Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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Bone targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain.

Tue, 08/15/2017 - 07:36

Bone targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain.

Nanomedicine (Lond). 2017 Aug 14;:

Authors: Gdowski AS, Ranjan A, Sarker MR, Vishwanatha JK

Abstract
AIM: The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment.
MATERIALS & METHODS: Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed.
RESULTS: This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb.
CONCLUSION: This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

PMID: 28805551 [PubMed - as supplied by publisher]

Discharges with surgical procedures performed less often than once per month per hospital account for two-thirds of hospital costs of inpatient surgery.

Tue, 08/15/2017 - 07:36
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Discharges with surgical procedures performed less often than once per month per hospital account for two-thirds of hospital costs of inpatient surgery.

J Clin Anesth. 2017 Sep;41:99-103

Authors: O'Neill L, Dexter F, Park SH, Epstein RH

Abstract
STUDY OBJECTIVE: Most surgical discharges (54%) at the average hospital are for procedures performed no more often than once per month at that hospital. We hypothesized that such uncommon procedures would be associated with an even greater percentage of the total cost of performing all surgical procedures at that hospital.
DESIGN: Observational study.
SETTING: State of Texas hospital discharge abstract data: 4th quarter of 2015 and 1st quarter of 2016.
PATIENTS: Inpatients discharged with a major therapeutic ("operative") procedure.
MEASUREMENTS: For each of N=343 hospitals, counts of discharges, sums of lengths of stay (LOS), sums of diagnosis related group (DRG) case-mix weights, and sums of charges were obtained for each procedure or combination of procedures, classified by International Classification of Diseases version 10 Procedure Coding System (ICD-10-PCS). Each discharge was classified into 2 categories, uncommon versus not, defined as a procedure performed at most once per month versus those performed more often than once per month.
MAIN RESULTS: Major procedures performed at most once per month per hospital accounted for an average among hospitals of 68% of the total inpatient costs associated with all major therapeutic procedures. On average, the percentage of total costs associated with uncommon procedures was 26% greater than expected based on their share of total discharges (P<0.00001). Average percentage differences were insensitive to the endpoint, with similar results for the percentage of patient days and percentage of DRG case-mix weights.
CONCLUSIONS: Approximately 2/3rd (mean 68%) of inpatient costs among surgical patients can be attributed to procedures performed at most once per month per hospital. The finding that such uncommon procedures account for a large percentage of costs is important because methods of cost accounting by procedure are generally unsuitable for them.

PMID: 28802622 [PubMed - in process]

Uncommon combinations of ICD10-PCS or ICD-9-CM operative procedure codes account for most inpatient surgery at half of Texas hospitals.

Tue, 08/15/2017 - 07:36
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Uncommon combinations of ICD10-PCS or ICD-9-CM operative procedure codes account for most inpatient surgery at half of Texas hospitals.

J Clin Anesth. 2017 Sep;41:65-70

Authors: O'Neill L, Dexter F, Park SH, Epstein RH

Abstract
STUDY OBJECTIVE: Recently, there has been interest in activity-based cost accounting for inpatient surgical procedures to facilitate "value based" analyses. Research 10-20years ago, performed using data from 3 large teaching hospitals, found that activity-based cost accounting was practical and useful for modeling surgeons and subspecialties, but inaccurate for individual procedures. We hypothesized that these older results would apply to hundreds of hospitals, currently evaluable using administrative databases.
DESIGN: Observational study.
SETTING: State of Texas hospital discharge abstract data for 1st quarter of 2016, 4th quarter of 2015, 1st quarter of 2015, and 4th quarter of 2014.
PATIENTS: Discharged from an acute care hospital in Texas with at least 1 major therapeutic ("operative") procedure.
MEASUREMENTS: Counts of discharges for each procedure or combination of procedures, classified by ICD-10-PCS or ICD-9-CM.
MAIN RESULTS: At the average hospital, most surgical discharges were for procedures performed at most once a month at the hospital (54%, 95% confidence interval [CI] 51% to 55%). At the average hospital, approximately 90% of procedures were performed at most once a month at the hospital (93%, CI 93% to 94%). The percentages were insensitive to the quarter of the year. The percentages were 3% to 6% greater with ICD-10-PCS than for the superseded ICD 9 CM.
CONCLUSIONS: There are many different procedure codes, and many different combinations of codes, relative to the number of different hospital discharges. Since most procedures at most hospitals are performed no more than once a month, activity-based cost accounting with a sample size sufficient to be useful is impractical for the vast majority of procedures, in contrast to analysis by surgeon and/or subspecialty.

