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

Recent Research Articles from UNTHSC - Tue, 08/01/2017 - 17:06
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The Essential Role of Neutrophils during Infection with the Intracellular Bacterial Pathogen Listeria monocytogenes.

J Immunol. 2016 Sep 01;197(5):1557-65

Authors: Witter AR, Okunnu BM, Berg RE

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

PMID: 27543669 [PubMed - indexed for MEDLINE]

Metabolic syndrome is associated with an increased incidence of subclinical hypothyroidism - A Cohort Study.

Recent Research Articles from UNTHSC - Sun, 07/30/2017 - 07:33
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Metabolic syndrome is associated with an increased incidence of subclinical hypothyroidism - A Cohort Study.

Sci Rep. 2017 Jul 28;7(1):6754

Authors: Chang CH, Yeh YC, Caffrey JL, Shih SR, Chuang LM, Tu YK

Abstract
Prior cross-sectional analyses have demonstrated an association between subclinical hypothyroidism and metabolic syndrome and selected components. However, the temporal relation between metabolic syndrome and declining thyroid function remains unclear. In a prospective study, an unselected cohort of 66,822 participants with and without metabolic syndrome were followed. A proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs for hypothyroidism. Exploratory analyses for the relation between components of metabolic syndrome and declining thyroid function were also undertaken. During an average follow-up of 4.2 years, the incident rates for subclinical hypothyroidism were substantially higher in participants who began the study with metabolic syndrome compared with metabolically normal controls. After controlling for risk factors, patients with metabolic syndrome were at a 21% excess risk of developing subclinical hypothyroidism (adjusted HR 1.21; 95% CI 1.03-1.42). When individual components were analyzed, an increased risk of subclinical hypothyroidism was associated with high blood pressure (1.24; 1.04-1.48) and high serum triglycerides (1.18; 1.00-1.39), with a trend of increasing risk as participants had additional more components. Individuals with metabolic syndrome are at a greater risk for developing subclinical hypothyroidism, while its mechanisms and temporal consequences of this observation remain to be determined.

PMID: 28754977 [PubMed - in process]

Mannich Ketones as Possible Antimycobacterial Agents.

Recent Research Articles from UNTHSC - Sat, 07/29/2017 - 07:42
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Mannich Ketones as Possible Antimycobacterial Agents.

Arch Pharm (Weinheim). 2017 Jul 28;:

Authors: Lutz Z, Orbán K, Bóna Á, Márk L, Maász G, Prókai L, Seress L, Lóránd T

Abstract
Twenty-three known unsaturated and fused Mannich ketones and their reduced derivatives (amino alcohols) were selected for an antituberculotic study. They were screened against several mycobacterial strains including Mycobacterium tuberculosis, M. xenopi, and M. gordonae, and minimum inhibitory concentration values were also determined using the standard antituberculotic drug isoniazid (INH) as a reference. Structure-activity relationships were also studied. The mode of action of the test compounds was investigated using transmission electron microscopy, high-performance liquid chromatography, and matrix-assisted desorption/ionization mass spectrometry. Several test substances proved to be as potent as INH, but their antimycobacterial spectra were broader than that of INH. Our findings suggest that their mode of action is probably through the inhibition of mycobacterial cell wall biosynthesis.

PMID: 28752666 [PubMed - as supplied by publisher]

Evaluation of InnoTyper® 21 in a sample of Rio de Janeiro population as an alternative forensic panel.

Recent Research Articles from UNTHSC - Fri, 07/28/2017 - 07:38
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Evaluation of InnoTyper® 21 in a sample of Rio de Janeiro population as an alternative forensic panel.

Int J Legal Med. 2017 Jul 26;:

Authors: Moura-Neto RS, Mello ICT, Silva R, Maette APC, Bottino CG, Woerner A, King J, Wendt F, Budowle B

Abstract
The use of bi-allelic markers such as retrotransposable element insertion polymorphisms or Innuls (for insertion/null) can overcome some limitations of short tandem repeat (STR) loci in typing forensic biological evidence. This study investigated the efficiency of the InnoTyper® 21 Innul markers in an urban admixed population sample in Rio de Janeiro (n = 40) and one highly compromised sample collected as evidence by the Rio de Janeiro police. No significant departures from Hardy-Weinberg equilibrium were detected after the Bonferroni correction (α' ≈ 0.05/20, p < 0.0025), and no significant linkage disequilibrium was observed between markers. Assuming loci independence, the cumulative random match probability (RMP) was 2.3 × 10(-8). A lower mean Fis value was obtained for this sample population compared with those of three North American populations (African-American, Southwest Hispanic, US Caucasian). Principal component analysis with the three North American populations and one from 21 East Asian population showed that African Americans segregated as an independent group while US Caucasian, Southwest Hispanic, East Asian, and Rio de Janeiro populations are in a single large heterogeneous group. Also, a full Innuls profile was produced from an evidence sample, despite the DNA being highly degraded. In conclusion, this system is a useful complement to standard STR kits.

