Recent Research Articles from UNTHSC

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

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
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Cardiac Structure and Function in Well-Healed Burn Survivors.

Thu, 01/17/2019 - 10:29

Cardiac Structure and Function in Well-Healed Burn Survivors.

J Burn Care Res. 2019 Jan 10;:

Authors: Samuel TJ, Nelson MD, Nasirian A, Jaffery M, Moralez G, Romero SA, Cramer MN, Huang M, Kouda K, Hieda M, Sarma S, Crandall CG

Abstract
Long-term burn survivors have reduced aerobic capacity, placing them at increased risk for cardiovascular disease, morbidity and mortality. However, the exact mechanism contributing to a reduced aerobic capacity remains incompletely understood, but may be related to adverse cardiovascular remodeling. We therefore hypothesized that well-healed burn survivors would exhibit adverse left ventricular (LV) remodeling and impaired LV function. To test this hypothesis, 22 well-healed moderately burned individuals (age: 41 ± 14 years; BMI: 27.7 ± 5.4 kg/m2; male/female: 12/10; extent of burn: 37 ± 12 %BSA), 11 well-healed severely burned individuals (age: 43 ± 12 years; BMI: 29.5 ± 5.8 kg/m2; male/female: 8/3; extent of burn: 73 ± 11 %BSA), and 12 healthy, age-matched controls (age: 34 ± 9 years; BMI: 28.6 ± 5.2 kg/m2; male/female: 5/7) were enrolled in the study. All subjects were sedentary, performing less than 30 minutes of aerobic exercise per day, three day per week. LV morphology and function were assessed via cardiac magnetic resonance imaging. In contrast to our hypothesis, neither the presence nor severity of burn injury adversely affected LV morphology or function, when compared to equally sedentary non-burned controls. However, of note, LV mass of all three groups was in the lowest 5th percentile compared to normative values. Finally, group differences in LV morphology were largely explained by differences in aerobic capacity. Taken together, these data suggest a prior burn injury itself does not result in pathological remodeling of the LV, and support a role for aerobic exercise training to improve cardiac function.

PMID: 30649454 [PubMed - as supplied by publisher]

Retention in HIV Care Among Participants in the Patient-Centered HIV Care Model: A Collaboration Between Community-Based Pharmacists and Primary Medical Providers.

Thu, 01/17/2019 - 10:29

Retention in HIV Care Among Participants in the Patient-Centered HIV Care Model: A Collaboration Between Community-Based Pharmacists and Primary Medical Providers.

AIDS Patient Care STDS. 2019 Jan 16;:

Authors: Byrd KK, Hardnett F, Clay PG, Delpino A, Hazen R, Shankle MD, Camp NM, Suzuki S, Weidle PJ, Patient-Centered HIV Care Model Team

Abstract
Poor retention in HIV care is associated with higher morbidity and mortality and greater risk of HIV transmission. The Patient-Centered HIV Care Model (PCHCM) integrated community-based pharmacists with medical providers. The model required sharing of patient clinical information and collaborative therapy-related action planning. The proportion of persons retained in care (≥1 medical visit in each 6-month period of a 12-month measurement period with ≥60 days between visits), pre- and post-PCHCM implementation, was modeled using log binomial regression. Factors associated with post-implementation retention were determined using multi-variable regression. Of 765 enrolled persons, the plurality were male (n = 555) and non-Hispanic black (n = 331), with a median age of 48 years (interquartile range = 38-55); 680 and 625 persons were included in the pre- and post-implementation analyses, respectively. Overall, retention improved 12.9% (60.7-68.5%, p = 0.002). The largest improvement was seen among non-Hispanic black persons, 22.6% increase (59.7-73.2%, p < 0.001). Persons who were non-Hispanic black [adjusted risk ratio (ARR) 1.27, 95% confidence interval (CI) 1.08-1.48] received one or more pharmacist-clinic developed action plan (ARR 1.51, 95% CI 1.18-1.93), had three or more pharmacist encounters (ARR 1.17, 95% CI 1.05-1.30), were more likely to be retained post-implementation. In the final multi-variable models, only race/ethnicity [non-Hispanic black (ARR 1.27, 95% CI 1.09-1.48) and "other or unknown" race/ethnicity (ARR 1.36, 95% CI 1.14-1.63)] showed an association with post-implementation retention. PCHCM demonstrated how collaborations between community-based pharmacists and primary medical providers can improve retention in HIV care. This care model may be particularly useful for non-Hispanic black persons who often are less likely to be retained in care.

