bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 Isolation in Healthy Population in Israel: Challenges in Daily Life, Mental Health, Resilience, and Quality of Life
Authors: Lipskaya-Velikovsky Lena
Published: January 2021

Background: Pandemics produce long-lasting secondary impacts on health, with a significant burden on people and society. Until now, the secondary impact of COVID-19 has been little estimated. Our aim was to investigate factors underlying quality of life (QOL) during COVID-19 lockdown among a healthy population, while QOL reduction expands vulnerability to the pandemic secondary impact. Methods: During the spring lockdown in Israel, 571 healthy adults completed a survey that included standard measurements for psychological distress, participation in daily life activities, a sense of social connectedness, resilience, and QOL. Results: We found a high level of psychological distress, significant reduction in participation dimensions, and in QOL (psychical, psychological, and social). These indices were even lower among women, younger adults, and the unemployed. Path analysis demonstrated that psychological distress, participation dimensions, social connectedness, and self-efficacy explained QOL, while participation dimensions were found to be the mediators. Conclusions: The COVID-19 has had a wide impact on the general population, with the potential for negative secondary impacts. Women, young adults, and the unemployed are at high risk for secondary effects. Public health strategies should address the reported factors and populations in order to improve QOL in a healthy population and limit the impact of the pandemic.
Assessment of Ambivalent Sexism in University Students in Colombia and Spain: A Comparative Analysis
Authors: Rodríguez-Burbano Aura Yolima , Cepeda Isabel , Vargas-Martínez Ana Magdalena , De-Diego-Cordero Rocío
Published: January 2021

(1) Background: Gender-based violence has no geographical, personal, or social boundaries. It constitutes a serious public health problem that affects the entire society. This research aims to identify and compare the level of ambivalent sexism in Spanish and Colombian university students and its relationship with sociodemographic factors. Ambivalent sexism, developed by Glick and Fiske (1996), is considered a new type of sexism since, for the first time, it combines negative and positive feelings that give rise to hostile and benevolent sexism, maintaining the subordination of women through punishment and rewards. (2) Methods: The methodology consisted of the application of the validated Spanish version of the Ambivalent Sexism Inventory (ASI) to a sample of 374 students in their final academic year of the Law program, of which 21.7% were students at the University of Santander (Bucaramanga, Colombia), 45.5% at the University Rey Juan Carlos (Madrid, Spain), and the remaining 32.9% at the University of Seville (Seville, Spain). (3) Results: A high level of ambivalent sexism is reported in Colombian students nowadays. In the two countries. there are similarities (e.g., the great weight of religion and the variation in attitudes towards sexism in people who identify themselves as women, compared to male or students consulted that prefer not to answer) and differences (e.g., absence in Colombia of gender-specific legislation, low number of students who have received gender education in Spain). (4) Conclusions: These findings may contribute to the construction of laws that take into account the particular problems of women and the development of educational programs on gender that are offered in a transversal and permanent way and that take into account cultural factors and equity between men and women as an essential element in the training of future judges who have the legal responsibility to protect those who report gender violence.
Improving Uptake and Sustainability of Sanitation Interventions in Timor-Leste: A Case Study
Authors: Clarke Naomi E , Dyer Clare E F , Amaral Salvador , Tan Garyn , Vaz Nery Susana
Published: January 2021

Open defecation (OD) is still a significant public health challenge worldwide. In Timor-Leste, where an estimated 20% of the population practiced OD in 2017, increasing access and use of improved sanitation facilities is a government priority. Community-led total sanitation (CLTS) has become a popular strategy to end OD since its inception in 2000, but evidence on the uptake of CLTS and related interventions and the long-term sustainability of OD-free (ODF) communities is limited. This study utilized a mixed-methods approach, encompassing quantitative monitoring and evaluation data from water, sanitation, and hygiene (WASH) agencies, and semi-structured interviews with staff working for these organizations and the government Department of Environmental Health, to examine sanitation interventions in Timor-Leste. Recommendations from WASH practitioners on how sanitation strategies can be optimized to ensure ODF sustainability are presented. Whilst uptake of interventions is generally good in Timor-Leste, lack of consistent monitoring and evaluation following intervention delivery may contribute to the observed slippage back to OD practices. Stakeholder views suggest that long-term support and monitoring after ODF certification are needed to sustain ODF communities.
A Study on the Causal Process of Virtual Reality Tourism and Its Attributes in Terms of Their Effects on Subjective Well-Being during COVID-19
Authors: Li Yu , Song HakJun , Guo Rui
Published: January 2021

In the landscape of Covid-19 pandemic, people’s well-being, to some extent, can be affected through virtual reality tourism because it has the opportunity to enhance their level of well-being and destination recovery. To verify this empirically an investigation was conducted among people who used Quanjingke, the largest tourism-related virtual reality website in China, during the pandemic. The specific the aim of this paper is to prove the effectiveness of virtual reality tourism in promoting people’s subjective well-being. Hence, an integrated model with the constructs of peripheral attribute, core attribute and pivotal attribute, presence, perceived value, satisfaction, and subjective well-being was proposed and tested. The results indicate that attributes of virtual reality tourism have a positive effect on presence during virtual reality experiences, which positively influences perceived value. The values of virtual reality tourism perceived by tourists result in their satisfaction. Eventually, it was found that tourists’ subjective well-being is improved due to their satisfaction with virtual reality tourism. Practical suggestions are also provided based on the findings.
First Report on Smoking and Infection Control Behaviours at Outdoor Hotspots during the COVID-19 Pandemic: An Unobtrusive Observational Study
Authors: Sun Yuying , Lam Tai Hing , Cheung Yee Tak Derek , Wang Man Ping , Wu Yongda , Chen Jianjiu , Zhang Xiaoyu , Li William H. C. , Ho Sai Yin
Published: January 2021

