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Long-Term Nonmalignant Disease Mortality in Subjects Exposed to Transmissible Agents Present in Animals Used for Food.

Recent Research Articles from UNTHSC - Fri, 09/02/2016 - 07:34

Long-Term Nonmalignant Disease Mortality in Subjects Exposed to Transmissible Agents Present in Animals Used for Food.

Vector Borne Zoonotic Dis. 2016 Sep 1;

Authors: Ndetan H, Ekanem US, Faramawi MF, Chedjieu IP, Thapa S, Johnson BK, Johnson KD, Surani SS, Johnson ES

Abstract
OBJECTIVE: To study mortality from nonmalignant diseases in subjects with high exposure to transmissible agents present in animals used for food, and in their raw or inadequately cooked products.
METHODS: Mortality was compared in a cohort of meat handlers in slaughtering and processing plants with that of the U.S. general population.
RESULTS: Excess mortality was observed for conditions known to be associated with infections-these include, septicemia, chronic nephritis, diseases of the kidney and ureter, diseases of the pancreas, cirrhosis of the liver, acute and subacute endocarditis, acute rheumatic fever, functional diseases of the heart, aortic aneurysm, intracranial and intraspinous abscess, and meningitis. Excess mortality was also observed for ischemic heart disease and diabetes, conditions without an established infectious etiology, but which have been linked with infections.
CONCLUSIONS: If transmissible agents present in food animals and their raw products cause long-term diseases and mortality in humans, this study importantly points to the likely diseases, many of which are already known to be associated with infections. The excess mortality observed for ischemic heart disease and diabetes is consistent with existing evidence linking these conditions with infections, and gives rise to the novel hypothesis that microbial agents present in food animals and their products may be candidates for an infective role in the occurrence of these conditions, and therefore needs further investigation.

PMID: 27585393 [PubMed - as supplied by publisher]

Aerobic Exericse Training Improves Orthostatic Tolearnce In Elderly Humans: 3861 Board #300 June 4, 9: 30 AM - 11: 00 AM.

Recent Research Articles from UNTHSC - Fri, 09/02/2016 - 07:34

Aerobic Exericse Training Improves Orthostatic Tolearnce In Elderly Humans: 3861 Board #300 June 4, 9: 30 AM - 11: 00 AM.

Med Sci Sports Exerc. 2016 May;48(5S Suppl 1):1085

Authors: Xu D, Chen S, Ross S, Olivencia-Yurvati A, Shi X

PMID: 27584535 [PubMed - as supplied by publisher]

Association of Sp1 and survivin in epithelial ovarian cancer: Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation.

Recent Research Articles from UNTHSC - Fri, 09/02/2016 - 07:34

Association of Sp1 and survivin in epithelial ovarian cancer: Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation.

Tumour Biol. 2016 Aug 31;

Authors: Sankpal UT, Ingersoll SB, Ahmad S, Holloway RW, Bhat VB, Simecka JW, Daniel L, Kariali E, Vishwanatha JK, Basha R

Abstract
The expression of specificity protein 1 (Sp1) and survivin was evaluated in clinical specimens of epithelial ovarian cancer (EOC) patients. When compared to normal tissue, EOC samples showed high expression of Sp1 and survivin using qPCR (Sp1: ∼2-fold; survivin: ∼5-fold) and Western blot (Sp1: >2.6-fold; survivin: >100-fold). The Sp1 inhibitor, and anti-cancer small molecule, tolfenamic acid (TA), was tested to enhance the response of Cisplatin (Cis) in EOC cell lines. Cell viability (CellTiter-Glo), combination index (CalcuSyn software), apoptosis (Annexin-V staining), cell cycle analyses (flow cytometry), and reactive oxygen species (flow cytometry) were determined. Cell migration and invasion was assessed using matrigel coated transwell chambers. Agilent Technologies proteomics analysis identified potential signaling pathways involved. The combination of TA (50 μM) and Cis (5 μM) synergistically increased the growth inhibition in ES2 (∼80 %, p < 0.001) and OVCAR-3 (60 %, p < 0.001) cells. TA or TA + Cis treatment in ES2 cells caused cell cycle arrest in G1 Phase (TA) or S-Phase (TA + Cis) and unregulated reactive oxygen species. Invasion and migration was decreased in ES2 cells. Global proteomic profiling showed modulation of proteins associated with oxidative phosphorylation, apoptosis, electron transport chain, DNA damage, and cell cycle proteins. These results demonstrate an association of Sp1 and survivin in EOC and confirm targeting these candidates with TA potentially sensitizes EOC cells to cisplatin.

