bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighborhood Environment Associates with Trimethylamine-N-Oxide (TMAO) as a Cardiovascular Risk Marker
Authors: Farmer Nicole , Gutierrez-Huerta Cristhian A. , Turner Briana S. , Mitchell Valerie M. , Collins Billy S. , Baumer Yvonne , Wallen Gwenyth R. , Powell-Wiley Tiffany M.
Published: April 2021

Background: Neighborhoods and the microbiome are linked to cardiovascular disease (CVD), yet investigations to identify microbiome-related factors at neighborhood levels have not been widely investigated. We sought to explore relationships between neighborhood deprivation index (NDI) and the microbial metabolite, trimethylamine-N-oxide. We hypothesized that inflammatory markers and dietary intake would be mediators of the relationship. Methods: African-American adults at risk for CVD living in the Washington, DC area were recruited to participate in a cross-sectional community-based study. US census-based neighborhood deprivation index (NDI) measures (at the census-tract level) were determined. Serum samples were analyzed for CVD risk factors, cytokines, and the microbial metabolite, trimethylamine-N-oxide (TMAO). Self-reported dietary intake based on food groups was collected. Results: Study participants (n = 60) were predominantly female (93.3%), with a mean (SD) age of 60.83 (+/−10.52) years. Mean (SD) NDI was −1.54 (2.94), and mean (SD) TMAO level was 4.99 (9.65) µmol/L. Adjusting for CVD risk factors and BMI, NDI was positively associated with TMAO (β = 0.31, p = 0.02). Using mediation analysis, the relationship between NDI and TMAO was significantly mediated by TNF-α (60.15%) and interleukin)-1 β (IL; 49.96%). When controlling for clustering within neighborhoods, the NDI-TMAO association was no longer significant (β = 5.11, p = 0.11). However, the association between NDI and IL-1 β (β = 0.04, p = 0.004) and TNF-α (β = 0.17, p = 0.003) remained. Neither NDI nor TMAO was significantly associated with daily dietary intake. Conclusion and Relevance: Among a small sample of African-American adults at risk for CVD, there was a significant positive relationship with NDI and TMAO mediated by inflammation. These hypothesis-generating results are initial and need to be confirmed in larger studies.
Women’s Depressive Symptoms during the COVID-19 Pandemic: The Role of Pregnancy
Authors: Yirmiya Karen , Yakirevich-Amir Noa , Preis Heidi , Lotan Amit , Atzil Shir , Reuveni Inbal
Published: April 2021

The Coronavirus Disease 2019 (COVID-19) pandemic has multiple ramifications for pregnant women. Untreated depression during pregnancy may have long-term effects on the mother and offspring. Therefore, delineating the effects of pregnancy on the mental health of reproductive-age women is crucial. This study aims to determine the risk for depressive symptoms in pregnant and non-pregnant women during COVID-19, and to identify its bio-psycho-social contributors. A total of 1114 pregnant and 256 non-pregnant women were recruited via social media in May 2020 to complete an online survey that included depression and anxiety questionnaires, as well as demographic, obstetric and COVID-19-related questionnaires. Pregnant women also completed the Pandemic-Related Pregnancy Stress Scale (PREPS). Pregnant women reported fewer depressive symptoms and were less concerned that they had COVID-19 than non-pregnant women. Among pregnant women, risk factors for depression included lower income, fewer children, unemployment, thinking that one has COVID-19, high-risk pregnancy, earlier gestational age, and increased pregnancy-related stress. Protective factors included increased partner support, healthy behaviors, and positive appraisal of the pregnancy. Thus, being pregnant is associated with reduced risk for depressive symptoms during the pandemic. Increased social support, engaging in health behaviors and positive appraisal may enhance resilience. Future studies of pregnant versus non-pregnant women could clarify the role of pregnancy during stressful events, and clarify aspects of susceptibility and resilience during pregnancy.
Assessment of the Hearing Status of School-Age Children from Rural and Urban Areas of Mid-Eastern Poland
Authors: Pilka Edyta , Jedrzejczak W. Wiktor , Kochanek Krzysztof , Pastucha Malgorzata , Skarzynski Henryk
Published: April 2021

(1) Background: The purpose of this study was to assess the prevalence of hearing loss in school-age children from rural and urban areas of mid-eastern Poland using standard audiological tests—pure tone audiometry (PTA), impedance audiometry (IA), and otoacoustic emissions (OAEs). (2) Methods: Data were collected from a group of 250 children aged 8 to 13, made up of 122 children from urban areas and 128 children from rural areas of mid-eastern Poland. Hearing was assessed in each of the subjects by means of PTA, IA (tympanometry), and transient-evoked OAEs (TEOAEs). Otoscopy was also performed. (3) Results: There were significantly fewer abnormal results in children from urban than rural areas: they were, respectively, 10.1% and 23.1% for IA, 3% and 9.7% for PTA, and 17.3% and 31.8% for TEOAEs. For hearing-impaired ears in rural areas (failed TEOAE), hearing thresholds were, on average, 11.5 dB higher at 0.5 kHz than for children in urban areas. Comparison of each PTA result with the corresponding IA showed that all cases of hearing loss were related to malfunction of the middle ear. (4) Conclusions: The results of all three hearing tests were significantly worse in children from rural areas compared to those from urban areas. This indicates that audiological healthcare in rural areas needs improvement and that universal hearing screening programs for school-age children would be helpful.
Influence of Recurrent Laryngeal Nerve Transient Unilateral Palsy on Objective Voice Parameters and on Voice Handicap Index after Total Thyroidectomy (Including Thyroid Carcinoma)
Authors: Veldova Zuzana , Holy Richard , Rotnagl Jan , Younus Temoore , Hlozek Jiri , Astl Jaromir
Published: April 2021

