Recent Research Articles from UNTHSC

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The many faces of the trabecular meshwork cell.

Sun, 07/24/2016 - 22:32
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The many faces of the trabecular meshwork cell.

Exp Eye Res. 2016 Jul 18;

Authors: Stamer WD, Clark AF

Abstract
With the combined purpose of facilitating useful vision over a lifetime, a number of ocular cells have evolved specialized features not found elsewhere in the body. The trabecular meshwork (TM) cell at the irido-corneal angle, which is a key regulator of intraocular pressure, is no exception. Examination of cells in culture isolated from the human TM has shown that they are unique in many ways, displaying characteristic features of several different cell types. Thus, these neural crest derived cells display expression patterns and behaviors typical of endothelia, fibroblasts, smooth muscle and macrophages, owing to the multiple roles and two distinct environments where they operate to maintain intraocular pressure homeostasis. In most individuals, TM cells function normally over a lifetime in the face of persistent stressors, including phagocytic, oxidative, mechanical and metabolic stresses. Study of TM cells isolated from ocular hypertensive eyes has shown a compromised ability to perform their daily duties. This review highlights the many responsibilities of the TM cell and its challenges, progress in our understanding of TM biology over the past 30 years, as well as discusses unanswered questions about TM dysfunction that results in IOP dysregulation and glaucoma.

PMID: 27443500 [PubMed - as supplied by publisher]

Are positive allosteric modulators of α7 nAChRs clinically safe?

Sun, 07/24/2016 - 22:32
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Are positive allosteric modulators of α7 nAChRs clinically safe?

J Neurochem. 2016 Jan;136(2):217-9

Authors: Uteshev V

PMID: 26182952 [PubMed - indexed for MEDLINE]

What's New in Musculoskeletal Infection: Update on Biofilms.

Fri, 07/22/2016 - 06:30

What's New in Musculoskeletal Infection: Update on Biofilms.

J Bone Joint Surg Am. 2016 Jul 20;98(14):1226-34

Authors: Nana A, Nelson SB, McLaren A, Chen AF

PMID: 27440572 [PubMed - in process]

The efficacy of novel anatomical sites for the assessment of muscle oxygenation during central hypovolemia.

Fri, 07/22/2016 - 06:30

The efficacy of novel anatomical sites for the assessment of muscle oxygenation during central hypovolemia.

Exp Biol Med (Maywood). 2016 Jul 19;

Authors: Sprick JD, Soller BR, Rickards CA

Abstract
Muscle tissue oxygenation (SmO2) can track central blood volume loss associated with hemorrhage. Traditional peripheral measurement sites (e.g., forearm) may not be practical due to excessive movement or injury (e.g., amputation). The aim of this study was to evaluate the efficacy of three novel anatomical sites for the assessment of SmO2 under progressive central hypovolemia. 10 male volunteers were exposed to stepwise prone lower body negative pressure to decrease central blood volume, while SmO2 was assessed at four sites-the traditional site of the flexor carpi ulnaris (ARM), and three novel sites not previously investigated during lower body negative pressure, the deltoid, latissimus dorsi, and trapezius. SmO2 at the novel sites was compared to the ARM sensor and to stroke volume responses. A reduction in SmO2 was detected by the ARM sensor at the first level of lower body negative pressure (-15 mmHg; P = 0.007), and at -30 (the deltoid), -45 (latissimus dorsi), and -60 mmHg lower body negative pressure (trapezius) at the novel sites (P ≤ 0.04). SmO2 responses at all novel sites were correlated with responses at the ARM (R ≥ 0.89), and tracked the reduction in stroke volume (R ≥ 0.87); the latissimus dorsi site exhibited the strongest linear correlations (R ≥ 0.96). Of the novel sensor sites, the latissimus dorsi exhibited the strongest linear associations with SmO2 at the ARM, and with reductions in central blood volume. These findings have important implications for detection of hemorrhage in austere environments (e.g., combat) when use of a peripheral sensor may not be ideal, and may facilitate incorporation of these sensors into uniforms.

PMID: 27439541 [PubMed - as supplied by publisher]

Stem geometry changes initial femoral fixation stability of a revised press-fit hip prosthesis: A finite element study.

