bluuebunny/crossref_metadata_2025 huggingface dataset:
Length of Hospital Stay, Hospitalization Costs, and Their Drivers in Adults with Diabetes in the Romanian Public Hospital System
Authors: Bala Cornelia , Rusu Adriana , Ciobanu Dana , Roman Gabriela
Published: August 2022

The aim of this analysis was to assess the costs associated with the hospitalizations of persons with diabetes in a Romanian public hospital. We performed a retrospective “top-down” cost analysis of all adult patients discharged from a tertiary care hospital with an ICD-10 primary or secondary code of diabetes mellitus (type 1, type 2, or specific forms) between 1 January 2015 and 31 December 2018. All costs were adjusted with the annual inflation rates and converted to EUR. We included 16,868 patients with diabetes and 28,055 episodes of hospitalization. The total adjusted hospitalization cost in the analyzed period was EUR 26,418,126.8 and the adjusted median cost/episode of hospitalization was EUR 596.5. The mean length of a hospital stay/episode was 7.3 days. In the multivariate regression analysis, higher adjusted average costs/episodes of hospitalization and longer lengths of hospital stays were associated with increasing age, the presence of cardiovascular diseases, chronic kidney disease, and foot ulcerations. Moreover, a significant association between the average cost/episode of hospitalization and the length of hospital stay was observed (β = 0.704, p < 0.001). This study shows the burden on Romanian public hospitals of inpatient diabetes care and the main drivers of the costs.
Prevalence and Factors Associated with Gaming Disorder in Latin America and the Caribbean: A Systematic Review
Authors: Hernández-Vásquez Akram , Vargas-Fernández Rodrigo , Visconti-Lopez Fabriccio J. , Comandé Daniel , Bendezu-Quispe Guido
Published: August 2022

We aimed to determine the prevalence and factors associated with gaming disorder (GD) in the population of Latin America and the Caribbean (LAC). A systematic review was performed (PROSPERO protocol registration: CRD42021230565). We included studies that identified participants with GD and/or factors associated with this condition, reported the prevalence of GD, or contained data that assisted in its estimation, were published after 2013 (the year of inclusion of GD in the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders) and were carried out in a population residing in an LAC country. Evaluation of the quality of the studies was carried out using the Joanna Briggs Institute Critical appraisal checklist tool. A qualitative synthesis of the data was performed. Of the total of 1567 records identified, 25 passed the full-text review phase, and 6 met the selection criteria. These studies were published between 2018 and 2021 and had a cross-sectional design (three in Brazil, one in Ecuador, Mexico, and the other was multi-country, including a LAC country [Peru]). The prevalence of GD ranged from 1.1% to 38.2%. The three studies in Brazil had the highest figures of GD prevalence (20.4–38.2%). Four studies evaluated factors associated with GD. Characteristics regarding the game (type), pattern of use (hours played), as well as gender (higher in men), tobacco and alcohol consumption, poor interpersonal relationships, and the presence of mental disorders were found to be associated with GD in LAC. Evidence on the prevalence and factors associated with GD in LAC is limited. Studies on GD in LAC evaluate different population subgroups, describing a wide prevalence of this condition (present in up to 38 out of 100 evaluated). Characteristics such as the type and hours of use of the games, sociodemographic data, lifestyles, interpersonal relationships, and the presence of mental disorders increase the probability of presenting GD.
Planetary Health and Health Education in Brazil: Towards Better Trained Future Health Professionals
Authors: Leal Filho Walter , Eustachio João Henrique Paulino Pires , Paucar-Caceres Alberto , Cavalcanti-Bandos Melissa Franchini , Nunes Cintia , Vílchez-Román Carlos , Quispe-Prieto Silvia , Brandli Luciana Londero
Published: August 2022

Brazil is Latin America’s largest country and has a strong economy, but it is also characterised by many inequalities. These are very conspicuous in the health sector, particularly in health education, which is expected to modernise according to the planetary health (PH) perspective. This paper describes the health education scenario in Brazil and undertakes an analysis of the postgraduate health programmes and policies in place, identifying the extent to which these support the cause of PH. To achieve this goal, this paper deploys a bibliometric analysis to gain a better understanding of the research streams related to higher education and PH. In addition, it presents and discusses selected case studies in the field and cross-checks documents from the Brazilian Ministry of Education against five domains of PH in education. The results indicate that despite some progress to date and the fact that some programmes are in place, there is a perceived need for policies and efforts from education organisations towards connecting PH principles in the education of current and future health professionals.
Doctor Clerk Implementation in Rural Community Hospitals for Effective Task Shifting of Doctors: A Grounded Theory Approach
Authors: Ohta Ryuichi , Yawata Miyuki , Sano Chiaki
Published: August 2022

