bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Objective Optimal Allocation of Water Resources Based on the NSGA-2 Algorithm While Considering Intergenerational Equity: A Case Study of the Middle and Upper Reaches of Huaihe River Basin, China
Authors: Zhang Jitao , Dong Zengchuan , Chen Tian
Published: December 2020

With the rapid development of society and the economy, the demand for water resources is increasing. This, combined with the increasing competition for water resources between current and future generations, hinders the sustainable development of society. To alleviate prominent water resources problems, achieve sustainable utilization of water resources and the sustainable development of society and economy, a multi-objective optimal water resources allocation model is proposed, in which different water sources and different water departments are considered to achieve the maximum social and economic benefits of the study area on the premise of water resources sustainability. To meet the needs of future generations, the discount value is introduced to measure intergenerational equity. A case study from seven cities in the upper and middle reaches of the Huaihe River Basin is given to verify the practicality and viability of the model. The non-dominated sorting Genetic Algorithms-2(NSGA-2) was used to find optimal water resources allocation schemes in 2020 and 2050 under the condition of a hydrological drought year (inflow guarantee rate p = 75%). Compared with previous models, the intergenerational equity model considers the sustainability of water resources, has higher social and economic benefits, and ensures the fair distribution of water resources among generations. According to the results, under balanced weight, the water shortage ratio of the seven cities will decrease from 5.24% in 2050 to 1.58% in 2020, and the economic benefit will increase from 79.46(1010CNY) to 168.3(1010CNY), respectively. In addition, the discount value of economic benefit in 2050 is 80.23(1010CNY), which is still higher than that in 2020. This shows that the water resource allocation scheme can eliminate the disparity between supply and demand for water resources and achieve intergenerational equity. Therefore, the intergenerational equity model can alleviate the contradiction of water resources and realize intergenerational equity.
Assessing the Prevalence and Association of Pulp Stones with Cardiovascular Diseases and Diabetes Mellitus in the Saudi Arabian Population—A CBCT Based Study
Authors: Srivastava Kumar Chandan , Shrivastava Deepti , Nagarajappa Anil Kumar , Khan Zafar Ali , Alzoubi Ibrahim A. , Mousa Mohammed Assayed , Hamza May , David Anju P. , Al-Johani Khalid , Sghaireen Mohammed Ghazi , Alam Mohammad Khursheed
Published: December 2020

The detection of pulp stone in a patient suffering from undiagnosed systemic diseases can be an early diagnostic indicator. Thus, the aim of the study was to assess the prevalence of pulp stones in the Saudi Arabian population with cardiovascular diseases and diabetes mellitus. In a retrospective study, we included cone-beam computed tomography (CBCT) scans of 73 patients with cardiovascular disease and 76 patients with diabetes mellitus as group I and II, respectively. Group III comprised of CBCT scan of 80 healthy controls. From a total of 229 scans, 4807 teeth were screened for pulp stones throughout the arches. A chi-square test was used for comparing the prevalence of pulp stones among the groups. Univariable and multivariable analysis was done to evaluate the independent risk indicators for pulp stones. The tooth-wise prevalence of pulp stones in group I, II, and III was found to be 16.65%, 9.01%, and 3.86%, respectively. Patient-wise (p < 0.01) and tooth-wise (p < 0.01) prevalence was recorded significantly highest in the cardiovascular group followed by the diabetic group. The control group had the least prevalence. Significantly (p < 0.01) higher number of pulp stones were found in cardiovascular patients with age > 50 years compared to other groups. Similarly, a significantly increased number of pulp stones were seen in the 1st molar (p < 0.05) and the maxillary jaw (p < 0.05) of patients with cardiovascular diseases. Subjects with cardiovascular disease and diabetes were found to have 2.94 times (p < 0.001; CI 1.54–3.10) and 1.81 times (p < 0.01; CI 0.48–2.06) higher risk of having pulp stones in comparison to healthy subjects. The first molar has 2.20 times (p < 0.001; CI 0.84–2.45) increased the risk of having pulp stones compared to other tooth types. Systemic disease such as cardiovascular disease and diabetes mellitus poses a higher risk for the development of pulp stones. Among the systemic disease group, patients in the cardiovascular group showed a higher risk for pulp stones and also reported the maximum number of pulp stones compared to the diabetic and healthy subjects.
Regularity of Clinical Visits and Medication Adherence of Patients with Hypertension or Diabetes in Rural Yunnan Province of China
Authors: Gao Qiufeng , Peng Lanxi , Min Wenbin , Nie Jingchun , Wang Aiqin , Shi Yaojiang , Shi Haonan , Teuwen Dirk E. , Yi Hongmei
Published: December 2020

Chronic diseases can be controlled through effective self-management. The purpose of this study is to explore the regularity of clinical visits and medication adherence of patients with hypertension or diabetes (PWHD), and its association with the first experience with care and individual factors in rural Southwestern China. This cross-sectional study was carried out in Yunnan province in 2018 and recruited 292 PWHD and 122 village clinics from 122 villages in 10 counties. Participants were interviewed using a structured questionnaire. Results show around 39% of hypertensive and 25% of diabetic patients neither visited physicians nor took medicine regularly during the preceding three months of the interview date. The regression results further indicated that individual characteristics of the PWHD, including patient age, health status, and economic level, as well as their first experience with care, were significantly associated with their regular healthcare behavior. In addition to providing medical services, on average each sample village clinic, with around two physicians, simultaneously managed 180 hypertensive and 45 diabetic patients. This study revealed the need for further reforms in terms of improving self-management and thus recommends an increase in the quantity and the quality of human resources in the primary healthcare realm in rural China.
Health-Related Quality of Life and Related Factors among Primary Caregivers of Children with Disabilities in Shanghai, China: A Cross-Sectional Study
Authors: Xia Cong , Sun Mei , Li Xinying , Lu Chenhao , Gao Xiu , Lu Jun , Chen Gang
Published: December 2020

