Recent Research Articles from UNTHSC

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

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Inhibitor of myogenic differentiation family isoform a, a new positive regulator of fibronectin production by glomerular mesangial cells.

Fri, 07/17/2020 - 07:41
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Inhibitor of myogenic differentiation family isoform a, a new positive regulator of fibronectin production by glomerular mesangial cells.

Am J Physiol Renal Physiol. 2020 03 01;318(3):F673-F682

Authors: Shotorbani PY, Chaudhari S, Tao Y, Tsiokas L, Ma R

Abstract
Overproduction of extracellular matrix proteins, including fibronectin by mesangial cells (MCs), contributes to diabetic nephropathy. Inhibitor of myogenic differentiation family isoform a (I-mfa) is a multifunctional cytosolic protein functioning as a transcriptional modulator or plasma channel protein regulator. However, its renal effects are unknown. The present study was conducted to determine whether I-mfa regulated fibronectin production by glomerular MCs. In human MCs, overexpression of I-mfa significantly increased fibronectin abundance. Silencing I-mfa significantly reduced the level of fibronectin mRNA and blunted transforming growth factor-β1-stimulated production of fibronectin. We further found that high glucose increased I-mfa protein content in a time course (≥48 h) and concentration (≥25 mM)-dependent manner. Although high glucose exposure increased I-mfa at the protein level, it did not significantly alter transcripts of I-mfa in MCs. Furthermore, the abundance of I-mfa protein was significantly increased in the renal cortex of rats with diabetic nephropathy. The I-mfa protein level was also elevated in the glomerulus of mice with diabetic kidney disease. However, there was no significant difference in glomerular I-mfa mRNA levels between mice with and without diabetic nephropathy. Moreover, H2O2 significantly increased I-mfa protein abundance in a dose-dependent manner in cultured human MCs. The antioxidants polyethylene glycol-catalase, ammonium pyrrolidithiocarbamate, and N-acetylcysteine significantly blocked the high glucose-induced increase of I-mfa protein. Taken together, our results suggest that I-mfa, increased by high glucose/diabetes through the production of reactive oxygen species, stimulates fibronectin production by MCs.

PMID: 31984795 [PubMed - indexed for MEDLINE]

Sex-Dependent Mechanisms of Glucocorticoid Regulation of the Mouse Hypothalamic Corticotropin-Releasing Hormone Gene.

Thu, 07/16/2020 - 07:23
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Sex-Dependent Mechanisms of Glucocorticoid Regulation of the Mouse Hypothalamic Corticotropin-Releasing Hormone Gene.

Endocrinology. 2020 01 01;161(1):

Authors: Heck AL, Thompson MK, Uht RM, Handa RJ

Abstract
To limit excessive glucocorticoid secretion following hypothalamic-pituitary-adrenal (HPA) axis stimulation, circulating glucocorticoids inhibit corticotropin-releasing hormone (CRH) expression in paraventricular nucleus (PVN) neurons. As HPA function differs between sexes and depends on circulating estradiol (E2) levels in females, we investigated sex/estrous stage-dependent glucocorticoid regulation of PVN Crh. Using NanoString nCounter technology, we first demonstrated that adrenalectomized (ADX'd) diestrous female (low E2), but not male or proestrous female (high E2), mice exhibited a robust decrease in PVN CRH mRNA following 2-day treatment with the glucocorticoid receptor (GR) agonist RU28362. Immunohistochemical analysis of PVN CRH neurons in Crh-IRES-Cre;Ai14 mice, where TdTomato fluorescence permanently tags CRH-expressing neurons, showed similarly abundant co-expression of GR-immunoreactivity in males, diestrous females, and proestrous females. However, we identified sex/estrous stage-related glucocorticoid regulation or expression of GR transcriptional coregulators. Out of 17 coregulator genes examined using nCounter multiplex analysis, mRNAs that were decreased by RU28362 in ADX'd mice in a sex/estrous stage-dependent fashion included: GR (males = diestrous females > proestrous females), signal transducer and activator of transcription 3 (STAT3) (males < diestrous = proestrous), and HDAC1 (males < diestrous > proestrous). Steroid receptor coactivator 3 (SRC-3), nuclear corepressor 1 (NCoR1), heterogeneous nuclear ribonucleoprotein U (hnrnpu), CREB binding protein (CBP) and CREB-regulated transcription coactivator 2 (CRTC2) mRNAs were lower in ADX'd diestrous and proestrous females versus males. Additionally, most PVN CRH neurons co-expressed methylated CpG binding protein 2 (MeCP2)-immunoreactivity in diestrous female and male Crh-IRES-Cre;Ai14 mice. Our findings collectively suggest that GR's sex-dependent regulation of PVN Crh may depend upon differences in the GR transcriptional machinery and an underlying influence of E2 levels in females.

PMID: 31754709 [PubMed - indexed for MEDLINE]

Responses of cerebral blood velocity and tissue oxygenation to low-frequency oscillations during simulated haemorrhagic stress in humans.

