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Methods
PMC10154324
Setting and procedure
vaginal infections, ’
VAGINAL INFECTION
This prospective, randomized, observer-blinded single-center study was performed at the Medical University of Vienna, Department of Obstetrics and Gynecology, after approval by the ethics committee of the Medical University of Vienna (protocol nr.: 2258/2016) in accordance with the Declaration of Helsinki and Good Clin...
PMC10154324
Study groups
According to the Nugent scoring system, we differentiated between two patient groups: (1) IMLN4: pregnant women with an intermediate vaginal microbiota and a Nugent score of 4
PMC10154324
Study endpoints
bleeding, vaginal or urinary tract infection, diarrhea, preterm premature rupture of the membranes and/or, constipation
SECONDARY, PRETERM LABOR, BLEEDING
The primary endpoint was restoration of the normal vaginal microbiota (Nugent score 0–3). The secondary endpoints were the incidence of PTD (defined as spontaneous birth at or before 36 + 6 gestational weeks) due to preterm premature rupture of the membranes and/or preterm labor, gestational age at delivery (recorded a...
PMC10154324
Acknowledgements
We thank Birgit Füssl, Germania Pharmazeutika, Vienna, Austria and Biose Pharmaceuticals (Arpajon-sur-Cère, France) for supplying the study medication.
PMC10154324
Author contributions
L.P. primary investigator, corresponding author, planed, organized and conducted study, wrote the main manuscript. AF. co-organized the study, co-wrote manuscript. I.R., N.J. recruited the patients, collection and saving of results. U.K., I.H. sample collection and recruited the patients. H.K. organization of the study...
PMC10154324
Data availability
Materials described in the manuscript, including all relevant raw data, will be freely available to any researcher wishing to use them for non-commercial purposes, without breaching participant confidentiality. Please contact coresponding author.
PMC10154324
Competing interests
The authors declare no competing interests.
PMC10154324
References
PMC10154324
Background and aims
NAFLD, PolandNon-alcoholic fatty liver
Edited by: Maria Rodriguez-Fernandez, Pontificia Universidad Católica de Chile, ChileReviewed by: Jingjie Zhao, Capital Medical University, China; Piotr Ossowski, Medical University of Silesia, PolandNon-alcoholic fatty liver disease(NAFLD) is common worldwide and has previously been reported to be associated with slee...
PMC10272397
Methods
NAFLD, MR
We proposed a bidirectional Mendelian randomization (MR) analysis and performed validation analyses to dissect the association between NAFLD and sleep traits. Genetic instruments were used as proxies for NAFLD and sleep. Data of genome-wide association study(GWAS) were obtained from the center for neurogenomics and cog...
PMC10272397
Results
NAFLD, Insomnia, Snoring
In total,7 traits associated with sleep and 4 traits associated with NAFLD are used in this study. A total of six results showed significant differences. Insomnia was associated with NAFLD (OR(95% CI)= 2.25(1.18,4.27), P = 0.01), Alanine transaminase levels (OR(95% CI)= 2.79(1.70, 4.56), P =4.71×10-5) and percent liver...
PMC10272397
Conclusion
NAFLD, sleep traits, insomnia
SLEEP APNEA SYNDROME
Genetic evidence suggests putative causal relationships between NAFLD and a set of sleep traits, indicating that sleep traits deserves high priority in clinical practice. Not only the confirmed sleep apnea syndrome, but also the sleep duration and sleep state (such as insomnia) deserve clinical attention. Our study pro...
PMC10272397
Introduction
NAFLD, Sleep, liver injuries, MR, cirrhosis and hepatocellular carcinoma
CHRONIC LIVER DISEASE, LIVER FIBROSIS, HEPATIC STEATOSIS, NONALCOHOLIC FATTY LIVER DISEASE, DISEASES, STEATOHEPATITIS
Nonalcoholic fatty liver disease (NAFLD), one of the most common chronic liver disease in the world, affects 25% of the population worldwide and its prevalence is expected to increase further in the near future. NAFLD and its associated consequences have become one of the major public health problems due to changes in ...
PMC10272397
Methods
PMC10272397
Research design
NAFLD, napping, sleep-related traits, snoring, insomnia, impairment of liver function, steatosis
STEATOSIS
In this study, we see insomnia, daytime dozing, morningness, ease of getting up, sleep duration, daytime napping and snoring as sleep-related traits. Since the main traits of NAFLD are steatosis of the liver and impairment of liver function, we used the diagnosis of NAFLD, alanine transaminase levels, aspartate aminotr...
