bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Autogenic Training in a Form of Audio Recording on Sleep Quality and Physiological Stress Reactions of University Athletes—Pilot Study
Authors: Litwic-Kaminska Kamila , Kotyśko Martyna , Pracki Tadeusz , Wiłkość-Dębczyńska Monika , Stankiewicz Błażej
Published: December 2022

Despite the growing popularity of relaxation training, the effectiveness of an autogenic training (AT) as a method of dealing with sleep problems in group of student athletes is unknown. Therefore, this study aimed to fill this gap. University athletes with decreased sleep quality (selected from 209 participants) were randomly assigned to the experimental (EG, n = 11) and control (CG, n = 11) groups similar in terms of sleep quality, age, gender, type of sport discipline and sport experience. During the 14 days dedicated to performing relaxation training in the form of an audio recording, electronic daily logs and actigraphy were used to monitor the athletes’ sleep and daily activity. The EG listened to the recording with suggestions based on AT and CG only to the background music. Pre- and post-measurements of sleep quality by means of the Pittsburg Sleep Quality Index (PSQI) and physiological stress reactions by biofeedback device were performed. In EG and CG, the parameters of sleep and daily activity obtained by actigraphy and daily logs as well as physiological indicators of emotional reactivity did not differ. Sleep quality in PSQI significantly increased after AT usage in EG. AT seems to be an effective method for university athletes in improving subjective sleep quality, but further studies are necessary.
Tegumentary Leishmaniasis in Northeastern Italy from 2017 to 2020: A Neglected Public Health Issue
Authors: Gaspari Valeria , Gritti Tommaso , Ortalli Margherita , Santi Annalisa , Galletti Giorgio , Rossi Arianna , Rugna Gianluca , Mattivi Andrea , Matteo Giulio , Belloli Gian L. , Mattei Giovanna , Varani Stefania ,   on behalf of the Skin_Leish_RER Network
Published: December 2022

Tegumentary leishmaniasis (TL) includes cutaneous (CL) and mucosal (ML) leishmaniasis; despite being endemic in southern Europe, it is often underdiagnosed and underreported. This study aimed to retrospectively examine data collected from patients with TL in a selected area of northeastern Italy (Emilia-Romagna region, RER). A network of 10 diagnostic units within RER was established, and TL cases diagnosed in RER from 2017 to 2020 were evaluated. A total of 135 TL cases were collected (62% male, 38% female); patients ranged from 1 to 84 years, with a median age of 57. Among these cases, 113 (84%) were notified to the public health authorities. The average annual incidence of TL was 0.76 cases per 100,000 inhabitants. Infections were acquired within the RER in 84% of cases; the 113 autochthonous cases were distributed in the foothills areas of the region. We provide evidence of a defined spatial distribution of TL cases in a selected area of northeastern Italy, as well as a relevant number of ML cases. Our observations suggest the need to raise awareness about TL among clinicians and pathologists, promote the molecular confirmation of cases by reference laboratories, and encourage the establishment of surveillance networks for this neglected disease.
Health Risk, Income Effect, and the Stability of Farmers’ Poverty Alleviation in Deep Poverty Areas: A Case Study of S-County in Qinba Mountain Area
Authors: Song Jie , Cai Yaping , Wang Yahong , Khan Salim
Published: December 2022

Health status and income level are both important factors in reducing poverty and accomplishing sustainable development in deep poverty areas of China. Therefore, the purpose of this study is to provide policy support for the sustainable poverty alleviation of farmers by analyzing the net effect of health risk on Farmers’ income poverty and its impact mechanism. Based on the data of more than 199,000 farmers, this study uses the Difference in Difference (DID) model to empirically analyze the effect of health-risk on farmers’ income poverty. The empirical findings obtained from DID model show that health risk has a significant and positive impact on income poverty, where the impact of disability is higher. Furthermore, the mechanism shows that the impact of health risks on income poverty is mainly influenced by farmers’ off-farm working choices and time. The heterogeneity analysis shows that the health risk significantly impacts non-vulnerable farmers’ poverty. With outdated healthcare facilities in poverty-stricken areas, people are more likely to fall into income poverty. Therefore, the study concludes that establishing an effective long-term mechanism of health risk prevention is essential to improving the endogenous development power of poor farmers and decreasing income poverty.
Assessment Tools of Biopsychosocial Frailty Dimensions in Community-Dwelling Older Adults: A Narrative Review
Authors: De Luca Vincenzo , Femminella Grazia Daniela , Patalano Roberta , Formosa Valeria , Lorusso Grazia , Rivetta Cristiano , Di Lullo Federica , Mercurio Lorenzo , Rea Teresa , Salvatore Elena , Korkmaz Yaylagul Nilufer , Apostolo Joao , Silva Rosa Carla , Dantas Carina , van Staalduinen Willeke H. , Liotta Giuseppe , Iaccarino Guido , Triassi Maria , Illario Maddalena
Published: December 2022

