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Intensive Care Unit Admission With Community-Acquired Pneumonia.

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Intensive Care Unit Admission With Community-Acquired Pneumonia.

Am J Med Sci. 2015 Nov;350(5):380-6

Authors: Vohra AS, Tak HJ, Shah MB, Meltzer DO, Ruhnke GW

Abstract
BACKGROUND: There has been a dramatic increase in the use of intensive care units (ICUs) over the past 25 years. Greater use of validated measures of illness severity may better inform ICU admission decisions in patients with community-acquired pneumonia. This article examined predictors of ICU admission and hospitalization costs, including the pneumonia severity index (PSI) and CURB-65 (confusion, uremia, respiratory rate, blood pressure, age ≥65 years) scores.
METHODS: The study identified 422 patients hospitalized for community-acquired pneumonia, ascertaining patient characteristics by chart review and extraction of administrative data. Multivariate logistic regression was performed to quantify the association of the PSI, CURB-65 and comorbidities with ICU admission. The predictors of cost were estimated using a generalized linear model.
RESULTS: Compared to 194 general medicine patients, certain clinical and radiographic findings were more common among 228 ICU patients. Compared to PSI reference group I/II/III, ICU admission was strongly associated with risk class IV (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.63-5.72) and V (OR, 4.84; CI, 2.44-9.62), and also CURB-65 ≥3 (OR, 2.90; CI, 1.51-5.56). The relative increase in mortality among PSI risk class V (compared to IV) patients was 2.68 times higher in general medicine, compared with the ICU. Among ICU admissions, risk class V was associated with an additional cost of $14,548 (95% CI, $4,232 to $24,864).
CONCLUSIONS: Illness severity and chronic pulmonary disease are strong predictors of ICU admission. More extensive use of the PSI may optimize site-of-care decisions, thereby minimizing mortality and unnecessary resource utilization.

PMID: 26445305 [PubMed - indexed for MEDLINE]

Randomized trial of a dry-powder, fibrin sealant in vascular procedures.

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Randomized trial of a dry-powder, fibrin sealant in vascular procedures.

J Vasc Surg. 2015 Nov;62(5):1288-95

Authors: Gupta N, Chetter I, Hayes P, O-Yurvati AH, Moneta GL, Shenoy S, Pribble JP, Zuckerman LA

Abstract
OBJECTIVE: Topical hemostats are important adjuncts for stopping surgical bleeding. The safety and efficacy of Fibrocaps, a dry-powder, fibrin sealant containing human plasma-derived thrombin and fibrinogen, was evaluated in patients undergoing vascular surgical procedures.
METHODS: In this single-blind trial (clinicaltrials.gov: NCT01527357), adult patients were randomized 2:1 to Fibrocaps plus gelatin sponge (Fibrocaps) vs gelatin sponge alone. Results are presented for the patient subset undergoing vascular procedures with suture hole bleeding. The primary efficacy endpoint compared time to hemostasis (TTH) over 5 minutes. Safety follow-up continued to day 29.
RESULTS: A total of 175 patients were randomized and treated (Fibrocaps, 117; gelatin sponge, 58). Patients were predominately male (69%) and underwent arterial bypass (81%), arteriovenous graft formation (9%), or carotid endarterectomy (9%). Fibrocaps significantly reduced TTH compared with gelatin sponge (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.5-3.1; median TTH, 2 minutes; 95% CI, 1.5-2.5 vs 4 minutes; 95% CI, 3.0-5.0; P < .002). Significant reductions were also observed in patients receiving concomitant antiplatelet agents alone (HR, 2.8; 95% CI, 1.0-7.4; P = .03; n = 33), anticoagulants alone (HR, 2.0; 95% CI, 1.0-4.0; P = .04; n = 43), or both antiplatelet agents and anticoagulants (Fibrocaps vs gelatin sponge, HR, 2.3; 95% CI, 1.2-4.3; P = .008; n = 65). Incidences of common adverse events (procedural pain, nausea, constipation) were generally comparable between treatment arms. Anti-thrombin antibodies developed in 2% of Fibrocaps-treated patients and no-gelatin-sponge patients.
CONCLUSIONS: Fibrocaps, a ready-to-use, dry-powder fibrin sealant, was well-tolerated and reduced TTH in patients undergoing vascular procedures, including those receiving antiplatelet agents and/or anticoagulants, demonstrating its safety and usefulness as an adjunct to hemostasis.

