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Spatial Microbial Composition Along the Gastrointestinal Tract of Captive Attwater's Prairie Chicken.

Recent Research Articles from UNTHSC - Wed, 10/19/2016 - 13:33

Spatial Microbial Composition Along the Gastrointestinal Tract of Captive Attwater's Prairie Chicken.

Microb Ecol. 2016 Oct 18;

Authors: Zhang Y, Simon SE, Johnson JA, Allen MS

Abstract
Gastrointestinal microbiota is increasingly recognized as an important component of individual health, and therefore, our ability to quantify its diversity accurately is central for exploring different ways to improve health. Non-invasive sampling methods, such as cloaca swabs, are often used to measure gastrointestinal microbiota diversity within an individual. However, few studies have addressed to what degree differences exist in microbial community composition along the gastrointestinal tract, and measures obtained from the cloaca may not actually represent the diversity present elsewhere in the gastrointestinal tract. In this study, we systematically characterized the gastrointestinal microbial community of the critically endangered Attwater's Prairie chicken (Tympanuchus cupido attwateri) by opportunistically sampling four different locations (ileum, cecum, large intestine, and cloaca) along the gastrointestinal tract of eight individuals. Spatial variation of microbial community was observed at different sampling locations within the gastrointestinal tract. The cecum harbored the most diverse and significantly different microbiota from the other locations, while the microbial α- and β-diversities were similar in the ileum, large intestine, and cloaca. The results of this study provide evidence that microbiota diversity can differ depending on sampling location and metric used to quantify diversity. As shown here, non-invasive cloacal sampling strategies may reflect microbiota diversity elsewhere in the gastrointestinal tract, yet caution is warranted when making generalizations in terms of the microbiota diversity correlations when samples are obtained from a single location within the gastrointestinal tract.

PMID: 27752719 [PubMed - as supplied by publisher]

Eyebrow restoration: the approach, considerations, and technique in follicular unit transplantation.

Recent Research Articles from UNTHSC - Wed, 10/19/2016 - 13:33
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Eyebrow restoration: the approach, considerations, and technique in follicular unit transplantation.

J Cosmet Dermatol. 2015 Dec;14(4):310-4

Authors: Tomc CM, Malouf PJ

Abstract
BACKGROUND: Eyebrows serve a key role in eye protection, communication, and self-expression. Trends in eyebrow grooming are constantly evolving, often requiring plucking, waxing, or laser hair removal to style. When combined with the natural thinning of the brow with aging, the result can be a sparse or even absent eyebrow hair over time. Follicular unit transplantation provides a means of restoring eyebrow fullness and architecture. With careful attention and augmentation of follicle transfer techniques, a natural end result is possible.

PMID: 26248542 [PubMed - indexed for MEDLINE]

Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates.

Recent Research Articles from UNTHSC - Tue, 10/18/2016 - 07:33
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Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates.

J Mass Spectrom. 2016 Oct;51(10):900-907

Authors: Prokai L, Fryčák P, Nguyen V, Forster MJ

Abstract
We report the evaluation of several mass spectrometry-based methods for the determination of carisoprodol and meprobamate in samples obtained from the rat brain by in vivo intracranial microdialyis. Among the techniques that aspire to perform analyses without chromatographic separation and thereby increase throughput, chip-based nanoelectrospray ionization and the use of an atmospheric pressure solids analysis probe fell short of requirements because of insufficient detection sensitivity and hard ionization, respectively. Although direct analysis in real time provided the required soft ionization, shortcomings of a tandem mass spectrometry-based assay also included inadequate detection sensitivity and, in addition, poor quantitative reproducibility. Therefore, liquid chromatography coupled with atmospheric pressure chemical ionization tandem mass spectrometry was developed to determine carisoprodol and meprobamate from artificial cerebrospinal fluid as the medium. No desalting and/or extraction of the samples was necessary. The assay, combined with in vivo sampling via intracranial microdialyis, afforded time-resolved concentration profiles for the drug and its major metabolite from the nucleus accumbens region of the brain in rats after systemic administration of carisoprodol. Copyright © 2016 John Wiley & Sons, Ltd.