PMC10272397
Data sources
NAFLD, insomnia
NON-ALCOHOLIC FATTY LIVER DISEASE
The GWAS data for insomnia obtained from the Open GWAS database, a dataset published by Neale LABS in 2017 that included a sample of 336,082 participants from European populations. In addition to this, we also used six sleep parameters from the center for neurogenomics and cognitive research database (Details of the GW...
PMC10272397
Selection of instrumental variables
For the selection of IVs, a more relaxed threshold was used in order to include more SNPs, and SNPs that were significant for the whole genome (<5 × 10-7) were used as a selection to become IVs, which has been used in many other MR studies (
PMC10272397
Statistical analysis
As assumed, three assumptions must be satisfied when using the MR method (1): the selected IVs must be strongly associated with the exposure (2); the selected IVs should not be associated with potential confounders (3); the selected IVs could only influence the outcomes through the exposure, but not other pathways We u...
PMC10272397
Results
NAFLD, sleep traits
NON-ALCOHOLIC FATTY LIVER DISEASE
We investigated the correlation of different sleep traits with NAFLD, with the IVW method providing the main results, while the results of the MR Egger and weighted median methods were also presented by us. Processes with P value < 0.05 for the IVW method and F value > 10 were considered as significant associations. We...
PMC10272397
Discussion
obesity, depression, mitochondrial dysfunction, sleep disorders, NAFLD.Although hepatic steatosis, hypoxia, inflammation, snoring, insomnia, sleep-related, sleep traits, liver damage, nonalcoholic steatohepatitis, hepatic steatosis, Insomnia, NAFLD, OSA, liver inflammation, MR, steatosis
OBESITY, CARDIOVASCULAR DISEASE, INSULIN RESISTANCE, OXIDATIVE STRESS, BREAST CANCER, HYPOXIA, INFLAMMATION, ALTERNATION, MITOCHONDRIAL DYSFUNCTION, DISEASES, PATHOGENESIS, POSITIVE, LIVER FIBROSIS, LIVER DAMAGE, NONALCOHOLIC STEATOHEPATITIS, HEPATIC STEATOSIS, TUMOR NECROSIS, DISEASE, HYPOXIC, STEATOSIS
Many previous reports have used MR studies to determine the causal relationship between sleep-related problems and various diseases and indicators, such as cardiovascular disease, breast cancer, depression and glycated hemoglobin (In the MR analysis of this paper, we systematically evaluated the causal relationship bet...
PMC10272397
Strength and limitations
NAFLD, anomalies, insomnia, MR, sleep traits
To our knowledge, this is the first bidirectional MR study that provides new insight into the causal associations between sleep traits and NAFLD. Our study has some strengths and limitations. The main advantage of this work is the use of bidirectional MR to explore the causal relationship between sleep traits and NAFLD...
PMC10272397
Future research
NAFLD, sleep traits
We are thrilled to have found further evidence on the impact of different sleep traits on NAFLD, indicating that enhancing sleep is essential for the prevention and development of NAFLD. In the future, we may explore the specific mechanisms of sleep’s effects on NAFLD, including metabolic and inflammatory pathways, to ...
PMC10272397
Conclusion
NAFLD
In summary, our findings suggest that sleep characteristics are associated with an elevated risk of NAFLD. Our study has significant implications for comprehending the causal relationship between sleep characteristics and NAFLD. Further research into their mechanisms and interactions is warranted.
PMC10272397
Data availability statement
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.
PMC10272397
Author contributions
JJ
ZS, JJ and LZ conceived the study design. KW,YH and TX performed the statistical analysis. ZS wrote the manuscript and performed the data visualization. QW and FC supervised the study. All authors provided critical revisions of the draft and approved the submitted draft.
PMC10272397
Acknowledgments
DISEASES
We sincerely acknowledge the contribution from the Open GWAS database, Neale lab, center for neurgenomics and cognitive research database, GWAS catalog database and all concerned investigators and consortiums for sharing the GWAS summary statistics on the diseases.
PMC10272397
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
PMC10272397
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or ...
PMC10272397
References
PMC10272397
Methods
PMC10212647
Study design
Barrett
BARRETT
Patients undergoing Barrett’s surveillance from the ACE-B trial
PMC10212647
Participants
Inclusion criteria were patients aged over 18 years with BE maximum circumferential length of ≥ 2 cm and/or maximum BE length of ≥ 3 cm (C2 and/or M3) diagnosed on pre-trial endoscopy (as per Prague Classification
PMC10212647
Endoscopic procedure
Patients received two endoscopy procedures during the trial period. In the standard arm, patients underwent HRWLE with diagnostic biopsies according to the gold standard (Seattle protocol). Briefly, the endoscopists were asked to perform a complete upper GI endoscopy with intubation to the second part of the duodenum,...
