needle positions in MRI2 or MRI3. Regression was used to model the average needle migration per implant and change in D90 clinical target volume, CTVprostate+3mm. The model fit was used for estimating the dosimetric impact in equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy.ResultsNeedle migration was on average 2.2 ± 1.8 mm SD from MRI1-MRI2 and 5.0 ± 3.0 mm SD from MRI1-MRI3. D90 CTVprostate+3mm was robust toward average needle migration ≤3 mm, whereas for migration >3 mm D90 decreased by 4.5% per mm. A 3 mm of needle migration resulted in a decrease of 0.9, 1.7, 2.3, 4.8, and 7.6 equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy, respectively.ConclusionsSubstantial needle migration in high-dose-rate brachytherapy occurs frequently in 1–3 hours following needle insertion. A 3-mm threshold of needle migration is proposed, but 2 mm may be considered for dose levels ≥15 Gy.



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Aortic aneurysm

Aortic aneurysm: An outpouching (a local widening) of the largest artery in the body, the aorta, involving that vessel in its course above the diaphragm (thoracic aortic aneurysm) or, more commonly, below the diaphragm (abdominal aortic aneurysm). The diagnosis of an aortic aneurysm can be straight forward or difficult. Around 1900 the eminent physician William Osler said: "There is no disease more conducive to clinical humility than aneurysm of the aorta." At the area of the aneurysm, there is typically a bulge and the wall is weakened and may rupture. Because of the volume of blood flowing under relatively high pressure through the aorta, a ruptured aneurysm of the aorta is a catastrophe.

The word "aneurysm" comes from the Greek "aneurysma" meaning "a widening."



MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
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Long term variations in erythema effective solar UV at Chilton, UK, from 1991 to 2015

Photochem. Photobiol. Sci., 2017, Accepted Manuscript
DOI: 10.1039/C7PP00053G, Paper
Rebecca J Hooke, Michael P Higlett, Nezahat Hunter, John B O'Hagan
In this paper erythema effective UV radiant exposure data from the PHE solar network Chilton site for the 25 year period from 1991 to 2015 are presented. The year with...
The content of this RSS Feed (c) The Royal Society of Chemistry


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Hémorragies digestives : qui ? quand ? place des nouveaux traitements ?



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Meltblown Polymer Fabrics as Candidate Scaffolds for Rotator Cuff Tendon Tissue Engineering

Tissue Engineering Part A Sep 2017, Vol. 23, No. 17-18: 958-967.


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Special Focus Issue on Strategic Directions in Musculoskeletal Tissue Engineering

Tissue Engineering Part A Sep 2017, Vol. 23, No. 17-18: 873-873.


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Selecting of a cytochrome P450cam SeSaM library with 3-Chloroindole and Endosulfan – Identification of mutants that Dehalogenate 3-Chloroindole

Publication date: Available online 18 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Shaima Kammoonah, Brinda Prasad, Priyadarshini Balaraman, Hemanshu Mundhada, Ulrich Schwaneberg, Erika Plettner
Cytochrome P450cam (a camphor hydroxylase) from the soil bacterium Pseudomonas putida shows potential importance in environmental applications such as the degradation of chlorinated organic pollutants. Seven P450cam mutants generated from Sequence Saturation Mutagenesis (SeSaM) and isolated by selection on minimal media with either 3-chloroindole or the insecticide endosulfan were studied for their ability to oxidize of 3-chloroindole to isatin. The wild-type enzyme did not accept 3-chloroindole as a substrate. Mutant (E156G/V247F/V253G/F256S) had the highest maximal velocity in the conversion of 3-chloroindole to isatin, whereas mutants (T56A/N116H/D297N) and (G60S/Y75H) had highest kcat/KM values. Six of the mutants had more than one mutation, and within this set, mutation of residues 297 and 179 was observed twice. Docking simulations were performed on models of the mutant enzymes; the wild-type did not accommodate 3-chloroindole in the active site, whereas all the mutants did. We propose two potential reaction pathways for dechlorination of 3-chloroindole.List of Chemical Compounds.1(R) (+)-camphor (PubChem CID 159055); 3-chloroindole (PubChem CID 177790); endosulfan (PubChem CID 3224); indigo (PubChem CID 5318432); isatin (PubChem CID 7054); m-chloroperbenzoic acid, m-CPBA (PubChem ID 70297); tricarbonylchloro(glycinato)ruthenium, CORM-3 (PubChem ID 91886169).