PMID: 27747995 [PubMed - in process]

Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

Recent Research Articles from UNTHSC - Tue, 10/18/2016 - 07:33
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Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

J Glaucoma. 2016 Oct;25(10):e834-e842

Authors: McDonnell FS, McNally SA, Clark AF, O'Brien CJ, Wallace DM

Abstract
BACKGROUND: Glaucoma is an optic neuropathy that affects 60 million people worldwide. There is an underlying fibrosis associated with the lamina cribrosa (LC) in glaucoma. DNA methylation is well established in regulating fibrosis and may be a therapeutic target for glaucoma. The purpose of this study was to compare global DNA methylation levels in primary human normal (NLC) and glaucomatous (GLC) cells, and to investigate DNA methylation in driving fibrosis through regulation of transforming growth factor β1 (TGFβ1).
MATERIALS AND METHODS: LC cells were cultured from normal and glaucomatous human donors. Global methylation was assessed by ELISA. qPCR was conducted for DNA methyltransferases (DNMTs), methyl-CpG-binding protein 2 (MeCP2), TGFβ 1 and 2, collagen 1α1 (COL1A1), and α-smooth muscle actin (αSMA). TGFβ1 and DNMT1 were examined by immunofluorescence. Methylation of the TGFβ1 promoter was determined by methylation-specific PCR (MSP).
RESULTS: Global DNA methylation demonstrated an increase in GLC compared with NLC cells (P<0.05). The previously mentioned methylation and matrix genes were increased in GLC compared with NLC cells (P<0.05). Immunofluorescence showed increased TGFβ1 and DNMT1 in GLC compared with NLC cells. MSP showed increased unmethylated DNA in the TGFβ1 promoter of GLC compared with NLC cells.
CONCLUSIONS: We found increased expression of fibrotic genes in GLC cells and demonstrated an increase in global DNA methylation and in associated enzymes in GLC cells. Furthermore, we showed decreased promoter methylation of TGFβ1 in GLC cells. Determining a role for methylation in glaucoma and in regulating TGFβ1 may provide a novel therapeutic approach.

PMID: 27300643 [PubMed - in process]

Glutaredoxins concomitant with optimal ROS activate AMPK through S-glutathionylation to improve glucose metabolism in type 2 diabetes.

Recent Research Articles from UNTHSC - Mon, 10/17/2016 - 07:35
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Glutaredoxins concomitant with optimal ROS activate AMPK through S-glutathionylation to improve glucose metabolism in type 2 diabetes.

Free Radic Biol Med. 2016 Oct 12;:

Authors: Dong K, Wu M, Liu X, Huang Y, Zhang D, Wang Y, Yan LJ, Shi D

Abstract
AMPK dysregulation contributes to the onset and development of type 2 diabetes (T2DM). AMPK is known to be activated by reactive oxygen species (ROS) and antioxidant interference. However the mechanism by which redox state mediates such contradictory result remains largely unknown. Here we used streptozotocin-high fat diet (STZ-HFD) induced-type 2 diabetic rats and cells lines (L02 and HEK 293) to explore the mechanism of redox-mediated AMPK activation. We show glutaredoxins (Grxs) concomitant with optimal ROS act as an essential mediator for AMPK activation. ROS level results in different mechanisms for AMPK activation. Under low ROS microenvironment, Grxs-mediated S-glutathionylation on AMPK-α catalytic subunit activates AMPK to improve glucose transportation and degradation while inhibiting glycogen synthesis and keeping redox balance. While, under high ROS microenvironment, AMPK is activated by an AMP-dependent mechanism, however sustained high level ROS also causes loss of AMPK protein. This finding provides evidence for a new approach to diabetes treatment by individual doses of ROS or antioxidant calibrated against the actual redox level in vivo. Moreover, the novel function of Grxs in promoting glucose metabolism may provide new target for T2DM treatment.

PMID: 27743883 [PubMed - as supplied by publisher]

Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging.

Recent Research Articles from UNTHSC - Sun, 10/16/2016 - 07:31
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Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging.

Oncotarget. 2016 Oct 11;:

Authors: Coder B, Wang W, Wang L, Wu Z, Zhuge Q, Su DM

Abstract
The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and "protective autoimmunity" provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neuro-degeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the "thymus-inflammaging-neurodegeneration axis".

PMID: 27738345 [PubMed - as supplied by publisher]

A two-stage approach to genetic risk assessment in primary care.

