bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of (Pro)renin Receptor-Mediated Oxidative Stress Alleviates Doxorubicin-Induced Heart Failure
Authors: Du Xiao-yi , Xiang Dao-chun , Gao Ping , Peng Hua , Liu Ya-li 
Published: April 2022

AimClinical utility of doxorubicin (DOX) is limited by its cardiotoxic side effect, and the underlying mechanism still needs to be fully elucidated. This research aimed to examine the role of (pro)renin receptor (PRR) in DOX-induced heart failure (HF) and its underlying mechanism.Main MethodsSprague Dawley (SD) rats were injected with an accumulative dosage of DOX (15 mg/kg) to induce HF. Cardiac functions were detected by transthoracic echocardiography examination. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum were detected, and oxidative stress related injuries were evaluated. Furthermore, the mRNA expression of PRR gene and its related genes were detected by real-time PCR (RT-PCR), and protein levels of PRR, RAC1, NOX4 and NOX2 were determined by Western blot. Reactive oxygen species (ROS) were determined in DOX-treated rats or cells. Additionally, PRR and RAC1 were silenced with their respective siRNAs to validate the in vitro impacts of PRR/RAC1 on DOX-induced cardiotoxicity. Moreover, inhibitors of PRR and RAC1 were used to validate their effects in vivo.Key FindingsPRR and RAC1 expressions increased in DOX-induced HF. The levels of CK and LDH as well as oxidative stress indicators increased significantly after DOX treatment. Oxidative injury and apoptosis of cardiomyocytes were attenuated both in vivo and in vitro upon suppression of PRR or RAC1. Furthermore, the inhibition of PRR could significantly down-regulate the expressions of RAC1 and NOX4 but not that of NOX2, while the inhibition of RAC1 did not affect PRR.SignificanceOur findings showed that PRR inhibition could weaken RAC1-NOX4 pathway and alleviate DOX-induced HF via decreasing ROS production, thereby suggesting a promising target for the treatment of DOX-induced HF.
The Role of Breastfeeding on Respiratory Outcomes Later in Childhood
Authors: Di Filippo Paola , Lizzi Mauro , Raso Massimiliano , Di Pillo Sabrina , Chiarelli Francesco , Attanasi Marina 
Published: April 2022

BackgroundBreastfeeding is associated with a lower risk of wheezing in early childhood, but its effect later in childhood remains unclear. We investigated the association of breastfeeding and respiratory outcomes in children aged 11 years.Materials and MethodsWe performed an observational longitudinal study including 110 prepubertal children. Information about breastfeeding duration, wheezing and asthma was collected by questionnaires. At 11 years of age, we measured spirometry parameters, lung volumes, diffusing lung capacity, and fractional exhaled nitric oxide. We used logistic and linear regression models to examine the associations of breastfeeding duration with the odds of asthma and lung function measures. All multivariable analyses were adjusted for sex, smoking during pregnancy, gestational age at birth, twins, and mode of delivery (confounder model).ResultsBreastfeeding duration was associated with FEV1 z-score [β = 0.04, CI 95% (0.02–0.09)], FEF75 z-score [β = 0.06, CI 95% (0.03–0.09)] and FEV1/FVC z-score [β = 0.03, CI 95% (0.00–0.07)], but not with diffusing lung capacity and fractional exhaled nitric oxide. No association of breastfeeding duration with preschool wheezing, ever asthma and current asthma was documented.ConclusionWe showed that children breastfed for longer time presented higher FEV1, FEV1/FVC, and FEF75 z-score values at 11 years of age compared to children breastfed for shorter time, suggesting a protective effect of breastfeeding on airways, and not on lung parenchyma (lung volumes and alveolar capillary membrane) or allergic airway inflammation. The positive effect of breastfeeding duration on lung function lays the foundation to promote breastfeeding more and more as effective preventive measure.
Kampo Formula-Pattern Models: The Development of 13 New Clinically Useful Standard Abdominal Pattern Models in the Fukushin Simulator
Authors: Yakubo Shuji , Baba Masaki , Odaguchi Hiroshi , Wakasugi Akino , Sekine Mariko , Hanawa Toshihiko , Mitsuma Tadamichi , Namiki Takao , Arai Makoto , Muramatsu Shin-Ichi , Shimada Yutaka , Shibahara Naotoshi 
Published: April 2022