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The reliability of different methods of manual volumetric segmentation of pharyngeal and sinonasal sub regions

Publication date: Available online 18 September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Bala Chakravarthy Neelapu, Om Prakash Kharbanda, Harish Kumar Sardana, Abhishek Gupta, Srikanth Vasamsetti, Rajiv Balachandran, Shailendra Singh Rana, Viren Sardana
Objectives: The purpose of the study was to test the intra- and interobserver reliability of manual volumetric segmentation of pharyngeal and sinonasal airway sub-regions. Study Design: CBCT data of 15 patients were collected from an orthodontic clinical database. Two experienced orthodontists independently performed manual segmentation of the airway sub-regions. Four performance measures were considered to test intra- and interobserver reliability of manual segmentation: (i) volume correlation, (ii) mean slice correlation, (iii) percentage of volume difference, and (iv) percentage of non-overlapping voxels. Results: Intra- and interobserver reliability was observed to be greater than 0.96 for the entire pharyngeal and sinonasal airway sinus sub-regions for both observers using the volume correlation method. Mean slice correlation was found to be greater than 0.84, showing the existence of non-overlapping voxels. Therefore, the percentage of non-overlapping voxels was used as a reliability measure and was found to be less than 20% for both intra- and interobserver markings. Conclusion: The mean slice correlation and percentage of non-overlapping voxels were the most reliable performance measures of segmentation correctness. Volume correlation and the percentage of volume difference were observed to be the most reliable performance measures for volume correctness.



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Evaluation of KGF, EGF, VEGF, bcl-2, IL-6 and ki67 expression in oral epithelium adjacent to bisphosphonate-related osteonecrosis and florid osseous dysplasia: a comparative immunohistochemical study

Publication date: Available online 18 September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Natália Santos Carneiro, Luciana Armada, Débora Lima Pereira, Pablo Agustin Vargas, Márcio Ajudarte Lopes, Fábio Ramôa Pires
Bisphosphonates are associated with impairment of epithelial proliferation and it is suggested that this feature can play a role in the pathogenesis of bisphosphonate-related osteonecrosis of the jaws (ON). Objective: to compare the expression of proliferative markers and apoptosis-associated proteins in the oral mucosa adjacent to bone sequestrum associated with ON and florid osseous dysplasia (OD). Study design: oral mucosal samples derived from surgical procedures performed for treatment of ON and OD (10 cases each) were retrieved. Histological analysis was done on hematoxylin and eosin stained slides; immunohistochemical reactions against epidermal growth factor (EGF), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), Bcl-2 protein, interleukin 6 (IL-6) and Ki-67 antigen were performed with the immunoperoxidase technique. Results: epithelium was hyperplastic in 60% and 22% of ON and OD samples, respectively. Cytoplasmic EGF and KGF expression and Bcl-2, VEGF and IL-6 expressions, and the mean epithelial proliferative index were not statistically different comparing both groups. Membranous EGF expression was more evident in samples showing hyperplastic epithelium. Conclusion: exposure to bisphosphonates did not alter the expression of KGF, EGF, VEGF, Bcl-2, IL-6 and the epithelial proliferating index in comparison with inflamed oral mucosa not exposed to bisphosphonates.



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Temporal distribution of alcohol related facial fractures

Publication date: Available online 19 September 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Kai Lee, Michael Qiu, Jiandong Sun
ObjectivesAlcohol intoxication as a common concomitant factor in facial fractures is well reported. However, less has been described on its temporal pattern of presentations. Studies have found such pattern to be dependent on factors such as seasonal climate variations, timing of social, leisure and sporting activities, and road traffic conditions.Study DesignThis study retrospectively examined the Victorian admitted episodes data-set (VAED) between year 2010 to 2013. VAED is a standardised set of data collected during all hospital presentations in Victoria.ResultsThe study found higher incidence of alcohol-related facial fracture presentations during weekends and during summer and spring months when compared with non-alcohol related fractures (statistically significant). Alcohol-related facial fractures are more likely to involve male patients in 20-29 year age group, occur as a result of interpersonal violence and require shorter hospital stay during weekend admissions (statistically significant). There are no statistically significant relationship observed in seasonal variation across all variables.ConclusionsThis study found distinct characteristics in temporal distribution of alcohol-related facial fractures. These characteristics are in particular significant in weekend trauma admissions. Such information is important in workforce planning, resource distribution and implementation of injury prevention programs.



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Single-subunit oligosaccharyltransferases of Trypanosoma brucei display different and predictable peptide acceptor specificities. [Microbiology]

Trypanosoma brucei causes African trypanosomiasis and contains three full-length oligosaccharyltransferase (OST) genes; two of which, TbSTT3A and TbSTT3B, are expressed in the bloodstream form of the parasite. These OSTs have different peptide acceptor and lipid-linked oligosaccharide donor specificities and trypanosomes do not follow many of the canonical rules developed for other eukaryotic N-glycosylation pathways, raising questions as to the basic architecture and detailed function of trypanosome OSTs. Here, we show by blue-native gel electrophoresis and stable isotope labelling in cell culture proteomics that the TbSTT3A and TbSTT3B proteins associate with each other in large complexes that contain no other detectable protein subunits. We probed the peptide acceptor specificities of the OSTs in vivo using a transgenic glycoprotein reporter system and performed glycoproteomics on endogenous parasite glycoproteins using sequential endoglycosidase-H and peptide-N-glycosidase-F digestions. This allowed us to assess the relative occupancies of numerous N-glycosylation sites by endoglycosidase-H resistant N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase-H sensitive N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B. Using machine learning we assessed the features that best define TbSTT3A and TbSTT3B substrates in vivo and built an algorithm to predict the types of N-glycan most likely to predominate at all the putative N-glycosylation sites in the parasite proteome. Lastly, molecular modelling was used to suggest why TbSTT3A has a distinct preference for sequons containing and/or flanked by acidic amino acid residues. Together, these studies provide insights into how a highly divergent eukaryote has re-wired protein N-glycosylation to provide protein sequence-specific N-glycan modifications. Data are available via ProteomeXchange with identifiers PXD007236, PXD007267 and PXD007268.

