bluuebunny/crossref_metadata_2025 huggingface dataset:
The Challenge of Subjective Cognitive Complaints and Executive Functions in Middle-Aged Adults as a Preclinical Stage of Dementia: A Systematic Review
Authors: Webster-Cordero Felipe , Giménez-Llort Lydia
Published: March 2022

Subjective cognitive complaints correspond to a heterogeneous construct that frequently occurs in the early stages of older adult life. Despite being a common source of worry for middle-aged people, it can be underestimated when clinical and neuropsychological assessments discard any underlying pathological processes. Negative age stereotyping but also self-stereotyping can contribute to doing so. Although its diagnosis is a challenge, its implication as a possible predictor of mild cognitive impairment or dementia increases the interest in its early diagnosis and intervention. The present systematic review analyzes the empirical data on the relationship between these complaints and early executive dysfunction with possible predictive value for preclinical stages of dementia. The sixteen papers obtained from the PubMed and Embase databases were exploratory, cross-sectional and prospective in scope. The studies corroborated the relationship between subjective cognitive complaints and some executive processes, which is noteworthy since many people with subjective executive complaints progress to dementia. The relational studies confirmed that impaired executive performance is associated with CSF biomarkers and reduced cortical volume in specific brain regions. However, the heterogeneity of reports in these studies demands stronger efforts in future research with specific tools applied in clinical and neuropsychological assessments and analyzed under a gender perspective.
Effectiveness of Constraint-Induced Movement Therapy (CIMT) on Balance and Functional Mobility in the Stroke Population: A Systematic Review and Meta-Analysis
Authors: Tedla Jaya Shanker , Gular Kumar , Reddy Ravi Shankar , de Sá Ferreira Arthur , Rodrigues Erika Carvalho , Kakaraparthi Venkata Nagaraj , Gyer Giles , Sangadala Devika Rani , Qasheesh Mohammed , Kovela Rakesh Krishna , Nambi Gopal
Published: March 2022

Constraint-induced movement therapy (CIMT) is one of the most popular treatments for enhancing upper and lower extremity motor activities and participation in patients following a stroke. However, the effect of CIMT on balance is unclear and needs further clarification. The aim of this research was to estimate the effect of CIMT on balance and functional mobility in patients after stroke. After reviewing 161 studies from search engines including Google Scholar, EBSCO, PubMed, PEDro, Science Direct, Scopus, and Web of Science, we included eight randomized controlled trials (RCT) in this study. The methodological quality of the included RCTs was verified using PEDro scoring. This systematic review showed positive effects of CIMT on balance in three studies and similar effects in five studies when compared to the control interventions such as neuro developmental treatment, modified forced-use therapy and conventional physical therapy. Furthermore, a meta-analysis indicated a statistically significant effect size by a standardized mean difference of 0.51 (P = 0.01), showing that the groups who received CIMT had improved more than the control groups. However, the meta-analysis results for functional mobility were statistically insignificant, with an effect size of −4.18 (P = 0.16), indicating that the functional mobility improvements in the investigated groups were not greater than the control group. This study’s findings demonstrated the superior effects of CIMT on balance; however, the effect size analysis of functional mobility was statistically insignificant. These findings indicate that CIMT interventions can improve balance-related motor function better than neuro developmental treatment, modified forced-use therapy and conventional physical therapy in patients after a stroke.
The Effectiveness of a Thanks, Sorry, Love, and Farewell Board Game in Older People in Taiwan: A Quasi-Experimental Study
Authors: Chen Mei-Fang , Tsai Chun-Chin
Published: March 2022

The objective of this study is to examine the effectiveness of the four themes of life (“thanks, sorry, love, and farewell”) board game to enhance interpersonal communication, interpersonal relationships, and self-efficacy; and decrease loneliness. The participants were a convenience sample of 91 older people recruited from two community activity centers in Taiwan. Using a quasi-experimental method, participants from one of the community activity centers were enrolled as the experimental group, and participants from the other center were enrolled as the control group. The experimental group played the four themes of life board game for 4 weeks. The control group participated in routine community center activities. Compared to the control group, the experimental group had statistically significantly larger improvements in scores on interpersonal communication, self-efficacy, and loneliness at 3 months after the end of the intervention. This study provides a reference for the design interventions for promoting health in older people.
Production and Characterization of a Bioflocculant from Pichia kudriavzevii MH545928.1 and Its Application in Wastewater Treatment
Authors: Tsilo Phakamani H. , Basson Albertus K. , Ntombela Zuzingcebo G. , Maliehe Tsolanku S. , Pullabhotla V.S.R. Rajasekhar
Published: March 2022