Frailty is a complex interplay between several factors, including physiological changes in ageing, multimorbidities, malnutrition, living environment, genetics, and lifestyle. Early screening for frailty risk factors in community-dwelling older people allows for preventive interventions on the clinical and social determinants of frailty, which allows adverse events to be avoided. By conducting a narrative review of the literature employing the International Narrative Systematic Assessment tool, the authors aimed to develop an updated framework for the main measurement tools to assess frailty risks in older adults, paying attention to use in the community and primary care settings. This search focused on the biopsychosocial domains of frailty that are covered in the SUNFRAIL tool. The study selected 178 reviews (polypharmacy: 20; nutrition: 13; physical activity: 74; medical visits: 0; falls: 39; cognitive decline: 12; loneliness: 15; social support: 5; economic constraints: 0) published between January 2010 and December 2021. Within the selected reviews, 123 assessment tools were identified (polypharmacy: 15; nutrition: 15; physical activity: 25; medical visits: 0; falls: 26; cognitive decline: 18; loneliness: 9; social support: 15; economic constraints: 0). The narrative review allowed us to evaluate assessment tools of frailty domains to be adopted for multidimensional health promotion and prevention interventions in community and primary care.
Umbilical Cord Stump Infections in Central Uganda: Incidence, Bacteriological Profile, and Risk Factors
Authors: Tumuhamye Josephine , Sommerfelt Halvor , Tumwine James K. , Mukunya David , Ndeezi Grace , Namugga Olive , Bwanga Freddie , Steinsland Hans , Nankabirwa Victoria
Published: December 2022

Umbilical cord stump infection (omphalitis) is a risk factor for neonatal sepsis and death. We assessed the incidence of omphalitis, described the bacteriological and antibiotic-resistance profile of potentially pathogenic bacteria isolated from the umbilical cord stump of omphalitis cases, and evaluated whether bacteria present in the birth canal during birth predicted omphalitis. We enrolled 769 neonates at birth at three primary healthcare facilities and followed them for 28 days with scheduled visits on days 3, 7, 14, and 28. Cox regression models were used to estimate the rates of omphalitis associated with potential risk factors. Sixty-five (8.5%) neonates developed omphalitis, with an estimated incidence of 0.095 cases per 28 child-days (95% CI 0.073, 0.12). Potentially pathogenic bacteria were isolated from the cord stump area of 41 (63.1%) of the 65 neonates with omphalitis, and the most commonly isolated species were Escherichia coli (n = 18), Klebsiella pneumoniae (n = 10), Citrobacter freundii (n = 5), and Enterobacter spp. (n = 4). The Enterobacteriaceace isolates were resistant to gentamicin (10.5%, 4/38), ampicillin (86.8%, 33/38), and ceftriaxone (13.2%, 5/38). Delayed initiation of breastfeeding was associated with an increased risk of omphalitis (aHR 3.1; 95% CI 1.3, 7.3); however, vaginal colonization with potentially pathogenic bacteria did not predict omphalitis.
Examining the Complex (Curvilinear and Contingent) Associations between Social Distancing Compliance and Subjective Health during a Global Health Crisis
Authors: Jung Jong Hyun , Choi Kyung Won , Kim Harris Hyun-soo
Published: December 2022

Objectives: This study investigated a potential curvilinear link between social distancing behavior and subjective health in later life. It also evaluated whether food insecurity and community social capital moderated the focal relationship. Methods: Data were drawn from three waves of the COVID Impact Survey (N = 19,234). Mixed-effects models were fitted. Results: Social distancing has a non-monotonic (U-shaped) relationship with subjective health, i.e., individuals with low and high levels of social distancing show relatively better health. Moreover, the negative linear relationship between social distancing and health is weaker among people suffering from food insecurity as well as those living in communities with lower stocks of social capital. Discussion: This study sheds new light on the health implications of social distancing during the pandemic. Our findings dovetail with the steeling hypothesis, i.e., that social distancing is less harmful for U.S. older adults exposed to prior stressful or vulnerable conditions.
Spatial and Temporal Variation and Prediction of Ecosystem Carbon Stocks in Yunnan Province Based on Land Use Change
Authors: Li Long , Fu Wei , Luo Mingcan
Published: December 2022

The function of ecosystems as carbon sinks has emerged as a key strategy for advancing the concept of “carbon neutrality” and “carbon peaking”. Ecosystem carbon stocks are impacted by land use changes that alter ecosystem structure and function. We evaluated the ecosystem carbon stocks of Yunnan Province in different periods with the aid of the carbon stock module of the InVEST model, analyzed the relationship between land use type shift and ecosystem carbon stock changes, and combine them with the CA-Markov model to predict land use types in 2030. The results showed that between 1990 and 2020, changes in land use primarily affected cropland, grassland, and forested areas. The ecosystem’s average carbon stock from 1990 to 2020 was 8278.97 × 106 t. The carbon stocks of cropland, grassland, and unused land decreased by 31.36 × 106 t, 32.18 × 106 t, and 4.18 × 106 t during 1990–2020, respectively, while the carbon stocks of forest land, water area, and construction land increased by 24.31 × 106 t, 7.34 × 106 t, and 22.08 × 106 t. The main cause of the increase in carbon stocks in the ecosystem in Yunnan Province throughout the process of land use type shift was the development of forest land area, whereas the main cause of the decline was the shrinkage of cropland and grassland areas.
Estimating Households’ Expenditures on Disability in Africa: The Uses and Limitations of the Standard of Living Method
Authors: Mont Daniel , Morris Zachary , Nasiir Mercoledi , Goodman Nanette
Published: December 2022

