Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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Non-Gradient Blue Native Polyacrylamide Gel Electrophoresis.

Fri, 02/03/2017 - 16:52

Non-Gradient Blue Native Polyacrylamide Gel Electrophoresis.

Curr Protoc Protein Sci. 2017 Feb 02;87:19.29.1-19.29.12

Authors: Luo X, Wu J, Jin Z, Yan LJ

Abstract
Gradient blue native polyacrylamide gel electrophoresis (BN-PAGE) is a well established and widely used technique for activity analysis of high-molecular-weight proteins, protein complexes, and protein-protein interactions. Since its inception in the early 1990s, a variety of minor modifications have been made to this gradient gel analytical method. Here we provide a major modification of the method, which we call non-gradient BN-PAGE. The procedure, similar to that of non-gradient SDS-PAGE, is simple because there is no expensive gradient maker involved. The non-gradient BN-PAGE protocols presented herein provide guidelines on the analysis of mitochondrial protein complexes, in particular, dihydrolipoamide dehydrogenase (DLDH) and those in the electron transport chain. Protocols for the analysis of blood esterases or mitochondrial esterases are also presented. The non-gradient BN-PAGE method may be tailored for analysis of specific proteins according to their molecular weight regardless of whether the target proteins are hydrophobic or hydrophilic. © 2017 by John Wiley & Sons, Inc.

PMID: 28150881 [PubMed - in process]

Adequate dietary fiber supplement along with TONE concept can help avoid surgery in most patients with advanced hemorrhoids.

Fri, 02/03/2017 - 16:52
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Adequate dietary fiber supplement along with TONE concept can help avoid surgery in most patients with advanced hemorrhoids.

Minerva Gastroenterol Dietol. 2017 Feb 01;:

Authors: Garg P, Singh P

Abstract
BACKGROUND: The root cause of hemorrhoids are three deranged defecation habits (DDH) - (1) increased straining, (2) prolonged defecation-time and, (3) frequent bowel-motions. These DDH are responsible for development of new hemorrhoids, progression of existing hemorrhoids and hemorrhoidal rupture (bleeding). DDH can be corrected by TONE concept. TONE entails specifying exact treatment goals (T-Three minutes at defecation, O-Once a day defecation- frequency, N-No straining during passing motions, E-Enough fiber). TONE can be implemented by proper counseling and by prescribing fiber supplement appropriately (5-6 teaspoonfuls of psyllium husk with 600 ml of water daily). Corrected DDH would prevent the progression of hemorrhoids and bleeding. An office procedure may be done to further downgrade the hemorrhoids.
METHODS: Patients with advanced hemorrhoids (grade III & IV) who were referred for surgery were prescribed fiber supplement and were counseled to follow TONE. The outcome parameters evaluated were- improvement in prolapse, bleeding episodes, satisfaction levels.
RESULTS: 102 patients (Male/Female: 75/10, age 46.0 ±13.5 years, 17 lost to follow-up) with advanced hemorrhoids (grades: early III-41, late III-38 & IV-6) were included in the study. All patients had symptoms of prolapsed and bleeding was present in 71.8% (61/85) patients. After the follow-up of 40 (12-96) months, 68.2% (58/85) patients were highly satisfied, 12.9% (11/85) were moderately satisfied and 18.9% (16/85) were not satisfied with treatment. Prolapse improved in 56.5%(48/85), didn't progress over time in 25.9(22/85) and continued to progress in 4.7 %(4/85) patients. 12.9% (11/85) underwent operation for hemorrhoids. Bleeding episodes decreased from 71.8% (61/85) to 29.4%(25/85) (p<0.0001,Fischer's).
CONCLUSIONS: Adequate fiber supplement coupled with TONE concept can correct deranged defecation habits and can thus prevent progression of hemorrhoids and bleeding and the need for surgery in most patients with advanced hemorrhoids.

PMID: 28150480 [PubMed - as supplied by publisher]

Primary Cutaneous Diffuse Large B-Cell Lymphoma With a MYC-IGH Rearrangement and Gain of BCL2: Expanding the Spectrum of MYC/BCL2 Double-Hit Lymphomas.

Wed, 02/01/2017 - 07:34
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Primary Cutaneous Diffuse Large B-Cell Lymphoma With a MYC-IGH Rearrangement and Gain of BCL2: Expanding the Spectrum of MYC/BCL2 Double-Hit Lymphomas.