A variety of flocculants have been used to aggregate colloidal substances. However, recently, owing to the adverse effects and high costs of conventional flocculants, natural flocculants such as microbial flocculants are gaining attention. The aim of the study was to produce and characterize a bioflocculant from Pichia kudriavzevii MH545928.1 and apply it in wastewater treatment. A mixture of butanol and chloroform (5:2 v/v) was used to extract the bioflocculant. Phenol–sulphuric acid, Bradford and Carbazole assays were utilized for the identification of carbohydrates, proteins and uronic acid, respectively. Scanning electron microscopy (SEM) and elemental detector were employed to determine the surface morphology and elemental compositions. The removal efficiencies were 73%, 49% and 47% for BOD, COD and P, respectively. The bioflocculant (2.836 g/L) obtained showed the presence of carbohydrates (69%), protein (11%) and uronic acid (16%). The bioflocculant displayed a cumulus-like structure and the elemental composition of C (16.92%), N (1.03%), O (43:76%), Na (0.18%), Mg (0.40%), Al (0.80%), P (14.44%), S (1.48%), Cl (0.31%), K (0.34%) and Ca (20.35). It showed the removal efficiencies of 43% (COD), 64% (BOD), 73% (P) and 50% (N) in coal mine wastewater. This bioflocculant is potentially viable to be used in wastewater treatment.
Adolescents and Resilience: Factors Contributing to Health-Related Quality of Life during the COVID-19 Pandemic
Authors: Tal-Saban Miri , Zaguri-Vittenberg Shahar
Published: March 2022

This study aimed to examine health-related quality of life of adolescents before and during the COVID-19 outbreak, and its relationship to resilience embodied in hope and a sense of coherence. Typically developed adolescents between the ages of 13 to 18 participated in the study; 84 were recruited before the pandemic outbreak and 64 in March to April 2020 during the worldwide outbreak. The participants completed the Pediatric Quality of Life Inventory, Sense of Coherence Scale, and Children’s Hope Scale. During the outbreak, adolescents reported higher physical health-related quality of life scores (F(1146) = 3.710, p < 0.05, η² = 0.027) and lower school health-related quality of life scores (F(1146) = 5.748, p < 0.05, η2 = 0.028), compared to adolescents during the pre-outbreak period. Furthermore, adolescents during the outbreak reported a significantly (p < 0.05) higher sense of coherence but no difference in levels of hope. Finally, the results of multiple linear regression indicated that resilience factors (hope and sense of coherence) contributed to the prediction of health-related quality of life, independent of socio-demographic variables. Hope and a sense of coherence were both found to positively impact one core aspect of health, which highlights the importance of addressing resilience factors in educational and therapeutic settings for adolescents thus that they are better able to adapt to stressful events such as pandemics.
The Mental Health of Employees with Job Loss and Income Loss during the COVID-19 Pandemic: The Mediating Role of Perceived Financial Stress
Authors: de Miquel Carlota , Domènech-Abella Joan , Felez-Nobrega Mireia , Cristóbal-Narváez Paula , Mortier Philippe , Vilagut Gemma , Alonso Jordi , Olaya Beatriz , Haro Josep Maria
Published: March 2022

The COVID-19 outbreak, which was followed by home confinement, is expected to have had profound negative impact on the mental health of people. Associated factors, such as losing jobs and income, can be expected to lead to an increased risk of suffering from psychopathological problems. Therefore, this study was aimed at researching the associations of job and income loss with mental health, as well as the possible mediating role of perceived financial stress during the COVID-19 outbreak. The sample included 2381 Spanish workers who were interviewed right after the first COVID-19 lockdown. Measures were taken for generalized anxiety disorder, panic attacks, depression, post-traumatic stress disorder, substance abuse, suicidal thoughts and behaviors, working conditions, sociodemographic variables, and perceived financial stress. Logistic regression models were calculated with psychological variables as outcomes, and with job loss and income loss as predictors. Mediation analyses were performed by adding the financial threat as a mediator. Nineteen point six percent and 33.9% of participants reported having lost their jobs and incomes due to the pandemic, respectively. Only income loss was related to a higher risk of suffering from depression and panic attacks. When adding financial stress as a mediator, the indirect effects of job and income loss on the mental health measures were found to be significant, therefore indicating mediation. These findings pinpoint the vulnerability of this population, and highlight the need for interventional and preventive programs targeting mental health in economic crisis scenarios, such as the current one. They also highlight the importance of implementing social and income policies during the COVID-19 pandemic to prevent mental health problems.
Telemedicine in the Management of Patients with Rheumatic Disease during COVID-19 Pandemic: Incidence of Psychiatric Disorders and Fibromyalgia in Patients with Rheumatoid Arthritis and Psoriatic Arthritis
Authors: Foti Rosario , Amato Giorgio , Dal Bosco Ylenia , Longo Antonio , Gagliano Caterina , Falsaperla Raffaele , Foti Roberta , Speranza Sergio , De Lucia Francesco , Visalli Elisa
Published: March 2022

The management of patients with immuno-rheumatological diseases has profoundly changed during the COVID-19 pandemic and telemedicine has played an important role in the disease follow-up. In addition to monitoring disease activity and any adverse events, especially infectious events, assessing the psychological situation of the patient can be fundamental. Furthermore, COVID-19 has a serious impact on mental health and, since the beginning of the pandemic, a significantly higher incidence of anxiety disorders and depressive symptoms especially in younger people was observed. In this study, we evaluated the incidence of depressive disorders, anxiety, and fibromyalgia (FM) in our patients with rheumatoid arthritis and psoriatic arthritis during the lockdown period due to the COVID-19 pandemic and we validate the use of telemedicine in the clinical management of these patients. Mental and physical stress during the COVID-19 pandemic can greatly worsen FM symptoms and intensify patients’ suffering without a clinical flare of the inflammatory disease for patients affected by rheumatoid arthritis. Telemedicine has allowed us to identify patients who needed a face-to-face approach for therapeutic reevaluation even if not related to a flare of the inflammatory disease. Even if our data does not allow us to draw definitive conclusions regarding the effectiveness of telemedicine as greater than or equal to the standard face-to-face approach, we continue to work by modifying our approach to try to ensure the necessary care in compliance with safety and, optimistically, this tool will become an important part of rheumatic disease management.
Early and Objective Evaluation of the Therapeutic Effects of ADHD Medication through Movement Analysis Using Video Recording Pixel Subtraction
Authors: Lee Ying-Han , Ouyang Chen-Sen , Chiu Yi-Hung , Chiang Ching-Tai , Wu Rong-Ching , Yang Rei-Cheng , Lin Lung-Chang
Published: March 2022

Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5–7% of school-age children. ADHD is usually marked by an ongoing pattern of inattention or hyperactivity–impulsivity, leading to functioning or developmental problems. A common ADHD assessment tool is the Swanson, Nolan, and Pelham (SNAP) questionnaire. However, such scales provide only a subjective perspective, and most of them are used to evaluate therapeutic effects at least 3–12 months after medication initiation. Therefore, we employed an objective assessment method to provide more accurate evaluations of therapeutic effects in 25 children with ADHD (23 boys and 2 girls). To evaluate the participants’ improvement and treatment’s effectiveness, the pixel subtraction technique was used in video analysis. We compared the efficacy of 1-month Ritalin or Concerta treatment by evaluating the movement in each video within 3 h of medication administration. The movement value was defined as the result of a calculation when using the pixel subtraction technique. Based on behavior observation and SNAP scores, both parent- and teacher-reported scores decreased after 1 month of medication (reduction rates: 19.61% and 16.38%, respectively). Specifically, the parent-reported hyperactivity subscale and teacher-reported oppositional subscale decreased more significantly. By contrast, the reduction rate was 39.27%, as evaluated using the average movement value (AMV). Considering symptomatic improvement as a >25% reduction in scores, the result revealed that the AMV decreased in 18 patients (72%) compared with only 44% and 56% of patients based on parent- and teacher-reported hyperactivity subscale scores. In conclusion, the pixel subtraction method can serve as an objective and reliable evaluation of the therapeutic effects of ADHD medication in the early stage.
Public Reporting on the Quality of Care in Patients with Acute Myocardial Infarction: The Korean Experience
Authors: Chae Kyunghee , Kim Mira , Kim Byung Ok , Jung Chai Young , Kang Hyun-Jae , Oh Dong-Jin , Jeon Dong Woon , Chung Woo-Young , Choi Cheol Ung , Han Kyoo-Rok , Hyon Min-Su , Quan Hude , Lee Sangmin , Kim Sukil
Published: March 2022

Public reporting is a way to promote quality of healthcare. However, evidence supporting improved quality of care using public reporting in patients with acute myocardial infarction (AMI) is disputed. This study aims to describe the impact of public reporting of AMI care on hospital quality improvement in Korea. Patients with AMI admitted to the emergency room with ICD-10 codes of I21.0 to I21.9 as the primary or secondary diagnosis were identified from the national health insurance claims data (2007–2012). Between 2007 and 2012, 43,240/83,378 (51.9%) patients manifested ST segment elevation myocardial infarction (STEMI). Timely reperfusion rate increased (β = 2.78, p = 0.001). The mortality rate of STEMI patients was not changed (β = −0.0098, p = 0.384) but that of NSTEMI patients decreased (β = −0.465, p = 0.001). Public reporting has a substantial impact on the process indicators of AMI in Korea because of the increased reperfusion rate. However, the outcome indicators such as mortality did not significantly change, suggesting that public reporting did not necessarily improve the quality of care.
Effects of Δ9-Tetrahydrocannibinol (THC) on Obesity at Different Stages of Life: A Literature Review
Authors: Fearby Nathan , Penman Samantha , Thanos Panayotis
Published: March 2022

The Cannabis sativa plant has historically been used for both recreational and medical purposes. With the recent surge in recreational use of cannabis among adolescents and adults in particular, there is an increased obligation to determine the short- and long-term effects that consuming this plant may have on several aspects of the human psyche and body. The goal of this article was to examine the negative effects of obesity, and how the use of Δ9-tetrahydrocannibinol (THC) or cannabidiol (CBD) can impact rates of this global pandemic at different timepoints of life. Conflicting studies have been reported between adult and adolescents, as there are reports of THC use leading to increased weight due to elevated appetite and consumption of food, while others observed a decrease in overall body weight due to the regulation of omega-6/omega-3 endocannabinoid precursors and a decrease in energy expenditure. Studies supported a positive correlation between prenatal cannabis use and obesity rates in the children as they matured. The data did not indicate a direct connection between prenatal THC levels in cannabis and obesity rates, but that this development may occur due to prenatal THC consumption leading to low birthweight, and subsequent obesity. There are few studies using animal models that directly measure the effects that prenatal THC administration on obesity risks among offspring. Thus, this is a critical area for future studies using a developmental framework to examine potential changes in risk across development.
Precarious Work as Risk Factor for 5-Year Increase in Depressive Symptoms
Authors: Demiral Yucel , Ihle Tobias , Rose Uwe , Conway Paul Maurice , Burr Hermann
Published: March 2022

