bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunocharacterization of the atypical basal lamina at cell‐tooth interfaces in laminin‐332 deficient mice (LB548)
Authors: Wazen Rima , Moffatt Pierre , Adair‐Kirk Tracy , Nanci Antonio 
Published: June 2021

Unlike elsewhere in the body, the atypical basal lamina (BL) at epithelial‐tooth interfaces must bind to mineral rather than connective tissue. Therefore, this BL has adapted by integrating specialized components. It is enriched in laminin‐332 (Lm‐332), and recently amelotin (AMTN), odontogenic ameloblast‐associated (ODAM), and secretory calcium‐binding phosphoprotein‐proline‐glutamine‐rich 1 (SCPPPQ1), members of the SCPP gene family, have been identified as novel constituents. To explore how these three small molecular weight proteins participate in BL structure and mediate cell‐mineral adhesion, we used a mouse model of Lm‐332 deficiency, which expresses a doxycycline‐controllable human Lm γ2 transgene under the cytokeratin 14 promoter on the Lm γ2 knockout background. Mandibles and maxillae from wild‐type and Lm‐332 deficient mice were paraffin‐embedded and sections were immunostained for AMTN, ODAM, or SCPPPQ1. In the maturation stage of amelogenesis, all three proteins localized very discretely in the BL at the ameloblast surface of wild‐type mice. However in Lm‐332 deficient mice, all three proteins accumulated as focal patches within the cell layer rather than at the cell apex. Thus, it is concluded that AMTN, ODAM, and SCPPPQ1 require Lm‐332 for their proper positioning in the BL and for mediating adhesion to the tooth surface. As such, the defects in teeth of patients with junctional epidermolysis bullosa resulting from mutation in Lm‐332 likely reflect altered interactions among these proteins.Grant Funding Source: Supported by CIHR, NIH/NHLBI P01HL029594, Shriners of North America
Synergistic effect of palmitate and nicotine treatments in diabetic heart (LB560)
Authors: Arunachalam Gnanapragasam , Samuel Samson , Ghosh Suparna , Ding Hong , Machaca Khaled , Triggle Chris 
Published: June 2021

Background: Metabolic disorders (hyperglycemia, dyslipidemia, hypertension) contribute to the development and progression of cardiovascular disease in individuals with type 2 diabetes. Risk factors such as obesity and cigarette smoking are also strongly associated with exacerbation of diabetes‐associated heart failure. Obesity is associated with hypertriglyceridemia and elevated circulating free fatty acids (FFA), result in endothelial dysfunction and heart failure. Recent findings have demonstrated that alterations in cardiac energy metabolism are primarily connected with the development of cardiomyopathy in the diabetic heart.Methods: In the current study, the synergistic effects of FFA flux and nicotine treatment were investigated in‐vitro, using endothelial (MMECs), myoblast (C2C12) and cardio myoblast (H9C2) cell culture models under hyperglycemic conditions.Results: Our data indicate that cells treated with palmitate/nicotine showed increased E2F1 transcription with altered PPAR‐α expression‐a transcription factor involved in lipid metabolism. In addition, combined effects of palmitate/nicotine on Rb‐phosphorylation and activation of cyclin‐dependent kinases (CDKs) and their cyclin partners (A/E/D), the upstream regulators of E2F1‐transcription were also studied. Conclusion: Our data demonstrate that elevated FFA and nicotine change PPAR‐α/CDK/E2F1 gene expression and promote apoptosis and genomic instability thus revealing a potential molecular mechanism in obesity and cigarette smoking‐associated heart failure in diabetic milieu.Grant Funding Source: This project was funded by grant NPRP 9‐413‐3‐104
Singular and combined effects of nebivolol and lifestyle modification on large artery stiffness in hypertensive adults (LB567)
Authors: Werner Tim 
Published: June 2021