Am J Dermatopathol. 2016 Oct;38(10):769-74

Authors: Testo N, Olson LC, Subramaniyam S, Hanson T, Magro CM

Abstract
Aggressive extracutaneous B-cell lymphomas span the various stages of B-cell ontogeny and include B-cell lymphoblastic lymphoma, Burkitt lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma. Diffuse large B-cell lymphomas represent the most common histologic subtype of non-Hodgkin lymphomas, comprising 30% of adult non-Hodgkin lymphomas in the United States. A distinctive form of diffuse large B-cell lymphoma is the double-hit lymphoma, with most cases exhibiting a combined MYC and BCL2 rearrangement, leading some hematopathologists to propose the term MYC/BCL2 lymphoma. More recently, MYC rearrangement with multiple copies/gain of BCL2 or multiple copies/gain of MYC with a BCL2 rearrangement have been described and exhibit a very similar clinical course to conventional double-hit lymphomas. We report the seventh case of diffuse large B-cell lymphoma exhibiting this distinct cytogenetic abnormality and the first reported case in the skin. The patient's clinical course was aggressive, succumbing to disease 18 months after his initial presentation.

PMID: 27391453 [PubMed - indexed for MEDLINE]

Massively parallel sequencing of forensic STRs: Considerations of the DNA commission of the International Society for Forensic Genetics (ISFG) on minimal nomenclature requirements.

Sat, 01/28/2017 - 07:32
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Massively parallel sequencing of forensic STRs: Considerations of the DNA commission of the International Society for Forensic Genetics (ISFG) on minimal nomenclature requirements.

Forensic Sci Int Genet. 2016 May;22:54-63

Authors: Parson W, Ballard D, Budowle B, Butler JM, Gettings KB, Gill P, Gusmão L, Hares DR, Irwin JA, King JL, Knijff Pd, Morling N, Prinz M, Schneider PM, Neste CV, Willuweit S, Phillips C

Abstract
The DNA Commission of the International Society for Forensic Genetics (ISFG) is reviewing factors that need to be considered ahead of the adoption by the forensic community of short tandem repeat (STR) genotyping by massively parallel sequencing (MPS) technologies. MPS produces sequence data that provide a precise description of the repeat allele structure of a STR marker and variants that may reside in the flanking areas of the repeat region. When a STR contains a complex arrangement of repeat motifs, the level of genetic polymorphism revealed by the sequence data can increase substantially. As repeat structures can be complex and include substitutions, insertions, deletions, variable tandem repeat arrangements of multiple nucleotide motifs, and flanking region SNPs, established capillary electrophoresis (CE) allele descriptions must be supplemented by a new system of STR allele nomenclature, which retains backward compatibility with the CE data that currently populate national DNA databases and that will continue to be produced for the coming years. Thus, there is a pressing need to produce a standardized framework for describing complex sequences that enable comparison with currently used repeat allele nomenclature derived from conventional CE systems. It is important to discern three levels of information in hierarchical order (i) the sequence, (ii) the alignment, and (iii) the nomenclature of STR sequence data. We propose a sequence (text) string format the minimal requirement of data storage that laboratories should follow when adopting MPS of STRs. We further discuss the variant annotation and sequence comparison framework necessary to maintain compatibility among established and future data. This system must be easy to use and interpret by the DNA specialist, based on a universally accessible genome assembly, and in place before the uptake of MPS by the general forensic community starts to generate sequence data on a large scale. While the established nomenclature for CE-based STR analysis will remain unchanged in the future, the nomenclature of sequence-based STR genotypes will need to follow updated rules and be generated by expert systems that translate MPS sequences to match CE conventions in order to guarantee compatibility between the different generations of STR data.

PMID: 26844919 [PubMed - indexed for MEDLINE]

M3 Macrophages Stop Division of Tumor Cells In Vitro and Extend Survival of Mice with Ehrlich Ascites Carcinoma.

Fri, 01/27/2017 - 07:33
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M3 Macrophages Stop Division of Tumor Cells In Vitro and Extend Survival of Mice with Ehrlich Ascites Carcinoma.

Med Sci Monit Basic Res. 2017 Jan 26;23:8-19

Authors: Kalish S, Lyamina S, Manukhina E, Malyshev Y, Raetskaya A, Malyshev I

Abstract
BACKGROUND M1 macrophages target tumor cells. However, many tumors produce anti-inflammatory cytokines, which reprogram the anti-tumor M1 macrophages into the pro-tumor M2 macrophages. We have hypothesized that the problem of pro-tumor macrophage reprogramming could be solved by using a special M3 switch phenotype. The M3 macrophages, in contrast to the M1 macrophages, should respond to anti-inflammatory cytokines by increasing production of pro-inflammatory cytokines to retain its anti-tumor properties. Objectives of the study were to form an M3 switch phenotype in vitro and to evaluate the effect of M3 macrophages on growth of Ehrlich ascites carcinoma (EAC) in vitro and in vivo. MATERIAL AND METHODS Tumor growth was initiated by an intraperitoneal injection of EAC cells into C57BL/6J mice. RESULTS 1) The M3 switch phenotype can be programed by activation of M1-reprogramming pathways with simultaneous inhibition of the M2 phenotype transcription factors, STAT3, STAT6, and/or SMAD3. 2) M3 macrophages exerted an anti-tumor effect both in vitro and in vivo, which was superior to anti-tumor effects of cisplatin or M1 macrophages. 3) The anti-tumor effect of M3 macrophages was due to their anti-proliferative effect. CONCLUSIONS Development of new biotechnologies for restriction of tumor growth using in vitro reprogrammed M3 macrophages is very promising.

