bluuebunny/crossref_metadata_2025 huggingface dataset:
Workplace Culture and Biomarkers of Health Risk
Authors: Shuck Brad , Hart Joy L. , Walker Kandi L. , Rai Jayesh , Srivastava Shweta , Srivastava Sanjay , Rai Shesh , Bhatnagar Aruni , Keith Rachel J.
Published: September 2022

Workplace culture has been studied for impact on health risk; however, connections with robust biologic markers of health remain to be established. We examined associations between the work environment and urinary levels of catecholamines and their metabolites as biomarkers of sympathetic nervous system activity, indicative of stress. We recruited participants (n = 219; 2018–2019) from a cardiovascular risk cohort to investigate workplace culture, well-being, and stress. Participants completed seven questionnaires. Urine samples were used to measure catecholamines and their metabolites by LC/MS/MS. Pearson correlation and linear regression models were used after adjusting for demographics and creatinine. Participants reporting higher well-being had lower urinary levels of dopamine, serotonin, and 3-methoxytyramine. Participants reporting a more engaged and more positive workplace had lower levels of dopamine and 3-methoxytyramine. Reported workplace isolation was correlated with higher levels of dopamine and 3-methoxytyramine. Given correlations between catecholamines, we used 3-methoxytyramine for linear regression. In fully adjusted models, in environments with a more positive culture, levels of 3-methoxytyramine remained lower (β = −0.065 ± 0.025, p = 0.01) and indicated a positive association between workplace isolation and 3-methoxytyramine (β = 0.064 ± 0.030, p = 0.04). These findings are consistent with an important relationship between workplace environment and sympathetic nervous system activity.
Gender Inequality in Low- and Middle-Income Countries: Associations with Parental Physical Abuse and Moderation by Child Gender
Authors: Ma Julie , Grogan-Kaylor Andrew C. , Lee Shawna J. , Ward Kaitlin P. , Pace Garrett T.
Published: September 2022

Gender inequality perpetuates women’s economic insecurity and a culture of violence. Parental distress caused by economic pressure may increase violence against children. High levels of gender inequality and interpersonal violence may contribute to higher levels of physical abuse. Using an ecological perspective, this study examines the association of country-level gender inequality and household-level parental physical abuse, and the moderating role of child gender in this association in low- and middle-income countries. We used data on over 420,000 households from the UNICEF Multiple Indicator Cluster Surveys and country-level indicators from the United Nations Development Program Human Development data. We employed multilevel logistic regression to examine the association between gender inequality with the log-odds of physical abuse after accounting for country- and individual-level covariates. In order to more fully explore our results, we calculated predicted probabilities of abuse for several scenarios. The results indicated that higher levels of gender inequality were associated with higher probabilities of physical abuse. This association was stronger for female children than for male children. The probabilities of abuse by child gender were indistinguishable, although rates of physical abuse converged as gender inequality increased, at a statistically marginal level. These findings indicate that macro-level interventions that reduce gender inequality are necessary to prevent and reduce child physical abuse.
Climate Changes, Natural Resources Depletion, COVID-19 Pandemic, and Russian-Ukrainian War: What Is the Impact on Habits Change and Mental Health?
Authors: Barchielli Benedetta , Cricenti Clarissa , Gallè Francesca , Sabella Elita Anna , Liguori Fabrizio , Da Molin Giovanna , Liguori Giorgio , Orsi Giovanni Battista , Giannini Anna Maria , Ferracuti Stefano , Napoli Christian
Published: September 2022

Climate Change, Natural Resources Depletion, COVID-19, and Wars are some of the great challenges of our time. The consequences will affect psychological well-being and could have a harmful impact on mental health. This study aimed to assess the level of preoccupation and fears surrounding issues of the 21st-century and the implication for psychological well-being of the general population from Central/Southern Italy among different age groups. A questionnaire that included sociodemographic characteristics, topics formulated ad-hoc about preoccupation, fears, habits, and willingness to change habits in the future related to the 21st-century challenges, and the Depression Anxiety Stress Scales 21 (DASS-21) was administered online. A sample of 1831 participants (61% F; mean age 47.71 ± 17.30) was obtained. Results showed that young adults and older adults, respectively, reported greater and less psychological well-being. Young adults reported higher scores for preoccupation, changing habits, and willingness to change habits in the future, while older adults reported the lowest scores except for changing habits, also controlling for gender. Results for this variable, as well as correlations between the many variables described, rely on the specificity of age, and 21st-century challenges. Moreover, the main fears related to the 21st-century concerns were different based on both age and gender. In conclusion, the various stresses of the 21st-century discussed in this study have a relationship with personal well-being, and it is important to consider potential global mental health issues resulting from these stressors.
Failures in Reflective Functioning and Reported Symptoms of Anxiety and Depression in Bereaved Individuals: A Study on a Sample of Family Caregivers of Palliative Care Patients
Authors: Lenzo Vittorio , Sardella Alberto , Musetti Alessandro , Petralia Maria Cristina , Grado Irene , Quattropani Maria C.
Published: September 2022