With the diversification of medical care and work reform, doctor clerks play a major role today and are recruited to mitigate the burden of doctors worldwide. Their recruitment can improve the working conditions of physicians, facilitate task shifting in rural community hospitals, improve patient care, and help address the lack of healthcare resources. This study used a qualitative method to investigate difficulties in the implementation of doctor clerks and ascertain the features of effective implementation by collecting ethnographic data through field notes and semi-structured interviews with workers. We observed and interviewed 4 doctor clerks, 10 physicians, 14 nurses, 2 pharmacists, 1 nutritionist, and 2 therapists for our study. We clarified the doctor clerk process in rural hospitals through four themes: initial challenge, balance between education and expansion, vision for work progression, and drive for quality of care. We further clarified effectiveness, difficulties, and enhancing factors in implementation. Doctor clerk recruitment and bridging of discrepancies among medical professionals can mitigate professional workloads and improve staff motivation, leading to better interprofessional collaboration and patient care.
The Association between Appetitive Aggression and Social Media Addiction Mediated by Cyberbullying: The Moderating Role of Inclusive Norms
Authors: Wong Natalie , Yanagida Takuya , Spiel Christiane , Graf Daniel
Published: August 2022

Appetitive aggression, i.e., the motivation to obtain rewards through aggressive behaviors, has been suggested as a key driver of cyberbullying. Due to the contextual properties of cyberspace (e.g., anonymity), it is assumed that the negative effects of cyberbullying are masked, leading to a preponderance of its positive outcomes (e.g., thrill). Since cyberbullying occurs predominantly in social media, reward-learning effects may lead to problematic social media use, such as addiction. Anti-cyberbullying inclusive norms might act as a buffering factor to break this chain. However, while inclusive norms are known to reduce cyberbullying in general, their influence on the indirect effect of appetitive aggression via cyberbullying on social media addiction is yet unknown. The present study examined this indirect effect, while taking the moderating role of inclusive norms into account. A total of 1064 adolescents (42.05% male, Mage = 14.07, SD = 2.15) completed questionnaires. Results revealed the indirect effect of appetitive aggression on social media addiction through cyberbullying as expected. Surprisingly, this indirect effect was amplified with increasing anti-cyberbullying inclusive norms. Our findings indicate that appetitive aggression, which manifests in cyberbullying, contributes to the development of social media addiction. The unexpected results and the implications of our findings were discussed.
Guided Endodontics as a Personalized Tool for Complicated Clinical Cases
Authors: Dąbrowski Wojciech , Puchalska Wiesława , Ziemlewski Adam , Ordyniec-Kwaśnica Iwona
Published: August 2022

The aim of this paper is to present a technique to individualize root canal localization in teeth with calcified root canals using a digitally planned, 3D-printed endodontic guide. Root canal calcification is characterized by the apposition of tertiary dentin along the canal wall. The endodontic treatment of teeth with calcified canals is often challenging. However, digital dentistry meets these challenges. Merging CBCT images with an intraoral scan allows a clinician to prepare an endodontic guide. This article describes the clinical and digital workflow of the guided endodontic access approach in teeth with difficulties in terms of root canal localization due to post-traumatic pulp canal obliteration (PCO) and canal calcification in elderly patients. The path of entry into the root canal system was planned using cone-beam computed tomography (CBCT). The template was printed on a 3D printer using transparent resin. During root canal treatment (RCT), the endodontic tool was inserted through the sleeve until the desired location was reached. The use of an endodontic guide allowed for minimally invasive RCT, avoiding the excessive loss of tooth structures. Navigated endodontics enables clinicians to perform RCT in a more predictable manner and allows clinicians to avoid iatrogenic complications, which improves the treatment prognosis.
Sedentary Behavior Counseling Received from Healthcare Professionals: An Exploratory Analysis in Adults at Primary Health Care in Brazil
Authors: Snége André , Silva Alexandre Augusto de Paula da , Mielke Grégore Iven , Rech Cassiano Ricardo , Siqueira Fernando Carlos Vinholes , Rodriguez-Añez Ciro Romelio , Fermino Rogério César
Published: August 2022

Counseling by health professionals has promising results in behavior change and is recommended as part of integrated community interventions. However, the knowledge about sedentary behavior (SB) counseling is incipient. The study aimed to identify the prevalence and explore the associated factors with SB counseling received from healthcare professionals by adults in primary health care (PHC) in Brazil. A cross-sectional study was conducted in 2019 that included a representative sample of 779 users in all 15 basic health units (BHU) in São José dos Pinhais, Paraná. We identified those who reported having received SB counseling during a consultation. The association between the sociodemographic factors, chronic diseases, access to health services, physical activity, SB, and counseling were analyzed using Poisson regression in a hierarchical model. The prevalence of counseling was 12.2% (95% CI: 10.1–14.7%); it was higher in women (PR: 1.77; 95% CI: 1.10–2.83), those aged ≥60 yrs (PR: 1.84; 95% CI: 1.14–2.98), BMI ≥ 30 kg/m2 (PR: 2.60; 95% CI: 1.31–5.17), who consume ≥3 medications (PR: 2.21; 95% CI: 1.06–4.59), and those who spend a prolonged period of the day engaged in SB (4th quartile PR: 3.44; 95% CI: 1.88–6.31). The results highlight that SB counseling is underutilized and incipient in PHC. Understanding these results can help managers and healthcare professionals in BHU teams to implement and direct specific actions to reduce SB in adults through counseling.
A Study of Sr Sorption Behavior in Claystone from a Candidate High-Level Radioactive Waste Geological Disposal Site under the Action of FeOOH Colloids
Authors: Wang Jinsheng , Cai Weihai , Zuo Rui , Du Can
Published: August 2022