Recent Research Articles from UNTHSC - Sun, 10/16/2016 - 07:31
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A two-stage approach to genetic risk assessment in primary care.

Breast Cancer Res Treat. 2016 Jan;155(2):375-83

Authors: Biswas S, Atienza P, Chipman J, Blackford AL, Arun B, Hughes K, Parmigiani G

Abstract
Genetic risk prediction models such as BRCAPRO are used routinely in genetic counseling for identification of potential BRCA1 and BRCA2 mutation carriers. They require extensive information on the counselee and her family history, and thus are not practical for primary care. To address this gap, we develop and test a two-stage approach to genetic risk assessment by balancing the tradeoff between the amount of information used and accuracy achieved. The first stage is intended for primary care wherein limited information is collected and analyzed using a simplified version of BRCAPRO. If the assessed risk is sufficiently high, more extensive information is collected and the full BRCAPRO is used (stage two: intended for genetic counseling). We consider three first-stage tools: BRCAPROLYTE, BRCAPROLYTE-Plus, and BRCAPROLYTE-Simple. We evaluate the two-stage approach on independent clinical data on probands with family history of breast and ovarian cancers, and BRCA genetic test results. These include population-based data on 1344 probands from Newton-Wellesley Hospital and mostly high-risk family data on 2713 probands from Cancer Genetics Network and MD Anderson Cancer Center. We use discrimination and calibration measures, appropriately modified to evaluate the overall performance of a two-stage approach. We find that the proposed two-stage approach has very limited loss of discrimination and comparable calibration as BRCAPRO. It identifies a similar number of carriers without requiring a full family history evaluation on all probands. We conclude that the two-stage approach allows for practical large-scale genetic risk assessment in primary care.

PMID: 26786860 [PubMed - indexed for MEDLINE]

Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway.

Recent Research Articles from UNTHSC - Sun, 10/16/2016 - 07:31
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Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway.

Int J Mol Med. 2016 Jan;37(1):258-66

Authors: Meng Y, Li WZ, Shi YW, Zhou BF, Ma R, Li WP

Abstract
Ischemia-reperfusion (I/R) plays an important role in myocardial injury. In the present study, we aimed to examine the protective effects of Danshensu (DSS) against I/R injury and to elucidate the underlying mechanisms. For this purpose, H9c2 cells were cultured in hypoxic solution in a hypoxic incubator for 2 h, and then cultured in a high oxygen incubator for various periods of time and pre-treated with or without DSS, ammonium pyrrolidine dithiocarbamate (PDTC) or SP600125 [a c-Jun N-terminal kinase (JNK) inhibitor]. Cell apoptosis and cytosolic free Ca2+ ([Ca2+]i) levels were analyzed by flow cytometry. The protein expression levels of JNK, phosphorylated (p-)JNK, nuclear factor-κB (NF-κB) and transient receptor potential cation channel, subfamily C, member 6 (TRPC6) were measured by western blot analysis. The mRNA expression levels of JNK were measured by RT-qPCR. The results revealed that TRPC6 protein expression, the cell apoptotic rate and the [Ca2+]i levels increased in a time-dependent manner in the H9c2 cells following the induction of I/R injury. The apoptotic rate and TRPC6 protein expression decreased when the cells were treated with DSS prior to the induction of I/R injury. The knockdown of JNK expression by siRNA decreased the p-JNK and TRPC6 protein expression levels in the H9c2 cells subjected to I/R injury. The protein expression levels of p-JNK and NF-κB in the nucleus increased significantly when the H9c2 cells were subjected to I/R injury, whereas NF-κB expression in the cytoplasm decreased in a time‑dependent manner. However, p-JNK, NF-κB and TRPC6 protein expression, the [Ca2+]i level and cell apoptosis decreased when the H9c2 cells were pre-treated with DSS or SP600125. Therefore, our data suggest that DSS prevents myocardial I/R injury by inhibiting p-JNK activation and NF-κB translocation, which potentially upregulate TRPC6 expression, increase the [Ca2+]i level, and result in the apoptosis of H9c2 cells.

PMID: 26718129 [PubMed - indexed for MEDLINE]

Racial and Ethnic Disparities in Health and Health Care: an Assessment and Analysis of the Awareness and Perceptions of Public Health Workers Implementing a Statewide Community Transformation Grant in Texas.