Aim: In Kampo medicine, there exists an important system of diagnosis called Fukushin, or abdominal diagnosis or palpation. By applying pressure to the abdomen of the patient, the physician can gain important information on the patient’s physical state and use those indications to choose a suitable Kampo formulation. We have previously developed a Fukushin simulator, a teaching tool that reproduces the important abdominal patterns that doctors will encounter in clinical practice and that has received favourable feedback for students and practitioners. In order to make diagnosis and prescription easier, it is desirable to have matched formula–pattern pairings. The present study aims to develop such pairings.Methods: With the previously developed models as a foundation, in the present study the production team (two members) used materials such as urethane foam and silicone rubber to build an additional 13 standard abdominal pattern models matched to Kampo herbal formulas commonly used by practitioners in Japan. Subsequently, the evaluation team (the remaining 10 authors) investigated the viability of these models.Results: The evaluation team determined that abdominal pattern models matched to the following typical Kampo formulas were created successfully: Dai-saiko-To (大柴胡湯), Dai-joki-To (大承気湯), Shigyaku-San (四逆散), Saiko-ka-ryukotsu-borei-To (柴胡加竜骨牡蛎湯), Keishi-bukuryo-Gan (桂枝茯苓丸), Hachimi-jio-Gan (八味地黄丸), Hange-shashin-To (半夏瀉心湯), Sho-saiko-To (小柴胡湯), Hochu-ekki-To (補中益気湯), Sho-kenchu-To (小建中湯), Toki-shakuyaku-San (当帰芍薬散), Ninjin-To (人参湯), and Dai-kenchu-To (大建中湯).Conclusion: We suggest that these new formula-pattern models can make an important contribution to the standardization of abdominal diagnosis and prescription and to Kampo education.
A 4/8 Subtype α-Conotoxin Vt1.27 Inhibits N-Type Calcium Channels With Potent Anti-Allodynic Effect
Authors: Wang Shuo , Bartels Peter , Zhao Cong , Yousuf Arsalan , Liu Zhuguo , Yu Shuo , Bony Anuja R. , Ma Xiaoli , Dai Qin , Sun Ting , Liu Na , Yang Mengke , Yu Rilei , Du Weihong , Adams David J. , Dai Qiuyun 
Published: April 2022

A novel 4/8 subtype α-conotoxin, Vt1.27 (NCCMFHTCPIDYSRFNC-NH2), was identified from Conus vitulinus in the South China Sea by RACE methods. The peptide was synthesized and structurally characterized. Similar to other α-conotoxins that target neuronal nicotinic acetylcholine receptor (nAChR) subtypes, Vt1.27 inhibited the rat α3β2 nAChR subtype (IC50 = 1160 nM) and was inactive at voltage-gated sodium and potassium channels in rat sensory neurons. However, Vt1.27 inhibited high voltage-activated N-type (CaV2.2) calcium channels expressed in HEK293T cells with an IC50 of 398 nM. An alanine scan of the peptide showed that residues Phe5, Pro9, Ile10, and Ser13 contribute significantly to the inhibitory activity of Vt1.27. The molecular dockings indicate that Vt1.27 inhibits the transmembrane region of CaV2.2, which is different from that of ω-conotoxins. Furthermore, Vt1.27 exhibited potent anti-allodynic effect in rat partial sciatic nerve injury (PNL) and chronic constriction injury (CCI) pain models at 10 nmol/kg level with the intramuscular injection. The pain threshold elevation of Vt1.27 groups was higher than that of α-conotoxin Vc1.1 in CCI rat models. These findings expand our knowledge of targets of α-conotoxins and potentially provide a potent, anti-allodynic peptide for the treatment of neuropathic pain.
Metformin Alleviates Airway Hyperresponsiveness in a Mouse Model of Diet-Induced Obesity
Authors: Gu Chenjuan , Loube Jeff , Lee Rachel , Bevans-Fonti Shannon , Wu Tianshi David , Barmine Jessica H. , Jun Jonathan C. , McCormack Meredith C. , Hansel Nadia N. , Mitzner Wayne , Polotsky Vsevolod Y. 
Published: April 2022