Colloids have a significant influence on the migration of nuclides in claystone, which is an important geological barrier. The sorption of strontium on claystone in the presence of FeOOH colloids was investigated in samples from the Suhongtu site, a candidate high-level radioactive waste disposal site in China. The effects of colloid amount, solid content, and pH were investigated by batch tests, and the sorption reaction mechanism was analyzed by kinetic modeling and microscopic characterization techniques. The results indicate that the sorption of Sr by claystone increased with the solids content, and the claystone had a stronger Sr sorption capacity under alkaline conditions. The Sr sorption kinetics were best described by the pseudo-first-order and pseudo-second-order models, which revealed that the progress is affected by physical diffusion and chemical sorption. Furthermore, the microscopic characterization results demonstrate that cation exchange reactions and surface complex reactions are the main sorption mechanisms for Sr sorption on claystone. Ca and Mg plasmas in claystone minerals can have cation replacement reactions with Sr, and functional groups such as -OH and [CO3]2− can have complexation reactions with Sr to adsorb Sr on the surface of the claystone. Additionally, the presence of the FeOOH colloid inhibited the sorption effect of claystone slightly. The FeOOH colloid could occupy sorption sites on the claystone surface, which reduces the activity of the functional groups and inhibits the sorption of Sr on claystone.
Codification and Prospect of China’s Codification of Environmental Law from the Perspective of Global Environmental Governance
Authors: Xu Kai , Tian Guangdong
Published: August 2022

Global environmental governance is the fundamental way to solve the human environmental crisis. With China as the world’s largest emitter of greenhouse gases, the development of China’s environmental law is a key component of global environmental governance. In order to better realize the construction of an ecological civilization, the compilation of China’s Environmental Code has been officially put on the work schedule of the legislature. The compilation of the code is a sincere action, showing that China has taken the initiative to assume its own responsibility for environmental governance. In the past 50 years, China’s environmental legislation has achieved a great leap forward: from nothing to something, from something to something more comprehensive. Aside from this progress, defects such as the internal imbalance of the environmental law system, the backwardness of some environmental legislation ideas, and the inability of environmental legislation and its academic research to fully match China’s national conditions also exist. With the helping hands of conditions and times, it is most appropriate for China to start the compilation of the Environmental Code now. Environmental Codes such as the Swedish Environmental Code, the French Environmental Code and the German Environmental Code (Draft of the Committee of Experts) provide many empirical references for the compilation of China’s Environmental Code. China will make important an contribution to world environmental governance again—an Environmental Code in line with international standards while maintaining native characteristics.
Physical and Functional Clinical Profile of Older Adults in Specialized Geriatric Rehabilitation Care Services in Saguenay-Québec: A Retrospective Study at La Baie Hospital
Authors: de Lima Maria do Carmo Correia , Dallaire Mathieu , Tremblay Catherine , Nicole Alexis , Fortin Émilie , Maluf Isabela Calixto , Nepton Josée , Severn Anne-France , Tremblay Patrice , Côté Sharlène , Bouchard Julie , da Silva Rubens A.
Published: August 2022

Musculoskeletal disorders, cardiovascular and neurological diseases were the most commonly debilitating conditions and risk factors associated with pain, mobility limitations, increased risk of falls and disability. Studies barely address the profile of older adults in care within a specialized geriatric rehabilitation service (SGRS) to provide subsidies for new actions within the public healthcare to reduce falls and improve management in health investments. This study aimed to establish a clinical physical and functional profile of the patients with neuromusculoskeletal and cognitive disorders and fallers in interventions within SGRS. From a retrospective study design, 127 medical records were compiled and analyzed to determine the physical and functional profile of older adults and differences according to sex, age groups and the benefits for local physical therapy intervention. The users were between 76 and 85 years of age, with diverse clinical diagnoses and debilitating conditions and impairments. A higher proportion presented gait and balance impairments and had two or more falls in 12 months. A significant effect for advanced age was observed. Overall, real benefits were reported with intervention for functional improvement, although the absence of a control group. These results have direct implications for a better understanding of a local SGRS and provide subsidies for developing new approaches for the assessment and treatment of older adults with high a risk of falls in order to reduce costs for the public health system.
Confidence in Dementia Management and Its Associated Factors among Primary Care Doctors in Malaysia
Authors: Sodri Nurul Izzah , Mohamed-Yassin Mohamed-Syarif , Mohamad Mariam , Baharudin Noorhida
Published: August 2022

Primary care doctors (PCDs) play an important role in the early diagnosis and management of dementia. This study aimed to determine the knowledge, attitude, and confidence in managing dementia among PCDs in Malaysia. It also aimed to determine the factors associated with higher confidence levels in dementia management. An online-based cross-sectional study using Google FormsTM was performed. Sociodemographic and work-related data were collected, and Dementia Knowledge among General Practitioners & General Practitioners Attitude and Confidence Scale for Dementia questionnaires were utilized to assess the knowledge, attitude, and confidence scores. Multiple linear regression was conducted to determine the association between sociodemographic factors, knowledge, and attitude with the confidence in dementia management score. A total of 239 PCDs participated, with the majority being female (72.4%) and Malay (64.4%) and working in public primary care clinics (67.4%). The mean (±SD) score for confidence was 2.96 (±0.76). Among the factors associated with higher confidence levels in managing dementia were higher dementia knowledge scores, higher attitude towards dementia scores, prior dementia education, and the availability of nearby referral services for dementia. Malaysian PCDs’ confidence in dementia management was comparable to the PCDs of other countries. Strategies addressing these factors should be implemented to improve the confidence of PCDs in managing dementia.
Transcriptomics and Genomics Analysis Uncover the Differentially Expressed Chlorophyll and Carotenoid-Related Genes in Celery
Authors: Song Xiaoming , Li Nan , Zhang Yingchao , Liang Yi , Zhou Rong , Yu Tong , Shen Shaoqin , Feng Shuyan , Zhang Yu , Li Xiuqing , Lin Hao , Wang Xiyin
Published: August 2022

