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INTRODUCTION
death, glucose tolerance, cancer, diabetes mellitus, biochemically-relapsed, non-cutaneous malignancy, metabolic syndrome, type II diabetes
CANCER, DIABETES MELLITUS, SECONDARY, INSULIN RESISTANCE, PROSTATE CANCER, METABOLIC SYNDROME, INCREASED INSULIN, TYPE II DIABETES
Background: Androgen deprivation therapy (ADT) can lead to metabolic syndrome (MS) and is implicated in ADT-resistance. Metformin showed antineoplastic activity through mTOR inhibition secondary AMPK-activation.Materials and Methods: To investigate whether metformin mitigated ADT-related MS, we conducted a randomized d...
PMC10278660
RESULTS
PMC10278660
Patients and treatments
Prostate Cancer
EXTENSIVE DISEASE, PROSTATE CANCER
Eligible patients who provided written informed consent were recruited at one center, University of Texas Health Science Center, San Antonio, United States between July of 2011 through July of 2015.During this period, three randomized phase III trials reported the clinical benefit of adding docetaxel to ADT: Chemohormo...
PMC10278660
CONSORT diagram: identification, enrollment and randomization of patients.
DISEASE CHARACTERISTIC
The baseline demographic and disease characteristics, including mean BMI, were well balanced between the two groups (
PMC10278660
Metabolic syndrome
metabolic syndrome
METABOLIC SYNDROME
At baseline, markers of metabolic syndrome including mean weight, WC, serum Insulin concentration in the metformin cohort were 187 lbs, 41.14 cm and 10.03 mIU/L respectively, and 177.65 lbs, 40.52 cm and 8.02 mIU/L in the placebo cohort. An increase in mean weight and serum insulin concentrations were seen across both ...
PMC10278660
Adverse events and serious adverse events
PMC10278660
HOMA-IR
INSULIN RESISTANCE
Homeostatic model assessment is a method for assessing beta-cell function and insulin resistance from basal (fasting) glucose and insulin concentrations [
PMC10278660
Mean HOMO-ir levels for metformin and placebo cohorts over time.
PMC10278660
PSA efficacy and pharmacodynamic analysis
The median baseline PSA for the placebo and metformin cohort was 31.95 (5.7–77.15) and 25 (6.2–58.7) respectively (Phospho-S6-kinase levels were analyzed from patient derived blood samples and although there were some downregulation in patients 7, 25, 34 and 37 who received metformin, overall variable regulation of pro...
PMC10278660
Variable changes in phosphorylation of S6 kinase 1 was observed in both cohorts.
(
PMC10278660
DISCUSSION
metabolic syndrome, diabetes
NON-SMALL CELL LUNG CANCER, RECURRENCE, MULTIPLE CANCER, ADVERSE EVENT, INSULIN RESISTANCE, METABOLIC SYNDROME, DIABETES
The results presented are after empiric therapy with metformin compared to placebo to measure its effects on the development of metabolic syndrome in patients with PC on ADT. We caveat that all results in are study are underpowered due to changes in the standard of care as described in Results which limits the generali...
PMC10278660
MATERIALS AND METHODS
PMC10278660
Trial Design and oversight
METASTATIC DISEASE
We present a randomized, prospective, double-blind, placebo-controlled phase II trial evaluating the efficacy of empiric glycemic control with metformin in castrated men with advanced PC (NCT:01620593). The trial was designed to enroll a total of 94 men with advanced metastatic PC and men with PC who were candidates fo...
PMC10278660
Patients
Tumors, visceral disease, disability, diabetes
IMPAIRED GLUCOSE TOLERANCE, METASTATIC DISEASE, TUMORS, METASTATIC PROSTATE CANCER, DIABETES
Patients had histologically proven PC and an ECOG performance status of 0 to 2 (on a 5-point scale, with 0 indicating an absence of disability and higher numbers indicating greater disability). Patients required castration therapy with either an LHRH analogue (continuous) or surgical castration. Patient were permitted ...
PMC10278660
Study end points
Cancer, hyperinsulinemia
CANCER, SECONDARY, INSULIN RESISTANCE, HYPERINSULINEMIA
The primary end point was a group of metrics that reflected the metabolic consequences of ADT including development of hyperinsulinemia and insulin resistance, comparing metformin to placebo in men receiving ADT. Subjects had normal oral glucose tolerance test at baseline. Measurements of metabolic consequences includi...
