bluuebunny/crossref_metadata_2025 huggingface dataset:
ENAM Gene Variation in Students Exposed to Different Fluoride Concentrations
Authors: Duran-Merino Denisse , Molina-Frechero Nelly , Sánchez-Pérez Leonor , Nevárez-Rascón Martina , González-González Rogelio , Tremillo-Maldonado Omar , Cassi Diana , Bologna-Molina Ronell
Published: March 2020

The ENAM gene is important in the formation of tooth enamel; an alteration can affect the lengthening of the crystals, and the thickness in enamel. The objective was to determine the presence of the single nucleotide variant (SNV) rs12640848 of the ENAM gene in students exposed to different concentrations of fluoride. Methods: A cross-sectional study was conducted on students exposed to high concentrations of fluoride in the city of Durango which were divided according to the severity of fluorosis and dental caries. Genotype determination was performed by DNA sequencing. The relationship between the severity of dental fluorosis and the allele distribution was determined by the Fisher’s exact and Kruskal–Wallis tests. Results: Seventy-one students were included for the sequencing. In the different allelic variations, for the normal genotype AA/TT, the control group presented 75%, for the AG/TC variation, 70.8% in the TF ≤ 4 group, 65% in TF ≥ 5, and 16.7% in TF = 0; with respect to GG/CC variation, 12.5% in TF ≤ 4, 22% in TF ≥ 5, and 8.3% in TF = 0 group (p = 0.000). Conclusion: The ENAM gene showed an association in the population exposed to different concentrations of fluoride.
Age Differences in Occupant Motion during Simulated In-Vehicle Swerving Maneuvers
Authors: Graci Valentina , Douglas Ethan , Seacrist Thomas , Kerrigan Jason , Mansfield Julie , Bolte John , Sherony Rini , Hallman Jason , Arbogast Kristy
Published: March 2020

Background: With active safety and automated vehicle features becoming more available, unanticipated pre-crash vehicle maneuvers, such as evasive swerving, may become more common, and they may influence the resulting effectiveness of occupant restraints, and consequently may affect injury risks associated with crashes. Therefore, the objective of this study was to quantify the influence of age on key occupant kinematic, kinetic, and muscular responses during evasive swerving in on-road testing. Methods: Seat belt-restrained children (10–12 years old), teens (13–17 years old), and adults (21–33 years old) experienced two evasive swerving maneuvers in a recent model sedan on a test track. Kinematics, muscle activity, and seat belt load distribution were determined and analyzed. Results: Compared to teens and adults, children showed greater head and trunk motion (p < 0.03), but similar muscle activation in the into-the-belt direction of swerving. In the out–of-the-belt direction, children showed head and trunk motion more similar to teens and adults (p < 0.02), but with greater muscle activation. Conclusions: Children showed different neuromuscular control of head and trunk motion compared to older occupants. This study highlights differences in the relationship between kinematics and muscle activation across age groups, and provides new validation data for active human body models across the age range.
Use of Tracer Elements for Estimating Community Exposure to Marcellus Shale Development Operations
Authors: Nye Maya , Knuckles Travis , Yan Beizhan , Ross James , Orem William , Varonka Matthew , Thurston George , Dzomba Alexandria , McCawley Michael
Published: March 2020

Since 2009, unconventional natural gas development (UNGD) has significantly increased in Appalachia’s Marcellus Shale formation. Elevations of fine particulate matter <2.5 µm (PM2.5), have been documented in areas surrounding drilling operations during well stimulation. Furthermore, many communities are experiencing increased industrial activities and probable UNGD air pollutant exposures. Recent studies have associated UNGD emissions with health effects based on distances from well pads. In this study, PM2.5 filter samples were collected on an active gas well pad in Morgantown, West Virginia, and three locations downwind during hydraulic stimulation. Fine particulate samples were analyzed for major and trace elements. An experimental source identification model was developed to determine which elements appeared to be traceable downwind of the UNGD site and whether these elements corresponded to PM2.5 measurements. Results suggest that 1) magnesium may be useful for detecting the reach of UNGD point source emissions, 2) complex surface topographic and meteorological conditions in the Marcellus Shale region could be modeled and confounding sources discounted, and 3) well pad emissions may be measurable at distances of at least 7 km. If shown to be more widely applicable, future tracer studies could enhance epidemiological studies showing health effects of UNGD-associated emissions at ≥15 km.
Smoking Prevalence and Secondhand Smoke Exposure during Pregnancy and Postpartum—Establishing Risks to Health and Human Rights before Developing a Tailored Programme for Smoking Cessation
Authors: Frazer Kate , Fitzpatrick Patricia , Brosnan Mary , Dromey Anne Marie , Kelly Sarah , Murphy Michael , O’Brien Denise , Kelleher Cecily C. , McAuliffe Fionnuala M.
Published: March 2020

