Κυριακή 5 Φεβρουαρίου 2017

Framingham risk assessment in Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a known association with obesity [1]. Evidence of an association between metabolic syndrome and HS has been reported [2]. The Framingham Risk Score (FRS) [3] is a gender-specific algorithm used to estimate an individual's 10-year cardiovascular risk. Despite limitations of its use, it remains one of the most widely used risk assessment tools. Patients scoring less than 10% are considered to be at low risk, those between 10% and 20% are at moderate risk and those scoring 20% or more are considered to be at high risk.

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Coronary artery aneurysm after implantation of a bioresorbable vascular scaffold: Case report and literature review

A 55-year-old man underwent successful percutaneous coronary intervention for the middle left circumflex artery with a 3.5 × 28-mm bioresorbable vascular scaffold (BVS). At 18 months, follow-up coronary angiography showed ectatic change with aneurysm formation over the BVS. Optical coherence tomography revealed absence of strut continuity at the aneurysm site, in the middle of the BVS. A literature review identified nine patients with intrascaffold aneurysm, including the present patient, which developed 6–32 months after BVS implantation. Of these nine patients, four underwent percutaneous coronary intervention for chronic total occlusion. The pathogenesis of coronary artery aneurysm is multifactorial. Most patients receive no further intervention, but long-term dual antiplatelet therapy is sometimes prescribed in conjunction with regular follow-up. © 2017 Wiley Periodicals, Inc.



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Corrigendum to “Comparison of Different Strategies for Selection/Adaptation of Mixed Microbial Cultures Able to Ferment Crude Glycerol Derived from Second-Generation Biodiesel”



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Interval-Valued Intuitionistic Fuzzy Ordered Weighted Cosine Similarity Measure and Its Application in Investment Decision-Making

We present the interval-valued intuitionistic fuzzy ordered weighted cosine similarity (IVIFOWCS) measure in this paper, which combines the interval-valued intuitionistic fuzzy cosine similarity measure with the generalized ordered weighted averaging operator. The main advantage of the IVIFOWCS measure provides a parameterized family of similarity measures, and the decision maker can use the IVIFOWCS measure to consider a lot of possibilities and select the aggregation operator in accordance with his interests. We have studied some of its main properties and particular cases such as the interval-valued intuitionistic fuzzy ordered weighted arithmetic cosine similarity (IVIFOWACS) measure and the interval-valued intuitionistic fuzzy maximum cosine similarity (IVIFMAXCS) measure. The IVIFOWCS measure not only is a generalization of some similarity measure, but also it can deal with the correlation of different decision matrices for interval-valued intuitionistic fuzzy values. Furthermore, we present an application of IVIFOWCS measure to the group decision-making problem. Finally the existing similarity measures are compared with the IVIFOWCS measure by an illustrative example.

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Multiple pregnancies may increase a woman’s risk of atrial fibrillation

Having multiple pregnancies increases a woman’s risk of developing atrial fibrillation in later life, data from the Women’s Health study published in the journal Circulation have suggested.1Women who...
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Hypoxia-inducible microRNA-210 regulates the DIMT1-IRF4 oncogenic axis in multiple myeloma

Summary

Multiple myeloma (MM) is characterized by the accumulation of a population of malignant plasma cells within the bone marrow and its microenvironment. A hypoxic niche is located within the microenvironment, which causes myeloma cells to become quiescent, anti-apoptotic, glycolytic, and immature. Cell heterogeneity may be related to distinct gene expression profiles under hypoxic and normoxic conditions. During hypoxia, myeloma cells acquire these phenotypes by downregulating interferon regulatory factor 4 (IRF4), an essential transcription factor in myeloma oncogenesis. To identify essential microRNAs and their targets regulated under hypoxic conditions, we performed microRNA and cDNA microarray analysis using hypoxia-exposed primary MM samples and myeloma cell lines. Under hypoxia, only miR-210 was highly upregulated and was accompanied by direct downregulation of an 18S rRNA base methyltransferase DIMT1. This inverse expression correlation was validated by qRT-PCR for primary MM samples. We further determined that DIMT1 has an oncogenic potential as its knockdown reduced tumorigenicity of myeloma cells through regulation of IRF4 expression. Notably, by analyzing gene expression omnibus datasets in the National Center for Biotechnology Information database, we found that DIMT1 expression increased gradually with MM progression. In summary, by screening for targets of hypoxia-inducible miR-210, we identified DIMT1 as a novel diagnostic marker and therapeutic target for all molecular subtypes of MM.

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HER2 somatic mutations are associated with poor survival in HER2-negative breast cancers

Summary

It is well documented that HER2 overexpression/amplification is associated with the poor survival in breast cancer patients. However, it is largely unknown whether HER2 somatic mutations are associated with the survival in HER2-negative breast cancer patients. Here, we identified HER2 somatic mutations in tumors from 1,348 unselected breast cancer patients by sequencing the entire HER2 coding region. All these mutations were tested for in corresponding blood samples to determine whether they were somatic or germline mutations. We further investigated the associations between the HER2 somatic mutations and recurrence-free survival (RFS) and distant recurrence-free survival (DRFS) in this cohort of patients. We found that 27 of 1,348 (2.0%) of these patients carried a HER2 somatic mutation. In vitro experiments demonstrated that some of novel mutations and those with unknown functions increased HER2 activity. HER2 status was available for 1,306 patients, and the HER2 somatic mutation rates in HER2-positive (n=353) and HER2-negative breast cancers (n=953) were 1.4% and 2.3%, respectively. Among the HER2-negative patients, those with a HER2 somatic mutation had a significantly worse recurrence-free survival (unadjusted hazard ratio [HR] =2.67; 95% confidence interval [CI]: 1.25-5.72, P=0.002) and distant recurrence-free survival (unadjusted HR=2.50; 95% CI: 1.10-5.68, P=0.004) than those with wild-type HER2. Taken together, our findings suggested that HER2 somatic mutations occur at a higher frequency in HER2-negative breast cancer, and HER2-negative breast cancer patients with these mutations have poor survival. Therefore, HER2-negative patients with a HER2 somatic mutation are potentially good candidates for HER2-targeted therapy.

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Brain Sciences, Vol. 7, Pages 14: NLRP12 Inflammasome Expression in the Rat Brain in Response to LPS during Morphine Tolerance

Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12 (NLRP12) inflammasome has been reported to have anti-inflammatory activity. In this study, we examined the expression of NLRP12 inflammasome related genes in the adult F344 rat brain in response to the bacterial endotoxin lipopolysaccharide (LPS) in the presence and absence of morphine tolerance. Morphine tolerance was elicited using the 2 + 4 morphine-pelleting protocol. On Day 1, the rats were pelleted subcutaneously with 2 pellets of morphine (75 mg/pellet) or a placebo; on Days 2 and 4 pellets were given. On Day 5, the animals were randomly assigned to receive either 250 µg/kg LPS or saline (i.p.). The expression of 84 inflammasome related genes in the rat brain was examined using a Ploymerase Chain Reaction (PCR) array. In response to LPS, there was a significant increase in the expression of the pro-inflammatory cytokine/chemokine genes interleukin-1 beta (Il-1β), interleukin-6 (Il-6), C-C motif chemokine ligand 2 (Ccl2), C-C motif chemokine ligand 7 (Ccl7), C-X-C motif chemokine ligand 1 (Cxcl1), and C-X-C motif chemokine ligand 3 (Cxcl3) and a significant decrease in the anti-inflammatory NLRP12 gene in both morphine-tolerant and placebo-control rats compared to saline-treated rats, although the changes were greater in the placebo-control animals. The Library of Integrated Network-Based Cellular Signatures’ (LINCS) connectivity map was used to analyze the list of affected genes to identify potential targets associated with the interactions of LPS and morphine tolerance. Our data indicate that, in the morphine tolerant state, the expression of NLRP12 and its related genes is altered in response to LPS and that the Vacuolar protein-sorting-associated protein 28 (VPS28), which is involved in the transport and sorting of proteins into sub-cellular vesicles, may be the key regulator of these alterations.

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Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults

Background: Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation.

Methods: We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMC) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults. Sex-specific associations between several blood OCM indices (folate, vitamin B12, choline, betaine, homocysteine) and PTHMs were examined at baseline using regression models, adjusted for multiple tests by controlling for the false discovery rate (PFDR). We also evaluated the effects of folic acid supplementation (400 μg/d for 12 weeks), compared with placebo, on PTHMs.

Results: Associations between choline and H3K36me2 and between vitamin B12 and H3K79me2 differed significantly by sex (Pdiff < 0.01 and <0.05, respectively). Among men, plasma choline was positively associated with H3K36me2 (PFDR < 0.05), and among women, plasma vitamin B12 was positively associated with H3K79me2 (PFDR < 0.01). Folic acid supplementation did not alter any of the PTHMs examined (PFDR = 0.80).

Conclusions: OCM indices may influence PTHMs in a sex-dependent manner, and folic acid supplementation, at this dose and duration, does not alter PTHMs in PBMCs.

Impact: This is the first study to examine the influences of OCM indices on PTHMs in a population that may have increased susceptibility to cancer development due to widespread exposure to arsenic-contaminated drinking water and a high prevalence of hyperhomocysteinemia. Cancer Epidemiol Biomarkers Prev; 26(2); 261–9. ©2016 AACR.



