bluuebunny/crossref_metadata_2025 huggingface dataset:
ADH1B, ADH1B/C and CYP2E1 Gene Polymorphism and the Risk of Fetal Alcohol Spectrum Disorder
Authors: Kukowka Arnold , Brzuchalski Bogusław , Kurzawski Mateusz , Malinowski Damian , Białecka Monika Anna
Published: July 2023

Increasing alcohol consumption by women of childbearing age contributes to more frequent cases of fetal alcohol spectrum disorder. The cause of the syndrome is fetal alcohol exposure, particularly what is referred to as high prenatal alcohol exposure. Low metabolic activity of fetal enzymes shifts the burden of ethanol removal to maternal metabolism. One of the factors influencing the pathogenesis of FASD is the genetic background. It can determine the rate of elimination of ethanol, thus increasing or decreasing the time of fetal exposure to ethanol and also decreasing its concentration. Genetic polymorphisms could potentially play a significant role in these processes. In the present study, we considered three polymorphisms of genes implicated in the synthesis of enzymes involved in ethanol metabolism, i.e., ADH1b (rs1229984), ADH1b/c (rs1789891), and CYP2E1 (rs3813867). The studied group consisted of 303 children and 251 mothers. Both mothers’ and children’s genotypes were considered in our analysis. There were no statistically significant differences between the respective groups of genotypes of the studied polymorphisms. However, the genetic background of FASD is still elusive.
Racial/Ethnic Patterns in Opioid Dispensing among Medicaid-Funded Young Children
Authors: Sivaraj Laksika B. , Truong Khoa , Basco William T.
Published: July 2023

Racial differences in opioid dispensing for diseases of the respiratory system (RESP) and injury (INJURY) outpatient visits among patients ≤ 3 years old were examined. Outpatient claims data of South Carolina Medicaid children were analyzed over three three-year periods. The variable of interest was the triennial rate of dispensed opioid prescriptions per 1000 visits for RESP and INJURY diagnoses across racial/ethnic groups. Overall, dispensed opioid prescription rates related to RESP declined for all racial/ethnic categories. White children had the highest dispensing rate for RESP indications in the first period (5.6), followed by Black (4.5), and Hispanic (4.1). The likelihood of White children being prescribed opioids was higher than Blacks, and this was persistent over the studied time (rate ratios from 1.24 to 1.22, respectively). Overall opioid dispensing rates related to injury declined during the studied time. Hispanics had the highest dispensing rate for INJURY (20.1 to 14.8 to 16.1, respectively) followed by White (16.1 to 13.1 to 10.4, respectively). Relative differences in the dispensing rates across groups increased over time (Hispanics vs. White: rate ratios from 1.25 to 1.55, Hispanics vs. Black: from 1.52 to 2.24, and White vs. Black: from 1.24 to 1.44, respectively). There are considerable differences in the dispensing rates across racial/ethnic groups, especially in injury-related prescribing.
Effects of Different Culture Times Genes Expression on Ginsenoside Biosynthesis of the Ginseng Adventitious Roots in Panax ginseng
Authors: Chen Hong , Li Xiangzhu , Zheng Yongjun , Liu Mingming , Wang Kangyu
Published: July 2023

Panax ginseng is an ancient and very potent herb, which has a long history of medicinal use, and recent studies have shown that ginsenosides are the main active substances in its pharmacological effects. However, the saponin content of wild ginseng and cultivated ginseng can hardly meet the market supply, and the ginseng adventitious root suspension culture technology can produce ginsenosides in a targeted manner. The length of culture time is an important factor affecting the growth and development of plants and the accumulation of secondary metabolites. After transcriptome sequencing of ginseng adventitious root material at different culture times, the results showed that a total of 5784 differentially expressed genes were screened, which contained 239 transcription factors. KEGG analysis showed that these differentially expressed genes were mainly enriched in metabolic pathways and biosynthesis of secondary metabolites. A proposed temporal analysis of differentially expressed genes among the two groups distributed the differentially expressed genes under nine clusters, and the differentially expressed genes under different clusters had the same expression trends, indicating that these genes can be jointly involved in specific biological processes. Extraction of ginsenosides from ginseng adventitious roots using water-saturated n-butanol and detection of ginsenoside content by high-performance liquid chromatography revealed a significant increase in total saponins and protopanaxadiol ginsenosides (particularly significant for ginsenosides Rd and Rb1), an increase in bioaccumulation of some protopanaxatriol ginsenosides, and a decrease in some protopanaxatriol ginsenosides (S-Rh1, R-Rg3, and Rf) saponin content decreased. We also found seven genes involved in ginsenoside biosynthesis and that the changes in these genes’ expression may be related to the accumulation of ginsenosides.
Correction: Mahmood et al. Aging in the Right Place for Older Adults Experiencing Housing Insecurity: An Environmental Assessment of Temporary Housing Program. Int. J. Environ. Res. Public Health 2022, 19, 14857
Authors: Mahmood Atiya , Patille Rachelle , Lam Emily , Mora Diana Juanita , Gurung Shreemouna , Bookmyer Gracen , Weldrick Rachel , Chaudhury Habib , Canham Sarah L.
Published: July 2023

