Recent Research Articles from UNTHSC

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

Subscribe to Recent Research Articles from UNTHSC  feed Recent Research Articles from UNTHSC
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]
Updated: 2 hours 49 min ago

Retrospective data analyses of social and environmental determinants of malaria control for elimination prospects in Eritrea.

Wed, 10/21/2020 - 07:47
Related Articles

Retrospective data analyses of social and environmental determinants of malaria control for elimination prospects in Eritrea.

Parasit Vectors. 2020 Mar 12;13(1):126

Authors: Mihreteab S, Lubinda J, Zhao B, Rodriguez-Morales AJ, Karamehic-Muratovic A, Goitom A, Shad MY, Haque U

Abstract
BACKGROUND: The present study focuses on both long- and short-term malaria transmission in Eritrea and investigates the risk factors. Annual aggregates of information on malaria cases, deaths, diagnostics and control interventions from 2001 to 2008 and monthly reported data from 2009 to 2017 were obtained from the National Malaria Control Programme. We used a generalized linear regression model to examine the associations among total malaria cases, death, insecticide-treated net coverage, indoor residual spraying and climatic parameters.
RESULTS: Reduction in malaria mortality is demonstrated by the milestone margins of over 97% by the end of 2017. Malaria incidence likewise declined during the period (from 33 to 5 per 1000 population), representing a reduction of about 86% (R2 = 0.3) slightly less than the decline in mortality. The distribution of insecticide treated nets generally declined between 2001 and 2014 (R2 = 0.16) before increasing from 2015 to 2017, while the number of people protected by indoor residual spraying slightly increased (R2 = 0.27). Higher rainfall was significantly associated with an increased number of malaria cases. The covariates rainfall and temperature are a better pair than IRS and LLIN to predict incidences. On the other hand, IRS and LLIN is a more significant pair to predict mortality cases.
CONCLUSIONS: While Eritrea has made significant progress towards malaria elimination, this progress should be maintained and further improved. Distribution, coverage and utilization of malaria control and elimination tools should be optimized and sustained to safeguard the gains made. Additionally, consistent annual performance evaluation of malaria indicators would ensure a continuous learning process from gains/threats of epidemics and resurgence in regions already earmarked for elimination.

PMID: 32164770 [PubMed - indexed for MEDLINE]

Proteomics Profiling of Autologous Blood and Semen Exosomes from HIV-infected and Uninfected Individuals Reveals Compositional and Functional Variabilities.

Wed, 10/21/2020 - 07:47
Related Articles

Proteomics Profiling of Autologous Blood and Semen Exosomes from HIV-infected and Uninfected Individuals Reveals Compositional and Functional Variabilities.

Mol Cell Proteomics. 2020 01;19(1):78-100

Authors: Kaddour H, Lyu Y, Welch JL, Paromov V, Mandape SN, Sakhare SS, Pandhare J, Stapleton JT, Pratap S, Dash C, Okeoma CM

Abstract
Blood and semen are important body-fluids that carry exosomes for bioinformation transmission. Therefore, characterization of their proteomes is necessary for understanding body-fluid-specific physiologic and pathophysiologic functions. Using systematic multifactorial proteomic profiling, we characterized the proteomes of exosomes and exosome-free fractions from autologous blood and semen from three HIV-uninfected and three HIV-infected participants (total of 24 samples). We identified exosome-based protein signatures specific to blood and semen along with HIV-induced tissue-dependent proteomic perturbations. We validated our findings with samples from 16 additional donors and showed that unlike blood exosomes (BE), semen exosomes (SE) are enriched in clusterin. SE but not BE promote Protein·Nucleic acid binding and increase cell adhesion irrespective of HIV infection. This is the first comparative study of the proteome of autologous BE and SE. The proteins identified may be developed as biomarkers applicable to different fields of medicine, including reproduction and infectious diseases.

PMID: 31676584 [PubMed - indexed for MEDLINE]

Effects of salt-loading on supraoptic vasopressin neurones assessed by ClopHensorN chloride imaging.

Wed, 10/21/2020 - 07:47
Related Articles

Effects of salt-loading on supraoptic vasopressin neurones assessed by ClopHensorN chloride imaging.

J Neuroendocrinol. 2019 08;31(8):e12752

Authors: Balapattabi K, Farmer GE, Knapp BA, Little JT, Bachelor M, Yuan JP, Cunningham JT