Wed, 07/15/2020 - 07:11
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Responses of cerebral blood velocity and tissue oxygenation to low-frequency oscillations during simulated haemorrhagic stress in humans.

Exp Physiol. 2019 08;104(8):1190-1201

Authors: Anderson GK, Sprick JD, Park FS, Rosenberg AJ, Rickards CA

Abstract
NEW FINDINGS: What is the central question of this study? Do low-frequency oscillations in arterial pressure and cerebral blood velocity protect cerebral blood velocity and oxygenation during central hypovolaemia? What is the main finding and its importance? Low-frequency oscillations in arterial pressure and cerebral blood velocity attenuate reductions in cerebral oxygen saturation but do not protect absolute cerebral blood velocity during central hypovolaemia. This finding indicates the potential importance of haemodynamic oscillations in maintaining cerebral oxygenation and therefore viability of tissues during challenges to cerebral blood flow and oxygen delivery.
ABSTRACT: Tolerance to both real and simulated haemorrhage varies between individuals. Exaggerated low-frequency (∼0.1 Hz) oscillations in mean arterial pressure and brain blood flow [indexed via middle cerebral artery velocity (MCAv)] have been associated with improved tolerance to reduced central blood volume. The mechanism for this association has not been explored. We hypothesized that inducing low-frequency oscillations in arterial pressure and cerebral blood velocity would attenuate reductions in cerebral blood velocity and oxygenation during simulated haemorrhage. Fourteen subjects (11 men and three women) were exposed to oscillatory (0.1 and 0.05 Hz) and non-oscillatory (0 Hz) lower-body negative pressure profiles with an average chamber pressure of -60 mmHg (randomized and counterbalanced order). Measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and cerebral oxygenation of the frontal lobe via near-infrared spectroscopy. Tolerance was higher during the two oscillatory profiles compared with the 0 Hz profile (0.05 Hz, P = 0.04; 0.1 Hz, P = 0.09), accompanied by attenuated reductions in stroke volume (P < 0.001) and cerebral oxygenation of the frontal lobe (P ≤ 0.02). No differences were observed between profiles for reductions in mean arterial pressure (P = 0.17) and MCAv (P = 0.30). In partial support of our hypothesis, cerebral oxygenation, but not cerebral blood velocity, was protected during the oscillatory profiles. Interestingly, more subjects tolerated the oscillatory profiles compared with the static 0 Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of haemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissues during haemorrhagic stress.

PMID: 31090115 [PubMed - indexed for MEDLINE]

Role of the afferent renal nerves in sodium homeostasis and blood pressure regulation in rats.

Wed, 07/15/2020 - 07:11
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Role of the afferent renal nerves in sodium homeostasis and blood pressure regulation in rats.

Exp Physiol. 2019 08;104(8):1306-1323

Authors: Frame AA, Carmichael CY, Kuwabara JT, Cunningham JT, Wainford RD

Abstract
NEW FINDINGS: What is the central question of this study? What are the differential roles of the mechanosensitive and chemosensitive afferent renal nerves in the reno-renal reflex that promotes natriuresis, sympathoinhibition and normotension during acute and chronic challenges to sodium homeostasis? What is the main finding and its importance? The mechanosensitive afferent renal nerves contribute to an acute natriuretic sympathoinhibitory reno-renal reflex that may be integrated within the paraventricular nucleus of the hypothalamus. Critically, the afferent renal nerves are required for the maintenance of salt resistance in Sprague-Dawley and Dahl salt-resistant rats and attenuate the development of Dahl salt-sensitive hypertension.
ABSTRACT: These studies tested the hypothesis that in normotensive salt-resistant rat phenotypes the mechanosensitive afferent renal nerve (ARN) reno-renal reflex promotes natriuresis, sympathoinhibition and normotension during acute and chronic challenges to fluid and electrolyte homeostasis. Selective ARN ablation was conducted prior to (1) an acute isotonic volume expansion (VE) or 1 m NaCl infusion in Sprague-Dawley (SD) rats and (2) chronic high salt intake in SD, Dahl salt-resistant (DSR), and Dahl salt-sensitive (DSS) rats. ARN responsiveness following high salt intake was assessed ex vivo in response to noradrenaline and sodium concentration (SD, DSR and DSS) and via in vivo manipulation of renal pelvic pressure and sodium concentration (SD and DSS). ARN ablation attenuated the natriuretic and sympathoinhibitory responses to an acute VE [peak natriuresis (µeq min-1 ) sham 52 ± 5 vs. ARN ablation 28 ± 3, P < 0.05], but not a hypertonic saline infusion in SD rats. High salt (HS) intake enhanced ARN reno-renal reflex-mediated natriuresis in response to direct increases in renal pelvic pressure (mechanoreceptor stimulus) in vivo and ARN responsiveness to noradrenaline ex vivo in SD, but not DSS, rats. In vivo and ex vivo ARN responsiveness to increased renal pelvic sodium concentration (chemoreceptor stimulus) was unaltered during HS intake. ARN ablation evoked sympathetically mediated salt-sensitive hypertension in SD rats [MAP (mmHg): sham normal salt 102 ± 2 vs. sham HS 104 ± 2 vs. ARN ablation normal salt 103 ± 2 vs. ARN ablation HS 121 ± 2, P < 0.05] and DSR rats and exacerbated DSS hypertension. The mechanosensitive ARNs mediate an acute sympathoinhibitory natriuretic reflex and counter the development of salt-sensitive hypertension.