Both smoking during pregnancy and secondhand smoke exposure are associated with reduced health outcomes. However, limited consistent evidence exists of risks of secondhand smoke exposure in pregnancy. Currently, inadequate smoking cessation services exist in Irish maternity hospitals. To identify the number of pregnant women smoking during pregnancy and to identify their exposure to secondhand smoke, we conducted a cross-sectional observational pilot study in one regional maternity hospital in Ireland in July/August 2018. Respondents were (1) women attending antenatal clinics and (2) postpartum women before discharge. Variables measured included smoking status of pregnant women and partner status, demographic variables, secondhand smoke exposure, and support for hospital smoke-free policy and development of smoking cessation services. The overall response rate was 42.2% in this study. The response rate was 56.5% (111/196) from postnatal wards and 37.3% (215/577) from antenatal clinics. Over 40% of respondents reported they had smoked during their lifetime. The majority of women (70%) reported quitting smoking before their pregnancy. Few women were active smokers. Almost 40% reported exposure to tobacco smoke in the previous week (38.5%); 16.9% reported living with a smoker, a critical factor in increased risk (Odds Ratio (OR) 3.89, 95% CI = 1.86–8.15, p < 0.001). Approximately 10% of postnatal mothers reported that their newborn would travel home with a smoker. Support for a no-smoking hospital policy was very high as was support for the development of cessation services. No documentation of secondhand smoke exposure for pregnant women or newborns is sought or recorded routinely in the hospital. A systems approach to develop smoking cessation programmes in maternity care should include screening and documenting of secondhand smoke exposure risks for women during pregnancy, and for their newborns at discharge, to improve health outcomes and protect human rights.
Courses on Basic Occupational Safety and Health: A Train-the-Trainer Educational Program for Rural Areas of Latin America
Authors: Garrido Marie Astrid , Encina Verónica , Solis-Soto María Teresa , Parra Manuel , Bauleo María Fernanda , Meneses Claudia , Radon Katja
Published: March 2020

Integrating basic occupational health services into primary care is encouraged by the Pan American Health Organization. However, concrete initiatives are still scarce. We aimed to develop a training program focusing on prevention of occupational risks for primary healthcare professionals. This train-the-trainer program was piloted at four universities in Chile and Peru. Occupational health or primary healthcare lecturers formed a team with representative(s) of one rural primary healthcare center connected to their university (Nparticipants = 15). Training started with a workshop on participatory diagnosis of working conditions. Once teams had conducted the participatory diagnosis in the rural communities, they designed in a second course an active teaching intervention. The intervention was targeted at the main occupational health problem of the community. After implementation of the intervention, teams evaluated the program. Evaluation results were very positive with an overall score of 9.7 out of 10. Teams reported that the methodology enabled them to visualize hazardous working conditions. They also stated that the training improved their abilities for problem analysis and preventive actions. Aspects like time constraints and difficult geographical access were mentioned as challenges. In summary, addressing occupational health in primary care through targeted training modules is feasible, but long-term health outcomes need to be evaluated.
Agility Training to Integratively Promote Neuromuscular, Cognitive, Cardiovascular and Psychosocial Function in Healthy Older Adults: A Study Protocol of a One-Year Randomized-Controlled Trial
Authors: Morat Mareike , Faude Oliver , Hanssen Henner , Ludyga Sebastian , Zacher Jonas , Eibl Angi , Albracht Kirsten , Donath Lars
Published: March 2020

Exercise training effectively mitigates aging-induced health and fitness impairments. Traditional training recommendations for the elderly focus separately on relevant physiological fitness domains, such as balance, flexibility, strength and endurance. Thus, a more holistic and functional training framework is needed. The proposed agility training concept integratively tackles spatial orientation, stop and go, balance and strength. The presented protocol aims at introducing a two-armed, one-year randomized controlled trial, evaluating the effects of this concept on neuromuscular, cardiovascular, cognitive and psychosocial health outcomes in healthy older adults. Eighty-five participants were enrolled in this ongoing trial. Seventy-nine participants completed baseline testing and were block-randomized to the agility training group or the inactive control group. All participants undergo pre- and post-testing with interim assessment after six months. The intervention group currently receives supervised, group-based agility training twice a week over one year, with progressively demanding perceptual, cognitive and physical exercises. Knee extension strength, reactive balance, dual task gait speed and the Agility Challenge for the Elderly (ACE) serve as primary endpoints and neuromuscular, cognitive, cardiovascular, and psychosocial meassures serve as surrogate secondary outcomes. Our protocol promotes a comprehensive exercise training concept for older adults, that might facilitate stakeholders in health and exercise to stimulate relevant health outcomes without relying on excessively time-consuming physical activity recommendations.
A Topology Preserving Gridding Method for Vector Features in Discrete Global Grid Systems
Authors: Zhou Liangchen , Lian Wenjie , Zhang Yudi , Lin Bingxian
Published: March 2020

Topological distortion seriously affects spatial cognition. To solve this problem caused by the integration of vector features in discrete global grid systems (DGGs), a topology-preserving gridding method for vector features is proposed. The method proposed determines the topological distortion according to the relationship between grid cells and then increases the local resolution of vector features by employing the multi-level resolution characteristic of DGGs, to repair three kinds of topological distortions. Experimental results show that the proposed method can effectively maintain the topological relationship between the original vector features, and the amount of data is stable, thus ensuring the correct integration of vector features in the DGGs.
Antifungal Activity of Anionic Defense Peptides: Insight into the Action of Galleria mellonella Anionic Peptide 2
Authors: Sowa-Jasiłek Aneta , Zdybicka-Barabas Agnieszka , Stączek Sylwia , Pawlikowska-Pawlęga Bożena , Grygorczuk-Płaneta Katarzyna , Skrzypiec Krzysztof , Gruszecki Wiesław I. , Mak Paweł , Cytryńska Małgorzata
Published: March 2020