PMID: 27581819 [PubMed - as supplied by publisher]

Continuous Infusion Nonsteroidal Anti-Inflammatory Drugs for Perioperative Pain Management.

Recent Research Articles from UNTHSC - Fri, 09/02/2016 - 07:34

Continuous Infusion Nonsteroidal Anti-Inflammatory Drugs for Perioperative Pain Management.

J Pharm Pract. 2016 Aug 31;

Authors: Howard ML, Isaacs AN, Nisly SA

Abstract
PURPOSE: To review the use of continuous infusion (CI) nonsteroidal anti-inflammatory drugs (NSAIDs) as an alternative modality for pain control in surgical patient populations.
METHODS: A PubMed and MEDLINE search was conducted from 1964 through February 2016 using the following search terms alone or in combinations: continuous, infusion, nonsteroidal anti-inflammatory drug, diclofenac, ibuprofen, indomethacin, ketoprofen, ketorolac, and surgery. All English-language, prospective and retrospective, adult and pediatric studies evaluating intravenous or intramuscular CI NSAIDs for surgical pain were evaluated for inclusion in this review.
RESULTS: Twenty four prospective and retrospective publications evaluating CI NSAIDs were identified: 12 in abdominal surgery, 7 in orthopedic surgery, and 5 in pediatric surgery. Specific CI NSAIDs utilized included diclofenac, indomethacin, ketoprofen, and ketorolac. Most studies compared the CI NSAID to placebo or an alternative analgesic and evaluated pain control, supplemental opioid use, and related adverse effects. In these surgical populations, CI NSAIDs decreased opioid consumption, alongside provision of adequate pain control. While long-term adverse effects were rarely collected, a decrease in nausea and sedation was often seen with the CI NSAID groups.
CONCLUSIONS: In the abdominal, orthopedic, and pediatric surgical populations, CI NSAIDs represent a feasible alternative modality for perioperative pain control.

PMID: 27580638 [PubMed - as supplied by publisher]

Evaluation of forensic DNA mixture evidence: protocol for evaluation, interpretation, and statistical calculations using the combined probability of inclusion.

Recent Research Articles from UNTHSC - Fri, 09/02/2016 - 07:34

Evaluation of forensic DNA mixture evidence: protocol for evaluation, interpretation, and statistical calculations using the combined probability of inclusion.

BMC Genet. 2016;17(1):125

Authors: Bieber FR, Buckleton JS, Budowle B, Butler JM, Coble MD

Abstract
BACKGROUND: The evaluation and interpretation of forensic DNA mixture evidence faces greater interpretational challenges due to increasingly complex mixture evidence. Such challenges include: casework involving low quantity or degraded evidence leading to allele and locus dropout; allele sharing of contributors leading to allele stacking; and differentiation of PCR stutter artifacts from true alleles. There is variation in statistical approaches used to evaluate the strength of the evidence when inclusion of a specific known individual(s) is determined, and the approaches used must be supportable. There are concerns that methods utilized for interpretation of complex forensic DNA mixtures may not be implemented properly in some casework. Similar questions are being raised in a number of U.S. jurisdictions, leading to some confusion about mixture interpretation for current and previous casework.
RESULTS: Key elements necessary for the interpretation and statistical evaluation of forensic DNA mixtures are described. Given the most common method for statistical evaluation of DNA mixtures in many parts of the world, including the USA, is the Combined Probability of Inclusion/Exclusion (CPI/CPE). Exposition and elucidation of this method and a protocol for use is the focus of this article. Formulae and other supporting materials are provided.
CONCLUSIONS: Guidance and details of a DNA mixture interpretation protocol is provided for application of the CPI/CPE method in the analysis of more complex forensic DNA mixtures. This description, in turn, should help reduce the variability of interpretation with application of this methodology and thereby improve the quality of DNA mixture interpretation throughout the forensic community.