PMID: 28802614 [PubMed - in process]

Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials.

Sun, 08/13/2017 - 07:37
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Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials.

J Exp Clin Cancer Res. 2017 Aug 11;36(1):108

Authors: Gdowski AS, Ranjan A, Vishwanatha JK

Abstract
BACKGROUND: Elucidation of mechanisms regulating bone metastasis has progressed significantly in recent years and this has translated to many new therapeutic options for patients with bone metastatic cancers. However, the rapid rate of progress in both the basic science literature and therapies undergoing clinical trials makes staying abreast with current developments challenging. This review seeks to provide an update on the current state of the science in bone metastasis research and give a snap shot of therapies in clinical trials for bone metastatic cancer.
MAIN BODY: Bone metastasis represents a difficult to treat clinical scenario due to pain, increased fracture risk, decreased quality of life and diminished overall survival outcomes. Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. This osteotropism was first described by Stephen Paget nearly 100 years ago as the 'seed and soil' hypothesis. Once cancer cells arrive at the bone they encounter a variety of cells native to the bone microenvironment which contribute to the establishment of bone metastatic lesions. In the first part of this review, the 'seed and soil' hypothesis is revisited while emphasizing recent developments in understanding the impact of native bone microenvironment cells on the metastatic process. Next, approved therapies for treating bone metastasis at the systemic level as well as those that target the bone microenvironment are discussed and current National Comprehensive Cancer Network (NCCN) guidelines relating to treatment of bone metastases are summarized. Finally, all open interventional clinical trials for therapies relating to treatment of bone metastasis have been complied and categorized.
CONCLUSION: Understanding the recent advancements in bone metastasis research is important for continued development of novel bone targeted therapies. The plethora of ongoing clinical trials will hopefully translate into improved treatments options for patients suffering from bone metastatic cancers.

PMID: 28800754 [PubMed - in process]

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

Sat, 08/12/2017 - 07:44
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Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology.

Cancer Res. 2016 Nov 01;76(21):6159-6162

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

Abstract
Complementary and integrative treatments, such as massage, acupuncture, and yoga, are used by increasing numbers of cancer patients to manage symptoms and improve their quality of life. In addition, such treatments may have other important and currently overlooked benefits by reducing tissue stiffness and improving mobility. Recent advances in cancer biology are underscoring the importance of connective tissue in the local tumor environment. Inflammation and fibrosis are well-recognized contributors to cancer, and connective tissue stiffness is emerging as a driving factor in tumor growth. Physical-based therapies have been shown to reduce connective tissue inflammation and fibrosis and thus may have direct beneficial effects on cancer spreading and metastasis. Meanwhile, there is currently little knowledge on potential risks of applying mechanical forces in the vicinity of tumors. Thus, both basic and clinical research are needed to understand the full impact of integrative oncology on cancer biology as well as whole person health. Cancer Res; 76(21); 6159-62. ©2016 AACR.

PMID: 27729327 [PubMed - indexed for MEDLINE]

Exosomal Annexin II Promotes Angiogenesis and Breast Cancer Metastasis.

Sat, 08/12/2017 - 07:44
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Exosomal Annexin II Promotes Angiogenesis and Breast Cancer Metastasis.

Mol Cancer Res. 2017 Jan;15(1):93-105

Authors: Maji S, Chaudhary P, Akopova I, Nguyen PM, Hare RJ, Gryczynski I, Vishwanatha JK