PMID: 26254451 [PubMed - indexed for MEDLINE]

An impaired neuroimmune pathway promotes the development of hypertension in systemic lupus erythematosus.

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An impaired neuroimmune pathway promotes the development of hypertension in systemic lupus erythematosus.

Am J Physiol Regul Integr Comp Physiol. 2015 Nov 1;309(9):R1074-7

Authors: Mathis KW

Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that affects nearly 2 million people in the United States. The majority of SLE cases occur in women at an age in which the prevalence of hypertension and cardiovascular disease is typically low. However, women with SLE have a high prevalence of hypertension for reasons that remain unclear. Because immune cells and chronic inflammation have been implicated in the pathogenesis of both hypertension and SLE and because inflammation has been shown to be regulated by the autonomic nervous system, studies investigating neuroimmune mechanisms of hypertension could have direct and significant clinical implications. The purpose of this review is to introduce a recently described neuroimmune pathway and discuss its potential importance in the development of hypertension and renal injury during SLE.

PMID: 26084696 [PubMed - indexed for MEDLINE]

Elevation of intraocular pressure in rodents using viral vectors targeting the trabecular meshwork.

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Elevation of intraocular pressure in rodents using viral vectors targeting the trabecular meshwork.

Exp Eye Res. 2015 Dec;141:33-41

Authors: Pang IH, Millar JC, Clark AF

Abstract
Rodents are increasingly being used as glaucoma models to study ocular hypertension, optic neuropathy, and retinopathy. A number of different techniques are used to elevate intraocular pressure in rodent eyes by artificially obstructing the aqueous outflow pathway. Another successful technique to induce ocular hypertension is to transduce the trabecular meshwork of rodent eyes with viral vectors expressing glaucoma associated transgenes to provide more relevant models of glaucomatous damage to the trabecular meshwork. This technique has been used to validate newly discovered glaucoma pathogenesis pathways as well as to develop rodent models of primary open angle glaucoma. Ocular hypertension has successfully been induced by adenovirus 5 mediated delivery of mutant MYOC, bioactivated TGFβ2, SFRP1, DKK1, GREM1, and CD44. Advantages of this approach are: selective tropism for the trabecular meshwork, the ability to use numerous mouse strains, and the relatively rapid onset of IOP elevation. Disadvantages include mild-to-moderate ocular inflammation induced by the Ad5 vector and sometimes transient transgene expression. Current efforts are focused at discovering less immunogenic viral vectors that have tropism for the trabecular meshwork and drive sufficient transgene expression to induce ocular hypertension. This viral vector approach allows rapid proof of concept studies to study glaucomatous damage to the trabecular meshwork without the expensive and time-consuming generation of transgenic mouse lines.

PMID: 26025608 [PubMed - indexed for MEDLINE]

Non-continuous measurement of intraocular pressure in laboratory animals.

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Non-continuous measurement of intraocular pressure in laboratory animals.

Exp Eye Res. 2015 Dec;141:74-90

Authors: Millar JC, Pang IH

Abstract
Glaucoma is a leading cause of blindness, which is treatable but currently incurable. Numerous animal models therefore have both been and continue to be utilized in the study of numerous aspects of this condition. One important facet associated with the use of such models is the ability to accurately and reproducibly measure (by cannulation) or estimate (by tonometry) intraocular pressure (IOP). At this juncture there are several different approaches to IOP measurement in different experimental animal species, and the list continues to grow. We feel therefore that a review of this subject matter is timely and should prove useful to others who wish to perform similar measurements. The general principles underlying various types of tonometric and non-tonometric techniques for non-continuous determination of IOP are considered. There follows discussion of specific details as to how these techniques are applied to experimental animal species involved in the research of this disease. Specific comments regarding anesthesia, circadian rhythm, and animal handling are also included, especially in the case of rodents. Brief consideration is also given to possible future developments.

PMID: 25933714 [PubMed - indexed for MEDLINE]

Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles.

Recent Research Articles from UNTHSC - Sun, 02/07/2016 - 06:31

Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles.

