bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a combination of arginine silicate complex and magnesium biotinate on the corneal phototoxic effect of UV exposure in rats
Authors: Sahin Nurhan , Orhan Cemal , Tuzcu Mehmet , Komorowski James R. , Ojalvo Sara Perez , Sylla Sarah , Sahin Kazim 
Published: April 2020

The purpose of this study was to investigate the effects of a combination of inositol‐stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on the prevention of corneal tissue damage after UVB exposure in rats. Twenty‐eight Sprague‐Dawley rats were randomized into one of the following groups; 1: Control, 2: UV (exposed to UV radiation with no other treatment), 3: UV+MgB Low Dose [L, 140 mg human equivalent dose (HED) of ASI and 1.5 mg HED of Biotin (B)], 4: UV+ASI+ MgB High Dose (H, 140 mg HED of ASI and 10 mg HED of B. Post UV exposure, ASI+MgB administration enhanced the reduced levels of corneal brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in rats. In addition, UV exposure increased the apoptotic protein Bax and glial fibrillary acid protein (GFAP), while decreasing the expression of Bcl‐2, neuronal remodeling marker protein growth‐associated protein‐43 (GAP43), and matrix metallopeptidase 9 (MMP‐9). However, ASI+MgB reduced the corneal Bax and GFAP levels and reversed the reduction of Bcl‐2, GAP‐43 and MMP‐3 levels after UV exposure. These results suggest ASI+MgB combination might be a potential complex that can prevent corneal damage from chronic UV exposure.Support or Funding InformationNutrition 21 Turkish Academy of Science (K.Sahin)
Temporal Changes in Pathologic Fibrosis Following Volumetric Muscle Loss Injury
Authors: Hoffman Daniel B. , Sorensen Jacob R. , Call Jarrod A. , Corona Benjamin T. , Greising Sarah M. 
Published: April 2020

Volumetric muscle loss (VML) is a devastating orthopaedic injury that results in chronic persistent functional deficits, loss of joint range of motion, pathologic fibrotic deposition and lifelong disability. Clinically, two major problems exist in the care of VML injuries: 1) no standard of care to address the loss of function and skeletal muscle mass, and 2) the pathologic fibrotic response impedes muscle healing and regeneration, causing destruction of muscle architecture and altering of the microenvironment of the muscle. However, to date there is only limited mechanistic understanding of the VML‐induced fibrosis. Our recent work indicates that through 21 days post‐VML there is a 22% loss in TA mass, 40% loss in total protein and mitochondrial content, and 45% loss in maximal isometric torque; however, how total collagen content changes over this time is unknown. We examined the temporal changes in the fibrotic deposition early after VML injury to identify a potential window of effective intervention. Adult male Lewis rats (n=42) underwent a full thickness ~20% (~85mg) VML injury to the tibialis anterior (TA) muscle or sham injury and were harvested for genetic and histologic evaluation. First, at 14 and 56 days post‐VML, fibrotic genes probed had biologically significant upregulation compared to control. Collagen I (Col1a1) and collagen III (Col3a1) had a 42‐ and 26‐fold upregulation in expression after 14 days, respectively. The upregulation was dampened at 56 days, yet still significant with Col1a1 and Col3a1 up 10‐ and 5‐fold from baseline. Interestingly, IL‐6 had the strongest upregulation between the 14 and 56‐day time points, from 4‐ to 59‐fold compared to controls. Second, in order to temporally track fibrotic changes more specifically, we evaluated extracellular proteins at 0, 3, 7, 14, 28, and 48 days post VML‐injury both biochemically and histologically. Histologic results indicate that following VML injury that significant fibrotic deposition begins to develop as early as 7 days post‐VML and there is a substantial cellular infiltration into the VML defect area. This suggests there is an initial attempt to follow a normal healing process; however, it is ultimately failed by a vast overcompensation by the immune system, which is supported by the escalating increase in IL‐6 expression. Additional work is needed to precisely probe the crosslinking of collagen fibers and overall makeup of the extracellular matrix across the early time frame after VML injury. Future work will help to identify potential therapeutic targets and assess the efficacy and timing of early rehabilitation, increased physical activity, and pharmacologic approaches to mitigate the fibrotic development after VML injury.Support or Funding InformationNone.
Ablation of PDE4B Protects from Lung Injury in a Mouse Model of Acute P. aeruginosa Infection
Authors: Saleh Lina Abou , Aragon Ileana V. , Boyd Abigail , McDonough Will , Koloteva Anna , Spadafora Domenico , Mneimneh Wadad , Barrington Robert A. , Richter Wito 
Published: April 2020