Table Correction [...]
Long-Term Impacts of the COVID-19 Pandemic on Drug/Alcohol Use Prevalence in a Population with Substance Use Disorders
Authors: Gili Alessio , Lancia Massimo , Gambelunghe Angela , Tomassini Luca , Nicoletti Alessia , Aroni Kyriaki , Gambelunghe Cristiana
Published: July 2023

As time passes, the long-term effects of the COVID-19 pandemic are becoming increasingly apparent. The extreme restrictions imposed during the pandemic have had detrimental impacts on the most vulnerable groups, such as individuals suffering from substance and/or alcohol disorders (SUDs). This study reports quarterly laboratory data on alcohol and drug use in 150 subjects with SUDs that were examined using hair analysis for 2 years before the start of pandemic until after the end of the Italian health emergency. Overall, it was found that the number of subjects who used heroin, cocaine, and MDMA all decreased during the 2020 and 2021 lockdowns, increasing during reopening and subsequently stabilizing close to pre-COVID levels. Cannabis use was less impacted, remaining stable throughout the pandemic. Alcohol and benzodiazepine use both increased significantly during the lockdowns, displaying an opposing trend. While benzodiazepine use progressively returned to baseline levels, alcohol remained at significantly increased levels, even in September 2022. Long-term heavy drinking combined with substance use should be seriously considered, since these results in several health and social problems alongside alcohol-related comorbidities. Thus, appropriate response plans should be implemented both during and after the pandemic, whilst focusing on those who are most vulnerable.
Exploring New Tools for Risk Classification among Adults with Several Degrees of Obesity
Authors: Westphal-Nardo Greice , Chaput Jean-Philippe , Faúndez-Casanova César , Fernandes Carlos Alexandre Molena , de Andrade Gonçalves Eliane Cristina , Utrila Raquel Tomiazzi , Oltramari Karine , Grizzo Felipe Merchan Ferraz , Nardo-Junior Nelson
Published: July 2023

The epidemic of obesity worldwide has been recognized as a very important challenge. Within its complexity, the identification of higher-risk patients is essential, as it is unsustainable to offer access to treatment to all people with obesity. Several new approaches have recently been presented as important tools for risk stratification. In this research, we applied several of these tools in a cross-sectional study involving adults with obesity classes I, II, III, and super-obesity. The participants had their cardiometabolic risk profiles assessed. The study included adults with obesity aged 18 to 50 years (n = 404), who were evaluated using anthropometric, body composition, hemodynamic, physical fitness, and biochemical assessments. These variables were used to identify the prevalence of risk factors for cardiometabolic diseases according to the classes of obesity by gender and age group. The results showed high prevalence of risk factors, especially among the upper classes of obesity (BMI > 35 kg/m2) using single parameters as the waist circumference, with almost 90% above the cut-off point. For smaller numbers such as Glycated Hemoglobin, however, the prevalence was around 30%. Indexes such as the atherogenic index of plasma (AIP) had the highest prevalence, with 100% of the male participants identified as being at increased risk for cardiovascular disease.
A Spatio-Temporal Analysis of OECD Member Countries’ Health Care Systems: Effects of Data Missingness and Geographically and Temporally Weighted Regression on Inference
Authors: Akioyamen Peter , Begen Mehmet A.
Published: July 2023

Determinants of health care quality and efficiency are of importance to researchers, policy-makers, and public health officials as they allow for improved human capital and resource allocation as well as long-term fiscal planning. Statistical analyses used to understand determinants have neglected to explicitly discuss how missing data are handled, and consequently, previous research has been limited in inferential capability. We study OECD health care data and highlight the importance of transparency in the assumptions grounding the treatment of data missingness. Attention is drawn to the variation in ordinary least squares coefficient estimates and performance resulting from different imputation methods, and how this variation can undermine statistical inference. We also suggest that parametric regression models used previously are limited and potentially ill-suited for analysis of OECD data due to the inability to deal with both spatial and temporal autocorrelation. We propose the use of an alternative method in geographically and temporally weighted regression. A spatio-temporal analysis of health care system efficiency and quality of care across OECD member countries is performed using four proxy variables. Through a forward selection procedure, medical imaging equipment in a country is identified as a key determinant of quality of care and health outcomes, while government and compulsory health insurance expenditure per capita is identified as a key determinant of health care system efficiency.
A RE-AIM Analysis of a Mental Health App for Undergraduate and Medical Students during the COVID-19 Pandemic: A Retrospective Cross-Sectional Study
Authors: Berreta Krisdaniel , Nguyen Cynthia , Stoner Alexis M. , Ridgeway Lindsey , Wilson Angela , Fadel Natalie , Biber Duke
Published: July 2023