PMID: 27580588 [PubMed - in process]

Toll-like Receptors in the Vascular System: Sensing the Dangers Within.

Recent Research Articles from UNTHSC - Thu, 09/01/2016 - 06:34
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Toll-like Receptors in the Vascular System: Sensing the Dangers Within.

Pharmacol Rev. 2016 Jan;68(1):142-67

Authors: Goulopoulou S, McCarthy CG, Webb RC

Abstract
Toll-like receptors (TLRs) are components of the innate immune system that respond to exogenous infectious ligands (pathogen-associated molecular patterns, PAMPs) and endogenous molecules that are released during host tissue injury/death (damage-associated molecular patterns, DAMPs). Interaction of TLRs with their ligands leads to activation of downstream signaling pathways that induce an immune response by producing inflammatory cytokines, type I interferons (IFN), and other inflammatory mediators. TLR activation affects vascular function and remodeling, and these molecular events prime antigen-specific adaptive immune responses. Despite the presence of TLRs in vascular cells, the exact mechanisms whereby TLR signaling affects the function of vascular tissues are largely unknown. Cardiovascular diseases are considered chronic inflammatory conditions, and accumulating data show that TLRs and the innate immune system play a determinant role in the initiation and development of cardiovascular diseases. This evidence unfolds a possibility that targeting TLRs and the innate immune system may be a novel therapeutic goal for these conditions. TLR inhibitors and agonists are already in clinical trials for inflammatory conditions such as asthma, cancer, and autoimmune diseases, but their study in the context of cardiovascular diseases is in its infancy. In this article, we review the current knowledge of TLR signaling in the cardiovascular system with an emphasis on atherosclerosis, hypertension, and cerebrovascular injury. Furthermore, we address the therapeutic potential of TLR as pharmacological targets in cardiovascular disease and consider intriguing research questions for future study.

PMID: 26721702 [PubMed - indexed for MEDLINE]

Roles of Pyruvate, NADH, and Mitochondrial Complex I in Redox Balance and Imbalance in β Cell Function and Dysfunction.

Recent Research Articles from UNTHSC - Thu, 09/01/2016 - 06:34
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Roles of Pyruvate, NADH, and Mitochondrial Complex I in Redox Balance and Imbalance in β Cell Function and Dysfunction.

J Diabetes Res. 2015;2015:512618

Authors: Luo X, Li R, Yan LJ

Abstract
Pancreatic β cells not only use glucose as an energy source, but also sense blood glucose levels for insulin secretion. While pyruvate and NADH metabolic pathways are known to be involved in regulating insulin secretion in response to glucose stimulation, the roles of many other components along the metabolic pathways remain poorly understood. Such is the case for mitochondrial complex I (NADH/ubiquinone oxidoreductase). It is known that normal complex I function is absolutely required for episodic insulin secretion after a meal, but the role of complex I in β cells in the diabetic pancreas remains to be investigated. In this paper, we review the roles of pyruvate, NADH, and complex I in insulin secretion and hypothesize that complex I plays a crucial role in the pathogenesis of β cell dysfunction in the diabetic pancreas. This hypothesis is based on the establishment that chronic hyperglycemia overloads complex I with NADH leading to enhanced complex I production of reactive oxygen species. As nearly all metabolic pathways are impaired in diabetes, understanding how complex I in the β cells copes with elevated levels of NADH in the diabetic pancreas may provide potential therapeutic strategies for diabetes.

PMID: 26568959 [PubMed - indexed for MEDLINE]

Authors' Response to Letter Regarding Alcohol Sales Tax and Sexually Transmitted Infections.