Background: We hypothesized that the combination of nebivolol and lifestyle modification would reduce large artery stiffness in middle‐aged and older hypertensive adults more than either intervention alone.Methods: To address this, 45 men and women (age 40‐75 years) with stage I hypertension were randomized to receive either nebivolol (NB; forced titration to 10 mg OD; n = 15; age 57.2 ± 11.4 years; body mass index [BMI] 30.8 ± 5.8 kg/m2), lifestyle modification (LM; 5‐10% weight loss via calorie restriction and physical activity; n = 15; age 52.7 ± 8.5 years; BMI 33.9 ± 7.2 kg/m2) or nebivolol plus lifestyle modification (NBLM; n = 15; age 58.9 ± 9.4 years; BMI 32.5 ± 4.9 kg/m2) for 12 weeks. β‐stiffness index, a blood‐pressure‐independent measure of arterial stiffness, and arterial compliance were measured via high‐resolution ultrasound and tonometry at baseline and after the 12‐week intervention. There was no difference between groups in age, body weight or composition, blood pressure, or in β‐stiffness index or arterial compliance at baseline (all p > 0.05).Results: Following the 12‐week intervention, body weight decreased ~5% (p < 0.05) in the LM and NBLM groups but did not change from baseline in the NB group (p > 0.05). Supine brachial and carotid systolic and diastolic blood pressure declined following treatment in each of the groups (p < 0.05). However, the magnitude of reduction was not different (p < 0.05) between groups. β‐stiffness index declined (‐2.03 ± 0.60, ‐1.87 ± 0.83 and −2.51 ± 0.90 U) and arterial compliance increased similarly (both p > 0.05) in the NB, LM and NBLM groups, respectively.Conclusion: In summary, our findings indicate that the combination of nebivolol and lifestyle modification reduced large artery stiffness to a similar degree as either intervention alone in middle‐aged and older hypertensive adults.Grant Funding Source: Supported by Forest Laboratories, Inc
Comparative effects of cinnamaldehyde and cinnamyl‐containing compounds on the viability of two human melanoma cell lines, SK‐MEL19 and SK‐MEL23 (LB611)
Authors: Muhammad Yosra , Kerr Stephen 
Published: June 2021

Trans‐cinnamaldehyde (CA) is an α,β‐unsaturated carbonyl compound, derived from cinnamon, and contains a “Michael acceptor” functionality capable of alkylating nucleophilic residues. Such Michael acceptors are believed to interact with cellular nucleophiles through a Michael addition reaction, making them potential anticancer alkylating agents. Methyl trans‐cinnamyl ketone (MeK), methyl trans‐cinnamic ester (MeCE), and trans‐cinnamic acid (CAC) are cinnamyl‐containing compounds, and are structurally similar to CA, where they have the α,β‐unsaturated carbonyl moiety. This study investigated the effects of these cinnamyl‐containing compounds, alone and in the presence of 100µM glutathione (GSH) and/or 50µM ethacrynic acid (EA), compared to that of CA on human melanoma cell lines: SK‐MEL23 and SK‐MEL19. The viability of the cells was evaluated by MTS assay following 24h of incubation with the treatments. The results show that CA and MeCK exhibited a concentration‐dependent cytotoxicity, with MeCK being less cytotoxic. In the co‐treatment studies, the presence of GSH with the cinnamyl‐containing compounds did not provide protection to the cells, while co‐treatment of EA with the test compounds enhanced the cytotoxicity on the treated cells as compared to the control. In the combination treatment studies, the viability of the cells did not improve when GSH and EA were combined with the test compounds (triple combination) as compared to the co‐treatment of the test compounds with EA. These results indicate that CA was the most cytotoxic among the test compounds, and CAC caused the least cytotoxicity. The results suggest that both the reactivity of the “Michael acceptor” functionality and the lipophilicity of the cinnamyl‐containing compounds play a role in their cytotoxicity.Grant Funding Source: MCPHS Faculty Development Fund
Physiological aspects of the development of mastication in early childhood (LB63)
Authors: Edelson Lisa , Le Révérend Benjamin , Alder Marc , Loret Chrystel 
Published: June 2021