RationaleNon‐selective inhibitors of Type 4 cAMP‐phosphodiesterases (PDE4s) exert well established anti‐inflammatory effects in non‐infectious models of lung inflammation, such as upon exposure to lipopolysaccharide or ovalbumin, and have demonstrated clinical efficacy in the treatment of COPD. However, they also produce side effects, including emesis, nausea, diarrhea, and weight loss, that limit their clinical utility. The PDE4 family comprises 4 subtypes (PDE4A‐D). As each plays unique and non‐overlapping physiological roles, targeting individual subtypes may serve to separate the therapeutically beneficial from side effects resulting from non‐selective PDE4 inhibition. PDE4B has been proposed as a primary target by which PAN‐PDE4 inhibitors exert anti‐inflammatory effects. Here, we assessed whether genetic ablation of PDE4B is per se sufficient to protect mice infected with live P.aeruginosa from acute lung injury and whether PDE4B ablation can dampen immune responses without worsening the bacterial infection.MethodsPDE4B knockout (PDE4BKO) mice and their wildtype (WT) littermates were infected intranasally with P.aeruginosa lab strain PA01 and bronchoalveolar lavage fluid (BALF) and lungs were harvested 16 h later to assess lung infection/inflammation.ResultsAt 16 h post‐infection, the levels of pro‐inflammatory cytokines in BALF and lung tissue (TNFα, IL1β, IL‐6, and KC) as well as lung histopathological scores were reduced in PDE4BKO mice compared to their WT littermates indicating anti‐inflammatory benefits of PDE4B ablation, whereas the total number of leukocytes or neutrophils in BALF was unchanged. Unexpectedly, despite dampening the immune response, bacterial load in BALF and lungs was significantly decreased in PDE4BKO compared to WT controls. The ability of PDE4BKO mice to clear the bacteria more efficiently correlates with their ability to alleviate the significant PA‐induced hypothermia observed in WT controls. Indeed, when differences in hypothermia between WT and PDE4BKO mice are equalized by externally warming the animals, the bacterial load in WT and KO mice are comparable whereas anti‐inflammatory benefits, such as reduced cytokines levels in PDE4BKO mice, are retained.ConclusionsOur results suggest that ablation of PDE4B per se is sufficient to alleviate lung inflammation in a model of acute P.aeruginosa infection without worsening the bacterial infection. Thus, PDE4B may represent a therapeutic target for inflammatory lung diseases associated with P.aeruginosa infections, such as ventilator associated pneumonia or cystic fibrosis.Support or Funding InformationSupported by grants from the Cystic Fibrosis Foundation (SALEH18H0, RICHTE16GO) and the NIH (HL76125, HL141473, HL066299).
Elevated Plasma Activin A Levels during Pregnancy Impairs Global Longitudinal Strain in the Heart
Authors: Bakrania Bhavisha A. , Shahul Sajid , Hall Michael E. , Granger Joey P. 
Published: April 2020