Wed, 07/20/2016 - 15:30
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Stem geometry changes initial femoral fixation stability of a revised press-fit hip prosthesis: A finite element study.

Technol Health Care. 2016 Jul 8;

Authors: Russell RD, Huo MH, Rodrigues DC, Kosmopoulos V

Abstract
BACKGROUND: Stable femoral fixation during uncemented total hip arthroplasty is critical to allow for subsequent osseointegration of the prosthesis. Varying stem designs provide surgeons with multiple options to gain femoral fixation.
OBJECTIVE: The purpose of this study was to compare the initial fixation stability of cylindrical and tapered stem implants using two different underreaming techniques (press-fit conditions) for revision total hip arthroplasty (THA).
METHODS: A finite element femur model was created from three-dimensional computed tomography images simulating a trabecular bone defect commonly observed in revision THA. Two 18-mm generic femoral hip implants were modeled using the same geometry, differing only in that one had a cylindrical stem and the other had a 2 degree tapered stem. Surgery was simulated using a 0.05-mm and 0.01-mm press-fit and tested with a physiologically relevant loading protocol.
RESULTS: Mean contact pressure was influenced more by the surgical technique than by the stem geometry. The 0.05-mm press-fit condition resulted in the highest contact pressures for both the cylindrical (27.35 MPa) and tapered (20.99 MPa) stems. Changing the press-fit to 0.01-mm greatly decreased the contact pressure by 79.8% and 78.5% for the cylindrical (5.53 MPa) and tapered (4.52 MPa) models, respectively. The cylindrical stem geometry consistently showed less relative micromotion at all the cross-sections sampled as compared to the tapered stem regardless of press-fit condition.
CONCLUSIONS: This finite element analysis study demonstrates that tapered stem results in lower average contact pressure and greater micromotion at the implant-bone interface than a cylindrical stem geometry. More studies are needed to establish how these different stem geometries perform in such non-ideal conditions encountered in revision THA cases where less bone stock is available.

PMID: 27434281 [PubMed - as supplied by publisher]

Mycobacterium Tuberculosis Infection, Immigration Status, and Diagnostic Discordance: A Comparison of Tuberculin Skin Test and QuantiFERON-TB Gold In-Tube Test Among Immigrants to the U.S.

Wed, 07/20/2016 - 15:30
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Mycobacterium Tuberculosis Infection, Immigration Status, and Diagnostic Discordance: A Comparison of Tuberculin Skin Test and QuantiFERON-TB Gold In-Tube Test Among Immigrants to the U.S.

Public Health Rep. 2016 Mar-Apr;131(2):303-10

Authors: Wilson FA, Miller TL, Stimpson JP

Abstract
OBJECTIVE: We used a recent source of nationally representative population data on tuberculosis (TB) infection to characterize concordance between the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) blood test for immigrants in the United States.
METHODS: We used TB screening data from the 2011-2012 National Health and Nutrition Examination Survey to examine concordance between the TST and QFT-GIT--an interferon-gamma release assay (IGRA) blood test--for 7,097 U.S. natives, naturalized citizens, and noncitizens.
RESULTS: Consistent with prior findings, one in five immigrants in the survey was identified with latent TB infection (LTBI), a rate 14 times higher than for U.S. natives. We also found higher rates of discordant TST/IGRA results among immigrants than among U.S. natives. Unadjusted discordance between TST and IGRA was 3% among U.S. natives (weighted N=5,684,274 of 191,179,213) but ranged up to 19% for noncitizens (weighted N=3,722,960 of 19,377,147). Adjusting for age, sex, and race/ethnicity, noncitizens had more than nine times the odds of having a positive TST result but negative QFT-GIT result compared with U.S. natives.
CONCLUSIONS: Our findings suggest that whether and how either of these tests should be deployed is highly context sensitive. Significant discordance in test results when used among immigrants raises the possibility of missed opportunities for harm reduction in this already at-risk population. However, we found little distinction between the tests in terms of diagnostic outcome when used in a U.S. native population, suggesting little benefit to the adoption and use of the QFT-GIT test in place of TST on the basis of test performance alone for this population.