This study was to observe smoking behaviours and infection control behaviours in smokers at outdoor smoking hotspots during the COVID-19 pandemic in Hong Kong. We conducted unobtrusive observations at nine hotspots during 1 July 2019–31 January 2020 (pre-outbreak, 39 observations), 1 February–30 April 2020 (outbreak, eight observations), and 1 May–11 June 2020 (since-outbreak, 20 observations). Sex, age group, type of tobacco products used, duration of stay, group smoking behaviours, face mask wearing and infection control behaviours of smokers, and mask wearing of non-smoking pedestrians were observed. Compared with pre-outbreak, lower volumes of smokers were observed during outbreak and since-outbreak. Smokers gathered more in a group (24.5% and 25.8% vs. 13.4%, respectively) and stayed longer (91.5% and 83.6% vs. 80.6% stayed ≥1 min) during outbreak and since-outbreak than pre-outbreak. Ninety-six percent smokers possessed a face mask. While smoking, 81.6% of smokers put the mask under the chin and 13.8% carried it in the hand, 32.4% did not wear a mask immediately after smoking, 98.0% did not sanitize hands, and 74.3% did not keep a distance of at least one metre. During the COVID-19 pandemic, smokers gathered closely and stayed longer at the hotspots, and few practised hand hygiene, all of which may increase the risk of infection.
The Paradox of Tik Tok Anti-Pro-Anorexia Videos: How Social Media Can Promote Non-Suicidal Self-Injury and Anorexia
Authors: Logrieco Giuseppe , Marchili Maria Rosaria , Roversi Marco , Villani Alberto
Published: January 2021

The literature shows that social pressure promotes non-suicidal self-injury (NSSI) Eating disorders, along with self-injury, are also favored by underregulated social media. Tik Tok is one of the most used social media platforms among adolescents. It has been shown that the time young children spend on this platform doubled during the lockdown. The theme of anorexia is very common on this platform. While most “pro-ana” (pro-anorexia) videos, where users exchanged advice on how to pathologically lose weight, have been censored by the application, other “anti-pro-ana” (anti-pro-anorexia) videos, officially aimed at raising awareness of the consequences of anorexia, have become increasingly popular. However, our case shows how even these safer videos paradoxically lead the users to emulate these “guilty” behaviors.
Effectiveness of Tele-Prescription of Therapeutic Physical Exercise in Patellofemoral Pain Syndrome during the COVID-19 Pandemic
Authors: Albornoz-Cabello Manuel , Barrios-Quinta Cristo J. , Barrios-Quinta Ana M. , Escobio-Prieto Isabel , Cardero-Durán María de los Angeles , Espejo-Antunez Luis
Published: January 2021

The health crisis caused by COVID-19 has had a huge impact on the provision of physiotherapists’ services during the pandemic. Patellofemoral pain syndrome (PFPS) is a major health problem and one of the most common causes of pain in the front of the knee in outpatients. The objective was to evaluate the effectiveness of a therapeutic physical exercise (TPE) program supervised by a physiotherapist using telematic channels in reducing pain and disability in a sample of 54 patients with PFPS in the Physiotherapy Service of the San José de la Rinconada Health Center (Seville). Subjects were evaluated pre- and post-intervention (4 weeks—12 treatment sessions). An analysis was made of perceived pain—using the visual analog scale (VAS) and the DN4 neuropathic pain questionnaire—and functional balance—through the Kujala Score test and the Lower Extremity Functional Scale. The supervised TPE program in patients with PFPS produced a reduction in pain: VAS F1, 52 = 8.68 (p = 0.005) η2 = 0.14 and DN4: F1, 52 = 69.94 (p = 0.000) η2 = 0.57; and in Lower Extremity Functional Scale (LEFS) disability: F1, 52 = 19.1 (p = 0.000) η2 = 0.27 and KUJALA: F1, 52 = 60.28 (p = 0.000) η2 = 0.54, which was statistically significant (p = 0.000 for p < 0.05). Hence, the TPE program presented was effective in reducing pain and disability in patients with PFPS.
Mirror Therapy and Action Observation Therapy to Increase the Affected Upper Limb Functionality in Children with Hemiplegia: A Randomized Controlled Trial Protocol
Authors: Palomo-Carrión Rocío , Zuil-Escobar Juan Carlos , Cabrera-Guerra Myriam , Barreda-Martínez Paloma , Martínez-Cepa Carmen Belén
Published: January 2021

The movements of the affected upper limb in infantile hemiplegia are slower and clumsy. This leads to a decrease in the use of the affected hand. The visual effect obtained using the mirror box and the observation of actions in another individual can activate the same structural neuronal cells responsible for the execution of these actions. This research will study the affected upper limb functionality in hemiplegia infantile from 6 to 12 years old after the application of two intervention protocols: observation action therapy and mirror therapy combined with observation action therapy. Children with a diagnose of congenital infantile hemiplegia will be recruited to participate in a randomized controlled trial with two intervention protocols during four weeks (1 h per/day; 5 sessions per/week): Mirror Therapy Action Observation (MTAO) or Action Observation Therapy (AOT). The study variables will be: spontaneous use, measured with the Assisting Hand Assessment (AHA); manual ability measured with the Jebsen Taylor Hand Function Test (JTHFT); surface electromyography of the flexors and extensors muscles of the wrist and grasp strength through a grip dynamometer. Four assessments will be performed: At baseline situation, at the end of treatment, 3 and 6 months after treatment (follow-up assessments). This study will study the effects of these therapies on the use of the affected upper limb in children with hemiplegia.
Noncanonical Sequences Involving NHERF1 Interaction with NPT2A Govern Hormone-Regulated Phosphate Transport: Binding Outside the Box
Authors: Mamonova Tatyana , Friedman Peter A.
Published: January 2021