Preeclampsia (PE) is a disorder prevalent in 3–8% of pregnancies, characterized by maternal hypertension, endothelial dysfunction and impaired cardiac function. PE is thought to develop in response to impaired spiral artery remodeling, leading to poor perfusion of the placenta. As a result, the ischemic placenta releases several anti‐angiogenic and pro‐inflammatory factors into the maternal circulation leading to widespread endothelial activation. Studies have also shown that preeclamptic women exhibit decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function that indicates fibrosis and tissue injury. Importantly, these findings were true independent of high blood pressure, suggesting that placental factors could play a role in the development of cardiac dysfunction in PE. A recent study showed Activin A, a pro‐fibrotic factor that is released by the placenta, is shown to be increased during PE pregnancy. Furthermore, increased circulating Activin A has been shown to be predictive of impaired GLS one year postpartum. PE is a multifaceted disease, and whether increased circulating Activin A alone induces cardiac dysfunction is not known. We hypothesized that chronic excess levels of Activin A during pregnancy induces cardiac dysfunction. To address this, rats were administered vehicle (n=6) or Activin A (n=6/group; A1, 1.25 μg/day, A2, 1.9μg/day, A3, 3 μg/day, A4, 6μg/day) via osmotic pump on gestational day (GD) 14. All animals had an indwelling carotid catheter placed on GD 18, followed by a comprehensive echocardiography assessment and blood pressure measurement on GD19. Activin A infusion resulted in significant increases in circulating Activin A in all treated groups (Vehicle, 585±47 pg/mL, A1, 2028±210 pg/mL, A2, 1895±382 pg/mL, A3, 2416±168 pg/mL, A4, 2864±181 pg/mL, P<0.01). At higher doses, Activin A infusion was associated with significantly impaired GLS (Vehicle, −22.1±0.8 %, A3, ‐ 16.9±0.9 %, P<0.01, A4, −14.9±0.5 %, P<0.01). Interestingly, mean arterial pressure was not significantly different between groups. These findings suggest that Activin A causes cardiac dysfunction in a dose dependent manner and may induce impaired GLS during pregnancy, independent of increases in blood pressure. This model could be useful in understanding the mechanisms by which Activin A induces these cardiac abnormalities in PE and whether blockade of this factor could improve outcomes for these women.Support or Funding InformationThis research was supported by the American Heart Association (18POST33990293) and the National Institutes of Health (P01HL051971, P20GM104357).
BDNF Augments NMDA‐signaling and Reduces GABAA‐signaling in the Paraventricular Nucleus of the Hypothalamus (PVN) to Elevate Blood Pressure
Authors: Thorsdottir Daniella , Einwag Zachary , Givant Madeleine , Erdos Benedek 
Published: April 2020

PVN presympathetic neurons, projecting to the rostral ventrolateral medulla (RVLM) or the spinal cord, play a critical role in the regulation of blood pressure. BDNF is a neurotrophic factor known to be upregulated in the PVN in response to hypertensive stimuli such as stress. However, the mechanisms by which BDNF modulates cardiovascular regulation in the PVN remains unclear. BDNF alters glutamatergic and GABAergic signaling, as well as neuronal morphology broadly in the central nervous system. Within the PVN, glutamatergic synaptic input and NMDA‐signaling are elevated, while GABAergic inhibition is reduced in hypertensive models. We tested the hypothesis that increased BDNF expression in the PVN elevates blood pressure by enhancing NMDA‐signaling, diminishing GABAA‐signaling and altering morphology of RVLM‐projecting PVN neurons. To simulate stress‐related upregulation of BDNF in the PVN, an AAV2 viral vector expressing BDNF was bilaterally injected into the PVN of Sprague Dawley rats, while control rats received AAV2‐GFP injections. Three weeks later, blood pressure and heart rate responses to PVN injections of NMDA and GABAA agonists and antagonists were recorded under anesthesia. Our results showed that inhibition of NMDA receptors with AP5 induced significantly larger decreases in blood pressure and heart rate in the BDNF group (−23±4 mmHg and −56±17 BPM) compared with the GFP group [5±1 mmHg (p<0.01) and −5±1 BPM (p<0.05)]. In contrast, activation of NMDA receptors with NMDA induced similar cardiovascular responses in GFP and BDNF animals. Inhibition of GABAA receptors with gabazine induced significantly smaller blood pressure increases in the BDNF group (32±6 mmHg) compared to GFP (61±11 mmHg, p<0.05), but heart rate responses were similar in the two groups. Activation of GABAA receptors with muscimol caused significantly reduced hypotensive responses in the BDNF group (−14±2 mmHg) compared to GFP (−23±4 mmHg, p<0.05), while changes in heart rate were similar. Quantitative RT‐PCR from PVN brain punches indicated that expression of NMDAR1 or GABAA‐Δ was unaffected by BDNF overexpression. However, immunofluorescence imaging in PVN brain sections demonstrated that BDNF significantly increased the soma size of RVLM‐projecting PVN neurons. In summary, our findings indicate that BDNF augments glutamate signaling in the PVN, primarily by increasing presynaptic glutamate release, and reduces GABA inhibition possibly through postsynaptic mechanisms. Finally, BDNF may also affect the balance of excitatory/inhibitory synaptic balance and regulation of blood pressure by increasing the soma size of PVN‐RVLM neurons.Support or Funding InformationR01 HL133211‐01A1.
Estrus Cycle Stages Differentially Alter Ventilatory Pattern Variability (VPV) in Septic Female Rats
Authors: Clifford Caitlyn , Campanaro Cara , Tackett Shiloh , Horton Kofi-Kermit , Nethery Dave , Hsieh Yee-Hsee , Jacono Frank , Dick Thomas 
Published: April 2020