Introduction. This study aims at examining the role of failures in reflective functioning in predicting anxiety and depression among family caregivers of palliative care patients deceased for at least one year. Methods. A sample of 157 bereaved participants (77.1% females, mean age = 43.50 ± 14.04 years) completed the Hospital Anxiety and Depression Scale (HADS) and the Reflective Functioning Questionnaire (RFQ). Results. Results of the correlational analysis showed that anxiety was positively correlated with uncertainty about mental states, indicating one type of impairment in reflective functioning. Anxiety was also negatively correlated with the certainty about mental states. Depression was negatively correlated with certainty but not with uncertainty about mental states. The results of regression analysis indicated that gender and certainty about mental states were statistically significant predictors of anxiety, with the final model explaining 23% of the variance. The results also showed that gender, the condition of being the main caregiver, and the certainty about mental states were significant predictors of depression, with the final model predicting 14% of the variance. Conclusions. Overall, the results of this study point out that the bereaved individuals who scored low on certainty about mental states reported more symptoms of anxiety and depression. Psychological interventions to prevent mental disorders and to promote psychological health in the context of palliative care should carefully consider these findings.
Offered Support and Knowledge about the Menstrual Cycle in the Athletic Community: A Cross-Sectional Study of 1086 Female Athletes
Authors: von Rosen Philip , Ekenros Linda , Solli Guro Strøm , Sandbakk Øyvind , Holmberg Hans-Christer , Hirschberg Angelica Lindén , Fridén Cecilia
Published: September 2022

Many female athletes perceive that symptoms related to the menstrual cycle such as dysmenorrhea, premenstrual symptoms, amenorrhea or side-effects of hormonal contraceptives negatively impact their training, performance, and general well-being. Knowledge and communication about female athletes’ health is therefore important in the sport community. The aims of this study were to explore the level of knowledge and communication about menstrual cycle issues and use of hormonal contraceptives in the athletic community and to describe the kinds of medical support offered to female athletes. A total of 1086 Swedish and Norwegian athletes from 57 different sports responded to a web-based questionnaire. Of these, 58% (n = 627) practiced team sports and 42% (n = 459) individual sports. Twenty-six percent (n = 278) of the athletes perceived their knowledge about female athlete health to be poor/very poor and the knowledge was most often acquired from medical staff. Fifty-three percent (n = 572) of the athletes perceived the knowledge acquired of their coaches as poor/very poor, even though a significantly (p < 0.001) higher proportion of athletes with a female coach (30%, n = 31) rated their coach’s knowledge as very good/good, compared to athletes with a male coach (5%, n = 31). Only 11% (n = 116) of the athletes discussed female health issues with their coach. The majority (81%, n = 842) of the athletes partly to strongly agreed that female athlete health is considered a taboo topic in the athletic community. Forty-seven percent (n = 510) of the athletes had access to a physiotherapist, while only three percent (n = 29) had access to a gynecologist. Low perceived knowledge, lack of communication and support demonstrate the need for a multi-professional medical team and enhanced educational efforts focused on female athlete health in the athletic community.
An Evidence-Based Somatic Acupressure Intervention Protocol for Managing the Breast Cancer Fatigue-Sleep Disturbance-Depression Symptom Cluster: Development and Validation following the Medical Research Council Framework
Authors: Tan Jing-Yu (Benjamin) , Wang Tao , Zhao Isabella , Polotan Mary Janice , Eliseeva Sabina
Published: September 2022

Background: Somatic acupoint stimulation (SAS) has been frequently utilised as a promising intervention for individual cancer-related symptom management, such as fatigue, sleep disturbance and depression. However, research evidence regarding the role of SAS in mitigating the fatigue-sleep disturbance-depression symptom cluster (FSDSC) has been scant. This study was conducted to develop an evidence-based SAS intervention protocol that can be further implemented in a Phase II randomized controlled trial (RCT) to manage the FSDSC in breast cancer survivors. Methods: The Medical Research Council Framework for Developing and Evaluating Complex Intervention (MRC framework) was employed to guide the development procedures of the SAS intervention protocol, including the identification of an existing evidence base, the identification of theories and practice standards, and the validation of the SAS intervention protocol. A content validity study was performed through an expert panel to assess the scientific and practical appropriateness of the SAS intervention protocol. The content validity index (CVI), including item-level CVI and protocol-level CVI, were calculated to evaluate the consensus level of the expert panel. Results: Key components of the SAS protocol, including the acupoint formula, the SAS modality, technique, intensity and frequency were identified for both a true and placebo SAS intervention based on the best available research evidence retrieved from systematic reviews, clinical trials, and relevant theories, particularly regarding the inflammatory process, yin-yang theory, zang-fu organs and meridians theory, and acupressure practical standards. The true SAS intervention was determined as daily self-administered acupressure on specific acupoints for seven weeks. The placebo SAS was designed as light acupressure on non-acupoints with the same frequency and duration as the true SAS. Excellent content validity was achieved after one round of expert panel assessment, with all the key components of the true and placebo SAS protocols rated as content valid (CVI ranged from 0.86 to 1.00). Conclusions: A research-informed, theory-driven and practically feasible SAS intervention protocol for the FSDSC management in breast cancer survivors was developed following the MRC framework. The feasibility and acceptability of the SAS intervention will be further tested in breast cancer survivors through a Phase II RCT.
Do Patients with Atrial Fibrillation and a History of Ischemic Stroke Overuse Reduced Doses of NOACs?—Results of the Polish Atrial Fibrillation (POL-AF) Registry
Authors: Szyszkowska Anna , Kuźma Łukasz , Wożakowska-Kapłon Beata , Gorczyca-Głowacka Iwona , Jelonek Olga , Uziębło-Życzkowska Beata , Krzesiński Paweł , Wójcik Maciej , Błaszczyk Robert , Gawałko Monika , Kapłon-Cieślicka Agnieszka , Tokarek Tomasz , Rajtar-Salwa Renata , Bil Jacek , Wojewódzki Michał , Szpotowicz Anna , Krzciuk Małgorzata , Bednarski Janusz , Bakuła Elwira , Wełnicki Marcin , Mamcarz Artur , Tomaszuk-Kazberuk Anna
Published: September 2022

