bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenetics Based Dose Prediction Model for Initial Tacrolimus Dosing in Renal Transplant Recipients
Authors: Srinivas Lekshmy , Gracious Noble , Nair Radhakrishnan R. 
Published: December 2021

Tacrolimus, an immunosuppressant used in solid organ transplantation, has a narrow therapeutic index and exhibits inter-individual pharmacokinetic variability. Achieving and maintaining a therapeutic level of the drug by giving appropriate doses is crucial for successful immunosuppression, especially during the initial post-transplant period. We studied the effect of CYP3A5, CYP3A4, and ABCB1 gene polymorphisms on tacrolimus trough concentrations in South Indian renal transplant recipients from Kerala to formulate a genotype-based dosing equation to calculate the required starting daily dose of tacrolimus to be given to each patient to attain optimal initial post-transplant period drug level. We also investigated the effect of these genes on drug-induced adverse effects and rejection episodes and looked into the global distribution of allele frequencies of these polymorphisms. One hundred forty-five renal transplant recipients on a triple immunosuppressive regimen of tacrolimus, mycophenolate mofetil, and steroid were included in this study. Clinical data including tacrolimus daily doses, trough levels (C0) and dose-adjusted tacrolimus trough concentration (C0/D) in blood at three time points (day 6, 6 months, and 1-year post-transplantation), adverse drug effects, rejection episodes, serum creatinine levels, etc., were recorded. The patients were genotyped for CYP3A5*3, CYP3A4*1B, CYP3A4*1G, ABCB1 G2677T, and ABCB1 C3435T polymorphisms by the PCR-RFLP method. We found that CYP3A5*3 polymorphism was the single most strongly associated factor determining the tacrolimus C0/D in blood at all three time points (p &lt; 0.001). Using multiple linear regression, we formulated a simple and easy to compute equation that will help the clinician calculate the starting tacrolimus dose per kg body weight to be administered to a patient to attain optimal initial post-transplant period tacrolimus level. CYP3A5 expressors had an increased chance of rejection than non-expressors (p = 0.028), while non-expressors had an increased risk for new-onset diabetes mellitus after transplantation (NODAT) than expressors (p = 0.018). Genotype-guided initial tacrolimus dosing would help transplant recipients achieve optimal initial post-transplant period tacrolimus levels and thus prevent the adverse effects due to overdose and rejection due to inadequate dose. We observed inter-population differences in allele frequencies of drug metabolizer and transporter genes, emphasizing the importance of formulating population-specific dose prediction models to draw results of clinical relevance.
Sex Differences in Behavioral Symptoms and the Levels of Circulating GFAP, Tau, and NfL in Patients With Traumatic Brain Injury
Authors: Sass Dilorom , Guedes Vivian A. , Smith Ethan G. , Vorn Rany , Devoto Christina , Edwards Katie A. , Mithani Sara , Hentig James , Lai Chen , Wagner Chelsea , Dunbar Kerri , Hyde David R. , Saligan Leorey , Roy Michael J. , Gill Jessica 
Published: December 2021