Recent Research Articles from UNTHSC - Tue, 08/30/2016 - 06:30
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Authors' Response to Letter Regarding Alcohol Sales Tax and Sexually Transmitted Infections.

Am J Prev Med. 2016 May;50(5):e161

Authors: Staras SA, Livingston MD, Wagenaar AC

PMID: 27102644 [PubMed - indexed for MEDLINE]

The interrelation between intestinal parasites and latent TB infections among newly resettled refugees in Texas.

Recent Research Articles from UNTHSC - Tue, 08/30/2016 - 06:30
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The interrelation between intestinal parasites and latent TB infections among newly resettled refugees in Texas.

Int Health. 2016 Jan;8(1):67-72

Authors: Board AR, Suzuki S

Abstract
BACKGROUND: Previous research has documented that parasite infection may increase vulnerability to TB among certain at risk populations. The purpose of this study was to identify whether an association exists between latent tuberculosis infection (LTBI) and intestinal parasite infection among newly resettled refugees in Texas while controlling for additional effects of region of origin, age and sex.
METHODS: Data for all refugees screened for both TB and intestinal parasites between January 2010 and mid-October 2013 were obtained from the Texas Refugee Health Screening Program and were analyzed using logistic regression.
RESULTS: A total of 9860 refugees were included. In multivariable logistic regression analysis, pathogenic and non-pathogenic intestinal parasite infections yielded statistically significant reduced odds of LTBI. However, when individual parasite species were analyzed, hookworm infection indicated statistically significant increased odds of LTBI (OR 1.674, CI: 1.126-2.488).
DISCUSSION: A positive association exists between hookworm infection and LTBI in newly arrived refugees to Texas. More research is needed to assess the nature and extent of these associations.

PMID: 25995214 [PubMed - indexed for MEDLINE]

The Association between Patient-Centered Attributes of Care and Patient Satisfaction.

Recent Research Articles from UNTHSC - Tue, 08/30/2016 - 06:30
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The Association between Patient-Centered Attributes of Care and Patient Satisfaction.

Patient. 2015 Apr;8(2):187-97

Authors: Tak H, Ruhnke GW, Shih YC

Abstract
BACKGROUND AND OBJECTIVE: Little is known about the attributes of care that most strongly impact satisfaction in real-world settings where patients' limited medical knowledge may restrict their ability to ascertain the true quality of care. We therefore examined the association between patient-centered attributes of physician care (thoroughness, explanation, and listening), in-office waiting time, and patient satisfaction.
METHODS: We used the Community Tracking Study Household Survey, a US nationally representative dataset (n = 71,594). Using logistic regression models, we analyzed the association between patient ratings of care attributes and patient satisfaction for the total sample and by subgroups, according to health status, physician type, and visit type.
RESULTS: Patients' perception of excellent or very good care attributes was strongly associated with being very satisfied with care received (thoroughness of care, odds ratio [OR] 2.64, 95 % confidence interval [CI] 2.31-3.02; listening, OR 2.04, 95 % CI 1.77-2.36; explanation, OR 1.63, 95 % CI 1.42-1.86), as was a waiting time of ≤10 min (OR 1.50, 95 % CI 1.39-1.63). The effect magnitude of thoroughness on satisfaction is particularly strong relative to high-quality listening and explanation among respondents in poor health, and for whom the most recent office visit was to see a generalist or for curative care.
CONCLUSIONS: Thoroughness of care was the strongest determinant of patient satisfaction, followed by physician listening and explanation. Especially with patients' improved access to current medical information, it is important for physicians to recognize that excellent communication cannot serve as a substitute for high-quality, thorough care.

PMID: 25011683 [PubMed - indexed for MEDLINE]

Characterization of Alzheimer's Disease and Mild Cognitive Impairment in Older Adults in Panama.

Recent Research Articles from UNTHSC - Mon, 08/29/2016 - 06:30

Characterization of Alzheimer's Disease and Mild Cognitive Impairment in Older Adults in Panama.