Background: The aim of our study was to assess if patients with AF (atrial fibrillation) and a history of ischemic stroke (IS) excessively receive reduced doses of NOACs (non-vitamin K antagonist oral anticoagulants). Methods: The Polish AF (POL-AF) registry is a prospective, observational, multicenter study, including patients with AF from 10 cardiology hospital centers. In this study we focused on patients with IS in their past. Results: Among 3999 patients enrolled in the POL-AF registry, 479 (12%) had a previous history of IS. Compared to patients without IS history, post-stroke subjects had a higher CHA2DS2-VASc score (median score 7 vs. 4, p < 0.05). Of these subjects, 439 (92%) had anticoagulation therapy, 83 (18.9%) were treated with a vitamin K antagonist (VKA), 135 (30.8%) with rivaroxaban, 112 (25.5%) with dabigatran, and 109 (24.8%) with apixaban. There were a significant number of patients after IS with reduced doses of NOACs (48.9% for rivaroxaban, 45.5% for dabigatran, and 36.7% for apixaban). In many cases, patients were prescribed reduced doses of NOACs without any indication for reduction (28.8% of rivaroxaban use, 56.9% of dabigatran use, and 60.0% of apixaban use—out of reduced dosage groups, p = 0.06). Conclusions: A significant proportion of AF patients received reduced doses of NOAC after ischemic stroke in a sizeable number of cases, without indication for dose reduction.
Impact of Antiretroviral Therapy on Oral Health among Children Living with HIV: A Systematic Review and Meta-Analysis
Authors: Lam Phoebe Pui Ying , Zhou Ni , Yiu Cynthia Kar Yung , Wong Hai Ming
Published: September 2022

Oral health is an integral component of general health and well-being but might be undermined among children living with HIV (CLWH) due to the condition itself or the antiretroviral therapy (ART) received. This review summarises the current evidence and compares the oral health status of the CLWH who were treatment-naïve with those undergoing different ART medications. Fourteen studies were included in the final qualitative and quantitative analyses. This review identified no significant difference in the prevalence of caries, periodontal conditions, and tooth development between both groups. Orofacial opportunistic infections were more prevalent in the CLWH without ART. Children undergoing ART with a duration longer than 3 years had a significantly lower prevalence of oral candidiasis and CD4+ T-cell counts. However, due to the insufficient number of well-administered case–control studies with adequate sample size, the quality of the evidence in all outcomes was of very low certainty.
Social Frailty among Community-Dwelling Older Adults during the COVID-19 Pandemic in Korea: A Cross-Sectional Study
Authors: Choi Seunghye , Ko Hana
Published: September 2022

Social frailty among older adults has become a growing concern from a public health perspective in the context of the coronavirus disease 2019 (COVID-19) pandemic. This study’s aim was to investigate the influence of various aspects of social frailty in community-dwelling older adults during the COVID-19 pandemic. This study carried out a secondary analysis of data collected from the 2020 National Survey of Older Koreans and performed multinomial logistic regression analysis to identify the predictive factors of social frailty. The affected factors for the social frailty group were health conditions (depression), behavioral and metabolic risk factors (exercise, nutritional status, current smoking status, drinking frequency), intrinsic capacity (cognitive functions, activities of daily living), and digital literacy (use of smartphone or tablet PCs). Since multidimensional factors could affect older adults’ social frailty, comprehensive strategies are urgently needed to reduce their rate of social frailty.
Metabolic Reprogramming in Tumor Endothelial Cells
Authors: García-Caballero Melissa , Sokol Liliana , Cuypers Anne , Carmeliet Peter
Published: September 2022

The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor immunity, and therapeutic responses. Angiogenesis is critical for tumor growth, and abnormal blood vessels contribute to hypoxia and acidosis in the tumor microenvironment. In this hostile environment, cancer and stromal cells have the ability to alter their metabolism in order to support the high energetic demands and favor rapid tumor proliferation. Recent advances have shown that tumor endothelial cell metabolism is reprogrammed, and that targeting endothelial metabolic pathways impacts developmental and pathological vessel sprouting. Therefore, the use of metabolic antiangiogenic therapies to normalize the blood vasculature, in combination with immunotherapies, offers a clinical niche to treat cancer.
Mutation of OsSAC3, Encoding the Xanthine Dehydrogenase, Caused Early Senescence in Rice
Authors: Xie Ziyu , Zhao Bingbing , Zhang Mengxue , Sang Xianchun , Zhao Fangming , Feng Ping , He Guanghua , Zhu Xiaoyan
Published: September 2022

In both animals and higher plants, xanthine dehydrogenase is a highly conserved housekeeping enzyme in purine degradation where it oxidizes hypoxanthine to xanthine and xanthine to uric acid. Previous reports demonstrated that xanthine dehydrogenase played a vital role in N metabolism and stress response. Is xanthine dehydrogenase involved in regulating leaf senescence? A recessive early senescence mutant with excess sugar accumulation, ossac3, was isolated previously by screening the EMS-induced mutant library. Here, we show that xanthine dehydrogenase not only plays a role in N metabolism but also involved in regulating carbon metabolism in rice. Based on map-based cloning, OsSAC3 was identified, which encodes the xanthine dehydrogenase. OsSAC3 was constitutively expressed in all examined tissues and the OsSAC3 protein located in the cytoplasm. Transcriptional analysis revealed purine metabolism, chlorophyll metabolism, photosynthesis, sugar metabolism and redox balance were affected in the ossac3 mutant. Moreover, carbohydrate distribution was changed, leading to the accumulation of sucrose and starch in the leaves containing ossac3 on account of decreased expression of OsSWEET3a, OsSWEET6a and OsSWEET14 and oxidized inactivation of starch degradation enzymes in ossac3. These results indicated that OsSAC3 played a vital role in leaf senescence by regulating carbon metabolism in rice.
Spatial Genomic Resource Reveals Molecular Insights into Key Bioactive-Metabolite Biosynthesis in Endangered Angelica glauca Edgew
Authors: Devi Amna , Seth Romit , Masand Mamta , Singh Gopal , Holkar Ashlesha , Sharma Shikha , Singh Ashok , Sharma Ram Kumar
Published: September 2022