Health-related quality of life (HRQOL) of caregivers of children with disabilities (CWD) is important for both children’s rehabilitation and caregivers’ life, but the corresponding attention is far from enough in mainland China. Thus, we investigated the HRQOL of 170 caregivers and related factors in Shanghai. The 12-item Short Form Health Survey (SF-12) was used to measure HRQOL. The potential factors were collected, including child characteristics, caregiver characteristics, and environmental factors. Univariate analysis and multiple linear regression were performed to identify the key factors that could be intervened. Compared with the general population, caregivers of CWD had a slightly higher score on the physical component summary (PCS, 52.57 ± 8.41), but the score of mental component summary (MCS, 31.58 ± 7.72) was extremely low. Caregiver’s illness condition, family size, and household income were significant factors of physical HRQOL. Caregivers with illness and caregivers living in an extended family were associated with higher mental HRQOL. Whereas these two factors had opposite effects on physical HRQOL. This finding indicated poor mental HRQOL among caregivers of CWD in Shanghai and thus requiring urgent attention and intervention. Improving physical fitness, maintaining family integration, and providing financial support should be considered when developing intervention for this population.
Antecedents and Consequences of Information Overload in the COVID-19 Pandemic
Authors: Hong Hyehyun , Kim Hyo Jung
Published: December 2020

The global outbreak of coronavirus disease (COVID-19) in 2020 has significantly affected the information environment as well as the daily life of individuals across the world, with information about COVID-19 dominating all media channels. The information provided at the time of a health crisis like COVID-19 is critical in helping people learn about the disease and the recommendations to prevent infection. However, studies have shown that when people are overwhelmed by too much information (referred to as ‘information overload’), this leads to adverse effects. This study examined the antecedents and consequences of information overload in the context of COVID-19. A survey was conducted among 627 residents in Seoul, South Korea, one of the earliest affected countries in the global outbreak. The results showed that cognitive capacity and the frequency of online news use and interpersonal communication were significant predictors of information overload. Information overload influenced how information is processed; it was associated with the tendency toward greater heuristic processing and less systematic processing. In addition, people were more likely to enact prevention behaviors when the information was processed systematically, as opposed to heuristically. The results are discussed considering both the theoretical and practical implications.
Psoriasis Increases the Risk of Sudden Sensorineural Hearing Loss: A Longitudinal Follow Up Study Using a National Sample Cohort
Authors: Choi Hyo Geun , Park Bumjung , Hong Seok Min , Park Il-Seok , Kim Sung Kyun
Published: December 2020

Psoriasis is a well-known immune-mediated disease. Its autoimmune pathophysiology is consistent with the immune-mediated systemic vascular hypothesis regarding the pathogenesis of sudden sensorineural hearing loss (SSNHL). The purpose of our study was to investigate whether psoriasis affects the prevalence of SSNHL in all age groups matched by age, sex, income, and region of residence. Korean Health Insurance Review and Assessment Service-National Patient Samples were collected from 2002 to 2013. A 1:4 matched psoriasis group (n = 12,864) and control group (n = 51,456) were selected. The crude (simple) and adjusted (Charlson comorbidity index) hazard ratios (HR) for psoriasis and SSNHL were analyzed using the stratified Cox proportional hazard model. The incidence of SSNHL was significantly higher in the psoriasis group than in the control group (0.5% vs. 0.4%, p = 0.004). Psoriasis increased the risk of SSNHL (adjusted HR = 1.44, 95% confidence interval (CI) = 1.09–1.90, p = 0.010). In the stratification analysis, the incidence of SSNHL was significantly higher in the 30–59-year-old group than other group SSNHL (adjusted HR = 1.50, 95% CI = 1.06–2.12, p = 0.023). In addition, SSNHL occurred significantly more frequently in men with psoriasis (adjusted HR = 1.70, 95% CI = 1.17–2.49, p = 0.006). Psoriasis increased the risk of SSNHL, and SSNHL was more prevalent in between the age of 30–59-year-olds and men with psoriasis.
A Scoping Review of How Income Affects Accessing Local Green Space to Engage in Outdoor Physical Activity to Improve Well-Being: Implications for Post-COVID-19
Authors: Spencer Llinos Haf , Lynch Mary , Lawrence Catherine L. , Edwards Rhiannon Tudor
Published: December 2020