PMID: 30648888 [PubMed - as supplied by publisher]

Neuroprotective effects of inhibitors of Acid-Sensing ion channels (ASICs) in optic nerve crush model in rodents.

Thu, 01/17/2019 - 10:29
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Neuroprotective effects of inhibitors of Acid-Sensing ion channels (ASICs) in optic nerve crush model in rodents.

Curr Eye Res. 2018 01;43(1):84-95

Authors: Stankowska DL, Mueller BH, Oku H, Ikeda T, Dibas A

Abstract
PURPOSE: The purpose of the current study was to assess the potential involvement of acid-sensing ion channel 1 (ASIC1) in retinal ganglion cell (RGC) death and investigate the neuroprotective effects of inhibitors of ASICs in promoting RGC survival following optic nerve crush (ONC).
RESULTS: ASIC1 protein was significantly increased in optic nerve extracts at day 7 following ONC in rats. Activated calpain-1 increased at 2 and 7 days following ONC as evidenced by increased degradation of α-fodrin, known substrate of calpain. Glial fibrillary acidic protein levels increased significantly at 2 and 7 days post-injury. By contrast, glutamine synthetase increased at 2 days while decreased at 7 days. The inhibition of ASICs with amiloride and psalmotoxin-1 significantly increased RGC survival in rats following ONC (p < 0.05, one-way ANOVA). The mean number of surviving RGCs in rats (n = 6) treated with amiloride (100 µM) following ONC was 1477 ± 98 cells/mm2 compared with ONC (1126 ± 101 cells/mm2), where psalmotoxin-1 (1 μM) treated rats (n = 6) and subjected to ONC had 1441 ± 63 RGCs/mm2 compared with ONC (1065 ± 76 RGCs/mm2). Average number of RGCs in control rats (n = 12) was 2092 ± 46 cells/mm2. Blocking of ASICs also significantly increased RGC survival from ischemic-like insult from 473 ± 80 to 842 ± 49 RGCs/mm2 (for psalmotoxin-1) and from 628 ± 53 RGCs/mm2 to 890 ± 55 RGCs/mm2 (for amiloride) with p ≤ 0.05, using one-way ANOVA. Acidification (a known activator of ASIC1) increased intracellular Ca2+ ([Ca2+]i) in rat primary RGCs, which was statistically blocked by pretreatment with 100 nM psalmotoxin-1.
CONCLUSIONS: ASIC1 up-regulation-induced influx of extracellular calcium may be responsible for activation of calcium-sensitive calpain-1 in the retina. Calpain-1 induced degradation of α-fodrin and leads to morphological changes and eventually neuronal death. Therefore, blockers of ASIC1 can be used as potential therapeutics in the treatment of optic nerve degeneration.
ABBREVIATIONS: 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF); acid-sensing ion channels (ASICs); analysis of variance (ANOVA); bicinchoninic acid (BCA); brain-derived neurotrophic factor (BDNF); central nervous system (CNS); ciliary neurotrophic factor (CNTF); dimethyl sulfoxide (DMSO); endoplasmic reticulum (ER); ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA); ethylenediaminetetraacetic acid (EDTA); Food and Drug Administration (FDA); glial fibrillary acidic protein (GFAP); glutamine synthetase (GS); intraocular pressure (IOP); kilodalton (kDa); Krebs-Ringer Buffer (KRB); optic nerve crush (ONC); phosphate-buffered saline (PBS); plasma membrane (PM); polymerase chain reaction (PCR); retinal ganglion cell (RGC); RNA Binding Protein With Multiple Splicing (RBPMS); room temperature (RT); standard error of the mean (SEM).

PMID: 29111855 [PubMed - indexed for MEDLINE]

Potassium as a pluripotency-associated element identified through inorganic element profiling in human pluripotent stem cells.

Thu, 01/17/2019 - 10:29
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Potassium as a pluripotency-associated element identified through inorganic element profiling in human pluripotent stem cells.