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Characterization of a cytoplasmic glucosyltransferase that extends the core trisaccharide of the Toxoplasma Skp1 E3 ubiquitin ligase subunit [Microbiology]

Skp1 is a subunit of the SCF (Skp1/Cullin-1/F-box protein) class of E3 ubiquitin ligases that are important for eukaryotic protein degradation. Unlike its animal counterparts, Skp1 from Toxoplasma gondii is hydroxylated by an O2-dependent prolyl-4-hydroxylase (PhyA), and the resulting hydroxyproline can subsequently be modified by a five-sugar chain. A similar modification is found in the social amoeba Dictyostelium, where it regulates SCF assembly and O2-dependent development. Homologous glycosyltransferases assemble a similar core trisaccharide in both organisms, and a bifunctional α-galactosyltransferase from CAZy family GT77 mediates addition of the final two sugars in Dictyostelium, generating Galα1,3Galα1,3Fucα1,2Galβ1,3GlcNAcα1-. Here, we found that Toxoplasma utilizes a cytoplasmic glycosyltransferase from an ancient clade of CAZy family GT32 to catalyze transfer of the fourth sugar. Catalytically active Glt1 was required for addition of the terminal disaccharide in cells, and cytosolic extracts catalyzed transfer of [3H]glucose from UDP-[3H]glucose to the trisaccharide form of Skp1 in a glt1-dependent fashion. Recombinant Glt1 catalyzed the same reaction, confirming that it directly mediates Skp1 glucosylation, and NMR demonstrated formation of a Glcα1,3Fuc linkage. Recombinant Glt1 strongly preferred the full core trisaccharide attached to Skp1, and labeled only Skp1 in glt1Δ extracts, suggesting specificity for Skp1. glt1-knockout parasites exhibited a growth defect not rescued by catalytically inactive Glt1, indicating that the glycan acts in concert with the first enzyme in the pathway, PhyA, in cells. A genomic bioinformatics survey suggested that Glt1 belongs to the ancestral Skp1 glycosylation pathway in protists and evolved separately from related Golgi-resident GT32 glycosyltransferases.

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Upregulation of autophagy-related gene 5 protects dopaminergic neurons in a zebrafish model of Parkinson's disease [Neurobiology]

Parkinson's disease (PD) is one of the most epidemic neurodegenerative diseases, and is characterized by movement disorders arising from loss of midbrain dopaminergic (DA) neurons. Recently, the relationship between PD and autophagy has received considerable attention, but information about the mechanisms involved is lacking. Here, we report that autophagy-related gene 5 (ATG5) is potentially important in protecting dopaminergic neurons in a 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in zebrafish. Using analyses of zebarfish swimming behavior, in situ hybridizatiton, immunofluorescence and expressions of genes and proteins related to PD and autophagy, we found that ATG5 expression level was decreased and autophagy flux was blocked in this model. The ATG5 down-regulation led to the upgrade of PDassociated proteins, such as β-synuclein, Parkin, and PINK1, aggravation of MPTP-induced PDmimicking pathological locomotor behavior, DA neuron loss labelled by tyrosine hydroxylase (TH) or dopamine transporter (DAT), and blocked autophagy flux in the zebrafish model. ATG5 overexpression alleviated or reversed these PD pathological features, rescued DA neuron cells as indicated by elevated TH /DAT levels, and restored autophagy flux. The role of ATG5 in protecting DA neurons was confirmed by expression of the human atg5 gene in the zebrafish model. Our findings reveal that ATG5 has a role in neuroprotection, and upregulation of ATG5 may serve as a goal in the development of drugs for PD prevention and management.

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O2 sensing associated glycosylation exposes the F-box combining site of the Dictyostelium Skp1 subunit in E3 ubiquitin ligases [Molecular Biophysics]