PMID: 31074108 [PubMed - indexed for MEDLINE]

Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines.

Tue, 07/14/2020 - 06:46
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Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines.

Breast Cancer (Auckl). 2020;14:1178223420913330

Authors: Amaral de Mascena Costa L, Harmon AC, Aguiar Coelho Teixeira A, Cássio Silva de Lima F, de Sousa Araújo S, Del Piero F, Diógenes da Silva Souza H, Filgueiras de Athayde Filho P, Alves Junior S, de Mascena Diniz Maia M, Wischral A, Adrião Gomes Filho M, Mathis JM

Abstract
In this work, we report the synthesis of a new 1,3-thiazolium-5-thiolate derivative of a mesoionic compound (MIH 2.4Bl) and the characterization of its selective cytotoxicity on a panel of breast cancer cells lines. The cytotoxic effect of MIH 2.4Bl on breast cancer cell lines was determined by XTT and crystal violet assays, flow cytometry analysis, electron microscopy characterization, and terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) apoptosis assays. As determined using XTT cell growth and survival assays, MIH 2.4Bl exhibited growth inhibition activity on most breast cancer cell lines tested, compared with normal human mammary epithelial cells. Three breast cancer cell lines (MCF-7, T-47D, and ZR-75-1) showed a more potent sensitivity index to growth inhibition by MIH 2.4Bl than the other breast cancer cell lines. Interestingly, these 3 cell lines were derived from tumors of Luminal A origin and have ER (estrogen receptor), PR (progesterone receptor), and HER2 (human epidermal growth factor receptor 2) positive expression. Additional analysis of cytotoxicity mediated by MIH 2.4Bl was performed using the MCF-7 cell line. MCF-7 cells displayed both time- and dose-dependent decreases in cell growth and survival, with a maximum cytotoxic effect observed at 72 and 96 hours. The MCF-7 cells were also characterized for cell cycle changes upon treatment with MIH 2.4Bl. Using flow cytometry analysis of cell cycle distribution, a treatment-dependent effect was observed; treatment of cells with MIH 2.4Bl increased the G2/M population to 34.2% compared with 0.1% in untreated (control) cells. Ultrastructural analysis of MFC-7 cells treated with MIH 2.4Bl at 2 different concentrations (37.5 and 75 μM) was performed by transmission electron microscopy. Cells treated with 37.5 μM MIH 2.4Bl showed morphologic changes beginning at 6 hours after treatment, while cells treated with 75 μM showed changes beginning at 3 hours after treatment. These changes were characterized by an alteration of nuclear morphology and mitochondrial degeneration consistent with apoptotic cell death. Results of a TUNEL assay performed on cells treated for 96 hours with MIH 2.4Bl supported the observation of apoptosis. Together, these results suggest that MIH 2.4Bl is a promising candidate for treating breast cancer and support further in vitro and in vivo investigation.

PMID: 32655277 [PubMed]

Drinking to cope with the pandemic: The unique associations of COVID-19-related perceived threat and psychological distress to drinking behaviors in American men and women.

Sun, 07/12/2020 - 06:00

Drinking to cope with the pandemic: The unique associations of COVID-19-related perceived threat and psychological distress to drinking behaviors in American men and women.

Addict Behav. 2020 Jun 27;110:106532

Authors: Rodriguez LM, Litt DM, Stewart SH

Abstract
The 2019 Coronavirus pandemic has brought about significant and unprecedented changes to the modern world, including stay-at-home orders, high rates of unemployment, and more than a hundred thousand deaths across the United States. Derived from the self-medication hypothesis, this research explored how perceived threat and psychological distress related to the COVID-19 pandemic are associated with drinking behavior among an American sample of adults. We also evaluated whether links between COVID-19-related perceived threat and psychological distress with drinking behavior are different for men and women. Participants (N = 754; 50% women) completed an online Qualtrics Panels study between April 17th and 23rd, 2020. Results suggested that psychological distress related to the COVID-19 pandemic was consistently related to alcohol use indices, and moderation results indicated this pattern was significant only among women for number of drinks consumed during the recent heaviest drinking occasion and number of drinks consumed on a typical evening. COVID-related distress' link to frequency of drinking and heavy drinking episodes was not different for men and women. Our results suggest that continued monitoring, particularly among women, should be conducted as this pandemic continues to evolve to identify the long-term public health impacts of drinking to cope with COVID-19 distress.