Recent Research Articles from UNTHSC - Fri, 10/14/2016 - 07:45
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Racial and Ethnic Disparities in Health and Health Care: an Assessment and Analysis of the Awareness and Perceptions of Public Health Workers Implementing a Statewide Community Transformation Grant in Texas.

J Racial Ethn Health Disparities. 2016 Mar;3(1):46-54

Authors: Akinboro O, Ottenbacher A, Martin M, Harrison R, James T, Martin E, Murdoch J, Linnear K, Cardarelli K

Abstract
INTRODUCTION: Little is known about the awareness of public health professionals regarding racial and ethnic disparities in health in the United States of America (USA). Our study objective was to assess the awareness and perceptions of a group of public health workers in Texas regarding racial health disparities and their chief contributing causes.
METHODS: We surveyed public health professionals working on a statewide grant in Texas, who were participants at health disparities' training workshops. Multivariable logistic regression was employed in examining the association between the participants' characteristics and their perceptions of the social determinants of health as principal causes of health disparities.
RESULTS: There were 106 respondents, of whom 38 and 35 % worked in health departments and non-profit organizations, respectively. The racial/ethnic groups with the highest incidence of HIV/AIDS and hypertension were correctly identified by 63 and 50 % of respondents, respectively, but only 17, and 32 % were knowledgeable regarding diabetes and cancer, respectively. Seventy-one percent of respondents perceived that health disparities are driven by the major axes of the social determinants of health. Exposure to information about racial/ethnic health disparities within the prior year was associated with a higher odds of perceiving that social determinants of health were causes of health disparities (OR 9.62; 95 % CI 2.77, 33.41).
CONCLUSION: Among public health workers, recent exposure to information regarding health disparities may be associated with their perceptions of health disparities. Further research is needed to investigate the impact of such exposure on their long-term perception of disparities, as well as the equity of services and programs they administer.

PMID: 26896104 [PubMed - indexed for MEDLINE]

Systolic pressure response to voluntary apnea predicts sympathetic tone in obstructive sleep apnea as a clinically useful index.

Recent Research Articles from UNTHSC - Fri, 10/14/2016 - 07:45
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Systolic pressure response to voluntary apnea predicts sympathetic tone in obstructive sleep apnea as a clinically useful index.

Auton Neurosci. 2016 Jan;194:38-45

Authors: Jouett NP, Hardisty JM, Mason JR, Niv D, Romano JJ, Watenpaugh DE, Burk JR, Smith ML

Abstract
The present investigation tested the hypotheses that systolic arterial pressure (SAP) responses to voluntary apnea (a) serve as a surrogate of sympathetic nerve activity (SNA), (b) can distinguish Obstructive Sleep Apnea (OSA) patients from control subjects and (c) can document autonomic effects of treatment. 9 OSA and 10 control subjects were recruited in a laboratory study; 44 OSA subjects and 78 control subjects were recruited in a clinical study; and 21 untreated OSA subjects and 14 well-treated OSA subjects were recruited into a treatment study. Each subject performed hypoxic and room air voluntary apneas in triplicate. Muscle SNA (MSNA) and continuous AP were measured during each apnea in the laboratory study, while systolic arterial pressure (SAP) responses were measured continuously and by standard auscultation in the clinical and treatment studies. OSA subjects exhibited increased mean arterial pressure (MAP), SAP and MSNA responses to hypoxic apnea (all P<0.01) and the SAP response highly correlated with the MSNA response (R(2)=0.72, P<0.001). Clinical assessment confirmed that OSA subjects exhibited markedly elevated SAP responses (P<0.01), while treated OSA subjects had a decreased SAP response to apnea (P<0.04) compared to poorly treated subjects. These data indicate that (a) OSA subjects exhibit increased pressor and MSNA responses to apnea, and that (b) voluntary apnea may be a clinically useful assessment tool of autonomic dysregulation and treatment efficacy in OSA.

PMID: 26774324 [PubMed - indexed for MEDLINE]

Comparison of Hallux Interphalangeal Joint Arthrodesis Fixation Techniques: A Retrospective Multicenter Study.

Recent Research Articles from UNTHSC - Fri, 10/14/2016 - 07:45
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Comparison of Hallux Interphalangeal Joint Arthrodesis Fixation Techniques: A Retrospective Multicenter Study.