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Determinants of Light and Intermittent Smoking in the United States: Results from Three Pooled National Health Surveys

Background: Light and/or intermittent smokers have been the fastest growing segment of cigarette smokers in the United States over the past two decades. Defining their behavioral characteristics is a critical public health priority.

Methods: Our sample included 78,229 U.S. adults from three pooled contemporary population-based surveys: the 2012 NHIS, 2012 NSDUH, and 2011–2012 NHANES. We classified current smokers into four categories (light and intermittent [LITS], light-daily, heavier-intermittent, and heavier-daily) and assessed smoking behaviors, illicit drug use, and mental health indicators using weighted analyses.

Results: Analyses associated smoking categories with nicotine dependence, age of smoking initiation, race/ethnicity, and other demographic and behavioral factors. Compared with heavier-daily smokers, smokers who were LITS were most likely to have mild or no nicotine dependence (weighted odds ratio [OR], 16.92; 95% confidence interval [CI], 13.10–21.85), to start smoking cigarettes regularly after age 21 (OR, 3.42; 95% CI, 2.84–4.12), and to be Hispanic (OR, 5.38; 95% CI, 4.38–6.61). Additional significant results were found for other categories of smokers.

Conclusions: Based on pooled data from three large national surveys, light and/or intermittent smokers differed in smoking, drug use, and mental health behaviors from heavier-daily, former, and never smokers. Notable differences by level of smoking frequency and intensity were observed for nicotine dependence, age of smoking initiation, and race/ethnicity.

Impact: Our results may help focus preventive measures and policies for the growing number of light and/or intermittent smokers in the United States because smoking patterns vary by behavioral and socioeconomic factors. Cancer Epidemiol Biomarkers Prev; 26(2); 228–39. ©2016 AACR.



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Metabolic Phenotype and Risk of Colorectal Cancer in Normal-Weight Postmenopausal Women

Background: The prevalence of metabolically unhealthy phenotype in normal-weight adults is 30%, and few studies have explored the association between metabolic phenotype and colorectal cancer incidence in normal-weight individuals. Our aim was to compare the risk of colorectal cancer in normal-weight postmenopausal women who were characterized by either the metabolically healthy phenotype or the metabolically unhealthy phenotype.

Methods: A large prospective cohort, the Women's Health Initiative, was used. The analytic sample included 5,068 postmenopausal women with BMI 18.5 to <25 kg/m2. Metabolic phenotype was defined using the Adult Treatment Panel-III definition, excluding waist circumference; therefore, women with one or none of the four components (elevated triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose) were classified as metabolically healthy. Multivariable Cox proportional hazards regression was used to estimate adjusted HRs for the association between metabolic phenotype and risk of colorectal cancer.

Results: Among normal-weight women, those who were metabolically unhealthy had higher risks of colorectal cancer (HR, 1.49; 95% CI, 1.02–2.18) compared with those who were metabolically healthy.

Conclusions: A metabolically unhealthy phenotype was associated with higher risk of colorectal cancer among normal-weight women.

Impact: Normal-weight women should still be evaluated for metabolic health and appropriate steps taken to reduce their risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 155–61. ©2017 AACR.



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The BRCA1/2 Parent-of-Origin Effect on Breast Cancer Risk--Letter



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Exploring Differences in the Aspirin-Colorectal Cancer Association by Sex and Race/Ethnicity: The Multiethnic Cohort Study

Background: Evidence has accumulated that long-term use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protects against colorectal cancer. We tested whether the inverse associations between NSAIDs and colorectal cancer is similarly observed across sexes and five racial/ethnic groups (Japanese, Latino, African American, Native Hawaiian, and white) in the Multiethnic Cohort (MEC) Study.

Methods: During a mean follow-up of 16.1 years, we identified 4,882 invasive incident colorectal cancer cases among 183,199 eligible participants. Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI).

Results: Use of aspirin and other NSAIDs was associated with a lower incidence of colorectal cancer in men (HR = 0.77; 95% CI, 0.69–0.86 for current vs. never users of aspirin) but not in women (Pinteraction = 0.005). Among male current users, a reduced risk was observed with ≥6 years of aspirin or total NSAID use. The inverse association with current NSAID use in men was observed in all racial/ethnic groups, except for Native Hawaiians, and was stronger in whites.

Conclusions: Our findings suggest that the benefit of NSAIDs for colorectal cancer may be strongest for white men and generalizes to African American, Japanese, and Latino, but not to Native Hawaiian men. The lack of inverse association observed in women and Native Hawaiian men in the MEC should be interpreted with caution.

Impact: As only very few ethnic/racial groups are likely to be represented in trials of NSAIDs and colorectal cancer, it is important to conduct prospective observational studies in various populations to test the generalizability of their results. Cancer Epidemiol Biomarkers Prev; 26(2); 162–9. ©2016 AACR.



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Evaluation of Buccal Cell Samples for Studies of Oral Microbiota

Background: The human microbiota is postulated to affect cancer risk, but collecting microbiota specimens with prospective follow-up for diseases will take time. Buccal cell samples have been obtained from mouthwash for the study of human genomic DNA in many cohort studies. Here, we evaluate the feasibility of using buccal cell samples to examine associations of human microbiota and disease risk.

Methods: We obtained buccal cells from mouthwash in 41 healthy participants using a protocol that is widely employed to obtain buccal cells for the study of human DNA. We compared oral microbiota from buccal cells with that from eight other oral sample types collected by following the protocols of the Human Microbiome Project. Microbiota profiles were determined by sequencing 16S rRNA gene V3–V4 region.

Results: Compared with each of the eight other oral samples, the buccal cell samples had significantly more observed species (P < 0.002) and higher alpha diversity (Shannon index, P < 0.02). The microbial communities were more similar (smaller beta diversity) among buccal cells samples than in the other samples (P < 0.001 for 12 of 16 weighted and unweighted UniFrac distance comparisons). Buccal cell microbial profiles closely resembled saliva but were distinct from dental plaque and tongue dorsum.

Conclusions: Stored buccal cell samples in prospective cohort studies are a promising resource to study associations of oral microbiota with disease.

Impact: The feasibility of using existing buccal cell collections in large prospective cohorts allows investigations of the role of oral microbiota in chronic disease etiology in large population studies possible today. Cancer Epidemiol Biomarkers Prev; 26(2); 249–53. ©2016 AACR.



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The Association between Alcohol Consumption and Breast Density: A Systematic Review and Meta-analysis

Background: Percent breast density (PBD) is a strong risk factor for breast cancer that is influenced by several other risk factors for the disease. Alcohol consumption is associated with an increased risk of breast cancer with an uncertain association with PBD. We have carried out a systematic review and meta-analysis to examine the association of alcohol consumption with PBD.

Methods: We searched nine databases to identify all relevant studies on the association between alcohol intake and breast density. Two independent investigators evaluated and selected 20 studies that were included in our analyses. We divided the studies into three groups according to the methods used to measure and analyze the association of breast density with alcohol consumption.

Results: Meta-analysis of the 11 studies that used quantitative methods to measure and analyze PBD as a continuous variable found a statistically significant difference in PBD when comparing the highest with the lowest alcohol level [β = 0.84; 95% confidence interval (CI), 0.12–1.56]. Three studies that used quantitative methods to measure PBD and categories of PBD for analysis had a summary OR = 1.81 (95% CI, 1.07–3.04). Five studies that used categories to classify PBD and analyze their association with alcohol intake had a summary OR = 1.78 (95% CI, 0.90–3.51).

Conclusions: These results suggest that there is a positive association between alcohol intake and PBD.

Impact: Alcohol may increase the risk of breast cancer associated with PBD. Cancer Epidemiol Biomarkers Prev; 26(2); 170–8. ©2016 AACR.



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Environmental Tobacco Smoke Exposure and Survival Following Breast Cancer

Background: Environmental tobacco smoke (ETS) exposure is hypothesized to influence survival after breast cancer, but few studies have examined this association.

Methods: A population-based cohort of women (N = 1,508) diagnosed with first primary invasive or in situ breast cancer in 1996 to 1997 was interviewed shortly after diagnosis and again approximately 5 years later to assess ETS exposure, and women were followed for more than 18 years using the National Death Index; 597 deaths (237 associated with breast cancer) were identified. Multivariable Cox regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for mortality among women with breast cancer as related to at-diagnosis and at-/postdiagnosis changes in ETS exposure.

Results: There was little or no association between at-diagnosis ETS exposure and all-cause (HR = 1.04; 95% CI, 0.78–1.40) or breast cancer–specific (HR = 0.98; 95% CI, 0.63–1.52) mortality. Mortality was elevated among women who reported cessation in postdiagnosis ETS exposure up to 1 year before the follow-up assessment, for all-cause (HR = 1.81; 95% CI, 0.87–3.74) and breast cancer mortality (HR = 1.89; 95% CI, 0.68–5.24); however, estimates were imprecise.

Conclusions: We found little evidence of an association between at-diagnosis ETS exposure and mortality after breast cancer. Postdiagnosis cessation of ETS exposure was positively associated with mortality, although we could not rule out chance and reverse causation as possible explanations.

Impact: Exposure to ETS does not appear to influence mortality after breast cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 278–80. ©2016 AACR.



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Associations of Postdiagnosis Physical Activity and Change from Prediagnosis Physical Activity with Quality of Life in Prostate Cancer Survivors

Background: This prospective study examined the associations between postdiagnosis physical activity and change from prediagnosis physical activity with quality of life (QoL) in prostate cancer survivors.