PMC10212647
Biopsy and histology
Tissue biopsies were fixed in formalin and embedded in paraffin for histopathological assessment. Targeted and random biopsies were reviewed by a GI pathologist with extensive expertise in BE in accordance with the Vienna classification
PMC10212647
Procedure time
The time taken to perform surveillance endoscopy was defined as the time interval between insertion of the endoscope to the time of patient extubation.
PMC10212647
Study outcomes
DDR, dysplasia
DYSPLASIA
Maximum BE lengths were classified into different strata: 2–5 cm, 6–10 cm, ≥ 11 cm. Time to perform endoscopy for each BE length strata was determined. To assess adherence to the Seattle protocol, the number of quadrantic biopsies taken per 2 cm length of BE was calculated by dividing total number of biopsies by half t...
PMC10212647
Statistical analysis
dysplasia
REGRESSION, DYSPLASIA
Median, interquartile range (IQR), and range were calculated for endoscopy duration at different BE length strata. Mean and range were determined for number of quadrantic biopsies. Comparison of endoscopy duration and number of biopsies at different BE length strata were compared using a one-way analysis of variance. ...
PMC10212647
Results
MAY
A total of 142 eligible patients completed the standard arm of the trial (HRWLE plus Seattle protocol biopsies) between May 2017 and October 2019. Baseline characteristics are shown in
PMC10212647
Patient demographics.
Barrett’s esophagus maximum length <, intramucosal carcinoma, dysplasia, LGD, Barrett, Barrett’s esophagus
BARRETT, DYSPLASIA
Age, mean (range), yearsMale sex, n (%)Maximum length, mean (range),Circumferential length of Barrett’s, mean (range)NDBEIndefinite for dysplasiaLGDHGD/IMCTotal number of tissue biopsies, nTargeted biopsies, n (%)Seattle protocol biopsies, n (%)Number of tissue biopsies per patient, mean (range)Targeted biopsies, mean ...
PMC10212647
Procedural time
Barrett’s esophagus
The median time to perform HRWLE with Seattle protocol biopsies was 16.5 minutes (IQR 14.0–19.0 minutes). The time to perform BE surveillance endoscopy for increasing lengths of BE is shown in  Endoscopy duration and number of biopsies according to Barrett’s esophagus (BE) length. Median, interquartile range, maximum...
PMC10212647
Adherence to the Seattle protocol
To evaluate adherence to the Seattle protocol, the number of quadrantic biopsies taken per 2 cm of BE was assessed. The mean number of biopsies in the different strata 2–5 cm, 6–10 cm, and ≥ 11 cm was 4.3 (range 1.3–8.0), 3.8 (range 0.8–5.3), and 4.0 (range 3.4–4.3), respectively. Even though adherence to the Seattle ...
PMC10212647
Endoscopist experience
dysplasia
DYSPLASIA
We evaluated whether endoscopist training grade influenced endoscopy performance. There was no difference in sensitivity for dysplasia detection from targeted (consultant 45.5 % vs. independent trainee 68.4 %;
PMC10212647
Dysplasia detection rate
REGRESSION
We then looked at the impact of endoscopy duration on DDR. Both DDR and endoscopy duration may be affected by BE length and endoscopist experience. Therefore, we performed multivariable logistic regression with endoscopy duration adjusting for BE length and endoscopist experience. As show in
PMC10212647
Multivariable logistic regression for detection of dysplasia obtained from targeted and Seattle protocol biopsies.
Barrett’s esophagus, dysplasia
REGRESSION, DYSPLASIA
OR, odds ratio.Adjusted OR for endoscopy duration, adjusted for endoscopist experience and Barrett’s esophagus maximum length from multivariable logistic regression.  Linear regression for dysplasia detection rate (DDR) and endoscopy duration per maximum Barrett’s esophagus (BE) length for all biopsies, targeted biopsi...
PMC10212647
Discussion
cancer, dysplasia, BE-related neoplasia
CANCER, DISEASE, DYSPLASIA
This study demonstrated that the median duration for an adequate BE endoscopic surveillance procedure was 16.5 minutes, no difference between consultant endoscopists and independent trainees who had completed specialist training. In addition, we found evidence that the duration of the endoscopy procedure correlated wit...