The development of feeding skills is a complex process influenced by four main factors: (1) Anatomy, (2) Neurophysiology, (3) Environment, (4) Society and culture. Feeding skills are therefore investigated by two fields of science: the behavioral science of feeding and the biomechanics of feeding (e.g. chewing and swallowing), with a particular emphasis on the first approach.Food intended to be fed to infants and toddlers are currently recommended based on motor and eating skills described by Speech Language Pathologists (SLPs) and feeding specialists. The biomechanical characterization of mastication and its development has been less addressed, even though it could bring a new insight in the design of developmentally appropriate food.In this work, we focus on the development of mastication in infants and toddlers. We aim to describe changes in the oral physiology (e.g. bone and muscle structure, teeth and soft tissues) of infants and toddlers, and its relationship to mastication abilities. Finally, we reviewed previous works on the effect of the food consistency on children’s mastication abilities and on their level of texture acceptance.Recommending products that are adapted to children’s mastication during weaning could facilitate their acceptance of new textures and support the development of healthy eating habits.
Interleukin ‐ 17 ‐ mediated immune responses in triptolide ‐ induced liver injury in mice (LB637)
Authors: Wang Xinzhi , Jiang Zhenzhou , Zhang Luyong 
Published: June 2021

The mechanisms of drug ‐ induced liver injury (DILI) have not been fully clariﬁed. Many factors, including oxidative stress and hepatic immune response, can contribute to the pathogenesis of DILI. Interleukin (IL) ‐ 17 secreted by helper T (Th) 17 cells are critical components of immune response in DILI. Triptolide (TP) has been reported to induce hepatocyte damage with inflammatory cells inﬁltration in the liver. To investigate the involvement of IL – 17 ‐ mediated immune response in the TP ‐ induced hepatotoxicity, we examined the plasma transaminase, histopathological changes, hepatic frequencies of Th17 cells, hepatic expression of transcriptional factors and cytokines genes and plasma IL ‐ 17 levels after oral administration of TP (600 μg/kg) to female C57BL/6 mice for 24 h. Mice treated with TP displayed acute liver injury with signiﬁcantly increased hepatic frequencies of Th17 cells, mRNA expression of retinoid ‐ related orphan receptor (ROR) ‐ γt and plasma IL ‐ 17 level as well as the plasma ALT and AST. Neutralization study using anti – IL ‐ 17 antibody ameliorated TP – induced liver injury. In contrast, when challenged by co ‐ administration of recombinant IL ‐ 17, hepatotoxicity was exacerbated in the triptolide ‐ administered mice. In summary, this report was demonstrated for the first time that IL ‐ 17 – mediated immune response is involved in the pathogenesis of TP ‐ induced liver injury in mice.Grant Funding Source: Supported by National Natural Science Foundation of China（No. No.81173651）
In vitro characterization of the immunotoxic potential of pH‐sensitive microspheres on macrophage Raw 264.7 (LB639)
Authors: Youan Bi Botti , Miezan Ezoulin, Miezan , Zhang Tao 
Published: June 2021

The objective of this study is to design pH‐sensitive microspheres (MS) for vagina delivery of microbicides to prevent HIV transmission. The MS were prepared by spray‐drying technique using pH‐sensitive polymethacrylate polymer (S‐100). The MS had a particle size of 76 ̶ 172 nm (in phosphate buffer, pH 7.3) and 6 ̶ 10 µm (in acetate buffer, pH 3.7) along with respective zeta potential in these media of ‐20 and ‐2 mV. It was hypothesized that because of the biocompatibility of the native materials, the MS will be non‐immunotoxic and suitable for the intended application. Methods: cultured murine macrophages RAW 264.7 were exposed for 24h to MS at 1‐1000 μg/mL. Cell membrane integrity, mitochondrial respiration, mitochondrial mass and membrane potential (∆Ψ), reactive oxygen species (ROS), glutathione (GSH) content, and the pro‐inflammatory mediator nitric oxide (NO°) were assessed using standardized in vitro assays. Results: the MS were shown to elicit no cell death at all concentrations tested. The mitochondrial functions were maintained intact except an increase in ∆Ψ (40%) at 1000 μg/mL MS. The MS had no effect on the cellular redox status reflected by the maintenance of ROS and GSH basal levels. Moreover, the MS did not activate the macrophages as evidenced by the basal level of NO°, suggesting an absence of iNOS‐induced inflammation. Conclusions: these findings further support the above working hypothesis, showing the MS as potential nanocarriers for HIV microbicides.Grant Funding Source: RO1A1087304
In vitro avian pro‐epicardial cell spreading challenges the notion of how epicardial cells spread during cardiac morphogenesis (LB65)
Authors: Vilches‐Moure Jose , Erickson Carol 
Published: June 2021