Background: The National Institute for Health and Care Excellence (NICE) has set out guidance for promoting physical activity (PA) in the physical environment to promote health and well-being. The aim of this selective scoping review was to investigate the influence of gross income on accessing local green spaces to engage in PA and the associated health benefits. Methods: A scoping review was conducted of international literature to facilitate the clarification of the research question. Findings: 15 papers were critically appraised under two themes: (1) environments and well-being and (2) PA and income/socioeconomic status and impact on the frequency, duration and opportunity to engage in PA. Interpretation: Income is related to differential use of green and blue spaces for PA, due mainly to access issues. People who live in lower socioeconomic areas tend to be more sedentary and there are also gender differences related to PA in built environments. Conclusion: There is an effect of income in using green spaces for PA, but the relationship is non-linear, and there is still a lack of knowledge about what kind of green spaces are best for health benefits. The COVID-19 pandemic highlighted the importance of accessing green local spaces to engage in physical exercise to improve well-being among the public.
Validity of Consumer Activity Monitors and an Algorithm Using Smartphone Data for Measuring Steps during Different Activity Types
Authors: Hartung Verena , Sarshar Mustafa , Karle Viktoria , Shammas Layal , Rashid Asarnusch , Roullier Paul , Eilers Caroline , Mäurer Mathias , Flachenecker Peter , Pfeifer Klaus , Tallner Alexander
Published: December 2020

Background: Consumer activity monitors and smartphones have gained relevance for the assessment and promotion of physical activity. The aim of this study was to determine the concurrent validity of various consumer activity monitor models and smartphone models for measuring steps. Methods: Participants completed three activity protocols: (1) overground walking with three different speeds (comfortable, slow, fast), (2) activities of daily living (ADLs) focusing on arm movements, and (3) intermittent walking. Participants wore 11 activity monitors (wrist: 8; hip: 2; ankle: 1) and four smartphones (hip: 3; calf: 1). Observed steps served as the criterion measure. The mean average percentage error (MAPE) was calculated for each device and protocol. Results: Eighteen healthy adults participated in the study (age: 28.8 ± 4.9 years). MAPEs ranged from 0.3–38.2% during overground walking, 48.2–861.2% during ADLs, and 11.2–47.3% during intermittent walking. Wrist-worn activity monitors tended to misclassify arm movements as steps. Smartphone data collected at the hip, analyzed with a separate algorithm, performed either equally or even superiorly to the research-grade ActiGraph. Conclusion: This study highlights the potential of smartphones for physical activity measurement. Measurement inaccuracies during intermittent walking and arm movements should be considered when interpreting study results and choosing activity monitors for evaluation purposes.
Gender Convergence in Alcohol Consumption Patterns: Findings from the Korea National Health and Nutrition Examination Survey 2007–2016
Authors: Kang Minkyung , Min Ari , Min Haeyoung
Published: December 2020

Gender differences in alcohol use have narrowed over the decades. This study aimed to explore changes in alcohol consumption patterns between 2007 and 2016 to identify gender convergence in alcohol use in Korea. Data from the Korea National Health and Nutrition Examination Survey were used. For all respondents (41,662 girls/women and 32,041 boys/men) aged ≥12 years, lifetime drinking, current drinking, age of drinking onset, heavy alcohol use, and binge drinking were analyzed. Gender differences in heavy alcohol use and binge drinking decreased from 2007 to 2016 (p = 0.001 and p < 0.001, respectively). The prevalence of heavy alcohol use and binge drinking decreased in boys/men (67.5% to 63.9%, p = 0.001; 63.4% to 60.9%, p = 0.001, respectively), but not in girls/women (50.2% to 50.4%, p = 0.279; 30.6% to 32.0%, p = 0.994, respectively). The proportion of lifetime abstainers decreased among both girls/women (24.3% to 19.1%, p < 0.001) and boys/men (12.1% to 9.7%, p = 0.01). In girls/women, the mean age of drinking onset decreased (from 24.1 to 23.6 years, p = 0.017); however, in boys/men, significant changes were not observed (from 18.9 to 18.7 years, p = 0.307). Healthcare providers should be aware of the growing health risks resulting from increased unhealthy alcohol use in women and develop gender-specific preventive interventions.
Associations between COVID-19 Incidence Rates and the Exposure to PM2.5 and NO2: A Nationwide Observational Study in Italy
Authors: Fiasca Fabiana , Minelli Mauro , Maio Dominga , Minelli Martina , Vergallo Ilaria , Necozione Stefano , Mattei Antonella
Published: December 2020

The COVID-19 outbreak disproportionately affected the elderly and areas with higher population density. Among the multiple factors possibly involved, a role for air pollution has also been hypothesized. This nationwide observational study demonstrated the significant positive relationship between COVID-19 incidence rates and PM2.5 and NO2 levels in Italy, both considering the period 2016–2020 and the months of the epidemic, through univariate regression models, after logarithmic transformation of the variables, as the data were not normally distributed. That relationship was confirmed by a multivariate analysis showing the combined effect of the two pollutants, adjusted for the old-age index and population density. An increase in PM2.5 and NO2 concentrations by one unit (1 µg/m3) corresponded to an increase in incidence rates of 1.56 and 1.24 × 104 people, respectively, taking into account the average levels of air pollutants in the period 2016–2020, and 2.79 and 1.24 × 104 people during March–May 2020. Considering the entire epidemic period (March–October 2020), these increases were 1.05 and 1.01 × 104 people, respectively, and could explain 59% of the variance in COVID-19 incidence rates (R2 = 0.59). This evidence could support the implementation of targeted responses by focusing on areas with low air quality to mitigate the spread of the disease.
Associations between Adherence to Combinations of 24-h Movement Guidelines and Overweight and Obesity in Japanese Preschool Children
Authors: Kim Hyunshik , Ma Jiameng , Harada Kenji , Lee Sunkyoung , Gu Ying
Published: December 2020