Objectives: The aim was to investigate the longitudinal relationship between precarious work and depressive symptoms in a representative cohort of employees in Germany. Methods: In the German Study on Mental Health at Work (S-MGA) (n = 2009), depressive symptoms were assessed by the Patient Health Questionnaire (PHQ−9). Precarious work was measured through baseline (2012) self-reported job insecurity, marginal part-time, fixed-term contract, hourly wage and—during follow-ups 2012–2017—unemployment. Among employees without depressive symptoms at baseline (2012), we ran logistic regression analyses stratified by gender with depressive symptoms at follow-up in 2017 as the dependent variable, adjusting for baseline (2012) age, gender, socioeconomic position and partner status. Results: Among men, job insecurity (OR: 2.47; 95% 95% CI: 1.37–4.48) and low wage (3.79; 1.64–8.72) at baseline were significantly associated with depressive symptoms at follow-up. Among women, indicators of precarious work were not associated with depressive symptoms at follow-up. Among men, a cumulative exposure index of precarious work was significantly associated with the development of depressive symptoms (one indicator: 1.84; 0.94–3.60, ≥two indicators: 7.65; 3.30–17.73). This index was not associated with depressive symptoms among women. The population attributable fraction of precarious work due to depressive symptoms among men was approximately 30%. Conclusions: Among employees in Germany, precarious work seems to be a risk factor for the subsequent development of depressive symptoms among men, but not among women. Research on precarious employment in different countries is needed.
Is Emissions Trading Scheme (ETS) an Effective Market-Incentivized Environmental Regulation Policy? Evidence from China’s Eight ETS Pilots
Authors: Chai Shanglei , Sun Ruixuan , Zhang Ke , Ding Yueting , Wei Wei
Published: March 2022

Climate change and environmental issues caused by carbon emissions have attracted the attention of governments around the world. Drawing on the experience of the EU, China is actively developing a national carbon emissions trading market, trying to encourage emission entities to incorporate carbon emissions reduction into production and consumption decisions through carbon pricing. Is this scheme an effective market-incentivized environmental regulatory policy? Since China successively launched ETS pilots in 2013, the effectiveness of reducing carbon emissions has become one of the current focus issues. This study uses the difference-in-differences (DID) method to evaluate the impact of ETS implementation on emissions reduction and employs the Super-SBM model in data envelopment analysis (DEA) to evaluate the emission-reduction efficiency of eight ETS pilots in China. We find that the carbon trading policy has achieved emission-reduction effects in the implementation stage, and the greenness of economic growth has a significant positive impact on regional GDP. The establishment of China’s unified carbon market should be coordinated with regional development. Some supporting measures for regional ecological compensation and the mitigation of regional development are yet to be adopted.
Different Mortality Risks of Long-Term Exposure to Particulate Matter across Different Cancer Sites
Authors: Shin Miyoun , Kim Ok-Jin , Yang Seongwoo , Choe Seung-Ah , Kim Sun-Young
Published: March 2022

Particulate matter (PM) air pollution has challenged the global community and the International Agency for Research on Cancer (IARC) classified airborne particulate matter as carcinogenic to humans. However, while most studies of cancer examined a single cancer type using different cohorts, few studies compared the associations of PM between different cancer types. We aimed to compare the association of long-term exposure to PM (PM10 and PM2.5) and cancer mortality across 17 different types of cancer using a population-based cohort in the Seoul Metropolitan Area (SMA), South Korea; Our study population includes 87,608 subjects (mean age: 46.58 years) residing in the SMA from the National Health Insurance Services–National Sample cohort (NHIS–NSC) and followed up for 2007–2015. We used the time-dependent Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of each cancer mortality per 10 μg/m3 increase in PM concentrations, after adjusting for individual and areal characteristics. During eight years of follow-up, 1487 people died with any of 17 cancer types. Lung cancer death was the highest, followed by liver and stomach cancer. Although we did not find the association for all cancer types, possibly because of limited cancer cases, HRs of PM2.5 were relatively high for lung, stomach, pancreas, non-Hodgkin’s lymphoma, prostate, esophagus, oral and pharynx, and brain cancer mortality (HRs = 1.44–7.14). High HRs for pancreas, non–Hodgkin’s lymphoma, esophagus, and oral and pharynx cancer were also seen for PM10; our findings suggest PM air pollution as a potential risk factor of cancer mortality for upper digestive tracts, mouth, pancreas, and non–Hodgkin’s lymphoma in a highly urbanized population with high exposure to PM for a long time.
The Effect of Task-Oriented Training on Upper-Limb Function, Visual Perception, and Activities of Daily Living in Acute Stroke Patients: A Pilot Study
Authors: Choi Wonho
Published: March 2022

This pilot study aimed to investigate the effects of task-oriented training on upper-limb functioning, visual perception, and activities of daily living (ADL) in acute stroke patients. Of 20 participants, 10 were randomly assigned in a 1:1 ratio to experimental and control groups. Task-oriented training and table-top activity training were implemented for 6 weeks. Change in upper-limb functioning was assessed with the Manual Function Test (MFT); visual perceptual skill and ADL performance were evaluated using the Motor-Free Visual Perception Test—Vertical (MVPT-V) and Korean Modified Barthel Index (K-MBI), respectively. There was a significant interaction in the MFT and MBI score between the group and time (p < 0.05), but the group effect was not significant (p > 0.05). The MFT and MBI score significantly increased in both groups after the intervention (p < 0.001), but the effect size was greater in the task-oriented training group than the table-top activity training group. No significant interaction with MVPT-V score was found between the group and time (p > 0.05), and no statistical group difference was found either (p > 0.05). Both groups showed significant improvement in their MVPT-V score after the intervention (p < 0.001). The pilot study findings demonstrate that both task-oriented training and table-top activity training are effective in recovering upper-limb function, visual perception, and ADL in acute stroke patients.
Competence in Daily Activities and Mental Well-Being among Technical Intern Trainees in Japan: A Cross-Sectional Study
Authors: Arita Kuniko , Shibanuma Akira , Carandang Rogie Royce , Jimba Masamine
Published: March 2022