Abstract
Salt-loading (SL) impairs GABAA inhibition of arginine vasopressin (AVP) neurones in the supraoptic nucleus (SON) of the hypothalamus. Based on previous studies, we hypothesised that SL activates tyrosine receptor kinase B (TrkB), down-regulating the activity of K+ /Cl- co-transporter2 (KCC2) and up-regulating Na+ /K+ /Cl- co-transporter1 (NKCC1). These changes in chloride transport would result in increased [Cl- ]i in SON AVP neurones. The study combined virally-mediated chloride imaging with ClopHensorN with a single-cell western blot analysis. An adeno-associated virus with ClopHensorN and a vasopressin promoter (AAV2-0VP1-ClopHensorN) was bilaterally injected in the SON of adult male Sprague-Dawley rats that were either euhydrated (Eu) or salt-loaded (SL) for 7 days. Acutely dissociated SON neurones expressing ClopHensorN were tested for decreases or increases in [Cl- ]i in response to focal application of the GABAA agonist muscimol (100 μmol L-1 ). SON AVP neurones from Eu rats showed muscimol-induced chloride influx (P < 0.05;23/35). SON AVP neurones from SL rats either significantly increased chloride efflux (P < 0.05;27/39) or did not change chloride flux (12/39). The SON AVP neurones that responded to muscimol appeared to be viable and expressed KCC2 and β-actin. Neurones that did not respond during chloride imaging did not show KCC2 and β-actin protein expression. The KCC2 antagonist (VU0240551,10 μmol L-1 ) significantly blocked the chloride influx in cells from Eu rats but did not affect cells from SL rats. A NKCC1 antagonist (bumetanide,10 μmol L-1 ) significantly blocked the chloride efflux in cells from SL rats but had no effect on cells from Eu rats. Blocking NKCC1 using bumetanide had less of an effect on the muscimol-induced Cl- influx in Eu rat neurones compared to the KCC2 antagonist. The TrkB antagonist (AnA-12) (50 μmol L-1 ) and protein kinase inhibitor (K252a) (100 nmol L-1 ) each significantly blocked chloride efflux in SON AVP neurones from SL rats. Salt-loading increases [Cl- ]i in SON AVP neurones via a TrKB-KCC2-NKCC1-dependent mechanism in rats.

PMID: 31136029 [PubMed - indexed for MEDLINE]

Effect of Endoplasmic Reticulum Stress on Endothelial Ischemia-Reperfusion Injury in Humans.

Wed, 10/21/2020 - 03:35

Effect of Endoplasmic Reticulum Stress on Endothelial Ischemia-Reperfusion Injury in Humans.

Am J Physiol Regul Integr Comp Physiol. 2020 Oct 14;:

Authors: Hemingway HW, Moore AM, Olivencia-Yurvati AH, Romero SA

Abstract
Endoplasmic reticulum stress contributes to ischemia-reperfusion (I/R) injury in rodent and cell models. However, the contribution of endoplasmic reticulum stress in the pathogenesis of endothelial I/R injury in humans is unknown. We tested the hypothesis that compared with placebo, inhibition of endoplasmic reticulum stress via ingestion of tauroursodeoxycholic acid would prevent the attenuation of endothelium-dependent vasodilation following I/R injury. Twelve young adults (six women) were studied following ingestion of a placebo or 1,500 mg tauroursodeoxycholic acid (TUDCA). Endothelium-dependent vasodilation was assessed via brachial artery flow-mediated dilation (duplex ultrasonography) before and after I/R injury, which was induced by 20 min of arm ischemia followed by 20 min of reperfusion. Endothelium-independent vasodilation (glyceryl trinitrate-mediated vasodilation) was also assessed after I/R injury. Compared with placebo, TUDCA ingestion increased circulating plasma concentrations by 145 ± 90 ng ml-1 and increased concentrations of the taurine unconjugated form, ursodeoxycholic acid by 560 ± 156 ng ml-1 (both P < 0.01). Ischemia-reperfusion injury attenuated endothelium-dependent vasodilation, an effect that did not differ between placebo (pre-I/R, 5.0 ± 2.1% vs. post-I/R 3.5 ± 2.2%) and TUDCA (pre-I/R, 5.6 ± 2.1% vs. post-I/R 3.9 ± 2.1%; P = 0.8) conditions. Similarly, endothelium-independent vasodilation did not differ between conditions (placebo, 19.6 ± 4.8% vs. TUDCA, 19.7 ± 6.1%; P = 0.9). Taken together, endoplasmic reticulum stress does not appear to contribute to endothelial I/R injury in healthy young adults.

PMID: 33074709 [PubMed - as supplied by publisher]

The impact of COVID-19 on globalization.

Wed, 10/21/2020 - 03:35

The impact of COVID-19 on globalization.

One Health. 2020 Oct 13;:100180

Authors: Shrestha N, Shad MY, Ulvi O, Khan MH, Karamehic-Muratovic A, Nguyen UDT, Baghbanzadeh M, Wardrup R, Aghamohammadi N, Cervantes D, Nahiduzzaman KM, Zaki RA, Haque U

Abstract
Globalization has altered the way we live our lives and earn a livelihood. Consequently, trade and travel have been recognized as significant determinants of the spread of disease. Additionally, rise in urbanization and the closer integration of the world economy has facilitated global interconnectedness. Therefore, globalization has emerged as an essential mechanism of disease transmission. This paper aims to examine the potential impacts of COVID-19 on globalization and global health in terms of mobility, trade, travel, and countries most impacted. The effect of globalization was operationalized in terms of mobility, economy, and healthcare systems. The mobility of individuals and its magnitude was assessed using airline and seaport trade data and travel information. The economic impact was measured based on the workforce, event cancellations, food and agriculture, academic institutions, and supply chain. The healthcare capacity was assessed by consideration of healthcare systems indicators and preparedness of countries. Utilizing a technique for order of preference by similarity to ideal solution (TOPSIS) we calculated a pandemic vulnerability index (PVI) creating a quantitative measure of the potential global health. The pandemic has placed an unprecedented burden on the world's economy, healthcare, and globalization through the travel, events cancellation, employment workforce, food chain, academia, and healthcare capacity. Based on PVI results, certain countries are more vulnerable than others. In Africa, more vulnerable countries include South Africa and Egypt; in Europe, they are Russia, Germany, and Italy; in Asia and Oceania, they are India, Iran, Pakistan, Saudi Arabia, and Turkey; and for the Americas, they are Brazil, USA, Chile, Mexico, and Peru. The impact on mobility, economy, and healthcare systems has only started to manifest. The findings of this study may help in the planning and implementation of strategies at the country level to help ease this emerging burden.