J Foot Ankle Surg. 2016 Jan-Feb;55(1):22-7

Authors: Thorud JC, Jolley T, Shibuya N, Lew E, Britt M, Butterfield T, Boike A, Hardy M, Brancheau SP, Motley T, Jupiter DC

Abstract
Few studies have investigated the complications that occur after hallux interphalangeal joint arthrodesis. The present study evaluated complications in 152 patients aged 18 to 80 years from 2005 to 2012 from 4 different academic institutions after hallux interphalangeal joint arthrodesis. Overall, 65.8% of the patients had ≥1 complication. Infections occurred in 16.5%, dehiscence in 12.5%, and reoperations in 27.0%. The clinical nonunion rate was ≥17.8%, and the radiographic nonunion rate was ≥13.8%. After logistic regression analysis, only the study site and peripheral neuropathy were associated with having ≥1 complication (p < .01 and p < .05, respectively). Single screw fixation compared with other fixation did not have a statistically significant influence on the postoperative complications. However, when fixation was expanded to 4 categories, single screw fixation had lower infection and reoperation rates than either crossed Kirschner wires or other fixation category but not compared with crossed screws on multivariate logistic regression analysis. Although additional studies are warranted, the findings from the present study might aid in both the prognosis of complications and the support of the use of a single screw over crossed Kirchner wire fixation in hallux interphalangeal joint arthrodesis.

PMID: 25960055 [PubMed - indexed for MEDLINE]

Principles of Ocular Pharmacology.

Recent Research Articles from UNTHSC - Thu, 10/13/2016 - 07:32
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Principles of Ocular Pharmacology.

Handb Exp Pharmacol. 2016 Oct 12;

Authors: Park Y, Ellis D, Mueller B, Stankowska D, Yorio T

Abstract
Recently, in a poll by Research America, a significant number of individuals placed losing their eyesight as having the greatest impact on their lives more so than other conditions, such as limb loss or memory loss. When they were also asked to rank which is the worst disease that could happen to them, blindness was ranked first by African-Americans and second by Caucasians, Hispanics, and Asians. Therefore, understanding the mechanisms of disease progression in the eye is extremely important if we want to make a difference in people's lives. In addition, developing treatment programs for these various diseases that could affect our eyesight is also critical. One of the most effective treatments we have is in the development of specific drugs that can be used to target various components of the mechanisms that lead to ocular disease. Understanding basic principles of the pharmacology of the eye is important if one seeks to develop effective treatments. As our population ages, the incidence of devastating eye diseases increases. It has been estimated that more than 65 million people suffer from glaucoma worldwide (Quigley and Broman. Br J Ophthalmol 90:262-267, 2006). Add to this the debilitating eye diseases of age-related macular degeneration, diabetic retinopathy, and cataract, the number of people effected exceeds 100 million. This chapter focuses on ocular pharmacology with specific emphasis on basic principles and outlining where in the various ocular sites are drug targets currently in use with effective drugs but also on future drug targets.

PMID: 27730396 [PubMed - as supplied by publisher]

Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology.

Recent Research Articles from UNTHSC - Thu, 10/13/2016 - 07:32
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Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology.

Cancer Res. 2016 Oct 11;

Authors: Langevin HM, Keely P, Mao J, Hodge LM, Schleip R, Deng G, Hinz B, Swartz MA, de Valois BA, Zick S, Findley T

Abstract
Complementary and integrative treatments, such as massage, acupuncture, and yoga, are used by increasing numbers of cancer patients to manage symptoms and improve their quality of life. In addition, such treatments may have other important and currently overlooked benefits by reducing tissue stiffness and improving mobility. Recent advances in cancer biology are underscoring the importance of connective tissue in the local tumor environment. Inflammation and fibrosis are well-recognized contributors to cancer, and connective tissue stiffness is emerging as a driving factor in tumor growth. Physical-based therapies have been shown to reduce connective tissue inflammation and fibrosis and thus may have direct beneficial effects on cancer spreading and metastasis. Meanwhile, there is currently little knowledge on potential risks of applying mechanical forces in the vicinity of tumors. Thus, both basic and clinical research are needed to understand the full impact of integrative oncology on cancer biology as well as whole person health. Cancer Res; 1-4. ©2016 AACR.