Objective: The purpose of this study was to use the RE-AIM framework to evaluate the implementation of a mental health app designed for undergraduate and medical students during the COVID-19 pandemic. Participants: Medical (n = 270) and undergraduate students (n = 1386) from five universities in the Appalachian region in the United States participated in this study. Methods: Universities from the United States were recruited to deploy the Sharpen app for medical and undergraduate students. The Sharpen app provided psychoeducational modules in mental health literacy, social-emotional learning, mindfulness-based stress reduction, and suicide prevention to promote protective factors for students. The utilization of the Sharpen app was analyzed using the RE-AIM framework using a retrospective, cross-sectional design. Results: Reach: A total of 12.72% of medical students and 6.00% of undergraduate students participated in the study. Efficacy: Medical students viewed significantly more pages, had a significantly higher unique page view average, and a statistically significant exit percentage when compared to undergraduate students. Adoption: A total of 100% of the universities that were recruited participated in the study. Implementation: Five out of six implementation criteria were included, indicating high implementation. Maintenance: All of the universities continued using the Sharpen app following the end of data collection, resulting in a 100% maintenance rate. Conclusions: The RE-AIM framework indicated usability and maintenance by medical and undergraduate students. Future research needs to implement a more rigorous design to determine the impact of the Sharpen app on mental health outcomes in medical and undergraduate students.
Educational Concepts of Digital Competence Development for Older Adults—A Scoping Review
Authors: Schirmer Marielle , Dalko Katharina , Stoevesandt Dietrich , Paulicke Denny , Jahn Patrick
Published: July 2023

The digital transformation of healthcare and nursing is becoming increasingly important due to demographic change and the growing shortage of skilled workers. In order to ensure the participation of senior citizens in digital assistive technologies, educational concepts and support services are needed to promote digital skills in older adults. Therefore, the specific needs and prerequisites of this target group have to be taken into consideration. This paper asks how educational programs for the support of digital competences of older adults are designed and implemented. A scoping review was conducted to systematically extract existing findings from the literature. Four databases (Cinahl, PubMed, Web of Science Social Sciences Citation Index (SSCI), ERIC) were searched using an exploratory strategy to identify studies that address educational concepts promoting digital competences for older adults. A total of 47 publications were included in the qualitative analysis and show a variety of strategies to deal with the promotion of digital competences for elderly people. In conclusion, programs dealing with the promotion of digital competences for elderly people should be flexibly adapted to the target group with its specific needs and challenges such as fears, lack of previous experience, or physical limitations. For successful implementation, social support is of outstanding importance.
Expectancy-Value Motivation and Physical Activity- and Health-Related Outcomes among At-Risk Children and Adolescents
Authors: Liu Jiling , Xiang Ping
Published: July 2023

Despite a large amount of research having been done to examine and promote physical activity and health among adolescents and children, relatively little attention has been paid attention to underrepresented populations. In this study, we investigated the relationships between expectancy-value motivation and physical activity- and health-related outcomes among a group of at-risk boys at a summer sports camp. The total participants included 107 boys (Mage = 11.78 years, SD = 1.20). The boys’ perceived expectancy beliefs (EXP), importance (IMP), interest (INT), usefulness (USE), effort (EFT), and intention for future participation (IFP) were assessed using established questions on a five-point Likert scale, and a PACER test was performed to estimate their cardiovascular fitness (CVF). Through a path analysis, we found that EXP positively predicted CVF (β = 0.19, p < 0.01), IMP positively predicted EFT (β = 0.26, p < 0.01), and INT positively predicted both EFT (β = 0.34, p < 0.01) and IFP (β = 0.28, p < 0.01), while USE had no statistically significant effect on either EFT, IFP, or CVF. We discussed the limitations and implications of the present study. We recommend including a diverse sample and employing the expectancy-value model in future research, and advocating expectancy beliefs and task values, especially importance and interest, among participants during physical activity promotion.
Emotional Regulation and Adolescent Concussion: Overview and Role of Neuroimaging
Authors: Lima Santos João Paulo , Jia-Richards Meilin , Kontos Anthony P. , Collins Michael W. , Versace Amelia
Published: July 2023

Emotional dysregulation symptoms following a concussion are associated with an increased risk for emotional dysregulation disorders (e.g., depression and anxiety), especially in adolescents. However, predicting the emergence or worsening of emotional dysregulation symptoms after concussion and the extent to which this predates the onset of subsequent psychiatric morbidity after injury remains challenging. Although advanced neuroimaging techniques, such as functional magnetic resonance imaging and diffusion magnetic resonance imaging, have been used to detect and monitor concussion-related brain abnormalities in research settings, their clinical utility remains limited. In this narrative review, we have performed a comprehensive search of the available literature regarding emotional regulation, adolescent concussion, and advanced neuroimaging techniques in electronic databases (PubMed, Scopus, and Google Scholar). We highlight clinical evidence showing the heightened susceptibility of adolescents to experiencing emotional dysregulation symptoms following a concussion. Furthermore, we describe and provide empirical support for widely used magnetic resonance imaging modalities (i.e., functional and diffusion imaging), which are utilized to detect abnormalities in circuits responsible for emotional regulation. Additionally, we assess how these abnormalities relate to the emotional dysregulation symptoms often reported by adolescents post-injury. Yet, it remains to be determined if a progression of concussion-related abnormalities exists, especially in brain regions that undergo significant developmental changes during adolescence. We conclude that neuroimaging techniques hold potential as clinically useful tools for predicting and, ultimately, monitoring the treatment response to emotional dysregulation in adolescents following a concussion.
Determinants of Care Pathways for C-PTSD Patients in French Psychotrauma Centers: A Qualitative Study
Authors: Salome Germain , Vignaud Philippe , Galia Perrine , Prieto Nathalie , Chauliac Nicolas
Published: July 2023