Sci Rep. 2017 07 10;7(1):5005

Authors: Lin VJT, Zolekar A, Shi Y, Koneru B, Dimitrijevich S, Di Pasqua AJ, Wang YC

Abstract
Despite their well-known function in maintaining normal cell physiology, how inorganic elements are relevant to cellular pluripotency and differentiation in human pluripotent stem cells (hPSCs) has yet to be systematically explored. Using total reflection X-ray fluorescence (TXRF) spectrometry and inductively coupled plasma mass spectrometry (ICP-MS), we analyzed the inorganic components of human cells with isogenic backgrounds in distinct states of cellular pluripotency. The elemental profiles revealed that the potassium content of human cells significantly differs when their cellular pluripotency changes. Pharmacological treatment that alters cell membrane permeability to potassium affected the maintenance and establishment of cellular pluripotency via multiple mechanisms in bona fide hPSCs and reprogrammed cells. Collectively, we report that potassium is a pluripotency-associated inorganic element in human cells and provide novel insights into the manipulation of cellular pluripotency in hPSCs by regulating intracellular potassium.

PMID: 28694442 [PubMed - indexed for MEDLINE]

Duty of Notification and Aviation Safety-A Study of Fatal Aviation Accidents in the United States in 2015.

Wed, 01/16/2019 - 07:29
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Duty of Notification and Aviation Safety-A Study of Fatal Aviation Accidents in the United States in 2015.

Int J Environ Res Public Health. 2018 06 13;15(6):

Authors: Vuorio A, Budowle B, Sajantila A, Laukkala T, Junttila I, Kravik SE, Griffiths R

Abstract
After the Germanwings accident, the French Safety Investigation Authority (BEA) recommended that the World Health Organization (WHO) and European Community (EC) develop clear rules for the duty of notification process. Aeromedical practitioners (AMEs) face a dilemma when considering the duty of notification and conflicts between pilot privacy and public and third-party safety. When balancing accountability, knowledge of the duty of notification process, legislation and the clarification of a doctor&rsquo;s own set of values should be assessed a priori. Relatively little is known of the magnitude of this problem in aviation safety. To address this, the National Transportation Safety Board (NTSB) database was searched to identify fatal accidents during 2015 in the United States in which a deceased pilot used a prescribed medication or had a disease that potentially reduced pilot performance and was not reported to the AME. Altogether, 202 finalized accident reports with toxicology were available from (the year) 2015. In 5% (10/202) of these reports, the pilot had either a medication or a disease not reported to an AME which according to the accident investigation was causal to the fatal accident. In addition, the various approaches to duty of notification in aviation in New Zealand, Finland and Norway are discussed. The process of notification of authorities without a pilot&rsquo;s express permission needs to be carried out by using a guidance protocol that works within legislation and professional responsibilities to address the pilot and the public, as well as the healthcare provider. Professional guidance defining this duty of notification is urgently needed.

PMID: 29899311 [PubMed - indexed for MEDLINE]

The role of the built environment and private rooms for reducing central line-associated bloodstream infections.

Tue, 01/15/2019 - 10:28
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The role of the built environment and private rooms for reducing central line-associated bloodstream infections.

PLoS One. 2018;13(7):e0201002

Authors: O'Neill L, Park SH, Rosinia F

Abstract
Private hospital rooms are believed to offer some protective effect against hospital-acquired infections, including central line-associated bloodstream infections. Yet a recent meta-analysis found the evidence-base to be lacking from a policy perspective. We sought to determine whether private rooms were associated with a lower risk of central-line infections. We examined the discharge records of more than one million inpatients from 335 Texas hospitals to determine patients that stayed in private rooms. Patients who stayed in bay rooms had 64 percent more central line infections than patients who stayed in private rooms. Even after adjusting for relevant covariates, patients assigned to bay rooms had a 21 percent greater relative risk of a central line infection (p = 0.005), compared with patients assigned to private rooms. At the hospital level, a 10% increase in private rooms was associated with an 8.6% decrease in central line infections (p<0.001), regardless of individual patients' room assignment. This study demonstrates and validates the use of private rooms as a structural measure and independent predictor of hospital quality.

PMID: 30052672 [PubMed - indexed for MEDLINE]

Transcription factor ΔFosB acts within the nucleus of the solitary tract to increase mean arterial pressure during exposures to intermittent hypoxia.