Methods: Prostate cancer survivors (N = 830) who participated in a case–control study with invasive stage ≥II disease were followed up to 2007 to capture QoL outcomes. At baseline and three time points postdiagnosis (2000–2007), interviews/questionnaires were used to collect data on physical activity, general QoL measured by the SF-36, and other treatment/lifestyle factors. Multivariable linear regression was used to test the relation between postdiagnosis physical activity and QoL as well as the change in physical activity over the diagnostic period and QoL.

Results: Both total and recreational physical activities were positively associated with physical QoL. Furthermore, when comparing changes in physical activity levels from pre- to postdiagnosis, men who consistently met physical activity guidelines had significantly higher physical [β = 6.01; 95% confidence interval (CI), 4.15–7.86] and mental (β = 2.32; 95% CI, 0.29–4.34) QoL scores compared with those who did not meet guidelines pre- or postdiagnosis. Furthermore, those who adopted and met guidelines had increased QoL, whereas those who relapsed experienced decreased QoL.

Conclusions: Postdiagnosis recreational physical activity is associated with better physical QoL in prostate cancer survivors. Moreover, prostate cancer survivors who maintain or adopt physical activity after diagnosis report substantially higher QoL than men who never exercised or stopped exercising after diagnosis.

Impact: Future intervention studies should focus on achieving and maintaining adherence to physical activity guidelines postdiagnosis in prostate cancer survivors. Cancer Epidemiol Biomarkers Prev; 26(2); 179–87. ©2016 AACR.



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Highlights of This Issue



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Six Serum-Based miRNAs as Potential Diagnostic Biomarkers for Gastric Cancer

Background: Circulating miRNAs in serum may serve as promising diagnostic biomarkers for patients with gastric cancer.

Methods: Using qRT-PCR-based Exiqon panel, we identified 58 differentially expressed miRNAs from three gastric cancer pool samples and one normal control (NC) pool in the initial screening phase. Identified miRNAs were further validated in the training (49 gastric cancer vs. 47 NCs) and validation phases (154 gastric cancer vs. 120 NCs) using qRT-PCR. The expression levels of the miRNAs were also determined in tissues, arterial serum, and exosomes.

Results: Consequently, six serum miRNAs (miR10b-5p, miR132-3p, miR185-5p, miR195-5p, miR-20a3p, and miR296-5p) were significantly overexpressed in gastric cancer compared with NCs. The areas under the receiver operating characteristic curve of the six-miRNA panel were 0.764 and 0.702 for the training and validation phases, respectively. miR10b-5p and miR296-5p were significantly upregulated in gastric cancer tissues (n = 188). In addition, patients who did not receive adjuvant chemotherapy with high expression of miR10b-5p or miR296-5p in tissues tended to suffer worse overall survival. Furthermore, the expression levels of miR10b-5p, miR195-5p, miR20a-3p, and miR296-5p were significantly elevated in exosomes from gastric cancer serum samples (n = 30).

Conclusions: We identified a six-miRNA panel in serum for the detection of gastric cancer.

Impact: Our findings provide a novel serum miRNA signature for gastric cancer diagnosis, and will serve as the basis of the application of circulating miRNAs in clinical for the detection of gastric cancer in the future. Cancer Epidemiol Biomarkers Prev; 26(2); 188–96. ©2016 AACR.



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A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus

Background: There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC.

Methods: We performed a multi-institutional case–control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days).

Results: The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P < 0.0001]. The classifier also provided independent prognostic information that outperformed the subspecialist and generalist diagnosis.

Conclusions: A tissue systems pathology test better predicts prevalent HGD/EAC in Barrett's esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test.

Impact: A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240–8. ©2016 AACR.



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The Stem Cell Factor HMGA2 Is Expressed in Non-HPV-Associated Head and Neck Squamous Cell Carcinoma and Predicts Patient Survival of Distinct Subsites

Background: The transcription factor high-mobility AT-hook 2 (HMGA2) is involved in stem cell renewal and is expressed in many tumor tissues. Head and neck squamous cell carcinomas (HNSCC) comprise tumors of the upper aerodigestive tract and are characterized by high recurrence rates that represent a challenge to patient management. The study addresses the potential of HMGA2 as a molecular biomarker for HNSCC patient survival.

Methods: Patients with HNSCC of the larynx, pharynx, tonsils, or oral cavity were recruited in a hospital-based case–control study (n = 202). Quantitative expression of HMGA2 in tumor tissues was measured by RT-PCR. In a 6- to 10-year follow-up, secondary cancers, vital status, and cause of death were ascertained. The HR and 95% confidence intervals (CI) for overall, tumor-specific, and progression-free survival were estimated by Cox proportional hazards with HMGA2 expression level as the independent variable.

Results: High HMGA2 expression in tumor tissues of HNSCC patients was significantly correlated with negative HPV status (P = 0.01), and associated with shorter overall survival time. In Cox regression modeling, HMGA2 expression yielded a risk increase for overall and tumor-specific death in subsets of HNSCC patients, that is, laryngeal cancer patients (overall survival: HR = 4.00; 95% CI, 1.18–13.62) and in oral cancer patients (tumor-specific survival: HR = 2.88; 95% CI, 1.06–7.84), but not in patients with pharyngeal and tonsillar HNSCC.

Conclusions: HMGA2 expression is associated with a risk increase for adverse outcomes in patients with HNSCC of the larynx and oral cavity.

Impact: The understanding of stem cell signaling in HNSCC may offer new strategies for cancer treatment. Cancer Epidemiol Biomarkers Prev; 26(2); 197–205. ©2016 AACR.



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Reallocating Time to Sleep, Sedentary Time, or Physical Activity: Associations with Waist Circumference and Body Mass Index in Breast Cancer Survivors

Background: Moderate-to-vigorous intensity physical activity (MVPA) is inversely associated with waist circumference and body mass index (BMI) among breast cancer survivors. Limited research has focused on behaviors that account for larger portions of the day [sleep, sedentary time, and light-intensity physical activity (LPA)]. We investigated the interdependent associations of self-reported sleep, objectively assessed prolonged and short bouts of sedentary time, total LPA, and total MVPA with waist circumference and BMI.

Methods: A cross-sectional sample of breast cancer survivors (N = 256, mean age = 60 years; mean time since diagnosis = 3 years) wore an Actigraph GT3X+ accelerometer during waking hours for 7 days. Participants completed the Pittsburgh Sleep Quality Index and self-reported their waist circumference, height, and weight. An isotemporal substitution approach was used in linear regression models to explore the associations of reallocating time to sleep, sedentary and active behaviors on waist circumference, and BMI, after adjusting for potential confounders.

Results: Reallocating 30 minutes to MVPA was significantly associated with lower waist circumference when allocated from sleep (–2.50 cm), prolonged sedentary time (–2.51 cm), or LPA (–2.71 cm). Reallocating 30 minutes of prolonged sedentary time to nonprolonged sedentary time was significantly associated with lower waist circumference (–0.94 cm). Similar results were observed for BMI.

Conclusions: Reallocating 30 minutes to MVPA was associated with significantly lower waist circumference and BMI, as was reallocating 30 minutes of prolonged sedentary time to 30 minutes of nonprolonged sedentary time.

Impact: Increasing MVPA levels and decreasing time spent in prolonged, unbroken sedentary bouts may be avenues for improving body composition in this population. Cancer Epidemiol Biomarkers Prev; 26(2); 254–60. ©2016 AACR.



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Does Insurance Status Influence a Patient’s Hospital Charge?

Abstract

Background

There is obscurity regarding how US hospitals determine patients’ charges. Whether insurance status influences a patient’s hospital charge has not been explored.

Objective

The objective of this study was to determine whether hospitals charge patients differently based on their insurance status.

Methods

This was an analysis of the Florida Hospital Inpatient Data File for fiscal years 2011–2012 (N = 4.7 million). Multivariable regression analysis was used to adjust for patients’ age, sex, length of stay, priority of admission, principal ICD-9-CM diagnosis, and All Payer Refined Diagnosis-Related Group subdivided by Severity of Illness subclass. Hospital fixed effects were included to account for differences in hospitals’ markups.

Results

Compared with those with no insurance, patients with private insurance received hospital bills that were an average of 10.7% higher and patients with Medicare received bills that were an average of 8.9% higher. The impact of Medicaid coverage was imprecisely estimated, but the magnitude of the point-estimate was consistent with 3.5% higher charges to Medicaid patients, relative to the uninsured.

Conclusion

Conditional on patient characteristics, length of stay, and expected intensity of resource utilization, patients with private insurance and patients with Medicare were charged more (before discounting) than their uninsured counterparts within the same hospital.



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Incidence of Facial Nerve Canal Dehiscence in Primary and Revision Cholesteatoma Surgery

Abstract

The aim of this retrospective study was to determine the incidence of facial canal dehiscence (FCD) in primary and revision cholesteatoma surgery in a tertiary referral center. Moreover, our second goal was to identify association between FCD and other intra-operative pathological findings in a group of patients with cholesteatoma surgery. Inclusion criteria were primary and revision canal wall up and canal wall down tympanomastoidectomy in patients who suffers from chronic otitis media (COM) with cholesteatoma. An exclusion criterion was charts with in adequate documentation. In addition tympanoplasty cases were excluded due to evaluate both tympanic and mastoid segments of facial nerve canal. Preoperative clinical data and intra-operative findings were documented in a formatted questionnaire. We found the incidence of FCD in COM surgery was 18%. There was no difference between the primary and revision surgeries regarding its incidence. In addition, there was association between some preoperative or intra-operative findings of COM, such as middle fossa dural dehiscence, external auditory canal polyp, facial nerve paralysis, labyrinthine fistula, and FCD. In conclusions we found that there was no difference between primary and revision surgeries regarding the incidence of FCD. Surgeons should consider effective measures to prevent intra-operative facial nerve trauma in COM surgeries.