PMC10278660
Quantification of metformin levels
A liquid chromatography/tandem mass spectrometry (LC-MS-MS) method was implemented for the quantitation of metformin as previously described [
PMC10278660
Pharmacodynamic analysis
Collection of peripheral blood mononuclear cells (PBMCs) were extracted from whole blood in a CPT Vacutainer as recommended by the manufacturer. Briefly, 8 ml of whole blood were collected from patients at baseline, week 12 and 28 and centrifuged at 1500 × g for 20 min at room temperature to isolate the PBMC fraction. ...
PMC10278660
Statistical analysis
In a cross-sectional study of men with PC and who received androgen deprivation therapy, the mean fasting insulin was 45.0 mU/mL ± 7.25 mU/mL and a mean HOMAUnder these assumptions, the same sample size requirement is attained using HOMA
PMC10278660
Availability of data and material
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC10278660
CONCLUSIONS
metabolic syndrome, cardiovascular death
METABOLIC SYNDROME, DISEASE
The present study has numerous strengths including the longitudinal, prospective and placebo-controlled design. The main limitation in assessing the effect of empiric metformin in this study is the limited sample size and variance in criteria to determine metabolic syndrome. Outside of our study, there is evidence to s...
PMC10278660
SUPPLEMENTARY MATERIALS
PMC10278660
ACKNOWLEDGMENTS AND FUNDING
ICH, Cancer
CANCER
Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio; San Antonio, TX. Cancer Center Support Grant P30CA054174. Bill and Ella Owens foundation grant. Christos Fountzilas was a recipient of a Cancer Research Training Award (RP 140105) funded by the C...
PMC10278660
REFERENCES
PMC10278660
Subject terms
Whereas cardiopulmonary responses are well understood in endurance training, they are rarely described in strength training. This cross-over study examined acute cardiopulmonary responses in strength training. Fourteen healthy male strength training-experienced participants (age 24.5 ± 2.9 years; BMI 24.1 ± 2.0 kg/mOpe...
PMC10126007
Introduction
stroke
HYPERTROPHIC, STROKE
The preventive and rehabilitative effects of physical exercise have generally been well-studiedThe cellular response to ST is widely acknowledged, as are the associated hypertrophic effects of skeletal muscleNot conclusively clarified and unlike endurance training, the acute hemodynamic adaptations (stroke volume and c...
PMC10126007
Materials and methods
PMC10126007
Participants
Our study was conducted in accordance with the latest version of the Declaration of Helsinki and approved by the Ethics Committee of the Medical Faculty of the University of Leipzig (272/21-ek). Written informed consent was obtained from all participants. The study group consisted of 14 healthy and strength training ex...
PMC10126007
Study design
cardiac and pulmonary maximum
After the initial pre-examination, all participants completed three experimental sessions involving standardized squats on a smith machine (Technogym Germany GmbH, Germany) over a three-week period. To standardize the training sessions, the individual three-repetition-maximum at 50%, 62.5% and 75% were used. The pre-ex...
PMC10126007
Strength training: squats in a smith machine with 50% 3-RM, 62.5% 3-RM, and 75% 3-RM
All participants took part in a warm up-period lasting 5 min on a bicycle ergometer (100 W; 75 rpm) at each training session, followed by one set of 10 repetitions without external load, five repetitions with 50% of the subsequent testing load and 3 repetitions with 75% of the subsequent load. For each training session...
PMC10126007
Incremental exertion test (IET)
RPE
The IET was performed on a semi-recumbent ergometer (ergometrics 900, ergoline GmbH, Bitz, Germany) at a constant speed of 60–70 rpm. The test started with a 50 W load, which was increased by 15 W every minute until exhaustion occurred. The criteria for exhaustion were a cycling cadence below 60 revolutions per minute,...
PMC10126007
Measurements during strength training
stroke
STROKE
The three strength training sessions in this study focused on mean exercise (three sets lasting 1 min), mean immediate post-exercise (1 min after three sets), and cumulated values (three sets with complete post-exercise period). Peak exercise and mean post-exercise values (4 min after three sets) are shown in the suppl...