People with disabilities face extra costs of living to participate in the social and economic lives of their communities on an equal basis with people without disabilities. If these extra costs are not accounted for, then their economic wellbeing will be overestimated. The Standard of Living (SOL) method is a way of generating these estimates and is thus useful for determining the economic impact of those costs in the current environment. However, previous studies have used different indicators for disability and different measures of the standard of living, so it is hard to compare estimates across different countries. This study applies a consistent set of indicators across seven African countries to produce comparable estimates. Our estimates of the extra costs of living in these lower-income countries are much lower than the results produced for higher-income countries in prior work. We argue that this finding highlights the limitations of the SOL method as a useful source of information for developing inclusive systems of social protection in lower-income countries because it captures what households spend but not what the person with a disability needs to fully participate in the social and economic lives of their community. In lower-income countries, people with disabilities are likely to have fewer opportunities to spend on needed items thus resulting in substantial unmet need for disability-related goods and services. Failing to account for these unmet needs can lead to inadequate systems of social protection if they are based solely on SOL estimates.
Thermographic of the Microcirculation in Healthy Children Aged 3–10 Months as an Objective and Noninvasive Method of Assessment
Authors: Ptak Agnieszka , Dębiec-Bąk Agnieszka , Stefańska Małgorzata
Published: December 2022

Background: The aim of this study was to assess if thermography as an objective and non-invasive research tool is capable of identifying the changes in the surface temperature of the body as a response to muscle stimulation in Vojta therapy. The research group consisted of children aged 3–10 months with slight abnormalities of the motor pattern, subjected to individually selected stimulation elements according to Vojta. Methods: The Vojta method of spontaneous motor assessment and the thermovision method of assessing the microcirculation properties of muscles were used for the evaluation. Results: In the study group, changes in the microcirculation parameters of the extensor muscles of the back occurred immediately after the therapy at the first examination. Conclusions: The analysis featuring an objective assessment allows physiotherapists to diagnose local temperature changes based on the effect of microcirculation parameters in the musculofascial structures. Trial registration: The research was conducted as a pilot study for a scientific project approved by the Commission for Scientific Research of the University of Health and Sport Sciences in Wroclaw No 24/2021. The study is currently in the registration process with the Australian New Zealand Clinical Trials Registry.
Translating Health Coaching Training into Clinical Practice
Authors: McGlynn Anna , O’Callaghan Cathy , McDougall Brendon , Osborne Julie , Harris-Roxas Ben
Published: December 2022

Health coaching can benefit people with managing chronic conditions. It considers people’s motivations, is person-centred and has the capacity to promote healthy lifestyles and address chronic disease risk factors. However, how health coaching training is translated into routine clinical practice at unit and service levels has been under explored. A metropolitan local health district in Sydney, Australia provided coaching training to health professionals, but the extent to which coaching skills were translated into clinical practice was unknown. A redesign methodology was used to identify barriers and facilitators for training-to-practice translation. Survey and workshop findings indicated that participants were satisfied with the coaching training but found it challenging to apply in clinical practice. Identified opportunities to support the application of health coaching were tailored practical training, post training support, and consensus on the definition of health coaching. Solutions were to develop an internal practical training program, use consistent terminology, and embed organisational support. Adoption of health coaching needs to occur on three levels; individual, workplace and organisation to ensure effective health care delivery. This case study demonstrates the importance of evaluation and diagnostics of contextual barriers and enablers to inform translation into practice.
Prevalence of Alcohol-Related Harms in Yi and Han Ethnic Groups in a Prefecture in Yunnan Province, China
Authors: Yu Zhen , He Liping , Wichaidit Wit , Li Jing , Song Ying , Assanangkornchai Sawitri
Published: December 2022

Background: Although differences in the prevalence of alcohol-related harm between ethnic minority and majority groups have been reported in many countries, such data are scarce in China. The findings of such assessment can provide empirical data to inform stakeholders in prioritization and allocation of resources for programs to manage and control alcohol-related problems. The objective of this study is to compare the prevalence of alcohol-related harm from others among Han and Yi populations in the Chuxiong Yi Autonomous Prefecture, Yunnan Province, China. Method: We conducted a cross-sectional study in 1370 households from 21 villages. Enumerators used convenient sampling to recruit one person aged 18 years or older from each selected household, obtained informed consent to participate, and conducted an interview using a structured questionnaire. The questionnaire included three parts: (1) demographic characteristics of the participant (including ethnic identity); (2) history of alcohol-related harm from other in the past 12 months, and; (3) drinking behaviors. We analyzed data using descriptive statistics and multivariate regression analyses, stratified by sex of the participant. Results: The prevalence of experiencing alcohol-related harm from others in Han men, Yi men, Han females, and Yi females, were 69.9%, 62.1%, 75.3%, and 63.4%, respectively. The Han vs. Yi disparity was higher among females (Adjusted OR = 2.06; 95% CI = 1.41, 3.01) than males (Adjusted OR = 1.47; 95% CI = 1.05, 2.07). The most common type of harm was feeling scared or threatened (36.9% among males, 32.4% among females) and the least common type was financial difficulty (3% among males, and 3.3% among females). Conclusions: Yi ethnic minorities in Yunnan Province had lower prevalence of alcohol-related harm from others than Han persons in the same region. However, measurement and translation-related issues of the study instrument and limited generalizability should be considered as caveats in the interpretation of the study findings.
Substance Use and Addiction in Athletes: The Case for Neuromodulation and Beyond
Authors: Dougherty John W. , Baron David
Published: December 2022