The interactions between movement behaviors (physical activity, screen time, and sleep) affect the health of preschool children. Therefore, we examined the status of adherence to combinations of 24-hour movement guidelines (24-h MG) in Japanese preschool children and determined the associations between overweight/obesity and adherence to these 24-h MG. This cross-sectional study was conducted with 421 children aged 3–5 years (216 boys and 199 girls) living in the northeastern region of Japan. To evaluate the 24-h MG, physical activity over one week was measured using a three-axis accelerometer. For screen time and sleep duration, a questionnaire survey was conducted. Children who failed to meet all the 24-h MG had a higher probability of overweight/obesity than those who met all the 24-h MG (odds ratio 1.139, 95% confidence interval: 1.009, 1.285). The percentage of adherence to the 24-h MG was 91.6% for physical activity, 82.5% for sleep duration, and 33.7% for screen time, and only 21.5% of the children adhered to all three areas of the guidelines. Our findings have important implications for developing public health policies and effective intervention programs for preschool children.
SARS-COV-2 Serological Profile in Healthcare Professionals of a Southern Italy Hospital
Authors: De Carlo Armando , Lo Caputo Sergio , Paolillo Carmela , Rosa Anna Maria , D’Orsi Umberto , De Palma Maria , Reveglia Pierluigi , Lacedonia Donato , Cinnella Gilda , Foschino Maria Pia , Margaglione Maurizio , Mirabella Lucia , Santantonio Teresa Antonia , Corso Gaetano , Dattoli Vitangelo
Published: December 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the first coronavirus that has caused a pandemic. Assessing the prevalence of anti-SARS-CoV-2 in healthcare worker groups offers a unique opportunity to study the correlation between seroconversion and immunization because of their occupational exposure and a higher risk of contagion. The study enrolled 3242 asymptomatic employees of “Policlinico Riuniti”, Foggia. After the first screening, we collected sequential serum samples for up to 23 weeks from the same subjects. In order to perform a longitudinal follow-up study and get information about the titration of IgG levels, we analyzed data from subjects (33) with at least two consecutive serological IgG—positive tests; 62 (1.9%; 95% CI: 1.4–2.3) tested positive for at least one anti-SARS-CoV-2 antibody. The seroprevalence was lower in the high-risk group 1.4% (6/428; 95% CI: 0.5–2.6) vs. the intermediate-risk group 2.0% (55/2736; 95% CI: 1.5–2.5). Overall, within eight weeks, we detected a mean reduction of –17% in IgG levels. Our data suggest a reduction of about 9.27 AU/mL every week (R2 = 0.35, p = 0.0003). This study revealed the prevalence of SARS-CoV-2 antibodies among Foggia’s hospital healthcare staff (1.9%). Moreover, the IgG level reduction suggests that the serological response fades fast in asymptomatic infections.
Impact of a Postoperative Intervention Educational Program on the Quality of Life of Patients with Hip Fracture: A Randomized, Open-Label Controlled Trial
Authors: Amarilla-Donoso Francisco Javier , Roncero-Martín Raúl , Lavado-García Jesus , Canal-Macías María de la Luz , Pedrera-Canal María , Chimpén-López Carlos , Toribio-Felipe Rosaura , Rico-Martin Sergio , Barrios-Fernández Sabina , López-Espuela Fidel
Published: December 2020

The objective of this study was to determine the impact of a postoperative educational intervention program on the health-related quality of life (HRQoL) of patients with hip fracture using a controlled clinical trial in a randomized, multicenter study. In total, 102 patients (45.5%) from trauma units at the two University Hospitals of the province of Cáceres received the educational program, whereas 122 (54.5%) did not. Patients were consecutively included in either an intervention or a control group. Patients from the intervention group received an educational program during admission and the postoperative period. Patients from the control group did not receive any educational program. These patients were managed according to routine protocols. The patients were predominantly female (76.3%), aged 84.6 years (SD 6.1). All dimensions in both groups at 12 months showed a significant decrease with respect to baseline, except for bodily pain in both groups (p = 0.447; p = 0.827) and social functioning in the intervention group (p = 0.268). Patients receiving the educational program showed higher levels in the dimensions of the Mental Component Summary (MCS-12) (p = 0.043), vitality (p = 0.010), and social functioning (p < 0.001), as well as in the dimensions of the SF-12 health survey questionnaire of HRQoL 12 months after surgery. In conclusion, our study of the intervention group showed that there were significant improvements in MCS-12, vitality, and social function dimensions compared to the control group.
Exploring Mental Health and Illness in the UK Sports Coaching Workforce
Authors: Smith Andy , Haycock David , Jones Jon , Greenough Kenny , Wilcock Rachel , Braid Ian
Published: December 2020