PMC10126007
Blood pressure assessement during strength training
RPE
BLOOD
Blood pressure (BP) and rating of perceived exertion (RPE; from 1 to 10, if 10 was total exhaustion) were observed at rest, immediately after each set, and after 1.30 and 2.30 min of recovery. On a separate day, participants had to perform the squats in a single-arm position in an additional examination to enable blood...
PMC10126007
Statistical analysis
All values are expressed as the means and standard deviation unless otherwise stated, and the significance level was defined as p < 0.05. Data were analyzed using Microsoft Office Excel
PMC10126007
Compliance with ethical standards
All procedures described in this study will be performed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the principles of the Declaration of Helsinki of 1964 and its latest version. Written informed consent or its equivalent will be o...
PMC10126007
Results
PMC10126007
Incremental exertion test
Maximum IET values are shown in Table
PMC10126007
Cardiopulmonary response during strength training sessions
Baseline values were measured prior to each session (values not shown), and we observed no significant hemodynamic differences. Figures Graphs show the mean cardiac response (n = 14) during strength training sessions with (Graphs show the mean pulmonary response (n = 14) during strength training sessions: (Graphs show ...
PMC10126007
Cardiopulmonary response immediately after training sessions
Table
PMC10126007
Discussion
The main finding of this randomized cross-over study was the specific post-exercise responses of cardiopulmonary parameters (SV, V
PMC10126007
Pulmonary response
COIn
During the exercise period, only VDuring the post-exercise period, all pulmonary parameters exhibited significant intensity-dependent differences. Breathing regulation after the exercise period seems to be affected by the exercise-related breathing pattern. Therefore, the training-induced oxygen deficit and COIn summar...
PMC10126007
Cardiovascular response
intensity-related increase
During the exercise period a significant intensity-related increase in HR and CO was evident (Tables The present results show that the HR and CO during exercise and during cumulative exercise and resting times was significantly higher at 75% intensity than at the two lower intensities (Table We recorded the blood press...
PMC10126007
Study limitations
The sample size is small, and we selected only male and recreationally-active participants for this study to prevent compromising interference from possible gender differences in cardiopulmonary function, and muscle performance differences. Therefore, the interpretability and generalizability of the results is limited ...
PMC10126007
Conclusions
muscle mass, stroke
BLOOD, STROKE
With this randomized cross-over study, we examined the acute hemodynamic response to standardized strength training at different intensities but of the same duration and muscle mass and during exercise and post-exercise periods. The cumulative cardiopulmonary response of exercise and post-exercise periods corresponds t...
PMC10126007
Supplementary Information
Supplementary Information.
PMC10126007
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-33873-x.
PMC10126007
Acknowledgements
We thank Carole Cürten for English editing.
PMC10126007
Author contributions
T.M., R.K. and J.L.
R.F., T.M., R.K. and J.L. conceived and designed this research. R.F., Z.U., T.M., R.K. and J.L. conducted experiments. R.F. and J.L. analyzed and interpreted the data. R.F. and J.L. drafted and revised the manuscript. All authors have read and approved the final version of this manuscript.
PMC10126007
Funding
Open Access funding enabled and organized by Projekt DEAL. No funds, grants, or other support was received.
PMC10126007
Data availability
The original contributions presented in the study are included in the article’s supplementary material; further inquiries can be directed to the corresponding author/s.
PMC10126007
Competing interests
The authors declare no competing interests.
PMC10126007
References
PMC10126007
Background
stroke, ’ disease
REGRESSION, STROKE
There are few reported studies on stigma in young and middle-aged stroke patients during the rehabilitation period, however, the rehabilitation period plays a key role in the patients’ disease regression. Exploring the level of stigma and the influencing factors in young and middle-aged stroke patients during the rehab...
PMC10067210
Methods
stroke, Stroke
REGRESSION, STROKE, POSITIVE, STROKE
Using a convenience sampling method, 285 young and middle-aged stroke patients admitted to the rehabilitation medicine department of a tertiary care hospital in Shenzhen, China, from November 2021 to September 2022 were selected and surveyed using a general information questionnaire, the Stroke Stigma Scale(SSS), the B...
PMC10067210
Results
SSS score of 45.08 
PMC10067210
Conclusion
stroke
STROKE
Young and middle-aged stroke patients have a moderate level of stigma. Medical staff should focus on young patients aged 18–44 years, those with high monthly income before the stroke, those with poor self-care ability, and those with low positive and high negative emotion scores, and conduct early assessments and adopt...
