CyTRANSFINDER: a Cytoscape 3.3 plugin for three-component (TF, gene, miRNA) signal transduction pathway construction

Background: Biological research increasingly relies on network models to study complex phenomena. Signal Transduction Pathways are molecular circuits that model how cells receive, process, and respond to information from the environment providing snapshots of the overall cell dynamics. Most of the attempts to reconstruct signal transduction pathways are limited to single regulator networks including only genes/proteins. However, networks involving a single type of regulator and neglecting transcriptional and post-transcriptional regulations mediated by transcription factors and microRNAs, respectively, may not fully reveal the complex regulatory mechanisms of a cell. We observed a lack of computational instruments supporting explorative analysis on this type of three-component signal transduction pathways. Results: We have developed CyTRANSFINDER, a new Cytoscape plugin able to infer three-component signal transduction pathways based on user defined regulatory patterns and including miRNAs, TFs and genes. Since CyTRANSFINDER has been designed to support exploratory analysis, it does not rely on expression data. To show the potential of the plugin we have applied it in a study of two miRNAs that are particularly relevant in human melanoma progression, miR-146a and miR-214. Conclusions: CyTRANSFINDER supports the reconstruction of small signal transduction pathways among groups of genes. Results obtained from its use in a real case study have been analyzed and validated through both literature data and preliminary wet-lab experiments, showing the potential of this tool when performing exploratory analysis.

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Synchronous malignancies of the gall bladder and common bile duct: a case report

Background: Synchronous malignancies of the gall bladder and common bile duct are a rare entity. Much of our knowledge on this topic comes from Japanese literature. Most of the synchronous carcinomas described in Japanese literature are associated with the presence of an anomalous pancreatic-bile duct junction (APBDJ).Case presentationWe report a case of synchronous malignancy of the extrahepatic biliary tree involving the fundus of the gall bladder and the intrapancreatic portion of the common bile duct (CBD). A 50-year-old female patient presented to us with clinical features of obstructive jaundice and on radiological evaluation was diagnosed to have a periampullary carcinoma; the patient underwent a pancreaticoduodenectomy, and histopathological examination revealed adenocarcinoma of the gall bladder and the intrapancreatic portion of the CBD. Conclusions: Synchronous malignancies have been rarely reported from the Indian subcontinent; therefore, it is essential for the clinician as well as the pathologist to maintain a high index of suspicion while evaluating such lesions and to look for the presence of an anamolous pancreatic-bile duct junction whenever indicated.

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Evidence of successful malaria case management policy implementation in Cambodia: results from national ACTwatch outlet surveys

Background: For over a decade, Cambodia has implemented a number of policies and innovative strategies to increase access to quality malaria case management services and address the drivers of multi-drug resistance. This paper utilizes outlet survey trend data collected by the ACTwatch project to demonstrate how changes in Cambodian policy and strategies have led to shifts in anti-malarial markets. Methods: Anti-malarial ACTwatch outlet surveys were conducted in Cambodia in 2009 (June–July), 2011 (June–August) and 2013 (September–October). A census of all outlets with the potential to sell or distribute anti-malarials was conducted within a nationally representative sample of communes. Drug information, sales/distribution in the previous week, and retail price were collected for each anti-malarial in stock. Information on availability of malaria blood testing was also collected. Results: A total of 7833 outlets were enumerated in 2009, 18,584 in 2011, and 16,153 in 2013. The percentage of public health facilities with at least one anti-malarial in stock on the day of the survey increased between 2009 (65.8 %) and 2011 (90.0 %) and remained high in 2013 (82.0 %). Similar trends were found for village malaria workers (VMW). Overall, private sector availability of anti-malarials declined over time and varied by outlet type. By 2013 most anti-malarial stocking public health facilities (81.5 %), VMW (95.4 %), private for-profit health facilities (64.8 %), and pharmacies (71.9 %) had the countries first-line artemisinin-based combination therapy (ACT) treatment in stock. In 2013, 60 % of anti-malarials were delivered through the private sector, 40 % through the public sector, and the most common anti-malarial to be sold or distributed was the first-line ACT, comprising 62.8 % of the national market share. Oral artemisinin monotherapy, which had accounted for 6 % of total anti-malarial market share in 2009, was no longer reportedly sold/distributed in 2013. Malaria blood testing availability remained high over time among public facilities and VMW, with availability over 90 % in 2011 and 2013. Moderate availability was observed in the private sector. Conclusions: Continued implementation of successful public and private sector strategies in support of evolving malaria drug treatment policies will be important to protect the efficacy of anti-malarial medicines and ultimately facilitate malaria elimination in Cambodia by 2025.

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Selecting an appropriate strategy to make quality 7.1 % chlorhexidine digluconate accessible for umbilical cord care

Achieving increased access to medicines in low- and middle-income countries is a complex issue that requires a holistic approach. Choosing an appropriate manufacturing strategy that can ensure a sustainable supply of these medicines is an essential component of that approach. The Chlorhexidine Working Group, a consortium of more than 25 international organizations, donors, and manufacturers led by PATH, has been working to increase access to 7.1 % chlorhexidine digluconate for umbilical cord care in low- and middle-income countries to reduce neonatal mortality due to infection. The working group initially considered two strategies for manufacture of this commodity: (1) production and global distribution by a multinational company; and (2) production and regional distribution by locally owned companies or subsidiaries of multinational companies based in low- and middle-income countries. Local production may be beneficial to public health and economic development in these countries, yet capability and capacity of pharmaceutical manufacturers, regulatory and legal provisions, and market factors must be carefully assessed and addressed to ensure that local production is the correct strategy and that it contributes to improved access to the medicine. To date, this effort to implement a local production strategy has resulted in successful registration of 7.1 % chlorhexidine digluconate for umbilical cord care by manufacturers in Bangladesh, Kenya, Nepal, and Nigeria. Additionally, the product is now available in domestic and export markets.

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A Strongly Greenish-blue-emitting Cu4Cl4 Cluster with Efficient Spin-Orbit Coupling (SOC): Fast Phosphorescence versus Thermally Activated Delayed Fluorescence

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC00809G, Communication

Xu-Lin Chen, Rong-Min Yu, Xiao-Yuan Wu, Dong Liang, Ji-Hui Jia, Can-Zhong Lu
In this communication, we report a new greenish-blue-emitting Cu(I) complex, Cu₄Cl₄(NP)₂, with high photoluminescence quantum yield of 90% and short decay time of 9.9 [small mu ]s. Due to the strong SOC...
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H-bonding directed programmed supramolecular assembly of naphthalene-diimide (NDI) derivatives

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC01983H, Feature Article

Anindita Das, Suhrit Ghosh
In this review we have collated various supramolecular designs, all surrounding H-bonding among well known functional groups (peptides, nucleic acid, amide, urea, carboxylic acid, pyridine-hydroxyl, urethane, imide and others), to...
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Off-duty paramedic, community come to injured CHP officer's aid

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Erratum to: FOXC1, a target of polycomb, inhibits metastasis of breast cancer cells

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Construction Site Paramedic/EMT in Brandywine, MD - Medcor Inc.

Paramedic / EMT-I / EMT-B Position Code 16-SNC-001 Required Licensure/Experience RN/Paramedic Position Type Regular Full Time Location MD - Brandywine Job Summary Job Summary: We are looking for a talented RN or Paramedic to work fulltime as a Medical Administrator at our worksite clinic located in Brandywine, MD. The days/hours for this position will be: Monday – Friday (Saturdays as needed) ...

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Bilingual Construction Site Paramedic or EMT needed - Medcor Inc.

Paramedic /EMT-I / EMT-B - Spanish Speaking Position Code 16-NEW-002 Required Licensure/Experience EMT-B/EMT-I/Paramedic Position Type Regular Full Time Location NY - New York City Job Summary Are you seeking a challenging, fast paced position with a strong, growing company" You have come to the right place! It's Better @ Medcor! Medcor clinics operate in facilities across a broad spectrum of industries ...