In 2018, the International Classification of Diseases (ICD-11) established a novel nosographic category within the stress-specific disorders known as complex post-traumatic stress disorder (C-PTSD). Characterized by distinctive clinical attributes and a limited response to conventional PTSD treatments, C-PTSD has prompted the reconsideration of care methods. Our study’s purpose was to explore the intricate factors shaping the care pathways for individuals suffering from C-PTSD. We used a grounded theorization technique involving professionals across a range of specialized French psychotraumatology institutions. The resulting comprehensive theoretical model offers valuable insights into the constitution mechanisms of these pathways, helping elucidate the varying care options. Interestingly, we found that differences in clinical perspectives were determined by the care provider’s viewpoint on clinical guidelines, screening tools, and treatment options, but also by structural and organizational factors. The distinctive dynamics and interrelationships identified in our research reveal potential areas of focus for incorporating C-PTSD care more effectively into specialized French trauma centers. This investigation offers a path toward improved understanding and management of C-PTSD, ultimately advancing patient outcomes.
Short-Term Effects of Climate Variability on Childhood Diarrhoea in Bangladesh: Multi-Site Time-Series Regression Analysis
Authors: Rahaman Md Rezanur , Dear Keith , Satter Syed M. , Tong Michael , Milazzo Adriana , Marshall Helen , Varghese Blesson M. , Rahman Mahmudur , Bi Peng
Published: July 2023

The aim of this study was to estimate the effects of climate on childhood diarrhoea hospitalisations across six administrative divisions in Bangladesh and to provide scientific evidence for local health authorities for disease control and prevention. Fortnightly hospital admissions (August/2013–June/2017) for diarrhoea in children under five years of age, and fortnightly average maximum temperature, relative humidity and rainfall recordings for six administrative divisions were modelled using negative binomial regression with distributed lag linear terms. Flexible spline functions were used to adjust models for seasonality and long-term trends. During the study period, 25,385 diarrhoea cases were hospitalised. Overall, each 1 °C rise in maximum temperature increased diarrhoea hospitalisations by 4.6% (IRR = 1.046; 95% CI, 1.007–1.088) after adjusting for seasonality and long-term trends in the unlagged model. Using lagged effects of maximum temperature, and adjusting for relative humidity and rainfall for each of the six administrative divisions, the relationship between maximum temperature and diarrhoea hospitalisations varied between divisions, with positive and negative effect estimates. The temperature-diarrhoea association may be confounded by seasonality and long-term trends. Our findings are a reminder that the effects of climate change may be heterogeneous across regions, and that tailored diarrhoea prevention strategies need to consider region-specific recommendations rather than relying on generic guidelines.
A Systematic Review of Qualitative Research Literature and a Thematic Synthesis of Older LGBTQ People’s Experiences of Quality of Life, Minority Joy, Resilience, Minority Stress, Discrimination, and Stigmatization in Japan and Sweden
Authors: Bratt Anna Sofia , Hjelm Ann-Christine Petersson , Wurm Matilda , Huntley Richard , Hirakawa Yoshihisa , Muraya Tsukasa
Published: July 2023

There is a lack of research on older lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) adults. This systematic review aimed to synthesize Japanese and Swedish qualitative research on LGBTQ adults aged 60 years or older following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Japanese and Swedish articles, published in English, were searched across ASSIA, CINAHL, Medline, PsychINFO, PubMed, Scopus, and Sociological Abstracts databases. Additional searches were conducted to include studies in Japanese or Swedish. There were no papers from Japan, whereas five from Sweden were reviewed. One article was excluded due to the wrong phenomenon. Four articles were included, involving 48 participants aged 60–94 years. We summarized the findings using a deductive thematic synthesis. Two major themes emerged: (a) quality of life, minority joy, and resilience (positive aspects), and (b) discrimination, stigmatization, and minority stress (negative aspects). The participants wished to be acknowledged for their own assets and unique life histories, and to be treated as everyone else. They emphasized the importance of knowledge of LGBTQ issues among nursing staff, so that older LGBTQ people are treated in a competent and affirmative way. The study revealed several important topics for understanding older LGBTQ adults’ life circumstances and the severe lack of qualitative studies in Japan and Sweden.
Air Pollution Health Literacy among Active Commuters in Hamilton, Ontario
Authors: Ciarloni Reed , Newbold K. Bruce
Published: July 2023

The promotion of active transportation (AT), which has been broadly defined as a physical effort performed by the traveller to produce motion, has been a popular strategy to reduce vehicular emissions, improve air quality, and promote physical activity. However, individuals who engage in AT may incur increased exposure to air pollutants and thus potential health impacts. This research sought to determine how active commuters understand the health risks associated with air pollution during their commutes, and whether they engage in any behaviours to limit exposure. An online survey was adapted from the Environmental Health Literacy framework to assess air pollution health literacy among active commuters in Hamilton, ON, and generated a sample size of 192 AT users. Analyses involved the use of frequency tables and cross-tabulations for the quantitative data, and the Health Belief Model and thematic analysis to interpret the qualitative data. Results revealed that most AT users do not adopt behaviours that would limit air pollution exposure on commutes and exhibited low self-rated knowledge of the health impacts of air pollution exposure. Issues of perceived susceptibility and severity, barriers, cues to action, and self-efficacy all further impacted the likelihood of adopting health protective behaviours. Conclusively, air pollution is an often-neglected consideration among active commuters, with air pollution knowledge predicting the likelihood of behavioural modification.
Transcriptome Metabolic Characterization of Tuber borchii SP1—A New Spanish Strain for In Vitro Studies of the Bianchetto Truffle
Authors: Tomazeli Emilia Chuina , Alfaro Manuel , Zambonelli Alessandra , Garde Edurne , Pérez Gumer , Jiménez Idoia , Ramírez Lucía , Salman Hesham , Pisabarro Antonio G.
Published: July 2023