Na+/H+ exchange factor-1 (NHERF1), a multidomain PDZ scaffolding phosphoprotein, is required for the type II sodium-dependent phosphate cotransporter (NPT2A)-mediated renal phosphate absorption. Both PDZ1 and PDZ2 domains are involved in NPT2A-dependent phosphate uptake. Though harboring identical core-binding motifs, PDZ1 and PDZ2 play entirely different roles in hormone-regulated phosphate transport. PDZ1 is required for the interaction with the C-terminal PDZ-binding sequence of NPT2A (-TRL). Remarkably, phosphocycling at Ser290 distant from PDZ1, the penultimate step for both parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) regulation, controls the association between NHERF1 and NPT2A. PDZ2 interacts with the C-terminal PDZ-recognition motif (-TRL) of G Protein-coupled Receptor Kinase 6A (GRK6A), and that promotes phosphorylation of Ser290. The compelling biological puzzle is how PDZ1 and PDZ2 with identical GYGF core-binding motifs specifically recognize distinct binding partners. Binding determinants distinct from the canonical PDZ-ligand interactions and located “outside the box” explain PDZ domain specificity. Phosphorylation of NHERF1 by diverse kinases and associated conformational changes in NHERF1 add more complexity to PDZ-binding diversity.
CYP450 Mediates Reactive Oxygen Species Production in a Mouse Model of β-Thalassemia through an Increase in 20-HETE Activity
Authors: Bou-Fakhredin Rayan , Dia Batoul , Ghadieh Hilda , Rivella Stefano , Cappellini Maria , Eid Assaad , Taher Ali
Published: January 2021

Oxidative damage by reactive oxygen species (ROS) is one of the main contributors to cell injury and tissue damage in thalassemia patients. Recent studies suggest that ROS generation in non-transfusion-dependent (NTDT) patients occurs as a result of iron overload. Among the different sources of ROS, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes and cytochrome P450 (CYP450) have been proposed to be major contributors for oxidative stress in several diseases. However, the sources of ROS in patients with NTDT remain poorly understood. In this study, Hbbth3/+ mice, a mouse model for β-thalassemia, were used. These mice exhibit an unchanged or decreased expression of the major NOX isoforms, NOX1, NOX2 and NOX4, when compared to their C57BL/6 control littermates. However, a significant increase in the protein synthesis of CYP4A and CYP4F was observed in the Hbbth3/+ mice when compared to the C57BL/6 control mice. These changes were paralleled by an increased production of 20-hydroxyeicosatetraenoic acid (20-HETE), a CYP4A and CYP4F metabolite. Furthermore, these changes corroborate with onset of ROS production concomitant with liver injury. To our knowledge, this is the first report indicating that CYP450 4A and 4F-induced 20-HETE production mediates reactive oxygen species overgeneration in Hbbth3/+ mice through an NADPH-dependent pathway.
Escape from X Chromosome Inactivation and the Female Predominance in Autoimmune Diseases
Authors: Youness Ali , Miquel Charles-Henry , Guéry Jean-Charles
Published: January 2021

Women represent 80% of people affected by autoimmune diseases. Although, many studies have demonstrated a role for sex hormone receptor signaling, particularly estrogens, in the direct regulation of innate and adaptive components of the immune system, recent data suggest that female sex hormones are not the only cause of the female predisposition to autoimmunity. Besides sex steroid hormones, growing evidence points towards the role of X-linked genetic factors. In female mammals, one of the two X chromosomes is randomly inactivated during embryonic development, resulting in a cellular mosaicism, where about one-half of the cells in a given tissue express either the maternal X chromosome or the paternal one. X chromosome inactivation (XCI) is however not complete and 15 to 23% of genes from the inactive X chromosome (Xi) escape XCI, thereby contributing to the emergence of a female-specific heterogeneous population of cells with bi-allelic expression of some X-linked genes. Although the direct contribution of this genetic mechanism in the female susceptibility to autoimmunity still remains to be established, the cellular mosaicism resulting from XCI escape is likely to create a unique functional plasticity within female immune cells. Here, we review recent findings identifying key immune related genes that escape XCI and the relationship between gene dosage imbalance and functional responsiveness in female cells.
CD200 Change Is Involved in Neuronal Death in Gerbil Hippocampal CA1 Field Following Transient Forebrain Ischemia and Postischemic Treatment with Risperidone Displays Neuroprotection without CD200 Change
Authors: Lee Tae-Kyeong , Shin Myoung Cheol , Ahn Ji Hyeon , Kim Dae Won , Kim Bora , Sim Hyejin , Lee Jae-Chul , Cho Jun Hwi , Park Joon Ha , Kim Young-Myeong , Won Moo-Ho , Lee Choong-Hyun
Published: January 2021