Tue, 01/15/2019 - 10:28
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Transcription factor ΔFosB acts within the nucleus of the solitary tract to increase mean arterial pressure during exposures to intermittent hypoxia.

Am J Physiol Heart Circ Physiol. 2018 02 01;314(2):H270-H277

Authors: Wu Q, Cunningham JT, Mifflin S

Abstract
ΔFosB is a member of the activator protein-1 family of transcription factors. ΔFosB has low constitutive expression in the central nervous system and is induced after exposure of rodents to intermittent hypoxia (IH), a model of the arterial hypoxemia that accompanies sleep apnea. We hypothesized ΔFosB in the nucleus of the solitary tract (NTS) contributes to increased mean arterial pressure (MAP) during IH. The NTS of 11 male Sprague-Dawley rats was injected (3 sites, 100 nl/site) with a dominant negative construct against ΔFosB (ΔJunD) in an adeno-associated viral vector (AAV)-green fluorescent protein (GFP) reporter. The NTS of 10 rats was injected with AAV-GFP as sham controls. Two weeks after NTS injections, rats were exposed to IH for 8 h/day for 7 days, and MAP was recorded using telemetry. In the sham group, 7 days of IH increased MAP from 99.8 ± 1.1 to 107.3 ± 0.5 mmHg in the day and from 104.4 ± 1.1 to 109.8 ± 0.6 mmHg in the night. In the group that received ΔJunD, IH increased MAP during the day from 95.9 ± 1.7 to 101.3 ± 0.4 mmHg and from 100.9 ± 1.7 to 102.8 ± 0.5 mmHg during the night (both IH-induced changes in MAP were significantly lower than sham, P < 0.05). After injection of the dominant negative construct in the NTS, IH-induced ΔFosB immunoreactivity was decreased in the paraventricular nucleus ( P < 0.05); however, no change was observed in the rostral ventrolateral medulla. These data indicate that ΔFosB within the NTS contributes to the increase in MAP induced by IH exposure. NEW & NOTEWORTHY The results of this study provides new insights into the molecular mechanisms that mediate neuronal adaptations during exposures to intermittent hypoxia, a model of the hypoxemias that occur during sleep apnea. These adaptations are noteworthy as they contribute to the persistent increase in blood pressure induced by exposures to intermittent hypoxia.

PMID: 29101166 [PubMed - indexed for MEDLINE]

Pyruvate-enriched resuscitation for shock.

Thu, 01/10/2019 - 07:28
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Pyruvate-enriched resuscitation for shock.

Exp Biol Med (Maywood). 2018 05;243(8):663-664

Authors: Mallet RT, Olivencia-Yurvati AH, Bünger R

Abstract
This commentary addresses the recent retraction of an article which reported favorable outcomes in septic patients treated with intravenous pyruvate. The retracted report was cited in the authors' recent minireview on the cellular mechanisms and clinical application of pyruvate to improve cardiac performance. Because the retracted article reports pyruvate-enhanced resuscitation of critically ill patients, the authors wish to inform the readership, especially critical care providers, that this particular clinical application of pyruvate is not now supported by robust evidence. After discussing the retraction's implications for the clinical application of pyruvate-enriched resuscitation for sepsis, this commentary summarizes the extensive preclinical evidence of the efficacy and mechanisms of pyruvate resuscitation in animal models of hemorrhagic and septic shock, which argues for renewed clinical investigation of pyruvate-enriched resuscitation. Impact statement This commentary addresses the recent retraction of a clinical report of significant benefits of intravenous pyruvate resuscitation in septic patients, including sharply lowered mortality and decreased circulating pro-inflammatory cytokines, which was cited in the authors' minireview in Experimental Biology and Medicine. The potential implications of the retraction, and the extensive preclinical evidence supporting the use of pyruvate-enriched resuscitation for shock states, are summarized and discussed.

PMID: 29763385 [PubMed - indexed for MEDLINE]

Stage Validity of the Health Action Process Approach in African American Breast Cancer Survivors.

Thu, 01/10/2019 - 07:28
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Stage Validity of the Health Action Process Approach in African American Breast Cancer Survivors.