PMID: 28123171 [PubMed - in process]

Kienböck Disease: A New Algorithm for the 21st Century.

Thu, 01/26/2017 - 07:34
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Kienböck Disease: A New Algorithm for the 21st Century.

J Wrist Surg. 2017 Feb;6(1):2-10

Authors: Lichtman DM, Pientka WF, Bain GI

Abstract
Background It has been over 100 years since the initial description of avascular necrosis of the lunate. Over the last two decades, there has been the introduction of advanced information regarding the etiology, natural history, classification, and treatment options for lunate osteonecrosis. There have been new classifications developed based on advanced imaging, perfusion studies of lunate viability, and arthroscopic assessment of the articular cartilage. Purpose This article brings together a new treatment algorithm, incorporating the traditional osseous classification system (Lichtman) with the perfusion/viability classification (Schmitt) and the articular cartilage classification (Bain). Methods We have developed a new algorithm to manage Kienböck avascular necrosis of the lunate. This new algorithm incorporates the current concepts of the diseased lunate and its effects on the remainder of the wrist. Conclusion For patients with a good prognosis and in the earliest stages, the "intact lunate" is initially protected utilizing nonoperative measures. If this fails, then appropriate lunate unloading procedures should be considered. If the lunate is "compromised" then it can be reconstructed with a medial femoral condyle graft or proximal row carpectomy (PRC). With the further collapse of the lunate, the wrist is then also compromised, with the development of secondary degeneration of the central column articulation. The "compromised wrist" will have functional articulations, which allows motion-preserving procedures to be utilized to maintain a functional wrist. With advanced disease (Kienböck disease advanced collapse), the wrist is not reconstructable, so only a salvage procedure can be performed. Other than these objective pathoanatomical factors, the final decision must accommodate the various patient factors (e.g., age, general health, lifestyle, financial constraints, and future demands on the wrist) and surgeon factors (skill set, equipment, and work environment).

PMID: 28119790 [PubMed - in process]

A home-based exercise program for children with congenital heart disease following interventional cardiac catheterization: study protocol for a randomized controlled trial.

Wed, 01/25/2017 - 07:33
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A home-based exercise program for children with congenital heart disease following interventional cardiac catheterization: study protocol for a randomized controlled trial.

Trials. 2017 Jan 23;18(1):38

Authors: Du Q, Salem Y, Liu HH, Zhou X, Chen S, Chen N, Yang X, Liang J, Sun K

Abstract
BACKGROUND: Cardiac catheterization has opened an innovative treatment field for cardiac disease; this treatment is becoming the most popular approach for pediatric congenital heart disease (CHD) and has led to a significant growth in the number of children with cardiac catheterization. Unfortunately, based on evidence, it has been demonstrated that the majority of children with CHD are at an increased risk of "non-cardiac" problems. Effective exercise therapy could improve their functional status significantly. As studies identifying the efficacy of exercise therapy are rare in this field, the aims of this study are to (1) identify the efficacy of a home-based exercise program to improve the motor function of children with CHD with cardiac catheterization, (2) reduce parental anxiety and parenting burden, and (3) improve the quality of life for parents whose children are diagnosed with CHD with cardiac catheterization through the program.
METHODS/DESIGN: A total of 300 children who will perform a cardiac catheterization will be randomly assigned to two groups: a home-based intervention group and a control group. The home-based intervention group will carry out a home-based exercise program, and the control group will receive only home-based exercise education. Assessments will be undertaken before catheterization and at 1, 3, and 6 months after catheterization. Motor ability quotients will be assessed as the primary outcomes. The modified Ross score, cardiac function, speed of sound at the tibia, functional independence of the children, anxiety, quality of life, and caregiver burden of their parents or the main caregivers will be the secondary outcome measurements.
DISCUSSION: The proposed prospective randomized controlled trial will evaluate the efficiency of a home-based exercise program for children with CHD with cardiac catheterization. We anticipate that the home-based exercise program may represent a valuable and efficient intervention for children with CHD and their families.
TRIAL REGISTRATION: http://www.chictr.org.cn/ on: ChiCTR-IOR-16007762 . Registered on 13 January 2016.