Anionic antimicrobial peptides constitute an integral component of animal innate immunity, however the mechanisms of their antifungal activity are still poorly understood. The action of a unique Galleria mellonella anionic peptide 2 (AP2) against fungal pathogen Candida albicans was examined using different microscopic techniques and Fourier transform infrared (FTIR) spectroscopy. Although the exposure to AP2 decreased the survival rate of C. albicans cells, the viability of protoplasts was not affected, suggesting an important role of the fungal cell wall in the peptide action. Atomic force microscopy showed that the AP2-treated cells became decorated with numerous small clods and exhibited increased adhesion forces. Intensified lomasome formation, vacuolization, and partial distortion of the cell wall was also observed. FTIR spectroscopy suggested AP2 interactions with the cell surface proteins, leading to destabilization of protein secondary structures. Regardless of the anionic character of the whole AP2 molecule, bioinformatics analyses revealed the presence of amphipathic α-helices with exposed positively charged lysine residues. High content of the α-helical structure was confirmed after deconvolution of the IR absorption spectrum and during circular dichroism measurements. Our results indicated that the antimicrobial properties of G. mellonella AP2 rely on the same general characteristics found in cationic defense peptides.
Reactive Oxygen Species in Venous Thrombosis
Authors: Gutmann Clemens , Siow Richard , Gwozdz Adam M. , Saha Prakash , Smith Alberto
Published: March 2020

Reactive oxygen species (ROS) have physiological roles as second messengers, but can also exert detrimental modifications on DNA, proteins and lipids if resulting from enhanced generation or reduced antioxidant defense (oxidative stress). Venous thrombus (DVT) formation and resolution are influenced by ROS through modulation of the coagulation, fibrinolysis, proteolysis and the complement system, as well as the regulation of effector cells such as platelets, endothelial cells, erythrocytes, neutrophils, mast cells, monocytes and fibroblasts. Many conditions that carry an elevated risk of venous thrombosis, such as the Antiphospholipid Syndrome, have alterations in their redox homeostasis. Dietary and pharmacological antioxidants can modulate several important processes involved in DVT formation, but their overall effect is unknown and there are no recommendations regarding their use. The development of novel antioxidant treatments that aim to abrogate the formation of DVT or promote its resolution will depend on the identification of targets that enable ROS modulation confined to their site of interest in order to prevent off-target effects on physiological redox mechanisms. Subgroups of patients with increased systemic oxidative stress might benefit from unspecific antioxidant treatment, but more clinical studies are needed to bring clarity to this issue.
Fibroblast Interaction with Different Abutment Surfaces: In Vitro Study
Authors: Canullo Luigi , Genova Tullio , Gross Trujillo Esperanza , Pradies Guillermo , Petrillo Sara , Muzzi Maurizio , Carossa Stefano , Mussano Federico
Published: March 2020

Background: Attaining an effective mucosal attachment to the transmucosal part of the implant could protect the peri-implant bone. Aim: To evaluate if chair side surface treatments (plasma of Argon and ultraviolet light) may affect fibroblast adhesion on different titanium surfaces designed for soft tissue healing. Methods: Grade 5 titanium discs with four different surface topographies were subdivided into 3 groups: argon-plasma; ultraviolet light, and no treatment. Cell morphology and adhesion tests were performed at 20 min, 24 h, and 72 h. Results: Qualitative observation of the surfaces performed at the SEM was in accordance with the anticipated features. Roughness values ranged from smooth (MAC Sa = 0.2) to very rough (XA Sa = 21). At 20 min, all the untreated surfaces presented hemispherical cells with reduced filopodia, while the cells on treated samples were more spread with broad lamellipodia. However, these differences in spreading behavior disappeared at 24 h and 72 h. Argon-plasma, but not UV, significantly increased the number of fibroblasts independently of the surface type but only at 20 min. Statistically, there was no surface in combination with a treatment that favored a greater cellular adhesion. Conclusions: Data showed potential biological benefits of treating implant abutment surfaces with the plasma of argon in relation to early-stage cell adhesion.
Design, Synthesis, and Renal Targeting of Methylprednisolone-Lysozyme
Authors: Pan Xingquan , Xie Fei , Xiao Dian , Zhou Xinbo , Xiao Junhai
Published: March 2020

Methylprednisolone (MP) is often used in the treatment of various kidney diseases, but overcoming the systemic side effects caused by its nonspecific distribution in the body is a challenge. This article reports the design, synthesis, and renal targeting of methylprednisolone–lysozyme (MPS–LZM). This conjugate was obtained by covalently linking MP with the renal targeting carrier LZM through a linker containing an ester bond, which could utilize the renal targeting of LZM to deliver MP to renal proximal tubular epithelial cells and effectively release MP. The reaction conditions for the preparation of the conjugate were mild, and the quality was controllable. The number of drug payloads per LZM was 1.1. Cell-level studies have demonstrated the safety and endocytosis of the conjugate. Further pharmacokinetic experiments confirmed that, compared with that of free MP, the conjugate increased the renal exposure (AUC0–t) of active MP from 17.59 to 242.18 h*ng/mL, and the targeting efficiency improved by approximately 14 times. Tissue and organ imaging further revealed that the conjugate could reach the kidneys quickly, and fluorescence could be detected in the kidneys for up to 12 h. This study preliminarily validates the feasibility of a renal targeting design strategy for MPS–LZM, which is expected to provide a new option for improving kidney-specific distribution of glucocorticoids.
New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells
Authors: Ciaffaglione Valeria , Intagliata Sebastiano , Pittalà Valeria , Marrazzo Agostino , Sorrenti Valeria , Vanella Luca , Rescifina Antonio , Floresta Giuseppe , Sultan Ameera , Greish Khaled , Salerno Loredana
Published: March 2020