J Alzheimers Dis. 2016 Aug 10;

Authors: Villarreal AE, Grajales S, O'Bryant SE, Edwards M, López L, Montalván A, Britton GB, and for the Panama Aging Research Initiative (PARI)

Abstract
Research on age-related cognitive impairment is scarce in Central America. We report factors associated with cognitive impairment among a sample of older adults in Panama diagnosed with Alzheimer's disease (AD, n = 31), mild cognitive impairment (MCI, n = 43), or no cognitive impairment (controls, n = 185). Apolipoprotein E (ApoE) genotype was assessed in a subset of cases (n = 135). Age (OR = 2.53, 95% CI = 1.03-6.17) and ApoE ɛ4 (OR = 5.14, 95% CI = 2.11-12.52) were significantly related to cognitive impairment (AD/MCI combined). Results underscore the potential of genetic screening in Panama for identifying those at risk of dementia.

PMID: 27567849 [PubMed - as supplied by publisher]

Methods and considerations for the analysis and standardization of assessing muscle sympathetic nerve activity in humans.

Recent Research Articles from UNTHSC - Mon, 08/29/2016 - 06:30
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Methods and considerations for the analysis and standardization of assessing muscle sympathetic nerve activity in humans.

Auton Neurosci. 2015 Dec;193:12-21

Authors: White DW, Shoemaker JK, Raven PB

Abstract
The technique of microneurography and the assessment of muscle sympathetic nerve activity (MSNA) are used in laboratories throughout the world. The variables used to describe MSNA, and the criteria by which these variables are quantified from the integrated neurogram, vary among studies and laboratories and, therefore, can become confusing to those starting to learn the technique. Therefore, the purpose of this educational review is to discuss guidelines and standards for the assessment of sympathetic nervous activity through the collection and analysis of MSNA. This review will reiterate common practices in the collection of MSNA, but will also introduce considerations for the evaluation and physiological inference using MSNA.

PMID: 26299824 [PubMed - indexed for MEDLINE]

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

Recent Research Articles from UNTHSC - Sun, 08/28/2016 - 06:30

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 - as supplied by publisher]

Effects of intermittent pressure imitating rolling manipulation on calcium ion homeostasis in human skeletal muscle cells.

Recent Research Articles from UNTHSC - Sat, 08/27/2016 - 06:30

Effects of intermittent pressure imitating rolling manipulation on calcium ion homeostasis in human skeletal muscle cells.

BMC Complement Altern Med. 2016;16(1):314

Authors: Zhang H, Liu H, Lin Q, Zhang G, Mason DC

Abstract
BACKGROUND: Homeostasis imbalance of intracellular Ca(2+) is one of the key pathophysiological factors in skeletal muscle injuries. Such imbalance can cause significant change in the metabolism of Ca(2+)-related biomarkers in skeletal muscle, such as superoxide dismutase (SOD), malondialdehyde (MDA) and creatine kinase (CK). Measurements of these biomarkers can be used to evaluate the degree of damage to human skeletal muscle cells (HSKMCs) injury. Rolling manipulation is the most popular myofascial release technique in Traditional Chinese Medicine. The mechanism of how this technique works in ameliorating muscle injury is unknown. This study aimed to investigate the possible Ca(2+) mediated effects of intermittent pressure imitating rolling manipulation (IPIRM) of Traditional Chinese Medicine in the injured HSKMCs.
METHODS: The normal HSKMCs was used as control normal group (CNG), while the injured HSKMCs were further divided into five different groups: control injured group (CIG), Rolling manipulation group (RMG), Rolling manipulation-Verapamil group (RMVG), static pressure group (SPG) and static pressure-Verapamil group (SPVG). RMG and RMVG cells were cyclically exposed to 9.5-12.5 N/cm(2) of IPIRM at a frequency of 1.0 Hz for 10 min. SPG and SPVG were loaded to a continuous pressure of 12.5 N/cm(2) for 10 min. Verapamil, a calcium antagonist, was added into the culture mediums of both RMVG and SPVG groups to block the influx of calcium ion.
RESULT: Compared with the CNG (normal cells), SOD activity was remarkably decreased while both MDA content and CK activity were significantly increased in the CIG (injured cells). When the injured cells were treated with the intermittent rolling manipulation pressure (RMG), the SOD activity was significantly increased and MDA content and CK activity were remarkably decreased. These effects were suppressed by adding the calcium antagonist Verapamil into the culture medium in RMVG. On the other hand, exposure to static pressure in SPG and SPVG affected neither the SOD activity nor the MDA content and CK activity in the injured muscle cells regardless of the presence of verapamil or not in the culture medium.
CONCLUSION: These data suggest that the intermittent rolling pressure with the manipulation could ameliorate HSKMCs injury through a Ca(2+) dependent pathway. Static pressure did not lead to the same results.