It has been reported that CD200 (Cluster of Differentiation 200), expressed in neurons, regulates microglial activation in the central nervous system, and a decrease in CD200 expression causes an increase in microglial activation and neuronal loss. The aim of this study was to investigate time-dependent changes in CD200 expression in the hippocampus proper (CA1, 2, and 3 fields) after transient forebrain ischemia for 5 min in gerbils. In this study, 5-min ischemia evoked neuronal death (loss) of pyramidal neurons in the CA1 field, but not in the CA2/3 fields, at 5 days postischemia. In the sham group, CD200 expression was found in pyramidal neurons of the CA1 field, and the immunoreactivity in the group with ischemia was decreased at 6 h postischemia, dramatically increased at 12 h postischemia, decreased (to level found at 6 h postischemia) at 1 and 2 days postischemia, and significantly increased again at 5 days postischemia. At 5 days postischemia, CD200 immunoreactivity was strongly expressed in microglia and GABAergic neurons. However, in the CA3 field, the change in CD200 immunoreactivity in pyramidal neurons was markedly weaker than that in the CA1 field, showing there was no expression of CD 200 in microglia and GABAergic neurons. In addition, treatment of 10 mg/kg risperidone (an atypical antipsychotic drug) after the ischemia hardly changed CD200 immunoreactivity in the CA1 field, showing that CA1 pyramidal neurons were protected from the ischemic injury. These results indicate that the transient ischemia-induced change in CD200 expression may be associated with specific and selective neuronal death in the hippocampal CA1 field following transient forebrain ischemia.
Mismatch between Tissue Partial Oxygen Pressure and Near-Infrared Spectroscopy Neuromonitoring of Tissue Respiration in Acute Brain Trauma: The Rationale for Implementing a Multimodal Monitoring Strategy
Authors: Forcione Mario , Ganau Mario , Prisco Lara , Chiarelli Antonio Maria , Bellelli Andrea , Belli Antonio , Davies David James
Published: January 2021

The brain tissue partial oxygen pressure (PbtO2) and near-infrared spectroscopy (NIRS) neuromonitoring are frequently compared in the management of acute moderate and severe traumatic brain injury patients; however, the relationship between their respective output parameters flows from the complex pathogenesis of tissue respiration after brain trauma. NIRS neuromonitoring overcomes certain limitations related to the heterogeneity of the pathology across the brain that cannot be adequately addressed by local-sample invasive neuromonitoring (e.g., PbtO2 neuromonitoring, microdialysis), and it allows clinicians to assess parameters that cannot otherwise be scanned. The anatomical co-registration of an NIRS signal with axial imaging (e.g., computerized tomography scan) enhances the optical signal, which can be changed by the anatomy of the lesions and the significance of the radiological assessment. These arguments led us to conclude that rather than aiming to substitute PbtO2 with tissue saturation, multiple types of NIRS should be included via multimodal systemic- and neuro-monitoring, whose values then are incorporated into biosignatures linked to patient status and prognosis. Discussion on the abnormalities in tissue respiration due to brain trauma and how they affect the PbtO2 and NIRS neuromonitoring is given.
Novel Biallelic Variants and Phenotypic Features in Patients with SLC38A8-Related Foveal Hypoplasia
Authors: Schiff Elena R. , Tailor Vijay K. , Chan Hwei Wuen , Theodorou Maria , Webster Andrew R. , Moosajee Mariya
Published: January 2021

Biallelic pathogenic variants in solute carrier family 38 member 8, SLC38A8, cause a pan-ocular autosomal recessive condition known as foveal hypoplasia 2, FVH2, characterised by foveal hypoplasia, nystagmus and optic nerve chiasmal misrouting. Patients are often clinically diagnosed with ocular albinism, but foveal hypoplasia can occur in several other ocular disorders. Here we describe nine patients from seven families who had molecularly confirmed biallelic recessive variants in SLC38A8 identified through whole genome sequencing or targeted gene panel testing. We identified four novel sequence variants (p.(Tyr88*), p.(Trp145*), p.(Glu233Gly) and c.632+1G>A). All patients presented with foveal hypoplasia, nystagmus and reduced visual acuity; however, one patient did not exhibit any signs of chiasmal misrouting, and three patients had features of anterior segment dysgenesis. We highlight these findings in the context of 30 other families reported to date. This study reinforces the importance of obtaining a molecular diagnosis in patients whose phenotype overlap with other inherited ocular conditions, in order to support genetic counselling, clinical prognosis and family planning. We expand the spectrum of SLC38A8 mutations which will be relevant for treatment through future genetic-based therapies.
Potential Role of Insulin Growth-Factor-Binding Protein 2 as Therapeutic Target for Obesity-Related Insulin Resistance
Authors: Boughanem Hatim , Yubero-Serrano Elena M. , López-Miranda José , Tinahones Francisco J. , Macias-Gonzalez Manuel
Published: January 2021

Evidence from observational and in vitro studies suggests that insulin growth-factor-binding protein type 2 (IGFBP2) is a promising protein in non-communicable diseases, such as obesity, insulin resistance, metabolic syndrome, or type 2 diabetes. Accordingly, great efforts have been carried out to explore the role of IGFBP2 in obesity state and insulin-related diseases, which it is typically found decreased. However, the physiological pathways have not been explored yet, and the relevance of IGFBP2 as an important pathway integrator of metabolic disorders is still unknown. Here, we review and discuss the molecular structure of IGFBP2 as the first element of regulating the expression of IGFBP2. We highlight an update of the association between low serum IGFBP2 and an increased risk of obesity, type 2 diabetes, metabolic syndrome, and low insulin sensitivity. We hypothesize mechanisms of IGFBP2 on the development of obesity and insulin resistance in an insulin-independent manner, which meant that could be evaluated as a therapeutic target. Finally, we cover the most interesting lifestyle modifications that regulate IGFBP2, since lifestyle factors (diet and/or physical activity) are associated with important variations in serum IGFBP2.
ZnJ6 Is a Thylakoid Membrane DnaJ-Like Chaperone with Oxidizing Activity in Chlamydomonas reinhardtii
Authors: Amiya Richa , Shapira Michal
Published: January 2021