Substance use, misuse and use disorders continue to be major problems in society as a whole and athletes are certainly not exempt. Substance use has surrounded sports since ancient times and the pressures associated with competition sometimes can increase the likelihood of use and subsequent misuse. The addiction field as a whole has very few answers to how to prevent and secondarily treat substance use disorders and the treatments overall do not necessarily agree with the role of being an athlete. With concerns for side effects that may affect performance coupled with organizational rules and high rates of recidivism in the general population, newer treatments must be investigated. Prevention strategies must continue to be improved and more systems need to be in place to find and treat any underlying causes leading to these behaviors. This review attempts to highlight some of the data regarding the field of substance misuse and addiction in the athletic population as well as explore possible future directions for treatment including Neuromodulation methods and Ketamine. There is a need for more rigorous, high-quality studies to look at addiction as a whole and in particular how to approach this vulnerable subset of the population.
Validation of Promoters and Codon Optimization on CRISPR/Cas9-Engineered Jurkat Cells Stably Expressing αRep4E3 for Interfering with HIV-1 Replication
Authors: Chupradit Koollawat , Sornsuwan Kanokporn , Saiprayong Kritayaporn , Wattanapanitch Methichit , Tayapiwatana Chatchai
Published: December 2022

Persistent and efficient therapeutic protein expression in the specific target cell is a significant concern in gene therapy. The controllable integration site, suitable promoter, and proper codon usage influence the effectiveness of the therapeutic outcome. Previously, we developed a non-immunoglobulin scaffold, alpha repeat protein (αRep4E3), as an HIV-1 RNA packaging interference system in SupT1 cells using the lentiviral gene transfer. Although the success of anti-HIV-1 activity was evidenced, the integration site is uncontrollable and may not be practical for clinical translation. In this study, we use the CRISPR/Cas9 gene editing technology to precisely knock-in αRep4E3 genes into the adeno-associated virus integration site 1 (AAVS1) safe harbor locus of the target cells. We compare the αRep4E3 expression under the regulation of three different promoters, including cytomegalovirus (CMV), human elongation factor-1 alpha (EF1α), and ubiquitin C (UbC) promoters with and without codon optimization in HEK293T cells. The results demonstrated that the EF1α promoter with codon-optimized αRep4E3mCherry showed higher protein expression than other promoters with non-optimized codons. We then performed a proof-of-concept study by knocking in the αRep4E3mCherry gene at the AAVS1 locus of the Jurkat cells. The results showed that the αRep4E3mCherry-expressing Jurkat cells exhibited anti-HIV-1 activities against HIV-1NL4-3 strain as evidenced by decreased capsid (p24) protein levels and viral genome copies as compared to the untransfected Jurkat control cells. Altogether, our study demonstrates that the αRep4E3 could interfere with the viral RNA packaging and suggests that the αRep4E3 scaffold protein could be a promising anti-viral molecule that offers a functional cure for people living with HIV-1.
Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays
Authors: García-García Ángela , Julián-Ortiz Jesus Vicente de , Gálvez Jorge , Font David , Ayats Carles , Guna Serrano María del Remedio , Muñoz-Collado Carlos , Borrás Rafael , Villalgordo José Manuel
Published: December 2022

A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets. It was also useful to select new potential antituberculosis compounds in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. The seven selected candidates were synthesized and six of them showed activity in vitro.
A 35-bp Conserved Region Is Crucial for Insl3 Promoter Activity in Mouse MA-10 Leydig Cells
Authors: Giner Xavier C. , Pierre Kenley Joule , Robert Nicholas M. , Tremblay Jacques J.
Published: December 2022