PMID: 32652385 [PubMed - as supplied by publisher]

Private patient rooms and hospital-acquired methicillin-resistant Staphylococcus aureus: A hospital-level analysis of administrative data from the United States.

Fri, 07/10/2020 - 05:32

Private patient rooms and hospital-acquired methicillin-resistant Staphylococcus aureus: A hospital-level analysis of administrative data from the United States.

PLoS One. 2020;15(7):e0235754

Authors: Park SH, Stockbridge EL, Miller TL, O'Neill L

Abstract
OBJECTIVE: To use hospital-level data from the US to determine whether private patient rooms (PPRs) are associated with fewer in hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) infections.
METHODS: We retrospectively analyzed Texas Inpatient Public Use Data with discharges between September 2015 and August 2016 merged with American Hospital Association annual survey data. We used negative binomial regression to estimate the association between the proportion of PPRs within a hospital and the count of discharges with HA-MRSA infections, adjusting for potentially confounding variables.
RESULTS: We analyzed data for 340 hospitals and 2,670,855 discharges. HA-MRSA incidence within these hospitals was 386 per 100,000 discharges (95% CI: 379, 393) and, on average, 62.73% (95% CI: 58.99, 66.46) of rooms in these hospitals were PPRs. PPRs were significantly associated with fewer HA-MRSA infections (unadjusted IRR = 0.973, 95% CI: 0.968, 0.979; adjusted IRR = 0.992, 95% CI: 0.991, 0.994; p<0.001 for both); at the hospital level, as the percentage of PPRs increased, HA-MRSA infection rates decreased. This association was non-linear; in hospitals with few PPRs there was a stronger association between PPRs and HA-MRSA infection rate relative to hospitals with many PPRs.
CONCLUSION: We identified 0.8% fewer HA-MRSA infections for each 1% increase in PPRs as a proportion of all rooms, suggesting that private rooms provide substantial protection from HA-MRSA. Small changes may not induce significant improvements in HA-MRSA incidence, and hospitals seeking tangible benefits in HAI reduction likely need to markedly increase the proportion of PPRs through large-scale renovations. The effect of private rooms is disproportionate across hospitals. Hospitals with proportionately fewer PPRs stand to gain the most from adding additional PPRs, while those with an already high proportion of PPRs are unlikely to see large benefits. Our findings enable hospital administrators to consider potential patient safety benefits as they make decisions about facility design and renovation.

PMID: 32645096 [PubMed - as supplied by publisher]

Dissemination of Evidence-Based School Asthma Management Programs: Piloting Asthma 411 in an Urban Texas School District.

Fri, 07/10/2020 - 05:32

Dissemination of Evidence-Based School Asthma Management Programs: Piloting Asthma 411 in an Urban Texas School District.

J Sch Health. 2020 Jul 09;:

Authors: Allsopp L, Sterling DA, Spence E, Aryal S

Abstract
BACKGROUND: The dissemination and implementation (D&I) of evidence-based initiative (EBIs) is critical to improved public health. The Asthma 411 EBI was piloted in Texas from 2013 to 2015. The pilot's evaluation assessed its effectiveness and identified approaches to support D&I of school-health EBIs.
METHODS: The pilot study was conducted in two schools; service categories included: a consulting physician, enhanced school asthma services, and support for links to community health resources. Data was collected on Emergency Medical Service (EMS) calls, aggregated nursing services, demographic characteristics, availability of medication provided through existing policies, and informal interviews.
RESULTS: During the pilot, school-day asthma-related Emergency Medical Service (EMS) calls were eliminated. Documented asthma self-management education, authorization for rescue medication, and efforts to communicate with parents and health providers increased. Between year-1 and year-2, the gap between unadjusted, weighted mean absences among students with and without asthma was reduced by 1.1 days. However, this difference was not seen in a fully adjusted negative, binomial regression model.
CONCLUSIONS: Evaluation of the Asthma 411 pilot suggests many EBI benefits were retained and identifies factors that may facilitate D&I of school health EBIs. Future research will clarify impacts on absenteeism and determine if observed benefits are sustained.

PMID: 32643214 [PubMed - as supplied by publisher]

A novel miR-1291-ERRα-CPT1C axis modulates tumor cell proliferation, metabolism and tumorigenesis.

Fri, 07/10/2020 - 05:32

A novel miR-1291-ERRα-CPT1C axis modulates tumor cell proliferation, metabolism and tumorigenesis.