Truffles are ascomycete hypogeous fungi belonging to the Tuberaceae family of the Pezizales order that grow in ectomycorrhizal symbiosis with tree roots, and they are known for their peculiar aromas and flavors. The axenic culture of truffle mycelium is problematic because it is not possible in many cases, and the growth rate is meager when it is possible. This limitation has prompted searching and characterizing new strains that can be handled in laboratory conditions for basic and applied studies. In this work, a new strain of Tuber borchii (strain SP1) was isolated and cultured, and its transcriptome was analyzed under different in vitro culture conditions. The results showed that the highest growth of T. borchii SP1 was obtained using maltose-enriched cultures made with soft-agar and in static submerged cultures made at 22 °C. We analyzed the transcriptome of this strain cultured in different media to establish a framework for future comparative studies, paying particular attention to the central metabolic pathways, principal secondary metabolite gene clusters, and the genes involved in producing volatile aromatic compounds (VOCs). The results showed a transcription signal for around 80% of the annotated genes. In contrast, most of the transcription effort was concentrated on a limited number of genes (20% of genes account for 80% of the transcription), and the transcription profile of the central metabolism genes was similar in the different conditions analyzed. The gene expression profile suggests that T. borchii uses fermentative rather than respiratory metabolism in these cultures, even in aerobic conditions. Finally, there was a reduced expression of genes belonging to secondary metabolite clusters, whereas there was a significative transcription of those involved in producing volatile aromatic compounds.
Cryopreservation Induces Acetylation of Metabolism-Related Proteins in Boar Sperm
Authors: Ali Malik Ahsan , Qin Ziyue , Dou Shan , Huang Anqi , Wang Yihan , Yuan Xiang , Zhang Yan , Ni Qingyong , Azmat Rameesha , Zeng Changjun
Published: July 2023

Cryodamage affects the normal physiological functions and survivability of boar sperm during cryopreservation. Lysine acetylation is thought to be an important regulatory mechanism in sperm functions. However, little is known about protein acetylation and its effects on cryotolerance or cryodamage in boar sperm. In this study, the characterization and protein acetylation dynamics of boar sperm during cryopreservation were determined using liquid chromatography–mass spectrometry (LC-MS). A total of 1440 proteins were identified out of 4705 modified proteins, and 2764 quantifiable sites were elucidated. Among the differentially modified sites, 1252 were found to be upregulated compared to 172 downregulated sites in fresh and frozen sperms. Gene ontology indicated that these differentially modified proteins are involved in metabolic processes and catalytic and antioxidant activities, which are involved in pyruvate metabolism, phosphorylation and lysine degradation. In addition, the present study demonstrated that the mRNA and protein expressions of SIRT5, IDH2, MDH2 and LDHC, associated with sperm quality parameters, are downregulated after cryopreservation. In conclusion, cryopreservation induces the acetylation and deacetylation of energy metabolism-related proteins, which may contribute to the post-thawed boar sperm quality parameters.
Exploring the Interplay between Polyphenols and Lysyl Oxidase Enzymes for Maintaining Extracellular Matrix Homeostasis
Authors: Añazco Carolina , Riedelsberger Janin , Vega-Montoto Lorenzo , Rojas Armando
Published: July 2023

Collagen, the most abundant structural protein found in mammals, plays a vital role as a constituent of the extracellular matrix (ECM) that surrounds cells. Collagen fibrils are strengthened through the formation of covalent cross-links, which involve complex enzymatic and non-enzymatic reactions. Lysyl oxidase (LOX) is responsible for catalyzing the oxidative deamination of lysine and hydroxylysine residues, resulting in the production of aldehydes, allysine, and hydroxyallysine. These intermediates undergo spontaneous condensation reactions, leading to the formation of immature cross-links, which are the initial step in the development of mature covalent cross-links. Additionally, non-enzymatic glycation contributes to the formation of abnormal cross-linking in collagen fibrils. During glycation, specific lysine and arginine residues in collagen are modified by reducing sugars, leading to the creation of Advanced Glycation End-products (AGEs). These AGEs have been associated with changes in the mechanical properties of collagen fibers. Interestingly, various studies have reported that plant polyphenols possess amine oxidase-like activity and can act as potent inhibitors of protein glycation. This review article focuses on compiling the literature describing polyphenols with amine oxidase-like activity and antiglycation properties. Specifically, we explore the molecular mechanisms by which specific flavonoids impact or protect the normal collagen cross-linking process. Furthermore, we discuss how these dual activities can be harnessed to generate properly cross-linked collagen molecules, thereby promoting the stabilization of highly organized collagen fibrils.
Of the Mechanisms of Paroxysmal Depolarization Shifts: Generation and Maintenance of Bicuculline-Induced Paroxysmal Activity in Rat Hippocampal Cell Cultures
Authors: Laryushkin Denis P. , Maiorov Sergei A. , Zinchenko Valery P. , Mal’tseva Valentina N. , Gaidin Sergei G. , Kosenkov Artem M.
Published: July 2023