Assembly of photosynthetic complexes is sensitive to changing light intensities, drought and pathogens, each of which induces a redox imbalance that requires the assistance of specific chaperones to maintain protein structure. Here we report a thylakoid membrane-associated DnaJ-like protein, ZnJ6 (Cre06.g251716.t1.2), in Chlamydomonas reinhardtii. The protein has four CXXCX(G)X(G) motifs that form two zinc fingers (ZFs). Site-directed mutagenesis (Cys > Ser) eliminates the ability to bind zinc. An intact ZF is required for ZnJ6 stability at elevated temperatures. Chaperone assays with recombinant ZnJ6 indicate that it has holding and oxidative activities. ZnJ6 is unable to reduce the disulfide bonds of insulin but prevents its aggregation in a reducing environment. It also assists in the reactivation of reduced denatured RNaseA, possibly by its oxidizing activity. ZnJ6 pull-down assays revealed interactions with oxidoreductases, photosynthetic proteins and proteases. In vivo experiments with a C. reinhardtii insertional mutant (∆ZnJ6) indicate enhanced tolerance to oxidative stress but increased sensitivity to heat and reducing conditions. Moreover, ∆ZnJ6 has reduced photosynthetic efficiency shown by the Chlorophyll fluorescence transient. Taken together, we identify a role for this thylakoid-associated DnaJ-like oxidizing chaperone that assists in the prevention of protein misfolding and aggregation, thus contributing to stress endurance, redox maintenance and photosynthetic balance.
MSC Based Therapies to Prevent or Treat BPD—A Narrative Review on Advances and Ongoing Challenges
Authors: Goetz Maurizio J. , Kremer Sarah , Behnke Judith , Staude Birte , Shahzad Tayyab , Holzfurtner Lena , Chao Cho-Ming , Morty Rory E. , Bellusci Saverio , Ehrhardt Harald
Published: January 2021

Bronchopulmonary dysplasia (BPD) remains one of the most devastating consequences of preterm birth resulting in life-long restrictions in lung function. Distorted lung development is caused by its inflammatory response which is mainly provoked by mechanical ventilation, oxygen toxicity and bacterial infections. Dysfunction of resident lung mesenchymal stem cells (MSC) represents one key hallmark that drives BPD pathology. Despite all progress in the understanding of pathomechanisms, therapeutics to prevent or treat BPD are to date restricted to a few drugs. The limited therapeutic efficacy of established drugs can be explained by the fact that they fail to concurrently tackle the broad spectrum of disease driving mechanisms and by the huge overlap between distorted signal pathways of lung development and inflammation. The great enthusiasm about MSC based therapies as novel therapeutic for BPD arises from the capacity to inhibit inflammation while simultaneously promoting lung development and repair. Preclinical studies, mainly performed in rodents, raise hopes that there will be finally a broadly acting, efficient therapy at hand to prevent or treat BPD. Our narrative review gives a comprehensive overview on preclinical achievements, results from first early phase clinical studies and challenges to a successful translation into the clinical setting.
Tissue Nonspecific Alkaline Phosphatase Function in Bone and Muscle Progenitor Cells: Control of Mitochondrial Respiration and ATP Production
Authors: Zhang Zhi , Nam Hwa Kyung , Crouch Spencer , Hatch Nan E.
Published: January 2021

Tissue nonspecific alkaline phosphatase (TNAP/Alpl) is associated with cell stemness; however, the function of TNAP in mesenchymal progenitor cells remains largely unknown. In this study, we aimed to establish an essential role for TNAP in bone and muscle progenitor cells. We investigated the impact of TNAP deficiency on bone formation, mineralization, and differentiation of bone marrow stromal cells. We also pursued studies of proliferation, mitochondrial function and ATP levels in TNAP deficient bone and muscle progenitor cells. We find that TNAP deficiency decreases trabecular bone volume fraction and trabeculation in addition to decreased mineralization. We also find that Alpl−/− mice (global TNAP knockout mice) exhibit muscle and motor coordination deficiencies similar to those found in individuals with hypophosphatasia (TNAP deficiency). Subsequent studies demonstrate diminished proliferation, with mitochondrial hyperfunction and increased ATP levels in TNAP deficient bone and muscle progenitor cells, plus intracellular expression of TNAP in TNAP+ cranial osteoprogenitors, bone marrow stromal cells, and skeletal muscle progenitor cells. Together, our results indicate that TNAP functions inside bone and muscle progenitor cells to influence mitochondrial respiration and ATP production. Future studies are required to establish mechanisms by which TNAP influences mitochondrial function and determine if modulation of TNAP can alter mitochondrial respiration in vivo.
Artemether-Loaded Zein Nanoparticles: An Innovative Intravenous Dosage Form for the Management of Severe Malaria
Authors: Boateng-Marfo Yaa , Dong Yuancai , Ng Wai Kiong , Lin Hai-Shu
Published: January 2021