J Control Release. 2016 Feb 2;

Authors: Pham K, Li D, Guo S, Penzak S, Dong X

Abstract
The aim of this study was to develop a nanotechnology to formulate a fixed-dose combination of poorly water-soluble drugs in a children-friendly, flexible solid dosage form. For diseases like HIV, pediatric patients are taking multiple drugs for effective treatments. Fixed-dose combinations could reduce pill burdens and costs as well as improving patient adherence. However, development of fixed-dose combinations of poorly water-soluble drugs for pediatric formulations is very challenging. We discovered a novel nanotechnology that produced in situ self-assembly nanoparticles (ISNPs) when the ISNP granules were introduced to water. In this study, antiretroviral drug granules, including lopinavir (LPV) ISNP granules and a fixed-dose combination of LPV/ritonavir (RTV) ISNP granules, were prepared using the ISNP nanotechnology, which spontaneously produced drug-loaded ISNPs in contact with water. Drug-loaded ISNPs had particle size less than 158nm with mono-dispersed distribution, over 95% entrapment efficiency for both LPV and RTV and stability over 8h in simulated physiological conditions. Drug-loaded ISNP granules with about 16% of LPV and 4% of RTV were palatable and stable at room temperature over 6months. Furthermore, LPV/RTV ISNP granules displayed a 2.56-fold increase in bioavailability and significantly increased LPV concentrations in tested tissues, especially in HIV sanctuary sites, as compared to the commercial LPV/RTV tablet (Kaletra®) in rats. Overall, the results demonstrated that the novel ISNP nanotechnology is a promising platform to manufacture palatable, "heat" stable, and flexible pediatric granules for fixed-dose combinations that can be used as sachets and sprinkles. To the best of our knowledge, this is the first report on this kind of novel nanotechnology for pediatric fixed-dose combinations of poorly water-soluble drugs.

PMID: 26849919 [PubMed - as supplied by publisher]

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

Recent Research Articles from UNTHSC - Fri, 02/05/2016 - 06:32

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

Forensic Sci Int Genet. 2016 Jan 21;22:54-63

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

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

PMID: 26844919 [PubMed - as supplied by publisher]

Evaluation of Xpert MTB/RIF to identify pulmonary tuberculosis in tuberculosis suspects from low and higher prevalence settings compared to acid fast smear and culture.

Recent Research Articles from UNTHSC - Thu, 02/04/2016 - 06:31

Evaluation of Xpert MTB/RIF to identify pulmonary tuberculosis in tuberculosis suspects from low and higher prevalence settings compared to acid fast smear and culture.

Clin Infect Dis. 2016 Feb 2;

Authors: Firnhaber C, Kendall MA, Wu X, Mazurek GH, Benator DA, Tuberculosis Trials Consortium, Arduino R, Fernandez M, Guy E, Johnson P, Metchock B, Sattler F, Telzak E, Wang YF, Weiner M, Swindells S, Sanne IM, Havlir DV, Grinsztejn B, Alland D, ACTG A5295 and TBTC Study 34 teams

Abstract
BACKGROUND:  Xpert MTB/RIF(Xpert) is a rapid nucleic acid amplification test widely used in high tuberculosis(TB) prevalence settings to detect tuberculosis as well as rpoB mutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation.
METHODS:  Xpert was compared to two sputa, each evaluated with AFB smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary TB from the US, Brazil, and South Africa.
RESULTS:  Of 992 participants enrolled with evaluable results, 22% had culture-confirmed TB. In 638(64%) US participants, one Xpert demonstrated sensitivity of 85.2%(96.7% in participants with AFB smear-positive(AFB+) sputum, 59.3% with AFB- sputum),specificity of 99.2%, NPV 97.6%, and PPV 94.9%. Results did not differ between higher and low prevalence settings. A second Xpert increased overall sensitivity to 91.1%(100% if AFB+, 71.4% if AFB-), with specificity of 98.9%. In US participants, a single negative Xpert predicted the absence of AFB+/culture+ tuberculosis with an NPV of 99.7%; NPV of two Xperts was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected TB DNA and mutations associated with rifampin resistance in five of seven participants with rifampin-resistant, culture+ tuberculosis. Specificity for rifampin resistance was 99.5%,NPV was 98.9%.
CONCLUSIONS:  In the US, Xpert testing performed comparably to two higher TB prevalence settings. These data support the use of Xpert in the initial evaluation of TB suspects and in algorithms assessing need for respiratory isolation.

PMID: 26839383 [PubMed - as supplied by publisher]

Neural Control of Blood Pressure in Chronic Intermittent Hypoxia.

Recent Research Articles from UNTHSC - Thu, 02/04/2016 - 06:31

Neural Control of Blood Pressure in Chronic Intermittent Hypoxia.