The peptide hormone insulin-like 3 (INSL3) is produced almost exclusively by Leydig cells of the male gonad. INSL3 has several functions such as fetal testis descent and bone metabolism in adults. Insl3 gene expression in Leydig cells is not hormonally regulated but rather is constitutively expressed. The regulatory region of the Insl3 gene has been described in various species; moreover, functional studies have revealed that the Insl3 promoter is regulated by various transcription factors that include the nuclear receptors AR, NUR77, COUP-TFII, LRH1, and SF1, as well as the Krüppel-like factor KLF6. However, these transcription factors are also found in several tissues that do not express Insl3, indicating that other, yet unidentified factors, must be involved to drive Insl3 expression specifically in Leydig cells. Through a fine functional promoter analysis, we have identified a 35-bp region that is responsible for conferring 70% of the activity of the mouse Insl3 promoter in Leydig cells. All tri- and dinucleotide mutations introduced dramatically reduced Insl3 promoter activity, indicating that the entire 35-bp sequence is required. Nuclear proteins from MA-10 Leydig cells bound specifically to the 35-bp region. The 35-bp sequence contains GC- and GA-rich motifs as well as potential binding elements for members of the CREB, C/EBP, AP1, AP2, and NF-κB families. The Insl3 promoter was indeed activated 2-fold by NF-κB p50 but not by other transcription factors tested. These results help to further define the regulation of Insl3 gene transcription in Leydig cells.
Investigating SH-SY5Y Neuroblastoma Cell Surfaceome as a Model for Neuronal-Targeted Novel Therapeutic Modalities
Authors: Gangras Pooja , Gelfanova Valentina , Williams Graham D. , Handelman Samuel K. , Smith Ryan M. , Debets Marjoke F.
Published: December 2022

The SH-SY5Y neuroblastoma cells are a widely used in vitro model approximating neurons for testing the target engagement of therapeutics designed for neurodegenerative diseases and pain disorders. However, their potential as a model for receptor-mediated delivery and uptake of novel modalities, such as antibody-drug conjugates, remains understudied. Investigation of the SH-SY5Y cell surfaceome will aid in greater in vitro to in vivo correlation of delivery and uptake, thereby accelerating drug discovery. So far, the majority of studies have focused on total cell proteomics from undifferentiated and differentiated SH-SY5Y cells. While some studies have investigated the expression of specific proteins in neuroblastoma tissue, a global approach for comparison of neuroblastoma cell surfaceome to the brain and dorsal root ganglion (DRG) neurons remains uninvestigated. Furthermore, an isoform-specific evaluation of cell surface proteins expressed on neuroblastoma cells remains unexplored. In this study, we define a bioinformatic workflow for the identification of high-confidence surface proteins expressed on brain and DRG neurons using tissue proteomic and transcriptomic data. We then delineate the SH-SY5Y cell surfaceome by surface proteomics and show that it significantly overlaps with the human brain and DRG neuronal surface proteome. We find that, for 32% of common surface proteins, SH-SY5Y-specific major isoforms are alternatively spliced, maintaining their protein-coding ability, and are predicted to localize to the cell surface. Validation of these isoforms using surface proteomics confirms a SH-SY5Y-specific alternative NRCAM (neuron-glia related cell adhesion molecule) isoform, which is absent in typical brain neurons, but present in neuroblastomas, making it a receptor of interest for neuroblastoma-specific therapeutics.
Onset of Adverse Abdominal Events Due to Intestinal Ischemia-Reperfusion Injury after Aortic Cross-Clamping Is Associated with Elevated HSP70 Serum Levels in the Early Postoperative Phase
Authors: Doukas Panagiotis , Hellfritsch Gabriel , Krabbe Hanif , Frankort Jelle , Jacobs Michael J. , Gombert Alexander , Simon Florian
Published: December 2022

Tissue injury of the viscera during open thoracoabdominal aortic (TAA) reconstructions has been reported as the aftermath of the ischemia-reperfusion mechanism following supracoeliac aortic cross-clamping. Abdominal complications after open aortic reconstructions, although rare through the intraoperative implementation of selective visceral artery blood perfusion, are associated with high rates of reinterventions and a poor prognosis. Recent animal experiments demonstrated that provoking mesenteric ischemia in rats induces the leukocyte-mediated transcription of heat-shock protein 70 (HSP70), a chaperone belonging to the danger-associated molecular pattern proteins (DAMPs). Translating these findings clinically, we investigated the serum levels of HSP70 in patients undergoing open aortic reconstructions with supracoeliac clamping. We postoperatively observed a relevant induction of HSP70, which remained significantly elevated in cases of postoperative abdominal complications (paralytic ileus, abdominal compartment syndrome, and visceral malperfusion). The receiver–operator curve analysis revealed the reliable prognostic accuracy of HSP70 as a biomarker for these complications as soon as 12 h post-operation (AUC 0.908, sensitivity 88.9%, specificity 83.3%). In conclusion, measuring HSP70 serum levels in the early postoperative phase may serve as a further adjutant in the diagnostic decision making for both the vascular surgeon and intensivist for the timely detection and management of abdominal complications following open TAA surgery.
Evaluation of a Rapid and Simple Method for Assessing Retinal Vessel Structures in Adult Zebrafish
Authors: Lee Yu-Ri , Son Myeongjoo , Kim Young Sook , Kim Jin Sook , Kim Cheol-Hee , Jung Seung-Hyun
Published: December 2022