Artemether, an artemisinin derivative, is used in the management of life-threatening severe malaria. This study aimed to develop an intravenous dosage form of artemether using nanotechnology. Artemether-loaded zein nanoparticles were prepared by modified antisolvent precipitation using sodium caseinate as a stabilizer. Subsequently, the physicochemical properties of the nanoparticles were characterized; the in vitro hemolytic property was examined with red blood cells, while the pharmacokinetic profile was evaluated in Sprague–Dawley rats after intravenous administration. The artemether-loaded zein nanoparticles were found to display good encapsulation efficiency, excellent physical stability and offer an in vitro extended-release property. Interestingly, encapsulation of artemether into zein nanoparticles substantially suppressed hemolysis, a common clinical phenomenon occurring after artemisinin-based antimalarial therapy. Upon intravenous administration, artemether-loaded zein nanoparticles extended the mean residence time of artemether by ~80% in comparison to the free artemether formulation (82.9 ± 15.2 versus 45.6 ± 16.4 min, p < 0.01), suggesting that the nanoparticles may prolong the therapeutic duration and reduce the dosing frequency in a clinical setting. In conclusion, intravenous delivery of artemether by artemether-loaded zein nanoparticles appears to be a promising therapeutic option for severe malaria.
Transcriptome Changes in Three Brain Regions during Chronic Lithium Administration in the Rat Models of Mania and Depression
Authors: Szczepankiewicz Dawid , Celichowski Piotr , Kołodziejski Paweł A. , Pruszyńska-Oszmałek Ewa , Sassek Maciej , Zakowicz Przemysław , Banach Ewa , Langwiński Wojciech , Sakrajda Kosma , Nowakowska Joanna , Socha Magdalena , Bukowska-Olech Ewelina , Pawlak Joanna , Twarowska-Hauser Joanna , Nogowski Leszek , Rybakowski Janusz K. , Szczepankiewicz Aleksandra
Published: January 2021

Lithium has been the most important mood stabilizer used for the treatment of bipolar disorder and prophylaxis of manic and depressive episodes. Despite long use in clinical practice, the exact molecular mechanisms of lithium are still not well identified. Previous experimental studies produced inconsistent results due to different duration of lithium treatment and using animals without manic-like or depressive-like symptoms. Therefore, we aimed to analyze the gene expression profile in three brain regions (amygdala, frontal cortex and hippocampus) in the rat model of mania and depression during chronic lithium administration (2 and 4 weeks). Behavioral changes were verified by the forced swim test, open field test and elevated maze test. After the experiment, nucleic acid was extracted from the frontal cortex, hippocampus and amygdala. Gene expression profile was done using SurePrint G3 Rat Gene Expression whole transcriptome microarrays. Data were analyzed using Gene Spring 14.9 software. We found that chronic lithium treatment significantly influenced gene expression profile in both mania and depression models. In manic rats, chronic lithium treatment significantly influenced the expression of the genes enriched in olfactory and taste transduction pathway and long non-coding RNAs in all three brain regions. We report here for the first time that genes regulating olfactory and taste receptor pathways and long non-coding RNAs may be targeted by chronic lithium treatment in the animal model of mania.
Aptamers Against the β-Conglutin Allergen: Insights into the Behavior of the Shortest Multimeric(Intra)Molecular DNA G-Quadruplex
Authors: O’ Sullivan Ciara K. , Mairal Teresa , Jauset-Rubio Miriam , Svobodova Marketa , Skouridou Vasso , Esposito Veronica , Virgilio Antonella , Galeone Aldo
Published: January 2021

In previous work, a 93-mer aptamer was selected against the anaphylactic allergen, β-conglutin and truncated to an 11-mer, improving the affinity by two orders of magnitude, whilst maintaining the specificity. This 11-mer was observed to fold in a G-quadruplex, and preliminary results indicated the existence of a combination of monomeric and higher-order structures. Building on this previous work, in the current study, we aimed to elucidate a deeper understanding of the structural forms of this 11-mer and the effect of the structure on its binding ability. A battery of techniques including polyacrylamide gel electrophoresis, high-performance liquid chromatography in combination with electrospray ionization time-of-flight mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight, thermal binding analysis, circular dichroism and nuclear magnetic resonance were used to probe the structure of both the 11-mer and the 11-mer flanked with TT- at either the 5′ or 3′ end or at both ends. The TT-tail at the 5′ end hinders stacking effects and effectively enforces the 11-mer to maintain a monomeric form. The 11-mer and the TT- derivatives of the 11-mer were also evaluated for their ability to bind its cognate target using microscale thermophoresis and surface plasmon resonance, and biolayer interferometry confirmed the nanomolar affinity of the 11-mer. All the techniques utilized confirmed that the 11-mer was found to exist in a combination of monomeric and higher-order structures, and that independent of the structural form present, nanomolar affinity was observed.
A Novel Role for the DNA Repair Enzyme 8-Oxoguanine DNA Glycosylase in Adipogenesis
Authors: Komakula Sai Santosh Babu , Blaze Bhavya , Ye Hong , Dobrzyn Agnieszka , Sampath Harini
Published: January 2021