Abstract
Tumor-derived exosomes are emerging mediators of tumorigenesis and tissue-specific metastasis. Proteomic profiling has identified Annexin II as one of the most highly expressed proteins in exosomes; however, studies focused on the biological role of exosomal Annexin II (exo-Anx II) are still lacking. In this study, mechanistic insight was sought regarding exo-Anx II and its function in angiogenesis and breast cancer metastasis. Multiple in vitro and in vivo techniques were used to study the role of exo-Anx II in angiogenesis. Using atomic force microscopy and Western blotting, exo-Anx II expression was characterized in normal and breast cancer cells. In addition, organ-specific metastatic breast cancer cells and animal models were used to define the role exo-Anx II in breast cancer metastasis. Results revealed that exo-Anx II expression is significantly higher in malignant cells than normal and premetastatic breast cancer cells. In vitro and in vivo studies demonstrated that exo-Anx II promotes tPA-dependent angiogenesis. Furthermore, in vivo analysis indicated that metastatic exosomes create a favorable microenvironment for metastasis, and exo-Anx II plays an important role in this process, as priming with Anx II-depleted exosomes reduces brain (∼4-fold) and lung (∼2-fold) metastasis. Upon delineating the mechanism, it was discovered that exo-Anx II causes macrophage-mediated activation of the p38MAPK, NF-κB, and STAT3 pathways and increased secretion of IL6 and TNFα. These data demonstrate an important role for exo-Anx II in breast cancer pathogenesis.
IMPLICATIONS: Exosome-associated Annexin II plays an important role in angiogenesis and breast cancer metastasis, which can be exploited as a potential biomarker as well as a therapeutic target for diagnosis and treatment of metastatic breast cancer. Mol Cancer Res; 15(1); 93-105. ©2016 AACR.

PMID: 27760843 [PubMed - indexed for MEDLINE]

The risk factors of 9-year follow-up on hypertension in middle-aged people in Tujia-Nationality settlement of China.

Fri, 08/11/2017 - 07:42

The risk factors of 9-year follow-up on hypertension in middle-aged people in Tujia-Nationality settlement of China.

J Hum Hypertens. 2017 Aug 10;:

Authors: Liu X, Liu C, Schenck H, Yi X, Wang H, Shi X

Abstract
The aim of this study was to investigate the risk factors of hypertension in middle-aged people within the Tujia-Nationality settlement in China. Demographics questionnaires and fitness tests were performed to identify the risk factors of hypertension in middle-aged people in the years 2005, 2010 and 2014 in the area of southwest Hubei of China. Of the 2428 participants, 568 were classified as hypertensive, giving an overall occurrence of hypertension at 23.4%, and the prevalence of hypertension was the highest in the year 2014 (34.9%). Furthermore, Tujia minority had a significantly higher risk for having hypertension (odds ratio=1.055 with 95% confidence interval (CI): 1.039-1.072; P=0.001) than Han people. Individuals with the lowest level of cardiorespiratory fitness (CRF) had a 2.483-fold risk for hypertension (95% CI, 1.530-4.031; P=0.001). Obesity and overweight individuals increased the risk by 3.470-fold and 2.124-fold, respectively, for having hypertension compared to normal weight people. Finally, white-collar workers had a 58.1 and 31.8% higher risk for hypertension than blue-collar workers in rural and urban areas, respectively. These results demonstrated that the prevalence of hypertension was higher between 2011 and 2014 in the area. The main risk factors for developing hypertension were found to be sex (as woman), Tujia minority, white-collar workers, overweight-obese, those with a middle school education, and those with the lowest CRF.Journal of Human Hypertension advance online publication, 10 August 2017; doi:10.1038/jhh.2017.58.

PMID: 28795685 [PubMed - as supplied by publisher]

The genetic structure of native Americans in North America based on the Globalfiler® STRs.

Fri, 08/11/2017 - 07:42
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The genetic structure of native Americans in North America based on the Globalfiler® STRs.

Leg Med (Tokyo). 2016 Nov;23:49-54

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

Abstract
Current forensic STR databases, such as CODIS, lack population genetic data on Native American populations. Information from a geographically diverse array of tribes is necessary to provide improved statistical estimates of the strength of associations with DNA evidence. The Globalfiler® STR markers were used to characterize the genetic structure of ten tribal populations from seven geographic regions in North America, including those not presently represented in forensic databases. Samples from the Arctic region, Baja California, California/Great Basin, the Southeast, Mexico, the Midwest, and the Southwest were analyzed for allele frequencies, observed and expected heterozygosities, and F-statistics. The tribal samples exhibited an FST or θ value above the conservative 0.03 estimate recommended by the National Research Council (NRC) for calculating random match probabilities among Native Americans. The greater differentiation among tribal populations computed here (θ=0.04) warrants the inclusion of additional regional Native American samples into STR databases.