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A study protocol of a randomised controlled trial to measure the effects of an augmented prescribed exercise programme (APEP) for frail older medical patients in the acute setting

Background: Older adults experience functional decline in hospital leading to increased healthcare burden and morbidity. The benefits of augmented exercise in hospital remain uncertain. The aim of this trial is to measure the short and longer-term effects of augmented exercise for older medical in-patients on their physical performance, quality of life and health care utilisation.Design & MethodsTwo hundred and twenty older medical patients will be blindly randomly allocated to the intervention or sham groups. Both groups will receive usual care (including routine physiotherapy care) augmented by two daily exercise sessions. The sham group will receive stretching and relaxation exercises while the intervention group will receive tailored strengthening and balance exercises. Differences between groups will be measured at baseline, discharge, and three months. The primary outcome measure will be length of stay. The secondary outcome measures will be healthcare utilisation, activity (accelerometry), physical performance (Short Physical Performance Battery), falls history in hospital and quality of life (EQ-5D-5 L).DiscussionThis simple intervention has the potential to transform the outcomes of the older patient in the acute setting.Trial registrationClinicalTrials.gov Identifier: NCT02463864, registered 26.05.2015.

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Structural and functional features of self-assembling protein nanoparticles produced in endotoxin-free Escherichia coli

Background: Production of recombinant drugs in process-friendly endotoxin-free bacterial factories targets to a lessened complexity of the purification process combined with minimized biological hazards during product application. The development of nanostructured recombinant materials in innovative nanomedical activities expands such a need beyond plain functional polypeptides to complex protein assemblies. While Escherichia coli has been recently modified for the production of endotoxin-free proteins, no data has been so far recorded regarding how the system performs in the fabrication of smart nanostructured materials. Results: We have here explored the nanoarchitecture and in vitro and in vivo functionalities of CXCR4-targeted, self-assembling protein nanoparticles intended for intracellular delivery of drugs and imaging agents in colorectal cancer. Interestingly, endotoxin-free materials exhibit a distinguishable architecture and altered size and target cell penetrability than counterparts produced in conventional E. coli strains. These variant nanoparticles show an eventual proper biodistribution and highly specific and exclusive accumulation in tumor upon administration in colorectal cancer mice models, indicating a convenient display and function of the tumor homing peptides and high particle stability under physiological conditions.DiscussionThe observations made here support the emerging endotoxin-free E. coli system as a robust protein material producer but are also indicative of a particular conformational status and organization of either building blocks or oligomers. This appears to be promoted by multifactorial stress-inducing conditions upon engineering of the E. coli cell envelope, which impacts on the protein quality control of the cell factory.

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Lipoxin A4 inhibits microglial activation and reduces neuroinflammation and neuropathic pain after spinal cord hemisection

Background: Spinal cord injury (SCI) is a severe neurological disorder with many disabling consequences, including persistent neuropathic pain, which develops in about 40 % of SCI patients and is induced and sustained by excessive and uncontrolled spinal neuroinflammation. Here, we have evaluated the effects of lipoxin A4 (LXA4), a member of a unique class of endogenous lipid mediators with both anti-inflammatory and analgesic properties, on spinal neuroinflammation and chronic pain in an experimental model of SCI. Methods: Spinal hemisection at T10 was carried out in adult male CD1 mice and Wistar rats. To test if LXA4 can reduce neuroinflammation and neuropathic pain, each animal received two intrathecal injections of LXA4 (300 pmol) or vehicle at 4 and 24 h after SCI. Sensitivity to mechanical stimulation of the hind paws was evaluated using von Frey monofilaments, and neuroinflammation was tested by measuring the mRNA and/or protein expression levels of glial markers and cytokines in the spinal cord samples after SCI. Also, microglia cultures prepared from murine cortical tissue were used to assess the direct effects of LXA4 on microglial activation and release of pro-inflammatory TNF-α. Results: LXA4 treatment caused significant reductions in the intensity of mechanical pain hypersensitivity and spinal expression levels of microglial markers and pro-inflammatory cytokines induced by SCI, when compared to rodents receiving control vehicle injections. Notably, the increased expressions of the microglial marker IBA-1 and of the pro-inflammatory cytokine TNF-α were the most affected by the LXA4 treatment. Furthermore, cortical microglial cultures expressed ALX/FPR2 receptors for LXA4 and displayed potentially anti-inflammatory responses upon challenge with LXA4. Conclusions: Collectively, our results suggest that LXA4 can effectively modulate microglial activation and TNF-α release through ALX/FPR2 receptors, ultimately reducing neuropathic pain in rodents after spinal cord hemisection. The dual anti-inflammatory and analgesic properties of LXA4, allied to its endogenous nature and safety profile, may render this lipid mediator as new therapeutic approach for treating various neuroinflammatory disorders and chronic pain with only limited side effects.

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Genetic engineering of Synechocystis PCC6803 for the photoautotrophic production of the sweetener erythritol

Background: Erythritol is a polyol that is used in the food and beverage industry. Due to its non-caloric and non-cariogenic properties, the popularity of this sweetener is increasing. Large scale production of erythritol is currently based on conversion of glucose by selected fungi. In this study, we describe a biotechnological process to produce erythritol from light and CO 2 , using engineered Synechocystis sp. PCC6803. Methods: By functionally expressing codon-optimized genes encoding the erythrose-4-phosphate phosphatase TM1254 and the erythrose reductase Gcy1p, or GLD1, this cyanobacterium can directly convert the Calvin cycle intermediate erythrose-4-phosphate into erythritol via a two-step process and release the polyol sugar in the extracellular medium. Further modifications targeted enzyme expression and pathway intermediates. Conclusions: After several optimization steps, the best strain, SEP024, produced up to 2.1 mM (256 mg/l) erythritol, excreted in the medium.

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Long-term spatiotemporal stability and dynamic changes in the haemoparasite community of spiny mice (Acomys dimidiatus) in four montane wadis in the St. Katherine Protectorate, Sinai, Egypt

Background: Long-term field studies of parasite communities are rare but provide a powerful insight into the ecological processes shaping host-parasite interactions. The aim of our study was to monitor long-term trends in the haemoparasite communities of spiny mice (Acomys dimidiatus) and to identify the principal factors responsible for changes over a 12 year period. Methods: To this end we sampled four semi-isolated populations of mice (n = 835) in 2000, 2004, 2008 and 2012 in four dry montane valleys (wadis) located in the Sinai Massif, Egypt. Results: Overall 76.2 % of spiny mice carried at least one of the five haemoparasite genera (Babesia, Bartonella, Haemobartonella, Hepatozoon, Trypanosoma) recorded in the study. Prevalence of haemoparasites varied significantly between the sites with the highest overall prevalence in Wadi Tlah and the lowest in W. El Arbaein, and this changed significantly with time. In the first two surveys there was little change in prevalence, but by 2008, when the first signs of a deepening drought in the region had become apparent, prevalence began to drift downwards, and by 2012 prevalence had fallen to the lowest values recorded from all four sites over the entire 12-year period. The overall mean species richness was 1.2 ± 0.03, which peaked in 2004 and then dropped by more than 50 % by 2012. Species richness was highest among mice from Wadi Tlah and peaked in age class 2 mice (young adults). Site was the most significant factor affecting the prevalence of individual parasite species, with Trypanosoma acomys and Hepatozoon sp. occurring mainly in two wadis (W. Tlah & W. Gharaba). In four of the five genera recorded in the study we observed a significant drop in prevalence or/and abundance since 2004, the exception being Hepatozoon sp. Conclusions: During the 12-year-long period of study in the Sinai, we observed dynamic changes and possibly even cycles of prevalence and abundance of infections which differed depending on parasite species. Although the exact reasons cannot be identified at this time, we hypothesize that the effects of a 15-year-long scarcity of rainfall in the local environment and a fall in host densities over the period of study may have been responsible for a drop in transmission rates, possibly by a negative impact on vector survival.