Migrant workers are at a greater risk of having low mental well-being compared to their local counterparts. The Japanese government accepts migrants through its Technical Intern Training programs, but the factors associated with their mental well-being remain unclear. This study aimed to (1) assess trainees’ competence and importance in daily activities and (2) examine the association between their competence and mental well-being. We conducted a cross-sectional study using self-administered questionnaires. We recruited trainees through their supervising organizations and social media. We used the Occupational Self-Assessment tool to measure competence and importance in daily activities and the World Health Organization-5 Well-being Index to measure mental well-being. Hierarchical regression analysis was used to examine the association between competence and mental well-being. Among 383 trainees, 30.6% felt difficulty expressing themselves, and 27.4% felt difficulty accomplishing goals. Almost 50% valued self-care, working towards their goals, and managing their finances. Higher competence scores were associated with higher mental well-being scores (B = 0.76; 95% CI = 0.52, 1.00). Competence may be a key to having higher mental well-being among migrant trainees in Japan. A supportive and enabling environment, as well as mental health promotion at the community level, may improve trainees’ competence in daily activities.
Ecological Predictors of Older Adults’ Participation and Retention in a Physical Activity Intervention
Authors: Peters Manuela , Ratz Tiara , Wichmann Frauke , Lippke Sonia , Voelcker-Rehage Claudia , Pischke Claudia R.
Published: March 2022

Research is still lacking regarding the question as to how programs to promote healthy ageing should be organized in order to increase acceptance and thus effectiveness. For older adults, ecological factors, such as the physical distance to program sites, might predict participation and retention. Thus, the key aim of this analysis was to examine these factors in a physical activity intervention trial. Adults (N = 8299) aged 65 to 75 years were invited to participate and n = 589 participants were randomly assigned to one of two intervention groups with 10 weeks of physical activity home practice and exercise classes or a wait-list control group. Response, participation, and dropout data were compared regarding ecological, individual, and study-related variables. Kaplan–Meier curves and Cox regression models were used to determine predictors of dropout. In total, 405 participants completed the study. Weekly class attendance rates were examined regarding significant weather conditions and holiday periods. The highest rates of nonresponse were observed in districts with very high neighborhood levels of socioeconomic status. In this study, ecological factors did not appear to be significant predictors of dropout, whereas certain individual and study-related variables were predictive. Future studies should consider these factors during program planning to mobilize and keep subjects in the program.
Complex of HIV-1 Integrase with Cellular Ku Protein: Interaction Interface and Search for Inhibitors
Authors: Ilgova Ekaterina , Galkin Simon , Khrenova Maria , Serebryakova Marina , Gottikh Marina , Anisenko Andrey
Published: March 2022

The interaction of HIV-1 integrase and the cellular Ku70 protein is necessary for HIV replication due to its positive effect on post-integration DNA repair. We have previously described in detail the Ku70 binding site within integrase. However, the integrase binding site in Ku70 remained poorly characterized. Here, using a peptide fishing assay and site-directed mutagenesis, we have identified residues I72, S73, and I76 of Ku70 as key for integrase binding. The molecular dynamics studies have revealed a possible way for IN to bind to Ku70, which is consistent with experimental data. According to this model, residues I72 and I76 of Ku70 form a “leucine zipper” with integrase residues, and, therefore, their concealment by low-molecular-weight compounds should impede the Ku70 interaction with integrase. We have identified such compounds by molecular docking and have confirmed their capacity to inhibit the formation of the integrase complex with Ku70. Our data demonstrate that the site of IN binding within Ku70 identified in the present work may be used for further search for inhibitors of the integrase binding to Ku70.
Protective Effects of Melatonin and Misoprostol against Experimentally Induced Increases in Intestinal Permeability in Rats
Authors: Peters Karsten , Dahlgren David , Egerszegi Péter Pál , Lennernäs Hans , Sjöblom Markus
Published: March 2022

Intestinal mucosal barrier dysfunction caused by disease and/or chemotherapy lacks an effective treatment, which highlights a strong medical need. Our group has previously demonstrated the potential of melatonin and misoprostol to treat increases in intestinal mucosal permeability induced by 15-min luminal exposure to a surfactant, sodium dodecyl sulfate (SDS). However, it is not known which luminal melatonin and misoprostol concentrations are effective, and whether they are effective for a longer SDS exposure time. The objective of this single-pass intestinal perfusion study in rats was to investigate the concentration-dependent effect of melatonin and misoprostol on an increase in intestinal permeability induced by 60-min luminal SDS exposure. The cytoprotective effect was investigated by evaluating the intestinal clearance of 51Cr-labeled EDTA in response to luminal SDS as well as a histological evaluation of the exposed tissue. Melatonin at both 10 and 100 µM reduced SDS-induced increase in permeability by 50%. Misoprostol at 1 and 10 µM reduced the permeability by 50 and 75%, respectively. Combination of the two drugs at their respective highest concentrations had no additive protective effect. These in vivo results support further investigations of melatonin and misoprostol for oral treatments of a dysfunctional intestinal barrier.
Active nNOS Is Required for Grp94-Induced Antioxidant Cytoprotection: A Lesson from Myogenic to Cancer Cells
Authors: Fornasiero Filippo , Scapin Cristina , Vitadello Maurizio , Pizzo Paola , Gorza Luisa
Published: March 2022