Curr Hypertens Rep. 2016 Mar;18(3):19

Authors: Shell B, Faulk K, Cunningham JT

Abstract
Sleep apnea (SA) is increasing in prevalence and is commonly comorbid with hypertension. Chronic intermittent hypoxia is used to model the arterial hypoxemia seen in SA, and through this paradigm, the mechanisms that underlie SA-induced hypertension are becoming clear. Cyclic hypoxic exposure during sleep chronically stimulates the carotid chemoreflexes, inducing sensory long-term facilitation, and drives sympathetic outflow from the hindbrain. The elevated sympathetic tone drives hypertension and renal sympathetic activity to the kidneys resulting in increased plasma renin activity and eventually angiotensin II (Ang II) peripherally. Upon waking, when respiration is normalized, the sympathetic activity does not diminish. This is partially because of adaptations leading to overactivation of the hindbrain regions controlling sympathetic outflow such as the nucleus tractus solitarius (NTS), and rostral ventrolateral medulla (RVLM). The sustained sympathetic activity is also due to enhanced synaptic signaling from the forebrain through the paraventricular nucleus (PVN). During the waking hours, when the chemoreceptors are not exposed to hypoxia, the forebrain circumventricular organs (CVOs) are stimulated by peripherally circulating Ang II from the elevated plasma renin activity. The CVOs and median preoptic nucleus chronically activate the PVN due to the Ang II signaling. All together, this leads to elevated nocturnal mean arterial pressure (MAP) as a response to hypoxemia, as well as inappropriately elevated diurnal MAP in response to maladaptations.

PMID: 26838032 [PubMed - in process]

A weighted U statistic for association analyses considering genetic heterogeneity.

Recent Research Articles from UNTHSC - Wed, 02/03/2016 - 06:36
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A weighted U statistic for association analyses considering genetic heterogeneity.

Stat Med. 2016 Feb 1;

Authors: Wei C, Elston RC, Lu Q

Abstract
Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright © 2016 John Wiley & Sons, Ltd.

PMID: 26833871 [PubMed - as supplied by publisher]

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

Recent Research Articles from UNTHSC - Wed, 02/03/2016 - 06:36
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Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.

Bioorg Med Chem Lett. 2015 Dec 11;

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 - as supplied by publisher]

Modified DOP-PCR for improved STR typing of degraded DNA from human skeletal remains and bloodstains.

Recent Research Articles from UNTHSC - Wed, 02/03/2016 - 06:36
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Modified DOP-PCR for improved STR typing of degraded DNA from human skeletal remains and bloodstains.

Leg Med (Tokyo). 2016 Jan;18:7-12

Authors: Ambers A, Turnbough M, Benjamin R, Gill-King H, King J, Sajantila A, Budowle B

Abstract
Forensic and ancient DNA samples often are damaged and in limited quantity as a result of exposure to harsh environments and the passage of time. Several strategies have been proposed to address the challenges posed by degraded and low copy templates, including a PCR based whole genome amplification method called degenerate oligonucleotide-primed PCR (DOP-PCR). This study assessed the efficacy of four modified versions of the original DOP-PCR primer that retain at least a portion of the 5' defined sequence and alter the number of bases on the 3' end. The use of each of the four modified primers resulted in improved STR profiles from environmentally-damaged bloodstains, contemporary human skeletal remains, American Civil War era bone samples, and skeletal remains of WWII soldiers over those obtained by previously described DOP-PCR methods and routine STR typing. Additionally, the modified DOP-PCR procedure allows for a larger volume of DNA extract to be used, reducing the need to concentrate the sample and thus mitigating the effects of concurrent concentration of inhibitors.

PMID: 26832369 [PubMed - in process]

Allosteric modulation of nicotinic acetylcholine receptors: the concept and therapeutic trends.

Recent Research Articles from UNTHSC - Wed, 02/03/2016 - 06:36
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Allosteric modulation of nicotinic acetylcholine receptors: the concept and therapeutic trends.

Curr Pharm Des. 2016 Jan 31;

Authors: Uteshev VV

Abstract
Expressing functional nicotinic acetylcholine receptors (nAChRs) may be beneficial to central neurons and neuronal networks because activation of nAChRs enhances neuronal resistance to injury, improves attention, cognitive performance, and produces robust anti-inflammatory and analgesic effects in mammals. Although exogenous orthosteric nAChR ligands present valuable tools in treatment of age- and trauma-related neurological deficits, therapeutic approaches that could amplify the brain's innate ability to maintain cholinergic homeostasis and resist injury may serve as intriguing and promising alternatives and have not been fully explored. One of these novel approaches utilizes positive allosteric modulators (PAMs) of nAChRs. Because of the ubiquitous expression of nAChRs in neuronal, glial and immune tissues, highly selective PAMs could amplify multiple endogenous neuroprotective, pro-cognitive, anti-inflammatory and anti-nociceptive cholinergic pathways to offset cholinergic hypofunction and generate therapeutic efficacy by targeting only a single player: i.e., nAChRs activated by endogenous cholinergic tone. In this article, I review the concept of allosteric modulation and current trends in therapeutic applications of nicotinic PAMs.