Celery (Apium graveolens L.), a plant from Apiaceae, is one of the most important vegetables and is grown worldwide. Carotenoids can capture light energy and transfer it to chlorophyll, which plays a central role in photosynthesis. Here, by performing transcriptomics and genomics analysis, we identified and conducted a comprehensive analysis of chlorophyll and carotenoid-related genes in celery and six representative species. Significantly, different contents and gene expression patterns were found among three celery varieties. In total, 237 and 290 chlorophyll and carotenoid-related genes were identified in seven species. No notable gene expansion of chlorophyll biosynthesis was detected in examined species. However, the gene encoding ζ-carotene desaturase (ZDS) enzyme in carotenoid was expanded in celery. Comparative genomics and RNA-seq analyses revealed 16 and 5 key genes, respectively, regulating chlorophyll and carotenoid. An intriguing finding is that chlorophyll and carotenoid-related genes were coordinately regulated by transcriptional factors, which could be distinctively classified into positive- and negative-regulation groups. Six CONSTANS (CO)-like transcription factors co-regulated chlorophyll and carotenoid-related genes were identified in celery. In conclusion, this study provides new insights into the regulation of chlorophyll and carotenoid by transcription factors.
Sensory-Motor Perturbations in Larval Zebrafish (Danio rerio) Induced by Exposure to Low Levels of Neuroactive Micropollutants during Development
Authors: Henry Jason , Bai Yutao , Kreuder Florian , Saaristo Minna , Kaslin Jan , Wlodkowic Donald
Published: August 2022

Due to increasing numbers of anthropogenic chemicals with unknown neurotoxic properties, there is an increasing need for a paradigm shift toward rapid and higher throughput behavioral bioassays. In this work, we demonstrate application of a purpose-built high throughput multidimensional behavioral test battery on larval stages of Danio rerio (zebrafish) at 5 days post fertilization (dpf). The automated battery comprised of the established spontaneous swimming (SS), simulated predator response (SPR), larval photomotor response (LPR) assays as well as a new thermotaxis (TX) assay. We applied the novel system to characterize environmentally relevant concentrations of emerging pharmaceutical micropollutants including anticonvulsants (gabapentin: 400 ng/L; carbamazepine: 3000 ng/L), inflammatory drugs (ibuprofen: 9800 ng/L), and antidepressants (fluoxetine: 300 ng/L; venlafaxine: 2200 ng/L). The successful integration of the thermal preference assay into a multidimensional behavioral test battery provided means to reveal ibuprofen-induced perturbations of thermal preference behaviors upon exposure during embryogenesis. Moreover, we discovered that photomotor responses in larval stages of fish are also altered by the as yet understudied anticonvulsant gabapentin. Collectively our results demonstrate the utility of high-throughput multidimensional behavioral ecotoxicity test batteries in prioritizing emerging risks associated with neuroactive drugs that can perturb neurodevelopment. Moreover, we showcase the added value of thermotaxis bioassays for preliminary screening of emerging contaminants.
Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma
Authors: Setlai Botle Precious , Mkhize-Kwitshana Zilungile Lynette , Mehrotra Ravi , Mulaudzi Thanyani Victor , Dlamini Zodwa
Published: August 2022

Malignant mesotheliomas (MM) are hard to treat malignancies with poor prognosis and high mortality rates. This cancer is highly misdiagnosed in Sub-Saharan African countries. According to literature, the incidence of MM is likely to increase particularly in low-middle-income countries (LMICs). The burden of asbestos-induced diseases was estimated to be about 231,000 per annum. Lack of awareness and implementation of regulatory frameworks to control exposure to asbestos fibers contributes to the expected increase. Exposure to asbestos fibers can lead to cancer initiation by several mechanisms. Asbestos-induced epigenetic modifications of gene expression machinery and non-coding RNAs promote cancer initiation and progression. Furthermore, microbiome–epigenetic interactions control the innate and adaptive immunity causing exacerbation of cancer progression and therapeutic resistance. This review discusses epigenetic mechanisms with more focus on miRNAs and their interaction with the microbiome. The potential use of epigenetic alterations and microbiota as specific biomarkers to aid in the early detection and/or development of therapeutic targets is explored. The advancement of combinatorial therapies to prolong overall patient survival or possible eradication of MM especially if it is detected early is discussed.
DNA Methyltransferases: From Evolution to Clinical Applications
Authors: Del Castillo Falconi Victor M. , Torres-Arciga Karla , Matus-Ortega Genaro , Díaz-Chávez José , Herrera Luis A.
Published: August 2022