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Advance care planning – a multi-centre cluster randomised clinical trial: the research protocol of the ACTION study

Background: Awareness of preferences regarding medical care should be a central component of the care of patients with advanced cancer. Open communication can facilitate this but can occur in an ad hoc or variable manner. Advance care planning (ACP) is a formalized process of communication between patients, relatives and professional caregivers about patients' values and care preferences. It raises awareness of the need to anticipate possible future deterioration of health. ACP has the potential to improve current and future healthcare decision-making, provide patients with a sense of control, and improve their quality of life.Methods/DesignWe will study the effects of the ACP program Respecting Choices on the quality of life of patients with advanced lung or colorectal cancer. In a phase III multicenter cluster randomised controlled trial, 22 hospitals in 6 countries will be randomised. In the intervention sites, patients will be offered interviews with a trained facilitator. In the control sites, patients will receive care as usual. In total, 1360 patients will be included. All participating patients will be asked to complete questionnaires at inclusion, and again after 2.5 and 4.5 months. If a patient dies within a year after inclusion, a relative will be asked to complete a questionnaire on end-of-life care. Use of medical care will be assessed by checking medical files. The primary endpoint is patients' quality of life at 2.5 months post-inclusion. Secondary endpoints are the extent to which care as received is aligned with patients' preferences, patients' evaluation of decision-making processes, quality of end-of-life care and cost-effectiveness of the intervention. A complementary qualitative study will be carried out to explore the lived experience of engagement with the Respecting Choices program from the perspectives of patients, their Personal Representatives, healthcare providers and facilitators.DiscussionTransferring the concept of ACP from care of the elderly to patients with advanced cancer, who on average are younger and retain their mental capacity for a larger part of their disease trajectory, is an important next step in an era of increased focus on patient centered healthcare and shared decision-making.Trial registrationInternational Standard Randomised Controlled Trial Number: ISRCTN63110516. Date of registration: 10/3/2014.

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Dosimetric advantages of using multichannel balloons compared to single-channel cylinders for high-dose-rate vaginal cuff brachytherapy

Publication date: Available online 8 April 2016
Source:Brachytherapy
Author(s): Xiaorong Hou, An Liu, Fuquan Zhang, Jeffrey Wong, Yi-Jen Chen
PurposeTo evaluate the dosimetric advantages of using multichannel balloons (MCBs) vs. single-channel cylinders (SCCs) for high-dose-rate vaginal cuff brachytherapy.Methods and MaterialsA total of 91 consecutive high-dose-rate vaginal cuff brachytherapy including 45 MCB and 46 SCC treatments were reviewed. The clinical target volume (CTV) was defined as a 0.5-cm uniform expansion of the applicator surface from vaginal apex for 3 cm. For dosimetric comparison, we normalized prescription dose per fraction to 700 cGy and optimized each plan to cover at least 90% of CTV. CTV-1 cm, the true vaginal cuff volume, was defined as proximal 1 cm of CTV from vaginal apex. Four quality indices including conformity index (CI), dose homogeneity index, dose nonuniformity index, and overdose index were compared.ResultsThe CTV and CTV-1 cm were significantly larger for MCB cases compared to SCC cases. Evaluating CTV coverage, the mean dose homogeneity index and dose nonuniformity index were superior for MCB than SCC. No differences were noted regarding CI and overdose index between MCB and SCC cases. However, focusing on CTV-1 cm, the difference of CI became significant in favor of MCB cases. In addition, the mean point dose at 0.5-cm depth from the apex was significantly lower in SCC cases compared to cases by MCB treatment, indicating inadequate vaginal apex coverage by SCC treatment.ConclusionsCompared to SCC, MCB treats a larger volume and offers a more conformal and homogeneous target coverage. In addition, a lower dose at the vaginal apex due to SCCs source anisotropy can be minimized.



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Silence of long noncoding RNA UCA1 inhibits malignant proliferation and chemotherapy resistance to adriamycin in gastric cancer

Abstract

Purpose

Urothelial carcinoma associated 1 (UCA1) gene is a long noncoding RNA (lncRNA), which shows expression and function abnormality in some kinds of malignant cancers. This study aimed to investigate its clinical significance and to examine its regulative effects of malignant proliferation and chemosensitivity to doxorubicin in gastric cancer cells.

Methods

The expression of UCA1 was detected by quantitative real-time PCR. Statistical analysis was used to determine the relationship between UCA1 expression and clinical features and the prognostic value of UCA1 for disease-free survival. MTT assay was used to detect cell proliferation ability and chemosensitivity. Dual-color flow cytometric method was used to detect cell apoptosis. The expression of cleaved PARP and Bcl-2 protein was examined by Western blot.

Results

UCA1 was highly expressed in gastric cancer tissues and cells, and its high expression level had a positive correlation with some malignant pathological characteristics of gastric cancer, such as higher grade and poor differentiation. Moreover, UCA1 was an independent prognostic biomarker of disease-free survival for gastric cancer patients. Silence of UCA1 could significantly inhibit the cell proliferation of gastric cancer BGC-823 and SGC7901 cells. The chemotherapy resistance to adriamycin of SGC7901/ADR cells was depressed by UCA1 silence, and IC50 for adriamycin presented a conspicuous depression. UCA1 silence advanced apoptosis induced by adriamycin in SGC7901/ADR cells, up-regulated cleaved PARP protein expression and depressed the expression of anti-apoptosis protein Bcl-2. These results demonstrated that chemotherapy resistance changes induced by UCA1 silence might be mediated by the cell apoptosis pathway.

Conclusions

In summary, lncRNA UCA1 was an independent prognostic biomarker of disease-free survival in gastric cancer patients and acted as an oncogene to regulate the malignant proliferation and resistance to adriamycin in gastric cancer cells. UCA1 might provide a new potential therapeutic target and stratagem for gastric cancer.

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Favorable outcome of primary mediastinal large B-cell lymphoma patients treated with sequential RCHOP-RICE regimen without radiotherapy

Abstract

Purpose

Outcomes in primary mediastinal B cell lymphoma (PMBL) improved with the introduction of dose intense treatments, consolidation radiotherapy and rituximab. DA-EPOCH-R, which omits radiotherapy has been adopted with worldwide enthusiasm, despite lack of proven superiority in randomized trials. We aimed to evaluate the course and outcome of PMBL using an alternative intensive rituximab-containing regimen, RCHOP-RICE. We also evaluated the prognostic value of ¹⁸FDG-PET-CT (PET-CT).

Methods

We reviewed the clinical, laboratory and imaging data of PMBL patients receiving 1st-line treatment in Hadassah Medical Center between 8/2002 and 10/2014.

Results

Of 47 PMBL patients, 24 (51 %) were treated with RCHOP-RICE and 23 (49 %) with other protocols. Overall, the 5-year progression-free survival was 93 % and the overall survival was 98 % (87 and 100 %, respectively, for the RCHOP-RICE regimen). Patient characteristics and treatment toxicities were balanced among protocols. A mean of 11.1 ± 1.3 hospitalization days/patient were needed to administer RCHOP-RICE regimen compared to 37 ± 2 days/patient for DA-EPOCH-R (n = 2). Radiotherapy was given to 3 patients (12 %) treated with RCHOP-RICE compared to 18 patients (78 %) treated with other protocols (p < 0.01). For patients followed with interim and end of treatment (EOT) PET-CT, we observed a significant reduction in the uptake between the two (p < 0.0001). Using a Deauville score cutoff of 3, the negative and positive predictive values (NPV and PPV) of EOT PET-CT were 94 and 33 %, respectively.

Conclusions

The RCHOP-RICE protocol results in excellent survival outcomes, generally permits omission of RT and is simpler to administer than DA-EPOCH-R. Interim PET-CT in PMBL may be unjustified; however, EOT Deauville scores ≤3 predicts a favorable outcome.

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Geographical Indications: A Corner Stone in Poverty Alleviation and Empowerment in the Indian Himalayan Region

Abstract

The Indian Himalayan region has huge social, cultural, ethnic and food diversity. This has lead to thousands of people engage themselves in the production of hundreds of indigenous products which are manufactured in small households or in small units. These products have premium value for the developed nations and first world market. However the unethical selling of fake products are eroding the charm and value of such novel products and poor people engaged in production of original products are getting socio-economically deprived. Under such circumstances the Geographical Indications protection has the potential to eliminate fake items and benefit both producer and consumers. This will boost export and tourism and indirectly lead to poverty alleviation and sustainable development of the Indian Himalayan region.