Abnormal depolarization of neuronal membranes called paroxysmal depolarization shift (PDS) represents a cellular correlate of interictal spikes. The mechanisms underlying the generation of PDSs or PDS clusters remain obscure. This study aimed to investigate the role of ionotropic glutamate receptors (iGluRs) in the generation of PDS and dependence of the PDS pattern on neuronal membrane potential. We have shown that significant depolarization or hyperpolarization (by more than ±50 mV) of a single neuron does not change the number of individual PDSs in the cluster, indicating the involvement of an external stimulus in PDS induction. Based on this data, we have suggested reliable protocols for stimulating single PDS or PDS clusters. Furthermore, we have found that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors are necessary for PDS generation since AMPAR antagonist NBQX completely suppresses bicuculline-induced paroxysmal activity. In turn, antagonists of NMDA (N-methyl-D-aspartate) and kainate receptors (D-AP5 and UBP310, respectively) caused a decrease in the amplitude of the first action potential in PDSs and in the amplitude of the oscillations of intracellular Ca2+ concentration occurring alongside the PDS cluster generation. The effects of the NMDAR (NMDA receptor) and KAR (kainate receptor) antagonists indicate that these receptors are involved only in the modulation of paroxysmal activity. We have also shown that agonists of some Gi-coupled receptors, such as A1 adenosine (A1Rs) or cannabinoid receptors (CBRs) (N6-cyclohexyladenosine and WIN 55,212-2, respectively), completely suppressed PDS generation, while the A1R agonist even prevented it. We hypothesized that the dynamics of extracellular glutamate concentration govern paroxysmal activity. Fine-tuning of neuronal activity via action on Gi-coupled receptors or iGluRs paves the way for the development of new approaches for epilepsy pharmacotherapy.
The Role of Activating Transcription Factor 3 in Metformin’s Alleviation of Gastrointestinal Injury Induced by Restraint Stress in Mice
Authors: Siwakoti Bijaya , Lien Te-Sheng , Lin You-Yen , Pethaperumal Subhashree , Hung Shih-Che , Sun Der-Shan , Cheng Ching-Feng , Chang Hsin-Hou
Published: July 2023

Metformin is one of the most commonly used drugs for type 2 diabetes mellitus. In addition to its anti-diabetic property, evidence suggests more potential applications for metformin, such as antiaging, cellular protection, and anti-inflammation. Studies have reported that metformin activates pathways with anti-inflammatory effects, enhances the integrity of gut epithelial tight junctions, and promotes a healthy gut microbiome. These actions contribute to the protective effect of metformin against gastrointestinal (GI) tract injury. However, whether metformin plays a protective role in psychological-stress-associated GI tract injury remains elusive. We aim to elucidate the potential protective effect of metformin on the GI system and develop an effective intervention strategy to counteract GI injury induced by acute psychological stress. By monitoring the levels of GI-nonabsorbable Evans blue dye in the bloodstream, we assessed the progression of GI injury in live mice. Our findings demonstrate that the administration of metformin effectively mitigated GI leakage caused by psychological stress. The GI protective effect of metformin is more potent when used on wild-type mice than on activating-transcription-factor 3 (ATF3)-deficient (ATF3−/−) mice. As such, metformin-mediated rescue was conducted in an ATF3-dependent manner. In addition, metformin-mediated protection is associated with the induction of stress-induced GI mRNA expressions of the stress-induced genes ATF3 and AMP-activated protein kinase. Furthermore, metformin treatment-mediated protection of CD326+ GI epithelial cells against stress-induced apoptotic cell death was observed in wild-type but not in ATF3−/− mice. These results suggest that metformin plays a protective role in stress-induced GI injury and that ATF3 is an essential regulator for metformin-mediated rescue of stress-induced GI tract injury.
Nitisinone Treatment Affects Biomarkers of Bone and Cartilage Remodelling in Alkaptonuria Patients
Authors: Genovese Federica , Frederiksen Peder , Bay-Jensen Anne-Christine , Karsdal Morten A. , Milan Anna M. , Olsson Birgitta , Rudebeck Mattias , Gallagher James A. , Ranganath Lakshminarayan R.
Published: July 2023

Nitisinone has been approved for treatment of alkaptonuria (AKU). Non-invasive biomarkers of joint tissue remodelling could aid in understanding the molecular changes in AKU pathogenesis and how these can be affected by treatment. Serological and urinary biomarkers of type I collagen and II collagen in AKU were investigated in patients enrolled in the randomized SONIA 2 (NCT01916382) clinical study at baseline and yearly until the end of the study (Year 4). The trajectories of the biomarkers over time were observed. After treatment with nitisinone, the biomarkers of type I collagen remodelling increased at Year 1 (19% and 40% increase in CTX-I and PRO-C1, respectively), which was potentially reflected in the higher degree of mobility seen following treatment. The biomarkers of type II collagen remodelling decreased over time in the nitisinone group: C2M showed a 9.7% decline at Year 1, and levels then remained stable over the following visits; CTX-II showed a 26% decline at Year 3 and 4 in the nitisinone-treated patients. Nitisinone treatment induced changes in biomarkers of bone and cartilage remodelling. These biomarkers can aid patient management and deepen our knowledge of the molecular mechanisms of this rare disease.
Effect of Microplastics on the Activity of Digestive and Oxidative-Stress-Related Enzymes in Peled Whitefish (Coregonus peled Gmelin) Larvae
Authors: Frank Yulia A. , Interesova Elena A. , Solovyev Mikhail M. , Xu Jiayi , Vorobiev Danil S.
Published: July 2023