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Psychological counseling as an adjunct to stuttering treatment: Clients’ experiences and perceptions

Publication date: Available online 5 February 2017
Source:Journal of Fluency Disorders
Author(s): Alanna Lindsay, Marilyn Langevin




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Koolen-de Vries syndrome

Koolen-de Vries syndrome: a genetic condition caused by changes that eliminate the function of one copy of a genes known as KANSL1. Symptoms include developmental delay and mild to moderate intellectual disability. Other birth defects can be associated with the condition, including a high, broad forehead; drooping of the eyelids (ptosis); narrow eye openings, prominent ears, a bulbous nose, and skin folds covering the inner corner of the eyes (called epicanthal folds). Defects in other organs such as the heart, skeleton, or kidneys, also may be present. It is inherited in an autosomal dominant pattern, meaning that the syndrome is present if one copy of the defective gene is inherited from either parent. Also known as Koolen syndrome.



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Intraoperative high-dose-rate brachytherapy: An American Brachytherapy Society consensus report

Publication date: Available online 5 February 2017
Source:Brachytherapy
Author(s): S. Lloyd, K.M. Alektiar, S. Nag, Y.J. Huang, C.L. Deufel, F. Mourtada, D.K. Gaffney
PurposeThis report presents recommendations from the American Brachytherapy Society for the use of intraoperative high-dose-rate (IOHDR) brachytherapy.Methods and MaterialsMembers of the American Brachytherapy Society with expertise in IOHDR formulated this document based on their clinical experience and a review of the literature. This report covers the use of IOHDR in colorectal cancer, soft tissue sarcoma, gynecologic cancers, head and neck cancers, and pediatric cancers. This report does not cover intraoperative brachytherapy for breast cancer. Details about treatment planning and delivery are emphasized so this document can serve as a guide to practices implementing this technique.ResultsIOHDR brachytherapy is generally most beneficial for patients with either close or positive margins and/or recurrent disease in a previous resection bed or previously irradiated area. IOHDR brachytherapy requires a well-coordinated multidisciplinary team. IOHDR brachytherapy is recommended in the treatment of both recurrent and primary locally advanced disease for colorectal and gynecologic malignancies, soft tissue sarcoma, and selected head and neck and pediatric malignancies. Other techniques such as perioperative fractionated brachytherapy are also acceptable in many cases with some advantages and disadvantages compared to IOHDR.ConclusionsIOHDR brachytherapy is a specialized technique in radiation therapy with unique properties and advantages in cancer control. Special considerations for treatment planning and delivery are outlined herein.



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Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and is the leading cause of blindness in young adults. Oxidative stress has been implicated as a critical cause of DR. Metabolic abnormalities induced by high-glucose levels are involved in the development of DR and appear to be influenced by oxidative stress. The imbalance between reactive oxygen species (ROS) production and the antioxidant defense system activates several oxidative stress-related mechanisms that promote the pathogenesis of DR. The damage caused by oxidative stress persists for a considerable time, even after the blood glucose concentration has returned to a normal level. Animal experiments have proved that the use of antioxidants is a beneficial therapeutic strategy for the treatment of DR, but more data are required from clinical trials. The aims of this review are to highlight the improvements to our understanding of the oxidative stress-related mechanisms underlying the development of DR and provide a summary of the main antioxidant therapy strategies used to treat the disease.

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The Benefit of Neuromuscular Blockade in Patients with Postanoxic Myoclonus Otherwise Obscuring Continuous Electroencephalography (CEEG)

Introduction. Myoclonus status epilepticus is independently associated with poor outcome in coma patients after cardiac arrest. Determining if myoclonus is of cortical origin on continuous electroencephalography (CEEG) can be difficult secondary to the muscle artifact obscuring the underlying CEEG. The use of a neuromuscular blocker can be useful in these cases. Methods. Retrospective review of CEEG in patients with postanoxic myoclonus who received cisatracurium while being monitored. Results. Twelve patients (mean age: 53.3 years; 58.3% male) met inclusion criteria of clinical postanoxic myoclonus. The initial CEEG patterns immediately prior to neuromuscular blockade showed myoclonic artifact with continuous slowing (50%), burst suppression with myoclonic artifact (41.7%), and continuous myogenic artifact obscuring CEEG (8.3%). After intravenous administration of cisatracurium (0.1 mg–2 mg), reduction in artifact improved quality of CEEG recordings in 9/12 (75%), revealing previously unrecognized patterns: continuous EEG seizures (33.3%), lateralizing slowing (16.7%), burst suppression (16.7%), generalized periodic discharges (8.3%), and, in the patient who had an initially uninterpretable CEEG from myogenic artifact, continuous slowing. Conclusion. Short-acting neuromuscular blockade is useful in determining background cerebral activity on CEEG otherwise partially or completely obscured by muscle artifact in patients with postanoxic myoclonus. Fully understanding background cerebral activity is important in prognostication and treatment, particularly when there are underlying EEG seizures.

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Internuclear Ophthalmoplegia Secondary to Cocaine Abuse

Purpose. To report a case of internuclear ophthalmoplegia (INO) caused by cocaine. Method. We report a case of a 54-year-old female who presented with a left INO three days after snorting cocaine, and we review the literature. Results. MRI of the brain demonstrated several small abnormal foci in the pons on FLAIR and diffusion weighted imaging consistent with ischemic infarction. The patient’s symptoms remained stable throughout her hospitalization. She was sent to a rehabilitation facility and was lost to follow-up. Conclusion. In cases of extraocular movement abnormalities, it is important to inquire about recreational drug use.

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A New Ranking Principle For Ordering Trapezoidal Intuitionistic Fuzzy Numbers

Modelling real life (industrial) problems using intuitionistic fuzzy numbers is inevitable in the present scenario due to their efficiency in solving problems and their accuracy in the results. Particularly, trapezoidal intuitionistic fuzzy numbers (TrIFNs) are widely used in describing impreciseness and incompleteness of a data. Any intuitionistic fuzzy decision-making problem requires the ranking procedure for intuitionistic fuzzy numbers. Ranking trapezoidal intuitionistic fuzzy numbers play an important role in problems involving incomplete and uncertain information. The available intuitionistic fuzzy decision-making methods cannot perform well in all types of problems, due to the partial ordering on the set of intuitionistic fuzzy numbers. In this paper, a new total ordering on the class of TrIFNs using eight different score functions, namely, imprecise score, nonvague score, incomplete score, accuracy score, spread score, nonaccuracy score, left area score, and right area score, is achieved and our proposed method is validated using illustrative examples. Significance of our proposed method with familiar existing methods is discussed.

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On the Development of Focused Ultrasound Liquid Atomizers

This paper reviews the evolution of focused ultrasonic transducers of various kinds for fluid atomization and vaporization. Ultrasonic transducers used for atomization purposes in biomedical, pharmaceutical, or industrial applications, such as surface acoustic wave (SAW) transducers, array of micromachined nozzles, and Fourier horn micromachined nozzles with or without a central channel, are all presented and compared. For simplicity of manufacturing and low cost, we focus on plates and curved and corrugated structures for biomedical humidification.

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Treatment of Adults with Anterior Mandibular Teeth Crowding: Reliability of Little’s Irregularity Index

The attempt of this article was to assess reliability of Little’s Irregularity Index (LII) as for stability of the treatment outcomes in adults with crowded mandibular incisors. LII was measured on a digital cast prior to an orthodontic treatment (T1) of the 302 patients thus allowing us to establish the treatment plan, which called for (a) expansion (group 1), interproximal stripping (group 2), or extraction of one of the mandibular incisors. LII was measured after debonding (T2) and a year after retention (T3). Treatment resulted in significant reduction of LII values after treatment, in T1-T2 period in all groups. As for T2-T3 period it brought significant but clinically irrelevant relapse that occurred in groups 1 and 2; group 3 presented with insignificant improvement of occlusion. Conclusively, 30 years after introducing LII it has been a reliable parameter that allows selection of optimal treatment methods, provided that the appropriate ranges of values displaying dentoalveolar discrepancy are obeyed, namely, (1) up to 3 mm: expansion, (2) from 3 to 5 mm: interproximal enamel reduction, and (3) above 5 mm: extraction.

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Comparison of the Fractional Exhaled Nitric Oxide Levels in Adolescents at Three Schools Located Three Different Distances from a Large Steel Mill

Objectives. Exposure to ambient metals and air pollutants in urban environments has been associated with impaired lung health and inflammation in the lungs. Fractional exhaled nitric oxide (FeNO) is a reliable marker of airway inflammation. In this study, we aimed to compare the FeNO levels of three schools that have different distances from iron and steel industry zone for assessing the effects of heavy metals and air pollution on their respiratory health. Methods. Pulmonary function test and FeNO measurements were evaluated in 387 adolescents in three schools which have different distance from plant. Results. FeNO levels were significantly higher in School I (;  ppb) and School II (;  ppb) than School III (;  ppb). Increased FeNO concentration was related to the distance of iron and steel industry zone in young adults. Conclusion. The FeNO concentrations in school children were inversely proportional to the distance from the steel mill. There are needed some studies that can evaluate the safe distance and legislation must consider these findings.