Angelica glauca Edgew, which is an endangered medicinal and aromatic herb, is a rich source of numerous industrially important bioactive metabolites, including terpenoids, phenolics, and phthalides. Nevertheless, genomic interventions for the sustainable utilization and restoration of its genetic resources are greatly offset due to the scarcity of the genomic resources and key regulators of the underlying specialized metabolism. To unravel the global atlas of the specialized metabolism, the first spatial transcriptome sequencing of the leaf, stem, and root generated 109 million high-quality paired-end reads, assembled de novo into 81,162 unigenes, which exhibit a 61.53% significant homology with the six public protein databases. The organ-specific clustering grouped 1136 differentially expressed unigenes into four subclusters differentially enriched in the leaf, stem, and root tissues. The prediction of the transcriptional-interactome network by integrating enriched gene ontology (GO) and the KEGG metabolic pathways identified the key regulatory unigenes that correspond to terpenoid, flavonoid, and carotenoid biosynthesis in the leaf tissue, followed by the stem and root tissues. Furthermore, the stem and root-specific significant enrichments of phenylalanine ammonia lyase (PAL), cinnamate-4-hydroxylase (C4H), and caffeic acid 3-O-methyltransferase (COMT) indicate that phenylalanine mediated the ferulic acid biosynthesis in the stem and root. However, the root-specific expressions of NADPH-dependent alkenal/one oxidoreductase (NADPH-AOR), S-adenosyl-L-methionine-dependent methyltransferases (SDMs), polyketide cyclase (PKC), and CYP72A15 suggest the “root” as the primary site of phthalide biosynthesis. Additionally, the GC-MS and UPLC analyses corresponded to the organ-specific gene expressions, with higher contents of limonene and phthalide compounds in the roots, while there was a higher accumulation of ferulic acid in the stem, followed by in the root and leaf tissues. The first comprehensive genomic resource with an array of candidate genes of the key metabolic pathways can be potentially utilized for the targeted upscaling of aromatic and pharmaceutically important bioactive metabolites. This will also expedite genomic-assisted conservation and breeding strategies for the revival of the endangered A. glauca.
Tumor Cell-Specific Retention and Photodynamic Action of Erlotinib-Pyropheophorbide Conjugates
Authors: Tracy Erin C. , Cheruku Ravindra R. , Pandey Ravindra K. , Baumann Heinz
Published: September 2022

To enhance uptake of photosensitizers by epithelial tumor cells by targeting these to EGFR, pyropheophorbide derivatives were synthesized that had erlotinib attached to different positions on the macrocycle. Although the addition of erlotinib reduced cellular uptake, several compounds showed prolonged cellular retention and maintained photodynamic efficacy. The aim of this study was to identify whether erlotinib moiety assists in tumor targeting through interaction with EGFR and whether this interaction inhibits EGFR kinase activity. The activity of the conjugates was analyzed in primary cultures of human head and neck tumor cells with high-level expression of EGFR, and in human carcinomas grown as xenografts in mice. Uptake of erlotinib conjugates did not correlate with cellular expression of EGFR and none of the compounds exerted EGFR-inhibitory activity. One derivative with erlotinib at position 3, PS-10, displayed enhanced tumor cell-specific retention in mitochondria/ER and improved PDT efficacy in a subset of tumor cases. Moreover, upon treatment of the conjugates with therapeutic light, EGFR-inhibitory activity was recovered that attenuated EGFR signal-dependent tumor cell proliferation. This finding suggests that tumor cell-specific deposition of erlotinib-pyropheophorbides, followed by light triggered release of EGFR-inhibitory activity, may improve photodynamic therapy by attenuating tumor growth that is dependent on EGFR-derived signals.
Unorthodox PCNA Binding by Chromatin Assembly Factor 1
Authors: Gopinathan Nair Amogh , Rabas Nick , Lejon Sara , Homiski Caleb , Osborne Michael J. , Cyr Normand , Sverzhinsky Aleksandr , Melendy Thomas , Pascal John M. , Laue Ernest D. , Borden Katherine L. B. , Omichinski James G. , Verreault Alain
Published: September 2022