Microplastics (MPs) are emergent pollutants in freshwater environments and may impact aquatic organisms, including those of nutritional value. The specific activities of digestive and antioxidant enzymes can be used as good bioindicators of the potential effects of MPs on fish in case of waterborne MP contamination. In this study, we used fluorescent polystyrene microplastics (PS-MPs) to analyze the alterations in enzyme activities in larvae of Coregonus peled Gmelin (peled or Northern whitefish), one of the most valuable commercial fish species of Siberia. Our results indicate that peled larvae can ingest 2 µm PS microspheres in a waterborne exposure model. A positive correlation (rs = 0.956; p < 0.01) was found between MP concentration in water and the number of PS microspheres in fish guts, with no significant differences between 24 h and 6-day exposure groups. The ingestion of MPs caused alterations in digestive enzyme activity and antioxidant responses at the whole-body level. The presence of PS-MPs significantly stimulated (p < 0.05) the specific activity of α-Amylase and non-specific esterases in peled larvae after 24 h. However, a pronounced positive effect (p < 0.05) of MPs on the activity of pancreatic trypsine and bile salt-activated lipase was only found after 6 days of exposure compared to after 24 h. Intestinal membrane enzyme aminopeptidase N was also stimulated in the presence of PS-MPs after 6-day exposure. We also observed a significant increase in the specific activity of catalase in peled larvae after 6 days of exposure, which indicates the MP-induced modulation of oxidative stress. Taken together, these results highlight the potential impact of environmental MPs on northern commercial fish, their importance for estimating fish stocks, and the sustainability of freshwater ecosystems.
Maresin: Macrophage Mediator for Resolving Inflammation and Bridging Tissue Regeneration—A System-Based Preclinical Systematic Review
Authors: Liu Wen-Chun , Yang Yu-Hsin , Wang Yu-Chin , Chang Wei-Ming , Wang Chin-Wei
Published: July 2023

Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and potentially serving as a therapeutic agent for chronic inflammatory diseases. The aim of this review was to systematically investigate preclinical and clinical studies on maresin to inform translational research. Two independent reviewers performed comprehensive searches with the term “Maresin (NOT) Review” on PubMed. A total of 137 studies were included and categorized into 11 human organ systems. Data pertinent to clinical translation were specifically extracted, including delivery methods, optimal dose response, and specific functional efficacy. Maresins generally exhibit efficacy in treating inflammatory diseases, attenuating inflammation, protecting organs, and promoting tissue regeneration, mostly in rodent preclinical models. The nervous system has the highest number of original studies (n = 25), followed by the cardiovascular system, digestive system, and respiratory system, each having the second highest number of studies (n = 18) in the field. Most studies considered systemic delivery with an optimal dose response for mouse animal models ranging from 4 to 25 μg/kg or 2 to 200 ng via intraperitoneal or intravenous injection respectively, whereas human in vitro studies ranged between 1 and 10 nM. Although there has been no human interventional clinical trial yet, the levels of MaR1 in human tissue fluid can potentially serve as biomarkers, including salivary samples for predicting the occurrence of cardiovascular diseases and periodontal diseases; plasma and synovial fluid levels of MaR1 can be associated with treatment response and defining pathotypes of rheumatoid arthritis. Maresins exhibit great potency in resolving disease inflammation and bridging tissue regeneration in preclinical models, and future translational development is warranted.
Study of Elastin, Hydrolyzed Collagen and Collagen-like Products in a Tri-Layered Chitosan Membrane to Test Anti-Aging Skin Properties
Authors: Guerle-Cavero Rocío , Balfagón-Costa Albert
Published: July 2023

The use of animal testing in the cosmetic industry is already prohibited in more than 40 countries, including those of the EU. The pressure for it to be banned worldwide in the future is increasing, so the need for animal alternatives is of great interest today. In addition, using animals and humans in scientific research is ethically reprehensible. This study aimed to prove some of the anti-aging properties of elastin (EL), hydrolyzed collagen (HC), and two vegan collagen-like products (Veg Col) in a tri-layered chitosan membrane that was ionically crosslinked with sodium tripolyphosphate (TPP). In the first approach, as a way of representing different layers of a biological system, such as the epidermis and the two dermis sublayers, EL, HC, or Veg Col were independently introduced into the two inner layers (2L(i+b)). Their effects were compared with those of their introduction into three layers (3L). Different experiments were performed on the membrane to test its elasticity, hydration, moisture retention, and pore reduction at different concentrations of EL, HC, and Veg Col, and the results were normalized vs. a blank membrane. This new alternative to animal or human testing can be suitable for proving certain efficacy claims for active ingredients or products in the pharmaceutical, nutritional, and cosmetic fields.
Generation of Synthetic Images of Trabecular Bone Based on Micro-CT Scans
Authors: Grande-Barreto Jonas , Polanco-Castro Eduardo , Peregrina-Barreto Hayde , Rosas-Mialma Eduardo , Puig-Mar Carmina
Published: July 2023