In the developing heart, the epicardium is derived from the pro‐epicardial organ (PEO), which spreads over the cardiac tube (purportedly as an epithelium), and then undergoes what is believed to be an epithelial‐to‐mesenchymal transition (EMT) to generate the subepicardial mesenchyme. We are interested in the process of epicardial cell spreading and the mechanisms that regulate the epicardial EMT. To study these processes, we have developed fluorescent labeling techniques to visualize the PEO and the spreading epicardium using time‐lapse confocal imaging in intact hearts and on a planar substratum. When the PEO is labeled and then explanted before it begins to spread in vivo, we saw that each cell has numerous filopodia and lamellipodia around its borders. Fixed images of spreading PEO cells labeled in ovo confirm the presence of numerous filopodia and lamellipodia in the spreading epicardium in vivo. Although the PEO has been assumed to spread as an epithelium with the force being generated at the free edge, our live‐cell imaging suggests that each cell in the epicardium is generating tractional force. These results show that real‐time behavior studies are critical since morphology alone does not reveal behavior. Our observations challenge the notion of how the PEO‐derived cells spread over the cardiac tube during cardiac morphogenesis.Grant Funding Source: Supported by NIHT32OD011147 (JV‐M), UCD GSSP Fellowship (JV‐M), UCD GGCP Fellowship (JV‐M), IOS1146480 (CAE)
Impaired cardiac parasympathetic control in healthy young people with type 1 diabetes (LB658)
Authors: Wilson Luke , Coffey Sean , Hoye Neil , Murray Angus , Lamberts Regis , Williams Michael , Wilkins Gerard , Baldi J,Chris 
Published: June 2021

Diabetes reduces heart rate (HR) reserve during maximal exercise. We measured HR during a low‐ and high‐dose (0.1 and 0.4 mg·kg‐1) atropine bolus followed by incremental dobutamine infusions (5 ‐ 40 μg·kg‐1·min‐1) up to 85% maximal HR to determine the roles of the parasympathetic and sympathetic nervous system in the diabetic HR response. Five 18 – 30 year old individuals with type 1 diabetes (T1D), but without cardiovascular disease or hypertension and four age‐, sex‐ and training‐matched non‐diabetic subjects (CON) performed a VO2max test (with ECG) on a cycle ergometer. On a second day, parasympathetic control was determined by comparing the change in HR during atropine doses using ANOVA. Sympathetic responsiveness was compared using the slope of the change in HR (after high‐dose atropine) across dobutamine infusion rates. VO2max and maximal HR during the exercise test were the same between groups (P > 0.05). Resting HR was greater in the T1D vs. CON (75 ± 4 vs. 62 ± 6 beats·min‐1; P < 0.05). Heart rate after high‐dose atropine was the same in T1D and CON (111 ± 19 vs. 123 ± 19 beats·min‐1; P > 0.05), but the change in HR after low‐ (18 ± 12 vs. 43 ± 9 beats·min‐1) and high‐dose atropine (40 ± 8 vs. 60 ± 11 beats) was smaller in the T1D vs. CON respectively. The percentage of maximal HR achieved with dobutamine (85 ± 2% vs. 84 ± 2%), dobutamine dose at 85% maximal HR (24 ± 11 vs. 20 ± 12 μg·kg‐1·min‐1) and sympathetic responsiveness (2.6 ± 1.0 vs. 2.6 ± 1.4 beats·μg·kg‐1·min‐1) were not different between T1D and CON respectively (P > 0.05). These data suggest that parasympathetic nervous activity is already impaired in healthy young individuals with type 1 diabetes, but the chronotropic response to sympathetic stimulation is unaffected.Grant Funding Source: Supported by Healthcare Otago Charitable trust
Transvenous vagal nerve stimulation (VNS) in acute myocardial infarction (AMI) markedly reduces the infarction size and improves chronic cardiac function (LB670)
Authors: Arimura Takahiro , Saku Keita , Kakino Takamori , Akashi Takuya , Takehara Takako , Nishizaki Akiko , Oga Yasuhiro , Ikeda Masataka , Fujii Kana , Ide Tomomi , Kishi Takuya , Sunagawa Kenji 
Published: June 2021