Introduction: Total thyroidectomy (TT) is one of the most common surgical endocrine surgeries. Voice impairment after TT can occur not only in patients with recurrent laryngeal nerve (RLN) transient paralysis, but also in cases of normal vocal cord mobility. Aim: To compare voice limits using a speech range profile (SRP) in patients before and 14 days after TT and to investigate the influence of the early results of voice quality after TT on the personal lives of patients. We focused on the perception of voice change before and shortly after TT. Materials and methods: A retrospective study, in the period 2018–2020, included 65 patients aged 22–75 years. We compared two groups of patients: group I (n = 45) (without RLN paresis) and group II (n = 20) (with early transient postoperative RLN paresis). Patients underwent video flexible laryngocopy, SRP, and Voice Handicap Index-30 (VHI-30). Results: In group I, the mean values of Fmax (maximum frequency) and Imax (maximum intensity) decreased in women (both p = 0.001), and VHI-30 increased (p = 0.001). In group II after TT in women, the mean Fmax and Imax values decreased (p = 0.005 and p = 0.034), and the frequency range of the voice was reduced from 5 to 2 semitones. The dynamic range of the voice was reduced by 3.4 dB in women and 5.1 dB in men.VHI-30 increased (p = 0.001). Conclusion: The study documented a worsening of the mean values of SRP, VHI-30, and voice parameters of patients in group II. Voice disorders also occurred in group I without RLN paresis. Non-paretic causes can also contribute to voice damage after TT. SRP and VHI-30 are suitable tools for comparing voice status in two groups of patients, including those with dysphonia. Our data support the claim that the diagnosis of a thyroid cancer does not necessarily imply a higher postoperative risk of impaired voice quality for the patient.
Structural Equation Model of Elementary School Students’ Quality of Life Related to Smart Devices Usage Based on PRECEDE Model
Authors: Lee Jin-Pyo , Lee Yang-Sook
Published: April 2021

Korean elementary school students have the lowest life satisfaction levels among OECD countries. The use of smart devices has led to smartphone addiction, which seriously affects their quality of life. This study aims to establish and test variables that affect the quality of life (QOL) of elementary school students based on the Predisposing, Reinforcing and Enabling Constructs in Educational Diagnosis and Evaluation (PRECEDE) model, using smart device-related parental intervention, self-efficacy, social support, health promotion behaviors, family environment, smart device addiction, and QOL as measurement variables. Three elementary schools in the Republic of Korea completed self-report questionnaires. Descriptive statistical analysis and hypothetical model fit and test were used for data analysis. The model was found to be valid. Smart device addiction directly affected QOL. In contrast, health promotion behaviors, self-efficacy, social support, and smart device parental intervention indirectly affected QOL. Health-promoting behaviors also directly affected smart device addiction, self-efficacy, and family environment had a direct effect on health-promoting behavior. Therefore, to improve the QOL of elementary school students, the government should focus on developing programs that can help them actively perform health promotion activities and improve self-efficacy, social support, and parental intervention for smart devices that indirectly affect them.
How Does a Community Respond to Changes in Aircraft Noise? A Comparison of Two Surveys Conducted 11 Years Apart in Ho Chi Minh City
Authors: Trieu Bach Lien , Nguyen Thu Lan , Hiraguri Yasuhiro , Morinaga Makoto , Morihara Takashi
Published: April 2021

There have been many arguments about findings of an increase in noise annoyance over time and a recommendation of stricter limits on aircraft noise levels to protect the health of residents around airports. It is crucial to examine if the established exposure–response relationship is suitable for designing future aircraft noise regulations. This study was focused on identifying changes in response to noise over time by comparing community responses from two surveys conducted in 2008 and 2019 at Tân Sơn Nhất (TSN) international airport. Annoyance was found to significantly reduce in 2019 compared to 2008; however, changes in sleep quality were relatively small. Unexpectedly, a gradual increase in the annoyance due to aircraft noise was not found. Results of multiple regression analysis indicated that differences in the reaction of the residents to noise in the two studies were significantly attributed to nonacoustic factors. Noise sensitivity and dissatisfaction with the living environment (e.g., inconvenience in accessing workplace) considerably affect noise annoyance, whereas noise sensitivity, age, and dissatisfaction with the green environment of living areas affect sleep quality. These findings suggest the fulfillment of desired living environment as effective measures for mitigating noise impacts on residents in the vicinity of busy airports.
Factors Associated with Non-Adherence to Drugs in Patients with Chronic Diseases Who Go to Pharmacies in Spain
Authors: Llorca Carmen Valdés y , Cortés Castell Ernesto , Ribera Casado José Manuel , de Lucas Ramos Pilar , Casteig Ayestarán José Luis , Casteig Blanco Amaia , Gil Guillén Vicente Francisco , Rizo Baeza Mercedes
Published: April 2021