Theranostics. 2020;10(16):7193-7210

Authors: Chen Y, Zhou Y, Han F, Zhao Y, Tu M, Wang Y, Huang C, Fan S, Chen P, Yao X, Guan L, Yu AM, Gonzalez FJ, Huang M, Bi H

Abstract
Rationale: MicroRNAs are known to influence the development of a variety of cancers. Previous studies revealed that miR-1291 has antiproliferative functions in cancer cells. Carnitine palmitoyltransferase 1C (CPT1C) has a vital role in mitochondrial energy metabolism and modulation of cancer cell proliferation. Since both miR-1291 and CPT1C regulate tumor cell metabolism and cancer progression, we hypothesized that they might be regulated synergistically. Methods: A series of cell phenotype indicators, such as BrdU, colony formation, cell cycle, ATP production, ROS accumulation and cell ability to resist metabolic stress, were performed to clarify the effects of miR-1291 and ERRα expression on tumor cell proliferation and metabolism. A xenograft tumor model was used to evaluate cell tumorigenesis. Meta-analysis and bioinformatic prediction were applied in the search for the bridge-link between miR-1291 and CPT1C. RT-qPCR, western-blot and IHC analysis were used for the detection of mRNA and protein expression. Luciferase assays and ChIP assays were conducted for in-depth mechanism studies. Results: The expression of miR-1291 inhibited growth and tumorigenesis as a result of modulation of metabolism. CPT1C expression was indirectly and negatively correlated with miR-1291 levels. ESRRA was identified as a prominent differentially expressed gene in both breast and pancreatic cancer samples, and estrogen-related receptor α (ERRα) was found to link miR-1291 and CPT1C. MiR-1291 targeted ERRα and CPT1C was identified as a newly described ERRα target gene. Moreover, ERRα was found to influence cancer cell metabolism and proliferation, consistent with the cellular changes caused by miR-1291. Conclusion: This study demonstrated the existence and mechanism of action of a novel miR-1291-ERRα-CPT1C cancer metabolism axis that may provide new insights and strategies for the development of miRNA-based therapies for malignant cancers.

PMID: 32641987 [PubMed - in process]

A Systematic Review and Meta-Analysis of Metolazone Compared to Chlorothiazide for Treatment of Acute Decompensated Heart Failure.

Thu, 07/09/2020 - 05:17

A Systematic Review and Meta-Analysis of Metolazone Compared to Chlorothiazide for Treatment of Acute Decompensated Heart Failure.

Pharmacotherapy. 2020 Jul 08;:

Authors: Steuber TD, Janzen KM, Howard ML

Abstract
INTRODUCTION: Treatment of volume overload in the setting of acute decompensated heart failure (ADHF) is typically achieved through the use of loop diurectics. While they are highly effective, some patients may develop loop diuretic resistance. One strategy to overcome this scenario includes sequential nephron blockade with a thiazide-type diuretic, however it is unknown which thiazide-type diuretic used in this setting is most effective.
METHODS: A systematic review and meta-analysis were performed to compare the efficacy and safety of chlorothiazide with metolazone as add-on therapy in the setting of loop diuretic resistance for the treatment of ADHF. Literature searches were conducted through Pubmed, Google Scholar, and Science Direct from inception through February 2020 using the following search terms alone or in combination: metolazone, chlorothiazide, acute decompensated heart failure, loop diuretic, and urine output. All English-language prospective and retrospective trials and abstracts comparing metolazone to chlorothiazide for the treatment of ADHF were evaluated. Studies were included if they analyzed urine output for at least 24 hours in patients with ADHF. Meta-analysis was conducted to evaluate pooled effect size by using a random-effect model. Primary outcomes included net and total urine output. Secondary outcomes included commonly reported safety outcomes.
RESULTS: Four studies comparing the use of metolazone to chlorothiazide as an adjunct to loop diuretics to treat ADHF were included in the evaluation. Metolazone was as effective as chlorothiazide to augment loop diuretic therapy in ADHF in most studies with no pooled difference in net or total urine output. However, there were notable differences in baseline loop diuretic dosing, ejection fraction, renal function, race, and endpoint timing across studies. Adverse effects were commonly observed and included electrolyte abnormalities, change in renal function, and hypotension but were comparable between groups.
CONCLUSION: Metolazone is as effective as chlorothiazide as add-on to loop diuretics in treating ADHF without an increase in safety concerns.

PMID: 32639593 [PubMed - as supplied by publisher]

A sensitive data analysis approach for detecting changes in dynamic postural stability.

Thu, 07/09/2020 - 05:17
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A sensitive data analysis approach for detecting changes in dynamic postural stability.