PMC10212647
Tables 1 s–4 s, Fig. 1 s
Supplementary materialZusatzmaterial
PMC10212647
References
PMC10212647
Purpose
RCC
ADVANCED RENAL CELL CARCINOMA, RCC
In the phase 3 CheckMate 9ER trial, intravenous nivolumab (240 mg every 2 weeks) plus oral cabozantinib (40 mg/day) improved progression-free survival (PFS) versus sunitinib as first-line therapy for advanced renal cell carcinoma (RCC). To support cabozantinib dosing with the combination, this exposure–response analysi...
PMC9905187
Methods
ADVERSE EVENTS, CPH
Dose modification was allowed with cabozantinib (holds and reductions) to manage adverse events (AEs). The population pharmacokinetics analysis was updated and used to generate individual predicted cabozantinib exposure measures. Kaplan–Meier plots and time-to-event Cox proportional hazard (CPH) exposure–response model...
PMC9905187
Results
palmar-plantar-erythrodysesthesia, diarrhea
CPH
Kaplan–Meier plots showed no clear difference in PFS across cabozantinib exposure quartiles. Cabozantinib exposure did not significantly affect the hazard of PFS in the CPH base model nor in the final model. In contrast, baseline albumin and nivolumab clearance had a significant effect on PFS. There was no significant ...
PMC9905187
Conclusion
RCC
RCC
To optimize individual cabozantinib exposure, these data support the dose modification strategies in CheckMate 9ER for cabozantinib in patients with advanced RCC when combined with nivolumab.
PMC9905187
Supplementary Information
The online version contains supplementary material available at 10.1007/s00280-022-04500-9.
PMC9905187
Keywords
PMC9905187
Introduction
renal cell carcinoma, death, genitourinary malignancies, RCC
RENAL CELL CARCINOMA, RCC
Over the last decade, improved understanding of the angiogenic and immunogenic biology of renal cell carcinoma (RCC) has led to development of tyrosine kinase inhibitors (TKI) that target the vascular endothelial growth factor receptor (VEGFR) and immune checkpoint inhibitors that target the programmed cell death 1 (PD...
PMC9905187
Materials and methods
PMC9905187
Study design and data
RCC
BLOOD, RCC
The exposure–response analyses were conducted using data from the phase 3 CheckMate 9ER trial of nivolumab plus cabozantinib versus sunitinib in first-line advanced RCC. CheckMate 9ER was an open-label, randomized phase 3 trial of nivolumab (240 mg intravenously every 2 weeks) plus cabozantinib (40 mg orally QD) versus...
PMC9905187
Population pharmacokinetic model
MALIGNANCIES
The PopPK analysis included plasma cabozantinib concentration–time data from CheckMate 9ER and 10 studies from a previously developed integrated PopPK model that characterized cabozantinib concentration data from healthy subjects and patients with various types of malignancies [The analytical data preparation has been ...
PMC9905187
Exposure–response analysis for time-to-event endpoints
PMC9905187
Efficacy and safety endpoints
fatigue/asthenia, death, hypertension, diarrhea
PALMAR-PLANTAR ERYTHRODYSESTHESIA, EVENTS, HYPERTENSION
Time-to-event analyses were performed to characterize the exposure–response relationship between cabozantinib exposure and PFS (defined as the time from randomization to radiographic progression per RECIST v1.1 by BICR, or death), cabozantinib dose modification, and each of the following AEs commonly associated with ca...
PMC9905187
Dataset construction and preliminary analyses
EVENT
Individual average cabozantinib concentrations from time zero to the event or censoring time (CAVG0T) were calculated from the estimated individual PK parameters of the final PopPK model and individual dosing history; CAVG0T was used for the exposure–response analysis dataset to link clinical endpoints with individual ...
PMC9905187
Cox proportional hazards (CPH) model
CPH
CPH models were used to describe the relative hazard for each of the clinical efficacy and safety endpoints.The general form of the CPH model is represented by the equation (Eq. 
PMC9905187
Model development
CPH
Separate CPH models were developed for each of the clinical endpoints using data from the CheckMate 9ER trial. The impact of cabozantinib exposure on relative hazard was evaluated during base model development. A drop in − 2 log likelihood (− 2LL) when including cabozantinib exposure in the CPH model was considered sig...
PMC9905187
Covariate analysis
tumor, RCC
DISEASE, LIVER METASTASIS, TUMOR, RCC
Covariate effects were assessed for the PFS model. Covariates were added to the base model simultaneously to form a full model followed by stepwise backward elimination to identify the most parsimonious model. Statistical significance of covariate-parameter relationships was assessed with the Wald test, at Covariates e...