The eukaryotic DNA replication fork is a hub of enzymes that continuously act to synthesize DNA, propagate DNA methylation and other epigenetic marks, perform quality control, repair nascent DNA, and package this DNA into chromatin. Many of the enzymes involved in these spatiotemporally correlated processes perform their functions by binding to proliferating cell nuclear antigen (PCNA). A long-standing question has been how the plethora of PCNA-binding enzymes exert their activities without interfering with each other. As a first step towards deciphering this complex regulation, we studied how Chromatin Assembly Factor 1 (CAF-1) binds to PCNA. We demonstrate that CAF-1 binds to PCNA in a heretofore uncharacterized manner that depends upon a cation-pi (π) interaction. An arginine residue, conserved among CAF-1 homologs but absent from other PCNA-binding proteins, inserts into the hydrophobic pocket normally occupied by proteins that contain canonical PCNA interaction peptides (PIPs). Mutation of this arginine disrupts the ability of CAF-1 to bind PCNA and to assemble chromatin. The PIP of the CAF-1 p150 subunit resides at the extreme C-terminus of an apparent long α-helix (119 amino acids) that has been reported to bind DNA. The length of that helix and the presence of a PIP at the C-terminus are evolutionarily conserved among numerous species, ranging from yeast to humans. This arrangement of a very long DNA-binding coiled-coil that terminates in PIPs may serve to coordinate DNA and PCNA binding by CAF-1.
Evaluation of the Sensitivity of Breast Cancer Cell Lines to Cardiac Glycosides Unveils ATP1B3 as a Possible Biomarker for the Personalized Treatment of ERα Expressing Breast Cancers
Authors: Acconcia Filippo
Published: September 2022

The molecular classification of breast cancer (BC) dictates pharmacological treatment. Estrogen receptor α (ERα) expressing tumors are treated with 4OH-tamoxifen or fulvestrant, which inhibits the receptor, or with aromatase inhibitors (i.e., anastrozole, letrozole, and exemestane) that reduce the 17β-estradiol (E2) circulating blood levels. Besides such endocrine therapy (ET) drugs, ERα-positive BCs can be treated with epidermal growth factor receptor (EGF-R) inhibitors (i.e., gefitinib, erlotinib, and lapatinib) according to HER2 expression. Notwithstanding these anti-BC drugs, novel personalized approaches for BC treatment are required because prolonged administration of those pharmaceutics determines resistant phenotypes, which result in metastatic BC. We have recently reported that the cardiac glycoside (CG) (i.e., Na/K ATPase inhibitor) ouabain could be repurposed for ERα-positive primary and metastatic BC treatment as it induces ERα degradation and kills BC cells. Here, we evaluated if other CGs could represent additional treatment options for ERα-positive BCs and if the Na/K ATPase could be considered a biomarker for ERα-positive BC treatment. The results indicate that the ATP1B3 Na/K ATPase isoform can educate the choice for the personalized treatment of ERα-positive BC with CGs and that CGs could be more efficacious if they are administered in association with gefitinib.
The TRPV1 Receptor Is Up-Regulated by Sphingosine 1-Phosphate and Is Implicated in the Anandamide-Dependent Regulation of Mitochondrial Activity in C2C12 Myoblasts
Authors: Standoli Sara , Pecchioli Sara , Tortolani Daniel , Di Meo Camilla , Fanti Federico , Sergi Manuel , Bacci Marina , Seidita Isabelle , Bernacchioni Caterina , Donati Chiara , Bruni Paola , Maccarrone Mauro , Rapino Cinzia , Cencetti Francesca
Published: September 2022

The sphingosine 1-phosphate (S1P) and endocannabinoid (ECS) systems comprehend bioactive lipids widely involved in the regulation of similar biological processes. Interactions between S1P and ECS have not been so far investigated in skeletal muscle, where both systems are active. Here, we used murine C2C12 myoblasts to investigate the effects of S1P on ECS elements by qRT-PCR, Western blotting and UHPLC-MS. In addition, the modulation of the mitochondrial membrane potential (ΔΨm), by JC-1 and Mitotracker Red CMX-Ros fluorescent dyes, as well as levels of protein controlling mitochondrial function, along with the oxygen consumption were assessed, by Western blotting and respirometry, respectively, after cell treatment with methanandamide (mAEA) and in the presence of S1P or antagonists to endocannabinoid-binding receptors. S1P induced a significant increase in TRPV1 expression both at mRNA and protein level, while it reduced the protein content of CB2. A dose-dependent effect of mAEA on ΔΨm, mediated by TRPV1, was evidenced; in particular, low doses were responsible for increased ΔΨm, whereas a high dose negatively modulated ΔΨm and cell survival. Moreover, mAEA-induced hyperpolarization was counteracted by S1P. These findings open new dimension to S1P and endocannabinoids cross-talk in skeletal muscle, identifying TRPV1 as a pivotal target.
Consequences of Autophagy Deletion on the Age-Related Changes in the Epidermal Lipidome of Mice
Authors: Yang Yiwen , Kremslehner Christopher , Derdak Sophia , Bauer Christina , Jelleschitz Sarah , Nagelreiter Ionela-Mariana , Rossiter Heidemarie , Narzt Marie Sophie , Gruber Florian , Sochorová Michaela
Published: September 2022

Autophagy is a controlled mechanism of intracellular self-digestion with functions in metabolic adaptation to stress, in development, in proteostasis and in maintaining cellular homeostasis in ageing. Deletion of autophagy in epidermal keratinocytes does not prevent the formation of a functional epidermis and the permeability barrier but causes increased susceptibility to damage stress and metabolic alterations and accelerated ageing phenotypes. We here investigated how epidermal autophagy deficiency using Keratin 14 driven Atg7 deletion would affect the lipid composition of the epidermis of young and old mice. Using mass spectrometric lipidomics we found a reduction of age-related accumulation of storage lipids in the epidermis of autophagy-deficient mice, and specific changes in chain length and saturation of fatty acids in several lipid classes. Transcriptomics and immunostaining suggest that these changes are accompanied by changes in expression and localisation of lipid and fatty acid transporter proteins, most notably fatty acid binding protein 5 (FABP5) in autophagy knockouts. Thus, maintaining autophagic activity at an advanced age may be necessary to maintain epidermal lipid homeostasis in mammals.
Effect of Hydrogel Contact Angle on Wall Thickness of Artificial Blood Vessel
Authors: Jin Wenyu , Liu Huanbao , Li Zihan , Nie Ping , Zhao Guangxi , Cheng Xiang , Zheng Guangming , Yang Xianhai
Published: September 2022