PMID: 28748403 [PubMed - as supplied by publisher]

Sleep and Mental Health in the General Population of Elderly Women.

Recent Research Articles from UNTHSC - Fri, 07/28/2017 - 07:38
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Sleep and Mental Health in the General Population of Elderly Women.

J Prim Prev. 2017 Jul 26;:

Authors: Thomas KM, Redd LA, Wright JD, Hartos JL

Abstract
Sleep and mental health complaints are prevalent in the elderly and share common risk factors. We assessed the relationship between sleep and mental health in three representative samples of elderly women while controlling for multiple risk factors common to both. We performed this cross sectional secondary data analysis in 2015 using 2013 data from the Behavioral Risk Factor Surveillance System (BRFSS) for females ages 65 years and older from California (N = 1912), Florida (N = 9120), and Pennsylvania (N = 2429). We conducted multiple logistic regression analysis to assess the relationship between sleep duration group (short, moderate/reference, or long) and mental health issues in the past 30 days (yes or no) in elderly females, while controlling for multiple covariates. About 25% of the elderly females reported mental health issues and 20% reported short or long sleep durations. In adjusted analysis, compared to the elderly females in the moderate sleep duration group (averaging 6-8 h of sleep per day), those in the short and long sleep duration groups had increased prevalence of mental health issues by 66% and 26%, respectively. Mental health was also related to physical health issues including general health status, activity limitations, and chronic health conditions. Overall, sleep was related to mental health in representative samples of elderly females even after controlling for risk factors common to both. Even though we could not determine the direction of influence, the findings indicate a need for clinicians to screen their elderly female patients for both sleep and mental health issues, especially in those with physical health comorbidities.

PMID: 28748316 [PubMed - as supplied by publisher]

Nanomaterial Applications for Neurological Diseases and Central Nervous System Injury.

Recent Research Articles from UNTHSC - Thu, 07/27/2017 - 07:35
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Nanomaterial Applications for Neurological Diseases and Central Nervous System Injury.

Prog Neurobiol. 2017 Jul 22;:

Authors: Huang L, Hu J, Huang S, Wang B, Siaw-Debrah F, Nyanzu M, Zhang Y, Zhuge Q

Abstract
The effectiveness of noninvasive treatment for neurological disease is generally limited by the poor entry of therapeutic agents into the central nervous system (CNS). Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier thus, overcoming this problem has become one of the most significant challenges in the development of neurological therapeutics. Nanotechnology has emerged as an innovative alternative for treating neurological diseases. In fact, rapid advances in nanotechnology have provided promising solutions to this challenge. This review highlights the applications of nanomaterials in the developing neurological field and discusses the evidence for their efficacies.

PMID: 28743465 [PubMed - as supplied by publisher]

Protection of hamsters from mortality by reducing fecal moxifloxacin concentration with DAV131A in a model of moxifloxacin-induced Clostridium difficile colitis.

Recent Research Articles from UNTHSC - Wed, 07/26/2017 - 07:46
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Protection of hamsters from mortality by reducing fecal moxifloxacin concentration with DAV131A in a model of moxifloxacin-induced Clostridium difficile colitis.

Antimicrob Agents Chemother. 2017 Jul 24;:

Authors: Burdet C, Sayah-Jeanne S, Nguyen TT, Miossec C, Saint-Lu N, Pulse M, Weiss W, Andremont A, Mentré F, de Gunzburg J

Abstract
BACKGROUND: Lowering the gut exposure to antibiotics during treatments can prevent microbiota disruption. We evaluated the effect of an activated charcoal-based adsorbent, DAV131A, on fecal free moxifloxacin concentration and mortality in a hamster model of moxifloxacin-induced C. difficile infection.
METHODS: 215 hamsters receiving moxifloxacin subcutaneously (D1-D5) were orally infected at D3 with C. difficile spores. They received various doses (0-1800mg/kg/day) and schedules (BID, TID) of DAV131A (D1-D8). Moxifloxacin concentration and C. difficile counts were determined at D3, and mortality at D12. We compared mortality, moxifloxacin concentration and C. difficile counts according to DAV131A regimens, and modelled the link between DAV131A regimen, moxifloxacin concentration and mortality.
RESULTS: All hamsters that received no DAV131A died, but none of those that received 1800mg/kg/day. A significant dose-dependent relationship between DAV131A dose and (i) mortality rates, (ii) moxifloxacin concentration and (iii) C. difficile counts was evidenced. Mathematical modeling suggested that (i) lowering moxifloxacin concentration at D3, which was 58μg/g (95%CI=50-66) without DAV131A, to 17μg/g (14-21) would reduce mortality by 90% and (ii) this would be achieved with a daily DAV131A dose of 703mg/kg (596-809).
CONCLUSIONS: In this model of C. difficile infection, DAV131A reduced mortality in a dose-dependent manner by decreasing fecal free moxifloxacin concentration.