J Biomech. 2020 Jul 17;108:109899

Authors: Moudy SC, Patterson RM, Bugnariu N

Abstract
Understanding the mechanisms of instability can aid in reducing fall risk. As a sensitive measure of fall risk, the distance between the center of pressure (COP) and center of mass (COM) is currently assessed through discrete points assumed to represent physiological important fall mechanisms. However, it is unclear if these discrete points are appropriate measures of fall risk. Statistical parametric mapping (SPM) is a waveform analysis technique that removes this possibly biased a priori approach. Sixteen healthy young adults (8 males, 8 females; Age: 29 ± 3.6 years, Height: 1.7 ± 0.9 m, Mass: 75 ± 16 kg) performed two tasks that disturbed dynamic stability: voluntary stepping at different step lengths, and forward perturbations at different accelerations. COP-COM distance magnitudes were extracted during the first step in both tasks at discrete points typically assessed in previous research. Discrete point analysis (DPA) was performed on these discrete points and SPM analysis was completed on the COP-COM distance waveform. The results from the study found that SPM analysis identified equivalent significant differences to DPA and identified additional significant differences elsewhere in the COP-COM distance waveform that were not able to be detected by DPA. Two key advantages from using SPM: (1) reduction of possibly biased a priori selection, and (2) increased efficiency and reduced time-cost in data post-processing as inherent variability can limit the detection of discrete points resulting in identifying physiologically different discrete points across trials. This study suggests the use of SPM as a sensitive data analysis approach in detecting fall risk as an alternative to DPA.

PMID: 32636010 [PubMed - in process]

ApoE Genotype-Dependent Response to Antioxidant and Exercise Interventions on Brain Function.

Wed, 07/08/2020 - 05:02
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ApoE Genotype-Dependent Response to Antioxidant and Exercise Interventions on Brain Function.

Antioxidants (Basel). 2020 Jun 25;9(6):

Authors: Chaudhari K, Wong JM, Vann PH, Como T, O'Bryant SE, Sumien N

Abstract
This study determined whether antioxidant supplementation is a viable complement to exercise regimens in improving cognitive and motor performance in a mouse model of Alzheimer's disease risk. Starting at 12 months of age, separate groups of male and female mice expressing human Apolipoprotein E3 (GFAP-ApoE3) or E4 (GFAP-ApoE4) were fed either a control diet or a diet supplemented with vitamins E and C. The mice were further separated into a sedentary group or a group that followed a daily exercise regimen. After 8 weeks on the treatments, the mice were administered a battery of functional tests including tests to measure reflex and motor, cognitive, and affective function while remaining on their treatment. Subsequently, plasma inflammatory markers and catalase activity in brain regions were measured. Overall, the GFAP-ApoE4 mice exhibited poorer motor function and spatial learning and memory. The treatments improved balance, learning, and cognitive flexibility in the GFAP-ApoE3 mice and overall the GFAP-ApoE4 mice were not responsive. The addition of antioxidants to supplement a training regimen only provided further benefits to the active avoidance task, and there was no antagonistic interaction between the two interventions. These outcomes are indicative that there is a window of opportunity for treatment and that genotype plays an important role in response to interventions.

PMID: 32630431 [PubMed]

Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer.

Wed, 07/08/2020 - 05:02
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Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer.

Cancers (Basel). 2020 Jul 01;12(7):

Authors: Buller CW, Mathew PA, Mathew SO

Abstract
Natural killer (NK) cells play a pivotal role in the immune system, especially in the recognition and clearance of cancer cells and infected cells. Their effector function is controlled by a delicate balance between the activating and inhibitory signals. We have identified 2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) as NK cell receptors regulating NK cell cytotoxicity. Lectin-like transcript 1 (LLT1), a member of the C-type lectin-like domain family 2 (CLEC2D), induced IFN-g production but did not directly regulate cytolytic activity. Interestingly, LLT1 expressed on other cells acts as a ligand for an NK cell inhibitory receptor NKRP1A (CD161) and inhibits NK cytolytic function. Extensive research has been done on novel therapies that target these receptors to increase the effector function of NK cells. The 2B4 receptor is involved in the rejection of melanoma cells in mice. Empliciti, an FDA-approved monoclonal antibody, explicitly targets the CS1 receptor and enhances the NK cell cytotoxicity against multiple myeloma cells. Our studies revealed that LLT1 is expressed on prostate cancer and triple-negative breast cancer cells and allows them to evade NK-cell-mediated killing. In this review, we describe NK cell receptors 2B4, CS1, and LLT1 and their potential in targeting cancer cells for NK-cell-mediated immunotherapy. New cancer immunotherapies like chimeric antigen receptor T (CAR-T) and NK (CAR-NK) cells are showing great promise in the treatment of cancer, and CAR cells specific to these receptors would be an attractive therapeutic option.

PMID: 32630303 [PubMed]

Racial and ethnic disparities in a state-wide registry of patients with pancreatic cancer and an exploratory investigation of cancer cachexia as a contributor to observed inequities.

Wed, 07/08/2020 - 05:02
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Racial and ethnic disparities in a state-wide registry of patients with pancreatic cancer and an exploratory investigation of cancer cachexia as a contributor to observed inequities.