PMID: 27561948 [PubMed - in process]

Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with response-adapted therapy.

Recent Research Articles from UNTHSC - Fri, 08/26/2016 - 06:29

Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with response-adapted therapy.

Leukemia. 2016 Aug 18;

Authors: Pui CH, Pei D, Raimondi SC, Coustan-Smith E, Jeha S, Cheng C, Bowman WP, Sandlund JT, Ribeiro RC, Rubnitz JE, Inaba H, Gruber TA, Leung WH, Yang JJ, Downing JR, Evans WE, Relling MV, Campana D

Abstract
To determine the clinical significance of minimal residual disease (MRD) in patients with prognostically relevant subtypes of childhood acute lymphoblastic leukemia (ALL), we analyzed data from 488 patients treated in St Jude Total Therapy Study XV with treatment intensity based mainly on MRD levels measured during remission induction. MRD levels on day 19 predicted treatment outcome for patients with hyperdiploid >50 ALL, NCI standard-risk B-ALL or T-cell ALL, while MRD levels on day 46 were prognostic for patients with NCI standard-risk or high-risk B-ALL. Patients with t(12;21)/(ETV6-RUNX1) or hyperdiploidy >50 ALL had the best prognosis; those with a negative MRD on day 19 had a particularly low risk of relapse: 1.9 and 3.8%, respectively. Patients with NCI high-risk B-ALL or T-cell ALL had an inferior outcome; even with undetectable MRD on day 46, cumulative risk of relapse was 12.7 and 15.5%, respectively. Among patients with NCI standard-risk B-ALL, the outcome was intermediate overall but was poor if MRD was ⩾1% on day 19 or MRD was detectable at any level on day 46. Our results indicate that the clinical impact of MRD on treatment outcome in childhood ALL varies considerably according to leukemia subtype and time of measurement.Leukemia accepted article preview online, 18 August 2016. doi:10.1038/leu.2016.234.

PMID: 27560110 [PubMed - as supplied by publisher]

A method for identifying discriminative isoform-specific peptides for clinical proteomics application.

Recent Research Articles from UNTHSC - Thu, 08/25/2016 - 06:32

A method for identifying discriminative isoform-specific peptides for clinical proteomics application.