Background. Pharmacological non-adherence in chronic diseases is 40–65%. No predictive profile of non-adherence exists in patients with multiple chronic diseases. Our study aimed to quantify the prevalence of non-adherence to pharmacological treatment and its associated factors in patients who visit pharmacies in Spain. Methods. This observational cross-sectional study included patients with one or more chronic diseases. The variables analyzed were demographics, diseases involved, self-medication, information about disease, and lifestyle. The main variable was adherence using the Morisky–Green test. A total of 132 pharmacies collaborated, providing 6327 patients representing all Spain regions (April–December 2016). Bivariate and multivariate analyses were performed and the area under the receiver operating characteristic (ROC) curve was calculated. Results. Non-adherence was 48.4% (95% confidence interval (CI): 47.2–49.7%). The variables that reached significance in the multivariate model were: difficulty in taking medication, self-medication, desire for more information, smoking, lower physical activity, younger age and number of chronic treatments. Discrimination was satisfactory (area under the ROC curve = 70%). Our study found that 50% patients was non-adherent and we obtained a profile of variables associated with therapeutic non-adherence. Conclusions. It is cause for concern that in patients with multiple diseases and taking multiple medications, there is an association between non-adherence, self-medication and worse lifestyle.
Comparison of Modern Drinking Water Network Maintenance Methods: Evaluation of Removed Deposits in the Form of Total Suspended Solids (TSS)
Authors: Jurek Vidlářová Petra , Heviánková Silvie
Published: April 2021

Water pipe sediment removal should be implemented as an integral part of water mains maintenance in order to steadily supply consumers with drinking water of high quality. Considering the number of different water pipe sediment removal methods, the article aims to evaluate the currently used methods to remove water pipe sediment from the pipes of the drinking water distribution system. The evaluation compares the implementation requirements of each method as well as the quality and the quantity of the removed products. The tested methods were unidirectional flushing, Comprex®, and Ice Pigging®. The results of the comparison are expressed in terms of total suspended solids (TSS) recovery, metals mass concentration and water consumption. Since contamination can settle along the entire surface of the pipeline, it is most appropriate to recalculate the results per unit area of the pipeline. The results point at the following efficiency the Comprex® method was the most efficient in removing TSS, Ice Pigging® was the next and unidirectional flushing removed a negligible amount of TSS compared to the other two methods. The absolute recovery of TSS was 0.12–3.01 g·m−2 in unidirectional flushing of plastic pipes, 1.58–8.54 g·m−2 in unidirectional flushing of metal pipes, 4.36–47.53 g·m−2 in Ice Pigging®, and 5.19–69.23 g·m−2 in Comprex®. The composition of the sediment was strongly influenced by particle origin: Pipe material affected the crystalline phase of the sediment and the water source and the age of the pipe affected the amorphous phase of the sediment. Therefore, it was found that evaluation of efficiency based on the amount of TSS removed is only suitable for sites that meet the same conditions as pipe material, water source and ideally the pipe age. It has further been found that the Comprex® method can be advantageously used in real conditions to clean pipes with insufficient hydraulic conditions (such as with a high level of incrustation), as the cleaning has low water flow velocity requirements.
Can Rules in Technical-Tactical Decisions Influence on Physical and Mental Load during Soccer Training? A Pilot Study
Authors: García-Calvo Tomás , Pulido Juan José , Ponce-Bordón José Carlos , López-Gajardo Miguel Ángel , Teoldo Costa Israel , Díaz-García Jesús
Published: April 2021

This study aimed to analyze the effects of rules limitations in pass decisions during soccer tasks on physical and mental load reported by players. Participants were 40 semiprofessional Spanish soccer players (Mage = 22.40, SD = 2.25) from two male teams. Two training sessions with four tasks (same tasks with different score system: two maintaining ball possession games with goalkeepers, and two maintaining ball possession games) in counterbalanced order between teams were completed. To achieve a goal during limitation tasks, a minimum number of players had to participate in the passes before the goal. Internal (perceived effort and heart rate) and external physical load (distances), mental load (validated adaptation of the NASA-TXL) and fatigue (VASfatigue) were quantified. Paired t-test and magnitude-based inference were conducted. The results showed significantly higher mean speeds (p < 0.01), effort perception (p < 0.001), and mental fatigue (very likely positive) during possession games with restrictions. Additionally, performance satisfaction obtained significantly higher values with goalkeepers and pass restrictions (very likely positive). External physical load showed no significant differences between situations. The influence of mental fatigue on internal load and the complexity of the tasks could explain these results. Coaches can use this information to manipulate the training load in ecological conditions.
Effect of Ethnicity on Changes in Fat and Carbohydrate Oxidation in Response to Short-Term High Intensity Interval Training (HIIT): A Pilot Study
Authors: Astorino Todd A. , De Revere Jamie L.
Published: April 2021

This study compared changes in substrate metabolism with high intensity interval training (HIIT) in women of different ethnicities. Twelve Caucasian (C) and ten Hispanic women (H) (age = 24 ± 5 yr) who were inactive completed nine sessions of HIIT at 85 percent peak power output (%PPO). Pre-training, changes in fat oxidation (FOx) and carbohydrate oxidation (CHOOx) during progressive cycling were measured on two days to compute the minimum difference (MD). This test was repeated after the last training session. Between baseline tests, estimates of FOx and CHOOx were not different (p > 0.05) and were highly related (intraclass correlation coefficient equal to 0.72 to 0.88), although the coefficient of variation of maximal fat oxidation (MFO) was equal to 30%. Training significantly increased MFO (p = 0.03) in C (0.19 ± 0.06 g/min to 0.21 ± 0.06 g/min, d = 0.66) and H (0.16 ± 0.03 g/min to 0.19 ± 0.03 g/min, d = 1.3) that was similar (p = 0.92) between groups. There was a significant interaction for FOx (p = 0.003) as it was only increased in H versus C, although both groups exhibited reduced CHO oxidation (p = 0.002) with training. Use of MD revealed that only 3 of 22 women show meaningful increases in MFO (>0.08 g/min). The preliminary data reveals that a small dose of low-volume HIIT does not alter fat and CHO oxidation and there is little effect of ethnicity on the response to training.
Impact of the COVID-19 Pandemic on Estonian Elite Athletes: Survey on Mental Health Characteristics, Training Conditions, Competition Possibilities, and Perception of Supportiveness
Authors: Parm Ülle , Aluoja Anu , Tomingas Tuuli , Tamm Anna-Liisa
Published: April 2021