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Peptidylation for determination of low-molecule-weight compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00604C, Paper

Feng Tang, Si-Ying Cen, Huan He, Yi Liu, Bi-Feng Yuan, Y.-Q. Feng
Determination of low-molecule-weight compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been a great challenging in analytical research field. Here we developed a universal peptide-based derivatization (peptidylation) strategy...
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A race against time in lethal aluminum phosphide intoxication: a case report

2016-04-08T07-25-01Z
Source: Medicine Science | International Medical Journal
Ismail Altintop, Mahmut Firat Kaynak.
Aluminum phosphide (AP) is a condition that results in death in case of use for suicide purpose. The phosphine gas, which is released as a result of aluminum phosphide intake, has high level of toxicity. It leads to cellular level hypoxia and inhibition of oxidative phosphorylation. Aluminum phosphide intoxication may cause metabolic acidosis, arrhythmia, acute respiratory distress syndrome, and shock. High-dose intakes may lead to death within hours. 22 year-old female patient was taken to our emergency service because of the suicide attempt with 6000mg aluminum phosphide tablet. We aimed to share our experience with our aluminum phosphide intoxication, which has no known antidote and leads to rapid death in follow-up. We aim to present our experiences with our case of intoxication from aluminum phosphide, which causes high mortality after the intake. 22 year-old female patient was transferred to our hospital due to suicide attempt with 6000mg aluminum phosphide tablet. The patients have no known comorbidities, medicine use or allergic history. We believe that, in preventing the high mortality rate in aluminum phosphide intoxication, metabolic acidosis, arrhythmia, ARDS and measures against the shock and the hemodialysis in early period should be performed. Although its efficiency has not been clearly proved and its use has not entered into algorithms, the use of MgSO4 and N-Acetyl-Cysteine in supportive care is an option for such cases. Further studies and proven treatment methods are needed in AP toxicity.


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Overexpression of MexAB-OprM efflux pump in carbapenem-resistant Pseudomonas aeruginosa

Abstract

Efflux pump systems are one of the most important mechanisms conferring multidrug resistance in Pseudomonas aeruginosa. MexAB-OprM efflux pump is one of the largest multi-drug resistant efflux pumps with high-level expression, which is controlled by regulatory genes mexR, nalC, and nalD. This study investigated the role of efflux pump MexAB-OprM in 75 strains of carbapenem-resistant P. aeruginosa and evaluated the influence of point mutation of the regulatory genes. The minimum inhibitory concentrations of imipenem and meropenem, with or without MC207110, an efflux pump inhibitor, were determined by agar dilution method to select the positive strains for an overexpressed active efflux pump. Carba NP test and EDTA-disk synergy test were used for the detection of carbapenemase and metallo-β-lactamases, respectively. The gene mexA, responsible for the fusion protein structure, and the reference gene rpoD of the MexAB-OprM pump were amplified by real-time PCR. The quantity of relative mRNA expression was determined simultaneously. By PCR method, the efflux regulatory genes mexR, nalC, and nalD and outer membrane protein OprD₂ were amplified for the strains showing overexpression of MexAB-OprM and subsequently analyzed by BLAST. Among the 75 P. aeruginosa strains, the prevalence of efflux pump-positive phenotype was 17.3 % (13/75). Carba NP test and EDTA-disk synergy test were all negative in the 13 strains. PCR assay results showed that ten strains overexpressed the MexAB-OprM efflux pump and were all positive for the regulatory genes mexR, nalC, and nalD. Sequence analysis indicated that of the ten isolates, nine had a mutation (Gly → Glu) at 71st amino acid position in NalC, and eight also had a mutation (Ser → Arg) at 209th position in NalC. Only one strain had a mutation (Thr → Ile) at the 158th amino acid position in NalD, whereas eight isolates had mutations in MexR. In conclusion, overexpression of efflux pump MexAB-OprM plays an important role in carbapenem-resistant P. aeruginosa. The mutations of regulatory genes may be a main factor contributing to overexpression of MexAB-OprM.

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Braquiterapia de alta tasa en el carcinoma escamoso de labio en estadios iniciales

Publication date: Available online 7 April 2016
Source:Acta Otorrinolaringológica Española
Author(s): Alejandro Mut, José Luis Guinot, Leoncio Arribas, Lorena Díez-Presa, María Isabel Tortajada, Miguel Ángel Santos, Josefa Samper, Paula Santamaría, Juan Bosco Vendrell
Introducción y objetivosAnalizar los resultados obtenidos en el tratamiento del carcinoma escamoso de labio en estadios iniciales (T1-T2) con braquiterapia de alta tasa y evaluar la eficacia para el control local y regional de dicho tratamiento.Material y métodosAnálisis retrospectivo de los tratamientos realizados entre marzo de 1999 y marzo de 2013 con braquiterapia de alta tasa de dosis con agujas rígidas, a 68 pacientes, 63 varones y 5 mujeres. Treinta y siete pacientes (54,4%) presentaban un tumor igual o menor de 2cm (T1), y 31 (45,6%) de 2-4cm (T2). En todos se indicó braquiterapia radical con una dosis total mediana de 45Gy, con una dosis por fracción de 5Gy x 9 fracciones, dos veces al día, en un ingreso de cinco días.ResultadosCon 56,4 meses de seguimiento medio el control local fue 96,9%. En pacientes con tumores T1 el control local fue del 100%, mientras en T2 fue 93,2% (2 recidivas locales). El control regional a 5 años, en T1 fue 93,8% y en T2 80,8%. En once casos con profilaxis cervical no hubo recaídas. En cuanto a toxicidad, ningún paciente presentó necrosis de tejidos blandos ni ósea y en todos ellos se consiguieron resultados cosméticos y funcionales buenos o excelentes.ConclusionesLa braquiterapia de alta tasa permite realizar métodos seguros y efectivos para tratamiento del carcinoma escamoso de labio, con buenos resultados estéticos y funcionales y mínimas complicaciones y puede considerarse una alternativa válida al tratamiento quirúrgico en estadios iniciales.Introduction and goalsTo analyze the results obtained after treatment of early stage (T1-T2) squamous cell carcinoma of the lip with high dose rate brachytherapy and evaluate the efficacy of this treatment in both local and regional control.Materials and methodsRetrospective analysis of the treatments performed at our department from March 1999 to March 2013 with high dose rate brachytherapy with rigid needles. We included 68 patients, 63 men and 5 women; 37 patients (54.4%) presented a T1 tumour, less than or equal to 2cm, while the other 31 (45.6%) were classified as T2. Median total dose was 45Gy, with a median dose per fraction of 5Gy x 9 fractions twice a day for 5 days.ResultsWith a mean follow-up of 56.4 months, local control was 96.9%. Stratifying by tumour size, local control of T1 cases was 100%, while T2 achieved 93.2% (2 local recurrences). Regional control at 5 years was 93.8% for T1, and 80.8% for T2. In 11 cases with elective cervical treatment, no regional failure happened. As for toxicity, no patient presented soft tissue, or bone, necrosis. All patients achieved good or excellent cosmetic and functional results.ConclusionsHigh dose rate brachytherapy allows effective, safe treatments for squamous cell carcinoma of the lip, with good aesthetic and functional results. It can be considered a valid alternative for surgery in early stage tumours.