Obese asthma is a unique phenotype of asthma characterized by non-allergic airway hyperresponsiveness (AHR) and inflammation which responds poorly to standard asthma therapy. Metformin is an oral hypoglycemic drug with insulin-sensitizing and anti-inflammatory properties. The objective of the current study was to test the effect of metformin on AHR in a mouse model of diet-induced obesity (DIO). We fed 12-week-old C57BL/6J DIO mice with a high fat diet for 8 weeks and treated them with either placebo (control, n = 10) or metformin (n = 10) added in drinking water (300 mg/kg/day) during the last 2 weeks of the experiment. We assessed AHR, metabolic profiles, and inflammatory markers after treatments. Metformin did not affect body weight or fasting blood glucose, but significantly reduced serum insulin (p = 0.0117). Metformin reduced AHR at 30 mg/ml of methacholine challenge (p = 0.0052) without affecting baseline airway resistance. Metformin did not affect circulating white blood cell counts or lung cytokine mRNA expression, but modestly decreased circulating platelet count. We conclude that metformin alleviated AHR in DIO mice. This finding suggests metformin has the potential to become an adjuvant pharmacological therapy in obese asthma.
Psychological Distress in Elite Sambo and Recreational Athletes
Authors: Tubić Tatjana , Živanović Bogdan , Lakićević Nemanja , Zenić Nataša , Gilić Barbara , Rudas Eduardas , Eliseev Sergey , Trivić Tatjana B. , Bianco Antonino , Drid Patrik 
Published: April 2022

BackgroundPrevious studies suggest that engagement in any type of physical activity can be protective against mental health issues, whereas elite-level athletes can endure various mental health challenges. The aim of this study was to determine variations in the prevalence of psychological distress among elite sambo athletes and their recreational counterparts.MethodsA sample consisting of 245 athletes (127 males and 118 females) was chosen. Out of the total sample, 105 were elite-level athletes while 140 were recreational athletes. Participants were accessed via the Depression Anxiety Stress Scales-21 to determine their stress in various domains at a given time.ResultsData indicated that all tested differences between elite sambo athletes and recreational athletes were statistically significant; recreational athletes had a higher score on the depression scale, anxiety and stress, and a general distress score than sambo athletes. Although there are no gender differences in psychological distress in the total sample of athletes, elite sambo athletes achieve significantly lower scores in all tested variants than recreational ones. Women who engage in recreational activities have stood out as a vulnerable subsample in psychological stress.ConclusionFuture epidemiological and interventional studies should explore optimal strategies to identify mental health needs based on specific sport activity, especially in terms of gender. There is a need to place special emphasis on psychological distress in the context of combat sports.
Investigating the Efficacy and Experiences With Narrative Exposure Therapy in Severe Mentally Ill Patients With Comorbid Post-traumatic Stress Disorder Receiving Flexible Assertive Community Treatment: A Mixed Methods Study
Authors: Mauritz Maria , Goossens Peter , Jongedijk Ruud , Vermeulen Hester , van Gaal Betsie 
Published: April 2022

BackgroundPatients with severe mental illness with repeated interpersonal trauma and post-traumatic stress disorder (PTSD) have a negative illness progression. Traumas are often not treated because of their vulnerability. Narrative exposure therapy (NET) is an effective trauma therapy. It is unknown whether NET is effective and tolerable in these patients receiving community mental healthcare.ObjectivesThe objectives of this study are (1) to gain insights into patients’ experiences before, during, and after NET concerning changes in PTSD, dissociative and severe mental ill symptoms, care needs (CAN), quality of life, and global functioning; (2) to identify factors that influence diagnostic changes after NET as compared to patients’ experiences. These insights will help to decide whether NET should be incorporated in usual care for these patients.DesignA mixed methods convergent design consists of a grounded theory approach with thematic analysis followed by a merged analysis, comparing quantitative, and qualitative data for each participant and by means of a joint matrix.ParticipantsAdult psychiatric outpatients (age, 21–65) with post-traumatic stress disorder (PTSD) related to repeated interpersonal trauma were indicted for the study.MethodsBaseline demographics and clinical characteristics were assessed. Qualitative data were collected 3 months after NET using individual semi-structured in-depth interviews. The merged analysis compared quantitative and qualitative results for each participant.ResultsTwenty-three outpatients (female, 82%) with a mean age of 49.9 years (SD 9.8) participated in the study. Participants experienced NET as intensive, and most of them tolerated it well. Afterward, eighteen participants perceived less symptoms. Mixed analysis showed substantial congruency between quantitative scores and participants’ perceptions of PTSD, dissociative symptoms, and CAN (Cohen’s kappa &gt; 0.4). Remission of PTSD was associated with sufficient experienced support.ConclusionOutpatients with severe mental illness underwent intensive NET, and most of them tolerate it well. This therapy is clearly efficacious in this group.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NL5608 (NTR5714)].
A Dynamic Approach to Economic Priority Setting to Invest in Youth Mental Health and Guide Local Implementation: Economic Protocol for Eight System Dynamics Policy Models
Authors: Lawson Kenny D. , Occhipinti Jo-An , Freebairn Louise , Skinner Adam , Song Yun Ju C. , Lee Grace Yeeun , Huntley Sam , Hickie Ian B. 
Published: April 2022