Traumatic brain injury (TBI) affects millions of Americans each year and has been shown to disproportionately impact those subject to greater disparities in health. Female sex is one factor that has been associated with disparities in health outcomes, including in TBI, but sex differences in biomarker levels and behavioral outcomes after TBI are underexplored. This study included participants with both blunt and blast TBI with majority rating their TBI as mild. Time since injury was 5.4 (2.0, 15.5) years for females and 6.8 (2.4, 11.3) years for males. The aim of this cross sectional study is to investigate the relationship between postconcussive, depression, and post-traumatic stress disorder (PTSD) symptoms, as well as health related quality of life (HRQOL), and the levels of glial fibrillary acidic protein (GFAP), total tau (t-tau), neurofilament light chain (NfL), and ubiquitin C-terminal hydrolase-L1 (UCH-L1). Behavioral outcomes were evaluated with the Neurobehavioral Symptom Inventory (NSI), Patient Health Questionnaire-9 (PHQ-9), PTSD Checklist- Civilian Version (PCL-C), short form (SF)-36, and plasma levels of total tau, GFAP, NfL, and UCHL-1 measured with the Simoa-HDX. We observed that females had significantly higher levels of GFAP and tau (ps &lt; 0.05), and higher PHQ-9 scores, NSI total scores, NSI- vestibular, NSI-somatosensory, NSI-affective sub-scale scores (ps &lt; 0.05)), than males. In addition, females had lower scores in HRQOL outcomes of role limitations due to emotional problems, vitality, emotional well-being, social functioning, and pain compared to males (ps &lt; 0.05). Correlation analysis showed positive associations between levels of tau and the NSI-total and NSI-cognitive sub-scale scores (ps &lt; 0.05) in females. No significant associations were found for NfL or GFAP with NSI scores. For female participants, negative correlations were observed between tau and NfL concentrations and the SF-36 physical function subscale (ps &lt; 0.05), as well as tau and the social function subscale (p &lt; 0.001), while GFAP levels positively correlated with role limitations due to emotional problems (p = 0.004). No significant associations were observed in males. Our findings suggest that sex differences exist in TBI-related behavioral outcomes, as well as levels of biomarkers associated with brain injury, and that the relationship between biomarker levels and behavioral outcomes is more evident in females than males. Future studies are warranted to corroborate these results, and to determine the implications for prognosis and treatment. The identification of candidate TBI biomarkers may lead to development of individualized treatment guidelines.
Synergetic Effect of 4-Phenylbutyric Acid in Combination with Cyclosporine A on Cardiovascular Function in Sepsis Rats via Inhibition of Endoplasmic Reticulum Stress and Mitochondrial Permeability Transition Pore Opening
Authors: Kuang Lei , Zhu Yu , Wu Yue , Peng Xiaoyong , Tian Kunlun , Liu Liangming , Li Tao 
Published: December 2021

Background: Sepsis/septic shock is a common complication in the intensive care unit, and the opening of the mitochondrial permeability transition pore (mPTP), as well as the endoplasmic reticulum stress (ERS), play important roles in this situation. Whether the combination of anti-ERS and anti-mPTP by 4-phenylbutyric acid (PBA) and Cyclosporine A (CsA) could benefit sepsis is unclear.Methods: The cecal ligation and puncture-induced septic shock models were replicated in rats, and lipopolysaccharide (LPS)-challenged primary vascular smooth muscle cells and H9C2 cardiomyocytes in vitro models were also used. The therapeutic effects of CsA, PBA, and combined administration on oxygen delivery, cardiac and vascular function, vital organ injury, and the underlying mechanisms were observed.Results: Septic shock significantly induced cardiovascular dysfunction, hypoperfusion, and organ injury and resulted in high mortality in rats. Conventional treatment including fluid resuscitation, vasoactive agents, and antibiotics slightly restored tissue perfusion and organ function in septic rats. Supplementation of CsA or PBA improved the tissue perfusion, organ function, and survival of septic shock rats. The combined application of PBA and CsA could significantly enhance the beneficial effects, compared with using PBA or CsA alone. Further study showed that PBA enhanced CsA-induced cardiovascular protection, which contributed to better therapeutic effects.Conclusion: Anti-ERS and anti-mPTP-opening by the combination of PBA and CsA was beneficial to septic shock. PBA enforced the CsA-associated cardiovascular protection and contributed to the synergetic effect.
An NIR-Triggered Au Nanocage Used for Photo-Thermo Therapy of Chronic Wound in Diabetic Rats Through Bacterial Membrane Destruction and Skin Cell Mitochondrial Protection
Authors: Ding Jiaxin , Gao Binbin , Chen Zhenhua , Mei Xifan 
Published: December 2021