PMID: 26831463 [PubMed - as supplied by publisher]

Effect of an acute increase in central blood volume on cerebral hemodynamics.

Recent Research Articles from UNTHSC - Tue, 02/02/2016 - 06:38
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Effect of an acute increase in central blood volume on cerebral hemodynamics.

Am J Physiol Regul Integr Comp Physiol. 2015 Oct 15;309(8):R902-11

Authors: Ogoh S, Hirasawa A, Raven PB, Rebuffat T, Denise P, Lericollais R, Sugawara J, Normand H

Abstract
Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (-26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight (P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance (r = -0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV.

PMID: 26310936 [PubMed - indexed for MEDLINE]

Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response.

Recent Research Articles from UNTHSC - Tue, 02/02/2016 - 06:38
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Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response.

J Proteome Res. 2015 May 1;14(5):2158-68

Authors: Allen MS, Hurst GB, Lu TY, Perry LM, Pan C, Lankford PK, Pelletier DA

Abstract
Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) σ factors. To begin to investigate the regulatory network of one of these ECF σ factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by tandem mass spectrometry from cultures episomally expressing the ECF σ(RPA4225) (ecfT) versus a WT control. Among the proteins with the greatest increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein, and several regulatory proteins. Alignment of the cognate promoter regions driving expression of several upregulated proteins suggested a conserved binding motif in the -35 and -10 regions with the consensus sequence GGAAC-18N-TT. Additionally, the putative anti-σ factor RPA4224, whose gene is contained in the same predicted operon as RPA4225, was identified as interacting directly with the predicted response regulator RPA4223 by mass spectrometry of affinity-isolated protein complexes. Furthermore, another gene (RPA4226) coding for a protein that contains a cytoplasmic histidine kinase domain is located immediately upstream of RPA4225. The genomic organization of orthologs for these four genes is conserved in several other strains of R. palustris as well as in closely related α-Proteobacteria. Taken together, these data suggest that ECF σ(RPA4225) and the three additional genes make up a sigma factor mimicry system in R. palustris.

PMID: 25853567 [PubMed - indexed for MEDLINE]

The cholinergic potential, the vagus nerve and challenges in treatment of traumatic brain injury.

Recent Research Articles from UNTHSC - Fri, 01/29/2016 - 06:33

The cholinergic potential, the vagus nerve and challenges in treatment of traumatic brain injury.

Curr Pharm Des. 2016 Jan 26;

Authors: Uteshev VV, Tenovuo O, Gaidhani N

Abstract
Existing treatments of traumatic brain injury (TBI) have failed to reverse tremendous losses in productivity, independence and overall quality of life among TBI victims and therefore, cannot be viewed as sufficient. Although there is no shortage of promising basic concepts that may translate to efficacious therapies after TBI, the accumulated knowledge has yet to deliver treatments that adequately meet clinical and social demands. In this article, we discuss novel concepts, recent advances and accompanying challenges in developing cholinergic and related therapies after TBI.

PMID: 26818869 [PubMed - as supplied by publisher]

Innovative diagnostic tools for early detection of Alzheimer's disease.

Recent Research Articles from UNTHSC - Fri, 01/29/2016 - 06:33
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Innovative diagnostic tools for early detection of Alzheimer's disease.

Alzheimers Dement. 2015 May;11(5):561-78

Authors: Laske C, Sohrabi HR, Frost SM, López-de-Ipiña K, Garrard P, Buscema M, Dauwels J, Soekadar SR, Mueller S, Linnemann C, Bridenbaugh SA, Kanagasingam Y, Martins RN, O'Bryant SE

Abstract
Current state-of-the-art diagnostic measures of Alzheimer's disease (AD) are invasive (cerebrospinal fluid analysis), expensive (neuroimaging) and time-consuming (neuropsychological assessment) and thus have limited accessibility as frontline screening and diagnostic tools for AD. Thus, there is an increasing need for additional noninvasive and/or cost-effective tools, allowing identification of subjects in the preclinical or early clinical stages of AD who could be suitable for further cognitive evaluation and dementia diagnostics. Implementation of such tests may facilitate early and potentially more effective therapeutic and preventative strategies for AD. Before applying them in clinical practice, these tools should be examined in ongoing large clinical trials. This review will summarize and highlight the most promising screening tools including neuropsychometric, clinical, blood, and neurophysiological tests.