PMID: 28739791 [PubMed - as supplied by publisher]

Canonical Transient Receptor Potential 6 Channel: A New Target of Reactive Oxygen Species in Renal Physiology and Pathology.

Recent Research Articles from UNTHSC - Tue, 07/25/2017 - 07:34
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Canonical Transient Receptor Potential 6 Channel: A New Target of Reactive Oxygen Species in Renal Physiology and Pathology.

Antioxid Redox Signal. 2016 Nov 01;25(13):732-748

Authors: Ma R, Chaudhari S, Li W

Abstract
SIGNIFICANCE: Regulation of Ca(2+) signaling cascade by reactive oxygen species (ROS) is becoming increasingly evident and this regulation represents a key mechanism for control of many fundamental cellular functions. Canonical transient receptor potential (TRPC) 6, a member of Ca(2+)-conductive channel in the TRPC family, is widely expressed in kidney cells, including glomerular mesangial cells, podocytes, tubular epithelial cells, and vascular myocytes in renal microvasculature. Both overproduction of ROS and dysfunction of TRPC6 channel are involved in renal injury in animal models and human subjects. Although regulation of TRPC channel function by ROS has been well described in other tissues and cell types, such as vascular smooth muscle, this important cell regulatory mechanism has not been fully reviewed in kidney cells. Recent Advances: Accumulating evidence has shown that TRPC6 is a redox-sensitive channel, and modulation of TRPC6 Ca(2+) signaling by altering TRPC6 protein expression or TRPC6 channel activity in kidney cells is a downstream mechanism by which ROS induce renal damage.
CRITICAL ISSUES: This review highlights how recent studies analyzing function and expression of TRPC6 channels in the kidney and their response to ROS improve our mechanistic understanding of oxidative stress-related kidney diseases.
FUTURE DIRECTIONS: Although it is evident that ROS regulate TRPC6-mediated Ca(2+) signaling in several types of kidney cells, further study is needed to identify the underlying molecular mechanism. We hope that the newly identified ROS/TRPC6 pathway will pave the way to new, promising therapeutic strategies to target kidney diseases such as diabetic nephropathy. Antioxid. Redox Signal. 25, 732-748.

PMID: 26937558 [PubMed - indexed for MEDLINE]

Identification and Characterization of Novel Matrix-Derived Bioactive Peptides: A Role for Collagenase from Santyl® Ointment in Post-Debridement Wound Healing?

Recent Research Articles from UNTHSC - Tue, 07/25/2017 - 07:34
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Identification and Characterization of Novel Matrix-Derived Bioactive Peptides: A Role for Collagenase from Santyl® Ointment in Post-Debridement Wound Healing?

PLoS One. 2016;11(7):e0159598

Authors: Sheets AR, Demidova-Rice TN, Shi L, Ronfard V, Grover KV, Herman IM

Abstract
Debridement, the removal of diseased, nonviable tissue, is critical for clinicians to readily assess wound status and prepare the wound bed for advanced therapeutics or downstream active healing. Removing necrotic slough and eschar through surgical or mechanical methods is less specific and may be painful for patients. Enzymatic debridement agents, such as Clostridial collagenase, selectively and painlessly degrade devitalized tissue. In addition to its debriding activities, highly-purified Clostridial collagenase actively promotes healing, and our past studies reveal that extracellular matrices digested with this enzyme yield peptides that activate cellular migratory, proliferative and angiogenic responses to injury in vitro, and promote wound closure in vivo. Intriguingly, while collagenase Santyl® ointment, a sterile preparation containing Clostridial collagenases and other non-specific proteases, is a well-accepted enzymatic debridement agent, its role as an active healing entity has never been established. Based on our previous studies of pure Clostridial collagenase, we now ask whether the mixture of enzymes contained within Santyl® produces matrix-derived peptides that promote cellular injury responses in vitro and stimulate wound closure in vivo. Here, we identify novel collagen fragments, along with collagen-associated peptides derived from thrombospondin-1, multimerin-1, fibronectin, TGFβ-induced protein ig-h3 and tenascin-C, generated from Santyl® collagenase-digested human dermal capillary endothelial and fibroblastic matrices, which increase cell proliferation and angiogenic remodeling in vitro by 50-100% over controls. Using an established model of impaired healing, we further demonstrate a specific dose of collagenase from Santyl® ointment, as well as the newly-identified and chemically-synthesized ECM-derived peptides significantly increase wound re-epithelialization by 60-100% over saline-treated controls. These results not only confirm and extend our earlier studies using purified collagenase- and matrix-derived peptides to stimulate healing in vitro and in vivo, but these Santyl®-generated, matrix-derived peptides may also represent exciting new opportunities for creating advanced wound healing therapies that are enabled by enzymatic debridement and potentially go beyond debridement.