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Estenosis glóticas posteriores de origen cicatricial. Nuestra experiencia

Publication date: Available online 7 April 2016
Source:Acta Otorrinolaringológica Española
Author(s): Ana Maeso-Plaza, María Dablanca-Blanco, Consuelo Ortega-Fernandez, Primitivo Ortega-del Álamo
Introducción y objetivosPresentar los resultados obtenidos en el tratamiento de estenosis glóticas posteriores cicatriciales.MétodosEstudio retrospectivo de 34 pacientes diagnosticados y tratados de estenosis glóticas posteriores cicatriciales por nuestro servicio.ResultadosEl 85,36% de nuestros pacientes fueron decanulados. Los pacientes con estenosis de localización únicamente glótica fueron decanulados en un 80%, mientras que paradójicamente en los que tenían asociada además otro tipo de estenosis laringotraqueal, el porcentaje de decanulación fue del 92,9%.El 70% de los pacientes requirieron más de un procedimiento quirúrgico, aunque la mayoría de ellos se hicieron por protocolo y con la finalidad de resolver pequeños problemas.El número de reintervenciones está condicionado por la localización de la estenosis, siendo mayor cuando la estenosis glótica posterior se asocia a otro tipo de estenosis laringotraqueal (p=0,001).ConclusionesLos resultados quirúrgicos obtenidos en el tratamiento de las estenosis glóticas posteriores cicatriciales son buenos, pero a diferencia de otro tipo de estenosis glóticas posteriores (como por ejemplo las parálisis de abductores de origen neurogénico) requieren más intervenciones para la decanulación definitiva.Los procedimientos endoscópicos juegan un papel destacado y suponen nuestra principal herramienta de trabajo.Introduction and objectivesPresentation of the results obtained in the treatment of cicatricial posterior glottic stenosis.MethodsA retrospective study of 34 patients diagnosed and treated for cicatricial posterior glottic stenosis in our ENT Department.ResultsIn our series, 85.36% of our patients were decannulated. Of these, 80% of the patients with glottic stenosis were decannulated, while 92.9% of the patients with other associated laryngotracheal stenosis were paradoxically decannulated.Of all the patients, 70% required more than 1 surgical procedure, although most of these interventions were to resolve minor issues following our protocol.The number of subsequent interventions was determined by the location of the stenosis, with there being more interventions when the posterior glottic stenosis was associated with another type of laryngotracheal stenosis (p=.001).ConclusionsThe surgical results for treating cicatricial posterior glottic stenosis are quite positive. However, unlike other types of posterior glottic stenosis (such as neurogenic abductor paralysis), it requires a greater number of interventions to achieve definitive decannulation. Endoscopic procedures play an important role and represent our main tool.



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Estenosis laringotraqueales de etiología autoinmune

Publication date: Available online 8 April 2016
Source:Acta Otorrinolaringológica Española
Author(s): Maria Dablanca, Ana Maeso, Desiree del C. Méndez, Primitivo Ortega
El origen autoinmune ocupa el 5.° lugar en la clasificación etiológica de las estenosis laringotraqueales. La enfermedad autoinmune que más se ha asociado a estenosis es la enfermedad de Wegener, pero existen otras enfermedades que también pueden relacionarse con estas. Presentamos un estudio descriptivo, retrospectivo, de 9 casos de estenosis laringotraqueal en pacientes con enfermedad autoinmune. Se trata de 8 mujeres y un hombre, con edad media de 27,9años. Cuatro de los pacientes padecían enfermedad de Wegener, uno colitis ulcerosa y otro púrpura vasculítica. Los otros 3 pacientes solamente eran anticuerpos antinucleares positivos. Tres de los casos fueron tratados únicamente con abordaje endoscópico y los otros 6 necesitaron además cirugía abierta, con resultados respiratorios aceptables. Pensamos que en todos los pacientes con estenosis laringotraqueal se deben estudiar los perfiles inmunológicos, ya que no solo la enfermedad de Wegener se asocia a esta enfermedad.Autoimmune origin ranks fifth in the etiologic classification of laryngotracheal stenosis. Wegener's disease is the autoimmune illness most associated with stenosis; however, there are other autoimmune diseases that may also be associated with it.A descriptive, retrospective study of 9 cases of laryngotracheal stenosis associated with autoimmune disease was carried out. There were 9 patients (8 females and 1 male) with an average age of 27.9 years. Four of the patients suffered from Wegener's disease, 1 from ulcerative colitis and 1 from purple vasculitis. The other 3 patients only had positive c-ANA. Endoscopic treatment was performed in 3 cases. The other 6 patients required open surgery. Respiratory results were acceptable. Based on our study, we feel that the immunological profiles should be studied in all patients with stenosis, given that not only Wegener's disease is linked to stenosis.



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The difference in Ezrin–pAkt signaling axis between lepidic and papillary predominant invasive adenocarcinomas of the lung

Abstract

Purpose

Histologic classification of invasive lung adenocarcinomas by predominant subtype has prognostic value. Papillary predominant adenocarcinoma (PPA) reportedly shows poorer prognosis than lepidic predominant adenocarcinoma (LPA); however, biological differences between PPA and LPA are unclear. The purpose of this study was to clarify biological differences between PPA and LPA.

Methods

Clinicopathological characteristics of invasive 62 PPAs and 117 LPAs smaller than 30 mm were investigated. Furthermore, we compared immunochemical staining scores of 9 molecular markers (E-cadherin, S100A4, fibronectin, integrinβ1, ezrin, GLUT1, ALDH1, SOX2 and Nanog) between PPA and LPA. We performed Western blot analysis using ezrin shRNA-knockdown lung adenocarcinoma cell lines to examine whether molecules that are highly expressed in PPA, such as ezrin, affect pAkt. Finally, we performed immunochemical staining to compare pAkt expression level in PPA and LPA.

Results

Lymphovascular and pleural invasion and lymph node metastasis were significantly more often detected in PPA than in LPA (lymphatic permeation: 31 vs 3 %, vascular invasion: 35 vs 3 %, pleural invasion: 29 vs 5 %, lymph node metastasis: 18 vs 1 %; all P < 0.01). Immunohistochemical (IHC) study revealed that expression score of ezrin was significantly higher in PPA than in LPA (38.3 vs 15.0; P < 0.01). The level of pAkt decreased in shEzrin-induced PC-9 and A549 cancer cells. Moreover, the IHC staining score of pAkt was significantly higher in PPA than in LPA (13.3 vs 0.0; P < 0.01).

Conclusions

Our results show that the activation of the ezrin–pAkt signaling axis is associated with the more aggressive clinicopathological features of PPA compared with LPA.

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Citizenship or Repression? Coca, Eradication and Development in the Andes

Grisaffi, T; Ledebur, K; (2016) Citizenship or Repression? Coca, Eradication and Development in the Andes. Stability: International Journal of Security and Development , 5 (1) pp. 1-19. 10.5334/sta.440 . Green open access

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Use and cumulation of evidence from modelling studies to inform policy on food taxes and subsidies: biting off more than we can chew?

Shemilt, I; Marteau, TM; Smith, RD; Ogilvie, D; (2015) Use and cumulation of evidence from modelling studies to inform policy on food taxes and subsidies: biting off more than we can chew? BMC Public Health , 15 , Article 297. 10.1186/s12889-015-1641-5 . Green open access

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Portion, package or tableware size for changing selection and consumption of food, alcohol and tobacco.

Hollands, GJ; Shemilt, I; Marteau, TM; Jebb, SA; Lewis, HB; Wei, Y; Higgins, JP; Hollands, GJ; Shemilt, I; Marteau, TM; Jebb, SA; Lewis, HB; Wei, Y; Higgins, JP; Ogilvie, D; - view fewer (2015) Portion, package or tableware size for changing selection and consumption of food, alcohol and tobacco. Cochrane Database of Systematic Reviews , 9 , Article CD011045. 10.1002/14651858.CD011045.pub2 . Green open access

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Biocompatibility Assessment of a New Biodegradable Vascular Graft via In Vitro Co-culture Approaches and In Vivo Model

Abstract

Following the implantation of biodegradable vascular grafts, macrophages and fibroblasts are the major two cell types recruited to the host-biomaterial interface. In-vitro biocompatibility assessment usually involves one cell type, predominantly macrophages. In this study, macrophage and fibroblast mono- and co-cultures, in paracrine and juxtacrine settings, were used to evaluate a new biodegradable thermoplastic polyurethane (TPU) vascular graft. Expanded-polytetrafluoroethylene (ePTFE) grafts served as controls. Pro/anti-inflammatory gene expression of macrophages and cytokines was assessed in vitro and compared to those of an in vivo rat model. Host cell infiltration and the type of proliferated cells was further studied in vivo. TPU grafts revealed superior support in cell attachment, infiltration and proliferation compared with ePTFE grafts. Expression of pro-inflammatory TNF-α/IL-1α cytokines was significantly higher in ePTFE, whereas the level of IL-10 was higher in TPU. Initial high expression of pro-inflammatory CCR7 macrophages was noted in TPU, however there was a clear transition from CCR7 to anti-inflammatory CD163 expression in vitro and in vivo only in TPU, confirming superior cell-biomaterial response. The co-culture models, especially the paracrine model, revealed higher fidelity to the immunomodulatory/biocompatibility behavior of degradable TPU grafts in vivo. This study established an exciting approach developing a co-culture model as a tool for biocompatibility evaluation of degradable biomaterials.