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Docetaxel-Induced Systemic Sclerosis with Internal Organ Involvement Masquerading as Congestive Heart Failure

Systemic sclerosis, or scleroderma, is a complex medical disorder characterized by limited or diffuse skin thickening with frequent involvement of internal organs such as lungs, gastrointestinal tract, or kidneys. Docetaxel is a chemotherapeutic agent which has been associated with cutaneous side effects. An uncommon cutaneous side effect of docetaxel is scleroderma-like skin changes that extend from limited to diffuse cutaneous systemic sclerosis. Several case reports have been published regarding the association of docetaxel and systemic sclerosis. However, those reports demonstrated the association between docetaxel and scleroderma-like skin changes without internal organ involvement. Here, we report a case of systemic sclerosis with pulmonary arterial hypertension and a microangiopathic kidney involvement induced by docetaxel chemotherapy. After an exhaustive literature review, this could be the first case of docetaxel-induced systemic sclerosis involving internal organs.

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Study of the Thermal Properties of Raffia Bamboo Vinifera L. Arecaceae

Raffia is a kind of fast-growing palm tree, from the family of Arecaceae, encountered in marshy areas and along rivers. In this study, the “Raffia Bamboo” is the stalk of a palm, made of a fragile marrow inside a thin shell, smooth and hard to protect the latter. In our region, this material is widely used to build all the low-cost traditional houses and furniture, to make granaries storage of dry products, to build chicken coops, to make decoration. Thus, various jobs are organized around this material, with the fight against poverty. To our knowledge, information on its thermal properties is almost nonexistent. The experimental determination of the transverse thermal properties of the dry shell, the dry marrow, and the whole dry bamboo helped to find, for each, a specific heat, a thermal diffusivity, a thermal conductivity, and finally a thermal effusivity. From the analysis of results, we deduce that the thermal properties of raffia bamboo vinifera L. Arecacea make it a very good thermal insulator.

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Assessment of Aerobic Exercise Adverse Effects during COPD Exacerbation Hospitalization

Introduction. Aerobic exercise performed after hospital discharge for exacerbated COPD patients is already recommended to improve respiratory and skeletal muscle strength, increase tolerance to activity, and reduce the sensation of dyspnea. Previous studies have shown that anaerobic activity can clinically benefit patients hospitalized with exacerbated COPD. However, there is little information on the feasibility and safety of aerobic physical activity performed by patients with exacerbated COPD during hospitalization. Objective. To evaluate the effects of aerobic exercise on vital signs in hospitalized patients with exacerbated COPD. Patients and Methods. Eleven COPD patients (63% female, FEV1: 34.2 ± 13.9% and age: 65 ± 11 years) agreed to participate. Aerobic exercise was initiated 72 hours after admission on a treadmill; speed was obtained from the distance covered in a 6-minute walk test (6MWT). Vital signs were assessed before and after exercise. Results. During the activity systolic blood pressure increased from 125.2 ± 13.6 to 135.8 ± 15.0 mmHg () and respiratory rate from 20.9 ± 4.4 to 24.2 ± 4.5 rpm () and pulse oximetry (SpO2) decreased from 93.8 ± 2.3 to 88.5 ± 5.7% (). Aerobic activity was considered intense, heart rate ranged from 99.2 ± 11.5 to 119.1 ± 11.1 bpm at the end of exercise (), and patients reached on average 76% of maximum heart rate. Conclusion. Aerobic exercise conducted after 72 hours of hospitalization in patients with exacerbated COPD appears to be safe.

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Clinical Analysis of Algerian Patients with Pompe Disease

Pompe’s disease is a metabolic myopathy caused by a deficiency of acid alpha-glucosidase (GAA), also called acid maltase, an enzyme that degrades lysosomal glycogen. The clinical presentation of Pompe’s disease is variable with respect to the age of onset and rate of disease progression. Patients with onset of symptoms in early infancy (infantile-onset Pompe disease (IOPD)) typically exhibit rapidly progressive hypertrophic cardiomyopathy and marked muscle weakness. Most of them die within the first year of life from cardiac and/or respiratory failure. In the majority of cases of Pompe’s disease, onset of symptoms occurs after infancy, ranging widely from the first to sixth decade of life (late-onset Pompe’s disease or LOPD). Progression of the disease is relentless and patients eventually progress to loss of ambulation and death due to respiratory failure. The objective of this study was to characterize the clinical presentation of 6 patients (3 with EOPD and the other 3 with LOPD) of 5 families from the East of Algeria. All our patients were diagnosed as having Pompe’s disease based on biochemical confirmations of GAA deficiency by dried blood spots (DBS) and GAA gene mutations were analyzed in all patients who consented (). Our results are similar to other ethnic groups.

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American Thyroid Association Awards Research Grant

research-grants.png

Supported by ThyCa: Thyroid Cancer Survivors’ Association, Inc. Research Grant to Trevor Angell, MD, Brigham and Women’s Hospital and Harvard Medical School

The American Thyroid Association (ATA) has awarded 85 thyroid research grants totaling over $2.2 million since the inception of the Research Fund. In addition, the ATA rigorously manages the selection of research projects and distribution of over $1.8 million generously donated to the ATA specifically for research grants from ThyCa: Thyroid Cancer Survivors’ Association, Inc. (ThyCa) and Bite Me Cancer.  For information on other research grants underway and funded by the ATA, see http://ift.tt/2l3TSGC.

The ATA has awarded a 2016 ThyCa Research Grant to Trevor Angell, MD, Instructor in the Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston MA, for his project entitled “Assessment of Circulation Immune Suppressor Cells for Predicating Treatment Response in Follicular Cell Derived Thyroid Carcinoma.” The goal of this prospective study is to determine whether changes in the levels of myeloid derived suppressor cells (MDSC) in the peripheral blood of patients with thyroid cancer before and after therapy can serve as a predictive biomarker for response to treatment.

MDSCs are a type of immune cell that prevents the body’s anti-tumor immune cells from doing their job and destroying cancer. Dr. Angell has proposed that MDSCs, which are rare in healthy individuals but tend to accumulate when cancer is present, can be used for personalized risk assessment and to monitor an individual’s response to treatment in patients with papillary or anaplastic thyroid cancer. The ability to use changes in MDSC levels as a biomarker for disease progression and therapeutic drug response would give clinicians valuable information to guide treatment decisions.

Dr. Angell says, “After initial diagnosis and treatment for thyroid cancer, many patients worry about the possibility of residual cancer, cancer recurrence, or progression of their disease. Thanks to scientific investigators and organizations such as the American Thyroid Association, there have been tremendous advances in predicting the course of thyroid cancer, but there continue to be many cases with uncertainty. Novel method to provide individualized risk assessment would help clinicians and patients better understand and treat thyroid cancer. We are excited to investigate MDSC measurement as a promising biomarker for cancer behavior, and gratefully acknowledge both the ATA and ThyCa for providing essential research grants and being passionate advocates for scientific exploration, innovation, and improved patient care.”

ThyCa: Thyroid Cancer Survivors’ Association, Inc. has provided funding in support of 60 special research grants totaling $1,680,000 focused on thyroid cancer and medullary thyroid cancer since 2003. ThyCa supported three research grants in 2016 and three renewing grants; and plans are underway for similar support in 2017. ThyCa is a member of the ATA Alliance for Patient Education. Find out more at www.thyca.org.

Bite Me Cancer (BMC) is our newest grant funder supporting five thyroid cancer grants since 2014 for a total of $143,750. BMC will be supporting a new thyroid cancer grant in 2016 and one renewing grant. BMC is a member of the ATA Alliance for Patient Education. Find out more at www.bitemecancer.org.

 

###

 

The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization for over 1,700 clinicians and researchers from 43 countries around the world, representing a broad diversity of medical disciplines. It also serves the public, patients and their family through education and awareness efforts

Celebrating its 94th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology, VideoEndocrinology and Clinical Thyroidology for the Public; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease.

The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization for over 1,700 clinicians and researchers from 43 countries around the world, representing a broad diversity of medical disciplines. It also serves the public, patients and their family through education and awareness efforts

Celebrating its 94th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, THYROID, Clinical Thyroidology, VideoEndocrinology and Clinical Thyroidology for the Public; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease.

More information about ATA is found at www.thyroid.org.

 

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Genotoxicity of lipid oxidation compounds

Publication date: Available online 5 February 2017
Source:Free Radical Biology and Medicine
Author(s): Peter M. Eckl, Nikolaus Bresgen
Lipid peroxidation, the oxidative degradation of membrane lipids by reactive oxygen species generates a large variety of breakdown products such as alkanes, aldehydes, ketones, alcohols, furans and others. Due to their reactivity aldehydes (alkanals, 2-alkenals, 2,4-alkadienals, 4-hydroxyalkenals) received a lot of attention, in particular because they can diffuse from the site of formation and interact with proteins and nucleic acids thus acting as second toxic messengers. The major aldehydic peroxidation product of membrane lipids is 4-hydroxynonenal (HNE). Since HNE and other 4-hydroxyalkenals are strong alkylating agents they have therefore been considered to be the biologically most important peroxidation products.Although initially research focused on the toxicological potential of these compounds it is now well known that they play also a crucial role in cell signaling under physiological and pathophysiological conditions.Thus, it is obvious that the biological effects will be determined by the intracellular concentrations which can trigger adaptation, DNA damage and cell death. This review will not cover all these aspects but will concentrate on the genotoxic properties of selected lipid oxidation products important in the context of pathophysiological developments together with a chapter on epigenetic modifications.