PMID: 27459729 [PubMed - indexed for MEDLINE]

Comparison of Outcomes between Individuals with Pure and Mixed Lupus Nephritis: A Retrospective Study.

Recent Research Articles from UNTHSC - Tue, 07/25/2017 - 07:34
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Comparison of Outcomes between Individuals with Pure and Mixed Lupus Nephritis: A Retrospective Study.

PLoS One. 2016;11(6):e0157485

Authors: Ilori TO, Enofe N, Oommen A, Cobb J, Navarrete J, Adedinsewo DA, Oshikoya O, Fevrier H, Farris AB, Plantinga L, Ojo AO

Abstract
INTRODUCTION: Lupus nephritis (LN) is a serious organ manifestation of systemic lupus erythematosus. Histologic overlap is relatively common in the six pathologic classes (I to VI) of LN. For example, mixed proliferative LN (MPLN) often includes features of classes III & V or classes IV & V combined. We performed a comparative evaluation of renal outcomes in patients with MPLN to patients with pure proliferative LN (PPLN) against pre-specified renal outcomes, and we also identified predictor of clinical outcomes among those with PPLN and MPLN.
HYPOTHESIS: Individuals with MPLN will have worse short-term renal outcomes compared to those with PPLN.
METHODS: We retrospectively reviewed 278 adult LN patients (≥18 years old) identified from an Emory University Hospital registry of native renal biopsies performed between January 2000 and December 2011. The final analytic sample consisted of individuals with a diagnosis of PPLN (n = 60) and MPLN (n = 96). We analyzed differences in clinical and laboratory characteristics at baseline. We also assessed associations between LN category and renal outcomes (complete remission and time to ESRD) with logistic and Cox proportional hazards models within two years of baseline.
RESULTS: The study population was predominantly female (83.97%) and African American (71.8%) with a mean age of 33.4 years at baseline. Over a median follow up of 1.02 years, we did not find any statistically significant associations between MPLN and the development of ESRD or remission when compared to patients with PPLN (adjusted HR = 0.30, 95% CI = 0.07, 1.26).
CONCLUSION: There was no association between mixed or pure histopathologic features of LN at presentation and rate of complete or partial remission but higher baseline eGFR was associated with a lower probability of complete remission among patients with lupus nephritis.

PMID: 27304068 [PubMed - indexed for MEDLINE]

Identification and analysis of mtDNA genomes attributed to Finns reveal long-stagnant demographic trends obscured in the total diversity.

Recent Research Articles from UNTHSC - Mon, 07/24/2017 - 01:35
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Identification and analysis of mtDNA genomes attributed to Finns reveal long-stagnant demographic trends obscured in the total diversity.

Sci Rep. 2017 Jul 21;7(1):6193

Authors: Översti S, Onkamo P, Stoljarova M, Budowle B, Sajantila A, Palo JU

Abstract
In Europe, modern mitochondrial diversity is relatively homogeneous and suggests an ubiquitous rapid population growth since the Neolithic revolution. Similar patterns also have been observed in mitochondrial control region data in Finland, which contrasts with the distinctive autosomal and Y-chromosomal diversity among Finns. A different picture emerges from the 843 whole mitochondrial genomes from modern Finns analyzed here. Up to one third of the subhaplogroups can be considered as Finn-characteristic, i.e. rather common in Finland but virtually absent or rare elsewhere in Europe. Bayesian phylogenetic analyses suggest that most of these attributed Finnish lineages date back to around 3,000-5,000 years, coinciding with the arrival of Corded Ware culture and agriculture into Finland. Bayesian estimation of past effective population sizes reveals two differing demographic histories: 1) the 'local' Finnish mtDNA haplotypes yielding small and dwindling size estimates for most of the past; and 2) the 'immigrant' haplotypes showing growth typical of most European populations. The results based on the local diversity are more in line with that known about Finns from other studies, e.g., Y-chromosome analyses and archaeology findings. The mitochondrial gene pool thus may contain signals of local population history that cannot be readily deduced from the total diversity.

PMID: 28733587 [PubMed - in process]

The many faces of the trabecular meshwork cell.

Recent Research Articles from UNTHSC - Sat, 07/22/2017 - 07:34
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The many faces of the trabecular meshwork cell.