PMID: 27890103 [PubMed - indexed for MEDLINE]

Strategies for the Management of Postoperative Anemia in Elective Orthopedic Surgery.

Fri, 08/11/2017 - 07:42
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Strategies for the Management of Postoperative Anemia in Elective Orthopedic Surgery.

Ann Pharmacother. 2016 Jul;50(7):578-85

Authors: Steuber TD, Howard ML, Nisly SA

Abstract
OBJECTIVE: To assess the use of oral iron, intravenous (IV) iron, and erythropoiesis-stimulating agents (ESAs) for the prevention and management of perioperative anemia in elective orthopedic surgery patients, and to provide a clinical algorithm for use.
DATA SOURCES: A PubMed and MEDLINE search was conducted from 1964 through March 2016 using the following search terms alone or in combination: orthopedic, surgery, elective, anemia, blood transfusion, iron, erythropoiesis-stimulating agents, and erythropoietin.
STUDY SELECTION AND DATA EXTRACTION: All English-language prospective and retrospective human studies and meta-analyses evaluating oral iron, IV iron, or ESA alone or in combination in elective orthopedic surgery patients were evaluated, provided they reported blood transfusion outcomes.
DATA SYNTHESIS: A total of 9 prospective and retrospective studies and 1 meta-analysis were identified and included. In the preoperative setting, administration of oral iron, IV iron, or ESA alone or in combination to correct underlying anemia led to significantly reduced transfusion rates. Transfusion requirements were generally less with combination therapy (ESA + oral or IV iron). In the short-term perioperative or postoperative period, use of oral or IV iron led to conflicting results, with some reporting a statistically significant reduction in blood transfusions, whereas others reported none.
CONCLUSIONS: In elective orthopedic surgery, IV or oral iron with or without an ESA may provide benefit in prevention of postoperative anemia and results in blood transfusion reduction without significantly increasing the risk of adverse events. These agents should be considered at the lowest effective dose with emphasis on administration prior to planned surgery.

PMID: 27147703 [PubMed - indexed for MEDLINE]

Cross-linked actin networks (CLANs) in glaucoma.

Thu, 08/10/2017 - 07:37
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Cross-linked actin networks (CLANs) in glaucoma.

Exp Eye Res. 2017 Jun;159:16-22

Authors: Bermudez JY, Montecchi-Palmer M, Mao W, Clark AF

Abstract
One of the major causes of decreased vision, irreversible vision loss and blindness worldwide is glaucoma. Increased intraocular pressure (IOP) is a major risk factor associated with glaucoma and its molecular mechanisms are not fully understood. The trabecular meshwork (TM) is the primary site of injury in glaucoma, and its dysfunction results in elevated IOP. The glaucomatous TM has increased extracellular matrix deposition as well as cytoskeletal rearrangements referred to as cross-linked actin networks (CLANs) that consist of dome like structures consisting of hubs and spokes. CLANs are thought to play a role in increased aqueous humor outflow resistance and increased IOP by creating stiffer TM cells and tissue. CLANs are inducible by glucocorticoids (GCs) and TGFβ2 in confluent TM cells and TM tissues. The signaling pathways of these induction agents give insight into the possible mechanisms of CLAN formation, but to date, the mechanism of CLANs regulation by these pathways has yet to be determined. Understanding the role CLANs play in IOP elevation and their mechanisms of induction and regulation may lead to novel treatment options to help prevent or intervene in glaucomatous damage to the trabecular meshwork.

PMID: 28238754 [PubMed - indexed for MEDLINE]

Predictors of Recall Error in Self-Report of Age at Alcohol Use Onset.

Thu, 08/10/2017 - 07:37
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Predictors of Recall Error in Self-Report of Age at Alcohol Use Onset.