Graphical abstract

image


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Proteomics Tracing the Footsteps of Infectious Disease [Perspective]

Every year, a major cause of human disease and death worldwide is infection with the various pathogens - viruses, bacteria, fungi, and protozoa - that are intrinsic to our ecosystem. In efforts to control the prevalence of infectious disease and develop improved therapies, the scientific community has focused on building a molecular picture of pathogen infection and spread. These studies have been aimed at defining the cellular mechanisms that allow pathogen entry into hosts cells, their replication and transmission, as well as the core mechanisms of host defense against pathogens. The past two decades have demonstrated the valuable implementation of proteomic methods in all these areas of infectious disease research. Here, we provide a perspective on the contributions of mass spectrometry and other proteomics approaches to understanding the molecular details of pathogen infection. Specifically, we highlight methods used for defining the composition of viral and bacterial pathogens and the dynamic interaction with their hosts in space and time. We discuss the promise of MS-based proteomics in supporting the development of diagnostics and therapies, and the growing need for multi-omics strategies for gaining a systems view of pathogen infection.



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Potential therapeutic targets of epithelial–mesenchymal transition in melanoma

Publication date: 10 April 2017
Source:Cancer Letters, Volume 391
Author(s): Ross L. Pearlman, Mary Katherine Montes de Oca, Harish Chandra Pal, Farrukh Afaq
Melanoma is a cutaneous neoplastic growth of melanocytes with great potential to invade and metastasize, especially when not treated early and effectively. Epithelial-mesenchymal transition (EMT) is the process by which melanocytes lose their epithelial characteristics and acquire mesenchymal phenotypes. Mesenchymal protein expression increases the motility, invasiveness, and metastatic potential of melanoma. Many pathways play a role in promotion of mesenchymal protein expression including RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, Wnt/β-catenin, and several others. Downstream effectors of these pathways induce expression of EMT transcription factors including Snail, Slug, Twist, and Zeb that promote repression of epithelial and induction of mesenchymal character. Emerging research has demonstrated that a variety of small molecule inhibitors as well as phytochemicals can influence the progression of EMT and may even reverse the process, inducing re-expression of epithelial markers. Phytochemicals are of particular interest as supplementary treatment options because of their relatively low toxicities and anti-EMT properties. Modulation of EMT signaling pathways using synthetic small molecules and phytochemicals is a potential therapeutic strategy for reducing the aggressive progression of metastatic melanoma. In this review, we discuss the emerging pathways and transcription factor targets that regulate EMT and evaluate potential synthetic small molecules and naturally occurring compounds that may reduce metastatic melanoma progression.



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The new issue is now available.Japanese Journal of Infection Prevention and Control

Vol.31 No.6

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The new issue is now available.Journal of Information and Communication Research

Vol.34 No.2

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The new issue is now available.Journal of the Principles of Home Economics

Vol.36

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The new issue is now available.Journal of Information and Communication Research

Vol.34 No.3

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The new issue is now available.Journal of the Principles of Home Economics

Vol.39

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The new issue is now available.Journal of the Principles of Home Economics

Vol.37

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The new issue is now available.Aeronautical and Space Sciences Japan

Vol.65 No.2

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The new issue is now available.Animal Behaviour and Management

Vol.43 No.1

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The new issue is now available.Animal Behaviour and Management

Vol.45 No.3

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The new issue is now available.Animal Behaviour and Management

Vol.45 No.4

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The new issue is now available.Chikyukagaku

Vol.43 No.2

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The new issue is now available.Angioscopy

Vol.3 No.1

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The new issue is now available.Japanese Journal of Electoral Studies

Vol.24 No.2

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The new issue is now available.Animal Behaviour and Management

Vol.52 No.1

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The new issue is now available.Animal Behaviour and Management

Vol.51 No.4

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The new issue is now available.Animal Behaviour and Management

Vol.43 No.4

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newly available online.Advanced Experimental Mechanics



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The new issue is now available.Animal Behaviour and Management

Vol.42 No.4

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The new issue is now available.Journal of the Principles of Home Economics

Vol.35

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The new issue is now available.Animal Behaviour and Management

Vol.44 No.4

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Nanoscale electrical properties of ZnO nanorods grown by chemical bath deposition

Abstract

Well-aligned zinc oxide nanorod arrays (ZNAs) synthesized using chemical bath deposition were fabricated on a gallium-doped zinc oxide substrate, and the effects of varying the precursor concentrations on the growth and nanoscale electrical properties of the ZNAs were investigated. The as-synthesized ZNAs were characterized using field-emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), conducting atomic force microscopy (CAFM), and scanning surface potential microscopy (SSPM). The FESEM and AFM images show that the growth rate in terms of length and diameter is highly sensitive to the precursor concentration. CAFM and SSPM analyses indicate that when concentrations of both the zinc acetate and hexamethylenetetramine solutions were 30 mM, the coverage percentages of the recordable and conducting regions on the ZNA surface were 48.3% and 0.9%, which is suitable for application in resistive random access memory devices.

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The typical I-V curve on ZNAs (inset) shows set and reset at the same polarity and such a relationship is expected for unipolar memory behavior.



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Comparative study of dental enamel loss after debonding braces by analytical scanning electron microscopy (SEM)

Abstract

Clinical procedures when shear forces are applied to brackets suggest adhesion forces between 2.8 and 10.0 MPa as appropriate. In this study dental enamel was evaluated by scanning electron microscopy (SEM) before and after removing the brackets. Thirty bicuspids (previous prophylaxis) with metallic brackets (Roth Inovation 0.022 GAC), Transbond Plus SEP 3M Unitek adhesive and Transbond XT 3M resin were used. The samples were preserved to 37°C during 24 hr and submited to tangential forces with the Instron Universal machine 1.0 mm/min speed load strength resistance debonding. Also the Adhesive Remanent Index (ARI) test was made, evaluating the bracket base and the bicuspid surface. All the bracket SEM images were processed with AutoCAD to determine the enamel detached area. The average value was 6.86 MPa (SD ± 3.2 MPa). ARI value 1= 63.3%, value 2= 20%, value 3= 13.3% and 33% presented value 0. All those samples with dental enamel loss, presented different situations as fractures, ledges, horizontal, and vertical loss in some cases, and some scratch lines. There is no association between the debonding resistance and enamel presence. Less than half of the remanent adhesive on the dental enamel was present in most of the samples when the ARI test was applied. When the resin area increases, the debonding resistance also increases, and when the enamel loss increases, the resin free metallic area of the bracket base decreases in the debonding.

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Bracket detachable at 3.34 MPa (clinically adequate value to avoid damage to the enamel), where we can observe resin (r), lost enamel (e) and mesh metal area (m), as well as edges, fractures and scratch lines in the limit of the enamel loss area.



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Persistent extra-radicular bacterial biofilm in endodontically treated human teeth: Scanning electron microscopy analysis after apical surgery

Abstract

Biofilms are the main cause of endodontic failures. Even the best executed endodontic treatment can fail, when the infection is resistant to treatment or when it is located in inaccessible areas, such as the external surface of the root apex. The purpose of this study was to evaluate, by scanning electron microscopy, the presence of bacterial biofilm on endodontically treated teeth considered clinical failures and suitable for apical surgery. Root apices were collected from 20 teeth undergoing apical surgery and one negative control and analyzed under SEM. Digital photomicrographs of the root apices of 21 specimens at different magnifications were taken. Data were analyzed using descriptive statistics. Apical biofilms were observed in 100% of root canal treatments considered endodontic failure. Topographical analysis of the root apices revealed areas of resorption, microcracks, and apical foramina in 90%, 80%, and 50% of cases, respectively. Within the limits of this study, it can be concluded that endodontic failures present bacterial biofilm in areas inaccessible to conventional endodontic treatment, such as the external surfaces of the root apex.



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Craniopharyngioma presenting with severe hyponatremia, hyponatremia-induced myopathy, and panhypopituitarism: a case report

Craniopharyngiomas are rare intracranial tumors commonly presenting with neurological symptoms. Reports of severe hyponatremia as a presenting manifestation of a craniopharyngioma and hyponatremia-induced myop...

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An Electrophysiological Investigation of Emotional Abnormalities in Groups at Risk for Schizophrenia-Spectrum Personality Disorders

Publication date: Available online 5 February 2017
Source:Biological Psychology
Author(s): Elizabeth A. Martin, Nicole R. Karcher, Bruce D. Bartholow, Greg J. Siegle, John G. Kerns
Both extreme levels of social anhedonia (SocAnh) and perceptual aberration/magical ideation (PerMag) are associated with risk for schizophrenia-spectrum disorders and with emotional abnormalities. Yet, the nature of any psychophysiological-measured affective abnormality, including the role of automatic/controlled processes, is unclear. We examined the late positive potential (LPP) during passive viewing (to assess automatic processing) and during cognitive reappraisal (to assess controlled processing) in three groups: SocAnh, PerMag, and controls. The SocAnh group exhibited an increased LPP when viewing negative images. Further, SocAnh exhibited greater reductions in the LPP for negative images when told to use strategies to alter negative emotion. Similar to SocAnh, PerMag exhibited an increased LPP when viewing negative images. However, PerMag also exhibited an increased LPP when viewing positive images as well as an atypical decreased LPP when increasing positive emotion. Overall, these results suggest that at-risk groups are associated with shared and unique automatic and controlled abnormalities.



