Miracle-dz/UniFAR-FTUs huggingface dataset:
Roles of Lipid Peroxidation-Derived Electrophiles in Pathogenesis of Colonic Inflammation and Colon Cancer

Redox stress is a common feature of gut disorders such as colonic inflammation (inflammatory bowel disease or IBD) and colorectal cancer (CRC). This leads to increased colonic formation of lipid-derived electrophiles (LDEs) such as 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), trans, trans-2,4-decadienal (tt-DDE), and epoxyketooctadecenoic acid (EKODE). Recent research by us and others support that treatment with LDEs increases the severity of colitis and exacerbates the development of colon tumorigenesis in vitro and in vivo, supporting a critical role of these compounds in the pathogenesis of IBD and CRC. In this review, we will discuss the effects and mechanisms of LDEs on development of IBD and CRC and lifestyle factors, which could potentially affect tissue levels of LDEs to regulate IBD and CRC development.
Rationalizing Inconsistent Consumer Behavior. Understanding Pathways That Lead to Negative Spillover of Pro-environmental Behaviors in Daily Life

Ideally, pro-environmental consumer behavior leads to a lower impact on the environment. However, due to negative behavioral spillovers environmentally friendly behavior could lead to an overall higher environmental impact if subsequent environmentally unfriendly behavior occurs. In this exploratory interview study we focused on two pathways leading to negative spillover: a psychological path (perceived effort, moral licensing) and an economic path (rebound effects). We wanted to gain insight into people’s motivations to behave environmentally unfriendly and to explore people’s level of awareness of both pathways. Our results indicate that pro-environmental behaviors that are associated with higher effort are performed less frequently, and that when people do not perform these behaviors they associate them with higher effort levels. When people perceive behaviors as more effortful they increasingly seem to use arguments to motivate and rationalize why performing the behavior is difficult or impossible. Moreover, we found that although some people can imagine that moral licensing and rebound effects could occur and can provide examples from their own lives, most people assess these concepts as not rational. People seem unaware of the relation between a first pro-environmental behavior (PEB) and a subsequent behavior, and therefore inconsistencies in behavior go unnoticed. As people are good at rationalizing why they do not perform specific PEBs, they in general feel satisfied with their own pro-environmental actions. In order to discourage negative spillovers, we describe a number of approaches and research ideas aimed at taking away the grounds for rationalization.
Using Telemedicine During the COVID-19 Pandemic: Attitudes of Adult Health Care Consumers in Israel

Introduction: The COVID-19 pandemic has affected health care services worldwide due to lockdowns, prevention measures, and social distancing. During this period, patients, including older adults and those with chronic conditions, need ways to obtain medical attention other than going physically to the clinic, such as telemedicine services. The purpose of the present study was to evaluate attitudes toward telemedicine during the COVID-19 lockdown in Israel, assess willingness to use such services in the future, and evaluate the extent to which consumers have changed their minds regarding these services. Method: A cross-sectional, descriptive, correlational study was conducted among adults (age 20–90) using social media networks (N = 693). Data were collected using an online questionnaire explicitly designed to measure attitudes toward telemedicine. Results: Most of the participants had to use telemedicine during the lockdown and were satisfied therewith. The majority also stated that they would continue using telemedicine in the future. However, only a third stated that they had changed their minds regarding telemedicine. The main predictors of willingness to use telemedicine in the future were the necessity of using such services during lockdown, preference for going to a clinic, and satisfaction with telemedicine, alongside gender and having a chronic illness. Importantly, we found that a preference for visiting the clinic was negatively correlated with willingness to use telemedicine in the future. Education and being single were predictors of the change of mind regarding telemedicine. Participants with chronic conditions are more likely to use these services, and specific attention should be directed to their needs. A small portion of the study sample prefers live appointments with a physician. Conclusions: Telemedicine use is rapidly changing. It is vital for health care providers to identify non-telemedicine users and their common characteristics. Monitoring patients' attitudes regarding telemedicine is essential in the future after the pandemic ends. Targeted outreach plans should be formulated. These plans should be directed at identifying barriers to using telemedicine, and they should generate specific, focused plans.
New Insights into Vaginal Environment During Pregnancy