PMID: 27729327 [PubMed - as supplied by publisher]

Whole mitochondrial genome genetic diversity in an Estonian population sample.

Recent Research Articles from UNTHSC - Thu, 10/13/2016 - 07:32
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Whole mitochondrial genome genetic diversity in an Estonian population sample.

Int J Legal Med. 2016 Jan;130(1):67-71

Authors: Stoljarova M, King JL, Takahashi M, Aaspõllu A, Budowle B

Abstract
Mitochondrial DNA is a useful marker for population studies, human identification, and forensic analysis. Commonly used hypervariable regions I and II (HVI/HVII) were reported to contain as little as 25% of mitochondrial DNA variants and therefore the majority of power of discrimination of mitochondrial DNA resides in the coding region. Massively parallel sequencing technology enables entire mitochondrial genome sequencing. In this study, buccal swabs were collected from 114 unrelated Estonians and whole mitochondrial genome sequences were generated using the Illumina MiSeq system. The results are concordant with previous mtDNA control region reports of high haplogroup HV and U frequencies (47.4 and 23.7% in this study, respectively) in the Estonian population. One sample with the Northern Asian haplogroup D was detected. The genetic diversity of the Estonian population sample was estimated to be 99.67 and 95.85%, for mtGenome and HVI/HVII data, respectively. The random match probability for mtGenome data was 1.20 versus 4.99% for HVI/HVII. The nucleotide mean pairwise difference was 27 ± 11 for mtGenome and 7 ± 3 for HVI/HVII data. These data describe the genetic diversity of the Estonian population sample and emphasize the power of discrimination of the entire mitochondrial genome over the hypervariable regions.

PMID: 26289416 [PubMed - indexed for MEDLINE]

Roles of disease severity and post-discharge outpatient visits as predictors of hospital readmissions.

Recent Research Articles from UNTHSC - Wed, 10/12/2016 - 13:41

Roles of disease severity and post-discharge outpatient visits as predictors of hospital readmissions.

BMC Health Serv Res. 2016 Oct 10;16(1):564

Authors: Wang H, Johnson C, Robinson RD, Nejtek VA, Schrader CD, Leuck J, Umejiego J, Trop A, Delaney KA, Zenarosa NR

Abstract
BACKGROUND: Risks prediction models of 30-day all-cause hospital readmissions are multi-factorial. Severity of illness (SOI) and risk of mortality (ROM) categorized by All Patient Refined Diagnosis Related Groups (APR-DRG) seem to predict hospital readmission but lack large sample validation. Effects of risk reduction interventions including providing post-discharge outpatient visits remain uncertain. We aim to determine the accuracy of using SOI and ROM to predict readmission and further investigate the role of outpatient visits in association with hospital readmission.
METHODS: Hospital readmission data were reviewed retrospectively from September 2012 through June 2015. Patient demographics and clinical variables including insurance type, homeless status, substance abuse, psychiatric problems, length of stay, SOI, ROM, ICD-10 diagnoses and medications prescribed at discharge, and prescription ratio at discharge (number of medications prescribed divided by number of ICD-10 diagnoses) were analyzed using logistic regression. Relationships among SOI, type of hospital visits, time between hospital visits, and readmissions were also investigated.
RESULTS: A total of 6011 readmissions occurred from 55,532 index admissions. The adjusted odds ratios of SOI and ROM predicting readmissions were 1.31 (SOI: 95 % CI 1.25-1.38) and 1.09 (ROM: 95 % CI 1.05-1.14) separately. Ninety percent (5381/6011) of patients were readmitted from the Emergency Department (ED) or Urgent Care Center (UCC). Average time interval from index discharge date to ED/UCC visit was 9 days in both the no readmission and readmission groups (p > 0.05). Similar hospital readmission rates were noted during the first 10 days from index discharge regardless of whether post-index discharge patient clinic visits occurred when time-to-event analysis was performed.
CONCLUSIONS: SOI and ROM significantly predict hospital readmission risk in general. Most readmissions occurred among patients presenting for ED/UCC visits after index discharge. Simply providing early post-discharge follow-up clinic visits does not seem to prevent hospital readmissions.

PMID: 27724889 [PubMed - in process]

Evaluation of the Illumina(®) Beta Version ForenSeq™ DNA Signature Prep Kit for use in genetic profiling.