There is growing international concern about the mental health of those who work in sport, including coaches. However, we currently know little about the prevalence of mental illness and the experience of mental health among coaches, and their perceptions and use of workplace mental health support services. Little is also known about coaches’ disclosure of mental illness to, and seeking help from, work colleagues. We explore these issues using data from 202 coaches who responded to the first United Kingdom survey of mental health in the sport and physical activity workforce. In total, 55% of coaches reported having ever experienced a mental illness, and 44% currently did, with coaches in grassroots/community settings being most likely to experience mental illness. Depression and anxiety were the most commonly reported conditions and many coaches preferred to access mental health support outside of the organisation for whom they worked or volunteered, with decisions to seek help from others in the workplace being shaped by complex organisational and personal considerations. The findings suggest there is an important public health challenge which needs to be met among coaches, so that we can better address a question of fundamental importance: ‘who is looking after the people looking after the people’?
Depression and Nicotine Withdrawal Associations with Combustible and Electronic Cigarette Use
Authors: Pergadia Michele L. , Newcomer John W. , Gilbert David G.
Published: December 2020

Depression is a risk factor for nicotine use and withdrawal. Population level epidemiologic studies that include users of either combustible or electronic cigarette (NICUSER) could inform interventions to reduce nicotine dependence in vulnerable populations. The current study examined the relationship between depression diagnosis (DEPDX), NICUSER, and lifetime rates of DSM-V nicotine withdrawal (NW) symptoms in a nationally representative sample of US adults (N = 979), who answered related questions in surveys administered through GfK’s KnowledgePanel. Over 42% of the sample reported lifetime ever combustible cigarette use, 15.6% electronic-cigarette use, and 45.9% either (NICUSER). Weighted logistic regression analyses (controlling for age and gender) found that DEPDX was associated with 2.3 times increased odds (ratio (OR); 95% Confidence Interval (CI): 1.5–3.5) of being a NICUSER. Regarding risks of NW symptoms among NICUSER, models that additionally controlled for frequency of nicotine use found that DEPDX was significantly associated with increased odds of concentration problems (OR = 2.4; 95% CI: 1.3–4.5) and depressed mood (OR = 2.2; 95% CI: 1.1–4.1) when quitting or cutting down on nicotine use. Results highlight the consistent comorbidity between depression, nicotine use, and symptomatic nicotine withdrawal in a population-based sample of combustible and electronic cigarette users.
Programming of Cardiovascular Dysfunction by Postnatal Overfeeding in Rodents
Authors: Josse Marie , Rigal Eve , Rosenblatt-Velin Nathalie , Rochette Luc , Zeller Marianne , Guenancia Charles , Vergely Catherine
Published: December 2020

Nutritional environment in the perinatal period has a great influence on health and diseases in adulthood. In rodents, litter size reduction reproduces the effects of postnatal overnutrition in infants and reveals that postnatal overfeeding (PNOF) not only permanently increases body weight but also affects the cardiovascular function in the short- and long-term. In addition to increased adiposity, the metabolic status of PNOF rodents is altered, with increased plasma insulin and leptin levels, associated with resistance to these hormones, changed profiles and levels of circulating lipids. PNOF animals present elevated arterial blood pressure with altered vascular responsiveness to vasoactive substances. The hearts of overfed rodents exhibit hypertrophy and elevated collagen content. PNOF also induces a disturbance of cardiac mitochondrial respiration and produces an imbalance between oxidants and antioxidants. A modification of the expression of crucial genes and epigenetic alterations is reported in hearts of PNOF animals. In vivo, a decreased ventricular contractile function is observed during adulthood in PNOF hearts. All these alterations ultimately lead to an increased sensitivity to cardiac pathologic challenges such as ischemia-reperfusion injury. Nevertheless, caloric restriction and physical exercise were shown to improve PNOF-induced cardiac dysfunction and metabolic abnormalities, drawing a path to the potential therapeutic correction of early nutritional programming.
Extracellular Vesicles in CNS Developmental Disorders
Authors: Gomes Ana Rita , Sangani Nasim Bahram , Fernandes Tiago G. , Diogo M. Margarida , Curfs Leopold M. G. , Reutelingsperger Chris P.
Published: December 2020

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.
Many Different LINE-1 Retroelements Are Activated in Bladder Cancer
Authors: Whongsiri Patcharawalai , Goering Wolfgang , Lautwein Tobias , Hader Christiane , Niegisch Günter , Köhrer Karl , Hoffmann Michèle J. , Schulz Wolfgang A.
Published: December 2020

Human genomes contain about 100,000 LINE-1 (L1) retroelements, of which more than 100 are intact. L1s are normally tightly controlled by epigenetic mechanisms, which often fail in cancer. In bladder urothelial carcinoma (UC), particularly, L1s become DNA-hypomethylated, expressed and contribute to genomic instability and tumor growth. It is, however, unknown which individual L1s are activated. Following RNA-immunoprecipitation with a L1-specific antibody, third generation nanopore sequencing detected transcripts of 90 individual elements in the VM-Cub-1 UC line with high overall L1 expression. In total, 10 L1s accounted for >60% of the reads. Analysis of five specific L1s by RT-qPCR revealed generally increased expression in UC tissues and cell lines over normal controls, but variable expression among tumor cell lines from bladder, prostate and testicular cancer. Chromatin immunoprecipitation demonstrated active histone marks at L1 sequences with increased expression in VM-Cub-1, but not in a different UC cell line with low L1 expression. We conclude that many L1 elements are epigenetically activated in bladder cancer in a varied pattern. Our findings indicate that expression of individual L1s is highly heterogeneous between and among cancer types.
PPARs and Myocardial Infarction
Authors: Wagner Kay-Dietrich , Wagner Nicole
Published: December 2020