PMID: 33072836 [PubMed - as supplied by publisher]

Evaluation of 16S rRNA Hypervariable Regions for Bioweapon Species Detection by Massively Parallel Sequencing.

Mon, 10/19/2020 - 19:52

Evaluation of 16S rRNA Hypervariable Regions for Bioweapon Species Detection by Massively Parallel Sequencing.

Int J Microbiol. 2020;2020:8865520

Authors: Dias VHG, Gomes PDSFC, Azevedo-Martins AC, Cabral BCA, Woerner AE, Budowle B, Moura-Neto RS, Silva R

Abstract
Molecular detection and classification of the bacterial groups in a sample are relevant in several areas, including medical research and forensics. Sanger sequencing of the 16S rRNA gene is considered the gold standard for microbial phylogenetic analysis. However, the development of massively parallel sequencing (MPS) offers enhanced sensitivity and specificity for microbiological analyses. In addition, 16S rRNA target amplification followed by MPS facilitates the combined use of multiple markers/regions, better discrimination of sample background, and higher sample throughput. We designed a novel set of 16S rRNA gene primers for detection of bacterial species associated with clinical, bioweapon, and biohazards microorganisms via alignment of 364 sequences representing 19 bacterial species and strains relevant to medical and forensics applications. In silico results indicated that the hypervariable regions (V1V2), (V4V5), and (V6V7V8) support the resolution of a selected group of bacteria. Interspecies and intraspecies comparisons showed 74.23%-85.51% and 94.48%-99.98% sequencing variation among species and strains, respectively. Sequence reads from a simulated scenario of bacterial species mapped to each of the three hypervariable regions of the respective species with different affinities. The minimum limit of detection was achieved using two different MPS platforms. This protocol can be used to detect or monitor as low as 2,000 genome equivalents of bacterial species associated with clinical, bioweapon, and biohazard microorganisms and potentially can distinguish natural outbreaks of pathogenic microorganisms from those occurring by intentional release.

PMID: 33061983 [PubMed]

Increasing body temperature with dynamic exercise and/or by wallowing/bathing in hot water or saunas: Effects on cerebral blood flow.

Mon, 10/19/2020 - 19:52
Related Articles

Increasing body temperature with dynamic exercise and/or by wallowing/bathing in hot water or saunas: Effects on cerebral blood flow.

J Physiol. 2020 04;598(8):1421-1422

Authors: Raven PB, Romero SA

PMID: 32080850 [PubMed - indexed for MEDLINE]

Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands.

Mon, 10/19/2020 - 19:52
Related Articles

Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands.

Bioorg Med Chem Lett. 2019 09 15;29(18):2690-2694

Authors: Chen PJ, Taylor M, Griffin SA, Amani A, Hayatshahi H, Korzekwa K, Ye M, Mach RH, Liu J, Luedtke RR, Gordon JC, Blass BE

Abstract
As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.

PMID: 31387791 [PubMed - indexed for MEDLINE]

Modern treatment of tibial shaft fractures: Is there a role today for closed treatment?

Wed, 10/14/2020 - 13:24

Modern treatment of tibial shaft fractures: Is there a role today for closed treatment?

Injury. 2020 Oct 05;:

Authors: Swart E, Lasceski C, Latario L, Jo J, Nguyen UDT

Abstract
PURPOSE: The decision to attempt closed treatment on tibial shaft fractures can be challenging. At our institution, we attempt treatment of nearly all closed, isolated tibial shaft fractures. The purpose of this study was to report the results of 10 years of experience to develop a tool to identify patients for whom non-operative treatment of tibial shaft fractures may be a viable option METHOD: This was a retrospective review of patients with tibial shaft fracture seen at a level 1 trauma center over 10 years. Patients with closed, isolated injuries underwent sedation, closed reduction, long-leg casting, and outpatient follow-up. Patients were converted to surgery for inability to obtain or maintain acceptable alignment or patient intolerance. Radiographic characteristics and patient demographics were extracted. Logistic regression analysis was used to develop a model to predict which patient and injury characteristics determined success of nonoperative treatment.
RESULTS: 334 patients were identified with isolated, closed tibial shaft fractures, who were reduced and treated in a long leg cast. 234 patients (70%) converted to surgical treatment due to inability to maintain alignment, patient intolerance, and nonunion. In a regression model, coronal/sagittal translation, sagittal angulation, fracture morphology, and smoking status were shown to be significant predictors of success of nonoperative treatment (p < 0.05). We developed a Tibial Operative Outcome Likelihood (TOOL) score designed to help predict success or failure of closed treatment. The TOOL score can be used to identify a subsegment of patients with injuries amenable to closed treatment (38% of injuries) with a nonoperative success rate over 60%.
CONCLUSION: Non-operative treatment of tibial shaft fractures is feasible, although there is a relatively high conversion rate to operative treatment. However, it is possible to use injury characteristics to identify a cohort of patients with a higher chance of success with closed treatment, which is potentially useful in a resource-constrained setting or for patients who wish to avoid surgery.
LEVEL OF EVIDENCE: Prognostic Level 3.