PMID: 28115007 [PubMed - in process]

Distinct Classes of Negative Alcohol-Related Consequences in a National Sample of Incoming First-Year College Students: A Latent Class Analysis.

Wed, 01/25/2017 - 07:33
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Distinct Classes of Negative Alcohol-Related Consequences in a National Sample of Incoming First-Year College Students: A Latent Class Analysis.

Alcohol Alcohol. 2016 Sep;51(5):602-8

Authors: Rinker DV, Diamond PM, Walters ST, Wyatt TM, DeJong W

Abstract
UNLABELLED: : First-year college students are at particular risk for experiencing negative alcohol-related consequences that may set the stage for experiencing such consequences in later life. Latent class analysis is a person-centered approach that, based on observable indicator variables, divides a population into mutually exclusive and exhaustive groups ('classes'). To date, no studies have examined the latent class structure of negative alcohol-related consequences experienced by first-year college students just before entering college.
AIMS: The aims of this study were to (a) identify classes of first-year college students based on the patterns of negative alcohol-related consequences they experienced just before entering college, and (b) determine whether specific covariates were associated with class membership.
METHODS: Incoming freshmen from 148 colleges and universities (N = 54,435) completed a baseline questionnaire as part of an alcohol education program they completed just prior to their first year of college. Participants answered questions regarding demographics and other personal characteristics, their alcohol use in the past 2 weeks, and the negative alcohol-related consequences they had experienced during that time.
RESULTS: Four distinct classes of students emerged: (a) No Problems, (b) Academic Problems, (c) Injured Self and (d) Severe Problems. Average number of drinks per drinking day, total number of drinking days, age of drinking initiation, intention to join a fraternity or sorority and family history of alcohol problems were associated with membership in all of the problem classes relative to the No Problems class.
CONCLUSIONS: These results can inform future campus-based prevention efforts.

PMID: 27325885 [PubMed - indexed for MEDLINE]

Nitric oxide- and cisplatin-releasing silica nanoparticles for use against non-small cell lung cancer.

Wed, 01/25/2017 - 07:33
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Nitric oxide- and cisplatin-releasing silica nanoparticles for use against non-small cell lung cancer.

J Inorg Biochem. 2015 Dec;153:23-31

Authors: Munaweera I, Shi Y, Koneru B, Patel A, Dang MH, Di Pasqua AJ, Balkus KJ

Abstract
Nitric oxide (NO) and cisplatin releasing wrinkle-structured amine-modified mesoporous silica (AMS) nanoparticles have been developed for the treatment of non-small cell lung cancer (NSCLC). The AMS and NO- and cisplatin-loaded AMS materials were characterized using TEM, BET surface area, FTIR and ICP-MS, and tested in cell culture. The results show that for NSCLC cell lines (i.e., H596 and A549), the toxicity of NO- and cisplatin-loaded silica nanoparticles (NO-Si-DETA-cisplatin-AMS) is significantly higher than that of silica nanoparticles loaded with only cisplatin (Si-DETA-cisplatin-AMS). In contrast, the toxicity of NO-Si-DETA-cisplatin-AMS toward normal lung cell lines is not significantly different from that of Si-DETA-cisplatin-AMS (normal lung fibroblast cells WI-38) or is even lower than that of Si-DETA-cisplatin-AMS (normal lung epithelial cells BEAS-2B). The NO-induced sensitization of tumor cell death demonstrates that NO is a promising enhancer of platinum-based lung cancer therapy.

PMID: 26402659 [PubMed - indexed for MEDLINE]

Whistle-blowing in Medical School: A National Survey on Peer Accountability and Professional Misconduct in Medical Students.

Wed, 01/25/2017 - 07:33
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Whistle-blowing in Medical School: A National Survey on Peer Accountability and Professional Misconduct in Medical Students.

Acad Psychiatry. 2016 Jun;40(3):530-3

Authors: Hodges LE, Tak HJ, Curlin FA, Yoon JD

Abstract
OBJECTIVE: This study examines medical students' attitudes towards peer accountability.
METHODS: A nationally representative sample of 564 third year medical students was surveyed. Students reported their agreement or disagreement with two statements: "I feel professionally obligated to report peers whose personal behaviors compromise their professional responsibilities" and "I feel professionally obligated to report peers who I believe are seriously unfit to practice medicine."
RESULTS: The majority of students (81.6 %) either agreed strongly or agreed somewhat that they feel obligated to report peers whose personal behaviors compromise their professional responsibilities. The majority (84.1 %) also agreed that they feel professionally obligated to report peers who they believe are seriously unfit to practice medicine.
CONCLUSION: In contrast with previous studies, this national study found that a significant majority of students reported that they feel obligated to report unfit peers.