Recent Research Articles from UNTHSC - Wed, 10/12/2016 - 13:41
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Evaluation of the Illumina(®) Beta Version ForenSeq™ DNA Signature Prep Kit for use in genetic profiling.

Forensic Sci Int Genet. 2016 Jan;20:20-9

Authors: Churchill JD, Schmedes SE, King JL, Budowle B

Abstract
While capillary electrophoresis-based technologies have been the mainstay for human identity typing applications, there are limitations with this methodology's resolution, scalability, and throughput. Massively parallel sequencing (MPS) offers the capability to multiplex multiple types of forensically-relevant markers and multiple samples together in one run all at an overall lower cost per nucleotide than traditional capillary electrophoresis-based methods; thus, addressing some of these limitations. MPS also is poised to expand forensic typing capabilities by providing new strategies for mixture deconvolution with the identification of intra-STR allele sequence variants and the potential to generate new types of investigative leads with an increase in the overall number and types of genetic markers being analyzed. The beta version of the Illumina ForenSeq DNA Signature Prep Kit is a MPS library preparation method with a streamlined workflow that allows for targeted amplification and sequencing of 63 STRs and 95 identity SNPs, with the option to include an additional 56 ancestry SNPs and 22 phenotypic SNPs depending on the primer mix chosen for amplification, on the MiSeq desktop sequencer (Illumina). This study was divided into a series of experiments that evaluated reliability, sensitivity of detection, mixture analysis, concordance, and the ability to analyze challenged samples. Genotype accuracy, depth of coverage, and allele balance were used as informative metrics for the quality of the data produced. The ForenSeq DNA Signature Prep Kit produced reliable, reproducible results and obtained full profiles with DNA input amounts of 1ng. Data were found to be concordant with current capillary electrophoresis methods, and mixtures at a 1:19 ratio were resolved accurately. Data from the challenged samples showed concordant results with current DNA typing methods with markers in common and minimal allele drop out from the large number of markers typed on these samples. This set of experiments indicates the beta version of the ForenSeq DNA Signature Prep Kit is a valid tool for forensic DNA typing and warrants full validation studies of this MPS technology.

PMID: 26433485 [PubMed - indexed for MEDLINE]

Heat Shock Protein 47 Promotes Glioma Angiogenesis.

Recent Research Articles from UNTHSC - Wed, 10/12/2016 - 13:41
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Heat Shock Protein 47 Promotes Glioma Angiogenesis.

Brain Pathol. 2016 Jan;26(1):31-42

Authors: Wu ZB, Cai L, Lin SJ, Leng ZG, Guo YH, Yang WL, Chu YW, Yang SH, Zhao WG

Abstract
Heat shock protein 47 (HSP47) is a collagen-binding protein, which has been recently found to express in glioma vessels. However, the expression profile of HSP47 in glioma patients and the underlying mechanisms of HSP47 on glioma angiogenesis are not fully explored. In the current study, we found that expression of HSP47 in glioma vessels was correlated with the grades of gliomas. HSP47 knockdown by siRNAs significantly decreased cell viability in vitro and tumor volume in vivo; moreover, it reduced the microvessel density (MVD) by CD31 immunohistochemistry in vivo. HSP47 knockdown significantly inhibited tube formation, invasion and proliferation of human umbilical vein endothelial cells (HUVECs). Furthermore, conditional medium derived from HSP47 knockdown cells significantly inhibited HUVECs tube formation and migration, while it increased chemosensitivity of HUVECs cells to Avastin. Silencing of HSP47 decreased VEGF expression in glioma cells consistently, and reduced glioma vasculature. Furthermore, HSP47 promoted glioma angiogenesis through HIF1α-VEGFR2 signaling. The present study demonstrates that HSP47 promotes glioma angiogenesis and highlights the importance of HSP47 as an attractive therapeutic target of GBM.

PMID: 25758142 [PubMed - indexed for MEDLINE]

Pathways between physical activity and quality of life in African-American breast cancer survivors.

Recent Research Articles from UNTHSC - Fri, 10/07/2016 - 07:38
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Pathways between physical activity and quality of life in African-American breast cancer survivors.