PMC9905187
Final model evaluation and simulations
CPH
The predictive performance of the PopPK model and time-to-event models was evaluated using visual predictive checks (VPC). Simulations were also performed using the final CPH model parameter estimates to predict the incidence of efficacy and safety endpoints for different dose levels.
PMC9905187
Software
REGRESSION
For PopPK modeling, analyses were performed using nonlinear mixed effects modeling methodology as implemented in the NONMEM software system, version 7.3 (ICON Development Solutions, Ellicott City, MD). For exposure–response analysis, time-to-event analyses were performed using the Cox proportional hazards regression (P...
PMC9905187
Results
PMC9905187
Exposure–response analyses
EVENTS, EVENT, CPH
For exposure–response analyses of PFS and safety endpoints, the number of patients in the CheckMate 9ER trial with events and the total number at risk are listed in Supplementary Table S3. These patients received at least one dose of nivolumab plus cabozantinib and had a baseline and/or at least one post-baseline asses...
PMC9905187
Progression-free survival
death
CPH, EVENT, DISEASE PROGRESSION
Figure Kaplan–Meier plot for progression-free survival by average exposure quartiles. Shaded regions represent 95% confidence intervals for each exposure quartile (Q#) of CAVG0T, the predicted average cabozantinib concentration from time zero to the event or censoringA linear CPH model including all 311 patients was us...
PMC9905187
Covariate effects for PFS
EVENT
Table Covariate effects in the final model of progression-free survival model. Reference is a male patient with nivolumab clearance of 0.009 L/h, baseline albumin of 41 g/L, and CAVG0T, the predicted average cabozantinib concentration from time zero to the event or censoring, of 558 ng/mL. Continuous covariates are tes...
PMC9905187
Safety endpoints
PMC9905187
Dose modifications
Among patients who received nivolumab plus cabozantinib, 318 were included in the analysis to characterize the relationship between individual predicted cabozantinib CL/F and the rate of dose modifications (Supplementary Table S3); 285 had a dose modification. The exploratory KM plot for cabozantinib dose modification ...
PMC9905187
Adverse events
diarrhea
PALMAR-PLANTAR ERYTHRODYSESTHESIA
Among the AE endpoints evaluated, exploratory KM plots by exposure quartile indicated an association of cabozantinib exposure with PPE (Grade ≥ 1) and diarrhea (Grade ≥ 3) but not with the other AE endpoints. The exploratory KM plots for PPE (Fig. Kaplan–Meier Plot for Grade ≥ 1 palmar-plantar erythrodysesthesia (
PMC9905187
Discussion
NSCLC, death, melanoma, diarrhea, rash, fatigue/asthenia, RCC, hypertension
NON-SMALL CELL LUNG CANCER, DISEASE PROGRESSION, MELANOMA, ADVERSE EVENTS, DISEASE, CPH, NSCLC, HYPOTHYROIDISM, HYPERTENSION, RCC
The CheckMate 9ER trial investigated the efficacy and safety of nivolumab in combination with cabozantinib compared with sunitinib in patients with previously untreated advanced RCC [Nivolumab plus cabozantinib significantly improved the primary efficacy endpoint of PFS compared with sunitinib [In patients receiving th...
PMC9905187
Acknowledgements
We thank the patients, their families, the investigators, and site staff. We thank Sravan Karumanchi (Ann Arbor Pharmacometrics Group) for providing support for the analyses and Linh Nguyen (Exelixis, Inc.) for her contributions to initial planning for the analyses. Writing and editorial assistance was provided by Ange...
PMC9905187
Author contributions
All authors analyzed and interpreted the data and provided critical review of the manuscript. BDT, JL, and RF drafted the manuscript. All authors approved the final version of the manuscript for submission and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or inte...
PMC9905187
Funding
The CheckMate 9ER study was funded by Bristol Myers Squibb in collaboration with Ono Pharmaceutical and with Exelixis, Ipsen Pharma, and Takeda Pharmaceutical. The analysis reported here was funded by Exelixis, Inc. (Alameda, CA, USA).
PMC9905187
Data availability
Inquiries can be directed to the corresponding author.
PMC9905187
Code availability
Inquiries can be directed to the corresponding author.
PMC9905187
Declarations
PMC9905187
Conflict of interest
All authors are employees and stockholders of Exelixis, Inc.