During pregnancy, the vaginal ecosystem undergoes marked changes, including a significant enrichment with Lactobacillus spp. and profound alterations in metabolic profiles. A deep comprehension of the vaginal environment may shed light on the physiology of pregnancy and may provide novel biomarkers to identify subjects at risk of complications (e.g., miscarriage, preterm birth). In this study, we characterized the vaginal ecosystem in Caucasian women with a normal pregnancy (n = 64) at three different gestational ages (i.e., first, second and third trimester) and in subjects (n = 10) suffering a spontaneous first trimester miscarriage. We assessed the vaginal bacterial composition (Nugent score), the vaginal metabolic profiles (1H-NMR spectroscopy) and the vaginal levels of two cytokines (IL-6 and IL-8). Throughout pregnancy, the vaginal microbiota became less diverse, being mainly dominated by lactobacilli. This shift was clearly associated with marked changes in the vaginal metabolome: over the weeks, a progressive reduction in the levels of dysbiosis-associated metabolites (e.g., biogenic amines, alcohols, propionate, acetate) was observed. At the same time, several metabolites, typically found in healthy vaginal conditions, reached the highest concentrations at the end of pregnancy (e.g., lactate, glycine, phenylalanine, leucine, isoleucine). Lower levels of glucose were an additional fingerprint of a normal vaginal environment. The vaginal levels of IL-6 and IL-8 were significantly associated with the number of vaginal leukocytes, as well as with the presence of vaginal symptoms, but not with a condition of dysbiosis. Moreover, IL-8 concentration seemed to be a good predictor of the presence of vaginal Candida spp. Cytokine concentrations were negatively correlated to lactate, serine, and glycine concentrations, whereas the levels of 4-hydroxyphenyllactate, glucose, O-acetylcholine, and choline were positively correlated with Candida vaginal loads. Finally, we found that most cases of spontaneous abortion were associated with an abnormal vaginal microbiome, with higher levels of selected metabolites in the vaginal environment (e.g., inosine, fumarate, xanthine, benzoate, ascorbate). No association with higher pro-inflammatory cytokines was found. In conclusion, our analysis provides new insights into the pathophysiology of pregnancy and highlights potential biomarkers to enable the diagnosis of early pregnancy loss.
Testing the Disgust-Based Mechanism of Homonegative Attitudes in the Context of the COVID-19 Pandemic

Negative attitudes and stigmatization can originate from the perception of a disease-related threat. Following the spread of the COVID-19 pandemic, it is often suggested that incidents of discriminatory behavior are the result of defense mechanisms aimed at avoiding pathogens. According to the behavioral immune system theory, people are motivated to distance themselves from individuals who show signs of infection, or who are only heuristically associated with a disease, primarily because of the disgust they evoke. In this paper we focus on negative attitudes toward gay men and lesbians who are among social groups that have been persistently framed as “unclean. ” In our correlational study (N = 500 heterosexual participants; Polish sample data collected during the first COVID-19 lockdown in Poland, in March/April 2020) we tested moderation models derived from the behavioral immune system theory. Specifically, we investigated whether perceived vulnerability to disease and perceived threat of contracting COVID-19 moderate the relation between disgust and homonegativity. We found that sexual disgust (but not pathogen nor moral disgust) predicted homonegative attitudes. This effect was stronger for participants expressing higher levels of perceived vulnerability to disease but was not dependent on the perception of the COVID-19 threat. The results reaffirm previous evidence indicating a pivotal role of disgust in disease-avoidance mechanisms. They also point to functional flexibility of the behavioral immune system by demonstrating the moderating role of perceived vulnerability to disease in shaping homonegative attitudes. Finally, they show that the threat of COVID-19 does not strengthen the relationship between disgust and homonegativity.
Association Between Alkaline Phosphatase and Muscle Mass, Strength, or Physical Performance in Patients on Maintenance Hemodialysis