Bacterial infection and its severe oxidative stress reaction will cause damage to skin cell mitochondria, resulting in long-lasting wound healing and great pain to patients. Thus, delayed wound healing in diabetic patients with Staphylococcus aureus infection is a principal challenge worldwide. Therefore, novel biomaterials with multifunction of bacterial membrane destruction and skin cell mitochondrial protection are urgently needed to be developed to address this challenge. In this work, novel gold cage (AuNCs) modified with epigallocatechin gallate (EGCG) were prepared to treat delayed diabetic wounds. The results showed that Au-EGCG had a high and stable photothermal conversion efficiency under near-infrared irradiation, and the scavenging rate of Au-EGCG for S. aureus could reach 95%. The production of large amounts of reactive oxygen species (ROS) leads to the disruption of bacterial membranes, inducing bacterial lysis and apoptosis. Meanwhile, Au-EGCG fused into hydrogel (Au-EGCG@H) promoted the migration and proliferation of human umbilical cord endothelial cells, reduced cellular mitochondrial damage and oxidative stress in the presence of infection, and significantly increased the basic fibroblast growth factor expression and vascular endothelial growth factor. In addition, animal studies showed that wound closure was 97.2% after 12 days of treatment, and the healing of chronic diabetic wounds was significantly accelerated. Au-EGCG nanoplatforms were successfully prepared to promote cell migration and angiogenesis in diabetic rats while removing S. aureus, reducing oxidative stress in cells, and restoring impaired mitochondrial function. Au-EGCG provides an effective, biocompatible, and multifunctional therapeutic strategy for chronic diabetic wounds.
Storax, A Promising Botanical Medicine for Treating Cardio-Cerebrovascular Diseases: A Review
Authors: Xu Zhuo , Lu Danni , Yuan Jianmei , Ren Mihong , Ma Rong , Xie Qian , Li Yong , Li Jinxiu , Wang Jian 
Published: December 2021

In recent years, the incidence and mortality of cardio-cerebrovascular diseases have been increasing year by year, which has become global burden and challenge. Based on the holistic thinking of “brain disease affects the heart” and “heart disease affects the brain,” as well as the characteristics of multi-target and multi-path effects of Chinese medicine, Chinese medicine is more advantageous in the treatment of cardio-cerebrovascular diseases. As a botanical medicine, storax is known for its resuscitation, filth avoidance and pain-relieving effects in the treatment of cardio-cerebrovascular diseases. By reviewing and collating the relevant domestic and international literature in the past 10 years, we have sorted out an overview of the medicinal parts, traditional uses and chemical composition of storax. For the first time, based on the idea of “cerebral and cardiac simultaneous treatment,” the pharmacological activities and mechanisms of heart and brain protection of storax for treating cardio-cerebrovascular diseases were summarized and analyzed, showing that storax has the pharmacological effects of anti-cerebral ischemia, regulation of blood-brain barrier, bidirectional regulation of the central nervous system, anti-myocardial ischemia, anti-arrhythmia, anti-thrombosis and anti-platelet aggregation. It mainly exerts its protective effects on the brain and heart through mechanisms such as inhibition of inflammatory immune factors, anti-oxidative stress, anti-apoptosis, pro-neovascularization and regulation of NO release. On the basis of the current findings and limitations, the future research strategies and perspectives of storax are proposed, with a view to providing a reference for further application and development of this medicine, as well as contributing new thoughts and visions for the clinical application of “treating brain-heart synchronously”.
Emotional Intelligence and Perceived Health Related to Expressed Compassion Fatigue: A Study in Health Sector at Regional Level
Authors: Ruiz Fernández María Dolores , Lirola María-Jesús , Ramos-Pichardo Juan Diego , Ortíz-Amo Rocío , Ibáñez-Masero Olivia , Rodríguez Gómez Susana , Ortega-Galán Ángela María 
Published: December 2021

Background: The work of health professionals often involves physical as well as psychological strain. They constantly deal with traumatic situations of pain and suffering, which destabilize the sense of well-being. Compassion fatigue is a feeling that appears in these cases and is related to other variables such as burnout or emotional drain.Aims: The principal aim of this project was to deepen the analysis of compassion fatigue and how it could be explained through the relationship with other constructs such as emotional intelligence and perceived health.Methods: This work followed the STROBE checklist for cross-sectional studies. In this study 1,521 nurses (Mage = 47.32; SD = 8.44) participated. The responses reported by the nurses were analyzed by classifying them as high or low compassion fatigue and the differences of both groups were analyzed for the variables of emotional intelligence, perceived health and quality of professional life.Results: It was obtained significant differences for all factors except for emotional intelligence factor. A linear regression analysis showed both emotional intelligence and perceived health helped to explain (12%) compassion fatigue.Conclusion: This study provides light on comprehending the conception of compassion fatigue. It highlights the importance of intervention programs that improve the quality of professional life.
Pilot Study of Mindfulness Training on the Self-Awareness of Motor Symptoms in Parkinson’s Disease – A Randomized Controlled Trial
Authors: Buchwitz Timo Marcel , Maier Franziska , Greuel Andrea , Thieken Franziska , Steidel Kenan , Jakobs Viktoria , Eggers Carsten 
Published: December 2021