BMC Genomics. 2016;17(Suppl 7):522

Authors: Zhang F, Chen JY

Abstract
BACKGROUND: Clinical proteomics application aims at solving a specific clinical problem within the context of a clinical study. It has been growing rapidly in the field of biomarker discovery, especially in the area of cancer diagnostics. Until recently, protein isoform has not been viewed as a new class of early diagnostic biomarkers for clinical proteomics. A protein isoform is one of different forms of the same protein. Different forms of a protein may be produced from single-nucleotide polymorphisms (SNPs), alternative splicing, or post-translational modifications (PTMs). Previous studies have shown that protein isoforms play critical roles in tumorigenesis, disease diagnosis, and prognosis. Identifying and characterizing protein isoforms are essential to the study of molecular mechanisms and early detection of complex diseases such as breast cancer. However, there are limitations with traditional methods such as EST sequencing, Microarray profiling (exon array, Exon-exon junction array), mRNA next-generation sequencing used for protein isoform determination: 1) not in the protein level, 2) no connectivity about connection of nonadjacent exons, 3) no SNPs and PTMs, and 4) low reproducibility. Moreover, there exist the computational challenges of clinical proteomics studies: 1) low sensitivity of instruments, 2) high data noise, and 3) high variability and low repeatability, although recent advances in clinical proteomics technology, LC-MS/MS proteomics, have been used to identify candidate molecular biomarkers in diverse range of samples, including cells, tissues, serum/plasma, and other types of body fluids.
RESULTS: Therefore, in the paper, we presented a peptidomics method for identifying cancer-related and isoform-specific peptide for clinical proteomics application from LC-MS/MS. First, we built a Peptidomic Database of Human Protein Isoforms, then created a peptidomics approach to perform large-scale screen of breast cancer-associated alternative splicing isoform markers in clinical proteomics, and lastly performed four kinds of validations: biological validation (explainable index), exon array, statistical validation of independent samples, and extensive pathway analysis.
CONCLUSIONS: Our results showed that alternative splicing isoform makers can act as independent markers of breast cancer and that the method for identifying cancer-specific protein isoform biomarkers from clinical proteomics application is an effective one for increasing the number of identified alternative splicing isoform markers in clinical proteomics.

PMID: 27557076 [PubMed - as supplied by publisher]

IL-7 and Depression: The importance of gender and blood fraction.

Recent Research Articles from UNTHSC - Thu, 08/25/2016 - 06:32

IL-7 and Depression: The importance of gender and blood fraction.

Behav Brain Res. 2016 Aug 20;

Authors: Hall JR, Wiechmann A, Edwards M, Johnson LA, O'Bryant SE

Abstract
Interleukin 7 (IL-7) is involved in B and T cell development and differentiation. Recent work suggests IL-7 may be altered in depression; however, we have previously shown that gender and blood fraction oftentimes impacts putative biomarker relationships among those with and without Alzheimer's disease (AD). The current study examined the impact of blood fraction (serum versus plasma) and gender on the IL7 depression link in a sample of elders with and without AD. Non-fasting serum (150 AD cases 150 controls) and plasma (100 AD cases, 100 controls) IL-7 levels were assayed via electrochemiluminescence. The correlation between serum and plasma for IL-7 was 0.34. In the total sample, serum (r(2)=0.16, p=0.006) and plasma (r(2)=-0.20, p=0.007) IL-7 levels were significantly, but inversely, correlated with GDS-30 scores. When split by gender, serum IL-7 levels were significantly positively associated with GDS scores among men (r(2)=0.34, p=0.001) whereas plasma IL-7 levels (r(2)=-0.23, p=0.008) were significantly negatively associated with GDS scores among women. A logistic regression model predicting depression status (GDS30>=10) included age, gender, education, plasma, and serum IL-7 levels, found both significantly associated with depression status, but in opposite directions. Our findings support a significant link between IL-7 and depression; however, we further highlight the importance of blood fraction and gender when examining this relationship. Additionally, these findings further support the need for additional work that could lead to targeted therapeutic interventions utilizing anti-inflammatory medications for individuals with depression.

PMID: 27555535 [PubMed - as supplied by publisher]

The Essential Role of Neutrophils during Infection with the Intracellular Bacterial Pathogen Listeria monocytogenes.

Recent Research Articles from UNTHSC - Sun, 08/21/2016 - 06:33

The Essential Role of Neutrophils during Infection with the Intracellular Bacterial Pathogen Listeria monocytogenes.

J Immunol. 2016 Sep 1;197(5):1557-65

Authors: Witter AR, Okunnu BM, Berg RE

Abstract
Neutrophils have historically been characterized as first responder cells vital to host survival because of their ability to contain and eliminate bacterial and fungal pathogens. However, recent studies have shown that neutrophils participate in both protective and detrimental responses to a diverse array of inflammatory and infectious diseases. Although the contribution of neutrophils to extracellular infections has been investigated for decades, their specific role during intracellular bacterial infections has only recently been appreciated. During infection with the Gram-positive intracellular pathogen Listeria monocytogenes, neutrophils are recruited from the bone marrow to sites of infection where they use novel bacterial-sensing pathways leading to phagocytosis and production of bactericidal factors. This review summarizes the requirement of neutrophils during L. monocytogenes infection by examining both neutrophil trafficking and function during primary and secondary infection.