Background: The postponement and cancellation of the competition season due to COVID-19 could cause significant mental health problems for an elite athlete. The aim of this study was to describe the mental health characteristics of Estonian elite athletes, their training conditions, competition possibilities, and the support they received during COVID-19. Methods: Athletes completed self-reported questionnaires (including Emotional State Questionnaire). The authors applied descriptive statistics, t-test, and χ2 test for comparison of study groups (p < 0.05). Results: Altogether 102 athletes (♂ = 44) were surveyed. The most disturbing issue for athletes was the closing of training centers (57.8%) and cancellation of competitions (50%); 64.7% of athletes reported a negative response from not being able to visit healthcare specialists. Fortunately, athletes could receive virtual coaching. Two-thirds of the athletes had some indication of distress (♀ > ♂): 25% of males and 39.7% of females had symptoms indicating depression; ♀ = 27.6%, ♂ = 13.6% anxiety; ♀ = 56.9%, ♂ = 31.8% fatigue (p = 0.021); ♀ = 55.1%, ♂ = 27.2% insomnia (p = 0.009); 27.5% thought about ending their career (frequency in high distress group compared with low: p = 0.022); and 2.9% were certain they would stop their training completely. Family members were the biggest emotional supporters; 16.7% did not get support from anyone. Conclusion: The Estonian sport community needs to adapt to life in a pandemic environment and help athletes to maintain training and competition activities and in turn, their mental health.
The Influence of a Psychosocial Rehabilitation Program in a Community Health Setting for Patients with Chronic Mental Disorders
Authors: Rasmus Paweł , Lipert Anna , Pękala Krzysztof , Timler Małgorzata , Kozłowska Elżbieta , Robaczyńska Katarzyna , Sobów Tomasz , Kozłowski Remigiusz , Marczak Michał , Timler Dariusz
Published: April 2021

Purpose: To examine (a) the amount of health-related behavior, (b) the level of generalized optimism, (c) the belief about patients’ abilities to cope with difficult situations and obstacles and (d) the subjective sense of social exclusion at baseline and at follow-up among patients with chronic mental health issues participating in a psychosocial rehabilitation program in a community mental health setting. Materials and Methods: This prospective study involved 52 participants aged 18–43 years and diagnosed with mental illness who participated in a 6-month psychosocial rehabilitation program, organized within a special community setting. Different questionnaires were used: the Health-Related Behavior Questionnaire, the Revised Life Orientation Test, the General Self-Efficacy Scale, the Personal Competence Scale and a self-made questionnaire concerning social exclusion problems. Results: Statistical analysis of the questionnaire results taken at the beginning and end of the six-month course, running from November 2015 to May 2016, revealed significant increases in health-related behavior (p = 0.006) and general self-efficacy (p = 0.01). Conclusions: Psychosocial rehabilitation programs offered by community mental health settings might serve as an easy, accessible strategy to deal with different interpersonal and intrapersonal problems and as a potential way to improve health behavior. Further research is required to evaluate other psychosocial rehabilitation programs in different community mental health settings in Lodz Voivodeship, Poland.
Second-Hand Smoke and Its Synergistic Effect with a Body-Mass Index of >24.9 kg/m2 Increase the Risk of Gout Arthritis in Indonesia
Authors: Kurniasari Maria Dyah , Karwur Ferry Fredy , Rayanti Rosiana Eva , Dharmana Edi , Rias Yohanes Andy , Chou Kuei Ru , Tsai Hsiu-Ting
Published: April 2021

To analyze the association between smoking status (active smoking and exposure to Second-Hand Smoking (SHS)) and the synergistic effect of smoking status and BMI with gout risk, a community-based case-control design was undertaken among 385 participants, including 304 healthy controls and 81 gout patients from seven community health services. Adjusted Odd Ratios (AORs) and 95% Confidence Interval (CIs) of gout for active smoking and SHS were 3.26 (95% CI = 1.07~9.90) and 4.67 (95% CI = 2.18~10.00) compared to non-smokers. Time-dependent manner of active smoking and SHS significantly increased gout risk with AORs and 95% CIs of 5.95 (1.41~25.03) and 10.12 (3.51~29.14). Dose-dependency of active smokers and SHS showed AORs and 95% CIs of 5.15 (1.28~20.63) and 4.37 (1.33~14.28). Smoking 20 cigarettes (one pack) per day for one year is equivalent to one pack-year. Active smoking >20 pack-year and SHS > 26.5 pack-year increased gout risk with AORs and 95% CIs of 7.18 (1.53~33.67) and 9.95 (3.64~27.22). Participants who smoked (active smoking and SHS) and with Body Mass Index (BMI) of > 24.9 kg/m2 synergistically increased gout risk, with an AOR of 9.65 and 95% CI of 3.25~28.65, compared to BMI ≤ 24.9 kg/m2 and non-smoker. Smoking status (active smoking and SHS) and the synergistic effect of smoking status and BMI increased gout risk in Indonesia.
Self-Esteem, Socioeconomic Status and Social Participation of Persons with Disabilities Living in Areas Affected by Armed Conflict in Colombia
Authors: Yamada Takuya , Sakisaka Kayako , Bermúdez Rodríguez Lady Nayibe , Yamaoka Kazue
Published: April 2021