Vascular replacement is one of the most effective tools to solve cardiovascular diseases, but due to the limitations of autologous transplantation, size mismatch, etc., the blood vessels for replacement are often in short supply. The emergence of artificial blood vessels with 3D bioprinting has been expected to solve this problem. Blood vessel prosthesis plays an important role in the field of cardiovascular medical materials. However, a small-diameter blood vessel prosthesis (diameter < 6 mm) is still unable to achieve wide clinical application. In this paper, a response surface analysis was firstly utilized to obtain the relationship between the contact angle and the gelatin/sodium alginate mixed hydrogel solution at different temperatures and mass percentages. Then, the self-developed 3D bioprinter was used to obtain the optimal printing spacing under different conditions through row spacing, printing, and verifying the relationship between the contact angle and the printing thickness. Finally, the relationship between the blood vessel wall thickness and the contact angle was obtained by biofabrication with 3D bioprinting, which can also confirm the controllability of the vascular membrane thickness molding. It lays a foundation for the following study of the small caliber blood vessel printing molding experiment.
Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients
Authors: Jørgensen Mette , Nørgaard Jens C. , Ilett Emma E. , Marandi Ramtin Z. , Noguera-Julian Marc , Paredes Roger , Murray Daniel D. , Lundgren Jens , MacPherson Cameron Ross , Sengeløv Henrik
Published: September 2022

Allogeneic hematopoietic stem cell transplantation (aHSCT) is a putative curative treatment for malignant hematologic disorders. During transplantation, the immune system is suppressed/eradicated through a conditioning regimen (non-myeloablative or myeloablative) and replaced with a donor immune system. In our previous study, we showed changes in gut taxonomic profiles and a decrease in bacterial diversity post-transplant. In this study, we expand the cohort with 114 patients and focus on the impact of the conditioning regimens on taxonomic features and the metabolic functions of the gut bacteria. This is, to our knowledge, the first study to examine the metabolic potential of the gut microbiome in this patient group. Adult aHSCT recipients with shotgun sequenced stool samples collected day −30 to +28 relative to aHSCT were included. One sample was selected per patient per period: pre-aHSCT (day −30–0) and post-aHSCT (day 1–28). In total, 254 patients and 365 samples were included. Species richness, alpha diversity, gene richness and metabolic richness were all lower post-aHSCT than pre-aHSCT and the decline was more pronounced for the myeloablative group. The myeloablative group showed a decline in 36 genera and an increase in 15 genera. For the non-myeloablative group, 30 genera decreased and 16 increased with lower fold changes than observed in the myeloablative group. For the myeloablative group, 32 bacterial metabolic functions decreased, and one function increased. For the non-myeloablative group, three functions decreased, and two functions increased. Hence, the changes in taxonomy post-aHSCT caused a profound decline in bacterial metabolic functions especially in the myeloablative group, thus providing new evidence for associations of myeloablative conditioning and gut dysbiosis from a functional perspective.
The Antivirulence Activity of Umbelliferone and Its Protective Effect against A. hydrophila-Infected Grass Carp
Authors: Zhao Ling , Jin Xiaoyu , Xiong Ziqian , Tang Huaqiao , Guo Hongrui , Ye Gang , Chen Defang , Yang Shiyong , Yin Zhongqiong , Fu Hualin , Zou Yuanfeng , Song Xu , Lv Cheng , Zhang Wei , Li Yinglun , Wang Xun
Published: September 2022

A. hydrophila is an important pathogen that mainly harms aquatic animals and has exhibited resistance to a variety of antibiotics. Here, to seek an effective alternative for antibiotics, the effects of umbelliferone (UM) at sub-MICs on A. hydrophila virulence factors and the quorum-sensing system were studied. Subsequently, RNA sequencing was employed to explore the potential mechanisms for the antivirulence activity of umbelliferone. Meanwhile, the protective effect of umbelliferone on grass carp infected with A. hydrophila was studied in vivo. Our results indicated that umbelliferone could significantly inhibit A. hydrophila virulence such as hemolysis, biofilm formation, swimming and swarming motility, and their quorum-sensing signals AHL and AI-2. Transcriptomic analysis showed that umbelliferone downregulated expression levels of genes related to exotoxin, the secretory system (T2SS and T6SS), iron uptake, etc. Animal studies demonstrated that umbelliferone could significantly improve the survival of grass carps infected with A. hydrophila, reduce the bacterial load in the various tissues, and ameliorate cardiac, splenic, and hepatopancreas injury. Collectively, umbelliferone can reduce the pathogenicity of A. hydrophila and is a potential drug for treating A. hydrophila infection.
A Rare Case of Successfully Treated Double Valve Infective Endocarditis Caused by Pseudomonas aeruginosa
Authors: Tomoaia Raluca , Oprea Alexandru , Sandu Irina , Danu Vlad , Pop Dana , Zdrenghea Dumitru , Dădârlat-Pop Alexandra , Minciună Ioan Alexandru , Chețan Ioana Maria , Hada Nicoleta Cosmina , Beyer Ruxandra Ștefana
Published: September 2022