J Stud Alcohol Drugs. 2016 Sep;77(5):811-8

Authors: Livingston MD, Xu X, Komro KA

Abstract
OBJECTIVE: The present study examined factors associated with recall error in the measurement of alcohol use onset and whether there was a tendency toward earlier or later self-reported age at alcohol use onset.
METHOD: This study estimated the effect of predictors on the presence and direction of recall error for age at alcohol use onset. The sample (n = 1,044) was from an existing longitudinal alcohol prevention trial in urban Chicago. Estimates were derived from a series of logistic regression models comparing agreement between a retrospective and a prospective measure of age at alcohol use onset.
RESULTS: Eligibility for free or reduced-price lunch in 6th grade, alcohol use in 6th grade, cigarette use in 12th grade, and alcohol use in 12th grade were significantly associated with recall error of age at alcohol use onset. Self-reported substance use (alcohol and tobacco) in 12th grade was also found to predict a later self-reported age at alcohol use onset when recalled.
CONCLUSIONS: Those most at risk for the negative outcomes associated with early alcohol initiation are also those most likely to misreport their age at alcohol use onset.

PMID: 27588540 [PubMed - indexed for MEDLINE]

Similarities in the Etiology of Alcohol Use Among Native American and Non-Native Young Women.

Thu, 08/10/2017 - 07:37
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Similarities in the Etiology of Alcohol Use Among Native American and Non-Native Young Women.

J Stud Alcohol Drugs. 2016 Sep;77(5):782-91

Authors: Komro KA, Livingston MD, Garrett BA, Boyd ML

Abstract
OBJECTIVE: This study examined social-and individual-level factors associated with alcohol use among young women and tested whether differences exist between Native American and non-Native young women.
METHOD: School-based surveys were conducted among 952 young women (ages 14-19) attending four high schools within the tribal jurisdictional service area of the Cherokee Nation in northeastern Oklahoma. Structural equation modeling using Mplus was used to assess the direct and indirect effects of social-and individual-level factors on subsequent alcohol use among Native and non-Native young women.
RESULTS: We found no differences in the level of risk and protective factors among Native and non-Native young women. Among Native and non-Native young women, alcohol access, parental communication, and best friends' alcohol use had statistically significant direct and/or indirect effects on alcohol use. Indirect effects were mediated through alcohol expectancies and norms. A history of alcohol problems by an adult in the household and depression were not retained as independent risk factors in either model.
CONCLUSIONS: We found more similarities than differences in level of and relations to alcohol use among social and individual risk and protective factors between Native American and non-Native young women from northeastern Oklahoma. The results provide support for universal prevention strategies, suggesting the importance of increasing perceptions that it is difficult to obtain alcohol and increasing parent-child communication.

PMID: 27588537 [PubMed - indexed for MEDLINE]

Relationships Among Chewing Tobacco, Cigarette Smoking, and Chronic Health Conditions in Males 18-44 Years of Age.

Wed, 08/09/2017 - 07:45
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Relationships Among Chewing Tobacco, Cigarette Smoking, and Chronic Health Conditions in Males 18-44 Years of Age.

J Prim Prev. 2017 Aug 07;:

Authors: Hernandez SL, Banks HE, Bailey AE, Bachman MJ, Kane J, Hartos JL

Abstract
As more public places are designated "non-smoking," chewing tobacco could be an alternative choice for tobacco use; however, controversy exists over the long-term health effects associated with it. This study assessed the relationship between chewing tobacco, cigarette smoking, and chronic health conditions in a representative sample of males 18-44 years of age, while controlling for other variables known to be related to tobacco use. This cross sectional analysis used 2013 data from the Behavioral Risk Factor Surveillance System (BRFSS). The results indicated that about 41% of males reported one or more chronic health conditions, and that about 15% used chewing tobacco only, 21% smoked cigarettes only, and 6% did both. From adjusted analyses, those who chewed tobacco only were 49% more likely to report one or more health conditions; those who smoked cigarettes only were 34% more likely to report one or more health conditions; and those who did both were 95% more likely to report at least one health condition. Overall, any combination of tobacco use was significantly and similarly related to the increased prevalence of chronic health conditions in males aged 18-44 years. Although chewing tobacco use may not be as prevalent in the general population as cigarette smoking, clinicians should be aware of the similar health risks associated with all tobacco use at ages younger than may be expected, and encourage cessation of any tobacco use.

PMID: 28785858 [PubMed - as supplied by publisher]

Negative regulation of Smad1 pathway and collagen IV expression by store-operated Ca(2+) entry in glomerular mesangial cells.

Wed, 08/09/2017 - 07:45
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Negative regulation of Smad1 pathway and collagen IV expression by store-operated Ca(2+) entry in glomerular mesangial cells.