The sex hormones, estrogen and progesterone, affect central respiratory control. Progesterone, increases respiratory frequency (fR). Sepsis, a disease process caused by a dysregulated systemic inflammatory response, also affects respiratory control that can be quantified by Ventilatory Pattern Variability (VPV). We hypothesized that natural hormone fluctuations during the female estrus cycle affect VPV and its differential control during sepsis. The estrus cycle of female Sprague Dawley rats (n = 19) was assessed by collecting, hematoxylin/eosin staining, and identifying vaginal epithelial cells. Proestrus, in which progesterone peaks, was determined by the absence of both leukocytes and cornified multinucleated epithelial cells. Rats were inoculated with fibrin pellets containing 0 (D0) or 100x 10^ 6 (D100) E. coli cells during proestrus. Before and 12 h after inoculation, we recorded the ventilatory pattern in conscious unrestrained rats using whole‐body plethysmography. VPV [coefficient of variation (CV) for the duration of the respiratory cycle (CV‐Ttot), autocorrelation function (AC), mutual information (MI), sample entropy (SampEn), and nonlinear complexity index (NLCI)] was compared across four experimental groups: 1) D0 proestrus rats (n = 3), 2) D100 proestrus rats (n = 7), 3) D0 non‐proestrus rats (n = 4), and 4) D100 non‐proestrus rats (n = 5) using one‐way analysis of variance (ANOVA). In the non‐proestrus groups, SampEn was greater in D0 than D100 (1.31±0.011 vs 1.14±0.002 Nats, p = 0.006), but in proestrus rats, SampEn did not vary with inoculation (D0, 1.26±0.003 vs D100, 1.26±0.004 Nats, NS). However, CV‐Ttot, AC and MI trended toward but did not reach significance given the low n. These preliminary data suggest that a decrease in VPV due to septicemia occurs in nonproestrus stages, whereas did not occur in proestrus.Support or Funding InformationFunded By: VA Research Service (I01BX004197); NIH (U01 EB021960)
The Influence of Behavioral Selection on Dental Variation in Domesticated Silver Foxes
Authors: Wood Emma K. , Maddux Scott D. , Southard Thomas E. , Kharlamova Anastasiya , Trut Lyudmila , Franciscus Robert G. 
Published: April 2020

The relationship between canine tooth size and social signaling has long been observed in wild carnivore and primate populations. In several of these species, it has been well‐established that larger canine size is directly correlated to social structures where agonistic interactions are commonplace. However, canine teeth are difficult to study in the wild because they serve multiple roles in addition to social signaling, such as food acquisition and guiding functional occlusion of the jaws. The Russian silver fox experiment represents a long‐term, controlled study where foxes have been selected for a behavioral phenotype toward either non‐aggression or hyper‐aggression. Results from the experiment have demonstrated that an increase in the range of variation of several soft tissue features accompanies selection for non‐aggression. In the absence of food‐related selective pressures, the influence of behavioral selection on dentition can be observed. The objective of this study is to compare the variation present in the gross dental sizes of canine teeth, which serve both social and food‐related roles, and carnassial teeth (maxillary P4 and mandibular M1), which play critical roles in mastication, as a result of selection solely on behavioral phenotype. We employed univariate and multivariate comparisons of maxillary canine, maxillary fourth premolar, mandibular first molar mesiodistal length and buccolingual breadth, as well as maximum height and crown height of the canine. These data were collected in sex‐balanced samples of unselected (n=51), tame (n=48), and hyper‐aggressive (n=50) experimental strains. Results indicate that the canine tooth is the most variable tooth across all three strains. This is in line with observations recorded in wild fox populations. However, foxes in the aggressive‐selected strain exhibit significantly reduced variation in canine crown height compared to the tame and control groups, further supporting hypotheses that the canine is strongly influenced by behavioral selective pressures favoring aggression. The patterns of variability in the tame‐selected strain tend to mirror those in the unselected strain, albeit with greater degrees of sexual dimorphism present in the variation. This provides further evidence that canine teeth are under strong selection relative to behavioral pressures and supports hypotheses that selection on behavior can affect the rate of variability of structures.Support or Funding InformationUniversity of Iowa College of Dentistry; University of Missouri; University of North Texas Health Science Center
Stent Graft Expulsion Outside the Skin: A Rare Case
Authors: Kalkan Asim , Bas Behlul , Kocer Taylan , Atis Seref Emre , Unver Sevilay Sema , Koca Yavuz Selim 
Published: April 2020