This cross-sectional study explored the association between self-esteem and social participation of persons with disabilities living in two municipalities affected by armed conflict in Colombia. We studied the socioeconomic status, communication level, social participation, and self-esteem of the participants. The Rosenberg Self-Esteem Scale (RSES) was used to evaluate the level of self-esteem. We performed bivariate analysis and multiple regression analysis to identify the determinants of higher self-esteem in the target populations. In total, there were 579 participants in the study. The mean RSES score was 28.8 (SD = 4.5). Self-esteem was associated with monthly household income (β = 0.45, p = 0.028), education level (β = 0.65, p = 0.048), current job (β = 1.00, p = 0.017), type of disability (β = −1.17, p = 0.002), frequency of communication with neighbors or friends (β = 0.53, p = 0.013), and participation in community organization activities (β = 0.89, p = 0.019). Frequent communication with their own community, higher levels of school education, and having a job were determinants of higher self-esteem in persons with disabilities. We suggest the importance of an active inclusive reconstruction program to support persons with disabilities in local municipalities affected by armed conflict in developing countries.
Citric Acid Cycle Metabolites Predict Infarct Size in Pigs Submitted to Transient Coronary Artery Occlusion and Treated with Succinate Dehydrogenase Inhibitors or Remote Ischemic Perconditioning
Authors: Consegal Marta , Núñez Norberto , Barba Ignasi , Benito Begoña , Ruiz-Meana Marisol , Inserte Javier , Ferreira-González Ignacio , Rodríguez-Sinovas Antonio
Published: April 2021

Succinate dehydrogenase (SDH) inhibition with malonate during reperfusion reduced myocardial infarction in animals, whereas its endogenous substrate, succinate, is detected in plasma from STEMI patients. We investigated whether protection by SDH inhibition is additive to that of remote ischemic perconditioning (RIC) in pigs submitted to transient coronary artery occlusion, and whether protective maneuvers influence plasma levels of citric acid cycle metabolites. Forty pigs were submitted to 40 min coronary occlusion and reperfusion, and allocated to four groups (controls, sodium malonate 10 mmol/L, RIC, and malonate + RIC). Plasma was obtained from femoral and great cardiac veins and analyzed by LC-MS/MS. Malonate, RIC, and malonate + RIC reduced infarct size (24.67 ± 5.98, 25.29 ± 3.92 and 29.83 ± 4.62% vs. 46.47 ± 4.49% in controls, p < 0.05), but no additive effects were detected. Enhanced concentrations of succinate, fumarate, malate and citrate were observed in controls during initial reperfusion in the great cardiac vein, and most were reduced by cardioprotective maneuvers. Concentrations of succinate, fumarate, and malate significantly correlated with infarct size. In conclusion, despite the combination of SDH inhibition during reperfusion and RIC did not result in additive protection, plasma concentrations of selected citric acid cycle metabolites are attenuated by protective maneuvers, correlate with irreversible injury, and might become a prognosis tool in STEMI patients.
A Metal-Free, Disulfide Oxidized Form of Superoxide Dismutase 1 as a Primary Misfolded Species with Prion-Like Properties in the Extracellular Environments Surrounding Motor Neuron-Like Cells
Authors: Takashima Chika , Kosuge Yasuhiro , Inoue Masahisa , Ono Shin-Ichi , Tokuda Eiichi
Published: April 2021

Superoxide dismutase 1 (SOD1) is a metalloenzyme with high structural stability, but a lack of Cu and Zn ions decreases its stability and enhances the likelihood of misfolding, which is a pathological hallmark of amyotrophic lateral sclerosis (ALS). A growing body of evidence has demonstrated that misfolded SOD1 has prion-like properties such as transmissibility between cells and intracellular propagation of misfolding of natively folded SOD1. Recently, we found that SOD1 is misfolded in the cerebrospinal fluid of sporadic ALS patients, providing a route by which misfolded SOD1 spreads via the extracellular environment of the central nervous system. Unlike intracellular misfolded SOD1, it is unknown which extracellular misfolded species is most relevant to prion-like properties. Here, we determined a conformational feature of extracellular misfolded SOD1 that is linked to prion-like properties. Using culture media from motor neuron-like cells, NSC-34, extracellular misfolded wild-type, and four ALS-causing SOD1 mutants were characterized as a metal-free, disulfide oxidized form of SOD1 (apo-SOD1S-S). Extracellular misfolded apo-SOD1S-S exhibited cell-to-cell transmission from the culture medium to recipient cells as well as intracellular propagation of SOD1 misfolding in recipient cells. Furthermore, culture medium containing misfolded apo-SOD1S-S exerted cytotoxicity to motor neuron-like cells, which was blocked by removal of misfolded apo-SOD1S-S from the medium. We conclude that misfolded apo-SOD1S-S is a primary extracellular species that is linked to prion-like properties.
Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development
Authors: Fuhrmann Lars , Lindner Saskia , Hauser Alexander-Thomas , Höse Clemens , Kretz Oliver , Cohen Clemens D. , Lindenmeyer Maja T. , Sippl Wolfgang , Jung Manfred , Huber Tobias B. , Wanner Nicola
Published: April 2021