Am J Physiol Renal Physiol. 2017 Jun 01;312(6):F1090-F1100

Authors: Wu P, Ren Y, Ma Y, Wang Y, Jiang H, Chaudhari S, Davis ME, Zuckerman JE, Ma R

Abstract
Collagen IV (Col IV) is a major component of expanded glomerular extracellular matrix in diabetic nephropathy and Smad1 is a key molecule regulating Col IV expression in mesangial cells (MCs). The present study was conducted to determine if Smad1 pathway and Col IV protein abundance were regulated by store-operated Ca(2+) entry (SOCE). In cultured human MCs, pharmacological inhibition of SOCE significantly increased the total amount of Smad1 protein. Activation of SOCE blunted high-glucose-increased Smad1 protein content. Treatment of human MCs with ANG II at 1 µM for 15 min, high glucose for 3 days, or TGF-β1 at 5 ng/ml for 30 min increased the level of phosphorylated Smad1. However, the phosphorylation of Smad1 by those stimuli was significantly attenuated by activation of SOCE. Knocking down Smad1 reduced, but expressing Smad1 increased, the amount of Col IV protein. Furthermore, activation of SOCE significantly attenuated high-glucose-induced Col IV protein production, and blockade of SOCE substantially increased the abundance of Col IV. To further verify those in vitro findings, we downregulated SOCE specifically in MCs in mice using small-interfering RNA (siRNA) against Orai1 (the channel protein mediating SOCE) delivered by the targeted nanoparticle delivery system. Immunohistochemical examinations showed that expression of both Smad1 and Col IV proteins was significantly greater in the glomeruli with positively transfected Orai1 siRNA compared with the glomeruli from the mice without Orai1 siRNA treatment. Taken together, our results indicate that SOCE negatively regulates the Smad1 signaling pathway and inhibits Col IV protein production in MCs.

PMID: 28298362 [PubMed - indexed for MEDLINE]

Impact of aging immune system on neurodegeneration and potential immunotherapies.

Tue, 08/08/2017 - 07:35
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Impact of aging immune system on neurodegeneration and potential immunotherapies.

Prog Neurobiol. 2017 Aug 03;:

Authors: Liang Z, Zhao Y, Ruan L, Zhu L, Jin K, Zhuge Q, Su DM, Zhao Y

Abstract
The interaction between the nervous and immune systems during aging is an area of avid interest, but many aspects remain unclear. This is due, not only to the complexity of the aging process, but also to a mutual dependency and reciprocal causation of alterations and diseases between both the nervous and immune systems. Aging of the brain drives whole body systemic aging, including aging-related changes of the immune system. In turn, the immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution that are sources of chronic inflammation in the elderly (termed inflammaging), potentially induces brain aging and memory loss in a reciprocal manner. Therefore, immunotherapeutics including modulation of inflammation, vaccination, cellular immune therapies and "protective autoimmunity" provide promising approaches to rejuvenate neuroinflammatory disorders and repair brain injury. In this review, we summarize recent discoveries linking the aging immune system with the development of neurodegeneration. Additionally, we discuss potential rejuvenation strategies, focusing aimed at targeting the aging immune system in an effort to prevent acute brain injury and chronic neurodegeneration during aging.

PMID: 28782588 [PubMed - as supplied by publisher]

Ontogenetic and functional modularity in the rodent mandible.

Sat, 08/05/2017 - 07:46
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Ontogenetic and functional modularity in the rodent mandible.

Zoology (Jena). 2017 Jun 08;:

Authors: Menegaz RA, Ravosa MJ

Abstract
The material properties of diets consumed by juvenile individuals are known to affect adult morphological outcomes. However, much of the current experimental knowledge regarding dietary effects on masticatory form is derived from studies in which individuals are fed a non-variable diet for the duration of their postweaning growth period. Thus, it remains unclear how intra-individual variation in diet, due to ontogenetic variation in feeding behaviors or seasonal resource fluctuations, affects the resulting adult morphology. Furthermore, the mandible is composed of multiple developmental and functional subunits, and the extent to which growth and plasticity among these modules is correlated may be misestimated by studies that examine non-variable masticatory function in adults only. To address these gaps in our current knowledge, this study raised Sprague Dawley rats (n=42) in four dietary cohorts from weaning to skeletal maturity. Two cohorts were fed a stable ("annual") diet of either solid or powdered pellets. The other two cohorts were fed a variable ("seasonal") diet consisting of solid/powdered pellets for the first half of the study, followed by a shift to the opposite diet. Results of longitudinal morphometric analyses indicate that variation in the mandibular corpus is more prominent at immature ontogenetic stages, likely due to processes of dental eruption and the growth of tooth roots. Furthermore, adult morphology is influenced by both masticatory function and the ontogenetic timing of this function, e.g., the consumption of a mechanically resistant diet. The morphology of the coronoid process was found to separate cohorts on the basis of their early weanling diet, suggesting that the coronoid process/temporalis muscle module may have an early plasticity window related to high growth rates during this life stage. Conversely, the morphology of the angular process was found to be influenced by the consumption of a mechanically resistant diet at any point during the growth period, but with a tendency to reflect the most recent diet. The prolonged plasticity window of the angular process/pterygomasseteric muscle module may be related to delayed ossification and muscular maturation within this module. The research presented here highlights the importance of more naturalistic models of mammalian feeding, and underscores the need for a better understanding of the processes of both morphological and behavioral maturation that follow weaning.

PMID: 28774721 [PubMed - as supplied by publisher]

Association Between Alcohol Outlets and HIV Prevalence in U.S. Counties.

Sat, 08/05/2017 - 07:46
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Association Between Alcohol Outlets and HIV Prevalence in U.S. Counties.

J Stud Alcohol Drugs. 2016 Nov;77(6):898-903

Authors: Rossheim ME, Thombs DL, Suzuki S

Abstract
OBJECTIVE: The current study examines associations between on- and off-premise alcohol retail outlets and HIV prevalence in counties across the United States during a 3-year period.
METHOD: Health department and U.S. Census Bureau surveillance data were analyzed from 1,523 counties in 47 states, representing more than 86% of the U.S. population. Multilevel Poisson regression models were used to examine the association between the number of on- and off-premise alcohol outlets in a county and HIV prevalence in the same county, adjusting for the between-year correlation of HIV prevalence within each county.
RESULTS: When we adjusted for potential confounders, number of on-premise alcohol outlets within a county was positively associated with HIV prevalence, whereas off-premise alcohol outlets were negatively associated with HIV prevalence.
CONCLUSIONS: The relations observed in this study are consistent with the niche theory of assortative drinking, which maintains that drinkers who are prone to risk taking may be attracted to alcohol outlets where they can expand their social networks to include similarly high-risk individuals who engage in both heavy drinking and sexual risk taking. This is the largest study conducted to date to examine the association between alcohol retail outlet types and HIV prevalence. Natural experiments are needed to examine specific policy changes that reduce outlet density and its association with HIV incidence.

PMID: 27797691 [PubMed - indexed for MEDLINE]

Cost of Illness in Inflammatory Bowel Disease.

Thu, 08/03/2017 - 07:35
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Cost of Illness in Inflammatory Bowel Disease.

Dig Dis Sci. 2017 Aug 01;:

Authors: Kamat N, Ganesh Pai C, Surulivel Rajan M, Kamath A

Abstract
BACKGROUND: Frequent relapses sometimes necessitating hospitalization and the absence of pharmacological cure contribute to substantial healthcare costs in inflammatory bowel diseases (IBDs). The costs of health care in Indian patients with IBD are unknown.
AIM: To evaluate the annual costs for treating Crohn's disease and ulcerative colitis.
METHODS: A prevalence-based, micro-costing method was used to assess the components of annual costs in a prospective, observational study conducted in a tertiary healthcare center enrolled over a 24-month period beginning of July 2014.
RESULTS: At enrollment, 43/59 (72.88%) patients with UC and 18/25 (72%) with CD were in remission. The annual median (IQR) cost per UC and CD patient in remission was INR 43,140 (34,357-51,031) [USD $707 (563-836)] and INR 43,763.5 (32,202-57,372) [USD $717 (527-940)], respectively, and in active disease was INR 52,436.5 (49,229-67,567.75) [$859 (807-1107)] and INR 72,145 (49,447-92,212) [USD $1182 (811-1512)], respectively. Compared with remission, active disease had a 1.4-fold higher cost for CD as compared to UC. In both groups, the greatest component of direct costs was drugs. Thirteen (22%) and 7 (28%) patients with UC and CD needed hospitalization accounting for 23.1 and 20.4% of the total costs, respectively. At one year, direct costs surmounted indirect costs in UC and CD (p < 0.001). Productivity losses contributed to 18.5 and 16% of the overall costs for UC and CD, respectively.
CONCLUSION: This first, panoptic, health economic study for IBD from India shows that the costs are driven by medication, productivity losses, and not merely hospitalization alone.