Skp1 is a conserved protein linking cullin-1 to F-box proteins in SCF (Skp1-Cullin1-F-box) E3 ubiquitin ligases, which modify protein substrates with polyubiquitin chains that typically target them for 26S proteasome-mediated degradation. In Dictyostelium (a social amoeba), Toxoplasma gondii (the agent for human toxoplasmosis), and other protists, Skp1 is regulated by a unique pentasaccharide attached to hydroxylated Pro-143 within its C-terminal F-box binding domain. Prolyl hydroxylation of Skp1 contributes to O2-dependent Dictyostelium development, but full glycosylation at that position is required for optimal O2 sensing. Previous studies have shown that the glycan promotes organization of the F-box binding region in Skp1, and aids in Skp1's association with F-box proteins. Here, nuclear magnetic resonance and mass spectrometry approaches were used to determine the glycan structure, and then a combination of NMR and molecular dynamics simulations were employed to characterize the impact of the glycan on the conformation and motions of the intrinsically flexible F-box binding domain of Skp1. MD trajectories of glycosylated Skp1 whose calculated monosaccharide relaxation kinetics and rotational correlation times agreed with the NMR data indicated that the glycan interacts with the loop connecting two alpha-helices of the F-box combining site. In these trajectories, the helices separated from one another to create a more accessible and dynamic F-box interface. These results offer an unprecedented view of how a glycan modification influences a disordered region of a full-length protein. The increased sampling of an open Skp1 conformation can explain how glycosylation enhances interactions with F-box proteins in cells.

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The serine protease homolog CLIPA14 modulates the intensity of the immune response in the mosquito Anopheles gambiae [Immunology]

CLIP domain serine protease homologues (cSPHs) are positive and negative regulators of Anopheles gambiae immune responses mediated by the complement-like protein TEP1 against Plasmodium malaria parasites and other microbial infections. We have previously reported that the SPH CLIPA2 is a negative regulator of the TEP1-mediated response by showing that CLIPA2 knockdown (kd) enhances mosquito resistance to infections with fungi, bacteria and Plasmodium parasites. Here, we identify another SPH, CLIPA14, as a novel regulator of mosquito immunity. We found that CLIPA14 is a hemolymph protein that is rapidly cleaved following a systemic infection. CLIPA14 kd mosquitoes elicited a potent melanization response against Plasmodium berghei ookinetes and exhibited significantly increased resistance to Plasmodium infections as well as to systemic and oral bacterial infections. The activity of the enzyme phenoloxidase, which initiates melanin biosynthesis, dramatically increased in the hemolymph of CLIPA14 kd mosquitoes in response to systemic bacterial infections. Ookinete melanization and hemolymph phenoloxidase activity were further increased after co-silencing CLIPA14 and CLIPA2, suggesting that these two SPHs act in concert to control the melanization response. Interestingly, CLIPA14 RNAi phenotypes and its infection-induced cleavage were abolished in a TEP1 loss-of-function background. Our results suggest that a complex network of SPHs functions downstream of TEP1 to regulate the melanization reaction.

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Peptides derived from evolutionarily conserved domains in Beclin1 and Beclin2 enhance the entry of lentiviral vectors into human cells [Methods and Resources]

Autophagy-related proteins such as Beclin1 are involved in an array of complex processes including antiviral responses, and may also modulate the efficiency of gene therapy viral vectors. The TatBeclin1 (TB1) peptide has been reported as an autophagy-inducing factor inhibiting the replication of pathogens such as HIV-1. Yet, autophagy-related proteins are also essential for the early steps of HIV-1 infection. Therefore, we examined here the effects of the Beclin1-evolutionarily conserved domain in TB1 on viral transduction and autophagy in single-round HIV infection or with nonreplicative HIV-1-derived lentiviral vectors (LV). TB1 enhanced transduction with various pseudotypes, but without inducing the autophagy process. TB1 augmented the transduction of human CD34+ hematopoietic stem/progenitor cells (HSPCs) while maintaining their capacity to engraft in vivo into humanized mice. TB1 was as effective as other transduction additives and functioned by enhancing the adhesion and fusion of viral particles with target cells, but not their aggregation. We also found that the N-terminal L1 loop was critical for TB1 transduction-enhancing activity. Interestingly, the Tat-Beclin2 (TB2) peptide, derived from the human Beclin2 protein, was even more potent than TB1 in promoting viral transduction and infection. Taken together, our findings suggest that the TB1 and TB2 peptides enhance the viral entry step. Tat-Beclin peptides therefore represent a new family of viral transduction enhancers for potential use in gene therapy.

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Antioxidant and antibacterial activities of bioactive peptides in buffalo’s yoghurt fermented with different starter cultures

Abstract

The effect of Lactobacillus acidophilus 20552 ATCC (T2) or Lactobacillus helveticus CH 5 (T3) in combination with yoghurt starter (1:1) on the antioxidant and antibacterial activities of the bioactive peptides present in buffalo's yoghurt was studied. The SDS-PAGE results indicate that all caseins were completely hydrolyzed by both strains, whereas whey protein fractions were still present. All starter cultures have the ability to produce low-molecular-weight bioactive peptides, most of which were originated from β-casein and fewer from αs1 casein. The antioxidant activity (%) of the water-soluble peptide extract from yoghurt samples increased in all samples during storage. Samples containing Lb. helveticus CH 5 showed the highest values. All yoghurt treatments displayed antibacterial activity against Escherichia coli. Control yoghurt and T3 showed higher antibacterial activity on E. coli, Staphylococcus aureus, and Bacillus cereus as compared to T2.