A growing body of evidence suggests that low nephron numbers at birth can increase the risk of chronic kidney disease or hypertension later in life. Environmental stressors, such as maternal malnutrition, medication and smoking, can influence renal size at birth. Using metanephric organ cultures to model single-variable environmental conditions, models of maternal disease were evaluated for patterns of developmental impairment. While hyperthermia had limited effects on renal development, fetal iron deficiency was associated with severe impairment of renal growth and nephrogenesis with an all-proximal phenotype. Culturing kidney explants under high glucose conditions led to cellular and transcriptomic changes resembling human diabetic nephropathy. Short-term high glucose culture conditions were sufficient for long-term alterations in DNA methylation-associated epigenetic memory. Finally, the role of epigenetic modifiers in renal development was tested using a small compound library. Among the selected epigenetic inhibitors, various compounds elicited an effect on renal growth, such as HDAC (entinostat, TH39), histone demethylase (deferasirox, deferoxamine) and histone methyltransferase (cyproheptadine) inhibitors. Thus, metanephric organ cultures provide a valuable system for studying metabolic conditions and a tool for screening for epigenetic modifiers in renal development.
Structure, Assembly and Function of Cuticle from Mechanical Perspective with Special Focus on Perianth
Authors: Skrzydeł Joanna , Borowska-Wykręt Dorota , Kwiatkowska Dorota
Published: April 2021

This review is devoted to the structure, assembly and function of cuticle. The topics are discussed from the mechanical perspective and whenever the data are available a special attention is paid to the cuticle of perianth organs, i.e., sepals, petals or tepals. The cuticle covering these organs is special in both its structure and function and some of these peculiarities are related to the cuticle mechanics. In particular, strengthening of the perianth surface is often provided by a folded cuticle that functionally resembles profiled plates, while on the surface of the petal epidermis of some plants, the cuticle is the only integral continuous layer. The perianth cuticle is distinguished also by those aspects of its mechanics and development that need further studies. In particular, more investigations are needed to explain the formation and maintenance of cuticle folding, which is typical for the perianth epidermis, and also to elucidate the mechanical properties and behavior of the perianth cuticle in situ. Gaps in our knowledge are partly due to technical problems caused by very small thicknesses of the perianth cuticle but modern tools may help to overcome these obstacles.
Integrated Analysis of the Transcriptome and Metabolome Revealed Candidate Genes Involved in GA3-Induced Dormancy Release in Leymus chinensis Seeds
Authors: Li Bing , Zhang Pan , Wang Fengdan , Li Ran , Liu Jian , Wang Qiannan , Liu Wei , Wang Bo , Hu Guofu
Published: April 2021

Leymus chinensis is a perennial forage grass that has good palatability, high yield and high feed value, but seed dormancy is a major problem limiting the widespread cultivation of L. chinensis. Here, we performed transcriptomic and metabolomic analysis of hulled and de-hulled seeds of L. chinensis treated with or without GA3 to investigate the changes in gene and metabolites associated with dormancy release induced by GA3. The germination test revealed that the optimum concentration of GA3 for disruption of L. chinensis seed dormancy was 577 μM. A total of 4327 and 11,919 differentially expressed genes (DEGs) and 871 and 650 differentially abundant metabolites were identified in de-hulled and hulled seeds treated with GA3, respectively, compared with seeds soaked in sterile water. Most of the DEGs were associated with starch and sucrose metabolism, protein processing in the endoplasmic reticulum, endocytosis and ribosomes. Furthermore, isoquinoline alkaloid biosynthesis, tyrosine metabolism, starch and sucrose metabolism, arginine and proline metabolism, and amino sugar and nucleotide sugar metabolism were significantly enriched pathways. Integrative analysis of the transcriptomic and metabolomic data revealed that starch and sucrose metabolism is one of the most important pathways that may play a key role in providing carbon skeletons and energy supply for the transition of L. chinensis seeds from a dormant state to germination by suppressing the expression of Cel61a, egID, cel1, tpsA, SPAC2E11.16c and TPP2, enhancing the expression of AMY1.1, AMY1.2, AMY1.6 and GLIP5, and inhibiting the synthesis of cellobiose, cellodextrin, and trehalose while promoting the hydrolysis of sucrose, starch, cellobiose, cellodextrin, and trehalose to glucose. This study identified several key genes and provided new insights into the molecular mechanism of seed dormancy release induced by GA3 in L. chinensis. These putative genes will be valuable resources for improving the seed germination rate in future breeding studies.
A Walk in the Memory, from the First Functional Approach up to Its Regulatory Role of Mitochondrial Bioenergetic Flow in Health and Disease: Focus on the Adenine Nucleotide Translocator
Authors: Atlante Anna , Valenti Daniela
Published: April 2021