BackgroundMental illness costs the world economy over US2.5 Bn each year, including premature mortality, morbidity, and productivity losses. Multisector approaches are required to address the systemic drivers of mental health and ensure adequate service provision. There is an important role for economics to support priority setting, identify best value investments and inform optimal implementation. Mental health can be defined as a complex dynamic system where decision makers are challenged to prospectively manage the system over time. This protocol describes the approach to equip eight system dynamics (SD) models across Australia to support priority setting and guide portfolio investment decisions, tailored to local implementation context.MethodsAs part of a multidisciplinary team, three interlinked protocols are developed; (i) the participatory process to codesign the models with local stakeholders and identify interventions for implementation, (ii) the technical protocol to develop the SD models to simulate the dynamics of the local population, drivers of mental health, the service system and clinical outcomes, and (iii) the economic protocol to detail how the SD models will be equipped to undertake a suite of economic analysis, incorporating health and societal perspectives. Models will estimate the cost of mental illness, inclusive of service costs (health and other sectors, where necessary), quality-adjusted life years (QALYs) lost, productivity costs and carer costs. To assess the value of investing (disinvesting) in interventions, economic analysis will include return-on-investment, cost-utility, cost benefit, and budget impact to inform affordability. Economic metrics are expected to be dynamic, conditional upon changing population demographics, service system capacities and the mix of interventions when synergetic or antagonistic interactions. To support priority setting, a portfolio approach will identify best value combinations of interventions, relative to a defined budget(s). User friendly dashboards will guide decision makers to use the SD models to inform resource allocation and generate business cases for funding.DiscussionEquipping SD models to undertake economic analysis is intended to support local priority setting and help optimise implementation regarding the best value mix of investments, timing and scale. The objectives are to improve allocative efficiency, increase mental health and economic productivity.
The Feasibility and Utility of Harnessing Digital Health to Understand Clinical Trajectories in Medication Treatment for Opioid Use Disorder: D-TECT Study Design and Methodological Considerations
Authors: Marsch Lisa A. , Chen Ching-Hua , Adams Sara R. , Asyyed Asma , Does Monique B. , Hassanpour Saeed , Hichborn Emily , Jackson-Morris Melanie , Jacobson Nicholas C. , Jones Heather K. , Kotz David , Lambert-Harris Chantal A. , Li Zhiguo , McLeman Bethany , Mishra Varun , Stanger Catherine , Subramaniam Geetha , Wu Weiyi , Campbell Cynthia I. 
Published: April 2022

IntroductionAcross the U.S., the prevalence of opioid use disorder (OUD) and the rates of opioid overdoses have risen precipitously in recent years. Several effective medications for OUD (MOUD) exist and have been shown to be life-saving. A large volume of research has identified a confluence of factors that predict attrition and continued substance use during substance use disorder treatment. However, much of this literature has examined a small set of potential moderators or mediators of outcomes in MOUD treatment and may lead to over-simplified accounts of treatment non-adherence. Digital health methodologies offer great promise for capturing intensive, longitudinal ecologically-valid data from individuals in MOUD treatment to extend our understanding of factors that impact treatment engagement and outcomes.MethodsThis paper describes the protocol (including the study design and methodological considerations) from a novel study supported by the National Drug Abuse Treatment Clinical Trials Network at the National Institute on Drug Abuse (NIDA). This study (D-TECT) primarily seeks to evaluate the feasibility of collecting ecological momentary assessment (EMA), smartphone and smartwatch sensor data, and social media data among patients in outpatient MOUD treatment. It secondarily seeks to examine the utility of EMA, digital sensing, and social media data (separately and compared to one another) in predicting MOUD treatment retention, opioid use events, and medication adherence [as captured in electronic health records (EHR) and EMA data]. To our knowledge, this is the first project to include all three sources of digitally derived data (EMA, digital sensing, and social media) in understanding the clinical trajectories of patients in MOUD treatment. These multiple data streams will allow us to understand the relative and combined utility of collecting digital data from these diverse data sources. The inclusion of EHR data allows us to focus on the utility of digital health data in predicting objectively measured clinical outcomes.DiscussionResults may be useful in elucidating novel relations between digital data sources and OUD treatment outcomes. It may also inform approaches to enhancing outcomes measurement in clinical trials by allowing for the assessment of dynamic interactions between individuals' daily lives and their MOUD treatment response.Clinical Trial RegistrationIdentifier: NCT04535583.
The Incidence of Catatonia Diagnosis Among Pediatric Patients Discharged From General Hospitals in the United States: A Kids' Inpatient Database Study
Authors: Luccarelli James , Kalinich Mark , Fernandez-Robles Carlos , Fricchione Gregory , Beach Scott R. 
Published: April 2022