PMID: 26957665 [PubMed - indexed for MEDLINE]

The effects of metal ion PCR inhibitors on results obtained with the Quantifiler(®) Human DNA Quantification Kit.

Tue, 07/19/2016 - 18:30
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The effects of metal ion PCR inhibitors on results obtained with the Quantifiler(®) Human DNA Quantification Kit.

Forensic Sci Int Genet. 2015 Nov;19:180-9

Authors: Combs LG, Warren JE, Huynh V, Castaneda J, Golden TD, Roby RK

Abstract
Forensic DNA samples may include the presence of PCR inhibitors, even after extraction and purification. Studies have demonstrated that metal ions, co-purified at specific concentrations, inhibit DNA amplifications. Metal ions are endogenous to sample types, such as bone, and can be introduced from environmental sources. In order to examine the effect of metal ions as PCR inhibitors during quantitative real-time PCR, 2800 M DNA was treated with 0.0025-18.750 mM concentrations of aluminum, calcium, copper, iron, nickel, and lead. DNA samples, both untreated and metal-treated, were quantified using the Quantifiler(®) Human DNA Quantification Kit. Quantification cycle (Cq) values for the Quantifiler(®) Human DNA and internal PCR control (IPC) assays were measured and the estimated concentrations of human DNA were obtained. Comparisons were conducted between metal-treated and control DNA samples to determine the accuracy of the quantification estimates and to test the efficacy of the IPC inhibition detection. This kit is most resistant to the presence of calcium as compared to all metals tested; the maximum concentration tested does not affect the amplification of the IPC or quantification of the sample. This kit is most sensitive to the presence of aluminum; concentrations greater than 0.0750 mM negatively affected the quantification, although the IPC assay accurately assessed the presence of PCR inhibition. The Quantifiler(®) Human DNA Quantification Kit accurately quantifies human DNA in the presence of 0.5000 mM copper, iron, nickel, and lead; however, the IPC does not indicate the presence of PCR inhibition at this concentration of these metals. Unexpectedly, estimates of DNA quantity in samples treated with 18.750 mM copper yielded values in excess of the actual concentration of DNA in the samples; fluorescence spectroscopy experiments indicated this increase was not a direct interaction between the copper metal and 6-FAM dye used to label the probe that targets human DNA in the Quantifiler(®) kit. Evidence of inhibition was observed for the human-specific assay at a lower metal concentration than detected by the IPC, for all metals examined except calcium. These results strongly suggest that determination of a "true negative" sample should not be based solely on the failure of the IPC to indicate the presence of a PCR inhibitor and indicate that amplification of all samples should be attempted, regardless of the quantification results.

PMID: 26240969 [PubMed - indexed for MEDLINE]

An evaluation of the PowerSeq™ Auto System: A multiplex short tandem repeat marker kit compatible with massively parallel sequencing.

Tue, 07/19/2016 - 18:30
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An evaluation of the PowerSeq™ Auto System: A multiplex short tandem repeat marker kit compatible with massively parallel sequencing.

Forensic Sci Int Genet. 2015 Nov;19:172-9

Authors: Zeng X, King J, Hermanson S, Patel J, Storts DR, Budowle B

Abstract
Capillary electrophoresis (CE) and multiplex amplification with fluorescent tagging have been routinely used for STR typing in forensic genetics. However, CE-based methods restrict the number of markers that can be multiplexed simultaneously and cannot detect any intra-repeat variations within STRs. Several studies already have indicated that massively parallel sequencing (MPS) may be another potential technology for STR typing. In this study, the prototype PowerSeq(™) Auto System (Promega) containing the 23 STR loci and amelogenin was evaluated using Illumina MiSeq. Results showed that single source complete profiles could be obtained using as little as 62 pg of input DNA. The reproducibility study showed that the profiles generated were consistent among multiple typing experiments for a given individual. The mixture study indicated that partial STR profiles of the minor contributor could be detected up to 19:1 mixture. The mock forensic casework study showed that full or partial profiles could be obtained from different types of single source and mixture samples. These studies indicate that the PowerSeq Auto System and the Illumina MiSeq can generate concordant results with current CE-based methods. In addition, MPS-based systems can facilitate mixture deconvolution with the detection of intra-repeat variations within length-based STR alleles.