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family. They are ligand-activated transcription factors and exist in three different isoforms, PPARα (NR1C1), PPARβ/δ (NR1C2), and PPARγ (NR1C3). PPARs regulate a variety of functions, including glucose and lipid homeostasis, inflammation, and development. They exhibit tissue and cell type-specific expression patterns and functions. Besides the established notion of the therapeutic potential of PPAR agonists for the treatment of glucose and lipid disorders, more recent data propose specific PPAR ligands as potential therapies for cardiovascular diseases. In this review, we focus on the knowledge of PPAR function in myocardial infarction, a severe pathological condition for which therapeutic use of PPAR modulation has been suggested.
Protein Levels of Several Arabidopsis Auxin Response Factors Are Regulated by Multiple Factors and ABA Promotes ARF6 Protein Ubiquitination
Authors: Li Keke , Wang Sheng , Wu Hong , Wang Hong
Published: December 2020

The auxin response factor (ARF) transcription factors are a key component in auxin signaling and play diverse functions in plant growth, development, and stress response. ARFs are regulated at the transcript level and posttranslationally by protein modifications. However, relatively little is known regarding the control of ARF protein levels. We expressed five different ARFs with an HA (hemagglutinin) tag and observed that their protein levels under the same promoter varied considerably. Interestingly, their protein levels were affected by several hormonal and environmental conditions, but not by the auxin treatment. ABA (abscisic acid) as well as 4 °C and salt treatments decreased the levels of HA-ARF5, HA-ARF6, and HA-ARF10, but not that of HA-ARF19, while 37 °C treatment increased the levels of the four HA-ARFs, suggesting that the ARF protein levels are regulated by multiple factors. Furthermore, MG132 inhibited the reduction of HA-ARF6 level by ABA and 4 °C treatments, suggesting that these treatments decrease HA-ARF6 level through 26S proteasome-mediated protein degradation. It was also found that ABA treatment drastically increased HA-ARF6 ubiquitination, without strongly affecting the ubiquitination profile of the total proteins. Together, these results reveal another layer of control on ARFs, which could serve to integrate multiple hormonal and environmental signals into the ARF-regulated gene expression.
Activation of the miR-371/372/373 miRNA Cluster Enhances Oncogenicity and Drug Resistance in Oral Carcinoma Cells
Authors: Lin Shu-Chun , Wu Hsiao-Li , Yeh Li-Yin , Yang Cheng-Chieh , Kao Shou-Yen , Chang Kuo-Wei
Published: December 2020

Oral squamous cell carcinoma (OSCC) is among the leading causes of cancer-associated deaths worldwide. Family members in miR-371/372/373 miRNA cluster, which is localized at human chromosome 19q13.4, are co-expressed in both human stem cells and malignancies. The individual miRNA in this cluster are also involved in modulating the pathogenesis of malignancies as either oncogenes or suppressors. The 19q13 region is frequently gained in head and neck cancers. High expression of miR-372 and miR-373 are survival predictors for OSCC. However, the role of the miR-371/372/373 cluster in oral carcinogenesis remains to be fully investigated. We use the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 system to establish OSCC cell subclones that had the miR-371/372/373 cluster deleted. In addition, further subclones were established that had the promoter of this cluster deleted. Concordant silencing in SAS cells of miR-371/372/373 decreased oncogenic potential, increased cisplatin sensitivity, activated p53, and upregulated the expression of Bad and DKK1. We also employed the CRISPR/dCas9 synergistic activation mediator system, which allowed robust transcriptional activation of the whole miR-371/372/373 cistron. Upregulation of endogenous miR-371/372/372 expression increased both oncogenicity and drug resistance. These were accompanied by a slight activation of AKT, β-catenin, and Src. This study identifies the oncogenic role of the miR-371/372/373 cluster in OSCC. Using CRISPR based strategy can be a powerful paradigm that will provide mechanistic insights into miRNA cluster functionality, which will also likely help the development of targeting options for malignancies.
Serine Racemase Deletion Affects the Excitatory/Inhibitory Balance of the Hippocampal CA1 Network
Authors: Ploux Eva , Bouet Valentine , Radzishevsky Inna , Wolosker Herman , Freret Thomas , Billard Jean-Marie
Published: December 2020

d-serine is the major co-agonist of N-methyl-D-aspartate receptors (NMDAR) at CA3/CA1 hippocampal synapses, the activation of which drives long-term potentiation (LTP). The use of mice with targeted deletion of the serine racemase (SR) enzyme has been an important tool to uncover the physiological and pathological roles of D-serine. To date, some uncertainties remain regarding the direction of LTP changes in SR-knockout (SR-KO) mice, possibly reflecting differences in inhibitory GABAergic tone in the experimental paradigms used in the different studies. On the one hand, our extracellular recordings in hippocampal slices show that neither isolated NMDAR synaptic potentials nor LTP were altered in SR-KO mice. This was associated with a compensatory increase in hippocampal levels of glycine, another physiologic NMDAR co-agonist. SR-KO mice displayed no deficits in spatial learning, reference memory and cognitive flexibility. On the other hand, SR-KO mice showed a weaker LTP and a lower increase in NMDAR potentials compared to controls when GABAA receptors were pharmacologically blocked. Our results indicate that depletion of endogenous D-serine caused a reduced inhibitory activity in CA1 hippocampal networks, altering the excitatory/inhibitory balance, which contributes to preserve functional plasticity at synapses and to maintain related cognitive abilities.
Anti-Inflammatory Effects of Analogues of N-Acyl Homoserine Lactones on Eukaryotic Cells
Authors: Peyrottes Agathe , Coquant Garance , Brot Loïc , Rainteau Dominique , Seksik Philippe , Grill Jean-Pierre , Mallet Jean-Maurice
Published: December 2020