The evaluation of retinal vascular structures is important for analyzing various ophthalmic diseases. Conventional trypsin digestion was used for separating retinal vasculatures in mouse, rat, and other animal models; however, the trypsin method alone is technically difficult to perform and has not been reported in zebrafish to date. In this study, we introduced a rapid and convenient method that allows the investigation of fine vessel structures at a cellular level in the relatively intact retinal vasculature of adult zebrafish. Using an anti-ZO-1 antibody, tight junction structures in retinal vessels were examined in detail and several different cell types constituting blood vessels in arterial and capillary areas were identified. In addition, using cell type-specific antibodies, we identified smooth muscle cells, blood cells, and endothelial cells in the retinal vasculature. Finally, using the hyperglycemic model, we observed the dilation of retinal vessels, the downregulation of tight junction proteins, and the reduction in smooth muscle cells. Based on these results, we provide a rapid and convenient method for the study of retinal vasculature disease in the zebrafish animal model.
Glomerular Endothelial Cell-Derived miR-200c Impairs Glomerular Homeostasis by Targeting Podocyte VEGF-A
Authors: Ursu Raluca , Sopel Nina , Ohs Alexandra , Tati Ramesh , Buvall Lisa , Nyström Jenny , Schiffer Mario , Müller-Deile Janina
Published: December 2022

Deciphering the pathophysiological mechanisms of primary podocytopathies that can lead to end-stage renal disease and increased mortality is an unmet need. Studying how microRNAs (miRs) interfere with various signaling pathways enables identification of pathomechanisms, novel biomarkers and potential therapeutic options. We investigated the expression of miR-200c in urine from patients with different renal diseases as a potential candidate involved in podocytopathies. The role of miR-200c for the glomerulus and its potential targets were studied in cultured human podocytes, human glomerular endothelial cells and in the zebrafish model. miR-200c was upregulated in urine from patients with minimal change disease, membranous glomerulonephritis and focal segmental glomerulosclerosis and also in transforming growth factor beta (TGF-β) stressed glomerular endothelial cells, but not in podocytes. In zebrafish, miR-200c overexpression caused proteinuria, edema, podocyte foot process effacement and glomerular endotheliosis. Although zinc finger E-Box binding homeobox 1/2 (ZEB1/2), important in epithelial to mesenchymal transition (EMT), are prominent targets of miR-200c, their downregulation did not explain our zebrafish phenotype. We detected decreased vegfaa/bb in zebrafish overexpressing miR-200c and could further prove that miR-200c decreased VEGF-A expression and secretion in cultured human podocytes. We hypothesize that miR-200c is released from glomerular endothelial cells during cell stress and acts in a paracrine, autocrine, as well as context-dependent manner in the glomerulus. MiR-200c can cause glomerular damage most likely due to the reduction of podocyte VEGF-A. In contrast, miR-200c might also influence ZEB expression and therefore EMT, which might be important in other conditions. Therefore, we propose that miR-200c-mediated effects in the glomerulus are context-sensitive.
How Functional Lipids Affect the Structure and Gating of Mechanosensitive MscS-like Channels
Authors: Flegler Vanessa Judith , Rasmussen Tim , Böttcher Bettina
Published: December 2022

The ability to cope with and adapt to changes in the environment is essential for all organisms. Osmotic pressure is a universal threat when environmental changes result in an imbalance of osmolytes inside and outside the cell which causes a deviation from the normal turgor. Cells have developed a potent system to deal with this stress in the form of mechanosensitive ion channels. Channel opening releases solutes from the cell and relieves the stress immediately. In bacteria, these channels directly sense the increased membrane tension caused by the enhanced turgor levels upon hypoosmotic shock. The mechanosensitive channel of small conductance, MscS, from Escherichia coli is one of the most extensively studied examples of mechanically stimulated channels. Different conformational states of this channel were obtained in various detergents and membrane mimetics, highlighting an intimate connection between the channel and its lipidic environment. Associated lipids occupy distinct locations and determine the conformational states of MscS. Not all these features are preserved in the larger MscS-like homologues. Recent structures of homologues from bacteria and plants identify common features and differences. This review discusses the current structural and functional models for MscS opening, as well as the influence of certain membrane characteristics on gating.
A Method for the Immobilization of Chitosan onto Urinary Catheters
Authors: Vesel Alenka , Recek Nina , Zaplotnik Rok , Kurinčič Albert , Kuzmič Katja , Zemljič Lidija Fras
Published: December 2022

A method for the immobilization of an antibacterial chitosan coating to polymeric urinary medical catheters is presented. The method comprises a two-step plasma-treatment procedure, followed by the deposition of chitosan from the water solution. In the first plasma step, the urinary catheter is treated with vacuum-ultraviolet radiation to break bonds in the polymer surface film and create dangling bonds, which are occupied by hydrogen atoms. In the second plasma step, polymeric catheters are treated with atomic oxygen to form oxygen-containing surface functional groups acting as binding sites for chitosan. The presence of oxygen functional groups also causes a transformation of the hydrophobic polymer surface to hydrophilic, thus enabling uniform wetting and improved adsorption of the chitosan coating. The wettability was measured by the sessile-drop method, while the surface composition and structure were measured by X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy. Non-treated samples did not exhibit successful chitosan immobilization. The effect of plasma treatment on immobilization was explained by noncovalent interactions such as electrostatic interactions and hydrogen bonds.
Design, Synthesis and Antimicrobial Properties of New Tetracyclic Quinobenzothiazine Derivatives
Authors: Kisiel-Nawrot Ewa , Pindjakova Dominika , Latocha Malgorzata , Bak Andrzej , Kozik Violetta , Suwinska Kinga , Sochanik Aleksander , Cizek Alois , Jampilek Josef , Zięba Andrzej
Published: December 2022