PMID: 26240968 [PubMed - indexed for MEDLINE]

Native American population data based on the Globalfiler(®) autosomal STR loci.

Sun, 07/17/2016 - 06:38

Native American population data based on the Globalfiler(®) autosomal STR loci.

Forensic Sci Int Genet. 2016 Jun 27;

Authors: Ng J, Oldt RF, McCulloh KL, Weise JA, Viray J, Budowle B, Smith DG, Kanthaswamy S

Abstract
Native American population data are limited and thus impact computing accurate statistical parameters for forensic investigations. Thus, additional information should be generated from geographically representative tribes in North America, particularly from those that are not included in existing population databases for forensic use. The Globafiler(®) PCR Amplification kit was used to produce STR genotypic data for 533 individuals who represent 31 Native American tribal populations derived from eight geographically diverse regions in North America. Population genetic estimates from 21 autosomal STRs are reported.

PMID: 27421760 [PubMed - as supplied by publisher]

Authors' Response.

Wed, 07/13/2016 - 06:30

Authors' Response.

J Forensic Sci. 2015 Nov;60(6):1669-1670

Authors: Moretti TR, Budowle B, Buckleton JS

PMID: 27404296 [PubMed - as supplied by publisher]

HDAC Inhibitor-Mediated Epigenetic Regulation of Glaucoma-Associated TGFβ2 in the Trabecular Meshwork.

Wed, 07/13/2016 - 06:30

HDAC Inhibitor-Mediated Epigenetic Regulation of Glaucoma-Associated TGFβ2 in the Trabecular Meshwork.

Invest Ophthalmol Vis Sci. 2016 Jul 1;57(8):3698-3707

Authors: Bermudez JY, Webber HC, Patel GC, Liu X, Cheng YQ, Clark AF, Mao W

Abstract
Purpose: Elevated intraocular pressure (IOP) in primary open-angle glaucoma (POAG) results from glaucomatous damage to the trabecular meshwork (TM). The glaucoma-associated factor TGFβ2 is increased in aqueous humor and TM of POAG patients. We hypothesize that histone acetylation has a role in dysregulated TGFβ2 expression.
Methods: Protein acetylation was compared between nonglaucomatous TM (NTM) and glaucomatous TM (GTM) cells using Western immunoblotting (WB). Nonglaucomatous TM cells were treated with 10 nM thailandepsin-A (TDP-A), a potent histone deacetylase inhibitor for 4 days. Total and nuclear proteins, RNA, and nuclear protein-DNA complexes were harvested for WB, quantitative PCR (qPCR), and chromatin immunoprecipitation (ChIP) assays, respectively. Paired bovine eyes were perfused with TDP-A versus DMSO, or TDP-A versus TDP-A plus the TGFβ pathway inhibitor LY364947 for 5 to 9 days. Intraocular pressure, TM, and perfusate proteins were compared.
Results: We found increased acetylated histone 3 and total protein acetylation in the GTM cells and TDP-A treated NTM cells. Chromatin immunoprecipitation assays showed that TDP-A induced histone hyperacetylation associated with the TGFβ2 promoter. This change of acetylation significantly increased TGFβ2 mRNA and protein expression in NTM cells. In perfusion-cultured bovine eyes, TDP-A increased TGFβ2 in the perfusate as well as elevated IOP. Histologic and immunofluorescent analyses showed increased extracellular matrix and cytoskeletal proteins in the TM of TDP-A treated bovine eyes. Cotreatment with the TGFβ pathway inhibitor LY364947 blocked TDP-A-induced ocular hypertension.
Conclusions: Our results suggest that histone acetylation has an important role in increased expression of the glaucoma-associated factor TGFβ2. Histone hyperacetylation may be the initiator of glaucomatous damage to the TM.

PMID: 27403998 [PubMed - as supplied by publisher]

Biomarkers in Sporadic and Familial Alzheimer's Disease.

Wed, 07/13/2016 - 06:30
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Biomarkers in Sporadic and Familial Alzheimer's Disease.