The endoplasmic reticulum (ER) chaperone Grp94/gp96 appears to be involved in cytoprotection without being required for cell survival. This study compared the effects of Grp94 protein levels on Ca2+ homeostasis, antioxidant cytoprotection and protein–protein interactions between two widely studied cell lines, the myogenic C2C12 and the epithelial HeLa, and two breast cancer cell lines, MDA-MB-231 and HS578T. In myogenic cells, but not in HeLa, Grp94 overexpression exerted cytoprotection by reducing ER Ca2+ storage, due to an inhibitory effect on SERCA2. In C2C12 cells, but not in HeLa, Grp94 co-immunoprecipitated with non-client proteins, such as nNOS, SERCA2 and PMCA, which co-fractionated by sucrose gradient centrifugation in a distinct, medium density, ER vesicular compartment. Active nNOS was also required for Grp94-induced cytoprotection, since its inhibition by L-NNA disrupted the co-immunoprecipitation and co-fractionation of Grp94 with nNOS and SERCA2, and increased apoptosis. Comparably, only the breast cancer cell line MDA-MB-231, which showed Grp94 co-immunoprecipitation with nNOS, SERCA2 and PMCA, increased oxidant-induced apoptosis after nNOS inhibition or Grp94 silencing. These results identify the Grp94-driven multiprotein complex, including active nNOS as mechanistically involved in antioxidant cytoprotection by means of nNOS activity and improved Ca2+ homeostasis.
Characteristics of Crosslinking Polymers Play Major Roles in Improving the Stability and Catalytic Properties of Immobilized Thermomyces lanuginosus Lipase
Authors: Mao Yuhong , Cai Zhenling , Zhou Chenxi , Lan Hangzhen , Ye Xiuyun
Published: March 2022

This study aimed to improve the stability and catalytic properties of Thermomyces lanuginosus lipase (TLL) adsorbed on a hydrophobic support. At the optimized conditions (pH 5 and 25 °C without any additions), the Sips isotherm model effectively fitted the equilibrium adsorption data, indicating a monolayer and the homogenous distribution of immobilized lipase molecules. To preserve the high specific activity of adsorbed lipase, the immobilized lipase (IL) with a moderate loading amount (approximately 40% surface coverage) was selected. Polyethylenimine (PEI) and chitosan (CS) were successfully applied as bridging units to in situ crosslink the immobilized lipase molecules in IL. At the low polymer concentration (0.5%, w/w) and with 1 h incubation, insignificant changes in average pore size were detected. Short-chain PEI and CS (MW ≤ 2 kDa) efficiently improved the lipase stability, i.e., the lipase loss decreased from 40% to <2%. Notably, CS performed much better than PEI in maintaining lipase activity. IL crosslinked with CS-2 kDa showed a two- to three-fold higher rate when hydrolyzing p-nitrophenyl butyrate and a two-fold increase in the catalytic efficiency in the esterification of hexanoic acid with butanol. These in situ crosslinking strategies offer good potential for modulating the catalytic properties of TLL for a specific reaction.
Sodium-Iodate Injection Can Replicate Retinal Degenerative Disease Stages in Pigmented Mice and Rats: Non-Invasive Follow-Up Using OCT and ERG
Authors: Koster Céline , van den Hurk Koen T. , ten Brink Jacoline B. , Lewallen Colby F. , Stanzel Boris V. , Bharti Kapil , Bergen Arthur A.
Published: March 2022

Purpose: The lack of suitable animal models for (dry) age-related macular degeneration (AMD) has hampered therapeutic research into the disease, so far. In this study, pigmented rats and mice were systematically injected with various doses of sodium iodate (SI). After injection, the retinal structure and visual function were non-invasively characterized over time to obtain in-depth data on the suitability of these models for studying experimental therapies for retinal degenerative diseases, such as dry AMD. Methods: SI was injected into the tail vein (i.v.) using a series of doses (0–70 mg/kg) in adolescent C57BL/6J mice and Brown Norway rats. The retinal structure and function were assessed non-invasively at baseline (day 1) and at several time points (1–3, 5, and 10-weeks) post-injection by scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and electroretinography (ERG). Results: After the SI injection, retinal degeneration in mice and rats yielded similar results. The lowest dose (10 mg/kg) resulted in non-detectable structural or functional effects. An injection with 20 mg/kg SI did not result in an evident retinal degeneration as judged from the OCT data. In contrast, the ERG responses were temporarily decreased but returned to baseline within two-weeks. Higher doses (30, 40, 50, and 70 mg/kg) resulted in moderate to severe structural RPE and retinal injury and decreased the ERG amplitudes, indicating visual impairment in both mice and rat strains. Conclusions: After the SI injections, we observed dose-dependent structural and functional pathological effects on the retinal pigment epithelium (RPE) and retina in the pigmented mouse and rat strains that were used in this study. Similar effects were observed in both species. In particular, a dose of 30 mg/kg seems to be suitable for future studies on developing experimental therapies. These relatively easily induced non-inherited models may serve as useful tools for evaluating novel therapies for RPE-related retinal degenerations, such as AMD.
HLA-G and Other Immune Checkpoint Molecules as Targets for Novel Combined Immunotherapies
Authors: Morandi Fabio , Airoldi Irma
Published: March 2022