PMID: 26319785 [PubMed - indexed for MEDLINE]

The anticancer drug sunitinib promotes autophagyand protects from neurotoxicity in an HIV-1 Tat model of neurodegeneration.

Sat, 01/21/2017 - 07:55
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The anticancer drug sunitinib promotes autophagyand protects from neurotoxicity in an HIV-1 Tat model of neurodegeneration.

J Neurovirol. 2017 Jan 19;:

Authors: Fields JA, Metcalf J, Overk C, Adame A, Spencer B, Wrasidlo W, Florio J, Rockenstein E, He JJ, Masliah E

Abstract
Despite the success of antiretroviral therapies to control systemic HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HANDs) has not decreased among aging patients with HIV. Autophagy pathway alterations, triggered by HIV-1 proteins including gp120, Tat, and Nef, might contribute to the neurodegenerative process in aging patients with HAND. Although no treatments are currently available to manage HAND, we have previously shown that sunitinib, an anticancer drug that blocks receptor tyrosine-kinase and cyclin kinase pathways, might be of interest. Studies in cancer models suggest that sunitinib might also modulate autophagy, which is dysregulated in our models of Tat-induced neurotoxicity. We evaluated the efficacy of sunitinib to promote autophagy in the CNS and ameliorate neurodegeneration using LC3-GFP-expressing neuronal cells challenged with low concentrations of Tat and using inducible Tat transgenic mice. In neuronal cultures challenged with low levels of Tat, sunitinib increased markers of autophagy such as LC3-II and reduced p62 accumulation in a dose-dependent manner. In vivo, sunitinib treatment restored LC3-II, p62, and endophilin B1 (EndoB1) levels in doxycycline-induced Tat transgenic mice. Moreover, in these animals, sunitinib reduced the hyperactivation of CDK5, tau hyperphosphorylation, and p35 cleavage to p25. Restoration of CDK5 and autophagy were associated with reduced neurodegeneration and behavioral alterations. Alterations in autophagy in the Tat tg mice were associated with reduced levels of a CDK5 substrate, EndoB1, and levels of total EndoB1 were normalized by sunitinib treatment. We conclude that sunitinib might ameliorate Tat-mediated autophagy alterations and may decrease neurodegeneration in aging patients with HAND.

PMID: 28105557 [PubMed - as supplied by publisher]

Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells.

Thu, 01/19/2017 - 07:35
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Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells.

Oncotarget. 2017 Jan 14;:

Authors: Sankpal UT, Goodison S, Jones-Pauley M, Hurtado M, Zhang F, Basha R

Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are being tested extensively for their role in the treatment and prevention of several cancers. Typically NSAIDs exhibit anti-tumor activities via modulation of cyclooxygenase (COX)-dependent mechanisms, however, an anti-cancer NSAID tolfenamic acid (TA) is believed to work through COX-independent pathways. Results from our laboratory and others have demonstrated the anti-cancer activity of TA in various cancer models including pancreatic cancer. TA has been shown to modulate certain cellular processes including, apoptosis, reactive oxygen species and signaling. In this study, molecular profiling was performed to precisely understand the mode of action of TA. Three pancreatic cancer cell lines, L3.6pl, MIA PaCa-2, and Panc1 were treated with TA (50 μM for 48 h) and the changes in gene expression was evaluated using the Affymetrix GeneChip Human Gene ST Array platform. Microarray results were further validated using quantitative PCR for seven genes altered by TA treatment in all three cell lines. Functional analysis of differentially expressed genes (2 fold increase or decrease, p < 0.05) using Ingenuity Pathway Analysis software, revealed that TA treatment predominantly affected the genes involved in cell cycle, cell growth and proliferation, and cell death and survival. Promoter analysis of the differentially expressed genes revealed that they are enriched for Sp1 binding sites, suggesting that Sp1 could be a major contributor in mediating the effect of TA. The gene expression studies identified new targets involved in TA's mode of action, while supporting the hypothesis about the association of Sp1 in TA mediated effects in pancreatic cancer.

PMID: 28099934 [PubMed - as supplied by publisher]

Enhancement of Pathologist's Routine Practice: Reuse of DNA Extracted from Immunostained Formalin-fixed Paraffin-embedded (FFPE) Slides in Downstream Molecular Analysis of Cancer.

Thu, 01/19/2017 - 07:35
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Enhancement of Pathologist's Routine Practice: Reuse of DNA Extracted from Immunostained Formalin-fixed Paraffin-embedded (FFPE) Slides in Downstream Molecular Analysis of Cancer.