Creating synthetic images of trabecular tissue provides an alternative for researchers to validate algorithms designed to study trabecular bone. Developing synthetic images requires baseline data, such as datasets of digital biological samples or templates, often unavailable due to privacy restrictions. Even when this baseline is available, the standard procedure combines the information to generate a single template as a starting point, reducing the variability in the generated synthetic images. This work proposes a methodology for building synthetic images of trabecular bone structure, creating a 3D network that simulates it. Next, the technical characteristics of the micro-CT scanner, the biomechanical properties of trabecular bones, and the physics of the imaging process to produce a synthetic image are simulated. The proposed methodology does not require biological samples, datasets, or templates to generate synthetic images. Since each synthetic image built is unique, the methodology is enabled to generate a vast number of synthetic images, useful in the performance comparison of algorithms under different imaging conditions. The created synthetic images were assessed using microarchitecture parameters of reference, and experimental results provided evidence that the obtained values match approaches requiring initial data. The scope of this methodology covers research aspects related to using synthetic images in further biomedical research or the development of educational training tools to understand the medical image.
The Adaptive Value of Chromosomal Inversions and Climatic Change—Studies on the Natural Populations of Drosophila subobscura from the Balkans
Authors: Zivanovic Goran , Arenas Concepció , Mestres Francesc
Published: July 2023

The adaptive value of the Drosophila subobscura chromosomal inversion polymorphism with regard to environmental effects is well-known. However, the specific details of the inversion adaptations to the global warming scenario deserve to be analyzed. Toward this aim, polymorphism and karyotypes were studied in 574 individuals from Petnica (Serbia) in annual samples taken in June for the period 2019–2022. Comparing the results of Petnica (Cfa: humid subtropical climate) with those from Avala (Serbia: Cfb, temperate oceanic climate) and Font Groga (Barcelona, Spain; Csa: hot-summer Mediterranean climate), significant differences were observed for their chromosomal polymorphism. In Petnica, inversions from U and E chromosomes mainly reacted significantly with regard to temperature, humidity, and rainfall. Moreover, the inversion polymorphism from Petnica (2019–2022) was compared with that from 1995. In this period, a significant increase in mean and maximum temperature was observed. However, to properly explain the observed variations of inversions over time, it was necessary to carefully analyze annual seasonal changes and particular heat wave episodes. Interestingly, yearly fluctuations of U chromosome ‘warm’-adapted inversions corresponded with opposite changes in ‘non-thermal’ inversions. Perhaps these types of inversions were not correctly defined with regard to thermal adaptation, or these fluctuations were also due to adaptations to other physical and/or biological variables. Finally, a joint study of chromosomal inversion polymorphism from many Balkan populations of D. subobscura indicated that different climatic regions presented distinct composition, including thermal-adapted inversions.
Conferring High IAA Productivity on Low-IAA-Producing Organisms with PonAAS2, an Aromatic Aldehyde Synthase of a Galling Sawfly, and Identification of Its Inhibitor
Authors: Hiura Takeshi , Yoshida Hibiki , Miyata Umi , Asami Tadao , Suzuki Yoshihito
Published: July 2023

Gall-inducing insects often contain high concentrations of phytohormones, such as auxin and cytokinin, which are suggested to be involved in gall induction, but no conclusive evidence has yet been obtained. There are two possible approaches to investigating the importance of phytohormones in gall induction: demonstrating either that high phytohormone productivity can induce gall-inducing ability in non-gall-inducing insects or that the gall-inducing ability is inhibited when phytohormone productivity in galling insects is suppressed. In this study, we show that the overexpression of PonAAS2, which encodes an aromatic aldehyde synthase (AAS) responsible for the rate-limiting step in indoleacetic acid (IAA) biosynthesis in a galling sawfly (Pontania sp.) that contains high levels of endogenous IAA, conferred high IAA productivity on Caenorhabditis elegans, as the model system. This result strongly suggests that PonAAS2 can also confer high IAA productivity on low-IAA-producing insects. We also successfully identified an inhibitor of PonAAS2 in a chemical library. This highly selective inhibitor showed stronger inhibitory activity against AAS than against aromatic amino acid decarboxylase, which belongs to the same superfamily as AAS. We also confirm that this inhibitor clearly inhibited IAA productivity in the high-IAA-producing C. elegans engineered here.
Minimal Access Aortic Valve Surgery
Authors: Kirmani Bilal H. , Akowuah Enoch
Published: July 2023

Minimally invasive approaches to the aortic valve have been described since 1993, with great hopes that they would become universal and facilitate day-case cardiac surgery. The literature has shown that these procedures can be undertaken with equivalent mortality rates, similar operative times, comparable costs, and some benefits regarding hospital length of stay. The competing efforts of transcatheter aortic valve implantation for these same outcomes have provided an excellent range of treatment options for patients from cardiology teams. We describe the current state of the art, including technical considerations, caveats, and complications of minimal access aortic surgery and predict future directions in this space.