PMID: 27543669 [PubMed - in process]

Tetracycline-Containing MCM-41 Mesoporous Silica Nanoparticles for the Treatment of Escherichia coli.

Recent Research Articles from UNTHSC - Sat, 08/20/2016 - 06:29
Related Articles

Tetracycline-Containing MCM-41 Mesoporous Silica Nanoparticles for the Treatment of Escherichia coli.

Molecules. 2015;20(11):19690-8

Authors: Koneru B, Shi Y, Wang YC, Chavala SH, Miller ML, Holbert B, Conson M, Ni A, Di Pasqua AJ

Abstract
Tetracycline (TC) is a well-known broad spectrum antibiotic, which is effective against many Gram positive and Gram negative bacteria. Controlled release nanoparticle formulations of TC have been reported, and could be beneficial for application in the treatment of periodontitis and dental bone infections. Furthermore, TC-controlled transcriptional regulation systems (Tet-on and Tet-off) are useful for controlling transgene expression in vitro and in vivo for biomedical research purposes; controlled TC release systems could be useful here, as well. Mesoporous silica nanomaterials (MSNs) are widely studied for drug delivery applications; Mobile crystalline material 41 (MCM-41), a type of MSN, has a mesoporous structure with pores forming channels in a hexagonal fashion. We prepared 41 ± 4 and 406 ± 55 nm MCM-41 mesoporous silica nanoparticles and loaded TC for controlled dug release; TC content in the TC-MCM-41 nanoparticles was 18.7% and 17.7% w/w, respectively. Release of TC from TC-MCM-41 nanoparticles was then measured in phosphate-buffered saline (PBS), pH 7.2, at 37 °C over a period of 5 h. Most antibiotic was released from both over this observation period; however, the majority of TC was released over the first hour. Efficacy of the TC-MCM-41 nanoparticles was then shown to be superior to free TC against Escherichia coli (E. coli) in culture over a 24 h period, while blank nanoparticles had no effect.

PMID: 26528964 [PubMed - indexed for MEDLINE]

Effects of age and acute muscle fatigue on reactive postural control in healthy adults.

Recent Research Articles from UNTHSC - Fri, 08/19/2016 - 06:29
Related Articles

Effects of age and acute muscle fatigue on reactive postural control in healthy adults.

Clin Biomech (Bristol, Avon). 2015 Dec;30(10):1108-13

Authors: Papa EV, Foreman KB, Dibble LE

Abstract
BACKGROUND: Falls can cause moderate to severe injuries such as hip fractures and head trauma in older adults. While declines in muscle strength and sensory function contribute to increased falls in older adults, skeletal muscle fatigue is often overlooked as an additional contributor to fall risk. The purpose of this investigation was to examine the effects of acute lower extremity muscle fatigue and age on reactive postural control in healthy adults.
METHODS: A sample of 16 individuals participated in this study (8 healthy older adults and 8 healthy young persons). Whole body kinematic and kinetic data were collected during anterior and posterior reproducible fall tests before (T0) and immediately after (T1) eccentric muscle fatiguing exercise, as well as after 15-min (T15) and 30-min (T30) of rest.
FINDINGS: Lower extremity joint kinematics of the stepping limb during the support (landing) phase of the anterior fall were significantly altered by the presence of acute muscle fatigue. Step velocity was significantly decreased during the anterior falls. Statistically significant main effects of age were found for step length in both fall directions. Effect sizes for all outcomes were small. No statistically significant interaction effects were found.
INTERPRETATION: Muscle fatigue has a measurable effect on lower extremity joint kinematics during simulated falls. These alterations appear to resolve within 15 min of recovery. The above deficits, coupled with a reduced step length, may help explain the increased fall risk in older adults.

PMID: 26351001 [PubMed - indexed for MEDLINE]

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