ABSTRACT
Patients who undergo stent grafting may present to the ED some time after the procedure with various related symptoms. The most common of these are stent graft occlusions or hematoma, although infection or abscess also may develop. In this case report, a 58-year-old man presented to the ED with a purulent wound on the stump of an amputated leg and a foreign body protruding from the wound site. The patient had a history of stent insertion with femoropopliteal bypass 11 years before this incident and an above-the-knee amputation because of stent occlusion 8 years prior. This wound had appeared with reddening of the skin 1 month before presentation, followed by the emergence and protrusion of a foreign body.
Comparison of clinical outcomes of 3 trifocal IOLs
Authors: Ribeiro Filomena , Ferreira Tiago B. 
Published: April 2020

Purpose:
To compare the clinical outcomes obtained after implantation of 1 of 3 models of diffractive trifocal IOLs.

Setting:
Hospital da Luz, Lisbon, Portugal.

Design:
Prospective randomized comparative study.

Methods:
Patients undergoing cataract surgery with bilateral implantation of 1 of 3 models of diffractive trifocal IOLs were enrolled. The IOL models implanted were the FineVision POD F, RayOne Trifocal, or the AcrySof IQ PanOptix IOL (30 eyes of 15 patients in each group). Visual acuity (VA), refraction, defocus curve, and contrast sensitivity outcomes were evaluated during a 3-month follow-up. Furthermore, the Quality of Vision questionnaire (QoV) was used to evaluate the frequency, severity, and discomfort of different visual symptoms.

Results:
A total of 90 eyes of 45 patients were included. No statistically significant differences were found between groups in distance, intermediate, and near VA (P ≥ .112) and postoperative refraction (P ≥ .059). Postoperative binocular uncorrected intermediate VA of 0.10 logarithm of the minimum angle of resolution (logMAR) or better was found in 14 (93.33%) patients in the 3 groups. Postoperative binocular uncorrected near VA of 0.10 logMAR or better was found in 13 (86.67%), 14 (93.33%), and 13 (86.67%) patients in the POD F, RayOne, and PanOptix IOLs groups, respectively. No statistically significant differences were found between groups in scotopic contrast sensitivity with and without glare and in the QoV scores (P ≥ .057), except for the difference between the POD F and RayOne IOLs groups in depth perception severity, which was less in the RayOne IOL group (P = .019).

Conclusions:
The 3 trifocal IOLs evaluated provided a complete visual restoration with good visual quality outcomes.
Validation of semi-automated flow-mediated dilation measurement in healthy volunteers
Authors: Dobbie Laurence J. , Mackin Sharon T. , Hogarth Katrina , Lonergan Frances , Kannenkeril Dennis , Brooksbank Katriona , Delles Christian 
Published: April 2020

Background
Flow-mediated dilation (FMD) is a non-invasive imaging modality used to measure endothelial function but has significant intra- and inter-observer variability. The use of semi-automated FMD devices could overcome this limitation. We assessed the reproducibility of same-day semi-automated FMD measurements by investigators who received basic training on the correct use of the device.

Methods
Forty-three healthy volunteers had two brachial artery FMD measurements performed 20 minutes apart using the UNEX EF 38G device, and automated outputs were produced. Images were also manually analysed using edge-detection software. The reproducibility of repeat FMD measurements within individuals was compared for automated and manual readings, and the correlation between analytical techniques was calculated.

Results
Twenty-five percent of scans were of non-diagnostic quality (n = 32). Automated analyses demonstrated sub-optimal reproducibility and measurement variability [intraclass correlation coefficient (ICCC) = 0.334, coefficient of variation (CV) = 45.87%]. In contrast, manually analysed scans had excellent reproducibility and low measurement variance (ICCC = 0.815, CV = 11.40%). FMD values obtained from automated and manual analysis correlated poorly (r = 0.164), whereas resting (r = 0.955) and maximal brachial artery diameters demonstrated excellent correlation (r = 0.867).

Conclusion
Manually evaluated serial UNEX EF readings have good reproducibility and therefore, the optimal FMD workflow involves manual analyses prior to independent automated interrogation. The high non-diagnostic scan rate is most likely the result of insufficient training and indicates that semi-automatic devices such as UNEX EF should be used by experienced investigators to achieve optimal results.