PMID: 28766243 [PubMed - as supplied by publisher]

Fluorescent biosensor for the detection of hyaluronidase: intensity-based ratiometric sensing and fluorescence lifetime-based sensing using a long lifetime azadioxatriangulenium (ADOTA) fluorophore.

Thu, 08/03/2017 - 07:35
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Fluorescent biosensor for the detection of hyaluronidase: intensity-based ratiometric sensing and fluorescence lifetime-based sensing using a long lifetime azadioxatriangulenium (ADOTA) fluorophore.

Anal Bioanal Chem. 2016 05;408(14):3811-21

Authors: Chib R, Mummert M, Bora I, Laursen BW, Shah S, Pendry R, Gryczynski I, Borejdo J, Gryczynski Z, Fudala R

Abstract
In this report, we have designed a rapid and sensitive, intensity-based ratiometric sensing as well as lifetime-based sensing probe for the detection of hyaluronidase activity. Hyaluronidase expression is known to be upregulated in various pathological conditions. We have developed a fluorescent probe by heavy labeling of hyaluronic acid with a new orange/red-emitting organic azadioxatriangulenium (ADOTA) fluorophore, which exhibits a long fluorescence lifetime (∼20 ns). The ADOTA fluorophore in water has a peak fluorescence lifetime of ∼20 ns and emission spectra centered at 560 nm. The heavily ADOTA-labeled hyaluronic acid (HA-ADOTA) shows a red shift in the peak emission wavelength (605 nm), a weak fluorescence signal, and a shorter fluorescence lifetime (∼4 ns) due to efficient self-quenching and formation of aggregates. In the presence of hyaluronidase, the brightness and fluorescence lifetime of the sample increase with a blue shift in the peak emission to its original wavelength at 560 nm. The ratio of the fluorescence intensity of the HA-ADOTA probe at 560 and 605 nm can be used as the sensing method for the detection of hyaluronidase. The cleavage of the hyaluronic acid macromolecule reduces the energy migration between ADOTA molecules, as well as the degree of self-quenching and aggregation. This probe can be efficiently used for both intensity-based ratiometric sensing as well as fluorescence lifetime-based sensing of hyaluronidase. The proposed method makes it a rapid and sensitive assay, useful for analyzing levels of hyaluronidase in relevant clinical samples like urine or plasma. Graphical Abstract Scheme showing cleavage of HA-ADOTA probe by hyaluronidase and the change in the emission spectrum of HA-ADOTA probe before and after cleavage by hyaluronidase.

PMID: 26993308 [PubMed - indexed for MEDLINE]

4-Chlorophenylguanidine is an ASIC3 agonist and positive allosteric modulator.

Wed, 08/02/2017 - 07:37
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4-Chlorophenylguanidine is an ASIC3 agonist and positive allosteric modulator.

J Pharmacol Sci. 2017 Mar;133(3):184-186

Authors: Agharkar AS, Gonzales EB

Abstract
Acid-sensing ion channels (ASICs) are proton-sensitive sodium channels that open in response to lowered extracellular pH and are expressed in the central and peripheral nervous systems. The ASIC3 subtype is found primarily in the periphery where the channel mediates pain signals caused by ischemia and inflammation. Here, we provide identify 4-chlorophenylguanidine (4-CPG) as an ASIC3 positive allosteric modulator and newest member of the growing group of guanidine modulators of ASICs. Furthermore, the 4-CPG reversed the effects of ASIC3 desensitization. The molecule 4-CPG offers a novel chemical backbone for the design of new ASIC3 ligands to study ASIC3 in vivo.

PMID: 28259560 [PubMed - indexed for MEDLINE]

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