Cells sustain constant oxidative stress from both exogenous and endogenous sources. When unmitigated by antioxidant defenses, reactive oxygen species damage cellular macromolecules, including DNA. Oxidative lesions in both nuclear and mitochondrial DNA are repaired via the base excision repair (BER) pathway, initiated by DNA glycosylases. We have previously demonstrated that the BER glycosylase 8-oxoguanine DNA glycosylase (OGG1) plays a novel role in body weight maintenance and regulation of adiposity. Specifically, mice lacking OGG1 (Ogg1−/−) are prone to increased fat accumulation with age and consumption of hypercaloric diets. Conversely, transgenic animals with mitochondrially-targeted overexpression of OGG1 (Ogg1Tg) are resistant to age- and diet-induced obesity. Given these phenotypes of altered adiposity in the context of OGG1 genotype, we sought to determine if OGG1 plays a cell-intrinsic role in adipocyte maturation and lipid accumulation. Here, we report that preadipocytes from Ogg1−/− mice differentiate more efficiently and accumulate more lipids than those from wild-type animals. Conversely, OGG1 overexpression significantly blunts adipogenic differentiation and lipid accretion in both pre-adipocytes from Ogg1Tg mice, as well as in 3T3-L1 cells with adenovirus-mediated OGG1 overexpression. Mechanistically, changes in adipogenesis are accompanied by significant alterations in cellular PARylation, corresponding with OGG1 genotype. Specifically, deletion of OGG1 reduces protein PARylation, concomitant with increased adipogenic differentiation, while OGG1 overexpression significantly increases PARylation and blunts adipogenesis. Collectively, these data indicate a novel role for OGG1 in modulating adipocyte differentiation and lipid accretion. These findings have important implications to our knowledge of the fundamental process of adipocyte differentiation, as well as to our understanding of lipid-related diseases such as obesity.
The Responses of Bioactive Betanin Pigment and Its Derivatives from a Red Beetroot (Beta vulgaris L.) Betalain-Rich Extract to Hypochlorous Acid
Authors: Starzak Karolina , Sutor Katarzyna , Świergosz Tomasz , Nemzer Boris , Pietrzkowski Zbigniew , Popenda Łukasz , Liu Shi-Rong , Wu Shu-Pao , Wybraniec Sławomir
Published: January 2021

Neutrophils produce hypochlorous acid (HOCl) as well as other reactive oxygen species as part of a natural innate immune response in the human body; however, excessive levels of HOCl can ultimately be detrimental to health. Recent reports suggest that betacyanin plant pigments can act as potent scavengers of inflammatory factors and are notably effective against HOCl. Comparison of the in vitro anti-hypochlorite activities of a novel betalain-rich red beetroot (Beta vulgaris L.) extract with its pure betalainic pigments revealed that the extract had the highest anti-hypochlorite activity, far exceeding the activity of all of the betalainic derivatives and selected reference antioxidants. This suggests that it may be an important food-based candidate for management of inflammatory conditions induced by excessive HOCl production. Among all pigments studied, betanidin exhibited the highest activity across the pH range.
Exogenous Application of Brassinosteroid 24-Norcholane 22(S)-23-Dihydroxy Type Analogs to Enhance Water Deficit Stress Tolerance in Arabidopsis thaliana
Authors: Díaz Katy , Espinoza Luis , Carvajal Rodrigo , Silva-Moreno Evelyn , Olea Andrés F. , Rubio Julia
Published: January 2021

Brassinosteroids (BRs) are plant hormones that play an essential role in plant development and have the ability to protect plants against various environmental stresses, such as low and high temperature, drought, heat, salinity, heavy metal toxicity, and pesticides. Mitigation of stress effects are produced through independent mechanisms or by interaction with other important phytohormones. However, there are few studies in which this property has been reported for BRs analogs. Thus, in this work, the enhancement of drought stress tolerance of A. thaliana was assessed for a series of 2-deoxybrassinosteroid analogs. In addition, the growth-promoting activity in the Rice Lamina Inclination Test (RLIT) was also evaluated. The results show that analog 1 exhibits similar growth activity as brassinolide (BL; used as positive control) in the RLIT bioassay. Interestingly, both compounds increase their activities by a factor of 1.2–1.5 when they are incorporated to polymer micelles formed by Pluronic F-127. On the other hand, tolerance to water deficit stress of Arabidopsis thaliana seedlings was evaluated by determining survival rate and dry weight of seedlings after the recovery period. In both cases, the effect of analog 1 is higher than that exhibited by BL. Additionally, the expression of a subset of drought stress marker genes was evaluated in presence and absence of exogenous applied BRs. Results obtained by qRT-PCR analysis, indicate that transcriptional changes of AtDREBD2A and AtNCED3 genes were more significant in A. thaliana treated with analog 1 in homogeneous solution than in that treated with BL. These changes suggest the activation of alternative pathway in response to water stress deficit. Thus, exogenous application of BRs synthetic analogs could be a potential tool for improvement of crop production under stress conditions.
Genetic Delivery and Gene Therapy in Pulmonary Hypertension
Authors: Rai Nabham , Shihan Mazen , Seeger Werner , Schermuly Ralph T. , Novoyatleva Tatyana
Published: January 2021