A new method for modifying the structure of tetracyclic quinobenzothiazinium derivatives has been developed, allowing introduction of various substituents at different positions of the benzene ring. The method consists of reacting appropriate aniline derivatives with 5,12-(dimethyl)thioquinantrenediinium bis-chloride. A series of new quinobenzothiazine derivatives was obtained with propyl, allyl, propargyl and benzyl substituents in 9, 10 and 11 positions, respectively. The structure of the obtained compounds was analyzed by 1H and 13C NMR (HSQC, HMBC) and X-ray analysis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212, and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). In addition, all the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. 9-Benzyloxy-5-methyl-12H-quino [3,4-b][1,4]benzothiazinium chloride (6j), 9-propoxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6a) and 9-allyloxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6d) demonstrated high activity against the entire tested microbial spectrum. The activities of the compounds were comparable with oxacillin, tetracycline and ciprofloxacinagainst staphylococcal strains and with rifampicin against both mycobacterial strains. Compound 6j had a significant effect on the inhibition of bacterial respiration as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity, but also bactericidal activity. Preliminary in vitro cytotoxicity screening of the compounds performed using normal human dermal fibroblasts (NHDF) proved that the tested compounds showed an insignificant cytotoxic effect on human cells (IC50 > 37 µM), making these compounds interesting for further investigation. Moreover, the intermolecular similarity of novel compounds was analyzed in the multidimensional space (mDS) of the structure/property-related in silico descriptors by means of principal component analysis (PCA) and hierarchical clustering analysis (HCA), respectively. The distance-oriented structure/property distribution was related with the experimental lipophilic data.
Cyclic Dimers of 4-n-Propyloxybenzoic Acid with Hydrogen Bonds in the Gaseous State
Authors: Giricheva Nina I. , Bubnova Ksenia E. , Krasnov Alexander V. , Girichev Georgiy V.
Published: December 2022

A comprehensive study of saturated vapors of 4-n-propyloxybenzoic acid (POBA) by gas electron diffraction (GED) and mass spectrometric (MS) methods supplemented by quantum chemical (QC) calculations was carried out for the first time. An attempt was made to detect dimeric forms of the acid in the gaseous state. It has been established that at the temperature of GED experiment, vapor over a solid sample contains up to 20 mol.% of cyclic dimers with two O-H...O hydrogen bonds. The main geometrical parameters of gaseous monomers and dimers of POBA are obtained. The distance r(O…O) = 2.574(12) Å in the cyclic fragment of the gaseous dimer is close to that in the crystal structure (2.611 Å). In the mass spectrum of the POBA recorded the ions of low intensity with a mass exceeding the molecular mass of the monomer were detected. The presence of ions, whose elemental composition corresponds to the dissociative ionization of the dimer, confirms the results of the GED experiment on the presence of POBA dimers in the gas state. The results of GED studies of acetic acid, benzoic acid, and POBA were compared. It is shown that the COOH fragment saves its geometric structure in monomers, as well as the COOH...HOOC fragment with two hydrogen bonds in dimers of different acids. The intermolecular interaction energy in considered acid dimers was estimated using QC calculations (B97D/6-311++G **). The significant value of last (>84 kJ/mol) is the reason for the noticeable presence of dimers in the gas phase.
Paternal Nicotine/Ethanol/Caffeine Mixed Exposure Induces Offspring Rat Dysplasia and Its Potential “GC-IGF1” Programming Mechanism
Authors: Liu Yi , Zhang Cong , Liu Yi , Zhu Jiayong , Qu Hui , Zhou Siqi , Chen Ming , Xu Dan , Chen Liaobin , Wang Hui
Published: December 2022

Clinical and animal studies suggest that paternal exposure to adverse environments (bad living habits and chronic stress, etc.) has profound impacts on offspring development; however, the mechanism of paternal disease has not been clarified. In this study, a meta-analysis was first performed to suggest that paternal exposure to nicotine, ethanol, or caffeine is a high-risk factor for adverse pregnancy outcomes. Next, we created a rat model of paternal nicotine/ethanol/caffeine mixed exposure (PME), whereby male Wistar rats were exposed to nicotine (0.1 mg/kg/d), ethanol (0.5 g/kg/d), and caffeine (7.5 mg/kg/d) for 8 weeks continuously, then mated with normal female rats to obtain a fetus (n = 12 for control group, n = 10 for PME group). Then, we analyzed the changes in paternal hypothalamic–pituitary–adrenal (HPA) axis activity, testicular function, pregnancy outcomes, fetal serum metabolic indicators, and multiple organ functions to explore the mechanism from the perspective of chronic stress. Our results demonstrated that PME led to enhanced paternal HPA axis activity, decreased sperm quality, and adverse pregnancy outcomes (stillbirth and absorption, decreased fetal weight and body length, and intrauterine growth retardation), abnormal fetal serum metabolic indicators (corticosterone, glucolipid metabolism, and sex hormones), and fetal multi-organ dysfunction (including hippocampus, adrenal, liver, ossification, and gonads). Furthermore, correlation analysis showed that the increased paternal corticosterone level was closely related to decreased sperm quality, adverse pregnancy outcomes, and abnormal offspring multi-organ function development. Among them, the decreased activity of the glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis may be the main mechanism of offspring development and multi-organ dysfunction caused by PME. This study explored the impact of common paternal lifestyle in daily life on offspring development, and proposed the GC-IGF1 programming mechanisms of paternal chronic stress-induced offspring dysplasia, which provides a novel insight for exploring the important role of paternal chronic stress in offspring development and guiding a healthy lifestyle for men.
MgADP Promotes Myosin Head Movement toward Actin at Low [Ca2+] to Increase Force Production and Ca2+-Sensitivity of Contraction in Permeabilized Porcine Myocardial Strips
Authors: Awinda Peter O. , Ma Weikang , Turner Kyrah L. , Zhao Jing , Gong Henry , Thompson Mindy S. , Campbell Kenneth S. , Irving Thomas C. , Tanner Bertrand C. W.
Published: December 2022