Cancer Genomics Proteomics. 2016 09-10;13(5):399-406

Authors: Al-Attas A, Assidi M, Al-Maghrabi J, Dallol A, Schulten HJ, Abu-Elmagd M, Chaudhary A, Abuzenadah A, Budowle B, Buhmeida A, Al-Qahtani M

Abstract
BACKGROUND/AIM: To date, the conventional formalin-fixed, paraffin-embedded (FFPE) technique is the gold-standard for preserving histomorphology. Once FFPE tissues are stained, slides are routinely archived along with their blocks at biobanks/hospitals. However, the reuse of fixed and stained biospecimens as DNA source is not a common routine practice worldwide and, thus, indicates the need of studies to investigate the feasibility of extracting DNA from already immunohistochemistry (IHC) FFPE-stained slides and its possible reuse in subsequent downstream molecular analyses.
MATERIALS AND METHODS: FFPE IHC slides from colorectal cancer (CRC) patients were prepared and stored in the CEGMR Biobank. The workflow consists of digitalization of IHC stained slide's image, removing the slide cover-slip, crude dissection and DNA extraction. Following DNA quality assessment, mutation analysis of CTNNB1 and methylation profile of CDH1 were performed.
RESULTS: High-quality DNA was obtained allowing 60% concordance between CDH1 methylation and membranous E-cadherin expression pattern. Clean CTNNB1 DNA chromatograms with evenly-spaced peaks were observed.
CONCLUSION: This study is a proof of concept to recycle and reuse DNA from IHC stained slides with suitable concentration and integrity for further downstream molecular applications. These findings will enhance the pathologists' knowledge, attitudes and practices (KAP) towards the use of these biospecimens and support the implementation of this approach in clinical pathology practice. Therefore, the scientific community will benefit from the largest comprehensive database of human fully annotated FFPE biospecimens already available at their disposal in order to demystify the complexity and the heterogeneity of many challenging diseases and foster the transition towards precision medicine.

PMID: 27566658 [PubMed - indexed for MEDLINE]

Magnetic Resonance Imaging (MRI): Operative Findings Correlation in 229 Fistula-in-Ano Patients.

Wed, 01/18/2017 - 13:37
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Magnetic Resonance Imaging (MRI): Operative Findings Correlation in 229 Fistula-in-Ano Patients.

World J Surg. 2017 Jan 17;:

Authors: Garg P, Singh P, Kaur B

Abstract
BACKGROUND: To correlate the operative findings of patients with fistula-in-ano with preoperative MRI and quantify the information added with MRI.
METHODS: All consecutive fistula-in-ano patients operated between July 2013 and May 2015 were prospectively enrolled. Preoperative MRI was done in every patient. The details of tracts, internal opening and "complex parameters" (additional tract or additional internal opening, horseshoe tract, associated abscess and supralevator extension) found at surgery were compared to the findings determined by MRI.
RESULTS: A total of 229 patients (424 tracts) with mean age-49.0 ± 11.3 years were included. M/F 198/31. James hospital classification: Type I 58, II 20, III 49, IV 86 and V 16. The sensitivity and specificity of MRI in diagnosing fistula tracts were 98.8 and 99.7%, respectively, and in identifying internal opening were 97.7 and 98.6%, respectively. MRI added significant information in 46.7% (107/229) patients which was presence of additional tracts in 71 (66.3%), horseshoe tract in 63 (58.8%), supralevator extension in 16 (14.9%), unsuspected abscess in 11 (10.3%) and multiple internal openings in one patient (1%). The proportion of simple/complex fistula (based on history and clinical examination alone) was 32.8/67.2% which changed to 21.4/78.6% after the MRI scan. MRI added significant information about unsuspecting complex parameters which were missed on history and clinical examination in more than one-third (26/75: 34.6%) of simple fistulae and more than half (81/154: 52.5%) of already known complex fistulae.
CONCLUSIONS: MRI is highly accurate in diagnosing fistula-in-ano and added significant information about unsuspected complex parameters in over one-third (34.6%) of simple and in half (52.5%) of complex fistula-in-ano.

PMID: 28097414 [PubMed - as supplied by publisher]

Prevalence and Predictors of Hypertension in the Labor Force Population in China: Results from a Cross-sectional Survey in Xinjiang Uygur Autonomous Region.

Wed, 01/18/2017 - 13:37
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Prevalence and Predictors of Hypertension in the Labor Force Population in China: Results from a Cross-sectional Survey in Xinjiang Uygur Autonomous Region.

Biomed Environ Sci. 2016 04;29(4):290-4

Authors: Xu de M, Li XF, Goan D, Yang de M, Li JM, Wang X, Huang YL, Chen YS

Abstract
The objective of this study was to examine the prevalence of hypertension and identify its contributory factors in the labor force population in Karamay. A total of 2819 adults (55.9% male adults) were interviewed and examined. The overall crude prevalence of hypertension was 32.4%. Among 914 hypertensive patients, 34.8% were aware of their diagnosis, 22.1% received treatment, and 5.6% achieved blood pressure control. Hypertension was significantly correlated with age, overweight/obesity, central obesity, diabetes, and dyslipidemia in both men and women. In addition, less education, alcohol consumption, and less walking were risk factors for men. Effective hypertension prevention and control programs are urgently needed to decrease the burden of hypertension in this region.