DNA methylation is an epigenetic mark that living beings have used in different environments. The MTases family catalyzes DNA methylation. This process is conserved from archaea to eukaryotes, from fertilization to every stage of development, and from the early stages of cancer to metastasis. The family of DNMTs has been classified into DNMT1, DNMT2, and DNMT3. Each DNMT has been duplicated or deleted, having consequences on DNMT structure and cellular function, resulting in a conserved evolutionary reaction of DNA methylation. DNMTs are conserved in the five kingdoms of life: bacteria, protists, fungi, plants, and animals. The importance of DNMTs in whether methylate or not has a historical adaptation that in mammals has been discovered in complex regulatory mechanisms to develop another padlock to genomic insurance stability. The regulatory mechanisms that control DNMTs expression are involved in a diversity of cell phenotypes and are associated with pathologies transcription deregulation. This work focused on DNA methyltransferases, their biology, functions, and new inhibitory mechanisms reported. We also discuss different approaches to inhibit DNMTs, the use of non-coding RNAs and nucleoside chemical compounds in recent studies, and their importance in biological, clinical, and industry research.
Combination RSL3 Treatment Sensitizes Ferroptosis- and EGFR-Inhibition-Resistant HNSCCs to Cetuximab
Authors: Liu Shujie , Yan Shuai , Zhu Jie , Lu Ruiqing , Kang Chujie , Tang Kang , Zeng Jinfeng , Ding Mingmei , Guo Zixiang , Lai Xianxin , Jiang Yinan , Wu Siqing , Zhou Lihua , Sun Litao , Zhou Zhong-Wei
Published: August 2022

Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of KRAS and ferritin heavy chain (FTH1) since a high level of FTH1 is associated with the poor prognostic survival of HNSCCs, but knocked down FTH1 can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody Cetuximab to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of FTH1 and a low level of EGFR, respectively. Our findings prove that FTH1 plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition.
Role of Vitamin D in Liver Disease and Complications of Advanced Chronic Liver Disease
Authors: Ravaioli Federico , Pivetti Alessandra , Di Marco Lorenza , Chrysanthi Christou , Frassanito Gabriella , Pambianco Martina , Sicuro Chiara , Gualandi Noemi , Guasconi Tomas , Pecchini Maddalena , Colecchia Antonio
Published: August 2022

Vitamin D is a crucial nutrient with many pleiotropic effects on health and various chronic diseases. The purpose of this review is to provide a detailed report on the pathophysiological mechanisms underlying vitamin D deficiency in patients with chronic liver disease, addressing the different liver etiologies and the condition of advanced chronic liver disease (cirrhosis) with related complications. To date, patients with liver disease, regardless of underlying etiology, have been shown to have reduced levels of vitamin D. There is also evidence of the predictive role of vitamin D values in complications and progression of advanced disease. However, specific indications of vitamin D supplementation are not conclusive concerning what is already recommended in the general population. Future studies should make an effort to unify and validate the role of vitamin D supplementation in chronic liver disease.
Effects of Human Activity on Markers of Oxidative Stress in the Intestine of Holothuria tubulosa, with Special Reference to the Presence of Microplastics
Authors: Lombardo Jessica , Solomando Antònia , Cohen-Sánchez Amanda , Pinya Samuel , Tejada Silvia , Ferriol Pere , Mateu-Vicens Guillem , Box Antonio , Faggio Caterina , Sureda Antoni
Published: August 2022

Pollution in the seas and oceans is a global problem, which highlights emerging pollutants and plastics, specifically microplastics (MPs), which are tiny (1 μm to 5 mm) ubiquitous plastic particles present in marine environments that can be ingested by a wide range of organisms. Holothurians are benthic organisms that feed on sediment; therefore, they can be exposed to contaminants present in the particles they ingest. The objective was to evaluate the effects of human activity on Holothuria tubulosa through the study of biomarkers. Specimens were collected in three different areas throughout the island of Eivissa, Spain: (1) a highly urbanized area, with tourist uses and a marina; (2) an urbanized area close to the mouth of a torrent; (3) an area devoid of human activity and considered clean. The results showed a higher presence of microplastics (MPs) in the sediments from the highly urbanized area in relation to the other two areas studied. Similarly, a higher number of MPs were observed in the digestive tract of H. tubulosa from the most affected area, decreasing with the degree of anthropic influence. Both in the sediment and in the holothurians, fibers predominated with more than 75% of the items. In the three areas, mesoplastics were analyzed by means of FTIR, showing that the main polymer was polypropylene (27%) followed by low-density polyethylene (17%) and polystyrene (16%). Regarding the biomarkers of oxidative stress, the intestine of H. tubulosa from the most impacted areas showed higher catalase, superoxide dismutase (SOD), glutathione reductase (GRd), and glutathione S-transferase (GST) activities and reduced glutathione (GSH) levels compared to the control area. The intermediate area only presented significant differences in GRd and GST with respect to the clean area. The activities of acetylcholinesterase and the levels and malondialdehyde presented similar values in all areas. In conclusion, human activity evaluated with the presence of MPs induced an antioxidant response in H. tubulosa, although without evidence of oxidative damage or neurotoxicity. H. tubulosa, due to its benthic animal characteristics and easy handling, can be a useful species for monitoring purposes.
ADAR1 Isoforms Regulate Let-7d Processing in Idiopathic Pulmonary Fibrosis
Authors: Díaz-Piña Gabriela , Rubio Karla , Ordoñez-Razo Rosa M. , Barreto Guillermo , Montes Eduardo , Becerril Carina , Salgado Alfonso , Cabrera-Fuentes Héctor , Aquino-Galvez Arnoldo , Carlos-Reyes Angeles , Ruiz Victor
Published: August 2022