In this paper, a novel series of imidazole-based heme oxygenase-1 (HO-1) inhibitors is reported. These compounds were obtained by modifications of previously described high potent and selective arylethanolimidazoles. In particular, simplification of the central linker and repositioning of the hydrophobic portion were carried out. Results indicate that a hydroxyl group in the central region is crucial for the potency as well as the spatial distribution of the hydrophobic portion. Docking studies revealed a similar interaction of the classical HO-1 inhibitors with the active site of the protein. The most potent and selective compound (5a) was tested for its potential cytotoxic activity against hormone-sensitive and hormone-resistant breast cancer cell lines (MCF-7 and MDA-MB-231).
Endocrine Disruptors in Water and Their Effects on the Reproductive System
Authors: Gonsioroski Andressa , Mourikes Vasiliki E. , Flaws Jodi A.
Published: March 2020

Anthropogenic contaminants in water can impose risks to reproductive health. Most of these compounds are known to be endocrine disrupting chemicals (EDCs). EDCs can impact the endocrine system and subsequently impair the development and fertility of non-human animals and humans. The source of chemical contamination in water is diverse, originating from byproducts formed during water disinfection processes, release from industry and livestock activity, or therapeutic drugs released into sewage. This review discusses the occurrence of EDCs in water such as disinfection byproducts, fluorinated compounds, bisphenol A, phthalates, pesticides, and estrogens, and it outlines their adverse reproductive effects in non-human animals and humans.
In Vitro Biophysical and Biological Characterization of Lipid Nanoparticles Co-Encapsulating Oncosuppressors miR-199b-5p and miR-204-5p as Potentiators of Target Therapy in Metastatic Melanoma
Authors: Fattore Luigi , Campani Virginia , Ruggiero Ciro Francesco , Salvati Valentina , Liguoro Domenico , Scotti Lorena , Botti Gerardo , Ascierto Paolo Antonio , Mancini Rita , De Rosa Giuseppe , Ciliberto Gennaro
Published: March 2020

Uncontrolled MAPK signaling is the main oncogenic driver in metastatic melanomas bearing mutations in BRAF kinase. These tumors are currently treated with the combination of BRAF/MEK inhibitors (MAPKi), but this therapy is plagued by drug resistance. In this context we recently discovered that several microRNAs are involved in the development of drug resistance. In particular miR-204-5p and miR-199b-5p were found to function as antagonists of resistance because their enforced overexpression is able to inhibit melanoma cell growth in vitro either alone or in combination with MAPKi. However, the use of miRNAs in therapy is hampered by their rapid degradation in serum and biological fluids, as well as by the poor intracellular uptake. Here, we developed lipid nanoparticles (LNPs) encapsulating miR-204-5p, miR-199b-5p individually or in combination. We obtained LNPs with mean diameters < 200 nm and high miRNA encapsulation efficiency. These formulations were tested in vitro on several melanoma cell lines sensitive to MAPKi or rendered drug resistant. Our results show that LNPs encapsulating combinations of the two oncosuppressor miRNAs are highly efficient in impairing melanoma cell proliferation and viability, affect key signaling pathways involved in melanoma cell survival, and potentiate the efficacy of drugs inhibiting BRAF and MEK. These results warrant further assessment of the anti-tumor efficacy of oncosuppressor miRNAs encapsulating LNPs in in vivo tumor models.
Molecular Characterization of PGC-1β (PPAR Gamma Coactivator 1β) and its Roles in Mitochondrial Biogenesis in Blunt Snout Bream (Megalobrama amblycephala)
Authors: Lu Kangle , Policar Tomas , Song Xiaojun , Rahimnejad Samad
Published: March 2020

This study aimed at achieving the molecular characterization of peroxisome proliferator-activated receptor-gamma coactivator 1β (PGC-1β) and exploring its modulatory roles in mitochondria biogenesis in blunt snout bream (Megalobrama amblycephala). A full-length cDNA of PGC-1β was cloned from liver which covered 3110 bp encoding 859 amino acids. The conserved motifs of PGC-1β family proteins were gained by MEME software, and the phylogenetic analyses showed motif loss and rearrangement of PGC-1β in fish. The function of PGC-1β was evaluated through overexpression and knockdown of PGC-1β in primary hepatocytes of blunt snout bream. We observed overexpression of PGC-1β along with enhanced mitochondrial transcription factor A (TFAM) expression and mtDNA copies in hepatocytes, and its knockdown led to slightly reduced NRF1 expression. However, knockdown of PGC-1β did not significantly influence TFAM expression or mtDNA copies. The alterations in mitochondria biogenesis were assessed following high-fat intake, and the results showed that it induces downregulation of PGC-1β. Furthermore, significant decreases in mitochondrial respiratory chain activities and mitochondria biogenesis were observed by high-fat intake. Our findings demonstrated that overexpression of PGC-1β induces the enhancement of TFAM expression and mtDNA amount but not NRF-1. Therefore, it could be concluded that PGC-1β is involved in mitochondrial biogenesis in blunt snout bream but not through PGC-1β/NRF-1 pathway.
Nutraceutical Boom in Cancer: Inside the Labyrinth of Reactive Oxygen Species
Authors: Calvani Maura , Pasha Amada , Favre Claudio
Published: March 2020