PMC9905187
Ethical approval
The studies included in the analysis were conducted in accordance with the Declaration of Helsinki and the good clinical practice guidelines and were approved by the institutional review board or ethics committee at each center.
PMC9905187
Consent to participate
All patients provided written informed consent
PMC9905187
Consent to publish
Not applicable.
PMC9905187
References
PMC9905187
1. Introduction
obesity, metabolic complications, Alzheimer’s disease, vascular disease
OBESITY, OXIDATIVE STRESS, VASCULAR DISEASE, METABOLIC DISORDERS
This study aimed to investigate the effects of Brazilian propolis on body fat mass and levels of adiponectin and reactive oxygen species among community-dwelling elderly females. This was a double-blind randomized placebo-controlled trial. Altogether, 78 females aged 66–84 years were randomly assigned to the propolis (...
PMC9861743
2. Materials and Methods
PMC9861743
2.1. Participants
psychiatric, dementia
DISEASES, DISORDERS
Healthy postmenopausal elderly females were recruited as trial volunteers for this study via the use of a public relations magazine in Mihara City, Japan. The inclusion criteria were healthy, postmenopausal females aged 65 years or older who were independent in their daily lives. Meanwhile, the exclusion criteria were ...
PMC9861743
2.2. Study Design
This was a randomized, double-blind, and placebo-controlled trial. The PRO group were given three soft capsules containing 227 mg/3 capsules of propolis twice per day, i.e., after breakfast and dinner (total intake: 454 mg/6 capsules/day) for 12 weeks. Meanwhile, the PLA group were given placebo capsules at the same do...
PMC9861743
2.3. Brazilian Propolis Supplementation
We prepared 227 mg/3 capsules of propolis supplement using Propolis 300
PMC9861743
2.4. Assessment Procedures
dehydration, hand dynamometer, dual-energy X-ray absorptiometry
DEHYDRATION, OXIDATIVE STRESS
All assessments were performed by a physician, radiologist, nurse, dietitian, and ten physical therapists. The assessments before and after the intervention lasted for approximately 60 min. They were conducted at the Mihara Campus of Prefectural University of Hiroshima using a standardized protocol by the same research...
PMC9861743
2.5. Statistical Analysis
All continuous data were presented as mean standard error of the mean or median (interquartile range) for parametric or nonparametric continuous variables, respectively. The baseline characteristics between the two groups were compared using a Student’s unpaired The sample size calculation and power analysis were perfo...
PMC9861743
4. Discussion
vascular disorders
OBESE, OXIDATIVE STRESS, DISORDERS, VASCULAR DISORDERS, INSULIN RESISTANCE, POSTMENOPAUSAL SYMPTOMS, TYPE 2 DIABETES, DISEASES
Our prospective interventional study showed that propolis had a positive effect on absolute and relative fat mass, relative lean body mass, and levels of adiponectin and ROS among community-dwelling elderly females. Therefore, propolis supplementation may be an effective strategy for preventing disorders caused by body...
PMC9861743
Author Contributions
N.M.
Conceptualization, M.K. and H.F.; methodology, M.K., R.N. and H.F.; software, T.I., N.T., M.T. and T.N.; validation, T.H. and H.F.; formal analysis, M.K., T.I., R.N., M.T. and T.N.; investigation, M.K., T.I., R.N., M.T., H.I., N.T., N.M., H.K. and T.H.; resources, M.K., T.I., H.K., T.H. and H.F.; data curation, R.N., N...
PMC9861743
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of the Prefectural University of Hiroshima (15MH064) and Kobe University Graduate School of Health Sciences (277-2). Furthermore, the trial was registered at the University Hospita...
PMC9861743
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
PMC9861743
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
PMC9861743
Conflicts of Interest
The authors declare no conflict of interest.
PMC9861743
References
toxicity
HIVES
CONSORT flowchart. PLA, placebo; PRO, propolis; ITT, intention-to-treat; PP, per-protocol. Obtained from honeybee hives and extracted using ethanol. Wheat germ oil is extracted by pressing the wheat germ and is used as a solvent for propolis supplements. Therefore, it was selected as a placebo in this study. The supple...
PMC9861743
1. Introduction
stress-related injuries, post-traumatic, ’ post-traumatic, fatigue
SECONDARY, STS
This randomized controlled trial examined the impact of a psychoeducational group program on the mental well-being of unit-based nurse leaders, specifically nurse managers and assistant nurse managers. The program was developed around the themes of resilience, insight, self-compassion, and empowerment to fight burnout ...
PMC10252280