Pulmonary hypertension (PH) is a progressive complex fatal disease of multiple etiologies. Hyperproliferation and resistance to apoptosis of vascular cells of intimal, medial, and adventitial layers of pulmonary vessels trigger excessive pulmonary vascular remodeling and vasoconstriction in the course of pulmonary arterial hypertension (PAH), a subgroup of PH. Multiple gene mutation/s or dysregulated gene expression contribute to the pathogenesis of PAH by endorsing the proliferation and promoting the resistance to apoptosis of pulmonary vascular cells. Given the vital role of these cells in PAH progression, the development of safe and efficient-gene therapeutic approaches that lead to restoration or down-regulation of gene expression, generally involved in the etiology of the disease is the need of the hour. Currently, none of the FDA-approved drugs provides a cure against PH, hence innovative tools may offer a novel treatment paradigm for this progressive and lethal disorder by silencing pathological genes, expressing therapeutic proteins, or through gene-editing applications. Here, we review the effectiveness and limitations of the presently available gene therapy approaches for PH. We provide a brief survey of commonly existing and currently applicable gene transfer methods for pulmonary vascular cells in vitro and describe some more recent developments for gene delivery existing in the field of PH in vivo.
Recycled Aggregates Concrete Compressive Strength Prediction Using Artificial Neural Networks (ANNs)
Authors: B K A Mohamad Ali Ridho , Ngamkhanong Chayut , Wu Yubin , Kaewunruen Sakdirat
Published: January 2021

The recycled aggregate is an alternative with great potential to replace the conventional concrete alongside with other benefits such as minimising the usage of natural resources in exploitation to produce new conventional concrete. Eventually, this will lead to reducing the construction waste, carbon footprints and energy consumption. This paper aims to study the recycled aggregate concrete compressive strength using Artificial Neural Network (ANN) which has been proven to be a powerful tool for use in predicting the mechanical properties of concrete. Three different ANN models where 1 hidden layer with 50 number of neurons, 2 hidden layers with (50 10) number of neurons and 2 hidden layers (modified activation function) with (60 3) number of neurons are constructed with the aid of Levenberg-Marquardt (LM) algorithm, trained and tested using 1030 datasets collected from related literature. The 8 input parameters such as cement, blast furnace slag, fly ash, water, superplasticizer, coarse aggregate, fine aggregate, and age are used in training the ANN models. The number of hidden layers, number of neurons and type of algorithm affect the prediction accuracy. The predicted recycled aggregates compressive strength shows the compositions of the admixtures such as binders, water–cement ratio and blast furnace–fly ash ratio greatly affect the recycled aggregates mechanical properties. The results show that the compressive strength prediction of the recycled aggregate concrete is predictable with a very high accuracy using the proposed ANN-based model. The proposed ANN-based model can be used further for optimising the proportion of waste material and other ingredients for different targets of concrete compressive strength.
Short-Term Forecasting Photovoltaic Solar Power for Home Energy Management Systems
Authors: Bot Karol , Ruano Antonio , Ruano Maria da Graça
Published: January 2021

Accurate photovoltaic (PV) power forecasting is crucial to achieving massive PV integration in several areas, which is needed to successfully reduce or eliminate carbon dioxide from energy sources. This paper deals with short-term multi-step PV power forecasts used in model-based predictive control for home energy management systems. By employing radial basis function (RBFs) artificial neural networks (ANN), designed using a multi-objective genetic algorithm (MOGA) with data selected by an approximate convex-hull algorithm, it is shown that excellent forecasting results can be obtained. Two case studies are used: a special house located in the USA, and the other a typical residential house situated in the south of Portugal. In the latter case, one-step-ahead values for unscaled root mean square error (RMSE), mean relative error (MRE), normalized mean average error (NMAE), mean absolute percentage error (MAPE) and R2 of 0.16, 1.27%, 1.22%, 8% and 0.94 were obtained, respectively. These results compare very favorably with existing alternatives found in the literature.
Myxomatous Mitral Valve Disease with Mitral Valve Prolapse and Mitral Annular Disjunction: Clinical and Functional Significance of the Coincidence
Authors: Wunderlich Nina , Ho Siew , Flint Nir , Siegel Robert
Published: January 2021

The morphological changes that occur in myxomatous mitral valve disease (MMVD) involve various components, ultimately leading to the impairment of mitral valve (MV) function. In this context, intrinsic mitral annular abnormalities are increasingly recognized, such as a mitral annular disjunction (MAD), a specific anatomical abnormality whereby there is a distinct separation between the mitral annulus and the left atrial wall and the basal portion of the posterolateral left ventricular myocardium. In recent years, several studies have suggested that MAD contributes to myxomatous degeneration of the mitral leaflets, and there is growing evidence that MAD is associated with ventricular arrhythmias and sudden cardiac death. In this review, the morphological characteristics of MAD and imaging tools for diagnosis will be described, and the clinical and functional aspects of the coincidence of MAD and myxomatous MVP will be discussed.
Role of Subtitles in L2 Acquisition and Comprehension: A Pilot Study of Hearing-Impaired Students
Authors: Vulchanova Mila , Kjølstad Lervåg Ingvild
Published: January 2021

The purpose of this study was to investigate whether subtitles can facilitate language processing in English as a second language (L2) and, if so, which subtitles would be more beneficial for hard-of-hearing students with Norwegian as their first language. In total, 14 advanced learners of L2 English were recruited and tested on English comprehension and target vocabulary items based on video material provided with subtitles in English or Norwegian in comparison to no subtitles (control condition). Subtitles aided comprehension of the plot, tested immediately after clip presentation, with an advantage for English subtitles over Norwegian subtitles and no subtitles. Furthermore, subtitles were found to enhance the performance of the participants with moderate hearing loss more than they did for mild hearing loss participants. The inclusion of English subtitles only marginally enhanced vocabulary understanding for both mild and moderate hearing loss students. The findings of this study can be transferred to classrooms and may supplement other methods of adjusting the academic environment, in order to meet the need of students with hearing loss.