PMID: 25443858 [PubMed - indexed for MEDLINE]

Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research.

Recent Research Articles from UNTHSC - Fri, 01/29/2016 - 06:33
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Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research.

Alzheimers Dement. 2015 May;11(5):549-60

Authors: O'Bryant SE, Gupta V, Henriksen K, Edwards M, Jeromin A, Lista S, Bazenet C, Soares H, Lovestone S, Hampel H, Montine T, Blennow K, Foroud T, Carrillo M, Graff-Radford N, Laske C, Breteler M, Shaw L, Trojanowski JQ, Schupf N, Rissman RA, Fagan AM, Oberoi P, Umek R, Weiner MW, Grammas P, Posner H, Martins R, STAR-B and BBBIG working groups

Abstract
The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement provides (1) a synopsis of selected preanalytical methods utilized in many international AD cohort studies, (2) initial draft guidelines/SOPs for preanalytical methods, and (3) a list of required methodological information and protocols to be made available for publications in the field to foster cross-validation across cohorts and laboratories.

PMID: 25282381 [PubMed - indexed for MEDLINE]

Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity.

Recent Research Articles from UNTHSC - Thu, 01/28/2016 - 06:33

Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity.

Aging Dis. 2016 Jan;7(1):90-110

Authors: Luo X, Wu J, Jing S, Yan LJ

Abstract
Diabetes and its complications are caused by chronic glucotoxicity driven by persistent hyperglycemia. In this article, we review the mechanisms of diabetic glucotoxicity by focusing mainly on hyperglycemic stress and carbon stress. Mechanisms of hyperglycemic stress include reductive stress or pseudohypoxic stress caused by redox imbalance between NADH and NAD(+) driven by activation of both the polyol pathway and poly ADP ribose polymerase; the hexosamine pathway; the advanced glycation end products pathway; the protein kinase C activation pathway; and the enediol formation pathway. Mechanisms of carbon stress include excess production of acetyl-CoA that can over-acetylate a proteome and excess production of fumarate that can over-succinate a proteome; both of which can increase glucotoxicity in diabetes. For hyperglycemia stress, we also discuss the possible role of mitochondrial complex I in diabetes as this complex, in charge of NAD(+) regeneration, can make more reactive oxygen species (ROS) in the presence of excess NADH. For carbon stress, we also discuss the role of sirtuins in diabetes as they are deacetylases that can reverse protein acetylation thereby attenuating diabetic glucotoxicity and improving glucose metabolism. It is our belief that targeting some of the stress pathways discussed in this article may provide new therapeutic strategies for treatment of diabetes and its complications.

PMID: 26816666 [PubMed - as supplied by publisher]

Comparison of antioxidant and antiproliferative activity between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and fraction PII separated by column chromatography.

Recent Research Articles from UNTHSC - Wed, 01/27/2016 - 06:44

Comparison of antioxidant and antiproliferative activity between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and fraction PII separated by column chromatography.

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jan 8;

Authors: Jing S, Chai W, Guo G, Zhang X, Dai J, Yan LJ

Abstract
The aim of the present study was to compare the antioxidant and antiproliferative effects on cancer cells between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and its fraction PII that were separated by Biologic low pressure (LP) chromatography system followed by DEAE cellulose column chromatography. Results of in vitro experiments showed that the reducing power and the scavenging capacity of KCCP towards hydroxyl radicals (OH) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals increased in a concentration dependent manner and were stronger than that of fraction PII. Results of the antiproliferative effect of KCCP and fraction PII on cervical cancer HeLa cells, esophagus cancer Eca109 cells, and mouse ascites hepatomas H22 cells indicated that both KCCP and its fraction PII possessed inhibitory activity on all the tested cancer cells at a dose- and time-dependent manner, with KCCP showing higher inhibitory activity than that of fraction PII. The present study demonstrates that KCCP and its fraction PII have antioxidant properties that may help fight cancers.

PMID: 26809376 [PubMed - as supplied by publisher]

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