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Profiling of human epigenetic regulators using a semi-automated real-time qPCR platform validated by next generation sequencing

Publication date: 20 April 2017
Source:Gene, Volume 609
Author(s): Amel Dudakovic, Martina Gluscevic, Christopher R. Paradise, Halil Dudakovic, Farzaneh Khani, Roman Thaler, Farah S. Ahmed, Xiaodong Li, Allan B. Dietz, Gary S. Stein, Martin A. Montecino, David R. Deyle, Jennifer J. Westendorf, Andre J. van Wijnen
Epigenetic mechanisms control phenotypic commitment of mesenchymal stromal/stem cells (MSCs) into osteogenic, chondrogenic or adipogenic lineages. To investigate enzymes and chromatin binding proteins controlling the epigenome, we developed a hybrid expression screening strategy that combines semi-automated real-time qPCR (RT-qPCR), next generation RNA sequencing (RNA-seq), and a novel data management application (FileMerge). This strategy was used to interrogate expression of a large cohort (n>300) of human epigenetic regulators (EpiRegs) that generate, interpret and/or edit the histone code. We find that EpiRegs with similar enzymatic functions are variably expressed and specific isoforms dominate over others in human MSCs. This principle is exemplified by analysis of key histone acetyl transferases (HATs) and deacetylases (HDACs), H3 lysine methyltransferases (e.g., EHMTs) and demethylases (KDMs), as well as bromodomain (BRDs) and chromobox (CBX) proteins. Our results show gender-specific expression of H3 lysine 9 [H3K9] demethylases (e.g., KDM5D and UTY) as expected and upregulation of distinct EpiRegs (n>30) during osteogenic differentiation of MSCs (e.g., HDAC5 and HDAC7). The functional significance of HDACs in osteogenic lineage commitment of MSCs was functionally validated using panobinostat (LBH-589). This pan-deacetylase inhibitor suppresses osteoblastic differentiation as evidenced by reductions in bone-specific mRNA markers (e.g., ALPL), alkaline phosphatase activity and calcium deposition (i.e., Alizarin Red staining). Thus, our RT-qPCR platform identifies candidate EpiRegs by expression screening, predicts biological outcomes of their corresponding inhibitors, and enables manipulation of the human epigenome using molecular or pharmacological approaches to control stem cell differentiation.



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Detailed expression profile of all six Glypicans and their modifying enzyme Notum during chick embryogenesis and their role in dorsal-ventral patterning of the neural tube

Publication date: 20 April 2017
Source:Gene, Volume 609
Author(s): Kawakeb Saad, Anthony Otto, Susanne Theis, Niki Kennerley, Andrea Munsterberg, Graham Luke, Ketan Patel
Vertebrate development is orchestrated by secreted signalling molecules that regulate cell behaviour and cell fate decisions during early embryogenesis. The activity of key signalling molecules including members of Hedgehog, Bone Morphogenetic Proteins and Wnt families are regulated by Glypicans, a family of GPI linked polypeptides. Glypicans either promote or inhibit the action of signalling molecules and add a layer of complexity that needs to be understood in order to fully decipher the processes that regulate early vertebrate development. Here we present a detailed expression profile of all six Glypicans and their modifying enzyme Notum during chick embryogenesis. Our results strongly suggest that these proteins have many as yet undiscovered roles to play during early embryogenesis. Finally, we have taken an experimental approach to investigate their role during the patterning of a key embryonic structure - the neural tube. In particular, we show that over-expression of Notum leads to the dorsalisation of this structure.



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Editorial Board

Publication date: 5 April 2017
Source:Gene, Volume 607





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Retinal Image Denoising via Bilateral Filter with a Spatial Kernel of Optimally Oriented Line Spread Function

Filtering belongs to the most fundamental operations of retinal image processing and for which the value of the filtered image at a given location is a function of the values in a local window centered at this location. However, preserving thin retinal vessels during the filtering process is challenging due to vessels’ small area and weak contrast compared to background, caused by the limited resolution of imaging and less blood flow in the vessel. In this paper, we present a novel retinal image denoising approach which is able to preserve the details of retinal vessels while effectively eliminating image noise. Specifically, our approach is carried out by determining an optimal spatial kernel for the bilateral filter, which is represented by a line spread function with an orientation and scale adjusted adaptively to the local vessel structure. Moreover, this approach can also be served as a preprocessing tool for improving the accuracy of the vessel detection technique. Experimental results show the superiority of our approach over state-of-the-art image denoising techniques such as the bilateral filter.

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Finite Temperature QCD Sum Rules: A Review

The method of QCD sum rules at finite temperature is reviewed, with emphasis on recent results. These include predictions for the survival of charmonium and bottonium states, at and beyond the critical temperature for deconfinement, as later confirmed by lattice QCD simulations. Also included are determinations in the light-quark vector and axial-vector channels, allowing analysing the Weinberg sum rules and predicting the dimuon spectrum in heavy-ion collisions in the region of the rho-meson. Also, in this sector, the determination of the temperature behaviour of the up-down quark mass, together with the pion decay constant, will be described. Finally, an extension of the QCD sum rule method to incorporate finite baryon chemical potential is reviewed.

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The Multiagent Planning Problem

The classical Multiple Traveling Salesmen Problem is a well-studied optimization problem. Given a set of goals/targets and agents, the objective is to find round trips, such that each target is visited only once and by only one agent, and the total distance of these round trips is minimal. In this paper we describe the Multiagent Planning Problem, a variant of the classical Multiple Traveling Salesmen Problem: given a set of goals/targets and a team of agents, subtours (simple paths) are sought such that each target is visited only once and by only one agent. We optimize for minimum time rather than minimum total distance; therefore the objective is to find the Team Plan in which the longest subtour is as short as possible (a min–max problem). We propose an easy to implement Genetic Algorithm Inspired Descent (GAID) method which evolves a set of subtours using genetic operators. We benchmarked GAID against other evolutionary algorithms and heuristics. GAID outperformed the Ant Colony Optimization and the Modified Genetic Algorithm. Even though the heuristics specifically developed for Multiple Traveling Salesmen Problem (e.g., -split, bisection) outperformed GAID, these methods cannot solve the Multiagent Planning Problem. GAID proved to be much better than an open-source Matlab Multiple Traveling Salesmen Problem solver.

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On Dynamical Behavior of a Friction-Induced Oscillator with 2-DOF on a Speed-Varying Traveling Belt

The dynamical behavior of a friction-induced oscillator with 2-DOF on a speed-varying belt is investigated by using the flow switchability theory of discontinuous dynamical systems. The mechanical model consists of two masses and a speed-varying traveling belt. Both of the masses on the traveling belt are connected with three linear springs and three dampers and are harmonically excited. Different domains and boundaries for such system are defined according to the friction discontinuity. Based on the above domains and boundaries, the analytical conditions of the passable motions, stick motions, and grazing motions for the friction-induced oscillator are obtained mathematically. An analytical prediction of periodic motions is performed through the mapping dynamics. With appropriate mapping structure, the simulations of the stick and nonstick motions in the two-degree friction-induced oscillator are illustrated for a better understanding of the motion complexity.

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The impact of different mutations at Arg54 on structure, chaperone-like activity and oligomerization state of human αA-crystallin: The pathomechanism underlying congenital cataract-causing mutations R54L, R54P and R54C

Publication date: Available online 4 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Kazem Khoshaman, Reza Yousefi, Ali Mohammad Tamaddon, Samira Sadat Abolmaali, Ahmad Oryan, Ali Akbar Moosavi-Movahedi, Boris I. Kurganov
A major part of cataractogenic mutations in human αA-Crystallin (αA-Cry) occurs at Arg residues. While Arg54 is highly conserved within different species, the cataractogenic mutations R54L, R54P and R54C have been recently identified in CRYAA gene, encoding human αA-Cry. The detailed structural and functional aspects, stability and amyloidogenic properties of αA-Cry were determined upon the above-mentioned missense mutations, using various spectroscopic techniques, gel electrophoresis, electron microscopy, size exclusion HPLC analyses, and chaperone-like activity assay. The different mutations at Arg54 result in diverse structural alterations among mutant proteins. In addition, the mutant proteins displayed reduced thermal stability, increased amyloidogenic properties and attenuated chaperone-like activity against aggregation of γ-Cry, catalase and lysozyme. The mutant proteins were also capable of forming larger oligomeric complexes with γ-Cry which is the natural partner of α-Cry in the eye lenses. The most significant structural and functional damages were observed upon R54L mutation which was also accompanied with increased oligomeric size distribution of the mutant protein. The cataractogenic nature of R54P mutation can be explained with its detrimental effect on chaperone-like activity, conformational stability and proteolytic digestibility of the mutant protein. Also, R54C αA-Cry displayed an important intrinsic propensity for disulfide protein cross-linking with significantly reduced chaperone-like activity against all client proteins. These mutations revealed a range of detrimental effects on the structure, stability and functional properties of αA-Cry which all together can explain the pathomechanisms underlying development of the associated congenital cataract disorders.