Exp Eye Res. 2017 May;158:112-123

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 stress. 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 - indexed for MEDLINE]

Developing new targeting strategy for androgen receptor variants in castration resistant prostate cancer.

Recent Research Articles from UNTHSC - Thu, 07/20/2017 - 07:37

Developing new targeting strategy for androgen receptor variants in castration resistant prostate cancer.

Int J Cancer. 2017 Jul 19;:

Authors: Wang B, Lo UG, Wu K, Kapur P, Liu X, Huang J, Chen W, Hernandez E, Santoyo J, Ma SH, Pong RC, He D, Cheng YQ, Hsieh JT

Abstract
The presence of androgen receptor variant 7 (AR-V7) variants becomes a significant hallmark of castration resistant prostate cancer (CRPC) relapsed from hormonal therapy and is associated with poor survival of CRPC patients because of lacking a ligand-binding domain. Currently, it still lacks an effective agent to target AR-V7 or AR-Vs in general. Here, we showed a novel class of agents (thailanstatins, TSTs, spliceostatin A analogs) can significantly suppress the expression of AR-V7 mRNA and protein but in a less extent on the full-length AR expression. Mechanistically, TST-D is able to inhibit AR-V7 gene splicing by interfering the interaction between U2AF65 and SAP155 and preventing them from binding to polypyrimidine tract located between the branch point and the 3' splice site. In vivo, TST-D exhibits a potent tumor inhibitory effect on human CRPC xenografts leading to cell apoptosis. The machinery associated with AR gene splicing in CRPC is a potential target for drugs. Based on their potency in the suppression of AR-V7 responsible for the growth/survival of CRPC, TSTs representing a new class of anti-AR-V agents warrant further development into clinical application. This article is protected by copyright. All rights reserved.

PMID: 28722220 [PubMed - as supplied by publisher]

HIV Tat Impairs Neurogenesis through Functioning As a Notch Ligand and Activation of Notch Signaling Pathway.

Recent Research Articles from UNTHSC - Thu, 07/20/2017 - 07:37
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HIV Tat Impairs Neurogenesis through Functioning As a Notch Ligand and Activation of Notch Signaling Pathway.

J Neurosci. 2016 Nov 02;36(44):11362-11373

Authors: Fan Y, Gao X, Chen J, Liu Y, He JJ

Abstract
Alterations in adult neurogenesis have been noted in the brain of HIV-infected individuals and are likely linked to HIV-associated neurocognitive deficits, including those in learning and memory. But the underlying molecular mechanisms are not fully understood. In the study, we took advantage of doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) and determined the relationship between Tat expression and neurogenesis. Tat expression in astrocytes was associated with fewer neuron progenitor cells (NPCs), fewer immature neurons, and fewer mature neurons in the dentate gyrus of the hippocampus of the mouse brain. In vitro NPC-derived neurosphere assays showed that Tat-containing conditioned media from astrocytes or recombinant Tat protein inhibited NPC proliferation and migration and altered NPC differentiation, while immunodepletion of Tat from Tat-containing conditioned media or heat inactivation of recombinant Tat abrogated those effects. Notch signaling downstream gene Hes1 promoter-driven luciferase reporter gene assay and Western blotting showed that recombinant Tat or Tat-containing conditioned media activated Hes1 transcription and protein expression, which were abrogated by Tat heat inactivation, immunodepletion, and cysteine mutation at position 30. Last, Notch signaling inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) significantly rescued Tat-impaired NPC differentiation in vitro and neurogenesis in vivo Together, these results show that Tat adversely affects NPCs and neurogenesis through Notch signaling and point to the potential of developing Notch signaling inhibitors as HIV/neuroAIDS therapeutics.
SIGNIFICANCE STATEMENT: HIV infection of the CNS causes cognitive and memory deficits, which have become more prevalent in the era of combination antiretroviral therapy (cART). Neurogenesis is impaired in HIV-infected individuals. But the underlying molecular mechanisms remain largely unknown. In this study, we have discovered that HIV Tat impairs neurogenesis through the Notch signaling pathway. These findings are particularly important because Tat protein has recently been detected in the brain of HIV-infected individuals with HIV replication in the periphery being effectively controlled by cART. The current study not only further highlights the importance of HIV Tat protein in HIV/neuroAIDS, but also presents a new strategy to develop novel HIV/neuroAIDS therapeutics, particularly in the era of cART.