J Immigr Minor Health. 2018 02;20(1):147-154

Authors: Meadows R, Paxton RJ

Abstract
The Health Action Process Approach (HAPA) has been applied in a number of populations because it proposes to overcome limitations from previous health behavior theories. However, it has yet to be applied to cancer survivors or racial/ethnic minorities. In this study, we examined the construct validity of the HAPA phase and stage algorithms in a sample of African American breast cancer survivors. A total of 259 African American breast cancer survivors (mean age = 54 years) participated in a Web-based survey that assessed sociodemographic and medical characteristics, physical activity, and HAPA constructs. Analysis of covariance was used to compare mean differences between HAPA phase/stage. Statistical significance was determined at p < 0.017 due to multiple comparisons. Phase and stage inconsistencies were observed for most constructs. However, adequate distinctions were made for motivational self-efficacy and intentions (i.e., P = I < A) by phase, and both action and coping planning (i.e., P < I < A) by stage. Our data indicate partial support of the HAPA algorithm to classify African American breast cancer survivors according to stage or phase. Modifying the staging algorithm or constructs are needed if stage- or phase-based interventions can be designed for this population.

PMID: 27785639 [PubMed - indexed for MEDLINE]

Admixture Effects on Coevolved Metabolic Systems.

Wed, 01/09/2019 - 07:29
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Admixture Effects on Coevolved Metabolic Systems.

Front Genet. 2018;9:634

Authors: Zascavage RR, Planz JV

Abstract
Oxidative phosphorylation (OXPHOS) is the primary energy generating system in eukaryotic organisms. The complexes within the OXPHOS pathway are of mixed genomic origin. Although most subunit-coding genes are located within the nuclear genome, several genes are coded for in the mitochondrial genome. There is strong evidence to support coadaptation between the two genomes in these OXPHOS gene regions in order to create tight protein interactions necessary for a functional energetics system. In this study, we begin to assess the physiological impact of separating coevolved protein motifs that make up the highly conserved energy production pathway, as we hypothesize that divergent matings will significantly diminish the protein interactions and therefore hinder efficient OXPHOS activity We measured mitochondrial activity in high energy-demanding tissues from six strains of Mus musculus with varying degrees of mixed ancestral background. Mice with divergent mitochondrial and nuclear backgrounds consistently yielded lower mitochondrial activity. Bioinformatic analysis of common single nucleotide variants across the nuclear and mitochondrial genomes failed to identify any non-synonymous variants that could account for the energetic differences, suggesting that interpopulational mating between ancestrally distinct groups influences energy production efficiency.

PMID: 30619461 [PubMed]

Active and secondhand smoke exposure throughout life and DNA methylation in breast tumors.

Wed, 01/09/2019 - 07:29
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Active and secondhand smoke exposure throughout life and DNA methylation in breast tumors.

Cancer Causes Control. 2019 Jan 07;:

Authors: Callahan CL, Bonner MR, Nie J, Wang Y, Tao MH, Shields PG, Marian C, Eng KH, Trevisan M, Freudenheim JL

Abstract
PURPOSE: Tobacco smoke exposure has been associated with altered DNA methylation. However, there is a paucity of information regarding tobacco smoke exposure and DNA methylation of breast tumors.
METHODS: We conducted a case-only analysis using breast tumor tissue from 493 postmenopausal and 225 premenopausal cases in the Western New York Exposures and Breast Cancer (WEB) study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A, CCND2, BRCA1, FHIT, and SYK) was measured with pyrosequencing. Participants reported their secondhand smoke (SHS) and active smoking exposure for seven time periods. Unconditional logistic regression was used to estimate odds ratios (OR) of having methylation higher than the median.
RESULTS: SHS exposure was associated with tumor DNA methylation among postmenopausal but not premenopausal women. Active smoking at certain ages was associated with increased methylation of GSTP1, FHIT, and CDKN2A and decreased methylation of SCGB3A1 and BRCA1 among both pre- and postmenopausal women.
CONCLUSION: Exposure to tobacco smoke may contribute to breast carcinogenesis via alterations in DNA methylation. Further studies in a larger panel of genes are warranted.

PMID: 30617699 [PubMed - as supplied by publisher]

Retraction notice to "Dopamine Ds3 receptor partial agonist LS-3-134 attenuates cocaine-motivated behaviors" [Pharmacology, Biochemistry and Behavior 171 (2018) 46-53].