HLA-G is an HLA-class Ib molecule that is involved in the establishment of tolerance at the maternal/fetal interface during pregnancy. The expression of HLA-G is highly restricted in adults, but the de novo expression of this molecule may be observed in different hematological and solid tumors and is related to cancer progression. Indeed, tumor cells expressing high levels of HLA-G are able to suppress anti-tumor responses, thus escaping from the control of the immune system. HLA-G has been proposed as an immune checkpoint (IC) molecule due to its crucial role in tumor progression, immune escape, and metastatic spread. We here review data available in the literature in which the interaction between HLA-G and other IC molecules is reported, in particular PD-1, CTLA-4, and TIM-3, but also IDO and TIGIT. Clinical trials using monoclonal antibodies against HLA-G and other IC are currently ongoing with cancer patients where antibodies and inhibitors of PD-1 and CTLA-4 showed encouraging results. With this background, we may envisage that combined therapies using antibodies targeting HLA-G and another IC may be successful for clinical purposes. Indeed, such immunotherapeutic protocols may achieve a better rescue of effective anti-tumor immune response, thus improving the clinical outcome of patients.
Mesenchymal Stem Cell-Derived Extracellular Vesicles: Pleiotropic Impacts on Breast Cancer Occurrence, Development, and Therapy
Authors: Guo Yiling , Zhai Yujia , Wu Longyuan , Wang Yazhuo , Wu Puzhen , Xiong Lixia
Published: March 2022

Breast cancer (BC) is one of the most devastating cancers, with high morbidity and mortality, among the female population worldwide. In BC, mesenchymal stem cells (MSCs), as pluripotent stromal stem cells, play a significant role in TME formation and tumor progression. Recently, an increasing number of studies have demonstrated that extracellular vesicles (EVs) are essential for the crosstalk between MSCs and BC cells. MSC-derived EVs (MSC-EVs) can deliver a diversity of molecules, including lipids, proteins, and nucleic acids, etc., to target cells, and produce corresponding effects. Studies have demonstrated that MSC-EVs exert both inhibitory and promotive effects in different situations and different stages of BC. Meanwhile, MSC-EVs provide novel therapeutic options for BC, such as EVs as carriers for drug delivery. Therefore, in this review, we summarize the role of MSC-EVs in BC progression and application in clinical treatment, in the hope of providing a basis for further research.
Aphid Resistance in Pisum Affects the Feeding Behavior of Pea-Adapted and Non-Pea-Adapted Biotypes of Acyrthosiphon pisum Differently
Authors: González Mauricio González , Simon Jean Christophe , Sugio Akiko , Ameline Arnaud , Cherqui Anas
Published: March 2022

Resistant genotypes of crops have emerged as an alternative and sustainable solution to pesticide use against pest insects. The resistance depends on the genetic diversity of the host plant and the pest species and can cause an alteration of the insect behavior. The aim of this work was to characterize the resistance level of different Pisum genotypes (one P. fulvum and five P. sativum genotypes) to two biotypes of the aphid Acyrthosiphon pisum, respectively adapted to pea and alfalfa, by measuring the individual aphid weight and analyzing aphid feeding behavior by electropenetrography (EPG). Aphid body mass was influenced by Pisum genotypes reflecting variation in their resistance level. P. fulvum was the most resistant to the A. pisum pea biotype (ArPo28 clone) and showed intermediate resistance to the A. pisum alfalfa biotype (LSR1 clone). The resistance levels of the five P. sativum genotypes to the two aphid biotypes were variable and more pronounced for the alfalfa biotype. EPG data showed that ArPo28 on P. fulvum and LSR1 on all the Pisum genotypes spent shorter time phloem feeding compared to ArPo28 on P. sativum genotypes, indicating that the resistance of Pisum genotypes to non-adapted A. pisum resides in mesophyll and phloem cells. In the meantime, ArPo28 on P. sativum genotypes with a different level of resistance spent a similar length of time phloem feeding, indicating that the quality of phloem sap of the resistance genotypes may not be optimal for the aphid. The study indicated that the resistance of Pisum genotypes to the two A. pisum biotypes involves different genetic factors and mechanisms that affect the aphid differently.
Differences in Accuracy and Radiation Dose in Placement of Iliosacral Screws: Comparison between 3D and 2D Fluoroscopy
Authors: Kułakowski Michał , Reichert Paweł , Elster Karol , Witkowski Jarosław , Ślęczka Paweł , Morasiewicz Piotr , Oleksy Łukasz , Królikowska Aleksandra
Published: March 2022