PMID: 27807176 [PubMed - indexed for MEDLINE]

"Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

Recent Research Articles from UNTHSC - Wed, 07/19/2017 - 19:39
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"Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

Colloids Surf B Biointerfaces. 2017 Jul 10;158:379-386

Authors: Pieretti S, Ranjan AP, Di Giannuario A, Mukerjee A, Marzoli F, Di Giovannandrea R, Vishwanatha JK

Abstract
Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia. PLGA-CUR administered intravenously was able to reduce the response to nociceptive stimuli in the formalin test and hyperalgesia induced by zymosan. Curcumin, instead, was inactive. Low-dose i.t. administration of PLGA-CUR significantly reduced allodynia produced by sciatic nerve ligation, whereas low doses of curcumin did not change the response to nociceptive stimuli. Long-lasting antinociceptive effects were observed when high doses of PLGA-CUR were administered intrathecally. At high doses, i.t. administration of curcumin only exerted rapid and transient antinociceptive effects. Measurement of cytokine and BDNF in the spinal cord of neuropathic mice demonstrate that the antinociceptive effects of PLGA-CUR depend on the reduction in cytokine release and BDNF in the spinal cord. The results demonstrate the effectiveness of PLGA-CUR and suggest that PLGA-CUR nanoformulation might be a new potential drug in the treatment of pain.

PMID: 28719859 [PubMed - as supplied by publisher]

Undiagnosed Liver Fibrosis in Patients Undergoing Pancreatoduodenectomy for Pancreatic Adenocarcinoma.

Recent Research Articles from UNTHSC - Wed, 07/19/2017 - 19:39
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Undiagnosed Liver Fibrosis in Patients Undergoing Pancreatoduodenectomy for Pancreatic Adenocarcinoma.

World J Surg. 2017 Jul 17;:

Authors: Gdowski A, Osman H, Butt U, Foster S, Jeyarajah DR

Abstract
BACKGROUND: Chronic obstruction of the biliary system may cause hepatic fibrosis and liver failure. The purpose of this study was to define the incidence of unrecognized liver fibrosis in patients undergoing pancreaticoduodenectomy (PD).
METHODS: Retrospective data were collected on patients undergoing PD during a 21-month period. Each patient had a core needle biopsy at the time of surgery by a hepatobiliary surgeon.
RESULTS: This study identified 36 consecutive patients who were referred to a tertiary center and underwent pancreatoduodenectomy during a period of 21 months. The majority of patients, 32 (88.8%), were diagnosed with pancreatic adenocarcinoma. Liver fibrosis was diagnosed in 23 (63.9%) patients. A total of 25 (69.4%) patients were found to have pathological evidence of cholestasis consistent with bile obstruction. Patients that were found to have evidence of obstruction had significantly increased odds that fibrosis stage 2 would be found on pathological diagnosis (OR 6.75, 95% CI 1.20-38.02, Fisher's exact test P value = 0.0312). There was no significant association in patients who were stented compared to non-stented patients and their diagnosis of high-grade fibrosis stage 2 (OR 1.5238, 95% CI 0.4019-5.7769, Fisher's exact test P value = 0.7360).
CONCLUSIONS: An astonishing 63.9% of patients who underwent PD were diagnosed with stage 1-4 liver fibrosis and half (47.2%) had fibrosis stage of 2 or more. Further, stent status had no significant impact on the degree of liver fibrosis. Liver fibrosis is currently underrecognized in patients undergoing PD, which is important for physicians to be conscious of as it is known that liver fibrosis increases morbidity and mortality.

PMID: 28717906 [PubMed - as supplied by publisher]

Systematic review of comparative effectiveness and health economics research relating to osteopathic manipulative treatment.

Recent Research Articles from UNTHSC - Tue, 07/18/2017 - 07:34

Systematic review of comparative effectiveness and health economics research relating to osteopathic manipulative treatment.

Musculoskelet Sci Pract. 2017 Jun;29:e16-e17

Authors: Licciardone JC

PMID: 28715303 [PubMed - in process]

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

Recent Research Articles from UNTHSC - Tue, 07/18/2017 - 07:34
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Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

Nat Genet. 2017 Jul 17;:

Authors: Sims R, van der Lee SJ, Naj AC, Bellenguez C, Badarinarayan N, Jakobsdottir J, Kunkle BW, Boland A, Raybould R, Bis JC, Martin ER, Grenier-Boley B, Heilmann-Heimbach S, Chouraki V, Kuzma AB, Sleegers K, Vronskaya M, Ruiz A, Graham RR, Olaso R, Hoffmann P, Grove ML, Vardarajan BN, Hiltunen M, Nöthen MM, White CC, Hamilton-Nelson KL, Epelbaum J, Maier W, Choi SH, Beecham GW, Dulary C, Herms S, Smith AV, Funk CC, Derbois C, Forstner AJ, Ahmad S, Li H, Bacq D, Harold D, Satizabal CL, Valladares O, Squassina A, Thomas R, Brody JA, Qu L, Sánchez-Juan P, Morgan T, Wolters FJ, Zhao Y, Garcia FS, Denning N, Fornage M, Malamon J, Naranjo MCD, Majounie E, Mosley TH, Dombroski B, Wallon D, Lupton MK, Dupuis J, Whitehead P, Fratiglioni L, Medway C, Jian X, Mukherjee S, Keller L, Brown K, Lin H, Cantwell LB, Panza F, McGuinness B, Moreno-Grau S, Burgess JD, Solfrizzi V, Proitsi P, Adams HH, Allen M, Seripa D, Pastor P, Cupples LA, Price ND, Hannequin D, Frank-García A, Levy D, Chakrabarty P, Caffarra P, Giegling I, Beiser AS, Giedraitis V, Hampel H, Garcia ME, Wang X, Lannfelt L, Mecocci P, Eiriksdottir G, Crane PK, Pasquier F, Boccardi V, Henández I, Barber RC, Scherer M, Tarraga L, Adams PM, Leber M, Chen Y, Albert MS, Riedel-Heller S, Emilsson V, Beekly D, Braae A, Schmidt R, Blacker D, Masullo C, Schmidt H, Doody RS, Spalletta G, Jr WTL, Fairchild TJ, Bossù P, Lopez OL, Frosch MP, Sacchinelli E, Ghetti B, Yang Q, Huebinger RM, Jessen F, Li S, Kamboh MI, Morris J, Sotolongo-Grau O, Katz MJ, Corcoran C, Dunstan M, Braddel A, Thomas C, Meggy A, Marshall R, Gerrish A, Chapman J, Aguilar M, Taylor S, Hill M, Fairén MD, Hodges A, Vellas B, Soininen H, Kloszewska I, Daniilidou M, Uphill J, Patel Y, Hughes JT, Lord J, Turton J, Hartmann AM, Cecchetti R, Fenoglio C, Serpente M, Arcaro M, Caltagirone C, Orfei MD, Ciaramella A, Pichler S, Mayhaus M, Gu W, Lleó A, Fortea J, Blesa R, Barber IS, Brookes K, Cupidi C, Maletta RG, Carrell D, Sorbi S, Moebus S, Urbano M, Pilotto A, Kornhuber J, Bosco P, Todd S, Craig D, Johnston J, Gill M, Lawlor B, Lynch A, Fox NC, Hardy J, ARUK Consortium, Albin RL, Apostolova LG, Arnold SE, Asthana S, Atwood CS, Baldwin CT, Barnes LL, Barral S, Beach TG, Becker JT, Bigio EH, Bird TD, Boeve BF, Bowen JD, Boxer A, Burke JR, Burns JM, Buxbaum JD, Cairns NJ, Cao C, Carlson CS, Carlsson CM, Carney RM, Carrasquillo MM, Carroll SL, Diaz CC, Chui HC, Clark DG, Cribbs DH, Crocco EA, DeCarli C, Dick M, Duara R, Evans DA, Faber KM, Fallon KB, Fardo DW, Farlow MR, Ferris S, Foroud TM, Galasko DR, Gearing M, Geschwind DH, Gilbert JR, Graff-Radford NR, Green RC, Growdon JH, Hamilton RL, Harrell LE, Honig LS, Huentelman MJ, Hulette CM, Hyman BT, Jarvik GP, Abner E, Jin LW, Jun G, Karydas A, Kaye JA, Kim R, Kowall NW, Kramer JH, LaFerla FM, Lah JJ, Leverenz JB, Levey AI, Li G, Lieberman AP, Lunetta KL, Lyketsos CG, Marson DC, Martiniuk F, Mash DC, Masliah E, McCormick WC, McCurry SM, McDavid AN, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Morris JC, Murrell JR, Myers AJ, O'Bryant S, Olichney JM, Pankratz VS, Parisi JE, Paulson HL, Perry W, Peskind E, Pierce A, Poon WW, Potter H, Quinn JF, Raj A, Raskind M, Reisberg B, Reitz C, Ringman JM, Roberson ED, Rogaeva E, Rosen HJ, Rosenberg RN, Sager MA, Saykin AJ, Schneider JA, Schneider LS, Seeley WW, Smith AG, Sonnen JA, Spina S, Stern RA, Swerdlow RH, Tanzi RE, Thornton-Wells TA, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Van Eldik LJ, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Wilhelmsen KC, Williamson J, Wingo TS, Woltjer RL, Wright CB, Yu CE, Yu L, Garzia F, Golamaully F, Septier G, Engelborghs S, Vandenberghe R, De Deyn PP, Fernadez CM, Benito YA, Thonberg H, Forsell C, Lilius L, Kinhult-Stählbom A, Kilander L, Brundin R, Concari L, Helisalmi S, Koivisto AM, Haapasalo A, Dermecourt V, Fievet N, Hanon O, Dufouil C, Brice A, Ritchie K, Dubois B, Himali JJ, Keene CD, Tschanz J, Fitzpatrick AL, Kukull WA, Norton M, Aspelund T, Larson EB, Munger R, Rotter JI, Lipton RB, Bullido MJ, Hofman A, Montine TJ, Coto E, Boerwinkle E, Petersen RC, Alvarez V, Rivadeneira F, Reiman EM, Gallo M, O'Donnell CJ, Reisch JS, Bruni AC, Royall DR, Dichgans M, Sano M, Galimberti D, St George-Hyslop P, Scarpini E, Tsuang DW, Mancuso M, Bonuccelli U, Winslow AR, Daniele A, Wu CK, GERAD/PERADES, CHARGE, ADGC, EADI, Peters O, Nacmias B, Riemenschneider M, Heun R, Brayne C, Rubinsztein DC, Bras J, Guerreiro R, Al-Chalabi A, Shaw CE, Collinge J, Mann D, Tsolaki M, Clarimón J, Sussams R, Lovestone S, O'Donovan MC, Owen MJ, Behrens TW, Mead S, Goate AM, Uitterlinden AG, Holmes C, Cruchaga C, Ingelsson M, Bennett DA, Powell J, Golde TE, Graff C, De Jager PL, Morgan K, Ertekin-Taner N, Combarros O, Psaty BM, Passmore P, Younkin SG, Berr C, Gudnason V, Rujescu D, Dickson DW, Dartigues JF, DeStefano AL, Ortega-Cubero S, Hakonarson H, Campion D, Boada M, Kauwe JK, Farrer LA, Van Broeckhoven C, Ikram MA, Jones L, Haines JL, Tzourio C, Launer LJ, Escott-Price V, Mayeux R, Deleuze JF, Amin N, Holmans PA, Pericak-Vance MA, Amouyel P, van Duijn CM, Ramirez A, Wang LS, Lambert JC, Seshadri S, Williams J, Schellenberg GD