PMC10067210
Trial Registration
Registration number of China Clinical Trials Registration Center: 20,220,328,004-FS01.
PMC10067210
Supplementary Information
The online version contains supplementary material available at 10.1186/s12883-023-03189-4.
PMC10067210
Keywords
PMC10067210
Introduction
death, Stroke, stroke, neurological deficits, disability
CIRCULATION DISORDERS, STROKE, STROKE, DISEASE, CEREBROVASCULAR ACCIDENT
Stroke is a group of acute episodes of neurological deficits caused by multiple causes of local cerebral blood circulation disorders, also known as stroke or cerebrovascular accident [It is the second-leading cause of death and disability worldwide [Stigma, originally from the Greek word meaning “brand,“ was first intr...
PMC10067210
Methods
PMC10067210
Research subjects
stroke
STROKE
Young and middle-aged stroke patients hospitalized in the rehabilitation medicine department of a tertiary care hospital in Shenzhen, China, were selected as the study population using a convenience sampling method. Inclusion criteria: (1) meeting stroke diagnostic criteria [
PMC10067210
Research tools
PMC10067210
General information questionnaire
comorbid chronic diseases, strokes
STROKES
It was designed by the investigators themselves and included two sections with demographic and sociological information (gender, age, marital status, occupation, education, pre-stroke monthly income, insurance type, smoking, drinking, primary caregiver) and disease-related information (comorbid chronic diseases, number...
PMC10067210
Stroke stigma scale (SSS)
The SSS, constructed by Zhu Minfang et al. [
PMC10067210
Positive and negative affect scale (PANAS)
The scale was developed by Watson et al. [
PMC10067210
Barthel index (BI)
It is an international rehabilitation medicine method for assessing patients’ ability to perform activities of daily living [
PMC10067210
Information collection
The researcher was mainly responsible for the receipt and distribution of questionnaires, and another graduate student assisted. Prior to the survey, the unified instructional language was used to explain the purpose of the survey and the method of filling out the questionnaire to the respondents, etc. All questionnair...
PMC10067210
Results
PMC10067210
Description of the patient screening process
In this study, 300 patients were initially included, and 15 cases with missing basic information were excluded, leaving 285 cases for the final data analysis, as detailed in the flow chart (Fig.  Description of the participant screening process
PMC10067210
General data description of young and middle-aged stroke patients
stroke
STROKE
The results showed statistically significant differences ( Description of general data of young and middle-aged stroke patients (N = 285)MaritalStatusMonthlyIncome(¥)Note: a represents
PMC10067210
SSS, PANAS and BI scores of young and middle-aged stroke patients
The results of the study showed that the SSS score for young and middle-aged people are 45.08  Scores on each scale (N = 285)
PMC10067210
Description of the linear relationship of factors influencing disease stigma in young and middle-aged stroke patients
PMC10067210
Multiple linear regression analysis of the factors influencing stigma
stroke, chronic disease status, primary caregiver
REGRESSION, STROKE
The SSS for young and middle-aged stroke patients was used as the dependent variable, and statistically significant data (age, occupation, education, monthly income, type of health insurance, chronic disease status, primary caregiver), the Barthel Index, positive emotions, and negative emotions were used as independent...
PMC10067210
Description of the non-linear relationship of factors influencing stigma in young and middle-aged stroke patients
PMC10067210
Relationship between general information and stigma
REGRESSION
The general information (age and monthly income) that was significant in the multiple linear regression analysis was described by smoothing curve fitting, where the red solid line indicates the smoothed curve fitting between the variables and the blue dashed line indicates the 95% confidence interval of the fitting. A ...
PMC10067210
The relationship between BI and stigma
The non-linear relationship between BI and stigma was observed by smoothed curve fitting, where the red solid line indicates the smoothed curve fitting between the variables and the blue dashed line indicates the 95% confidence interval of the fitting, where it can be observed that there are different decreasing trends...
PMC10067210
Relationship between PANAS and stigma
The relationship between positive and negative emotions and stigma was observed through a smoothed curve fit, where the red solid line indicates the smoothed curve fit between the variables and the blue dashed line indicates the 95% confidence interval of the fit. We observed that when positive emotions were scored at ...