Background: Since acyl-homoserine lactone (AHL) profiling has been described in the gut of healthy subjects and patients with inflammatory bowel disease (IBD), the potential effects of these molecules on host cells have raised interest in the medical community. In particular, natural AHLs such as the 3-oxo-C12-HSL exhibit anti-inflammatory properties. Our study aimed at finding stable 3-oxo-C12-HSL-derived analogues with improved anti-inflammatory effects on epithelial and immune cells. Methods: We first studied the stability and biological properties of the natural 3-oxo-C12-HSL on eukaryotic cells and a bacterial reporter strain. We then constructed and screened a library of 22 AHL-derived molecules. Anti-inflammatory effects were assessed by cytokine release in an epithelial cell model, Caco-2, and a murine macrophage cell line, RAW264.7, (respectively, IL-8 and IL-6) upon exposure to the molecule and after appropriate stimulation (respectively, TNF-α 50 ng/mL and IFN-γ 50 ng/mL, and LPS 10 ng/mL and IFN-γ 20 U/mL). Results: We found two molecules of interest with amplified anti-inflammatory effects on mammalian cells without bacterial-activating properties in the reporter strain. The molecules furthermore showed improved stability in biological medium compared to the native 3-oxo-C12-HSL. Conclusions: We provide new bio-inspired AHL analogues with strong anti-inflammatory properties that will need further study from a therapeutic perspective.
Molecular Insights into Determinants of Translational Readthrough and Implications for Nonsense Suppression Approaches
Authors: Lombardi Silvia , Testa Maria Francesca , Pinotti Mirko , Branchini Alessio
Published: December 2020

The fidelity of protein synthesis, a process shaped by several mechanisms involving specialized ribosome regions and external factors, ensures the precise reading of sense and stop codons. However, premature termination codons (PTCs) arising from mutations may, at low frequency, be misrecognized and result in PTC suppression, named ribosome readthrough, with production of full-length proteins through the insertion of a subset of amino acids. Since some drugs have been identified as readthrough inducers, this fidelity drawback has been explored as a therapeutic approach in several models of human diseases caused by nonsense mutations. Here, we focus on the mechanisms driving translation in normal and aberrant conditions, the potential fates of mRNA in the presence of a PTC, as well as on the results obtained in the research of efficient readthrough-inducing compounds. In particular, we describe the molecular determinants shaping the outcome of readthrough, namely the nucleotide and protein context, with the latter being pivotal to produce functional full-length proteins. Through the interpretation of experimental and mechanistic findings, mainly obtained in lysosomal and coagulation disorders, we also propose a scenario of potential readthrough-favorable features to achieve relevant rescue profiles, representing the main issue for the potential translatability of readthrough as a therapeutic strategy.
Molecular Mechanisms in Early Diabetic Kidney Disease: Glomerular Endothelial Cell Dysfunction
Authors: Lassén Emelie , Daehn Ilse S.
Published: December 2020

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), with prevalence increasing at an alarming rate worldwide and today, there are no known cures. The pathogenesis of DKD is complex, influenced by genetics and the environment. However, the underlying molecular mechanisms that contribute to DKD risk in about one-third of diabetics are still poorly understood. The early stage of DKD is characterized by glomerular hyperfiltration, hypertrophy, podocyte injury and depletion. Recent evidence of glomerular endothelial cell injury at the early stage of DKD has been suggested to be critical in the pathological process and has highlighted the importance of glomerular intercellular crosstalk. A potential mechanism may include reactive oxygen species (ROS), which play a direct role in diabetes and its complications. In this review, we discuss different cellular sources of ROS in diabetes and a new emerging paradigm of endothelial cell dysfunction as a key event in the pathogenesis of DKD.
Supramolecular Architectures of Nucleic Acid/Peptide Hybrids
Authors: Higashi Sayuri L. , Rozi Normazida , Hanifah Sharina Abu , Ikeda Masato
Published: December 2020

Supramolecular architectures that are built artificially from biomolecules, such as nucleic acids or peptides, with structural hierarchical orders ranging from the molecular to nano-scales have attracted increased attention in molecular science research fields. The engineering of nanostructures with such biomolecule-based supramolecular architectures could offer an opportunity for the development of biocompatible supramolecular (nano)materials. In this review, we highlighted a variety of supramolecular architectures that were assembled from both nucleic acids and peptides through the non-covalent interactions between them or the covalently conjugated molecular hybrids between them.
Peptide-Based Identification of Phytophthora Isolates and Phytophthora Detection in Planta
Authors: Berka Miroslav , Greplová Marie , Saiz-Fernández Iñigo , Novák Jan , Luklová Markéta , Zelená Pavla , Tomšovský Michal , Brzobohatý Břetislav , Černý Martin
Published: December 2020