Abstract
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10(-4)) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10(-8)) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10(-10), odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10(-10), OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10(-14), OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

PMID: 28714976 [PubMed - as supplied by publisher]

Expansion of Microbial Forensics.

Recent Research Articles from UNTHSC - Tue, 07/18/2017 - 07:34
Related Articles

Expansion of Microbial Forensics.

J Clin Microbiol. 2016 Aug;54(8):1964-74

Authors: Schmedes SE, Sajantila A, Budowle B

Abstract
Microbial forensics has been defined as the discipline of applying scientific methods to the analysis of evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes. Over the past 15 years, technology, particularly massively parallel sequencing, and bioinformatics advances now allow the characterization of microorganisms for a variety of human forensic applications, such as human identification, body fluid characterization, postmortem interval estimation, and biocrimes involving tracking of infectious agents. Thus, microbial forensics should be more broadly described as the discipline of applying scientific methods to the analysis of microbial evidence in criminal and civil cases for investigative purposes.

PMID: 26912746 [PubMed - indexed for MEDLINE]

Hookah use among adolescents: Differential cognitions about hookah and cigarettes.

Recent Research Articles from UNTHSC - Mon, 07/17/2017 - 07:36

Hookah use among adolescents: Differential cognitions about hookah and cigarettes.

Addict Behav. 2017 Jul 09;75:75-78

Authors: Barnett TE, Livingston MD

Abstract
Background Hookah use is prevalent among adolescent and young adult populations. The study assessed how positive cognitions toward cigarettes moderate the impact of positive hookah cognitions on past 30day hookah use among a representative sample of youth. Understanding cognitions about products can contribute to effective interventions. Methods Data from the 2015 Florida Youth Tobacco Survey was used to determine cognitions and use patterns among high school students. Weighted means and proportions were used for demographic comparisons for cognitions about products. t-Tests and chi-square analysis were conducted for differences between users and non-users. Logistic regressions were conducted for the modeling of interaction between hookah and cigarette cognition. Results Nearly one out of ten (9.6%) of adolescents reported current hookah use. Across all cognition measures, positive hookah cognitions were associated with current hookah use. Additionally, there was a pattern of hookah cognitions being more strongly associated with current hookah use among those students that did not endorse the equivalent cognition for traditional cigarettes. Conclusions Hookah cognitions were generally more associated with hookah use among youth who did not endorse positive cognitions for cigarettes compared to those that did endorse positive cognitions for cigarettes. This finding is novel given youth who feel negatively about cigarettes are more influenced by their hookah-specific cognitions. Youth who believe cigarettes pose harm may benefit from messaging about the harms of hookah. Interventions or prevention efforts that draw strong comparisons between cigarettes and hookah may be effective among youth.

PMID: 28711747 [PubMed - as supplied by publisher]

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