PMID: 33046252 [PubMed - as supplied by publisher]

Risk Assessment of Recreational Noise-Induced Hearing Loss from Exposure through a Personal Audio System-iPod Touch.

Wed, 10/14/2020 - 13:24
Related Articles

Risk Assessment of Recreational Noise-Induced Hearing Loss from Exposure through a Personal Audio System-iPod Touch.

J Am Acad Audiol. 2019 Jul/Aug;30(7):619-633

Authors: Gopal KV, Mills LE, Phillips BS, Nandy R

Abstract
BACKGROUND: Recreational noise-induced hearing loss (RNIHL) is a major health issue and presents a huge economic burden on society. Exposure to loud music is not considered hazardous in our society because music is thought to be a source of relaxation and entertainment. However, there is evidence that regardless of the sound source, frequent exposure to loud music, including through personal audio systems (PAS), can lead to hearing loss, tinnitus, difficulty processing speech, and increased susceptibility to age-related hearing loss.
PURPOSE: Several studies have documented temporary threshold shifts (TTS) (a risk indicator of future permanent impairment) in subjects that listen to loud music through their PAS. However, there is not enough information regarding volume settings that may be considered to be safe. As a primary step toward quantifying the risk of RNIHL through PAS, we assessed changes in auditory test measures before and after exposure to music through the popular iPod Touch device set at various volume levels.
RESEARCH DESIGN: This project design incorporated aspects of both between- and within-subjects and used repeated measures to analyze individual groups.
STUDY SAMPLE: A total of 40 adults, aged 18-31 years with normal hearing were recruited and randomly distributed to four groups. Each group consisted of five males and five females.
DATA COLLECTION AND ANALYSIS: Subjects underwent two rounds of testing (pre- and postmusic exposure), with a 30-min interval, where they listened to a playlist consisting of popular songs through an iPod at 100%, 75%, 50%, or 0% volume (no music). Based on our analysis on the Knowles Electronic Manikin for Acoustic Research, with a standardized 711 coupler, it was determined that listening to the playlist for 30 min through standard earbuds resulted in an average level of 97.0 dBC at 100% volume, 83.3 dBC at 75% volume, and 65.6 dBC at 50% volume. Pure-tone thresholds from 500-8000 Hz, extended high-frequency pure tones between 9-12.5 kHz, and distortion product otoacoustic emissions (DPOAE) were obtained before and after the 30-min music exposure. Analysis of variance (ANOVA) was performed with two between-subjects factors (volume and gender) and one within-subjects factor (frequency). Change (shift) in auditory test measures was used as the outcome for the ANOVA.
RESULTS: Results indicated significant worsening of pure-tone thresholds following music exposure only in the group that was exposed to 100% volume at the following frequencies: 2, 3, 4, 6 and 8 kHz. DPOAEs showed significant decrease at 2000 and 2822 Hz, also only for the 100% volume condition. No significant changes were found between pre- and postmusic exposure measures in groups exposed to 75%, 50%, or 0% volume conditions. Follow-up evaluations conducted a week later indicated that pure-tone thresholds had returned to the premusic exposure levels.
CONCLUSIONS: These results provide quantifiable information regarding safe volume control settings on the iPod Touch with standard earbuds. Listening to music using the iPod Touch at 100% volume setting for as little as 30 min leads to TTS and worsening of otoacoustic emissions, a risk for permanent auditory damage.

PMID: 30395532 [PubMed - indexed for MEDLINE]

Prevalence and predictors of weight loss during induction therapy for childhood acute lymphoblastic leukemia.

Tue, 10/13/2020 - 14:25

Prevalence and predictors of weight loss during induction therapy for childhood acute lymphoblastic leukemia.

Nutrition. 2020 Jul 03;81:110937

Authors: Hill R, Hamby T, Johnson D, Boren C, Downs H, Ray A

Abstract
Children with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma often experience significant weight gain during induction therapy. However, a subgroup of patients may experience weight loss, which can impact outcomes; thus, identifying and understanding this underrecognized concern is important. Our aim was to identify the prevalence and predictors for weight loss during ALL induction therapy. This was a single-institution retrospective study of 187 patients, ages 2 to 20 y, diagnosed with ALL or lymphoblastic lymphoma. We analyzed weight trends during induction therapy and predictors of weight loss. Significant weight loss (≥5%) occurred in 17% of patients. Having high-risk disease, trisomy 21, overweight/obese status at the time of diagnosis, and/or hyperglycemia were positively associated with weight loss and negatively associated with weight gain during induction therapy. Future studies should aim to better understand the etiology and importance of weight loss during induction therapy.