PMID: 27241740 [PubMed - indexed for MEDLINE]

Chemical Conditioning as an Approach to Ischemic Stroke Tolerance: Mitochondria as the Target.

Tue, 01/17/2017 - 07:34
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Chemical Conditioning as an Approach to Ischemic Stroke Tolerance: Mitochondria as the Target.

Int J Mol Sci. 2016 Mar 08;17(3):351

Authors: Jin Z, Wu J, Yan LJ

Abstract
It is well established that the brain can be prepared to resist or tolerate ischemic stroke injury, and mitochondrion is a major target for this tolerance. The preparation of ischemic stroke tolerance can be achieved by three major approaches: ischemic conditioning, hypoxic conditioning and chemical conditioning. In each conditioning approach, there are often two strategies that can be used to achieve the conditioning effects, namely preconditioning (Pre-C) and postconditioning (Post-C). In this review, we focus on chemical conditioning of mitochondrial proteins as targets for neuroprotection against ischemic stroke injury. Mitochondrial targets covered include complexes I, II, IV, the ATP-sensitive potassium channel (mitoKATP), adenine dinucleotide translocase (ANT) and the mitochondrial permeability transition pore (mPTP). While numerous mitochondrial proteins have not been evaluated in the context of chemical conditioning and ischemic stroke tolerance, the paradigms and approaches reviewed in this article should provide general guidelines on testing those mitochondrial components that have not been investigated. A deep understanding of mitochondria as the target of chemical conditioning for ischemic stroke tolerance should provide valuable insights into strategies for fighting ischemic stroke, a leading cause of death in the world.

PMID: 27005615 [PubMed - indexed for MEDLINE]

People's reasons for wanting to complete probation: Use and predictive validity in an e-health intervention.

Mon, 01/16/2017 - 07:41
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People's reasons for wanting to complete probation: Use and predictive validity in an e-health intervention.

Eval Program Plann. 2017 Jan 06;61:144-149

Authors: Spohr SA, Taxman FS, Walters ST

Abstract
The criminal justice system tends to emphasize external contingencies (e.g., fees, jail time) to motivate offender compliance. However, people's reasons for desistance vary considerably. This study evaluated the acceptability, utility, and predictive validity of questions that ask about people's reasons for wanting to successfully complete probation. Substance-using probationers (N=113) participated in a web-based computer intervention that targeted substance use and treatment initiation. Questions around seven dimensions of reasons for completing probation were developed to provide tailored feedback during the web-based program. A principle components factor analysis found that survey items loaded onto two distinct factors. Factor one, "Tangible Loss" focused on external and present-focused reasons. Factor two, "Better Life" focused on internal and future-focused reasons. There was a significant negative association between Better Life scores and days of substance use after two months (β=-0.31, SE=0.13, p<0.05). There was a significant positive association with Better Life scores and days of treatment attendance (β=1.46, SE=0.26, p<0.001). Tangible Loss scores were no associated with substance use and treatment attendance. These findings may help to create more effective motivational tracks in e-health interventions, and may complement traditional motivation measures with an explicit focus on people's stated reasons for wanting to complete probation.

PMID: 28088674 [PubMed - as supplied by publisher]

Cullin Neddylation May Allosterically Tune Polyubiquitin Chain Length and Topology.

Sat, 01/14/2017 - 07:43
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Cullin Neddylation May Allosterically Tune Polyubiquitin Chain Length and Topology.

Biochem J. 2017 Jan 12;:

Authors: Onel M, Sumbul F, Liu J, Nussinov R, Haliloglu T

Abstract
Conjugation of Nedd8 (neddylation) to Cullins in Cullin-RING E3 ligases (CRL) stimulates ubiquitination and polyubiquitination of protein substrates. CRL is made up of two Cullin-flanked arms: one consists of the substrate-binding and adaptor proteins; the other of E2 and Ring-box protein (Rbx). Polyubiquitin chain length and topology determines the substrate fate. Here we ask how polyubiquitin chains are accommodated in the limited space available between the two arms and what determines the polyubiquitin linkage topology. We focus on Cullin 5 (Cul5) and Rbx1 in three states: before Cul5 neddylation (closed state), after neddylation (open state), and after deneddylation, exploiting molecular dynamics (MD) simulations and the Gaussian Network Model (GNM). We observe that regulation of substrate ubiquitination and polyubiquitination takes place through Rbx1 rotations, which are controlled by Nedd8-Rbx1 allosteric communication. Allosteric propagation proceeds from Nedd8 via Cul5 dynamic hinges and hydrogen bonds between the C-terminal domain of Cul5 (Cul5CTD) and Rbx1 (Cul5CTD residues R538/R569 and Rbx1 residue E67, or Cul5CTD E474/E478/N491 and Rbx1 K105). Importantly, at each ubiquitination step (homogeneous or heterogeneous, linear or branched), the polyubiquitin linkages fit into the distances between the two arms, and these match the inherent CRL conformational tendencies. Hinge sites may constitute drug targets.