Introduction: Alkaline phosphatase (ALP) is an indicator for checking liver or bone disorders, but recent studies have shown the possibility of an additive indicator beyond the simple mineral-bone status in dialysis patients. The aim of the study was to evaluate the ALP level and various indicators for malnutrition, physical performance, or hospitalization in patients on hemodialysis (HD). Methods: This study was an observational study (n = 84). We included all patients undergoing HD with the following criteria: age ≥ 20 years, duration of dialysis ≥ 6 months, ability to ambulate without an assistive device, ability to communicate with the interviewer, and no hospitalization within the last 3 months before enrollment. Furthermore, none of the patients had liver disease. We recommended abstinence of alcohol for ≥ 1 month for the duration of the study. The patients were divided into tertiles based on the ALP level. Muscle mass [appendicular muscle mass index using dual-energy X-ray absorptiometry (ASM/Ht2), thigh muscle area index using computed tomography (TMA/Ht2)], strength [handgrip strength (HGS)], and physical performance [gait speed (GS), sit-to-stand for 30-s test (STS30), 6-min walk test (6-MWT), or Short Physical Performance Battery test (SPPB)] were evaluated. The number of hospitalizations was also evaluated. Results: The ALP level in the low, middle, and high tertiles was 50.5 ± 7.5, 69.8 ± 5.4, and 113.3 ± 47.3 IU/l, respectively. The high tertile group showed the poorest trends in ASM/Ht2, TMA/Ht2, HGS, GS, STS30, and 6-MWT compared to the other tertile groups. Logistic regression analysis showed that the high tertile group for low HGS, low GS, or low SPPB had a higher odds ratio compared to the other tertiles. Subgroup analyses according to age, sex and diabetes mellitus showed similar trends as in the total cohort. Hospitalization-free survival rates after 300 days in the high tertile and the other tertiles were 53.8 and 77.2%, respectively (P = 0.105). Conclusion: The present study demonstrated that ALP is associated with muscle mass, strength, and physical performance in patients on maintenance HD. In addition, the trend showed better hospitalization-free survival in the low or middle tertiles than in the high tertile. ALP can be considered as a simple and useful indicator to detect malnutrition, physical performance, or hospitalization in patients on HD.
Amelioration of Beta Interferon Inhibition by NS4B Contributes to Attenuating Tembusu Virus Virulence in Ducks

Our previous studies reported that duck Tembusu virus nonstructural protein 2A (NS2A) is a major inhibitor of the IFNβ signaling pathway through competitively binding to STING with TBK1, leading to a reduction in TBK1 phosphorylation. Duck TMUV NS2B3 could cleave and bind STING to subvert the IFNβ signaling pathway. Here, we found that overexpression of duck TMUV NS4B could compete with TBK1 in binding to STING, reducing TBK1 phosphorylation and inhibiting the IFNβ signaling pathway by using the Dual-Glo® Luciferase Assay System and the NanoBiT protein-protein interaction (PPI) assay. We further identified the E2, M3, G4, W5, K10 and D34 residues in NS4B that were important for its interaction with STING and its inhibition of IFNβ induction, which were subsequently introduced into a duck TMUV replicon and an infectious cDNA clone. We found that the NS4B M3A mutant enhanced RNA replication and exhibited significantly higher titer levels than WT at 48-72 hpi but significantly decreased mortality (80%) in duck embryos compared to WT (100%); the NS4B G4A and R36A mutants slightly reduced RNA replication but exhibited the same titer levels as WT. However, the NS4B R36A mutant did not attenuate the virulence in duck embryos, whereas the G4A mutant significantly decreased the mortality (70%) of duck embryos. In addition, the NS4B W5A mutant did not affect viral replication, whereas the D34A mutant slightly reduced RNA replication, and both mutants exhibited significantly lower titer levels than the WT and significantly decreased mortality (90% and 70%, respectively) in duck embryos. Hence, our findings provide new insight into the development of attenuated flaviviruses by targeting the disabling viral strategies used to evade the innate defense mechanisms.
M2-AChR Mediates Rapid Antidepressant-Like Effects of Scopolamine Through Activating the mTORC1-BDNF