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Analysis of pelvic strain in different gait configurations in a validated cohort of computed tomography based finite element models

Publication date: Available online 19 September 2017
Source:Journal of Biomechanics
Author(s): Zoryana Salo, Maarten Beek, David Wright, Asmaa Maloul, Cari Marisa Whyne
The pelvis functions to transmit upper body loads to the lower limbs and is critical in human locomotion. Semi-automated, landmark-based finite element (FE) morphing and mapping techniques eliminate the need for segmentation and have shown to accelerate the generation of multiple specimen-specific pelvic FE models to enable the study of pelvic mechanical behaviour. The purpose of this research was to produce an experimentally validated cohort of specimen-specific FE models of the human pelvis and to use this cohort to analyze pelvic strain patterns during gait. Using an initially segmented specimen-specific pelvic FE model as a source model, four more specimen-specific pelvic FE models were generated from target clinical CT scans using landmark-based morphing and mapping techniques. FE strains from the five models were compared to the experimental strains obtained from cadaveric testing via linear regression analysis, (R2 values ranging from 0.70 to 0.93). Inter-specimen variability in FE strain distributions was seen among the five specimen-specific pelvic FE models. The validated cohort of specimen-specific pelvic FE models was utilized to examine pelvic strains at different phases of the gait cycle. Each validated specimen-specific FE model was reconfigured into gait cycle phases representing heel-strike/heel-off and midstance/midswing. No significant difference was found in the double-leg stance and heel-strike/heel-off models (p=0.40). A trend was observed between double-leg stance and midstance/midswing models (p=0.07), and a significant difference was found between heel-strike/heel-off models and midstance/midswing models (p=0.02). Significant differences were also found in comparing right vs. left models (heel-strike/heel-off p=0.14, midstance/midswing p=0.04).



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Effect of noise and filtering on largest Lyapunov exponent of time series associated with human walking

Publication date: Available online 19 September 2017
Source:Journal of Biomechanics
Author(s): Sina Mehdizadeh, Mohammad Ali Sanjari
This study aimed to determine the effect of added noise, filtering and time series length on the largest Lyapunov exponent (LyE) value calculated for time series obtained from a passive dynamic walker. The simplest passive dynamic walker model comprising of two massless legs connected by a frictionless hinge joint at the hip was adopted to generate walking time series. The generated time series was used to construct a state space with the embedding dimension of 3 and time delay 100 samples. The LyE was calculated as the exponential rate of divergence of neighboring trajectories of the state space using Rosenstein's algorithm. To determine the effect of noise on LyE values, seven levels of Gaussian white noise (SNR=55dB to 25dB with 5dB steps) were added to the time series. In addition, the filtering was performed using a range of cutoff frequencies from 3Hz to 19Hz with 2Hz steps. The LyE was calculated for both noise-free and noisy time series with different lengths of 6, 50, 100 and 150 strides. Results demonstrated a high percent error in the presence of noise for LyE. Therefore, these observations suggest that Rosenstein's algorithm might not perform well in the presence of added experimental noise. Furthermore, findings indicated that at least 50 walking strides are required to calculate LyE to account for the effect of noise. Finally, observations support that a conservative filtering of the time series with a high cutoff frequency might be more appropriate prior to calculating LyE.



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Exploiting mitochondrial and oxidative vulnerabilities with a synthetic analog of pancratistatin in combination with piperlongumine for cancer therapy [Research]

Harsh adverse effects as a result of nonspecific targeting of chemotherapeutics currently pose obstacles in cancer therapy; thus, it would be invaluable to devise novel approaches to specifically target cancer cells. The natural compound pancratistatin (PST) has been shown to preferentially induce apoptosis in a variety of cancer cell types. Recently, several analogs of PST were shown to be efficacious in inducing apoptosis in a variety of aggressive cancer cell types via cancer cell mitochondrial targeting; it caused dissipation of mitochondrial membrane potential and decreased oxygen consumption, and with isolated mitochondria, it induced the release of apoptogenic factors. The natural compound piperlongumine has been shown to target the stress response to reactive oxygen species in cancer cells. We explored the combinatorial potential of 2 small molecules (SVTH-6 and piperlongumine) that target these vulnerabilities in cancer cells. Interestingly, when combined with the PST analog, SVTH-6, an increase in mitochondrial dysfunction was observed, leading to an enhanced cytotoxic effect against several human cancer cell types. Additionally, this combination treatment was effective in reducing cancer cell growth in physiologically more relevant 3-dimensional spheroid cell cultures. This enhanced effect was found to be dependent on reactive oxygen species generation because an antioxidant could rescue cancer cells from this combination treatment. Importantly, noncancerous cells were markedly less sensitive to this combination treatment. Thus, targeting mitochondrial and oxidative stress vulnerabilities of cancer cells could be an effective strategy for cancer therapy.—Ma, D., Gilbert, T., Pignanelli, C., Tarade, D., Noel, M., Mansour, F., Gupta, M., Ma, S., Ropat, J., Curran, C., Vshyvenko, S., Hudlicky, T., Pandey. S. Exploiting mitochondrial and oxidative vulnerabilities with a synthetic analog of pancratistatin in combination with piperlongumine for cancer therapy.