J Alzheimers Dis. 2015;47(2):291-317

Authors: Lista S, O'Bryant SE, Blennow K, Dubois B, Hugon J, Zetterberg H, Hampel H

Abstract
Most forms of Alzheimer's disease (AD) are sporadic (sAD) or inherited in a non-Mendelian fashion, and less than 1% of cases are autosomal-dominant. Forms of sAD do not exhibit familial aggregation and are characterized by complex genetic and environmental interactions. Recently, the expansion of genomic methodologies, in association with substantially larger combined cohorts, has resulted in various genome-wide association studies that have identified several novel genetic associations of AD. Currently, the most effective methods for establishing the diagnosis of AD are defined by multi-modal pathways, starting with clinical and neuropsychological assessment, cerebrospinal fluid (CSF) analysis, and brain-imaging procedures, all of which have significant cost- and access-to-care barriers. Consequently, research efforts have focused on the development and validation of non-invasive and generalizable blood-based biomarkers. Among the modalities conceptualized by the systems biology paradigm and utilized in the "exploratory biomarker discovery arena", proteome analysis has received the most attention. However, metabolomics, lipidomics, transcriptomics, and epigenomics have recently become key modalities in the search for AD biomarkers. Interestingly, biomarker changes for familial AD (fAD), in many but not all cases, seem similar to those for sAD. The integration of neurogenetics with systems biology/physiology-based strategies and high-throughput technologies for molecular profiling is expected to help identify the causes, mechanisms, and biomarkers associated with the various forms of AD. Moreover, in order to hypothesize the dynamic trajectories of biomarkers through disease stages and elucidate the mechanisms of biomarker alterations, updated and more sophisticated theoretical models have been proposed for both sAD and fAD.

PMID: 26401553 [PubMed - indexed for MEDLINE]

Investigation of the Dermal Absorption and Irritation Potential of Sertaconazole Nitrate Anhydrous Gel.

Tue, 07/12/2016 - 06:41

Investigation of the Dermal Absorption and Irritation Potential of Sertaconazole Nitrate Anhydrous Gel.

Pharmaceutics. 2016;8(3)

Authors: Manian M, Madrasi K, Chaturvedula A, Banga AK

Abstract
Effective topical therapy of cutaneous fungal diseases requires the delivery of the active agent to the target site in adequate concentrations to produce a pharmacological effect and inhibit the growth of the pathogen. In addition, it is important to determine the concentration of the drug in the skin in order to evaluate the subsequent efficacy and potential toxicity for topical formulations. For this purpose, an anhydrous gel containing sertaconazole nitrate as a model drug was formulated and the amount of the drug in the skin was determined by in vitro tape stripping. The apparent diffusivity and partition coefficients were then calculated by a mathematical model describing the dermal absorption as passive diffusion through a pseudo-homogenous membrane. The skin irritation potential of the formulation was also assessed by using the in vitro Epiderm™ model. An estimation of the dermal absorption parameters allowed us to evaluate drug transport across the stratum corneum following topical application. The estimated concentration for the formulation was found to be higher than the MIC100 at the target site which suggested its potential efficacy for treating fungal infections. The skin irritation test showed the formulation to be non-irritating in nature. Thus, in vitro techniques can be used for laying the groundwork in developing efficient and non-toxic topical products.

PMID: 27399763 [PubMed - as supplied by publisher]

The Effect of the Sigma-1 Receptor Selective Compound LS-1-137 on the DOI-Induced Head Twitch Response in Mice.

Tue, 07/12/2016 - 06:41

The Effect of the Sigma-1 Receptor Selective Compound LS-1-137 on the DOI-Induced Head Twitch Response in Mice.

Pharmacol Biochem Behav. 2016 Jul 7;

Authors: Malik M, Rangel-Barajas C, Mach RH, Luedtke RR

Abstract
Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (±)-2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds.

PMID: 27397487 [PubMed - as supplied by publisher]

Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline.

Tue, 07/12/2016 - 06:41
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Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline.