Objective:This study aims to evaluate feasibility and effects of a newly developed mindfulness intervention tailored to specific needs of patients with Parkinson’s disease (PD).Background:The phenomenon of impaired self-awareness of motor symptoms (ISAm) in PD might be reduced by increasing patients’ mindfulness. A PD-specific mindfulness intervention has been developed and evaluated as a potential treatment option: IPSUM (“Insight into Parkinson’s Disease Symptoms by using Mindfulness”).Methods:IPSUM’s effectiveness is evaluated by comparing an intervention with a waitlist-control group. Applying a pre-post design, patients were assessed before, directly after and 8weeks after treatment. The primary outcome was the change in a quantitative ISAm score from baseline to post-assessment. Secondary outcome measures were PD-related affective changes and neuropsychological test performance. Feasibility was evaluatedviafeedback forms.Results:In total, 30 non-depressed and non-demented PD patients were included (intervention:n=14, waitlist-control:n=16). ISAm score did not change significantly, but the training group showed greater performance in sustained attention and language tasks over time. Additional changes included greater mindfulness as well as less sleeping problems and anxiety. Cognitive disturbances, apathy, and sleeping problems worsened only in the waitlist-control group. Patients’ feedback regarding the training concept and material was excellent.Conclusion:Insight into Parkinson’s Disease Symptoms by using Mindfulness has not been capable of reducing ISAm in PD patients but appears to be a feasible and effective concept to, among others, support mental health in the mid-term. It has to be noted though that the study was stopped beforehand because of the SARS CoV-2 pandemic. The lack of findings might therefore be caused by a lack of statistical power. The need for further research to better understand the mechanisms of ISAm and its connection to mindfulness in PD is highlighted.
Subgroups in Late Adulthood Are Associated With Cognition and Wellbeing Later in Life
Authors: Radhoe Tulsi A. , Agelink van Rentergem Joost A. , Kok Almar A. L. , Huisman Martijn , Geurts Hilde M. 
Published: December 2021

Objectives: In this study, we aim to discover whether there are valid subgroups in aging that are defined by modifiable factors and are determinant of clinically relevant outcomes regarding healthy aging.Method: Data from interviews were collected in the Longitudinal Aging Study Amsterdam at two measurement occasions with a 3-year interval. Input for the analyses were seven well-known vulnerability and protective factors of healthy aging. By means of community detection, we tested whether we could distinguish subgroups in a sample of 1478 participants (T1-sample, aged 61–101 years). We tested both the external validity (T1) and predictive validity (T2) for wellbeing and subjective cognitive decline. Moreover, replicability and long-term stability were determined in 1186 participants (T2-sample, aged 61–101 years).Results: Three similar subgroups were identified at T1 and T2. Subgroup A was characterized by high levels of education with personal vulnerabilities, subgroup B by being physically active with low support and low levels of education, and subgroup C by high levels of support with low levels of education. Subgroup C showed the lowest wellbeing and memory profile, both at T1 and T2. On most measures of wellbeing and memory, subgroups A and B did not differ from each other. At T2, the same number of subgroups was identified and subgroup profiles at T1 and T2 were practically identical. Per T1 subgroup 47–62% retained their membership at T2.Discussion: We identified valid subgroups that replicate over time and differ on external variables at current and later measurement occasions. Individual change in subgroup membership over time shows that transitions to subgroups with better outcomes are possible.
The Role of Oxidative Stress in Suicidal Behaviour Among Bipolar Patients: A Cross-Sectional Study in a Malaysian Sample
Authors: Loo Jiann Lin , Mohamad Kamal Nurul Ain , Goon Jo Aan , Ahmad Damanhuri Hanafi , Tan Jaclyn Ai Chin , Abdul Murad Nor Azian , Shah Shamsul Azhar , Sulaiman Siti Aishah , Fazry Shazrul , Sharip Shalisah , Mohamed Saini Suriati , Gunasekaran Geetha , Maniam Thambu , A. Jamal A. Rahman , Wan Ngah Wan Zurinah , Mohd Badli Shah Fatimatul Syahirah , Chan Lai Fong 
Published: December 2021