Cancer Med. 2019 06;8(6):3314-3324

Authors: Permuth JB, Clark Daly A, Jeong D, Choi JW, Cameron ME, Chen DT, Teer JK, Barnett TE, Li J, Powers BD, Kumar NB, George TJ, Ali KN, Huynh T, Vyas S, Gwede CK, Simmons VN, Hodul PJ, Carballido EM, Judge AR, Fleming JB, Merchant N, Trevino JG

Abstract
Pancreatic cancer (PC) is characterized by racial/ethnic disparities and the debilitating muscle-wasting condition, cancer cachexia. Florida ranks second in the number of PC deaths and has a large and understudied minority population. We examined the primary hypothesis that PC incidence and mortality rates may be highest among Black Floridians and the secondary hypothesis that biological correlates of cancer cachexia may underlie disparities. PC incidence and mortality rates were estimated by race/ethnicity, gender, and county using publicly available state-wide cancer registry data that included approximately 2700 Black, 25 200 Non-Hispanic White (NHW), and 3300 Hispanic/Latino (H/L) Floridians diagnosed between 2004 and 2014. Blacks within Florida experienced a significantly (P < 0.05) higher incidence (12.5/100 000) and mortality (10.97/100 000) compared to NHW (incidence = 11.2/100 000; mortality = 10.3/100 000) and H/L (incidence = 9.6/100 000; mortality = 8.7/100 000), especially in rural counties. To investigate radiologic and blood-based correlates of cachexia, we leveraged data from a subset of patients evaluated at two geographically distinct Florida Cancer Centers. In Blacks compared to NHW matched on stage, markers of PC-induced cachexia were more frequent and included greater decreases in core musculature compared to corresponding healthy control patients (25.0% vs 10.1% lower), greater decreases in psoas musculature over time (10.5% vs 4.8% loss), lower baseline serum albumin levels (3.8 vs 4.0 gm/dL), and higher platelet counts (332.8 vs 268.7 k/UL). Together, these findings suggest for the first time that PC and cachexia may affect Blacks disproportionately. Given its nearly universal contribution to illness and PC-related deaths, the early diagnosis and treatment of cachexia may represent an avenue to improve health equity, quality of life, and survival.

PMID: 31074202 [PubMed - indexed for MEDLINE]

Development of a motivational interviewing genetic counseling intervention to increase cascade cholesterol screening in families of children with familial hypercholesterolemia.

Tue, 07/07/2020 - 07:39
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Development of a motivational interviewing genetic counseling intervention to increase cascade cholesterol screening in families of children with familial hypercholesterolemia.

J Genet Couns. 2019 10;28(5):1059-1064

Authors: Kruger V, Redlinger-Grosse K, Walters ST, Ash E, Cragun D, McCarthy Veach P, Zierhut HA

PMID: 31273864 [PubMed - indexed for MEDLINE]

Human papillomavirus risk perceptions and relationship status: a barrier to HPV vaccination?

Tue, 07/07/2020 - 07:39
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Human papillomavirus risk perceptions and relationship status: a barrier to HPV vaccination?

J Behav Med. 2019 Oct;42(5):991-997

Authors: Thompson EL, Vamos CA, Piepenbrink R, Kadono M, Vázquez-Otero C, Matthes S, Daley EM

Abstract
The purpose of this study was to assess the association between relationship status and perceived risk for human papillomavirus (HPV) among young adults. College adults, aged 18-26 years, completed an online survey from November 2016-April 2017 (n = 385). The survey assessed HPV vaccination status, perceived HPV risk, and current relationship status. Logistic regression models estimated the odds of perceived high risk for HPV, stratified by vaccination status. Among unvaccinated women, relationship status and HPV risk perception were significantly associated, with dating women more likely (OR = 5.33, 95%CI 1.16-24.50) to perceive a high risk for HPV compared to women in a committed relationship. Women in relationships were less likely to perceive themselves at high risk for HPV, even though HPV infection is prevalent among young adults. This association is not present for vaccinated women, suggesting that relationship status and risk perceptions may represent barriers to HPV vaccine uptake.

PMID: 30879225 [PubMed - indexed for MEDLINE]

Pharmacy educator evaluation of web-based learning.

Tue, 07/07/2020 - 07:39
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Pharmacy educator evaluation of web-based learning.

Clin Teach. 2019 12;16(6):630-635

Authors: Isaacs AN, Walton AM, Gonzalvo JD, Howard ML, Nisly SA

Abstract
BACKGROUND: Web-based learning (WBL), instruction facilitated through the Internet, has demonstrated utility in classroom and clinical education settings; however, there is a void of literature about the use of WBL by clinical educators within pharmacy. The purpose of this research is to evaluate a WBL initiative within clinical pharmacy education.
METHODS: Based on the results of a pilot survey, 10 asynchronous WBL clinical modules (videos and interactive patient cases) were developed for pharmacy educators and students in clinical education affiliated with two schools of pharmacy in the midwest USA. A 21-item, cross-sectional, electronic survey was administered to pharmacy educators within acute and primary care to assess the use of WBL within clinical pharmacy education.
RESULTS: Of the 115 eligible clinical educators, 69 participated in the survey (60% response rate), with the majority working within acute care; 38% of educators encouraged the use of WBL. Respondents not using WBL stated a lack of awareness (48%) or existing student time commitments (33%) as reasons. For educators encouraging WBL, 87% agreed that it enhanced student clinical knowledge, 68% stated that it decreased direct instruction time commitments and 100% stated they would encourage its use for future clinical education.
CONCLUSIONS: Clinical pharmacy educators reported that the WBL initiative resulted in a perceived stronger student clinical foundation, and all pharmacy educators using WBL encouraged its continued use for future clinical education. Web-based learning provides clinical educators with a learning tool to augment clinical experiences by reinforcing student knowledge, at the same time minimising direct instruction time.