PMID: 33045486 [PubMed - as supplied by publisher]

Canaloplasty and Trabeculotomy with the OMNI System in Pseudophakic Patients with Open-Angle Glaucoma: the ROMEO Study.

Tue, 10/13/2020 - 14:25

Canaloplasty and Trabeculotomy with the OMNI System in Pseudophakic Patients with Open-Angle Glaucoma: the ROMEO Study.

Ophthalmol Glaucoma. 2020 Oct 09;:

Authors: Vold SD, Williamson BK, Hirsch L, Aminlari AE, Cho AS, Nelson C, Dickerson JE

Abstract
PURPOSE: Provide outcomes up to 12 months post-surgically for sequential canaloplasty and trabeculotomy with the OMNI surgical system (OMNI) in pseudophakic patients with mild to moderate open-angle glaucoma (OAG).
DESIGN: Retrospective, multicenter, single arm study conducted at 10 multi-subspecialty ophthalmology practices and surgery centers located in seven states (AR, CA, KS, LA, MO, NY, TX).
SUBJECTS: Eligible patients were pseudophakic, with mild/moderate OAG, 12-month follow-up, and medicated intraocular pressure (IOP) ≤36 mmHg on ≤ 4 medications preoperatively. One eye per patient was enrolled.
METHODS: IRB approved. All available cases meeting eligibility criteria were enrolled. Analysis of secondary endpoints was stratified by baseline (BL) IOP; >18 mmHg (Group 1), ≤ 18 mmHg (Group 2) recognizing that treatment goals differed depending on BL IOP.
MAIN OUTCOME MEASURES: Primary success was defined as proportion of patients with ≥ 20% reduction in IOP from BL OR IOP between 6 and 18 mmHg (inclusive) AND on the same or fewer medications without secondary surgical intervention (SSI). Other effectiveness endpoints included mean IOP and number of medications at 12 months. Safety endpoints were best corrected visual acuity (BCVA), adverse events (AE), and secondary surgical interventions (SSI).
RESULTS: Forty-eight patients were enrolled, 24 in each group. Primary success was met by 73%. Mean IOP was reduced in Group 1 (21.8 to 15.6 mmHg, p < 0.0001), and remained controlled in Group 2 (15.4 to 13.9 mmHg, p = 0.24). Medications went from 1.7 ± 1.3 to 1.2 ± 1.3, P = .024 (Group 1) and from 2.0 ± 1.3 to 1.3 ± 1.3, P = .003 (Group 2). AE were typical for the patient population undergoing angle surgery. Those reasonably related to the procedure were mild inflammation (13%), IOP spikes, (6%), hyphema, corneal edema, and BCVA loss, all (4%). 5 patients (10%) required an SSI.
CONCLUSIONS: The sequential combination of canaloplasty followed by trabeculotomy performed as standalone procedures using the OMNI system in pseudophakic patients with open angle glaucoma provides effective IOP reduction or sustained IOP control, and meaningful medication reduction for up to 12 months postoperative.

PMID: 33045423 [PubMed - as supplied by publisher]

Takotsubo Syndrome in Patients with COVID-19: a Systematic Review of Published Cases.

Tue, 10/13/2020 - 14:25

Takotsubo Syndrome in Patients with COVID-19: a Systematic Review of Published Cases.

SN Compr Clin Med. 2020 Oct 06;:1-7

Authors: Singh S, Desai R, Gandhi Z, Fong HK, Doreswamy S, Desai V, Chockalingam A, Mehta PK, Sachdeva R, Kumar G

Abstract
Takotsubo syndrome (TTS) is caused by catecholamine surge, which is also observed in COVID-19 disease due to the cytokine storm. We performed a systematic literature search using PubMed/Medline, SCOPUS, Web of Science, and Google Scholar databases to identify COVID-19-associated TTS case reports and evaluated patient-level demographics, clinical attributes, and outcomes. There are 12 cases reported of TTS associated with COVID-19 infection with mean age of 70.8 ± 15.2 years (range 43-87 years) with elderly (66.6% > 60 years) female (66.6%) majority. The time interval from the first symptom to TTS was 8.3 ± 3.6 days (range 3-14 days). Out of 12 cases, 7 reported apical ballooning, 4 reported basal segment hypo/akinesia, and 1 reported median TTS. Out of 12 cases, during hospitalization, data on left ventricular ejection fraction (LVEF) was reported in only 9 of the cases. The mean LVEF was 40.6 ± 9.9% (male, 46.7 ± 5.7%, and female, 37.7 ± 10.6%). Troponin was measured in all 12 cases and was elevated in 11 (91.6%) without stenosis on coronary angiography except one. Out of 11 cases, 6 developed cardiac complications with 1 case each of cardiac tamponade, heart failure, myocarditis, hypertensive crisis, and cardiogenic shock in 2. Five patients required intubation, 1 patient required continuous positive airway pressure, and 1 patient required venovenous extracorporeal membrane oxygenation. The outcome was reported in terms of recovery in 11 (91.6%) out of 12 cases, and a successful recovery was noted in 10 (90.9%) cases. COVID-19-related TTS has a higher prevalence in older women. Despite a lower prevalence of cardiac comorbidities in COVID-19 patients, direct myocardial injury, inflammation, and stress may contribute to TTS with a high complication rate.