Myosin cross-bridges dissociate from actin following Mg2+-adenosine triphosphate (MgATP) binding. Myosin hydrolyses MgATP into inorganic phosphate (Pi) and Mg2+-adenosine diphosphate (ADP), and release of these hydrolysis products drives chemo-mechanical energy transitions within the cross-bridge cycle to power muscle contraction. Some forms of heart disease are associated with metabolic or enzymatic dysregulation of the MgATP-MgADP nucleotide pool, resulting in elevated cytosolic [MgADP] and impaired muscle relaxation. We investigated the mechanical and structural effects of increasing [MgADP] in permeabilized myocardial strips from porcine left ventricle samples. Sarcomere length was set to 2.0 µm at 28 °C, and all solutions contained 3% dextran T-500 to compress myofilament lattice spacing to near-physiological values. Under relaxing low [Ca2+] conditions (pCa 8.0, where pCa = −log10[Ca2+]), tension increased as [MgADP] increased from 0-5 mM. Complementary small-angle X-ray diffraction measurements show that the equatorial intensity ratio, I1,1/I1,0, also increased as [MgADP] increased from 0 to 5 mM, indicating myosin head movement away from the thick-filament backbone towards the thin-filament. Ca2+-activated force-pCa measurements show that Ca2+-sensitivity of contraction increased with 5 mM MgADP, compared to 0 mM MgADP. These data show that MgADP augments tension at low [Ca2+] and Ca2+-sensitivity of contraction, suggesting that MgADP destabilizes the quasi-helically ordered myosin OFF state, thereby shifting the cross-bridge population towards the disordered myosin ON state. Together, these results indicate that MgADP enhances the probability of cross-bridge binding to actin due to enhancement of both thick and thin filament-based activation mechanisms.
Two-Component Systems of Streptomyces coelicolor: An Intricate Network to Be Unraveled
Authors: Sánchez de la Nieta Ricardo , Santamaría Ramón I. , Díaz Margarita
Published: December 2022

Bacteria of the Streptomyces genus constitute an authentic biotech gold mine thanks to their ability to produce a myriad of compounds and enzymes of great interest at various clinical, agricultural, and industrial levels. Understanding the physiology of these organisms and revealing their regulatory mechanisms is essential for their manipulation and application. Two-component systems (TCSs) constitute the predominant signal transduction mechanism in prokaryotes, and can detect a multitude of external and internal stimuli and trigger the appropriate cellular responses for adapting to diverse environmental conditions. These global regulatory systems usually coordinate various biological processes for the maintenance of homeostasis and proper cell function. Here, we review the multiple TCSs described and characterized in Streptomyces coelicolor, one of the most studied and important model species within this bacterial group. TCSs are involved in all cellular processes; hence, unravelling the complex regulatory network they form is essential for their potential biotechnological application.
Offsite Construction Methods—What We Learned from the UK Housing Sector
Authors: Ofori-Kuragu Joseph Kwame , Osei-Kyei Robert , Wanigarathna Nadeeshani
Published: December 2022

Offsite construction has become popular in recent times due to the numerous benefits it offers compared to traditional construction methods. This paper explores the different offsite construction methods, the motivations for adopting these approaches, and the cost-effectiveness of these methods in the UK housing sector using multiple case studies. Firstly, the literature and data were obtained from various sources including professional body reports, industry reports, government websites, and journal articles. Following the review, twelve completed housing projects from the UK which used offsite construction approaches were analyzed. The review of these projects showed that different offsite methods were used in these projects. These include Structural Insulated Panels (SIPs), Timber Frames, Precast Concrete, Steel Frames, Volumetric Construction, Gyproc Habito Plasterboards, and Light Gauge Steel (LGS) technology. The key motivations for adopting offsite construction in these projects include the speed of construction, durability of the products, aesthetic considerations, thermal quality, low air leakage requirements, and quality of construction. Of the 12 cases, only two recorded a higher cost for the offsite construction method compared with the alternative using traditional approaches. The outputs of this paper provide evidence-based strategies which would inform practitioners on the best practices for adopting offsite construction methods and what to expect.