Background: Although VNS is known to have a powerful anti‐infarct effect, the technical difficulty associated with VNS precludes its application under emergent settings of AMI. We developed a novel technique where we stimulate the vagal system transvenously and evaluated how the VNS affects the infarction size and cardiac function in the long term.Method: We ligated a left anterior descending coronary artery for 3 hours, then reperfused. For transvenous VNS, we performed the field electrical stimulation by pacing catheter in the superior vena cava. VNS reduced mean heart rate about 20‐30% during I/R. One month after ischemia‐reperfusion, we compared the infarct size, hemodynamics and load insensitive cardiac function, i.e., end‐systolic elastance (Ees) (Millar pressure and sonomicrometric volumetry) with or without VNS treatment.Results: In comparison with no VNS, transvenous VNS significantly decreased the infarction size more than 80% (1.1±1.2 vs. 7.8±1.2cm2, p<0.05), doubled left ventricular Ees (6.5±1.7 vs. 13.2±0.6 mmHg/ml, p<0.05), and decreased NT‐pro BNP (3667±1637 vs. 843±256 pmol/ml, p<0.05).Conclusion: Transvenous VNS in AMI markedly reduces the infarct size and improves cardiac function in the chronic phase (4 weeks after AMI). Transvenous VNS would be a novel therapy of AMI to prevent heart failure in the long term.
Molecular mechanism of lung oedema clearance by AP301: dependence of ENaC pore forming subunits (LB781)
Authors: Shabbir Waheed , Hasanovic Minela , Jenn Soja , Tzotzos Susan , Fischer Bernhard , Pietschmann Helmut , Fischer Hendrik , Lucas Rudolf , Lemmens‐Gruber Rosa 
Published: June 2021

Pulmonary oedema is a life threatening condition, caused by acute lung injury. Although failure of gas exchange in the alveolar spaces causes most of the morbidity and mortality, it remained uncertain how epithelial sodium channel lose their liquid clearance ability. Furthermore, the subunit composition of native ENaC in diseased pulmonary epithelium is still unknown. AP301, a lectin‐like domain derived peptide of TNF‐α, increases amiloride‐sensitive current in A549 cells as well as in heterologously expressed hENaC, an effect which is lost after deglycosylation. Consequently, the present study was undertaken to determine the interaction of AP301 with hENaC glycosylation sites and subunit compositions of hENaC. We substituted asparagine to glutamine in α‐hENaC, and studied the AP301 induced increase in sodium current in different subunit compositions. The effect of AP301 in HEK and CHO cells heterologously expressing human ENaC WT and mutants in addition to different subunit compositions (α, ß, γ and δ) was measured in patch clamp experiments. Indeed, AP301 weakly activated single as well as multiple asparagine mutants of α‐hENaC. For maximal AP301 activity αβγ‐ or δβγ‐hENaC co‐expression was required. Conclusively, αβγδ‐hENaC elicited a robust AP301 response at very low EC50 values. These findings suggest that specific interaction of AP301 ENaC requires precedent binding to glycosylated extracellular loop and pore‐forming α or δ delta subunits.Grant Funding Source: Supported by Austrian Research Promotion Agency (FFG).
Association Between Problem Gambling and Functional Disability: A Nationally Representative Study Conducted in the United Kingdom
Authors: Jacob Louis , López-Sánchez Guillermo F. , Oh Hans , Kostev Karel , Koyanagi Ai , Haro Josep Maria , Pardhan Shahina , Shin Jae Il , Smith Lee 
Published: June 2021