Support Care Cancer. 2016 Oct 5;:

Authors: Meadows R, Bonner T, Dobhal M, Borra S, Killion JA, Paxton R

Abstract
INTRODUCTION: Several studies have indicated that the relationship between physical activity and quality of life is not directed but mediated through various pathways. The purpose of this study was to assess the role of cancer-related fatigue, disability, and functional status as potential mediators in African-American breast cancer survivors.
METHODS: African-American breast cancer survivors (N = 135, mean age = 63) aged 55 years and older participated in a web-based survey consisting of measures assessing physical activity, functional status, cancer-related fatigue, disability, quality of life, and sociodemographic and medical characteristics. Structural equation modeling was used to assess the structural relationships among the constructs.
RESULTS: The initial structural model fit the data and revealed a significant relationship between physical activity and quality of life (β = 0.34, P < 0.01). Subsequent structural models with proposed complementary and mediating paths of fatigue, function, and disability fit the data. The adjusted model indicated that physical activity was no longer associated with quality of life (β = 0.11, P > 0.05) and mediated through pathways of functional status and fatigue (total β = 0.16, P < 0.01). The final adjusted model accounted for 32 % of the variance in quality of life.
CONCLUSION: Our data suggest that physical activity may be indirectly related to quality of life through pathways consisting of fatigue and functional status. Further longitudinal studies are needed to test the pathways through which varying levels of physical activity influence cancer-related and quality of life outcomes in minority cancer survivors.

PMID: 27709312 [PubMed - as supplied by publisher]

Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.

Recent Research Articles from UNTHSC - Fri, 10/07/2016 - 07:38
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Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.

Bioorg Med Chem Lett. 2016 Mar 1;26(5):1490-4

Authors: Acharya S, Rogers P, Krishnamoorthy RR, Stankowska DL, Dias HV, Yorio T

Abstract
Synthesis and bioactivity of novel dual acting nitric oxide releasing and reactive oxygen scavenging hybrid compound SA-2 is described. The hybrid molecule SA-2 significantly increased the superoxide dismutase enzyme level and protected the photoreceptor cells from H2O2 induced oxidative stress. Synthesis of ocular esterase sensitive aceloxy alkyl carbamate prodrug SA-4 with improved aqueous half-life is achieved to aid topical ocular formulation. This class of hybrid molecule and prodrug may have dual potential of improved IOP lowering and neuroprotection in glaucomatous optic neuropathy.

PMID: 26832784 [PubMed - indexed for MEDLINE]

CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders.

Recent Research Articles from UNTHSC - Fri, 10/07/2016 - 07:38
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CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders.

Curr Drug Targets. 2016;17(1):111-21

Authors: Mamik MK, Ghorpade A

Abstract
Chemokine CXCL8 is a low molecular weight neutrophil chemoattractant implicated in various neurodegenerative disorders including Alzheimer's disease and stroke. Increased expression of CXCL8 has been reported in serum, plasma and brain of human immunodeficiency virus (HIV)-1 infected individuals with neurocognitive impairment, indicating its role in neuroinflammation associated with HIV-1 infection of the brain. Since chemokines are critical in eliciting immune responses in the central nervous system (CNS), CXCL8 is of particular importance for being one of the first chemokines described in the brain. Activation of astrocytes and microglia by HIV-1 and virus associated proteins results in production of this chemokine in the brain microenvironment. Consequently, CXCL8 exerts its effect on target cells via Gprotein coupled receptors CXCR1 and CXCR2. Neutrophils are the main target cells for CXCL8; however, microglia and neurons also express CXCR1/CXCR2 and therefore are important targets for CXCL8-mediated crosstalk. The objective of this review is to focus on CXCL8 production, signaling and regulation in neuronal and glial cells in response to HIV-1 infection. We highlight the role of HIV-1 secreted proteins such as trans-activator of transcription, envelope glycoprotein, negative regulatory factor and viral protein r in the regulation of CXCL8. We discuss dual role of CXCL8 in neurodegeneration as well as neuroprotection in the CNS. Thus, targeting CXCL8 through the development of CXCR1/CXCR2-based therapeutic strategies to either selectively agonize or antagonize receptors may be able to selectively promote neuroprotective and anti-inflammatory outcomes, leading to significant clinical applications in many neuroinflammatory CNS diseases, including HIV-associated neurocognitive disorders.

PMID: 26112047 [PubMed - indexed for MEDLINE]

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