Pseudomonas aeruginosa is a rare yet particularly aggressive infective endocarditis pathogen. We describe a case of successfully managed double-valve P. aeruginosa infective endocarditis, in which the presumed source of bacteremia was a long-term tunneled central venous catheter used for hemodialysis.
Molecular Docking and In-Silico Analysis of Natural Biomolecules against Dengue, Ebola, Zika, SARS-CoV-2 Variants of Concern and Monkeypox Virus
Authors: Dassanayake Mackingsley Kushan , Khoo Teng-Jin , Chong Chien Hwa , Di Martino Patrick
Published: September 2022

The emergence and rapid evolution of human pathogenic viruses, combined with the difficulties in developing effective vaccines, underline the need to develop innovative broad-spectrum antiviral therapeutic agents. The present study aims to determine the in silico antiviral potential of six bacterial antimicrobial peptides (AMPs), two phytochemicals (silvestrol, andrographolide), and two bacterial secondary metabolites (lyngbyabellin A, hapalindole H) against dengue virus, Zika virus, Ebola virus, the major variants of SARS-CoV-2 and monkeypox virus. The comparison of docking scores obtained with natural biomolecules was performed with specific neutralizing antibodies (positive controls for ClusPro) and antiviral drugs (negative controls for Autodock Vina). Glycocin F was the only natural biomolecule tested to show high binding energies to all viral surface proteins and the corresponding viral cell receptors. Lactococcin G and plantaricin ASM1 also achieved high docking scores with all viral surface proteins and most corresponding cell surface receptors. Silvestrol, andrographolide, hapalindole H, and lyngbyabellin A showed variable docking scores depending on the viral surface proteins and cell receptors tested. Three glycocin F mutants with amino acid modifications showed an increase in their docking energy to the spike proteins of SARS-CoV-2 B.1.617.2 Indian variant, and of the SARS-CoV-2 P.1 Japan/Brazil variant, and the dengue DENV envelope protein. All mutant AMPs indicated a frequent occurrence of valine and proline amino acid rotamers. AMPs and glycocin F in particular are the most promising biomolecules for the development of broad-spectrum antiviral treatments targeting the attachment and entry of viruses into their target cell.
Factors Associated with Increased Analgesic Use in German Women with Endometriosis during the COVID-19 Pandemic
Authors: Schwab Roxana , Stewen Kathrin , Kottmann Tanja , Schmidt Mona W. , Anic Katharina , Theis Susanne , Hamoud Bashar Haj , Elger Tania , Brenner Walburgis , Hasenburg Annette
Published: September 2022

(1) Background: Endometriosis is a frequent chronic pain condition in women of fertile age. Pain management with analgesics is frequently used by women with endometriosis. During the COVID-19 pandemic, access to health services was temporarily restricted in various countries for persons without serious conditions, resulting in increased physical and mental health issues. The present study was conducted in order to assess the risk factors predicting increased analgesic intake by women with endometriosis during the COVID-19 pandemic. (2) Methods: The increased intake of over-the-counter (OTC) and prescription-only (PO) analgesics was assessed with an anonymous online questionnaire, along with demographic, pandemic-specific, disease-specific, and mental health characteristics. Anxiety and depression were assessed with the Generalized Anxiety Disorder Scale (GAD-2) and the Patient Health Questionnaire for Depression (PHQ-2), respectively. Pain-induced disability was assessed with the pain-induced disability index (PDI). (3) Results: A high educational level (OR 2.719; 95% CI 1.137–6.501; p = 0.025) and being at higher risk for depressive disorders, as measured by PHQ-2 ≥ 3 (OR 2.398; 95% CI 1.055–5.450; p = 0.037), were independent risk factors for an increased intake of OTC analgesics. Current global pain-induced disability (OR 1.030; 95% CI 1.007–1.054; p = 0.010) was identified as a risk factor for an increased intake of PO pain medication. The degree of reduction in social support and in social networks were independent predictors of an increased intake of PO analgesics in a univariate logistic regression analysis, but lost significance when adjusted for additional possible influencing factors. (4) Conclusions: In this population, an increased intake of OTC analgesics was related to a higher educational level and having a depressive disorder, while a higher pain-induced disability was an independent risk factor for an increased intake of PO analgesics. Pandemic-specific factors did not significantly and independently influence an increased intake of analgesics in women with endometriosis during the first wave of the COVID-19 pandemic in Germany. Healthcare providers should be aware of the possible factors related to increased analgesic use in women with endometriosis in order to identify persons at risk for the misuse of pain medication and to prevent potential adverse effects.
Vasoplegic Syndrome after Cardiac Surgery for Infective Endocarditis
Authors: Lim Pascal , Le Maistre Margaux , Campanini Lucas Benoudiba , De Roux Quentin , Mongardon Nicolas , Landon Valentin , Bouguerra Hassina , Aouate David , Woerther Paul-Louis , Vincent Fihman , Galy Adrien , Tacher Vania , Galien Sébastien , Ennezat Pierre-Vladimir , Fiore Antonio , Folliguet Thierry , Huguet Raphaelle , Mekontso-Dessap Armand , Iung Bernard , Lepeule Raphael
Published: September 2022