Wed, 01/09/2019 - 07:29
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Retraction notice to "Dopamine Ds3 receptor partial agonist LS-3-134 attenuates cocaine-motivated behaviors" [Pharmacology, Biochemistry and Behavior 171 (2018) 46-53].

Pharmacol Biochem Behav. 2019 Jan;176:111

Authors: Powell GL, Bonadonna JP, Vannan A, Xu K, Mach RH, Luedtke RR, Neisewander JL

PMID: 30616777 [PubMed - in process]

Survival analysis of extracorporeal membrane oxygenation in neonatal and pediatric patients - A nationwide cohort study.

Tue, 01/08/2019 - 07:28
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Survival analysis of extracorporeal membrane oxygenation in neonatal and pediatric patients - A nationwide cohort study.

J Formos Med Assoc. 2019 Jan 04;:

Authors: Hsu J, Chang CH, Chiang LT, Caffrey JL, Lin JW, Chen YS

Abstract
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides short-term cardiopulmonary support for patients with acute cardiac and respiratory failure. This study reported the survival rate for pediatric patients from Taiwan's national cohort.
METHODS: Patients under the age of 18 who received ECMO from January 1, 2002 to December 31, 2012 were identified from the Taiwan National Health Insurance Research Database. The underlying etiology for ECMO use was categorized into post-operative (n = 410), cardiac (245), pulmonary (146) groups, and others (120). A Cox regression model was used to determine hazard ratios and to compare 30-day and 1-year survival rates using post-operative group as a reference.
RESULTS: The average age of all 921 patients was 4.83 ± 5.84 years, and 59.1% were male. The overall mortality rate was 29.2% at 1 month, and 46.9% at 1 year. The cardiac origin group, consisting mostly of congenital heart disease without surgical intervention, myocarditis, and heart failure had a better outcome with an adjusted hazard ratio of 0.69 (95% CI 0.49-0.96, p = 0.008) at 30 days and 0.50 (95% CI 0.38-0.66, p < 0.001) at 1 year, as compared to the post-operative group.
CONCLUSION: In contrast to the widespread use of ECMO in respiratory distress syndrome in western countries, pediatric ECMO in Taiwan was more often applied to patients with underlying cardiovascular diseases. Mortality rates varied according to age groups and various etiologies. The results of this large pediatric cohort provides a different prospective in critical care outcomes in medical environments where ECMO is more widely available.

PMID: 30612882 [PubMed - as supplied by publisher]

Cannulated Screws.

Tue, 01/08/2019 - 07:28
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Cannulated Screws.

J Foot Ankle Surg. 2019 Jan 03;:

Authors: Carpenter B, Bohay D, Early JS, Jennings M, Pomeroy G, Schuberth JM, Wukich DK

PMID: 30612868 [PubMed - as supplied by publisher]

Tissue Plasminogen Activator-Porous Magnetic Microrods for Targeted Thrombolytic Therapy after Ischemic Stroke.

Tue, 01/08/2019 - 07:28
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Tissue Plasminogen Activator-Porous Magnetic Microrods for Targeted Thrombolytic Therapy after Ischemic Stroke.

ACS Appl Mater Interfaces. 2018 Oct 03;10(39):32988-32997

Authors: Hu J, Huang S, Zhu L, Huang W, Zhao Y, Jin K, ZhuGe Q

Abstract
Tissue plasminogen activator (tPA) is the only FDA approved thrombolytic drug for acute ischemic stroke but concerns regarding its limitations remain. Here, we developed a new strategy by incorporating tPA into porous magnetic iron oxide (Fe3O4)-microrods (tPA-MRs) for targeted thrombolytic therapy in ischemic stroke induced by distal middle cerebral artery occlusion. We showed that intra-arterial injection of tPA-MRs could target the cerebral blood clot in vivo under the guidance of an external magnet, where tPA was subsequently released at the site of embolism. When applied with an external rotating magnetic field, rotating tPA-MRs significantly improved not only the mass transport of the tPA-clot reaction, but also mechanically disrupted the clot network, which thus increased clot interaction and penetration of tPA. Importantly, intravenously injected MRs could be discharged from the kidney, and the function of liver and kidney were not damaged at different durations after administration of tPA-MRs. Our data suggest that tPA-MRs overcome the limitations of thrombolytic therapy with tPA alone, which may be not only just for the treatment of ischemic stroke but also have majorly impact on other thrombotic diseases.