Double-stranded RNA adenosine deaminase 1 (ADAR1) is significantly down-regulated in fibroblasts derived from Idiopathic Pulmonary Fibrosis (IPF) patients, and its overexpression restored levels of miRNA-21, PELI1, and SPRY2. There are two ADAR1 isoforms in humans, ADAR1-p110 and ADAR1-p150, generated by an alternative promoter. Let-7d is considered an essential microRNA in Pulmonary Fibrosis (PF). In silico analysis revealed COL3A1 and SMAD2, proteins involved in the development of IPF, as Let-7d targets. We analyzed the role of ADAR1-p110 and ADAR1-p150 isoforms in the regulation of Let-7d maturation and the effect of this regulation on the expression of COL3A1 and SMAD2 in IPF fibroblast. We demonstrated that differential expression and subcellular distribution of ADAR1 isoforms in fibroblasts contribute to the up-regulation of pri-miR-Let-7d and down-regulation of mature Let-7d. Induction of overexpression of ADAR1 reestablishes the expression of pri-miR-Let-7d and Let-7d in lung fibroblasts. The reduction of mature Let-7d upregulates the expression of COL3A1 and SMAD2. Thus, ADAR1 isoforms and Let-7d could have a synergistic role in IPF, which is a promising explanation in the mechanisms of fibrosis development, and the regulation of both molecules could be used as a therapeutic approach in IPF.
Small-Molecules as Chemiluminescent Probes to Detect Lipase Activity
Authors: La Rocca Paolo , Mingione Alessandra , Casati Silvana , Ottria Roberta , Allevi Pietro , Ciuffreda Pierangela , Rota Paola
Published: August 2022

The set-up of highly sensitive detection tools to evaluate lipase activity remains a central goal in different fields. In this context, we proposed new chemiluminescent 1,2-dioxetane luminophores, sharing an octanoyl triggerable group, to monitor lipase activity. We herein report the synthesis and both the evaluation of their luminescence emission profile and their enzyme–substrate specificity, generated by three different commercial lipases (Candida cylindracea, Pseudomonas fluorescens, and Mucor miehei) and one esterase (porcine liver esterase, PLE, as a literature control). Remarkably, the present study confirmed the applicability of these 1,2-dioxetane luminophores as (i) highly efficient, broad-range, chemiluminescent probes for the detection and the enzymatic activity evaluation of lipases and as (ii) promising candidates for the future development of both flash- and glow-type luminescence assays.
Clinical Translationality of KCNJ5 Mutation in Aldosterone Producing Adenoma
Authors: Kitamoto Takumi , Nishikawa Tetsuo
Published: August 2022

Hypertension due to primary aldosteronism poses a risk of severe cardiovascular complications compared to essential hypertension. The discovery of the KCNJ5 somatic mutation in aldosteroene producing adenoma (APA) in 2011 and the development of specific CYP11B2 antibodies in 2012 have greatly advanced our understanding of the pathophysiology of primary aldosteronism. In particular, the presence of CYP11B2-positive aldosterone-producing micronodules (APMs) in the adrenal glands of normotensive individuals and the presence of renin-independent aldosterone excess in normotensive subjects demonstrated the continuum of the pathogenesis of PA. Furthermore, among the aldosterone driver mutations which incur excessive aldosterone secretion, KCNJ5 was a major somatic mutation in APA, while CACNA1D is a leading somatic mutation in APMs and idiopathic hyperaldosteronism (IHA), suggesting a distinctive pathogenesis between APA and IHA. Although the functional detail of APMs has not been still uncovered, its impact on the pathogenesis of PA is gradually being revealed. In this review, we summarize the integrated findings regarding APA, APM or diffuse hyperplasia defined by novel CYP11B2, and aldosterone driver mutations. Following this, we discuss the clinical implications of KCNJ5 mutations to support better cardiovascular outcomes of primary aldosteronism.
Genome-Wide Identification and Analysis of the Growth-Regulating Factor Family in Zanthoxylum armatum DC and Functional Analysis of ZaGRF6 in Leaf Size and Longevity Regulation
Authors: Huang Yanhui , Chen Jiajia , Li Jianrong , Li Yan , Zeng Xiaofang
Published: August 2022