PMID: 28082425 [PubMed - as supplied by publisher]

Losartan Reduces the Immediate and Sustained Increases in Muscle Sympathetic Nerve Activity after Hyper-Acute Intermittent Hypoxia.

Sat, 01/14/2017 - 07:43
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Losartan Reduces the Immediate and Sustained Increases in Muscle Sympathetic Nerve Activity after Hyper-Acute Intermittent Hypoxia.

J Appl Physiol (1985). 2017 Jan 12;:jap.00683.2016

Authors: Jouett NP, Moralez G, Raven PB, Smith ML

Abstract
Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia (IH), which produces elevations in sympathetic nerve activity (SNA) and associated hypertension in experimental models that persist beyond the initial exposure. We tested the hypotheses that angiotensin receptor blockade in humans using Losartan attenuates the immediate and immediately persistent increases in (a) SNA discharge and (b) mean arterial pressure (MAP) after hyper-acute intermittent hypoxia training (IHT) using a randomized, placebo controlled repeated-measures experimental design. We measured ECG and photoplethysmographic arterial pressure in 9 healthy human subjects, while muscle sympathetic nerve activity (MSNA) was recorded in 7 subjects using microneurography. Subjects were exposed to a series of hypoxic apneas in which they inhaled 2-3 breaths of nitrogen, followed by a 20-second apnea and 40 seconds of room air breathing every minute for 20 minutes. Hyper-acute IHT produced substantial and persistent elevations in MSNA burst frequency (baseline: 15.3 ± 1.8, IHT: 24 ± 1.5, post-IHT 20.0 ± 1.3 bursts/min, all P < 0.01) and MAP (baseline: 89.2 ± 3.3, IHT: 92.62 ± 3.1, post-IHT: 93.83 ± 3.1 mm Hg mm Hg, all P < 0.02). Losartan attenuated the immediate and sustained increases in MSNA (baseline: 17.3 ± 2.5, IHT: 18.6 ± 2.2, post-IHT 20.0 ± 1.3 bursts/min, all P < 0.001) and MAP (baseline: 81.9 ± 2.6, IHT: 81.1 ± 2.8, post-IHT: 81.3 ± 3.0 mm Hg, all P >0.70). This investigation confirms the role of angiotensin II type 1a receptors in the immediate and persistent sympathoexcitatory and pressor responses to IHT.

PMID: 28082332 [PubMed - as supplied by publisher]

Impact of air quality guidelines on COPD sufferers.

Sat, 01/14/2017 - 07:43
Related Articles

Impact of air quality guidelines on COPD sufferers.

Int J Chron Obstruct Pulmon Dis. 2016;11:839-72

Authors: Liu Y, Yan S, Poh K, Liu S, Iyioriobhe E, Sterling DA

Abstract
BACKGROUND: COPD is one of the leading causes of morbidity and mortality in both high- and low-income countries and a major public health burden worldwide. While cigarette smoking remains the main cause of COPD, outdoor and indoor air pollution are important risk factors to its etiology. Although studies over the last 30 years helped reduce the values, it is not very clear if the current air quality guidelines are adequately protective for COPD sufferers.
OBJECTIVE: This systematic review was to summarize the up-to-date literature on the impact of air pollution on the COPD sufferers.
METHODS: PubMed and Google Scholar were utilized to search for articles related to our study's focus. Search terms included "COPD exacerbation", "air pollution", "air quality guidelines", "air quality standards", "COPD morbidity and mortality", "chronic bronchitis", and "air pollution control" separately and in combination. We focused on articles from 1990 to 2015. We also used articles prior to 1990 if they contained relevant information. We focused on articles written in English or with an English abstract. We also used the articles in the reference lists of the identified articles.
RESULTS: Both short-term and long-term exposures to outdoor air pollution around the world are associated with the mortality and morbidity of COPD sufferers even at levels below the current air quality guidelines. Biomass cooking in low-income countries was clearly associated with COPD morbidity in adult nonsmoking females.
CONCLUSION: There is a need to continue to improve the air quality guidelines. A range of intervention measures could be selected at different levels based on countries' socioeconomic conditions to reduce the air pollution exposure and COPD burden.

PMID: 27143874 [PubMed - indexed for MEDLINE]

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