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Endogenous glucocorticoid signaling in chondrocytes attenuates joint inflammation and damage [Research]

Previous studies demonstrated that endogenous glucocorticoid signaling in osteoblasts promotes inflammation in murine immune arthritis. The current study determined whether disruption of endogenous glucocorticoid signaling in chondrocytes also modulates the course and severity of arthritis. Tamoxifen-inducible chondrocyte-targeted glucocorticoid receptor knockout (chGRKO) mice were generated by breeding GRflox/flox mice with tamoxifen-inducible Collagen 2a1 Cre mice (Col2a1-CreERT2). Antigen-induced arthritis (AIA) and K/BxN serum transfer–induced arthritis (STIA) were induced in both chGRKO mice and their Cre-negative GRflox/flox littermates [wild type (WT)]. Arthritis was assessed by measurement of joint swelling and histology of joints collected at d 14. Neutrophil activity and gene expression patterns associated with cartilage damage were also evaluated. In both arthritis models clinical (joint swelling) and histologic indices of inflammatory activity were significantly greater in chGRKO than in WT mice. The STIA model was characterized by early up-regulation of CXCR2/CXCR2 ligand gene expression in ankle tissues, and significant and selective expansion of splenic CXCR2+ neutrophils in chGRKO arthritic compared to WT arthritic mice. At later stages, gene expression of enzymes involved in cartilage degradation was up-regulated in chGRKO but not WT arthritic mice. Therefore, we summarize that chondrocytes actively mitigate local joint inflammation, cartilage degradation and systemic neutrophil activity via a glucocorticoid-dependent pathway.—Tu, J., Stoner, S., Fromm, P. D., Wang, T., Chen, D., Tuckermann, J., Cooper, M. S., Seibel, M. J., Zhou, H. Endogenous glucocorticoid signaling in chondrocytes attenuates joint inflammation and damage.



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EVI and MDS/EVI are required for adult intestinal stem cell formation during postembryonic vertebrate development [Research]

The gene ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI encode zinc-finger proteins that have been recognized as important oncogenes in various types of cancer. In contrast to the established role of EVI and MDS/EVI in cancer development, their potential function during vertebrate postembryonic development, especially in organ-specific adult stem cells, is unclear. Amphibian metamorphosis is strikingly similar to postembryonic development around birth in mammals, with both processes taking place when plasma thyroid hormone (T3) levels are high. Using the T3-dependent metamorphosis in Xenopus tropicalis as a model, we show here that high levels of EVI and MDS/EVI are expressed in the intestine at the climax of metamorphosis and are induced by T3. By using the transcription activator–like effector nuclease gene editing technology, we have knocked out both EVI and MDS/EVI and have shown that EVI and MDS/EVI are not essential for embryogenesis and premetamorphosis in X. tropicalis. On the other hand, knocking out EVI and MDS/EVI causes severe retardation in the growth and development of the tadpoles during metamorphosis and leads to tadpole lethality at the climax of metamorphosis. Furthermore, the homozygous knockout animals have reduced adult intestinal epithelial stem cell proliferation at the end of metamorphosis (for the few that survive through metamorphosis) or during T3-induced metamorphosis. These findings reveal a novel role of EVI and/or MDS/EVI in regulating the formation and/or proliferation of adult intestinal adult stem cells during postembryonic development in vertebrates.—Okada, M., Shi, Y.-B. EVI and MDS/EVI are required for adult intestinal stem cell formation during postembryonic vertebrate development.



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Carbonic anhydrase III protects osteocytes from oxidative stress [Research]

Osteocytes are master orchestrators of bone remodeling; they control osteoblast and osteoclast activities both directly via cell-to-cell communication and indirectly via secreted factors, and they are the main postnatal source of sclerostin and RANKL (receptor activator of NF-kB ligand), two regulators of osteoblast and osteoclast function. Despite progress in understanding osteocyte biology and function, much remains to be elucidated. Recently developed osteocytic cell lines—together with new genome editing tools—has allowed a closer look at the biology and molecular makeup of these cells. By using single-cell cloning, we identified genes that are associated with high Sost/sclerostin expression and analyzed their regulation and function. Unbiased transcriptome analysis of high vs. low Sost/sclerostin–expressing cells identified known and novel genes. Dmp1 (dentin matrix protein 1), Dkk1 (Dickkopf WNT signaling pathway inhibitor 1), and Phex were among the most up-regulated known genes, whereas Srpx2, Cd200, and carbonic anhydrase III (CAIII) were identified as novel markers of differentiated osteocytes. Aspn, Enpp2, Robo2, Nov, and Serpina3g were among the transcripts that were most significantly suppressed in high-Sost cells. Considering that CAII was recently identified as being regulated by Sost/sclerostin and capable of controlling mineral homeostasis, we focused our attention on CAIII. Here, we report that CAIII is highly expressed in osteocytes, is regulated by parathyroid hormone both in vitro and in vivo, and protects osteocytes from oxidative stress.—Shi, C., Uda, Y., Dedic, C., Azab, E., Sun, N., Hussein, A. I., Petty, C. A., Fulzele, K., Mitterberger-Vogt, M. C., Zwerschke, W., Pereira, R., Wang, K., Divieti Pajevic, P. Carbonic anhydrase III protects osteocytes from oxidative stress.