The mitochondrial adenine nucleotide translocator (ANT) plays the fundamental role of gatekeeper of cellular energy flow, carrying out the reversible exchange of ADP for ATP across the inner mitochondrial membrane. ADP enters the mitochondria where, through the oxidative phosphorylation process, it is the substrate of Fo-F1 ATP synthase, producing ATP that is dispatched from the mitochondrion to the cytoplasm of the host cell, where it can be used as energy currency for the metabolic needs of the cell that require energy. Long ago, we performed a method that allowed us to monitor the activity of ANT by continuously detecting the ATP gradually produced inside the mitochondria and exported in the extramitochondrial phase in exchange with externally added ADP, under conditions quite close to a physiological state, i.e., when oxidative phosphorylation takes place. More than 30 years after the development of the method, here we aim to put the spotlight on it and to emphasize its versatile applicability in the most varied pathophysiological conditions, reviewing all the studies, in which we were able to observe what really happened in the cell thanks to the use of the “ATP detecting system” allowing the functional activity of the ANT-mediated ADP/ATP exchange to be measured.
The Role of Extracellular Vesicles in Mediating Resistance to Anticancer Therapies
Authors: Maleki Saeideh , Jabalee James , Garnis Cathie
Published: April 2021

Although advances in targeted therapies have driven great progress in cancer treatment and outcomes, drug resistance remains a major obstacle to improving patient survival. Several mechanisms are involved in developing resistance to both conventional chemotherapy and molecularly targeted therapies, including drug efflux, secondary mutations, compensatory genetic alterations occurring upstream or downstream of a drug target, oncogenic bypass, drug activation and inactivation, and DNA damage repair. Extracellular vesicles (EVs) are membrane-bound lipid bilayer vesicles that are involved in cell–cell communication and regulating biological processes. EVs derived from cancer cells play critical roles in tumor progression, metastasis, and drug resistance by delivering protein and genetic material to cells of the tumor microenvironment. Understanding the biochemical and genetic mechanisms underlying drug resistance will aid in the development of new therapeutic strategies. Herein, we review the role of EVs as mediators of drug resistance in the context of cancer.
Unique Regulation of Intestinal Villus Epithelial Cl−/HCO3− Exchange by Cyclooxygenase Pathway Metabolites of Arachidonic Acid in a Mouse Model of Spontaneous Ileitis
Authors: Rahman M Motiur , Borthakur Alip , Afroz Sheuli , Arthur Subha , Sundaram Uma
Published: April 2021

Electrolytes (NaCl) and fluid malabsorption cause diarrhea in inflammatory bowel disease (IBD). Coupled NaCl absorption, mediated by Na+/H+ and Cl−/HCO3− exchanges on the intestinal villus cells brush border membrane (BBM), is inhibited in IBD. Arachidonic acid metabolites (AAMs) formed via cyclooxygenase (COX) or lipoxygenase (LOX) pathways are elevated in IBD. However, their effects on NaCl absorption are not known. We treated SAMP1/YitFc (SAMP1) mice, a model of spontaneous ileitis resembling human IBD, with Arachidonyl Trifluoro Methylketone (ATMK, AAM inhibitor), or with piroxicam or MK-886, to inhibit COX or LOX pathways, respectively. Cl−/HCO3− exchange, measured as DIDS-sensitive 36Cl uptake, was significantly inhibited in villus cells and BBM vesicles of SAMP1 mice compared to AKR/J controls, an effect reversed by ATMK. Piroxicam, but not MK-886, also reversed the inhibition. Kinetic studies showed that inhibition was secondary to altered Km with no effects on Vmax. Whole cell or BBM protein levels of Down-Regulated in Adenoma (SLC26A3) and putative anion transporter-1 (SLC26A6), the two key BBM Cl−/HCO3− exchangers, were unaltered. Thus, inhibition of villus cell Cl−/HCO3− exchange by COX pathway AAMs, such as prostaglandins, via reducing the affinity of the exchanger for Cl−, and thereby causing NaCl malabsorption, could significantly contribute to IBD-associated diarrhea.
Diverse Roles of Mitochondria in Renal Injury from Environmental Toxicants and Therapeutic Drugs
Authors: Lash Lawrence H.
Published: April 2021

Mitochondria are well-known to function as the primary sites of ATP synthesis in most mammalian cells, including the renal proximal tubule. Other functions have also been associated with different mitochondrial activities, including the regulation of redox status and the initiation of mitophagy and apoptosis. Mechanisms for the membrane transport of glutathione (GSH) and various GSH-derived metabolites across the mitochondrial inner membrane of renal proximal tubular cells are critical determinants of these functions and may serve as pharmacological targets for potential therapeutic approaches. Specific interactions of reactive intermediates, derived from drug metabolism, with molecular components in mitochondria have been identified as early steps in diverse forms of chemically-induced nephrotoxicity. Applying this key observation, we developed a novel hypothesis regarding the identification of early, sensitive, and specific biomarkers of exposure to nephrotoxicants. The underlying concept is that upon exposure to a diverse array of environmental contaminants, as well as therapeutic drugs whose efficacy is limited by nephrotoxicity, renal mitochondria will release both high- and low-molecular-weight components into the urine or the extracellular medium in an in vitro model. The detection of these components may then serve as indicators of exposure before irreversible renal injury has occurred.
Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC
Authors: Longo Miriam , Paolini Erika , Meroni Marica , Dongiovanni Paola
Published: April 2021