J Alzheimers Dis. 2015 Sep 24;48 Suppl 1:S171-91

Authors: Lista S, Molinuevo JL, Cavedo E, Rami L, Amouyel P, Teipel SJ, Garaci F, Toschi N, Habert MO, Blennow K, Zetterberg H, O'Bryant SE, Johnson L, Galluzzi S, Bokde AL, Broich K, Herholz K, Bakardjian H, Dubois B, Jessen F, Carrillo MC, Aisen PS, Hampel H

Abstract
There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer's disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials.

PMID: 26402088 [PubMed - indexed for MEDLINE]

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.

Sat, 07/09/2016 - 06:30

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 Jul 7;

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 - as supplied by publisher]

No increased risk of hospitalization for heart failure for patients treated with dipeptidyl peptidase-4 inhibitors in Taiwan.

Sat, 07/09/2016 - 06:30

No increased risk of hospitalization for heart failure for patients treated with dipeptidyl peptidase-4 inhibitors in Taiwan.

Int J Cardiol. 2016 Jun 24;220:14-20

Authors: Chang CH, Chang YC, Lin JW, Caffrey JL, Wu LC, Lai MS, Chuang LM

Abstract
BACKGROUND: Saxagliptin has been reported to be associated with an increased risk of hospitalization for heart failure (HF). The objective of this study was to test whether the increased risk is drug specific or a class effect for dipeptidyl peptidase-4 (DPP-4) inhibitors.
METHODS: Diabetic patients prescribed sitagliptin, saxagliptin, and vildagliptin between 2011 and 2013 were identified from Taiwan's National Health Insurance (NHI) claims database. The outcome of interest was the first hospitalization for HF. The patients were followed for one year from drug initiation to outcome occurrence, death, or study termination (December 31, 2013). A Cox proportional hazards regression model was used to calculate the hazard ratios (HR) and their 95% confidence intervals, using sitagliptin as the reference group.
RESULTS: A total of 239,669 patients, including 159,330 sitagliptin, 38,561 saxagliptin, and 41,778 vildagliptin initiators, were included in the analysis. With a follow-up period ranging from 269days (vildagliptin) to 313days (sitagliptin), the crude incidence rate of HF was 2.77, 2.63, and 1.91 per 100 person-years for sitagliptin, saxagliptin, and vildagliptin, respectively. Saxagliptin had a similar risk (HR: 0.98, 95% CI: 0.91-1.06) to sitagliptin, while vildagliptin was associated with a lower risk of HF (HR: 0.85, 95% CI: 0.78-0.93). Auxiliary analyses using acarbose (n=130,800) as a reference group consistently showed no increased risk of HF associated with DDP-4 inhibitors.
CONCLUSION: Three DPP-4 inhibitors studied seem to be safe regarding the risk of HF, while the reduced risk of vildagliptin might be a spurious association or a chance finding.

PMID: 27389437 [PubMed - as supplied by publisher]

Glucocorticoid Therapy and ocular hypertension.

Sat, 07/09/2016 - 06:30

Glucocorticoid Therapy and ocular hypertension.

Eur J Pharmacol. 2016 Jul 4;

Authors: Dibas A, Yorio T

Abstract
The projected number of people who will develop age-related macular degeneration in estimated at 2020 is 196 million and is expected to reach 288 million in 2040. Also, the number of people with Diabetic retinopathy will grow from 126.6 million in 2010 to 191.0 million by 2030. In addition, it is estimated that there are 2.3 million people suffering from uveitis worldwide. Because of the anti-inflammatory properties of glucocorticoids (GCs), they are often used topically and/or intravitreally to treat ocular inflammation conditions or edema associated with macular degeneration and diabetic retinopathy. Unfortunately, ocular GC therapy can lead to severe side effects. Serious and sometimes irreversible eye damage can occur as a result of the development of GC-induced ocular hypertension causing secondary open-angle glaucoma. According to the world health organization, glaucoma is the second leading cause of blindness in the world and it is estimated that 80 million will suffer from glaucoma by 2020. In the current review, mechanisms of GC-induced damage in ocular tissue, GC-resistance, and enhancing GC therapy will be discussed.

PMID: 27388141 [PubMed - as supplied by publisher]

Cross-sectional and longitudinal risk of physical impairment in a cohort of postmenopausal women who experience physical and verbal abuse.