PMID: 33043251 [PubMed - as supplied by publisher]

Electronic cigarette explosion/burn and poisoning related emergency department visits, 2018-2019.

Tue, 10/13/2020 - 14:25

Electronic cigarette explosion/burn and poisoning related emergency department visits, 2018-2019.

Am J Emerg Med. 2020 Aug 16;:

Authors: Rossheim ME, McDonald KK, Soule EK, Gimm GW, Livingston MD, Barnett TE, Jernigan DH, Thombs DL

Abstract
BACKGROUND: Electronic cigarette (ECIG) use has increased dramatically in recent years. Negative ECIG-related acute health effects have included explosion/burn injuries from battery failure and child ingestion/poisoning of liquid nicotine. However, there is an urgent need for continued surveillance of ECIG health effects to determine whether these outcomes change as ECIG devices and liquids rapidly evolve. This study updates national estimates of ECIG-related emergency department (ED) visits and describes the context of these injuries.
METHODS: A keyword search of case narrative text was used to identify ECIG-related ED visits in the National Electronic Injury Surveillance System (NEISS) data. These cross-sectional data are designed to be weighted to provide national estimates of consumer product-related injuries treated in EDs. ECIG-related injuries were described and categorized, and sampling weights applied to model national estimates.
RESULTS: From 2015 to 2019 there were an estimated 3369 ED visits from ECIG explosion/burn injuries (95% CI = 2020, 4718), and an estimated 676 visits from 2019 alone (95% CI = 315, 1036). In 2018-2019, there were an estimated 1550 cases of children <5 years old ingesting ECIG liquids (95% CI = 778, 2322).
CONCLUSIONS: Despite a notable shift in the US market towards ECIG devices that use lower electrical power and disposable "pods" (e.g., JUUL), liquid chemical ingestion among young children and ECIG explosion/burn injuries persist. Improved product regulations are urgently needed to prevent negative health effects caused by ECIGs, as well as prevent their ingestion and use by children.

PMID: 33041151 [PubMed - as supplied by publisher]

Inhibition of interleukin-6 on matrix protein production by glomerular mesangial cells and the pathway involved.

Thu, 10/08/2020 - 06:12
Related Articles

Inhibition of interleukin-6 on matrix protein production by glomerular mesangial cells and the pathway involved.

Am J Physiol Renal Physiol. 2020 06 01;318(6):F1478-F1488

Authors: Chaudhari S, Yazdizadeh Shotorbani P, Tao Y, Davis ME, Mallet RT, Ma R

Abstract
Activation of immunological pathways and disturbances of extracellular matrix (ECM) dynamics are important contributors to the pathogenesis of chronic kidney diseases. Glomerular mesangial cells (MCs) are critical for homeostasis of glomerular ECM dynamics. Interleukin-6 (IL-6) can act as a pro/anti-inflammatory agent relative to cell types and conditions. This study investigated whether IL-6 influences ECM protein production by MCs and the regulatory pathways involved. Experiments were carried out in cultured human MCs (HMCs) and in mice. We found that overexpression of IL-6 and its receptor decreased the abundance of fibronectin and collagen type IV in MCs. ELISA and immunoblot analysis demonstrated that thapsigargin [an activator of store-operated Ca2+ entry (SOCE)], but not the endoplasmic reticulum stress inducer tunicamycin, significantly increased IL-6 content. This thapsigargin effect was abolished by GSK-7975A, a selective inhibitor of SOCE, and by silencing Orai1 (the channel protein mediating SOCE). Furthermore, inhibition of NF-κB pharmacologically and genetically significantly reduced SOCE-induced IL-6 production. Thapsigargin also stimulated nuclear translocation of the p65 subunit of NF-κB. Moreover, MCs overexpressing IL-6 and its receptor in HMCs increased the content of the glucagon-like peptide-1 receptor (GLP-1R), and IL-6 inhibition of fibronectin was attenuated by the GLP-1R antagonist exendin 9-39. In agreement with the HMC data, specific knockdown of Orai1 in MCs using the targeted nanoparticle delivery system in mice significantly reduced glomerular GLP-1R levels. Taken together, our results suggest a novel SOCE/NF-κB/IL-6/GLP-1R signaling pathway that inhibits ECM protein production by MCs.

PMID: 32390515 [PubMed - indexed for MEDLINE]

Probing Protein Allostery as a Residue-Specific Concept via Residue Response Maps.

Thu, 10/08/2020 - 06:12
Related Articles

Probing Protein Allostery as a Residue-Specific Concept via Residue Response Maps.