ObjectiveCatatonia is a neuropsychiatric condition occurring across the age spectrum and associated with great morbidity and mortality. While prospective cohorts have investigated catatonia incidence among psychiatric patients, no studies have comprehensively explored the incidence of catatonia in general hospitals. We examine the incidence of catatonia diagnosis, demographics of catatonia patients, comorbidities, and inpatient procedures utilized among pediatric patients hospitalized with catatonia in the United States.MethodsThe Kids' Inpatient Database, a national all-payors sample of pediatric hospitalizations in general hospitals, was examined for the year 2019. Hospitalizations with a discharge diagnosis of catatonia were included in the analysis. Hospitalizations with catatonia as the primary discharge diagnosis were compared to hospitalizations with catatonia as a secondary discharge diagnosis.ResultsA total of 900 (95% CI: 850–949) pediatric discharges (291 with catatonia as a primary diagnosis, 609 with catatonia as a secondary diagnosis) occurred during the study year. Mean age was 15.6 ± 2.6 years, and 9.9% were under age 13. Comorbidities were common among patients with catatonia, with psychotic disorders (165; 18.3%), major depressive disorder (69; 7.7%), bipolar disorder (39; 4.3%) and substance-related disorders (20; 2.2%) as the most common primary diagnoses. There was significant comorbidity with neurologic illness, developmental disorders, autism spectrum disorder, and inflammatory conditions. In total 390 catatonia discharges (43.3%) included at least one procedure during admission.Conclusionscatatonia is rarely diagnosed in pediatric patients in general hospitals but is associated with significant and severe psychiatric and medical comorbidities. Further research is needed into the optimal diagnosis, workup, and treatment of catatonia in pediatric patients.
The Perceptions of Women About Their High Experience of Using Crack Cocaine
Authors: Tractenberg Saulo G. , Schneider Jaluza A. , Mattos Bernardo P. de , Bicca Carla H. M. , Kluwe-Schiavon Bruno , de Castro Thiago G. , Habigzang Luísa F. , Grassi-Oliveira Rodrigo 
Published: April 2022

IntroductionThe aim of this study was to explore the perceptions of women about their experience in using crack cocaine, discussing their motivations for using it and the repercussions in their lives.ObjectiveTo investigate these experiences, a qualitative exploratory study was conducted, using the inductive thematic analyses of the content.MethodsEight female crack cocaine users took part in this study. They were assessed by a semi-structured interview, addressing the crack cocaine use experience. Four main themes emerged in the interviews: (1) crack cocaine “high” experience; (2) symptoms related to crack cocaine use; (3) circumstances of crack cocaine use; and (4) crack cocaine use consequences.ResultsThe main perceptions reported by the users were related to a feeling of being disconnected to the world preceded by a pleasant experience, especially during the first moments of use. They revealed that the drug fulfills a key role of coping strategy to handle with negative thoughts, emotions or life experiences. An important influence of social issues was reported in relation to the onset of crack cocaine use. Negative consequences and significant impact on their lives appeared in their reports, regarding the loss of family ties, involvement with prostitution, traumatic experiences and violence.ConclusionTaking together all women's perceptions suggests that beyond the positive immediate rewarding effect, the maintenance of use might be related to the dissociative experience and self-medication role, acting as negative reward by relieving of negative life experiences that, in turn, are both cause and consequence of the drug use.