PMC10067210
Discussion
PMC10067210
Current status of stigma in young and middle-aged patients recovering from stroke
The results of this study showed that the total stigma score of 45.08 
PMC10067210
Factors influencing stigma in young and middle-aged patients recovering from stroke
PMC10067210
Age was negatively correlated with the level of stigma
According to the criteria for delineating the age of Chinese residents and the age cut-off for Chinese residents in previous studies in the cardiovascular literature, middle-aged and young adults are defined as 18–64 years old, 18–44 years old as young adults, and 45–64 years old as middle-aged [
PMC10067210
Monthly income was positively correlated with the level of stigma
In 2021, the average annual salary of urban non-private sector employees in 31 provinces in China was ¥106,837 [
PMC10067210
BI was negatively correlated with the level of stigma
stroke
STROKE
This study found that the poorer the ability to perform daily living, the higher the stigma score, which is consistent with a cross-sectional survey of 72 stroke patients by Tong Qi [
PMC10067210
Emotional state correlates with disease stigma
stroke, vessel disease
STROKE
The present study showed that positive emotions were negatively correlated with stigma and negative emotions were positively correlated with stigma in young and middle-aged patients recovering from stroke, which is In line with Wang Xiao [However, there are some limitations to our study. On one side, it was a cross-sec...
PMC10067210
Conclusion
stroke, ’
STROKE
The research results show that the sense of stigma among middle-aged and young stroke patients is at a moderate or higher level. Currently, solutions for stroke patients’ feelings of stigma have yielded positive results [In conclusion, this study not only lays the foundation for future interventional studies on stigma ...
PMC10067210
Acknowledgements
The authors would like to thank Miss. Xinlin Chen and Mr. Chi Chen of the Empower.Institute for their help.
PMC10067210
Author Contribution
RS, HL
ZZ contributed to the drafting of the manuscript; ZZ, YZ, HL contributed to the data collection; ZZ, RS, YW contributed to Analysis and interpretation of data; CY contributed to the conception and critical revision of the manuscript; and approved the final version of the submitted manuscript.
PMC10067210
Funding
stroke
STROKE
This work was supported by ID (LHGJ20220676). A study of the impact of a PERMA model-based intervention program on stigma in young and middle-aged stroke patients.
PMC10067210
Data Availability
All data generated or analyzed during this study are included in this published article [and its supplementary information files: Additional File 1].
PMC10067210
Declarations
PMC10067210
Conflicts of interest
The authors declare that they have no conflicts of interest.
PMC10067210
Ethics approval and consent to participate
Firstly, in this study, all methods used by the researcher throughout the questionnaire survey of the study participants were carried out in accordance with the relevant guidelines and regulations.Secondly, this study was approved by the Clinical Research Ethics Committee of the Shenzhen Second People’s Hospital (appro...
PMC10067210
Consent for publication
Not applicable.
PMC10067210
Abbreviations
Stroke
STROKE
Stroke Stigma ScalePositive and Negative Affect ScaleBarthel Index
PMC10067210
References
PMC10067210
Condensed Abstract
obesity, coronary artery disease, nonvalvular atrial fibrillation
OBESITY, CORONARY ARTERY DISEASE
We hypothesize that a novel tailor-made cardiac rehabilitation (CR) program for obesity patients (OPTICARE XL) has better outcomes as compared to usual CR regarding parameters of cardiac function as measured by conventional and advanced transthoracic echocardiography. This is an open-label, randomized controlled trial....
PMC10160212
Keywords
PMC10160212
Introduction
overweight, weight loss
CARDIAC DISEASE
Cardiac rehabilitation (CR) is a valuable treatment for patients with a broad spectrum of cardiac disease. Currently, CR has a class 1 recommendation (evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective) in several European society of cardiology (ESC) and American coll...
PMC10160212
Methods
PMC10160212
Study population and design
obesity, Weight loss, weight loss
OBESITY
The OPTICARE XL CR (OPTImal CArdiac REhabilitation XL CR) study is an open-label, randomized controlled trial [The experimental group participated in OPTICARE XL CR, and the controls received standard CR as recommended by the guidelines [In order to enter cardiac rehabilitation, patients are exposed to a symptom-limite...
PMC10160212