Graphical abstract

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Crystallographic structure of recombinant Lactococcus lactis prolidase to support proposed structure-function relationships

Publication date: Available online 4 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Oarabile Kgosisejo, Jian An Chen, Pawel Grochulski, Takuji Tanaka
Lactococcus lactis prolidase (Xaa-Pro dipeptidase; EC.3.4.13.9) is unique from other prolidases by showing allosteric behaviour, substrate inhibition, and metal-dependent substrate specificity. We have previously shown several critical residues for these characteristics using site-directed mutagenesis and amino acid sequence-based models. In this present study, the three-dimensional structure of recombinant L. lactis prolidase was determined by X-ray crystallography at 2.25Å resolution in order to provide evidences of the proposed mechanism. Three molecules are located in the crystal asymmetric unit where molecule A forms a dimer with molecule B, while molecule C forms a dimer with molecule C″” in the adjacent asymmetric unit. Of all the three molecules, molecule C is less defined and incomplete. While this fact compromises the overall quality of the refined model, the functional interpretation of the structure is not compromised since the biologically-functional homodimeric configuration of L. lactis prolidase is represented by well-defined molecules A and B. The refined model confirmed that there is a twelve-residue (residues 32–43) loop structure from one subunit over the active site of the other subunit, proving the existence of the putative loop structure in our previous study. This loop is three amino acids longer than the loops of prolidases of Pyrococcus furious (1pv9) and Pyrococcus horikoshii OT3 (1wy2). The crystal structure shows the loop structure can form two states (“open” and “closed” states) through interaction between the loop and active site proximity. It supports the proposed formation of allosteric site by the loop and Arg 293.



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Perihepatic, Pulmonary, and Renal Abscesses Due to Spilled Gallstones

Publication date: Available online 4 February 2017
Source:The Journal of Emergency Medicine
Author(s): Jacob Lentz, Maria A. Tobar, Caleb P. Canders
BackgroundSpilled gallstones are common during laparoscopic cholecystectomy; however, they rarely lead to postoperative complications. Perihepatic abscesses develop in < 0.1% of patients with spilled gallstones and are typically contained within the peritoneal cavity.Case ReportWe present a 57-year-old man with history of cholecystectomy 2 years prior who presented with cough and flank pain and was discovered to have a perihepatic abscess invading his lung and kidney secondary to a spilled gallstone.Why Should Emergency Physicians Be Aware of This?Although most perihepatic abscesses can be treated with percutaneous drainage and antibiotics, abscesses secondary to spilled gallstones usually require open or laparoscopic surgery to drain the abscess and retrieve the gallstone. Prompt identification of spilled gallstones in patients with intra-abdominal and intrathoracic abscesses can thereby guide disposition and decrease morbidity and mortality.



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Emergency Medicine Myths: Epinephrine in Cardiac Arrest

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Publication date: Available online 4 February 2017
Source:The Journal of Emergency Medicine
Author(s): Brit Long, Alex Koyfman
BackgroundSudden cardiac arrest accounts for approximately 15% of deaths in developed nations, with poor survival rate. The American Heart Association states that epinephrine is reasonable for patients with cardiac arrest, though the literature behind its use is not strong.ObjectiveTo review the evidence behind epinephrine for cardiac arrest.DiscussionSudden cardiac arrest causes over 450,000 deaths annually in the United States. The American Heart Association recommends epinephrine may be reasonable in patients with cardiac arrest, as part of Advanced Cardiac Life Support. This recommendation is partly based on studies conducted on dogs in the 1960s. High-dose epinephrine is harmful and is not recommended. Epinephrine may improve return of spontaneous circulation, but does not improve survival to discharge or neurologic outcome. Literature suggests that three phases of resuscitation are present: electrical, circulatory, and metabolic. Epinephrine may improve outcomes in the circulatory phase prior to 10 min post arrest, though further study is needed. Basic Life Support measures including adequate chest compressions and early defibrillation provide the greatest benefit.ConclusionsEpinephrine may improve return of spontaneous circulation, but it does not improve survival to discharge or neurologic outcome. Timing of epinephrine may affect patient outcome, but Basic Life Support measures are the most important aspect of resuscitation and patient survival.



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Ileal Neobladder: An Important Cause of Non-Anion Gap Metabolic Acidosis

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Publication date: Available online 4 February 2017
Source:The Journal of Emergency Medicine
Author(s): Jesse W. St. Clair, Matthew L. Wong
BackgroundThe differential diagnosis for a non-anion gap metabolic acidosis is probably less well known than the differential diagnosis for an anion gap metabolic acidosis. One etiology of a non-anion gap acidosis is the consequence of ileal neobladder urinary diversion for the treatment of bladder cancer.Case ReportWe present a case of a patient with an ileal neobladder with a severe non-anion gap metabolic acidosis caused by a urinary tract infection and ureteroenterostomy.Why Should an Emergency Physician Be Aware of This?Part of the ileal neobladder surgery includes ureteroenterostomy and predisposes patients to several clinically significant metabolic derangements, including a non-anion gap metabolic acidosis. These patients have an increased chronic acid load, bicarbonate deficit, and hypokalemia, which should be appreciated when resuscitating these patients.



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Acute Hypotonia in an Infant

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Publication date: Available online 4 February 2017
Source:The Journal of Emergency Medicine
Author(s): Jimme Sierakowski, Jason Arthur, Todd Wylie
BackgroundAcute flaccid myelitis (AFM) is increasing in incidence in the United States and presenting to emergency departments (EDs) across the country. This clinical entity presents as acute paralysis, with magnetic resonance imaging changes in the gray matter only in children younger than 21 years of age. The etiology is unknown, although preceding viral illnesses are common. There are no consensus guidelines regarding treatment.Case ReportA 4-month-old girl presented with decreased bilateral arm movement. The history consisted of a recent upper respiratory illness and abrupt decline in movement. She was found to have truncal and peripheral hypotonia, while maintaining her airway. Magnetic resonance imaging found gray matter hyperintensity at C2–C6, with no white matter changes. The patient was positive for enterovirus. Intravenous steroids and intravenous immunoglobulin were given, with slight improvement prior to discharge to an inpatient rehabilitation center.Why Should an Emergency Physician Be Aware of This?AFM was largely nonexistent in the United States after implementation of the polio vaccine, but the incidence has recently increased. Pediatric patients are now presenting to EDs with acute hypotonia, and emergency physicians must recognize how to differentiate this emerging diagnosis from other causes of acute flaccid paralysis. The clinical course of AFM does not seem to change acutely, in stark contrast to disease entities like botulism, which can change in hours. Patients with AFM do not need aggressive ED diagnostic evaluation, but rather transfer to a pediatric hospital for further care. Therefore, discerning the etiology of pediatric hypotonia with history and physical examination alone is important.



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Parental High-Fat Diet Promotes Inflammatory and Senescence-Related Changes in Prostate

Background. Obesity and dietary habits are associated with increased incidences of aging-related prostatic diseases. The present study was aimed to investigate transgenerational effects of chronic high-fat diet (HFD) feeding on inflammation and senescence-related changes in prostate. Methods. Sprague-Dawley rats were kept on either normal or HFD one. Senescence-associated β-galactosidase (SA β-gal) activity, inflammation, and cellular proliferation were determined in the prostate. Results. Increased SA β-gal activity, expression of p53, and cell proliferation marker PCNA were observed in ventral prostate of HFD-fed rats. Immunostaining for p53 and PCNA revealed that the p53 immunopositive cells were primarily in stroma while PCNA immunopositive cells were epithelial cells. An increase in expression of cycloxygenase-2 (COX-2) and phosphorylation of nuclear factor-kappa B (NF-kB) was observed in prostate of weaning pups HFD-fed parents. However, in adult pups, irrespective of dietary habit, a significant increase in the expression of COX-2, PCNA, phosphorylation of NF-kB, infiltration of inflammatory cells, and SA β-gal activity was observed. Conclusions. Present investigation reports that HFD feeding promotes accumulation of p53 expressing cells, proliferation of epithelial cells, and senescence-related changes in prostate. Further, parental HFD-feeding upholds inflammatory, proliferative, and senescence-related changes in prostate of pups.

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Assessment of Antiretroviral Treatment Adherence among Children Attending Care at a Tertiary Hospital in Southeastern Nigeria

Background. Adherence is the strongest predictor of successful treatment outcome among children infected with HIV. Our aim was to assess the antiretroviral drugs adherence status of HIV-infected children attending care at a tertiary hospital in Southeastern Nigeria. Method. The study involved a cross-sectional survey of 210 HIV-infected children attending care at a tertiary hospital in Southeastern Nigeria using self-report method of assessment. Optimal ART adherence is defined as patient taking not missing more than 1 dose of combined antiretroviral therapy medication in the preceding 2 weeks prior to the study. Result. A majority of the subjects 191 (91%) had good adherence. There was a significant relationship between adherence and patient educational level (), duration of treatment (), drug administrator (), and orphan status (). The motivating factor for adherence was “not falling sick as before” while stigma was the most discouraging factor. Conclusion. The adherence level in this study was good. Stigma was an important reason given by patient/caregivers for nonadherence. There is need for concerted effort in addressing this barrier to improve adherence and prevent the emergence of drug resistance and treatment failure.

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