PMID: 30746845 [PubMed - indexed for MEDLINE]

Modeling the cornea in 3-dimensions: Current and future perspectives.

Sat, 07/04/2020 - 06:55
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Modeling the cornea in 3-dimensions: Current and future perspectives.

Exp Eye Res. 2020 Jun 30;:108127

Authors: McKay TB, Hutcheon AEK, Guo X, Zieske JD, Karamichos D

Abstract
The cornea is an avascular, transparent ocular tissue that serves as a refractive and protective structure for the eye. Over 90% of the cornea is composed of a collagenous-rich extracellular matrix within the stroma with the other 10% composed by the corneal epithelium and endothelium layers and their corresponding supporting collagen layers (e.g., Bowman's and Descemet's membranes) at the anterior and posterior cornea, respectively. Due to its prominent role in corneal structure, tissue engineering approaches to model the human cornea in vitro have focused heavily on the cellular and functional properties of the corneal stroma. In this review, we discuss model development in the context of culture dimensionality (e.g., 2-dimensional versus 3-dimensional) and expand on the optical, biomechanical, and cellular functions promoted by the culture microenvironment. We describe current methods to model the human cornea with focus on organotypic approaches, compressed collagen, bioprinting, and self-assembled stromal models. We also expand on co-culture applications with the inclusion of relevant corneal cell types, such as epithelial, stromal keratocyte or fibroblast, endothelial, and neuronal cells. Further advancements in corneal tissue model development will markedly improve our current understanding of corneal wound healing and regeneration.

PMID: 32619578 [PubMed - as supplied by publisher]

Pexidartinib (TURALIO™): The First FDA-Indicated Systemic Treatment for Tenosynovial Giant Cell Tumor.

Sat, 07/04/2020 - 06:55
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Pexidartinib (TURALIO™): The First FDA-Indicated Systemic Treatment for Tenosynovial Giant Cell Tumor.

Drugs R D. 2020 Jul 02;:

Authors: Monestime S, Lazaridis D

Abstract
Tenosynovial giant cell tumor is a rare proliferative tumor that arises from the synovium, bursae, or tendon sheaths due to an overproduction of colony-stimulating factor 1. Historically, treatment options for patients with local or diffuse tenosynovial giant cell tumor have been limited to surgical interventions. However, for some patients, surgical resection could worsen functional limitations and/or morbidity. In August 2019, the FDA approved pexidartinib (TURALIO™, Daiichi Sankyo), the first systemic treatment option for adult patients with symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations that were not amenable to improvement with surgery. Pexidartinib is an oral tyrosine kinase inhibitor with selective inhibition of colony-stimulating factor 1 receptor and is the first systemic therapy to show significant improvement in overall response rates when compared with placebo. Clinicians using pexidartinib should monitor for liver-related adverse events, which may require treatment interruption, dose reduction, or treatment discontinuation. Pexidartinib provides a novel non-surgical treatment option for patients with tenosynovial giant cell tumor that may significantly improve patients' overall response, range of motion, physical function, tumor volume, and stiffness.

PMID: 32617868 [PubMed - as supplied by publisher]

Gamer's Thrombosis: A Review of Published Reports.

Fri, 07/03/2020 - 06:28
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Gamer's Thrombosis: A Review of Published Reports.

Ochsner J. 2020;20(2):182-186

Authors: Rambaran KA, Alzghari SK

Abstract
Background: Thrombosis, well known as a condition of the elderly, is occurring in the otherwise healthy adolescent population. Immobility is a significant risk factor for venous thromboembolism (VTE), and adolescents who play video games are immobile for extended periods of time. Some are presenting with VTE. When other risk factors such as obesity are present, the risk of VTE formation increases. We provide a review of published case reports regarding gaming and thrombosis. Methods: We searched PubMed, Scopus, Web of Science, and EBSCO for articles published through July 2019, using the keywords "computer game thrombosis," "computer game pulmonary embolism," "computer game deep vein thrombosis," "video game thrombosis," "video game pulmonary embolism," and "video game deep vein thrombosis." Results: Of the 26 articles we identified, we included 12 articles in our review that report a total of 15 cases, of which 2 resulted in fatalities. Modifiable risk factors included cigarette use, being overweight, birth control use, and prolonged immobility. Anticoagulation was the principal treatment modality in patients presenting with gaming thrombosis. Conclusion: We strongly encourage screening gamers for possible VTEs if clinically warranted.

PMID: 32612473 [PubMed]

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