In recent years, epidemiological studies have shown that food is a very powerful means for maintaining a state of well-being and for health prevention. Many degenerative, autoimmune and neoplastic diseases are related to nutrition and the nutrient–organism interaction could define the balance between health and disease. Nutrients and dietary components influence epigenetic phenomena and modify drugs response; therefore, these food–host interactions can influence the individual predisposition to disease and its potential therapeutic response. Do nutraceuticals have positive or negative effects during chemotherapy? The use of nutraceutical supplements in cancer patients is a controversial debate without a definitive conclusion to date. During cancer treatment, patients take nutraceuticals to alleviate drug toxicity and improve long-term results. Some nutraceuticals may potentiate the effect of cytotoxic chemotherapy by inducing cell growth arrest, cell differentiation, and alteration of the redox state of cells, but in some cases, high levels of them may interfere with the effectiveness of chemotherapy, making cancer cells less reactive to chemotherapy. In this review, we highlighted the emerging opinions and data on the pros and cons on the use of nutraceutical supplements during chemotherapy.
Dopaminergic Modulation of Orofacial Mechanical Hypersensitivity Induced by Infraorbital Nerve Injury
Authors: Maegawa Hiroharu , Usami Nayuka , Kudo Chiho , Hanamoto Hiroshi , Niwa Hitoshi
Published: March 2020

While the descending dopaminergic control system is not fully understood, it is reported that the hypothalamic A11 nucleus is its principle source. To better understand the impact of this system, particularly the A11 nucleus, on neuropathic pain, we created a chronic constriction injury model of the infraorbital nerve (ION-CCI) in rats. ION-CCI rats received intraperitoneal administrations of quinpirole (a dopamine D2 receptor agonist). ION-CCI rats received microinjections of quinpirole, muscimol [a gamma-aminobutyric acid type A (GABAA) receptor agonist], or neurotoxin 6-hydroxydopamine (6-OHDA) into the A11 nucleus. A von Frey filament was used as a mechanical stimulus on the maxillary whisker pad skin; behavioral and immunohistochemical responses to the stimulation were assessed. After intraperitoneal administration of quinpirole and microinjection of quinpirole or muscimol, ION-CCI rats showed an increase in head-withdrawal thresholds and a decrease in the number of phosphorylated extracellular signal-regulated kinase (pERK) immunoreactive (pERK-IR) cells in the superficial layers of the trigeminal spinal subnucleus caudalis (Vc). Following 6-OHDA microinjection, ION-CCI rats showed a decrease in head-withdrawal thresholds and an increase in the number of pERK-IR cells in the Vc. Our findings suggest the descending dopaminergic control system is involved in the modulation of trigeminal neuropathic pain.
Disruption of Exocytosis in Sympathoadrenal Chromaffin Cells from Mouse Models of Neurodegenerative Diseases
Authors: de Diego Antonio M. G. , Ortega-Cruz Diana , García Antonio G.
Published: March 2020

Synaptic disruption and altered neurotransmitter release occurs in the brains of patients and in murine models of neurodegenerative diseases (NDDs). During the last few years, evidence has accumulated suggesting that the sympathoadrenal axis is also affected as disease progresses. Here, we review a few studies done in adrenal medullary chromaffin cells (CCs), that are considered as the amplifying arm of the sympathetic nervous system; the sudden fast exocytotic release of their catecholamines—stored in noradrenergic and adrenergic cells—plays a fundamental role in the stress fight-or-flight response. Bulk exocytosis and the fine kinetics of single-vesicle exocytotic events have been studied in mouse models carrying a mutation linked to NDDs. For instance, in R6/1 mouse models of Huntington’s disease (HD), mutated huntingtin is overexpressed in CCs; this causes decreased quantal secretion, smaller quantal size and faster kinetics of the exocytotic fusion pore, pore expansion, and closure. This was accompanied by decreased sodium current, decreased acetylcholine-evoked action potentials, and attenuated [Ca2+]c transients with faster Ca2+ clearance. In the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS), CCs exhibited secretory single-vesicle spikes with a slower release rate but higher exocytosis. Finally, in the APP/PS1 mouse model of Alzheimer’s disease (AD), the stabilization, expansion, and closure of the fusion pore was faster, but the secretion was attenuated. Additionally, α-synuclein that is associated with Parkinson’s disease (PD) decreases exocytosis and promotes fusion pore dilation in adrenal CCs. Furthermore, Huntington-associated protein 1 (HAP1) interacts with the huntingtin that, when mutated, causes Huntington’s disease (HD); HAP1 reduces full fusion exocytosis by affecting vesicle docking and controlling fusion pore stabilization. The alterations described here are consistent with the hypothesis that central alterations undergone in various NDDs are also manifested at the peripheral sympathoadrenal axis to impair the stress fight-or-flight response in patients suffering from those diseases. Such alterations may occur: (i) primarily by the expression of mutated disease proteins in CCs; (ii) secondarily to stress adaptation imposed by disease progression and the limitations of patient autonomy.
Excess Accumulation of Lipid Impairs Insulin Sensitivity in Skeletal Muscle
Authors: Park Sung Sup , Seo Young-Kyo
Published: March 2020