Phytophthora is arguably one of the most damaging genera of plant pathogens. This pathogen is well suited to transmission via the international plant trade, and globalization has been promoting its spread since the 19th century. Early detection is essential for reducing its economic and ecological impact. Here, a shotgun proteomics approach was utilized for Phytophthora analysis. The collection of 37 Phytophthora isolates representing 12 different species was screened for species-specific peptide patterns. Next, Phytophthora proteins were detected in planta, employing model plants Solanum tuberosum and Hordeum vulgare. Although the evolutionarily conserved sequences represented more than 10% of the host proteome and limited the pathogen detection, the comparison between qPCR and protein data highlighted more than 300 protein markers, which correlated positively with the amount of P. infestans DNA. Finally, the analysis of P. palmivora response in barley revealed significant alterations in plant metabolism. These changes included enzymes of cell wall metabolism, ROS production, and proteins involved in trafficking. The observed root-specific attenuation in stress–response mechanisms, including the biosynthesis of jasmonates, ethylene and polyamines, and an accumulation of serotonin, provided the first insight into molecular mechanisms behind this particular biotic interaction.
Behaviour of Vascular Smooth Muscle Cells on Amine Plasma-Coated Materials with Various Chemical Structures and Morphologies
Authors: Nemcakova Ivana , Blahova Lucie , Rysanek Petr , Blanquer Andreu , Bacakova Lucie , Zajíčková Lenka
Published: December 2020

Amine-coated biodegradable materials based on synthetic polymers have a great potential for tissue remodeling and regeneration because of their excellent processability and bioactivity. In the present study, we have investigated the influence of various chemical compositions of amine plasma polymer (PP) coatings and the influence of the substrate morphology, represented by polystyrene culture dishes and polycaprolactone nanofibers (PCL NFs), on the behavior of vascular smooth muscle cells (VSMCs). Although all amine-PP coatings improved the initial adhesion of VSMCs, 7-day long cultivation revealed a clear preference for the coating containing about 15 at.% of nitrogen (CPA-33). The CPA-33 coating demonstrated the ideal combination of good water stability, a sufficient amine group content, and favorable surface wettability and morphology. The nanostructured morphology of amine-PP-coated PCL NFs successfully slowed the proliferation rate of VSMCs, which is essential in preventing restenosis of vascular replacements in vivo. At the same time, CPA-33-coated PCL NFs supported the continuous proliferation of VSMCs during 7-day long cultivation, with no significant increase in cytokine secretion by RAW 264.7 macrophages. The CPA-33 coating deposited on biodegradable PCL NFs therefore seems to be a promising material for manufacturing small-diameter vascular grafts, which are still lacking on the current market.
Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice
Authors: Debreceni Ivy L. , Chimenti Michael S. , Serreze David V. , Geurts Aron M. , Chen Yi-Guang , Lieberman Scott M.
Published: December 2020

Sjögren syndrome (SS) is an immunologically complex, chronic autoimmune disease targeting lacrimal and salivary glands. Nonobese diabetic (NOD) mice spontaneously develop inflammation of lacrimal and salivary glands with histopathological features similar to SS in humans including focal lymphocytic infiltrates in the affected glands. The innate immune signals driving lymphocytic infiltration of these glands are not well-defined. Here we evaluate the role of Toll-like receptor (TLR) 7 in the development of SS-like manifestations in NOD mice. We created a Tlr7 knockout NOD mouse strain and performed histological and gene expression studies to characterize the effects of TLR7 on autoimmunity development. TLR7 was required for male-specific lacrimal gland inflammation but not for female-specific salivary gland inflammation. Moreover, TLR7 was required for type 1 diabetes development in male but not female NOD mice. RNA sequencing demonstrated that TLR7 was associated with a type I interferon (IFN) response and a type I IFN-independent B cell response in the lacrimal glands. Together these studies identify a previously unappreciated pathogenic role for TLR7 in lacrimal gland autoimmunity and T1D development in male NOD mice adding to the growing body of evidence supporting sex differences in mechanisms of autoimmune disease in NOD mice.
In-Situ Investigation on Nanoscopic Biomechanics of Streptococcus mutans at Low pH Citric Acid Environments Using an AFM Fluid Cell
Authors: Nguyen Linh Thi Phuong , Liu Bernard Haochih
Published: December 2020

Streptococcus mutans (S. mutans) is widely regarded as the main cause of human dental caries via three main virulence factors: adhesion, acidogenicity, and aciduricity. Citric acid is one of the antibiotic agents that can inhibit the virulence capabilities of S. mutans. A full understanding of the acidic resistance mechanisms (ARMs) causing bacteria to thrive in citrate transport is still elusive. We propose atomic force microscopy (AFM) equipped with a fluid cell to study the S. mutans ARMs via surface nanomechanical properties at citric acid pH 3.3, 2.3, and 1.8. Among these treatments, at pH 1.8, the effect of the citric acid shock in cells is demonstrated through a significantly low number of high adhesion zones, and a noticeable reduction in adhesion forces. Consequently, this study paves the way to understand that S. mutans ARMs are associated with the variation of the number of adhesion zones on the cell surface, which is influenced by citrate and proton transport. The results are expected to be useful in developing antibiotics or drugs involving citric acid for dental plaque treatment.