Background: Oxidative stress markers are found to be linked with depression and suicide attempts in bipolar disorder (BD), although the role of DNA damage as a marker of suicidal ideation and attempt has yet to be determined. We aim to investigate the association between DNA damage and suicidal behaviour, i.e., suicidal ideation and suicide attempt, among suicidal ideators in BD patients while accounting for clinical and psychosocial risk factors.Methods: A cross-sectional study was conducted in the Universiti Kebangsaan Malaysia Medical Centre on 62 consecutive BD patients diagnosed using the M.I.N.I. Neuropsychiatric Interview and 26 healthy control participants. Socio-demographic and clinical assessments were performed using the Columbia Suicide Severity Rating Scale (C-SSRS) for lifetime suicidal ideation and attempt, Quick Inventory of Depressive Symptomatology (QIDS) for depression severity, Clinical Global Impression for Bipolar Disorder (CGI-BD) for illness severity [both mania (CGI-Mania) and major depressive episode (CGI-MDE)], Social Readjustment Rating Scale (SRRS) for change in life events, and Barratt Impulsiveness Scale (BIS) for behavioural impulsivity. The degree of DNA damage in peripheral blood samples was determined using a standard protocol of comet assay.Results: Multivariable logistic regression revealed higher scores of CGI-MDE as the sole significant factor for lifetime suicidal ideation (OR = 1.937, 95% CI = 1.799–2.076). Although initial bivariate analysis showed a significant association between DNA damage, malondialdehyde (MDA), catalase (CAT), and suicidal behaviour, the findings were not seen in multivariable logistic regression. Bivariate subgroup analysis showed that moderate and severe DNA damage (p = 0.032 and p = 0.047, respectively) was significantly associated with lifetime suicide attempts among lifetime suicidal ideators. The study is the first to look at the connexion between DNA damage and suicidal risk in bipolar patients. It is limited by the small sample size and lack of information on illicit substance use.Conclusions: More severe DNA damage was significantly associated with lifetime suicide attempts among lifetime suicidal ideators in BD. However, the severity of depression was found to be independently associated with lifetime suicidal ideation per se rather than DNA damage in BD. Larger prospective studies are required to ascertain the potential of DNA damage as a biomarker for the transition from suicidal ideation to a suicide attempt.
Age- and Sex-Related Cortical Gray Matter Volume Differences in Adolescent Cannabis Users: A Systematic Review and Meta-Analysis of Voxel-Based Morphometry Studies
Authors: Allick Aliyah , Park Grace , Kim Kwon , Vintimilla Michelle , Rathod Krutika , Lebo Rachael , Nanavati Julie , Hammond Christopher J. 
Published: December 2021

Introduction: Adolescent-onset cannabis use is rising in the era of marijuana legalization. Recent imaging studies have identified neuroanatomical differences between adult cannabis users and controls that are more prominent in early-onset users. Other studies point to sex-dependent effects of cannabis.Methods: A systematic review following PRISMA guidelines and subsequent effect-size seed-based d mapping (SDM) meta-analyses were conducted to investigate relationships between age (across the 12-to-21-year-old developmental window), sex, and gray matter volume (GMV) differences between cannabis using (CU) and typically developing (TD) youth.Results: Our search identified 1,326 citations, 24 of which were included in a qualitative analysis. A total of 6 whole-brain voxel-based morphometry (VBM) studies comparing regional GMV between 357 CU [mean (SD) age = 16.68 (1.28); 71% male] and 404 TD [mean (SD) age = 16.77 (1.36); 63% male] youth were included in the SDM-meta-analysis. Meta-analysis of whole-brain VBM studies identified no regions showing significant GMV difference between CU and TD youth. Meta-regressions showed divergent effects of age and sex on cortical GMV differences in CU vs. TD youth. Age effects were seen in the superior temporal gyrus (STG), with older-aged CU youth showing decreased and younger-aged CU youth showing increased STG GMV compared to age-matched TD youth. Parallel findings in the STG were also observed in relation to duration of CU (years) in supplemental meta-regressions. Regarding sex effects, a higher proportion of females in studies was associated with increased GMV in the middle occipital gyrus in CU vs. TD youth.Conclusions: These findings suggest that GMV differences between CU and TD youth, if present, are subtle, and may vary as a function of age, cumulative cannabis exposure, and sex in young people. Whether age- and sex-related GMV differences are attributable to common predispositional factors, cannabis-induced neuroadaptive changes, or both warrant further investigation.