PMID: 30192506 [PubMed - indexed for MEDLINE]

Cerebral ischemia induces angiogenesis in the peri-infarct regions via Notch1 signaling activation.

Tue, 01/08/2019 - 07:28
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Cerebral ischemia induces angiogenesis in the peri-infarct regions via Notch1 signaling activation.

Exp Neurol. 2018 06;304:30-40

Authors: Ren C, Yao Y, Han R, Huang Q, Li H, Wang B, Li S, Li M, Mao Y, Mao X, Xie L, Zhou L, Hu J, Ji X, Jin K

Abstract
The Notch1 signaling pathway is considered as one of important regulators of angiogenesis during development, but its role in cerebral ischemia-induced angiogenesis is less well understood. Here, we used human and rodent brains to explore whether Notch1 signaling was involved in the angiogenesis after focal cerebral ischemia. Using immunohistochemistry on surgically resected ischemic stroke brain tissue, we found that the area, volume, and length of the blood vessels in the peri-infarct regions were significantly increased after ischemic stroke in humans, compared with non-ischemic stroke specimens. In addition, the expression of the activated form of Notch1 (Notch intracellular domain; NICD) was increased in endothelial cells of the peri-infarct region. The Notch1 ligand, Jagged1, also increased in abundance in the peri-infarct regions in human. We further confirmed that Notch1 signaling was activated in the peri-infarct regions in a mouse distal middle cerebral artery occlusion (dMCAO) model. Lentivirus-mediated Notch1 knockdown reduced ischemia-induced angiogenesis in the peri-infarct regions of the brain. Our findings suggest that ischemic stroke in human can also induce angiogenesis in the peri-infarct regions as does in animal models of focal ischemia and that Notch1 signaling plays a critical role in mediating this process, which may provide fundamental knowledge regarding the potential mechanisms underlying angiogenesis after ischemic stroke.

PMID: 29481785 [PubMed - indexed for MEDLINE]

Clotam enhances anti-proliferative effect of vincristine in Ewing sarcoma cells.

Sun, 01/06/2019 - 07:28
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Clotam enhances anti-proliferative effect of vincristine in Ewing sarcoma cells.

Apoptosis. 2019 Jan 04;:

Authors: Shelake S, Sankpal UT, Eslin D, Bowman WP, Simecka JW, Raut S, Ray A, Basha R

Abstract
Current therapeutic strategies used in Ewing sarcoma (ES) especially for relapsed patients have resulted in modest improvements in survival over the past 20 years. Combination therapeutic approach presents as an alternative to overcoming drug resistance in metastatic ES. This study evaluated the effect of Clotam (tolfenamic acid or TA), a small molecule and inhibitor of Specificity protein1 (Sp1) and survivin for sensitizing ES cell lines to chemotherapeutic agent, vincristine (VCR). ES cells (CHLA-9 and TC-32) were treated with TA or VCR or TA + VCR (combination), and cell viability was assessed after 24/48/72 h. Effect of TA or VCR or TA + VCR treatment on cell cycle arrest and apoptosis were evaluated using propidium iodide, cell cycle assay and Annexin V flow cytometry respectively. The apoptosis markers, caspase 3/7 (activity levels) and cleaved-PARP (protein expression) were measured. Cardiomyocytes, H9C2 were used as non-malignant cells. While, all treatments caused time- and dose-dependent inhibition of cell viability, interestingly, combination treatment caused significantly higher response (~ 80% inhibition, p < 0.05). Cell viability inhibition was accompanied by inhibition of Sp1 and Survivin. TA + VCR treatment significantly (p < 0.05) increased caspase 3/7 activity which strongly correlated with upregulated c-PARP level and Annexin V staining. Cell cycle arrest was observed at G0/G1 (TA) or G2/M (VCR and TA + VCR). All treatments did not cause cytotoxicity in H9C2 cells. These results suggest that TA could enhance the anti-cancer activity of VCR in ES cells. Therefore, TA + VCR combination could be further tested to develop as safe/effective therapeutic strategy for treating ES.

PMID: 30610505 [PubMed - as supplied by publisher]

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes⁻4.

Fri, 01/04/2019 - 07:29
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Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes⁻4.