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Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1 [Research]

Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store-operated Ca2+ entry (SOCE) channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca2+ oscillations and fast cell proliferation in human ESCC cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1-mediated cell proliferation remains unknown. The present study shows that zinc supplementation significantly inhibits proliferation of ESCC cell lines and that the effect of zinc is reversible with N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine, a specific Zn2+ chelator, whereas nontumorigenic esophageal epithelial cells are significantly less sensitive to zinc treatment. Fluorescence live cell imaging revealed that extracellular Zn2+ exerted rapid inhibitory effects on Orai1-mediated SOCE and on intracellular Ca2+ oscillations in the ESCC cells. Knockdown of Orai1 or expression of Orai1 mutants with compromised zinc binding significantly diminished sensitivity of the cancer cells to zinc treatment in both SOCE and cell proliferation analyses. These data suggest that zinc may inhibit cell proliferation of esophageal cancer cells through Orai1-mediated intracellular Ca2+ oscillations and reveal a possible molecular basis for zinc-induced cancer prevention and Orai1-SOCE signaling pathway in cancer cells.—Choi, S., Cui, C., Luo, Y., Kim, S.-H., Ko, J.-K., Huo, X., Ma, J., Fu, L.-W., Souza, R. F., Korichneva, I., Pan, Z. Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1.



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The Influence of Sleep Disorders on Voice Quality

To verify the influence of sleep quality on the voice.

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I'm so glad dentists don't try and transplant syphilitic teeth any more

Human beings have always struggled to maintain a healthy set of gnashers, fortunately that's easier and less painful than ever before I've got the dentist next week. I can't wait.



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Roles for Innate Immunity in Combination Immunotherapies

Immunity to infectious agents involves a coordinated response of innate and adaptive immune cells working in concert, with many feed-forward and regulatory interactions between both arms of the immune system. In contrast, many therapeutic strategies to augment immunity against tumors have focused predominantly on stimulation of adaptive immunity. However, a growing appreciation of the potential contributions of innate immune effectors to antitumor immunity, especially in the context of combination immunotherapy, is leading to novel strategies to elicit a more integrated immune response against cancer. Here we review antitumor activities of innate immune cells, mechanisms of their synergy with adaptive immune responses against tumors, and discuss recent studies highlighting the potential of combination therapies recruiting both innate and adaptive immune effectors to eradicate established tumors. Cancer Res; 77(19); 1–7. ©2017 AACR.

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New Advances and Challenges of Targeting Cancer Stem Cells

The second International Cancer Stem Cell Conference in Cleveland, Ohio, on September 20–23, 2016, convened 330 attendees from academic, industrial, and clinical organizations. It featured a debate on the concepts and challenges of the cancer stem cells (CSC) as well as CSC-centered scientific sessions on clinical trials, genetics and epigenetics, tumor microenvironment, immune suppression, metastasis, therapeutic resistance, and emerging novel concepts. The conference hosted 35 renowned speakers, 100 posters, 20 short talks, and a preconference workshop. The reported advances of CSC research and therapies fostered new collaborations across national and international borders, and inspired the next generation's young scientists. Cancer Res; 77(19); 1–6. ©2017 AACR.

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Effective instruction for persisting dyslexia in upper grades: Adding hope stories and computer coding to explicit literacy instruction

Abstract

Children in grades 4 to 6 (N = 14) who despite early intervention had persisting dyslexia (impaired word reading and spelling) were assessed before and after computerized reading and writing instruction aimed at subword, word, and syntax skills shown in four prior studies to be effective for treating dyslexia. During the 12 two-hour sessions once a week after school they first completed HAWK Letters in Motion© for manuscript and cursive handwriting, HAWK Words in Motion© for phonological, orthographic, and morphological coding for word reading and spelling, and HAWK Minds in Motion© for sentence reading comprehension and written sentence composing. A reading comprehension activity in which sentences were presented one word at a time or one added word at a time was introduced. Next, to instill hope they could overcome their struggles with reading and spelling, they read and discussed stories about struggles of Buckminister Fuller who overcame early disabilities to make important contributions to society. Finally, they engaged in the new Kokopelli's World (KW)©, blocks-based online lessons, to learn computer coding in introductory programming by creating stories in sentence blocks (Thompson and Tanimoto 2016). Participants improved significantly in hallmark word decoding and spelling deficits of dyslexia, three syntax skills (oral construction, listening comprehension, and written composing), reading comprehension (with decoding as covariate), handwriting, orthographic and morphological coding, orthographic loop, and inhibition (focused attention). They answered more reading comprehension questions correctly when they had read sentences presented one word at a time (eliminating both regressions out and regressions in during saccades) than when presented one added word at a time (eliminating only regressions out during saccades). Indicators of improved self-efficacy that they could learn to read and write were observed. Reminders to pay attention and stay on task needed before adding computer coding were not needed after computer coding was added.