Objectives:
Problem gambling is associated with multiple detrimental health outcomes. However, to date, no study has investigated the association between problem gambling and functional disability. Therefore, the aim of this study was to investigate the association between problem gambling and functional disability in a UK nationally representative sample.

Methods:
Cross-sectional data from the 2007 Adult Psychiatric Morbidity Survey were analyzed. Problem gambling was assessed using a questionnaire including 10 DSM-IV criteria, whereas functional disability referred to at least 1 difficulty in 1 of 7 activities of daily living and instrumental activities of daily living. Control variables included sociodemographic factors, smoking status, alcohol dependence, drug use, the number of chronic physical conditions, depression, and anxiety disorder. The problem gambling-functional disability relationship was studied using a logistic regression model.

Results:
This study included 6941 adults aged ≥16 years (51.2% women; mean [SD] age 46.3 [18.6] years). The prevalence of functional disability was significantly higher in the at-risk problem gambling/problem gambling group than in the no problem gambling group (46.2% vs 32.1%, P value < 0.001). After adjusting for control variables, both at-risk problem gambling (OR = 1.55, 95% CI = 1.03–2.35) and problem gambling (OR = 3.05, 95% CI = 1.09–8.52) were positively and significantly associated with functional disability.

Conclusions:
In this large representative sample of UK adults, problem gambling was associated with higher odds for functional disability. If confirmed with longitudinal studies, these results suggest that those suffering from problem gambling should receive targeted intervention to aid in the prevention of functional disability.
Participant Experiences of a Quit Smoking Attempt Through Either Nicotine Replacement Therapy (NRT) Methods or the Use of an E-cigarette
Authors: Jones Gareth , McIntosh Emma , Brose Leonie S. , Klonizakis Markos 
Published: June 2021

Objectives
There is a lack of evidence exploring experiences of using e-cigarettes for smoking cessation. The study’s main aim was to explore participant experiences of e-cigarettes compared to nicotine replacement therapy (NRT) delivered through stop smoking services.

Methods
Semi-structured, face-to-face, and telephone interviews at 3-month post-quit follow-up in a randomized controlled trial comparing nicotine-containing e-cigarettes, nicotine-free e-cigarettes, and NRT for smoking cessation. N = 17 participants, 9 were male, mean age 44 years, 5 using nicotine-containing e-cigarettes, 7 nicotine-free e-cigarettes, and 5 NRT. Interviews were transcribed and analyzed using thematic analysis.

Results
Two global themes and 5 organizing themes were identified. Global themes included: (1) experiences of e-cigarette and NRT quit aids (e-cigarette positive impact and dilemmas, NRT perceptions and experiences), and (2) key mechanisms to support quit attempt (physical aids, advice and support, feedback and structure). E-cigarettes were viewed with caution, however, generally evaluated positively alongside NRT methods, finding e-cigarettes useful during a quit attempt due to their versatility in application. Nicotinecontaining e-cigarettes were favored due to their support with nicotine cravings. Participants were, however, wary of replacing smoking addiction with vaping habit.

Conclusions
Participant e-cigarette experience were generally positive; however, concerns over long-term application were noted. There was a noticeable preference for nicotine-containing e-cigarettes, but further research is required to better understand how nicotine is used in conjunction with e-cigarettes long-term as a quit aid alongside other NRT.