Growth-regulating factors (GRFs) are plant-specific transcription factors that play an important role in plant growth and development. In this study, fifteen GRF gene members containing QLQ and WRC domains were identified in Zanthoxylum armatum. Phylogenetic and collinearity analysis showed that ZaGRFs were closely related to CsGRFs and AtGRFs, and distantly related to OsGRFs. There are a large number of cis-acting elements related to hormone response and stress induction in the GRF gene promoter region of Z. armatum. Tissue-specific expression analysis showed that except for ZaGRF7, all the ZaGRFs were highly expressed in young parts with active growth and development, including terminal buds, seeds, and young flowers, suggesting their key roles in Z. armatum growth and development. Eight ZaGRFs were selected to investigate the transcriptional response to auxin, gibberellin and drought treatments. A total of six ZaGRFs in the NAA treatment, four ZaGRFs in the GA3 treatment, and six ZaGRFs in the PEG treatment were induced and significantly up-regulated. Overexpression of ZaGRF6 increased branching and chlorophyll content and delayed senescence of transgenic Nicotiana benthamiana. ZaGRF6 increased the expression of CRF2 and suppressed the expression of ARR4 and CKX1, indicating that ZaGRF6 is involved in cytokinin metabolism and signal transduction. These research results lay a foundation for further analysis of the GRF gene function of Z. armatum and provide candidate genes for growth, development, and stress resistance breeding of Z. armatum.
Osteoporosis in Light of a New Mechanism Theory of Delayed Onset Muscle Soreness and Non-Contact Anterior Cruciate Ligament Injury
Authors: Sonkodi Balázs , Bardoni Rita , Poór Gyula
Published: August 2022

Osteoporosis is a disorder, with a largely unknown pathomechanism, that is often marked as a “silent thief”, because it usually only becomes undisguised when fractures occur. This implies that the pathological damage occurs earlier than the sensation of pain. The current authors put forward a non-contact injury model in which the chronic overloading of an earlier autologously microinjured Piezo2 ion channel of the spinal proprioceptor terminals could lead the way to re-injury and earlier aging in a dose-limiting and threshold-driven way. As a result, the aging process could eventually lead the way to the metabolic imbalance of primary osteoporosis in a quad-phasic non-contact injury pathway. Furthermore, it is emphasised that delayed onset muscle soreness, non-contact anterior cruciate injury and osteoporosis could have the same initiating proprioceptive non-contact Piezo2 channelopathy, at different locations, however, with different environmental risk factors and a different genetic predisposition, therefore producing different outcomes longitudinally. The current injury model does not intend to challenge any running pathogenic theories or findings, but rather to highlight a principal injury mechanism.
Psoriasis and Cardiometabolic Diseases: Shared Genetic and Molecular Pathways
Authors: Piaserico Stefano , Orlando Gloria , Messina Francesco
Published: August 2022

A convincing deal of evidence supports the fact that severe psoriasis is associated with cardiovascular diseases. However, the precise underlying mechanisms linking psoriasis and cardiovascular diseases are not well defined. Psoriasis shares common pathophysiologic mechanisms with atherosclerosis and cardiovascular (CV) risk factors. In particular, polymorphism in the IL-23R and IL-23 genes, as well as other genes involved in lipid and fatty-acid metabolism, renin–angiotensin system and endothelial function, have been described in patients with psoriasis and with cardiovascular risk factors. Moreover, systemic inflammation in patients with psoriasis, including elevated serum proinflammatory cytokines (e.g., TNF-α, IL-17, and IL-23) may contribute to an increased risk of atherosclerosis, hypertension, alteration of serum lipid composition, and insulin resistance. The nonlinear and intricate interplay among various factors, impacting the molecular pathways in different cell types, probably contributes to the development of psoriasis and cardiovascular disease (CVD). Future research should, therefore, aim to fully unravel shared and differential molecular pathways underpinning the association between psoriasis and CVD.
Oxidative Stress and DNA Damage in Peripheral Blood Mononuclear Cells from Normal, Obese, Prediabetic and Diabetic Persons Exposed to Thyroid Hormone In Vitro
Authors: Djelić Ninoslav , Borozan Sunčica , Dimitrijević-Srećković Vesna , Pajović Nevena , Mirilović Milorad , Stopper Helga , Stanimirović Zoran
Published: August 2022

Diabetes, a chronic group of medical disorders characterized byhyperglycemia, has become a global pandemic. Some hormones may influence the course and outcome of diabetes, especially if they potentiate the formation of reactive oxygen species (ROS). There is a close relationship between thyroid disorders and diabetes. The main objective of this investigation was to find out whether peripheral blood mononuclear cells (PBMCs) are more prone to DNA damage by triiodothyronine (T3) (0.1, 1 and 10 μM) at various stages of progression through diabetes (obese, prediabetics, and type 2 diabetes mellitus—T2DM persons). In addition, some biochemical parameters of oxidative stress (catalase-CAT, thiobarbituric acid reactive substances—TBARS) and lactate dehydrogenase (LDH) were evaluated. PBMCs from prediabetic and diabetic patients exhibited increased sensitivity for T3 regarding elevated level of DNA damage, inhibition of catalase, and increase of TBARS and LDH. PBMCs from obese patients reacted in the same manner, except for DNA damage. The results of this study should contribute to a better understanding of the role of thyroid hormones in the progression of T2DM.
Lamin-A/C Is Modulated by the Involvement of Histamine-Mediated Calcium/Calmodulin-Dependent Kinase II in Lung Cancer Cells
Authors: Kim Hyeong-Jae , Lee Peter C. W. , Hong Jeong Hee
Published: August 2022