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third-leading cause of cancer-related mortality. Currently, the global burden of nonalcoholic fatty liver disease (NAFLD) has dramatically overcome both viral and alcohol hepatitis, thus becoming the main cause of HCC incidence. NAFLD pathogenesis is severely influenced by lifestyle and genetic predisposition. Mitochondria are highly dynamic organelles that may adapt in response to environment, genetics and epigenetics in the liver (“mitochondrial plasticity”). Mounting evidence highlights that mitochondrial dysfunction due to loss of mitochondrial flexibility may arise before overt NAFLD, and from the early stages of liver injury. Mitochondrial failure promotes not only hepatocellular damage, but also release signals (mito-DAMPs), which trigger inflammation and fibrosis, generating an adverse microenvironment in which several hepatocytes select anti-apoptotic programs and mutations that may allow survival and proliferation. Furthermore, one of the key events in malignant hepatocytes is represented by the remodeling of glucidic–lipidic metabolism combined with the reprogramming of mitochondrial functions, optimized to deal with energy demand. In sum, this review will discuss how mitochondrial defects may be translated into causative explanations of NAFLD-driven HCC, emphasizing future directions for research and for the development of potential preventive or curative strategies.
Antifungal Activity and DNA Topoisomerase Inhibition of Hydrolysable Tannins from Punica granatum L.
Authors: Brighenti Virginia , Iseppi Ramona , Pinzi Luca , Mincuzzi Annamaria , Ippolito Antonio , Messi Patrizia , Sanzani Simona Marianna , Rastelli Giulio , Pellati Federica
Published: April 2021

Punica granatum L. (pomegranate) fruit is known to be an important source of bioactive phenolic compounds belonging to hydrolysable tannins. Pomegranate extracts have shown antifungal activity, but the compounds responsible for this activity and their mechanism/s of action have not been completely elucidated up to now. The aim of the present study was the investigation of the inhibition ability of a selection of pomegranate phenolic compounds (i.e., punicalagin, punicalin, ellagic acid, gallic acid) on both plant and human fungal pathogens. In addition, the biological target of punicalagin was identified here for the first time. The antifungal activity of pomegranate phenolics was evaluated by means of Agar Disk Diffusion Assay and minimum inhibitory concentration (MIC) evaluation. A chemoinformatic analysis predicted for the first time topoisomerases I and II as potential biological targets of punicalagin, and this prediction was confirmed by in vitro inhibition assays. Concerning phytopathogens, all the tested compounds were effective, often similarly to the fungicide imazalil at the label dose. Particularly, punicalagin showed the lowest MIC for Alternaria alternata and Botrytis cinerea, whereas punicalin was the most active compound in terms of growth control extent. As for human pathogens, punicalagin was the most active compound among the tested ones against Candida albicans reference strains, as well as against the clinically isolates. UHPLC coupled with HRMS indicated that C. albicans, similarly to the phytopathogen Coniella granati, is able to hydrolyze both punicalagin and punicalin as a response to the fungal attack. Punicalagin showed a strong inhibitory activity, with IC50 values of 9.0 and 4.6 µM against C. albicans topoisomerases I and II, respectively. Altogether, the results provide evidence that punicalagin is a valuable candidate to be further exploited as an antifungal agent in particular against human fungal infections.
Localization and Maintenance of Engrafted Mesenchymal Stem Cells Administered via Renal Artery in Kidneys with Ischemia-Reperfusion Injury
Authors: Yamada Yumi , Nakashima Ayumu , Doi Shigehiro , Ishiuchi Naoki , Kanai Ryo , Miyasako Kisho , Masaki Takao
Published: April 2021

Mesenchymal stem cells (MSCs) are a potential therapeutic tool for preventing the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). Herein, we investigated the localization and maintenance of engrafted human bone marrow-derived MSCs in rats subjected to a renal ischemia-reperfusion injury (IRI) and compared the effectiveness of two intravascular injection routes via the renal artery or inferior vena cava. Renal artery injection of MSCs was more effective than intravenous injection at reducing IRI-induced renal fibrosis. Additionally, MSCs injected through the renal artery persisted in injured kidneys for over 21 days, whereas MSCs injected through the inferior vena cava survived for less than 7 days. This difference may be attributed to the antifibrotic effects of MSCs. Interestingly, MSCs injected through the renal artery were localized primarily in glomeruli until day 3 post-IRI, and they decreased in number thereafter. In contrast, the number of MSCs localized in tubular walls, and the interstitium increased gradually until day 21 post-IRI. This localization change may be related to areas of damage caused by IRI because ischemia-induced AKI leads to tubular cell damage. Taken together, these findings suggest renal artery injection of MSCs may be useful for preventing the progression of AKI to CKD.
Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System
Authors: Skiba Dominik S. , Szczepaniak Piotr , Siedliński Mateusz , Poznański Piotr , Łazarczyk Marzena , Jaskuła Kinga , Religa Piotr , Sacharczuk Mariusz , Gaciong Zbigniew
Published: April 2021

The opioid system is well-known for its role in modulating nociception and addiction development. However, there are premises that the endogenous opioid system may also affect blood pressure. The main goal of the present study was to determine the impact of different endogenous opioid system activity and its pharmacological blockade on blood pressure. Moreover, we examined the vascular function in hyper- and hypoactive states of the opioid system and its pharmacological modification. In our study, we used two mouse lines which are divergently bred for high (HA) and low (LA) swim stress-induced analgesia. The obtained results indicated that individuals with low endogenous opioid system activity have higher basal blood pressure compared to those with a hyperactive opioid system. Additionally, naloxone administration only resulted in the elevation of blood pressure in HA mice. We also showed that the hypoactive opioid system contributes to impaired vascular relaxation independent of endothelium, which corresponded with decreased guanylyl cyclase levels in the aorta. Together, these data suggest that higher basal blood pressure in LA mice is a result of disturbed mechanisms in vascular relaxation in smooth muscle cells. We believe that a novel mechanism which involves endogenous opioid system activity in the regulation of blood pressure will be a promising target for further studies in hypertension development.