Both glucose and free fatty acids (FFAs) are used as fuel sources for energy production in a living organism. Compelling evidence supports a role for excess fatty acids synthesized in intramuscular space or dietary intermediates in the regulation of skeletal muscle function. Excess FFA and lipid droplets leads to intramuscular accumulation of lipid intermediates. The resulting downregulation of the insulin signaling cascade prevents the translocation of glucose transporter to the plasma membrane and glucose uptake into skeletal muscle, leading to metabolic disorders such as type 2 diabetes. The mechanisms underlining metabolic dysfunction in skeletal muscle include accumulation of intracellular lipid derivatives from elevated plasma FFAs. This paper provides a review of the molecular mechanisms underlying insulin-related signaling pathways after excess accumulation of lipids.
Inconclusive Diagnosis after Newborn Screening for Cystic Fibrosis
Authors: Munck Anne
Published: March 2020

An unintended consequence of newborn screening for cystic fibrosis (CF) is the identification of infants with a positive screening test but an inconclusive diagnostic testing. These infants are designated as CF transmembrane conductance regulator-related metabolic syndrome (CRMS) in the US and CF screen-positive, inconclusive diagnosis (CFSPID) in Europe. Recently, experts agreed on a unified international definition of CRMS/CFSPID which will improve our knowledge on the epidemiology and outcomes of these infants and optimize comparisons between cohorts. Many of these children will remain free of symptoms, but a number may develop clinical features suggestive of CFTR-related disorder (CFTR-RD) or CF later in life. Clinicians should to be prepared to identify these infants and communicate with parents about this challenging and stressful situation for both healthcare professionals and families. In this review, we present the recent publications on infants designated as CRMS/CFSPID, including the definition, the incidence across Europe, the assessment of the CFTR protein function, the outcomes with the rates of conversion to a final diagnosis of CF and their management.
Detecting Embankment Instability Using Measurable Track Geometry Data
Authors: Kite David , Siino Giulia , Audley Matthew
Published: March 2020

The British railway system is the oldest in the world. Most railway embankments are aged around 150 years old and the percentage of disruption reports that feature them is frequently higher than other types of railway infrastructure. Remarkable works have been done to understand embankment deterioration and develop asset modelling. Nevertheless, they do not represent a sufficient way of managing assets in detail. As a result, reactive approaches combined with proactive ones would improve the whole asset management scenario. To guarantee good system performance, geotechnical asset management (GAM) aims to reduce uncertainty through informed, data driven decisions and optimisation of resources. GAM approaches are cost sensitive. Thus, data driven approaches that utilize existing resources are highly prized. Track geometry data has been routinely collected by Network Rail, over many years, to identify track defects and subsequently plan track maintenance interventions. Additionally, in 2018 Network Rail commissioned AECOM to undertake a study, described in this paper, to investigate the use of track geometry data in the detection of embankment instabilities. In this study, track geometry data for over 1800 embankments were processed and parameters offering the best correlation with embankment movements were identified and used by an algorithm to generate an embankment instability metric. The study successfully demonstrated that the instability of railway embankments is clearly visible in track geometry data and the metric gives an indication of the worsening of track geometry, that is likely due to embankment instability.
High Levels of Kinesiophobia at Discharge from the Hospital May Negatively Affect the Short-Term Functional Outcome of Patients Who Have Undergone Knee Replacement Surgery
Authors: De Vroey Henri , Claeys Kurt , Shariatmadar Keivan , Weygers Ive , Vereecke Evie , Van Damme Geert , Hallez Hans , Staes Filip
Published: March 2020

Background: Kinesiophobia is a psycho-cognitive factor that hampers recovery after orthopedic surgery. No evidence exists on the influence of kinesiophobia on the short-term recovery of function in patients with knee replacement (KR). Therefore, the aim of the present study is to investigate the impact of kinesiophobia on short-term patient-reported outcomes (PROMs) and performance-based measures (PBMs). Methods: Forty-three KR patients filled in the Tampa scale for kinesiophobia (TSK) at time of discharge. Patients with TSK ≥ 37 were allocated to the kinesiophobia group (n = 24), others to the no-kinesiophobia group (n = 19). Patients were asked to complete PROMs and to execute PBMs at discharge and at 6-weeks follow-up. An independent samples t-test was used to compare group differences for PROMs and PBMs at both measurement sessions. Multiple linear regression analysis models were used to model PBM outcomes from age, pain and TSK scores. Results: Significant differences were observed between groups for PROMs and PBMs. Kinesiophobia significantly contributed to the reduced functional outcomes. Conclusion: At discharge from the hospital, 55.8% of KR patients demonstrated high levels of kinesiophobia (TSK ≥ 37). This may negatively influence short-term recovery of these patients, by putting them at higher risk for falling and reduced functionality.
Cerebral and Splanchnic Vein Thrombosis: Advances, Challenges, and Unanswered Questions
Authors: Riva Nicoletta , Ageno Walter
Published: March 2020