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Performance Variability as a Predictor of Response to Aphasia Treatment.

Performance Variability as a Predictor of Response to Aphasia Treatment.

Neurorehabil Neural Repair. 2016 Apr 6;

Authors: Duncan ES, Schmah T, Small SL

Abstract
BACKGROUND: Performance variability in individuals with aphasia is typically regarded as a nuisance factor complicating assessment and treatment.
OBJECTIVE: We present the alternative hypothesis that intraindividual variability represents a fundamental characteristic of an individual's functioning and an important biomarker for therapeutic selection and prognosis.
METHODS: A total of 19 individuals with chronic aphasia participated in a 6-week trial of imitation-based speech therapy. We assessed improvement both on overall language functioning and repetition ability. Furthermore, we determined which pretreatment variables best predicted improvement on the repetition test.
RESULTS: Significant gains were made on the Western Aphasia Battery-Revised (WAB) Aphasia Quotient, Cortical Quotient, and 2 subtests as well as on a separate repetition test. Using stepwise regression, we found that pretreatment intraindividual variability was the only predictor of improvement in performance on the repetition test, with greater pretreatment variability predicting greater improvement. Furthermore, the degree of reduction in this variability over the course of treatment was positively correlated with the degree of improvement.
CONCLUSIONS: Intraindividual variability may be indicative of potential for improvement on a given task, with more uniform performance suggesting functioning at or near peak potential.

PMID: 27053642 [PubMed - as supplied by publisher]

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Pharyngeal Electrical Stimulation in Dysphagia Poststroke: A Prospective, Randomized Single-Blinded Interventional Study.

Pharyngeal Electrical Stimulation in Dysphagia Poststroke: A Prospective, Randomized Single-Blinded Interventional Study.

Neurorehabil Neural Repair. 2016 Apr 6;

Authors: Vasant DH, Michou E, O'Leary N, Vail A, Mistry S, Hamdy S, Greater Manchester Stroke Research Network

Abstract
Background Pharyngeal electrical stimulation (PES) appears to promote cortical plasticity and swallowing recovery poststroke.Objective We aimed to assess clinical effectiveness with longer follow-up.Methods Dysphagic patients (n = 36; median = 71 years; 61% male) recruited from 3 trial centers within 6 weeks of stroke, received active or sham PES in a single-blinded randomized design via an intraluminal pharyngeal catheter (10 minutes, for 3days). The primary outcome measure was the Dysphagia Severity Rating (DSR) scale (<4, no-mild; ≥4, moderate-severe). Secondary outcomes included unsafe swallows on the Penetration-Aspiration Scale (PAS ≥ 3), times to hospital discharge, and nasogastric tube (NGT) removal. Data were analyzed using logistic regression. Odds/hazard ratios (ORs/HRs) >1 for DSR <4, hospital discharge, and NGT removal and OR <1 for PAS ≥3, indicated favorable outcomes for active PES.Results Two weeks post-active PES, 11/18 (61%) had DSR <4: OR (95% CI) = 2.5 (0.52, 14). Effects of active versus sham for secondary outcomes included the following: PAS ≥3 at 2 weeks, OR (95% CI) = 0.61 (0.27, 1.4); times to hospital discharge, 39 days versus 52 days, HR (95% CI) = 1.2 (0.55, 2.5); NGT removal 8 versus 14 days, HR (95% CI) = 2.0 (0.51, 7.9); and DSR <4 at 3 months, OR (95% CI) = 0.97 (0.13, 7.0). PES was well tolerated, without adverse effects or associations with serious complications (chest infections/death).Conclusions Although the direction of observed differences were consistent with PES accelerating swallowing recovery over the first 2 weeks postintervention, suboptimal recruitment prevents definitive conclusions. Our study design experience and outcome data are essential to inform a definitive, multicenter randomized trial.

PMID: 27053641 [PubMed - as supplied by publisher]

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Investigating the Causal Role of rightOFA in Holistic Detection of Mooney Faces and Objects: an fMRI-Guided TMS Study

Publication date: Available online 8 April 2016
Source:Brain Stimulation
Author(s): Silvia Bona, Zaira Cattaneo, Juha Silvanto
BackgroundThe right occipital face area (rOFA) is known to be involved in face discrimination based on local featural information. Whether this region is involved in global, holistic stimulus processing is not known.ObjectiveWe used fMRI-guided transcranial magnetic stimulation (TMS) to investigate whether rOFA is causally implicated in stimulus detection based on holistic processing, by the use of Mooney stimuli.MethodsTwo studies were carried out: In Experiment 1, participants performed a detection task involving Mooney faces and Mooney objects; Mooney stimuli lack distinguishable local features and can be detected solely via holistic processing (i.e. at a global level) with top-down guidance from previously stored representations. Experiment 2 required participants to detect shapes which are recognized via bottom-up integration of local (collinear) Gabor elements and was performed to control for specificity of rightOFA's implication in holistic detection.ResultsIn Experiment 1, TMS over rOFA and rLO impaired detection of all stimulus categories, with no category-specific effect. In Experiment 2, shape detection was impaired when TMS was applied over rLO but not over rOFA.ConclusionsOur results demonstrate that rOFA is causally implicated in the type of top-down holistic detection required by Mooney stimuli and that such role is not face-selective. In contrast, rOFA does not appear to play a causal role in in detection of shapes based on bottom-up integration of local components, demonstrating that its involvement in processing non-face stimuli is specific for holistic processing.



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Examining clinical outcomes utilizing low-pressure pneumoperitoneum during robotic-assisted radical prostatectomy

Abstract

The objective of the study was to assess the safety and clinical outcomes of performing RARP utilizing LPP 12 mmHg with locally confined adenocarcinoma of the prostate. Utilizing the Metro Health RALP database registry and the Michigan Urological Clinic records, we retrospectively reviewed the records of consecutive RALPs performed between December 2012 and March 2015 by a single robotic surgeon. 100 patients underwent RARP utilizing 15 mmHg of standard pressure pneumoperitoneum (SPP) and 100 patients underwent RALP utilizing 12 mmHg lower pressure pneumoperitoneum (LPP). Intraoperative parameters reviewed included operative time (OT) and blood loss (BL). Postoperative parameters reviewed included length of hospital stay (LOS), postoperative ileus, fistulas, urinary retention and hematoma formation. Surgical outcomes reviewed included pathological stage and combined Gleason score. Patient age, BMI, mean combined Gleason score and pathological stage were similar in both groups. Mean OT for the LPP group was 105.49 (66–166) and for the standard pressure pneumoperitoneum (SPP) group 111.31 (61–231) min. The length of stay in both groups was similar, averaging 1.53 (1–6) days for the LPP group and 1.57 (1–6) days for the SPP group. The LPP group had a lower postop ileus rate of 4 vs 8 % in the SPP group, but they were not statistically different. Likewise, the positive margin rate, readmission rate, hematoma rate, retention rate and urinary fistula rate were similar and not statistically different for both groups. Pneumoperitoneum of 12 mmHg is noninferior to 15 mmHg during RARP and does not alter the clinical outcomes.