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A targeted next-generation sequencing panel reveals novel mutations in Japanese patients with primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The early diagnosis of PCD is important for the prevention of long-term sequelae; however, this is often challenging because of the phenotypic heterogeneity of PCD and difficulty in genetic analysis. The majority of PCD patients in Japan are not diagnosed properly. To diagnose PCD more accurately, we developed a targeted next-generation sequencing (NGS) panel.

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A targeted next-generation sequencing panel reveals novel mutations in Japanese patients with primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The early diagnosis of PCD is important for the prevention of long-term sequelae; however, this is often challenging because of the phenotypic heterogeneity of PCD and difficulty in genetic analysis. The majority of PCD patients in Japan are not diagnosed properly. To diagnose PCD more accurately, we developed a targeted next-generation sequencing (NGS) panel.

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Human CD40L-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells

ILC3-mediated induction of Breg cells is a novel, innate immunoregulatory mechanism that may contribute to the maintenance of immune tolerance and become insufficient in allergy, as the frequency of ILC3s is reduced in allergic diseases.

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High prevalence of severe asthma in a large random population study

Every third asthmatic showed at least one sign of asthma severity which indicates that there are still many unmet needs in managing this disease. Asthma severity phenotypes are very diverse prompting an individualized approach to patients.

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TLR7/8 agonists stimulate plasmacytoid dendritic cells to initiate a Th17-deviated acute contact dermatitis in humans

Stimulation of TLR7/8 in human skin induces an acute contact dermatitis with pDC as primary sensors and IL-23 as essential driver of the reaction, thus constituting a standardized, but limited model of human psoriasis.

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Th1 Signatures Are Present in the Lower Airways of Children with Severe Asthma, Regardless of Allergic Status

A Th1 signature dominates the lower airways of children with severe asthma, regardless of allergic status. Our findings warrant further investigation of the contributions of Th1 cells to the development and maintenance of severe asthma.

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Few novel antibiotics in the pipeline, WHO warns

The World Health Organization has reiterated its warning that there is a serious lack of new antibiotics under development to combat the growing threat of antimicrobial resistance.Only eight of the...

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Incorporating single best answer questions into revision lectures results in increased student satisfaction with lecture-based teaching

Sophie Fitzsimmons, Aliya Bryce, Sean Main

Education for Health 2017 30(2):185-185



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Influence of pharmacy students on the attitudes of medical students following an interprofessional course

Fatemeh Dabaghzadeh, Bahare Zihayat, Farhad Sarafzadeh

Education for Health 2017 30(2):103-107

Background: Clinical interprofessional education (IPE) can promote mutual understanding of other health professions and respectful behaviors among health-care professionals. The aims of this study were to evaluate the effects of IPE on the attitudes of medical and pharmacy students in an inpatient hospital setting and, in particular, the influence of pharmacy students on the attitudes of medical students. Methods: The 6th year doctor of pharmacy students and medical students were enrolled in a prospective cohort study. They were paired and each pair was responsible for three beds and all the patients occupying these mentioned beds over the 2-week course. The Readiness for Interprofessional Learning Scale (RIPLS) questionnaire was used to assess the students' attitudes before and after the course. Results: The attitudes of the medical students changed positively after the IPE course based on RIPLS teamwork and collaboration and professional identity subscales. Changes in the attitudes of the pharmacy students were not statistically significant based on the mentioned scale and subscales. Discussion: IPE could improve the attitudes of the medical students regarding interprofessional teamwork, communication, and sharing learning experience. Based on the current investigation, IPE did not have an effect on pharmacy students.

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An interprofessional education program's impact on attitudes toward and desire to work with older adults

Kaitlyn McManus, Katherine Shannon, Darson L Rhodes, Julia D Edgar, Carolyn Cox

Education for Health 2017 30(2):172-175

Background: Insufficient numbers of health professions students aspire to work with the increasing numbers of the elderly. Although programs exist to promote interest in serving this population, inadequate numbers of health professionals remain an issue. Methods: This study sample consisted of medical (n = 75) and health profession students (n = 210) enrolled in a semester-long interprofessional clinical education program designed to enhance interprofessional teamwork and provide positive exposure to elderly in the community. Each team of three visited an assigned elder three times during the semester. Students were acquainted with their elder and also administered a comprehensive geriatric physical and socioemotional battery of assessments. After each visit, the teams met and held a debriefing with faculty. Attitudes toward older adults and the desire to work with older adults were assessed using the Carolina Opinion of Care of Older Adults. The survey was administered twice: before initiating the semester-long program and immediately after program completion. Results: Total score and subscale scores were compared pre- and post-experience. Scores on the subscale "Early Interest in Geriatrics" were significantly higher postexperience compared to pre-experience. Scores on the remaining subscales and the total score remained unchanged. Discussion: Results indicate that exposure to elderly adults may increase the interest in working with this population and does not diminish attitudes toward the elderly. Longer exposure may be needed to invoke attitudinal changes across additional subtests.

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