Molecules. 2018 Dec 31;24(1):

Authors: Mangoni AA, Guillou C, Vanden Eynde JJ, Hulme C, Jampilek J, Li W, Prokai-Tatrai K, Rautio J, Collina S, Tuccinardi T, Sousa ME, Sabatier JM, Galdiero S, Karaman R, Kokotos G, Torri G, Luque FJ, Vasconcelos MH, Hadjipavlou-Litina D, Siciliano C, Gütschow M, Ragno R, Gomes PAC, Agrofoglio LA, Muñoz-Torrero D

Abstract
Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules. [...].

PMID: 30602690 [PubMed - in process]

Applying Organizational Health Literacy to Maternal and Child Health.

Thu, 01/03/2019 - 07:29
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Applying Organizational Health Literacy to Maternal and Child Health.

Matern Child Health J. 2019 Jan 02;:

Authors: Vamos CA, Thompson EL, Griner SB, Liggett LG, Daley EM

Abstract
Purpose Describe the development of an innovative teaching activity that applies organizational health literacy to maternal and child health (MCH). Description Health literacy is a strong predictor of health behavior and outcomes. While the study of health literacy has traditionally been confined to skills and capacities of individuals, the significant role of the social and physical environmental contexts in facilitating or hindering one's ability to obtain, understand, and make informed decision about their health has been recognized. MCH organizations play a critical role in influencing health literacy across system levels. This teaching activity aims to equip students with knowledge and skills needed to foster organizational health literacy. Assessment The teaching activity is assembled within a toolkit which includes the following: (1) instructor lesson plan; (2) interactive PowerPoint presentation with instructor notes; (3) field assignment description; (4) health literacy attribute assessment worksheets; and (5) grading rubric. The teaching tool was pilot tested by a student research team member to assess the educational value and assignment logistics, resulting in minor edits (i.e., addition of interviewer probes, and option of a group project-format to permit triangulation of multiple organizational interviews). Conclusion The field of MCH is expanding in complexity, and the demands of health systems on women, children, and families must be mediated by conscious efforts within organizations. Through teaching the importance and function of organizational health literacy to students in MCH, educators can prepare an emerging workforce to improve health literacy, and ultimately the quality of healthcare for women, children, and families.

PMID: 30600522 [PubMed - as supplied by publisher]

NIST interlaboratory studies involving DNA mixtures (MIX13): A modern analysis.

Thu, 01/03/2019 - 07:29
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NIST interlaboratory studies involving DNA mixtures (MIX13): A modern analysis.

Forensic Sci Int Genet. 2018 11;37:172-179

Authors: Buckleton JS, Bright JA, Cheng K, Budowle B, Coble MD

Abstract
MIX13 was an interlaboratory exercise directed by NIST in 2013. The goal of the exercise was to evaluate the general state of interpretation methods in use at the time across the forensic community within the US and Canada and to measure the consistency in mixture interpretation. The findings were that there was a large variation in analysts' interpretations between and within laboratories. Within this work, we sought to evaluate the same mock mixture cases analyzed in MIX13 but with a more current view of the state-of-the-science. Each of the five cases were analyzed using the Identifiler™ multiplex and interpreted with the combined probability of inclusion, CPI, and four different modern probabilistic genotyping systems. Cases 1-4 can be interpreted without difficulty by any of the four PG systems examined. Cases 1 and 4 could also be interpreted successfully with the CPI by assuming two donors. Cases 2 and 3 cannot be interpreted successfully with the CPI because of potential of allele dropout. Case 3 demonstrated the need to consider relevant background information before interpretation of the profile. This case does not show that there is some barrier to interpretation caused by relatedness beyond the increased allelic overlap that can occur. Had this profile been of better template it might have been interpreted using the CPI despite the (potential) relatedness of contributors. Case 5 suffers from over-engineering. It is unclear whether reference 5C, a non-donor, can be excluded by manual methods. Inclusion of reference 5C should be termed an adventitious match not a false inclusion. Beyond this statement this case does not contribute to the interlaboratory study of analyst/laboratory interpretation method performance, instead, it explores the limits of DNA analysis. Taken collectively the analysis of these five cases demonstrates the benefits of changing from CPI to a PG system.

PMID: 30176439 [PubMed - indexed for MEDLINE]

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