J Chem Inf Model. 2019 11 25;59(11):4691-4705

Authors: Hayatshahi HS, Ahuactzin E, Tao P, Wang S, Liu J

Abstract
Allosteric regulation is a well-established phenomenon defined as a distal conformational or dynamical change of the protein upon allosteric effector binding. Here, we developed a novel approach to delineate allosteric effects in proteins. In this approach, we applied robust machine learning methods, including deep neural network and random forest, on extensive molecular dynamics (MD) simulations to distinguish otherwise similar allosteric states of proteins. Using the PDZ3 domain of PDS-95 as a model protein, we demonstrated that the allosteric effects could be represented as residue-specific properties through two-dimensional property-residue maps, which we refer to as "residue response maps". These maps were constructed through two machine learning methods and could accurately describe how different properties of various residues are affected upon allosteric perturbation on protein. Based on the "residue response maps", we propose allostery as a residue-specific concept, suggesting that all residues could be considered as allosteric residues because each residue "senses" the allosteric events through changing its single or multiple attributes in a quantitatively unique way. The "residue response maps" could be used to fingerprint a protein based on the unique patterns of residue responses upon binding events, providing a novel way to systematically describe the protein allosteric effects of each residue upon perturbation.

PMID: 31589429 [PubMed - indexed for MEDLINE]

Chronic unilateral cervical vagotomy reduces renal inflammation, blood pressure, and renal injury in a mouse model of lupus.

Wed, 10/07/2020 - 11:41
Related Articles

Chronic unilateral cervical vagotomy reduces renal inflammation, blood pressure, and renal injury in a mouse model of lupus.

Am J Physiol Renal Physiol. 2020 08 01;319(2):F155-F161

Authors: Pham GS, Shimoura CG, Chaudhari S, Kulp DV, Mathis KW

Abstract
Systemic lupus erythematosus (SLE) is characterized by hypertension that results from chronic renal inflammation and dysautonomia in the form of dampened vagal tone. In health, the vagus nerve regulates inflammatory processes through mechanisms like the cholinergic anti-inflammatory pathway; so in the case of SLE, reduced efferent vagus nerve activity may indirectly affect renal inflammation and therefore hypertension. In this study, we sought to investigate the impact of disrupting vagal neurotransmission on renal inflammation and hypertension in the setting of chronic inflammatory disease. Female SLE (NZBWF1) and control (NZW) mice were subjected to a right unilateral cervical vagotomy or sham surgery and 3 wk later were implanted with indwelling catheters to measure blood pressure. Indices of splenic and renal inflammation, as well as renal injury, were assessed. Unilateral vagotomy blunted SLE-induced increases in mean arterial pressure, albumin excretion rate, and glomerulosclerosis. This protection was associated with reduced splenic T cells and attenuated SLE-induced increases in renal proinflammatory mediators. In summary, these data indicate that unilateral vagotomy reduces renal inflammation and reduces blood pressure in SLE mice. The vagus nerves have myriad functions, and perhaps other neuroimmune interactions compensate for the ligation of one nerve.

PMID: 32538149 [PubMed - indexed for MEDLINE]

Feasibility Trial of an eHealth Intervention for Health-Related Quality of Life: Implications for Managing Patients with Chronic Pain during the COVID-19 Pandemic.

Wed, 10/07/2020 - 05:34

Feasibility Trial of an eHealth Intervention for Health-Related Quality of Life: Implications for Managing Patients with Chronic Pain during the COVID-19 Pandemic.

Healthcare (Basel). 2020 Oct 01;8(4):

Authors: Licciardone JC, Pandya V

Abstract
PURPOSE: This study was conducted to determine the feasibility of providing an eHealth intervention for health-related quality of life (HRQOL) to facilitate patient self-management.
METHODS: A randomized controlled trial was conducted from 2019-2020 within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation. Eligible patients included those with chronic low back pain and a SPADE (sleep disturbance, pain interference with activities, anxiety, depression, and low energy/fatigue) cluster score ≥ 55 based on the relevant scales from the Patient-Reported Outcomes Measurement Information System instrument with 29 items (PROMIS-29). Patients were randomized to the eHealth treatment group, which received a tailored HRQOL report and interpretation guide, or to a wait-list control group. The primary outcome was change in the SPADE cluster score, including its five component scales, over 3 months. Secondary outcomes were changes in low back pain intensity and back-related disability. Treatment effects were measured using the standardized mean difference (SMD) in change scores between groups. The eHealth intervention was also assessed by a survey of the experimental treatment group 1 month following randomization.
RESULTS: A total of 102 patients were randomized, including 52 in the eHealth treatment group and 50 in the wait-list control group, and 100 (98%) completed the trial. A majority of patients agreed that the HRQOL report was easy to understand (86%), provided new information (79%), and took actions to read or learn more about self-management approaches to improve their HRQOL (77%). Although the eHealth intervention met the criteria for a small treatment effect in improving the overall SPADE cluster score (SMD = 0.24; p= 0.23) and anxiety (SMD = 0.24; p = 0.23), and for a small-to-medium treatment effect in improving depression (SMD = 0.37; p = 0.06) and back-related disability (SMD = 0.36; p = 0.07), none of these results achieved statistical significance because of limited sample size.
CONCLUSION: Given the feasibility of rapid online deployment, low cost, and low risk of adverse events, this eHealth intervention for HRQOL may be useful for patients with chronic pain during the COVID-19 pandemic.

PMID: 33019676 [PubMed]

Mechanisms of sympathetic restraint in human skeletal muscle during exercise: role of α-adrenergic and nonadrenergic mechanisms.