Background: Scopolamine, a non-selective muscarinic acetylcholine receptor (M1~5-AChR) antagonist, has rapid and robust antidepressant effects in humans and other species. However, which of the five M-AChRs mediates these therapeutic effects has not been fully identified. Several studies implicate M2-AChR as a potential antidepressant target of scopolamine. This study aimed to explore the role of M2-AChR in scopolamine's antidepressant-like effects and determine the underlying mechanisms. Methods: We used the classic novelty suppressed feeding test (NSFT), open field test (OFT) and forced swim test (FST) to observe antidepressant-related behaviors of normal rats, medial prefrontal cortex (mPFC) neuron silenced rats and M2-AChR knockdown rats treated with scopolamine. In a further experiment, the M2 cholinergic receptor antagonist methoctramine (MCT) was injected intracerebroventricularly into normal rats. Levels of mTORC1 and brain-derived neurotrophic factor (BDNF) in the mPFC of animals were analyzed by Western blotting. Results: Consistent with previous studies, mPFC was required for the antidepressant-like effects of scopolamine, and intracerebroventricular injection of MCT into rats could produce similar antidepressant-like effects. Use of AAV-shRNA to knock down M2-AChR in the mPFC resulted in the antidepressant-like effects of scopolamine being blunted. Furthermore, Western blotting demonstrated increased expression of mTORC1 signaling and BDNF in MCT-treated rats. Conclusion: Our results indicate that M2-AChR in the mPFC mediates the antidepressant-like effects of scopolamine by increasing the expression of BDNF and activating the mTORC1 signaling pathway.
Cognitive and Emotional Disturbances Due to COVID-19: An Exploratory Study in the Rehabilitation Setting

The coronavirus disease 19 (COVID-19) can cause neurological, psychiatric, psychological, and psychosocial impairments. Literature regarding cognitive impact of COVID-19 is still limited. The aim of this study was to evaluate cognitive deficits and emotional distress among COVID-19 and post–COVID-19 patients who required functional rehabilitation. Specifically, this study explored and compared cognitive and psychological status of patients in the subacute phase of the disease (COVID-19 group) and patients in the postillness period (post–COVID-19 group). Forty patients admitted to rehabilitation units were enrolled in the study and divided into two groups according to the phase of the disease: (a) COVID-19 group (n = 20) and (b) post–COVID-19 group (n = 20). All patients underwent a neuropsychological assessment including Mini-Mental State Evaluation (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Rating Scale for Depression, and Impact of Event Scale–Revised (IES-R). A larger part of the COVID group showed neuropsychological deficits in the total MMSE (35%) compared to the post-COVID group (5%), whereas the majority of both groups (75–70%) reported cognitive impairments in the total MoCA. The post-COVID group reported significantly higher score in MMSE subtests of language (p = 0.02) and in MoCA subtests of executive functions (p = 0.05), language (p = 0.01), and abstraction (p = 0.02) compared to the COVID group. Regarding emotional disturbances, ~40% of patients presented with mild to moderate depression (57.9–60%). The post–COVID-19 group reported significantly higher levels of distress at the IES-R compared to the COVID group (p = 0.02). These findings highlight the gravity of neuropsychological and psychological symptoms that can be induced by COVID-19 infection and the need for tailored rehabilitation, including cognitive training and psychological support.
Changes in Availability, Utilization, and Prices of Medicines and Protection Equipment for COVID-19 in an Urban Population of Northern Nigeria