Purpose: Post-operative vasoplegic syndrome is a dreaded complication in infective endocarditis (IE). Methods and Results: This retrospective study included 166 consecutive patients referred to cardiac surgery for non-shocked IE. Post-operative vasoplegic syndrome was defined as a persistent hypotension (mean blood pressure < 65 mmHg) refractory to fluid loading and cardiac output restoration. Cardiac surgery was performed 7 (5–12) days after the beginning of antibiotic treatment, 4 (1–9) days after negative blood culture and in 72.3% patients with adapted anti-biotherapy. Timing of cardiac surgery was based on ESC guidelines and operating room availability. Most patients required valve replacement (80%) and cardiopulmonary bypass (CPB) duration was 106 (95–184) min. Multivalvular surgery was performed in 43 patients, 32 had tricuspid valve surgery. Post-operative vasoplegic syndrome was reported in 53/166 patients (31.9%, 95% confidence interval of 24.8–39.0%) of the whole population; only 15.1% (n = 8) of vasoplegic patients had a post-operative documented infection (6 positive blood cultures) and no difference was reported between vasoplegic and non-vasoplegic patients for valve culture and the timing of cardiac surgery. Of the 23 (13.8%) in hospital-deaths, 87.0% (n = 20) occurred in the vasoplegic group and the main causes of death were multiorgan failure (n = 17) and neurological complications (n = 3). Variables independently associated with vasoplegic syndrome were CPB duration (1.82 (1.16–2.88) per tertile) and NTproBNP level (2.11 (1.35–3.30) per tertile). Conclusions: Post-operative vasoplegic syndrome is frequent and is the main cause of death after IE cardiac surgery. Our data suggested that the mechanism of vasoplegic syndrome was more related to inflammatory cardiovascular injury rather than the consequence of ongoing bacteremia.
A New Look on Long-COVID Effects: The Functional Brain Fog Syndrome
Authors: Orfei Maria Donata , Porcari Desirée Estela , D’Arcangelo Sonia , Maggi Francesca , Russignaga Dario , Ricciardi Emiliano
Published: September 2022

Epidemiological data and etiopathogenesis of brain fog are very heterogeneous in the literature, preventing adequate diagnosis and treatment. Our study aimed to explore the relationship between brain fog, neuropsychiatric and cognitive symptoms in the general population. A sample of 441 subjects underwent a web-based survey, including the PANAS, the DASS-21, the IES-R, the Beck Cognitive Insight Scale, and a questionnaire investigating demographic information, brain fog, subjective cognitive impairments (Scc) and sleep disorders. ANOVA, ANCOVA, correlation and multiple stepwise regression analyses were performed. In our sample, 33% of participants were defined as Healthy Subjects (HS; no brain fog, no Scc), 27% as Probable Brain Fog (PBF; brain fog or Scc), and 40% as Functional Brain Fog (FBF; brain fog plus Scc). PBF and FBF showed higher levels of neuropsychiatric symptoms than HS, and FBF showed the worst psychological outcome. Moreover, worse cognitive symptoms were related to the female gender, greater neuropsychiatric symptoms, sleep disorders, and rumination/indecision. Being a woman and more severe neuropsychiatric symptoms were predictors of FBF severity. Our data pointed out a high prevalence and various levels of severity and impairments of brain fog, suggesting a classificatory proposal and a multifaceted etiopathogenic model, thus facilitating adequate diagnostic and therapeutic approaches.
Catheter Ablation versus Medical Therapy of Atrial Fibrillation in Patients with Heart Failure: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Magnocavallo Michele , Parlavecchio Antonio , Vetta Giampaolo , Gianni Carola , Polselli Marco , De Vuono Francesco , Pannone Luigi , Mohanty Sanghamitra , Cauti Filippo Maria , Caminiti Rodolfo , Miraglia Vincenzo , Monaco Cinzia , Chierchia Gian-Battista , Rossi Pietro , Di Biase Luigi , Bianchi Stefano , de Asmundis Carlo , Natale Andrea , Della Rocca Domenico Giovanni
Published: September 2022

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist and synergistically contribute to an increased risk of hospitalization, stroke, and mortality. Objective: To compare the efficacy of catheter ablation (CA) versus medical therapy (MT) in HF patients with AF. Methods: Electronic databases were queried for randomized controlled trials (RCTs) of CA versus MT of AF in patients with HF. Risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs) were measured using the Mantel–Haenszel method. Results: A total of nine RCTs enrolling 2155 patients met the inclusion criteria. Compared to MT, CA led to a significant reduction in the composite of all-cause mortality and HF hospitalization (24.6% vs. 37.1%; RR: 0.65 (95% CI: 0.53–0.80); p < 0.0001), all-cause mortality (8.8% vs. 13.6%; RR: 0.65 (95% CI: 0.51–0.82); p = 0.0005), HF hospitalization (15.4% vs. 22.4%; (RR: 0.67 (95% CI: 0.54–0.82); p = 0.0001), AF recurrence (31.8% vs. 77.0%; RR: 0.36 (95% CI: 0.24–0.54); p < 0.0001), and cardiovascular (CV) death (4.9% vs. 8.4%; RR: 0.58 (95% CI: 0.39–0.86); p = 0.007). CA improved the left ventricular ejection fraction (MD:4.76% (95% CI: 2.35–7.18); p = 0.0001), 6 min walk test (MD: 20.48 m (95% CI: 10.83–30.14); p < 0.0001), peak oxygen consumption (MD: 3.1 2mL/kg/min (95% CI: 1.01–5.22); p = 0.004), Minnesota Living with Heart Failure Questionnaire score (MD: −6.98 (95% CI: −12–03, −1.93); p = 0.007), and brain natriuretic peptide levels (MD:−133.94 pg/mL (95% CI: −197.33, −70.55); p < 0.0001). Conclusions: In HF patients, AF catheter ablation was superior to MT in reducing CV and all-cause mortality. Further significant benefits occurred within the ablation group in terms of HF hospitalizations, AF recurrences, the systolic function, exercise capacity, and quality of life.