Wed, 10/07/2020 - 05:34
Related Articles

Mechanisms of sympathetic restraint in human skeletal muscle during exercise: role of α-adrenergic and nonadrenergic mechanisms.

Am J Physiol Heart Circ Physiol. 2020 07 01;319(1):H192-H202

Authors: Hansen AB, Moralez G, Romero SA, Gasho C, Tymko MM, Ainslie PN, Hofstätter F, Rainer SL, Lawley JS, Hearon CM

Abstract
Sympathetic vasoconstriction is mediated by α-adrenergic receptors under resting conditions. During exercise, increased sympathetic nerve activity (SNA) is directed to inactive and active skeletal muscle; however, it is unclear what mechanism(s) are responsible for vasoconstriction during large muscle mass exercise in humans. The aim of this study was to determine the contribution of α-adrenergic receptors to sympathetic restraint of inactive skeletal muscle and active skeletal muscle during cycle exercise in healthy humans. In ten male participants (18-35 yr), mean arterial pressure (intra-arterial catheter) and forearm vascular resistance (FVR) and conductance (FVC) were assessed during cycle exercise (60% total peak workload) alone and during combined cycle exercise + handgrip exercise (HGE) before and after intra-arterial blockade of α- and β-adrenoreceptors via phentolamine and propranolol, respectively. Cycle exercise caused vasoconstriction in the inactive forearm that was attenuated ~80% with adrenoreceptor blockade (%ΔFVR, +81.7 ± 84.6 vs. +9.7 ± 30.7%; P = 0.05). When HGE was performed during cycle exercise, the vasodilatory response to HGE was restrained by ~40% (ΔFVC HGE, +139.3 ± 67.0 vs. cycle exercise: +81.9 ± 66.3 ml·min-1·100 mmHg-1; P = 0.03); however, the restraint of active skeletal muscle blood flow was not due to α-adrenergic signaling. These findings highlight that α-adrenergic receptors are the primary, but not the exclusive mechanism by which sympathetic vasoconstriction occurs in inactive and active skeletal muscle during exercise. Metabolic activity or higher sympathetic firing frequencies may alter the contribution of α-adrenergic receptors to sympathetic vasoconstriction. Finally, nonadrenergic vasoconstrictor mechanisms may be important for understanding the regulation of blood flow during exercise.NEW & NOTEWORTHY Sympathetic restraint of vascular conductance to inactive skeletal muscle is critical to maintain blood pressure during moderate- to high-intensity whole body exercise. This investigation shows that cycle exercise-induced restraint of inactive skeletal muscle vascular conductance occurs primarily because of activation of α-adrenergic receptors. Furthermore, exercise-induced vasoconstriction restrains the subsequent vasodilatory response to hand-grip exercise; however, the restraint of active skeletal muscle vasodilation was in part due to nonadrenergic mechanisms. We conclude that α-adrenergic receptors are the primary but not exclusive mechanism by which sympathetic vasoconstriction restrains blood flow in humans during whole body exercise and that metabolic activity modulates the contribution of α-adrenergic receptors.

PMID: 32502375 [PubMed - indexed for MEDLINE]

HIV-1 Impairment via UBE3A and HIV-1 Nef Interactions Utilizing the Ubiquitin Proteasome System.

Tue, 10/06/2020 - 07:28
Related Articles

HIV-1 Impairment via UBE3A and HIV-1 Nef Interactions Utilizing the Ubiquitin Proteasome System.

Viruses. 2019 11 27;11(12):

Authors: Pyeon D, Rojas VK, Price L, Kim S, Meharvan S, Park IW

Abstract
Molecular basis of HIV-1 life cycle regulation has thus far focused on viral gene stage-specificity, despite the quintessence of post-function protein elimination processes in the virus life cycle and consequent pathogenesis. Our studies demonstrated that a key pathogenic HIV-1 viral protein, Nef, interacted with ubiquitin (Ub)-protein ligase E3A (UBE3A/E6AP), suggesting that interaction between Nef and UBE3A is integral to regulation of viral and cellular protein decay and thereby the competing HIV-1 and host cell survivals. In fact, Nef and UBE3A degraded reciprocally, and UBE3A-mediated degradation of Nef was significantly more potent than Nef-triggered degradation of UBE3A. Further, UBE3A degraded not only Nef but also HIV-1 structural proteins, Gag, thus significantly inhibiting HIV-1 replication in Jurkat T cells only in the presence of Nef, indicating that interaction between Nef and UBE3Awas pivotal for UBE3A-mediated degradation of the viral proteins. Mechanistic study showed that Nef and UBE3A were specific and antagonistic to each other in regulating proteasome activity and ubiquitination of cellular proteins in general, wherein specific domains of Nef overlapping with the long terminal repeat (LTR) were essential for the observed actions. Further, Nef itself reduced the level of intracellular Gag by degrading a cardinal transcription regulator, Tat, demonstrating a broad role for Nef in the regulation of the HIV-1 life cycle. Taken together, these data demonstrated that the Nef and UBE3A complex plays a crucial role in coordinating viral protein degradation and hence HIV-1 replication, providing insights as to the nature of pathobiologic and defense strategies of HIV-1 and HIV-infected host cells.

PMID: 31783587 [PubMed - indexed for MEDLINE]

Pages