Sat, 07/09/2016 - 06:30
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Cross-sectional and longitudinal risk of physical impairment in a cohort of postmenopausal women who experience physical and verbal abuse.

BMC Womens Health. 2015;15:98

Authors: Cannell MB, Weitlauf JC, Garcia L, Andresen EM, Margolis KL, Manini TM

Abstract
BACKGROUND: Exposure to interpersonal violence, namely verbal and physical abuse, is a highly prevalent threat to women's health and well-being. Among older, post-menopausal women, several researchers have characterized a possible bi-directional relationship of abuse exposure and diminished physical functioning. However, studies that prospectively examine the relationship between interpersonal abuse exposure and physical functioning across multiple years of observation are lacking. To address this literature gap, we prospectively evaluate the association between abuse exposure and physical functioning in a large, national cohort of post-menopausal women across 12 years of follow-up observation.
METHODS: Multivariable logistic regression was used to measure the adjusted association between experiencing abuse and physical function score at baseline in 154,902 Women's Health Initiative (WHI) participants. Multilevel modeling, where the trajectories of decline in physical function were modeled as a function of time-varying abuse exposure, was used to evaluate the contribution of abuse to trajectories of physical function scores over time.
RESULT: Abuse was prevalent among WHI participants, with 11 % of our study population reporting baseline exposure. Verbal abuse was the most commonly reported abuse type (10 %), followed by combined physical and verbal abuse (1 %), followed by physical abuse in the absence of verbal abuse (0.2 %). Abuse exposure (all types) was associated with diminished physical functioning, with women exposed to combined physical and verbal abuse presenting baseline physical functioning scores consistent with non-abused women 20 years senior. Results did not reveal a differential rate of decline over time in physical functioning based on abuse exposure.
CONCLUSIONS: Taken together, our findings suggest a need for increased awareness of the prevalence of abuse exposure among postmenopausal women; they also underscore the importance of clinician's vigilance in their efforts toward the prevention, early detection and effective intervention with abuse exposure, including verbal abuse exposure, in post-menopausal women. Given our findings related to abuse exposure and women's diminished physical functioning at WHI baseline, our work illuminates a need for further study, particularly the investigation of this association in younger, pre-menopausal women so that the temporal ordering if this relationship may be better understood.

PMID: 26554450 [PubMed - indexed for MEDLINE]

Aquaporins: Their role in gastrointestinal malignancies.

Thu, 07/07/2016 - 06:33
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Aquaporins: Their role in gastrointestinal malignancies.

Cancer Lett. 2016 Apr 1;373(1):12-8

Authors: Nagaraju GP, Basha R, Rajitha B, Alese OB, Alam A, Pattnaik S, El-Rayes B

Abstract
Aquaporins (AQPs) are small (~30 kDa monomers) integral membrane water transport proteins that allow water to flow through cell membranes in reaction to osmotic gradients in cells. In mammals, the family of AQPs has thirteen (AQP0-12) unique members that mediate critical biological functions. Since AQPs can impact cell proliferation, migration and angiogenesis, their role in various human cancers is well established. Recently, AQPs have been explored as potential diagnostic and therapeutic targets in gastrointestinal (GI) cancers. GI cancers encompass multiple sites including the colon, esophagus, stomach and pancreas. Research in the last three decades has revealed biological aspects and signaling pathways critical for the development of GI cancers. Since the majority of these cancers are very aggressive and rapidly metastasizes, identifying effective targets is crucial for treatment. Preclinical studies have utilized inhibitors of specific AQPs and knock down of AQP expression using siRNA. Although several studies have explored the role of AQPs in colorectal, esophageal, gastric, hepatocellular and pancreatic cancers, there is no comprehensive review compiling the available information on GI cancers as has been published for other malignancies such as ovarian cancer. Due to the similarities and association of various sites of GI cancers, it is helpful to consider these results collectively in order to better understand the role of specific AQPs in critical GI cancers. This review summarizes the current knowledge of the role of AQPs in GI malignancies with particular focus on diagnosis and therapeutic applications.

PMID: 26780474 [PubMed - indexed for MEDLINE]

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