Percutaneous iliosacral screw fixation is a widely accepted method of stabilizing the posterior pelvic ring. Recently developed tools such as 3D-navigated fluoroscopy and computed navigation seem to prevent a surgeon from conducting screw misplacement. The study aimed to comparatively assess the introduction of sacroiliac screw placement using 2D and 3D fluoroscopy in terms of accuracy and radiation exposure. Iliosacral screws were introduced in 37 patients using 2D (group N1) and in 36 patients using 3D fluoroscopy (group N2) techniques. Overall, 61 and 56 screws were introduced in groups N1 and N2, respectively. Screw placement accuracy was assessed using postoperative computed tomography and Smith’s scale. Intraoperative radiation exposure was also assessed. No differences were noted between groups in terms of screw positioning accuracy and radiation dose. Both 2D and 3D fluoroscopy provide good visualization for safely placing percutaneous iliosacral joint screws. Using 3D fluoroscopy-based navigation in comparison with 2D fluoroscopy is not advantageous.
Conditional Process Analysis for Effective Lens Position According to Preoperative Axial Length
Authors: Yoo Young-Sik , Whang Woong-Joo
Published: March 2022

Purpose: To predict the effective lens position (ELP) using conditional process analysis according to preoperative axial length. Setting: Yeouido St. Mary hospital. Design: A retrospective case series. Methods: This study included 621 eyes from 621 patients who underwent conventional cataract surgery at Yeouido St. Mary Hospital. Preoperative axial length (AL), mean corneal power (K), and anterior chamber depth (ACD) were measured by partial coherence interferometry. AL was used as an independent variable for the prediction of ELP, and 621 eyes were classified into four groups according to AL. Using conditional process analysis, we developed 24 structural equation models, with ACD and K acting as mediator, moderator or not included as variables, and investigated the model that best predicted ELP. Results: When AL was 23.0 mm or shorter, the predictability for ELP was highest when ACD and K acted as moderating variables (R2 = 0.217). When AL was between 23.0 mm and 24.5 mm or longer than 26.0 mm, the predictability was highest when K acted as a mediating variable and ACD acted as a moderating variable (R2 = 0.217 and R2 = 0.401). On the other hand, when AL ranged from 24.5 mm to 26.0 mm, the model with ACD as a mediating variable and K as a moderating variable was the most accurate (R2 = 0.220). Conclusions: The optimal structural equation model for ELP prediction in each group varied according to AL. Conditional process analysis can be an alternative to conventional multiple linear regression analysis in ELP prediction.
SGLT2 Inhibitors in Type 2 Diabetes Mellitus and Heart Failure—A Concise Review
Authors: Keller Daria M. , Ahmed Natasha , Tariq Hamza , Walgamage Malsha , Walgamage Thilini , Mohammed Azad , Chou Jadzia Tin-Tsen , Kałużna-Oleksy Marta , Lesiak Maciej , Straburzyńska-Migaj Ewa
Published: March 2022

The incidence of both diabetes mellitus type 2 and heart failure is rapidly growing, and the diseases often coexist. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new antidiabetic drug class that mediates epithelial glucose transport at the renal proximal tubules, inhibiting glucose absorption—resulting in glycosuria—and therefore improving glycemic control. Recent trials have proven that SGLT2i also improve cardiovascular and renal outcomes, including reduced cardiovascular mortality and fewer hospitalizations for heart failure. Reduced preload and afterload, improved vascular function, and changes in tissue sodium and calcium handling may also play a role. The expected paradigm shift in treatment strategies was reflected in the most recent 2021 guidelines published by the European Society of Cardiology, recommending dapagliflozin and empagliflozin as first-line treatment for heart failure patients with reduced ejection fraction. Moreover, the recent results of the EMPEROR-Preserved trial regarding empagliflozin give us hope that there is finally an effective treatment for patients with heart failure with preserved ejection fraction. This review aims to assess the efficacy and safety of these new anti-glycemic oral agents in the management of diabetic and heart failure patients.
Selecting the Target Population for Screening of Hepatic Fibrosis in Primary Care Centers in Korea
Authors: Park Huiyul , Yoon Eileen L. , Kim Mimi , Cho Seon , Kim Jung-Hwan , Jun Dae Won , Nah Eun-Hee
Published: March 2022

Screening strategies for hepatic fibrosis are heavily focused on patients with fatty liver on sonography in primary care centers. This study aimed to investigate the target population for screening significant hepatic fibrosis in primary care centers. This retrospective cross-sectional cohort study used data from 13 nationwide centers. A total of 5111 subjects who underwent both abdominal sonography and magnetic resonance elastography as part of their health check-up were included. Subjects with viral hepatitis and/or a history of significant alcohol consumption were excluded. Significant and advanced hepatic fibrosis was defined as ≥3.0 kPa and ≥3.6 kPa in the MRE test, respectively. The prevalence of significant and advanced hepatic fibrosis was 7.3% and 1.9%, respectively. Among the subjects with significant hepatic fibrosis, 41.3% did not have fatty liver. Hepatic fibrosis burden increased according to the number of metabolic risk abnormalities. Nearly 70% of subjects with significant hepatic fibrosis also had two or more metabolic risk abnormalities and/or diabetes. However, the prevalence of fibrosis did not differ between the groups with and without fatty liver. The presence of two or more metabolic risk abnormalities was an independent risk factor for significant hepatic fibrosis regardless of the fatty liver. Therefore, in the setting of primary care centers, screening for hepatic fibrosis would better be extended to subjects with metabolically unhealthy status beyond those with fatty liver.