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The HLA-DRB1 allele polymorphisms and nasopharyngeal carcinoma

Abstract

Human leukocyte antigen (HLA)-DRB1 has been reported to influence individual's susceptibility to nasopharyngeal carcinoma (NPC) by many studies in recent years; however, these studies provided controversial results. The meta-analysis was thus conducted here to estimate the relationship between HLA-DRB1 polymorphisms and NPC. After an extensive review of journals from various databases (PubMed, the Web of Science, Embase, China National Knowledge Internet (CNKI), and Wanfang Database), 8 out of 69 case-control studies, including 778 cases and 1148 controls, were extracted. The results showed that 4 of 13 polymorphisms allele are statistically significantly associated with NPC, among them, HLA-DRB1*3, HLA-DRB1*9, and HLA-DRB1*10 may increase the risk of NPC while HLA-DRB1*01 has the opposite effect. The pooled odds ratio and 95 % confidence interval (CI) were 1.702 [95 % CI (1.047, 2.765)], 1.363 [95 % CI (1.029, 1.806)], 1.989 [95 % CI (1.042, 3.799)], and 0.461 [95 % CI (0.315, 0.676)], respectively. In a further ethnicity-based subgroup analysis, HLA-DRB1*08, HLA-DRB1*11, and HLA-DRB1*16 were found to be linked with NPC in Asian, Tunisian, and Caucasian, respectively. In Asian, HLA-DRB1*03, 08, and 10 may elevate the risk whereas HLA-DRB1*09 could lower it. In Tunisian, HLA-DRB1*01 and 11 are the protective factors while HLA-DRB1*03 is the only risk factor. In Caucasian, HLA-DRB1*01 and 03 increase the risk and HLA-DRB1*16 lowers it. The most frequent statistically associated gene is found to be HLA-DRB1*03 which has protective influence on Asian and Tunisian. In conclusion, HLA-DRB1*01, DRB1*03, DRB1*09, and DRB1*10 are related with NPC susceptibility, and the association of HLA-DRB1*08, DRB1*11, and DRB1*16 with NPC risk are significantly different in different ethnicities.

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Genome-wide mitochondrial DNA sequence variations and lower expression of OXPHOS genes predict mitochondrial dysfunction in oral cancer tissue

Abstract

Several studies reported that mtDNA mutations may play important roles in carcinogenesis although the mechanism is not clear yet. Most of the studies compared mtDNA sequences in a tumor with those in normal tissues from different individuals ignoring inter-individual variations. In this study, 271 SNPs, 7 novel SNPs (or SNVs), and 15 somatic mutations were detected in mtDNA of 8 oral cancer tissues with respect to reference (rCRS) and adjacent normal tissues, respectively, using Ion PGM next generation sequencing method. Most of the sequence variations (76 SNPs and 1 somatic) are present in D-loop region followed by CyB (36 SNPs), ATP6 (24 SNPs), ND5 (17 SNPs and 5 somatic), ND4 (18 coding and 2 somatic) and other non-coding and coding DNA sequences. A total of 53 and 8 non-synonymous SNPs and somatic mutations, respectively, were detected in tumor tissues and some of these variations may have deleterious effects on the protein function as predicted by bioinformatic analysis. Moreover, significantly low mtDNA contents and expression of several mitochondrial genes in tumor compared to adjacent normal tissues may have also affected mitochondrial functions. Taken together, this study suggests that mtDNA mutations as well as low expression of mtDNA coded genes may play important roles in tumor growth. Although the sample size is low, an important aspect of the study is the use of adjacent control tissues to find out somatic mutations and a change in the expression of mitochondrial genes, to rule out inter-individual and inter-tissue variations which are important issues in the study of mitochondrial genomics.

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TGFβ1-Induced PAI-1 Contributes to a Pro-Fibrotic Network in Eosinophilic Esophagitis

Publication date: Available online 8 April 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Renee Rawson, Tom Yang, Robert O. Newbury, Melissa Aquino, Ashmi Doshi, Braxton Bell, David H. Broide, Ranjan Dohil, Richard Kurten, Seema S. Aceves
BackgroundEosinophilic esophagitis is an allergic disease of increasing worldwide incidence. Complications are due to tissue remodeling and involve transforming growth factor-β1 (TGFβ1) mediated fibrosis. Plasminogen Activator Inhibitor-1 (PAI-1/serpinE1) can be induced by TGFβ1 but its role in EoE is not known.ObjectiveTo understand the expression and role of PAI-1 in EoEMethodsWe used esophageal biopsy specimens and plasma samples from control and EoE subjects, primary human esophageal epithelial cells, and EoE fibroblasts in immunohistochemistry, quantitative PCR, and immunoassay experiments to understand the induction of PAI-1 by TGFβ1, the relationship between PAI-1 and esophageal fibrosis, and the role of PAI-1 in fibrotic gene expression.ResultsPAI-1 expression was significantly elevated in epithelial cells of active EoE biopsies as compared with inactive EoE or control biopsies (p<0.001). Treatment of primary esophageal epithelial cells with recombinant TGFβ1 increased PAI-1 transcription, intracellular protein expression, and secretion. Esophageal PAI-1 expression correlated with basal zone hyperplasia, a fibrosis, and markers of esophageal remodeling including vimentin, TGFβ1, collagen I, fibronectin, and matrix metalloproteases and plasma PAI-1 levels correlated with plasma TGFβ1. PAI-1 inhibition significantly decreased baseline and TGFβ1-induced fibrotic gene expression.ConclusionsPAI-1 is significantly elevated in the EoE epithelium, reflects fibrosis, and its inhibition decreases TGFβ1-induced gene expression. Epithelial PAI-1 may serve as a marker of EoE severity and form part of a TGFβ1-induced pro-fibrotic network.

Teaser

PAI-1 has not been previously studied in EoE. This study shows that PAI-1 may be an epithelial marker of fibrotic severity, and could be a new therapeutic target in EoE.


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Book review: Jukka Vuori, Roland Blonk and Richard H Price (eds), Sustainable Working Lives: Managing Work Transitions and Health throughout the Life Course

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Why are young adults willing to cooperate with the police and comply with traffic laws?

The question why people are willing to comply with the law and to cooperate with the police has received more attention the past several years. According to the procedural justice model this is caused by the fact that when civilians trust the police to treat them honestly and fairly, they will perceive the police as a legitimate institution that deserves respect and obedience. The perception that the police is legitimate is necessary so the police can enforce authority and civilians will be willing to comply with the law and to cooperate with the police. This study attempts to test an expanded version of the procedural justice model. The added value of this study is, firstly, that it takes into account several intermediary mechanisms that might influence the relations between perceptions about the procedural justice and effectiveness of the police, and the compliance with the law and the willingness to cooperate with the police. More specifically, the perceived legitimacy of the law and legal cynicism are added as intermediary variables to the model. Secondly the model is adapted for compliance with traffic laws. Two alternative paths are examined more closely as well, this way we verify what role perceived deterrence and personal morality play in the explanation of the willingness of young adults to comply with traffic laws and cooperate with the police. The test was executed according to path models with the aid of a large-scale student survey (N= 1 659). On the one hand, the results show that procedural justice has an effect on the result variables through several pathways, i.e. through the perceived legitimacy of the police, the perceived legitimacy of the law and legal cynicism. On the other hand, the explanatory power of the model is limited. We wish to nuance the results by formulating several critical remarks.

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STEP: op naar een grondige hervorming van het vennootschapsrecht?

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Implementation of an automatic program partitioner on a homogeneous multiprocessor

The design and the first results of a prototype multiprocessor featuring the automatic partitioning of Fortran programs are presented. The conversion of the source program to a task schedule is based on a dataflow analysis that takes into account the task size, the number of processors, and the communication between tasks. Various levels of task granularity can be selected, which allows a tradeoff between the amount of parallelism and the communication overhead. The architecture consists of up to 20 off-the-shelf processor boards, configured around the IEEE-796 bus. Each board has a dual port memory, used for semaphore storage and distributed synchronization. Experiments using the automatic partitioner for five programs show a near-linear speedup, even for small problems, and a high utilization of the floating-point processor when the tasks size is large.