Cerebral vein thrombosis (CVT) and splanchnic vein thrombosis (SVT) are two manifestations of venous thromboembolism (VTE) at unusual sites. They have an incidence at least 25–50 times lower than usual site VTE, but represent true clinical challenges. Recent evidence on the epidemiology, risk factors, prognosis, and treatment of CVT and SVT has been published in the last two decades, thus contributing to a better understanding of these diseases. The improvement in imaging techniques and a higher degree of clinical suspicion may have led to the observed increased frequency, whereas a better knowledge of provoking mechanisms could have contributed to reducing the proportion of events classified as unprovoked or idiopathic (13–21% of CVT, 15–27% of SVT). Few small randomized clinical trials and a number of observational studies, although hampered by heterogeneous therapeutic approaches, shed light on the safety and effectiveness of anticoagulant therapy in these populations. However, there are still some grey areas that warrant future research. In this narrative review, we discuss recent advances and therapeutic challenges in CVT and SVT.
Enhanced Inflammation and Nitrosative Stress in the Saliva and Plasma of Patients with Plaque Psoriasis
Authors: Skutnik-Radziszewska Anna , Maciejczyk Mateusz , Flisiak Iwona , Krahel Julita , Kołodziej Urszula , Kotowska-Rodziewicz Anna , Klimiuk Anna , Zalewska Anna
Published: March 2020

Psoriasis is the most common inflammatory skin disease, characterized by the release of proinflammatory cytokines from lymphocytes, keratinocytes, and dendritic cells. Although psoriasis is considered an immune-mediated inflammatory disease, its effect on secretory activity of salivary glands and quantitative composition of saliva is still unknown. The aim of this study was to evaluate the secretion of saliva as well as several selected inflammation and nitrosative stress biomarkers in unstimulated and stimulated saliva as well as plasma of psoriasis patients. We demonstrated that, with progressing severity and duration of the disease, the secretory function of the parotid and submandibular salivary glands is lost, which is manifested as decreased unstimulated and stimulated saliva secretion and reduced salivary amylase activity and total protein concentration. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and interferon-gamma (INF-γ) were significantly higher, whereas interleukin-10 (IL-10) content was considerably lower in unstimulated and stimulated saliva of patients with psoriasis compared to the controls, and the changes increased with the disease duration. Similarly, we observed that the intensity of nitrosative stress in the salivary glands of psoriasis patients depended on the duration of the disease. By means of receiver operating characteristic (ROC) analysis, we showed that the evaluation of nitric oxide (NO), nitrotyrosine, and IL-2 concentration in non-stimulated saliva with high sensitivity and specificity differentiated psoriasis patients on the basis of the rate of saliva secretion (normal salivation vs. hyposalivation). In summary, the dysfunction of salivary glands in psoriasis patients is caused by inflammation and nitrosative stress.
An Overview on Primary Sclerosing Cholangitis
Authors: Vlăduţ Cătălina , Ciocîrlan Mihai , Bilous Dana , Șandru Vasile , Stan-Ilie Mădălina , Panic Nikola , Becheanu Gabriel , Jinga Mariana , Costache Raluca S. , Costache Daniel O. , Diculescu Mircea
Published: March 2020

Primary sclerosing cholangitis is a progressive liver disease characterized by chronic inflammation leading to liver fibrosis and cirrhosis. Even though the exact pathogenesis is still unclear, a combination of autoimmune, environmental, and ischemic factors could explain certain aspects of the disease. The most important diagnostic step is cholangiography, which can be obtained either by endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiography (MRCP as the gold standard), or percutaneous transhepatic cholangiography. It shows multifocal short biliary duct strictures leading to the “beaded” aspect. Cholangiocarcinoma and colorectal adenocarcinoma are the most feared complications in patients with Primary sclerosing cholangitis (PSC). Continuous screening consists of annual clinical, biochemical, and ultrasound assessments in asymptomatic patients and annual colonoscopy in patients with PSC and inflammatory bowel disease. In newly diagnosed patients with PSC, colonoscopy is mandatory and, if negative, then, a repeat colonoscopy should be performed in 3–5 years. The lack of efficient curative medical treatment makes invasive treatments such as liver transplant and endoscopy the mainstream for managing PSC and its complications. Until now, even though only ursodeoxycholic acid has shown a moderate clinical, biochemical, and even histological improvement, it has no significant influence on the risk of cholangiocarcinoma, liver transplant need, or death risk and it is no longer recommended in treating early PSC. Further studies are in progress to establish the effect of molecular-targeted therapies in PSC.
Salivary Oxidative Stress Increases with the Progression of Chronic Heart Failure
Authors: Klimiuk Anna , Zalewska Anna , Sawicki Robert , Knapp Małgorzata , Maciejczyk Mateusz
Published: March 2020

The aim of the study was to evaluate the rate of reactive oxygen species (ROS) production, antioxidant barrier, and oxidative damage in non-stimulated (NWS) and stimulated (SWS) saliva as well as plasma/erythrocytes of 50 patients with chronic heart failure (HF) divided into the two subgroups: NYHA II (33 patients) and NYHA III (17 patients). The activity of superoxide dismutase and catalase was statistically increased in NWS of HF patients as compared to healthy controls. The free radical formation, total oxidant status, level of uric acid, advanced glycation end products (AGE), advanced oxidation protein products and malondialdehyde was significantly elevated in NWS, SWS, and plasma of NYHA III patients as compared to NYHA II and controls. We were the first to demonstrate that with the progression of HF, disturbances of enzymatic and non-enzymatic antioxidant defense, and oxidative damage to proteins and lipids occur at both central (plasma/erythrocytes) and local (saliva) levels. In the study group, we also observed a decrease in saliva secretion, total salivary protein and salivary amylase activity compared to age- and gender-matched control group, which indicates secretory dysfunction of salivary glands in patients with HF. Salivary AGE may be a potential biomarker in differential diagnosis of HF.
Therapeutic Potential of Proanthocyanidins in Ulcerative Colitis in Remission
Authors: Głąbska Dominika , Guzek Dominika , Gałązka Karolina , Lech Gustaw
Published: March 2020