Objective: Measures are ongoing to prevent the spread of COVID-19 and treat it with medicines and personal protective equipment (PPE). However, there has been considerable controversy surrounding treatments such as hydroxychloroquine with misinformation fuelling prices hikes and suicides. Shortages have also appreciably increased costs of PPE, potentially catastrophic among lower- and middle-income countries such as Nigeria with high copayment levels. Consequently, a need to investigate changes in availability, utilization, and prices of relevant medicines and PPE during the pandemic in Nigeria. Methods: Exploratory study among community pharmacists with a survey tool comprising four sections including questions on changes in consumption, prices, and shortages of medicines and PPE from the beginning of March 2020 to the end of June 2020. In addition, suggestions from community pharmacists and co-authors on ways to reduce misinformation. Findings: 30 out of 34 pharmacists participated giving a response rate of 88.2%. Significant increases were seen (3-fold or more increase) in the consumption of hydroxychloroquine (100%), vitamins/immune boosters (96.7%) and antibiotics (46.7%) as well as PPE (100%). Considerable price increases (50% increase or greater) also seen for antimalarials (96.7%), antibiotics (93.3%), vitamins/immune boosters (66.7%), and PPE (100%). Shortages are also seen for hydroxychloroquine and vitamins/immune boosters but most severe for PPE (80% of pharmacies). Conclusion: Encouraging to see increases in the utilization of vitamins/immune boosters and PPE. However, a considerable increase in the utilization and prices of antimicrobials is a concern that needs addressing including misinformation. Community pharmacists have a key role in providing evidence-based advice and helping moderate prices.
Mechanical effects of ranolazine on normal and diabetic-isolated rat heart

Background and purpose: Diabetic cardiomyopathy is a complication of diabetes defined as cardiac dysfunction without the involvement of pericardial vessels, hypertension, or cardiac valve disorders. Ranolazine, an antianginal drug, acts through blocking of cardiac late sodium channels and/or inhibiting beta-oxidation of fatty acids. With regard to its mechanism of action, the present work has been carried out to investigate the potential useful effects of ranolazine on the systolic and diastolic dysfunctions in an experimental rat model of diabetic cardiomyopathy. Lidocaine, as a sodium channel blocker, was used to have a clearer image of the involved mechanisms. Experimental approach: Diabetes was induced by streptozocin. After 8 weeks, the effects of cumulative concentrations of ranolazine and lidocaine were evaluated on diabetic and normal hearts by the Langendorff method. Finally, the hearts were isolated from the Langendorff system and adenosine three phosphates (ATP) and adenosine diphosphate (ADP) concentrations were measured to assay the metabolic effect of ranolazine. Findings/Results: Ranolazine significantly decreased the velocity of systolic contraction (+dP/dt) and the velocity of diastolic relaxation (-dP/dt) and developed pressure in normal and diabetic rat hearts. However, this negative effect was greater in normal hearts compared to diabetics. Ranolazine (100 μM) decreased the ATP level only in normal hearts and the ATP/ADP ratio decreased significantly (P < 0.05) in both groups. This reduction was more prominent in normal hearts. Conclusion and implications: It is concluded that in the isolated rat heart preparation, ranolazine has no benefit on diabetic cardiomyopathy and may even worsen it. It seems that these effects are related to the metabolic effects of ranolazine.
Effect of moderate exercises and curcumin on hepatic transcriptional factors associated with lipid metabolism and steatosis in elderly male rat

Background and purpose: The specific molecular mediators involved in dyslipidemia in older people are not yet clearly understood. The current study was, thus, an attempt to investigate whether moderate aerobic exercises and curcumin administration alleviates the abnormalities caused by aging in the rats’ liver. Experimental approach: Thirty-two eight-year-old young rats were classified into five groups, namely, young control, aged control, aged-curcumin, aged-exercise, and aged-curcumin-exercise co-treatment. The rats in the exercise groups were trained on an animal treadmill for 60 min/day five times per week for eight weeks. Findings/Results: The results revealed a significant increase in FAT/CD36, PTP1B, significantly decreased HNF4α genes expression, increase in LDL and cholesterol in the aged group compared to the young control. Compared to those in the young control group, no significant changes in HDL and TG amounts in the aged control were observed. Moreover, compared to the young control, the aged group showed liver histological changes such as fibrosis and mild or grade 1 steatohepatitis. Moderate aerobic exercise and curcumin alone or in combination completely masked this effect. Conclusion and implications: The findings revealed dyslipidemia and liver steatosis related to aging might be partly associated with changes in hepatic transcriptional factors which can be mitigated via moderate aerobic exercise and curcumin.