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Application of Sigma Metrics Analysis for the Assessment and Modification of Quality Control Program in the Clinical Chemistry Laboratory of a Tertiary Care Hospital

Abstract

Sigma is a metric that quantifies the performance of a process as a rate of Defects-Per-Million opportunities. In clinical laboratories, sigma metric analysis is used to assess the performance of laboratory process system. Sigma metric is also used as a quality management strategy for a laboratory process to improve the quality by addressing the errors after identification. The aim of this study is to evaluate the errors in quality control of analytical phase of laboratory system by sigma metric. For this purpose sigma metric analysis was done for analytes using the internal and external quality control as quality indicators. Results of sigma metric analysis were used to identify the gaps and need for modification in the strategy of laboratory quality control procedure. Sigma metric was calculated for quality control program of ten clinical chemistry analytes including glucose, chloride, cholesterol, triglyceride, HDL, albumin, direct bilirubin, total bilirubin, protein and creatinine, at two control levels. To calculate the sigma metric imprecision and bias was calculated with internal and external quality control data, respectively. The minimum acceptable performance was considered as 3 sigma. Westgard sigma rules were applied to customize the quality control procedure. Sigma level was found acceptable (≥3) for glucose (L2), cholesterol, triglyceride, HDL, direct bilirubin and creatinine at both levels of control. For rest of the analytes sigma metric was found <3. The lowest value for sigma was found for chloride (1.1) at L2. The highest value of sigma was found for creatinine (10.1) at L3. HDL was found with the highest sigma values at both control levels (8.8 and 8.0 at L2 and L3, respectively). We conclude that analytes with the sigma value <3 are required strict monitoring and modification in quality control procedure. In this study application of sigma rules provided us the practical solution for improved and focused design of QC procedure.

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Curcumin and Ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells

Publication date: July 2016
Source:Biomedicine & Pharmacotherapy, Volume 81
Author(s): Devbrat Kumar, Soumya Basu, Lucy Parija, Deeptimayee Rout, Sanjeet Manna, Jagneshwar Dandapat, Priya Ranjan Debata
Cervical cancer and precancerous lesions of the cervix continue to be a global health issue, and the medication for the treatment for chronic HPV infection so far has not been effective. Potential anticancer and anti HPV activities of two known phytochemicals, Curcumin and Ellagic acid were evaluated in HeLa cervical cancer cells. Curcumin is a natural compound found in the root of Curcuma longa plant and Ellagic acid a polyphenol found in fruits of strawberries, raspberries and walnuts. The combination of Curcumin and Ellagic acid at various concentrations showed better anticancer properties than either of the drug when used alone as evidenced by MTT assay. Besides this, Curcumin and Ellagic acid also restore p53, induce ROS formation and DNA damage. Mechanistic study further indicated that Curcumin and Ellagic acid show anti-HPV activity as evidenced by decrease in the HPV E6 oncoprotein on HeLa cells.



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MiR-125a regulates ovarian cancer proliferation and invasion by repressing GALNT14 expression

Publication date: May 2016
Source:Biomedicine & Pharmacotherapy, Volume 80
Author(s): Juan Yang, Guiyuan Li, Keqiang Zhang
Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to tumor progression. The miR-125a was downregulated in several types of cancer, however, the molecular mechanism of miR-125a in the ovarian cancer remains unclear. The aim of the paper was to reveal the mechanism of miR-125a regulating cell proliferation and metastasis in ovarian cancer. In this study, western blotting, immunohistochemistry and serum-ELISA assay revealed that polypeptide N-acetylgalactosaminyl transferase 14 (GALNT14) expression was upregulated and correlated with the cancer stage in ovarian cancer. The expression levels of miR-125a were downregulated and negatively related to GALNT14 expression in clinical ovarian cancer tissues. Moreover, luciferase reporter assay identified polypeptide N-acetylgalactosaminyl transferase 14 (GALNT14) as a direct target of miR-125a, and overexpression of miR-125a markedly reduced the expression of GALNT14 in ovarian cancer. Functional characterization of miR-125a was accomplished by reconstitution of miR-125a and silencing GALNT14 expression in ovarian cancer cells to determine changes in proliferation and invasion. The MTT assay and transwell assay revealed that miR-125a transfectant significantly inhibits cell proliferation and invasion, by repressing GALNT14 expression. Furthermore, the gelatin zymography assay miR-125a mimics and GALNT14 siRNA suppressed the activity of MMP2 and MMP9. Taken together, our findings show that miR-125a functions as tumor suppressor in ovarian cancer by targeting GALNT14, and miR-125a may therefore serve as a biomarker for diagnosis and therapeutics in ovarian cancer.



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Activity tracker app calls for help if wearer is under attack

A Hack for Her team designed the app which syncs with a Microsoft Band to help users report domestic violence

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Nosocomial infection in China: Management status and solutions

Publication date: Available online 7 April 2016
Source:American Journal of Infection Control
Author(s): Bingwei Sun




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Extended-spectrum β-lactamase–producing Enterobacteriaceae in cell phones of health care workers from Peruvian pediatric and neonatal intensive care units

Publication date: Available online 7 April 2016
Source:American Journal of Infection Control
Author(s): Steev Loyola, Luz R. Gutierrez, Gertrudis Horna, Kyle Petersen, Juan Agapito, Jorge Osada, Paul Rios, Andres G. Lescano, Jesus Tamariz
BackgroundHealth care workers (HCWs) use their mobile phones during working hours or medical care. There is evidence that the instruments are colonized with pathogenic microorganisms. Here, we describe levels of Enterobacteriaceae contamination (EC) in cell phones and the risk factors associated with EC in Peruvian intensive care units (ICUs).MethodsThis was a 5-month cohort study among 114 HCWs of 3 pediatric and 2 neonatology ICUs from 3 Peruvian hospitals. A baseline survey collected data on risk factors associated with EC. Swabs were collected from HCWs' phones every other week.ResultsThree-quarters of HCWs never decontaminated their phones, and 47% reported using the phones in the ICU >5 times while working. EC was frequent across samplings and sites and was substantially higher in subjects with longer follow-up. Potential risk factors identified did not have strong associations with positive samples (relative risk, 0.7-1.5), regardless of significance. Half of the phones were colonized with an Enterobacteriaceae at least once during the 4 samplings attained on average during the study period. Half of the isolates were multidrug resistant (MDR), and 33% were extended-spectrum β-lactamase producers.ConclusionsEC on HCWs' phones was frequent and apparently randomly distributed through the hospitals without clear clustering or strongly associated risk factors for having a positive sample. Based on the level of EC, phones may be considered as potential bacterial reservoirs of MDR and ESBL bacteria.



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Are we sending the wrong message when we ask health care workers to wash their hands?

Publication date: Available online 7 April 2016
Source:American Journal of Infection Control
Author(s): Sharon L. Kurtz
When asking healthcare workers to wash their hands, perhaps a better message would be to ask them not to transmit diseases. This changes the emphasis from a single act of adherence to a concept of behavior change. Proper hand hygiene, proper use of personal protective equipment, and cough etiquette are the means to an end, to stop the transfer to organisms and disease, but not the ultimate goal itself. The ultimate goal is to stop the transmission of diseases and ultimately to decrease the occurrence of healthcare associated infections.



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Vancomycin-resistant Enterococcus co-colonization rates with methicillin-resistant Staphylococcus aureus and Clostridium difficile in critically ill veterans

Publication date: Available online 7 April 2016
Source:American Journal of Infection Control
Author(s): Linda McKinley, Benjamin Becerra, Helene Moriarty, Thomas H. Short, Mary Hagle, Abigail Reymann, Susan Valentine, Megan Duster, Simone Warrack, Nasia Safdar
A prospective study was conducted to identify risk factors for vancomycin-resistant Enterococcus, including co-colonization with methicillin-resistant Staphylococcus aureus and Clostridium difficile infection in patients admitted to the intensive care unit in 2 Veterans Affairs facilities. Methicillin-resistant Staphylococcus aureus and Clostridium difficile infection co-colonization were significant risk factors for vancomycin-resistant Enterococcus colonization. Further studies are needed to identify measures for preventing co-colonization of these major organisms in veterans.



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