Lamins are nuclear envelope proteins involved in various cellular functions, such as DNA modulation, cellular differentiation, and development. In this study, we investigate the role of histamine in lung cancer biology. Since it is known that lamin-A/C is negatively regulated in lung cancer, we hypothesize that histamine signaling is related to nuclear lamin-A/C regulation and cancer progression. Our findings reveal that histamine stimulation enhances lamin-A/C expression in lung cancer cells. Lamin-A/C expression is dependent on histamine-mediated intracellular calcium signaling and subsequent calcium/calmodulin-dependent kinase II (Ca/CaMKII) activation. The nuclear protein nestin, which stabilizes lamin-A/C expression, is also modulated by Ca/CaMKII. However, histamine-mediated lamin-A/C expression is independent of Akt/focal adhesion kinase or autophagy signaling. Histamine stimulation attenuates lung cancer motility in the presence of enhanced lamin-A/C expression. In conclusion, we propose a regulatory mechanism that accounts for the modulation of lamin-A/C levels through the involvement of Ca/CaMKII in cancer cells and provides molecular evidence of histamine signaling in lamin-A/C biology.
The Role of Inflammation, Hypoxia, and Opioid Receptor Expression in Pain Modulation in Patients Suffering from Obstructive Sleep Apnea
Authors: Kaczmarski Piotr , Karuga Filip Franciszek , Szmyd Bartosz , Sochal Marcin , Białasiewicz Piotr , Strzelecki Dominik , Gabryelska Agata
Published: August 2022

Obstructive sleep apnea (OSA) is a relatively common disease in the general population. Besides its interaction with many comorbidities, it can also interact with potentially painful conditions and modulate its course. The association between OSA and pain modulation has recently been a topic of concern for many scientists. The mechanism underlying OSA-related pain connection has been linked with different pathophysiological changes in OSA and various pain mechanisms. Furthermore, it may cause both chronic and acute pain aggravation as well as potentially influencing the antinociceptive mechanism. Characteristic changes in OSA such as nocturnal hypoxemia, sleep fragmentation, and systemic inflammation are considered to have a curtailing impact on pain perception. Hypoxemia in OSA has been proven to have a significant impact on increased expression of proinflammatory cytokines influencing the hyperalgesic priming of nociceptors. Moreover, hypoxia markers by themselves are hypothesized to modulate intracellular signal transduction in neurons and have an impact on nociceptive sensitization. Pain management in patients with OSA may create problems arousing from alterations in neuropeptide systems and overexpression of opioid receptors in hypoxia conditions, leading to intensification of side effects, e.g., respiratory depression and increased opioid sensitivity for analgesic effects. In this paper, we summarize the current knowledge regarding pain and pain treatment in OSA with a focus on molecular mechanisms leading to nociceptive modulation.
Impact of Non-Pharmacological Interventions on the Mechanisms of Atherosclerosis
Authors: Matei Daniela , Buculei Ioana , Luca Catalina , Corciova Calin-Petru , Andritoi Doru , Fuior Robert , Iordan Daniel-Andrei , Onu Ilie
Published: August 2022

Atherosclerosis remains the leading cause of mortality and morbidity worldwide characterized by the deposition of lipids and fibrous elements in the form of atheroma plaques in vascular areas which are hemodynamically overloaded. The global burden of atherosclerotic cardiovascular disease is steadily increasing and is considered the largest known non-infectious pandemic. The management of atherosclerotic cardiovascular disease is increasing the cost of health care worldwide, which is a concern for researchers and physicians and has caused them to strive to find effective long-term strategies to improve the efficiency of treatments by managing conventional risk factors. Primary prevention of atherosclerotic cardiovascular disease is the preferred method to reduce cardiovascular risk. Fasting, a Mediterranean diet, and caloric restriction can be considered useful clinical tools. The protective impact of physical exercise over the cardiovascular system has been studied in recent years with the intention of explaining the mechanisms involved; the increase in heat shock proteins, antioxidant enzymes and regulators of cardiac myocyte proliferation concentration seem to be the molecular and biochemical shifts that are involved. Developing new therapeutic strategies such as vagus nerve stimulation, either to prevent or slow the disease’s onset and progression, will surely have a profound effect on the lives of millions of people.
Stage-Specific Genetic Interaction between FgYCK1 and FgBNI4 during Vegetative Growth and Conidiation in Fusarium graminearum
Authors: Zhu Jindong , Hu Denghui , Liu Qianqian , Hou Rui , Xu Jin-Rong , Wang Guanghui
Published: August 2022

CK1 casein kinases are well conserved in filamentous fungi. However, their functions are not well characterized in plant pathogens. In Fusarium graminearum, deletion of FgYCK1 caused severe growth defects and loss of conidiation, fertility, and pathogenicity. Interestingly, the Fgyck1 mutant was not stable and often produced fast-growing spontaneous suppressors. Suppressor mutations were frequently identified in the FgBNI4 gene by sequencing analyses. Deletion of the entire FgBNI4 or disruptions of its conserved C-terminal region could suppress the defects of Fgyck1 in hyphal growth and conidiation, indicating the genetic relationship between FgYCK1 and FgBNI4. Furthermore, the Fgyck1 mutant showed defects in polarized growth, cell wall integrity, internalization of FgRho1 and vacuole fusion, which were all partially suppressed by deletion of FgBNI4. Overall, our results indicate a stage-specific functional relationship between FgYCK1 and FgBNI4, possibly via FgRho1 signaling for regulating polarized hyphal growth and cell wall integrity.