A number of bioactive components of diet are indicated as potential dietary factors for the management of ulcerative colitis, while the recent study conducted in an animal model revealed that proanthocyanidins from grape seeds exert a broadly positive impact. The aim of the study was to verify the influence of dietary proanthocyanidins intake on the symptoms of ulcerative colitis in remission in human subjects. The study was conducted in a group of 55 participants (19 males, 36 females) in remission of ulcerative colitis confirmed based on both the Mayo Scoring system and Rachmilewitz index. Their habitual dietary intake of proanthocyanidins and intake recalculated per 1000 kcal of diet was assessed and it was verified whether they are associated with symptoms of ulcerative colitis. The energy value of diet and intake of other nutrients were analyzed as potential interfering factors. Participants declaring the presence of mucus in their stool compared with other participants were characterized by higher proanthocyanidins intake (142 vs. 75 mg; p = 0.0441) and intake per 1000 kcal (91 vs. 37 mg/1000 kcal; p = 0.0092), while for no other nutrient such association was stated. Participants declaring constipation compared with other participants were characterized by higher proanthocyanidins intake (214 vs. 82 mg; p = 0.0289) and intake per 1000 kcal (118 vs. 41 mg/1000 kcal; p = 0.0194). Similar association for constipation was observed in the case of energy value of diet and protein intake, but only for proanthocyanidins intake, it was confirmed in the logistic regression model (p = 0.0183; OR = 1.01; 95% CI 1.00–1.02). The positive influence of habitual dietary intake of proanthocyanidins was confirmed in the studied group of patients with ulcerative colitis in remission, as this intake may have increased the production of mucus, which is beneficial for intestinal healing, and may have reduced the frequency of bowel movements. However, further experimental human studies are necessary to confirm the potential influence of proanthocyanidins intake in patients with ulcerative colitis in remission.
Accuracy of Edentulous Computer-Aided Implant Surgery as Compared to Virtual Planning: A Retrospective Multicenter Study
Authors: Vinci R. , Manacorda M. , Abundo R. , Lucchina A.G. , Scarano A. , Crocetta C. , Lo Muzio L. , Gherlone E.F. , Mastrangelo F.
Published: March 2020

Purpose: To evaluate the accuracy of computer-aided dental implant positions obtained with mucosal-supported templates as compared to Three-Dimensional (3D) planning. Materials and methods: One-hundred implants were inserted into 14 edentulous patients using the All-on-4/6 protocol after surgical virtual planning with RealGUIDE, 3DIEMME, and Geomagic software. After 6 months, three-dimensional neck (V) and apex (S) spatial coordinates of implants and angle inclination displacements as compared to virtual plans were evaluated. Results: The S maxilla coordinates revealed a significant discrepancy between clinical and virtual implant positions (p-value = 0.091). The V coordinates showed no significant differences (p-value = 0.71). The S (p-value = 0.017) and V (p-value = 0.038) mandible coordinates showed significant discrepancies between the clinical and virtual positions of the screws. Implant evaluation showed a 1-mm in average of the horizontal deviation in the V point and a 1.6-mm deviation in the S point. A mean 5° angular global deviation was detected. The multivariate permutation test of the S (p-value = 0.02) confirmed the difference. Greater errors in the mandible were detected as compared to the maxilla, and a higher S discrepancy was found in the posterior jaw compared to the anterior section of both the mandible and maxilla. Conclusions: Computer-aided surgery with mucosal-supported templates is a predictable procedure for implant placement. Data showed a discrepancy between the actual dental implant position as compared to the virtual plan, but this was not statistically significant. However, the horizontal and angle deviations detected indicated that flap surgery should be used to prevent implant positioning errors due to poor sensitivity and accuracy in cases of severe jaw atrophy.
Breast Mammographic Density: Stromal Implications on Breast Cancer Detection and Therapy
Authors: Fernández-Nogueira Patricia , Mancino Mario , Fuster Gemma , Bragado Paloma , Prats de Puig Miquel , Gascón Pere , Casado Francisco Javier , Carbó Neus
Published: March 2020

Current evidences state clear that both normal development of breast tissue as well as its malignant progression need many-sided local and systemic communications between epithelial cells and stromal components. During development, the stroma, through remarkably regulated contextual signals, affects the fate of the different mammary cells regarding their specification and differentiation. Likewise, the stroma can generate tumour environments that facilitate the neoplastic growth of the breast carcinoma. Mammographic density has been described as a risk factor in the development of breast cancer and is ascribed to modifications in the composition of breast tissue, including both stromal and glandular compartments. Thus, stroma composition can dramatically affect the progression of breast cancer but also its early detection since it is mainly responsible for the differences in mammographic density among individuals. This review highlights both the pathological and biological evidences for a pivotal role of the breast stroma in mammographic density, with particular emphasis on dense and malignant stromas, their clinical meaning and potential therapeutic implications for breast cancer patients.