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2.2.2. Exclusion Criteria
hyperlordosis, fibromyalgia, Orthopedic malformations
RHEUMATOID ARTHRITIS, FIBROMYALGIA, DEGENERATION
Orthopedic malformations or neurosurgical diseases;Disc degeneration or other conditions that may affect the interpretation of results (severe fibromyalgia and rheumatoid arthritis, in combination with other treatments);Surgery or pregnancy within 30 d;Breastfeeding;Wearing a hyperlordosis treatment device;Participatio...
PMC10744921
2.3. Sample Size
In previous studies, a reduction in the LLA resulted in an effect size of d = 0.92 [
PMC10744921
2.4. Randomization and Blinding
The participants were randomly allocated to two groups using Random Allocation Software for Windows ver. 2.0, developed by Isfahan University, Iran. One group was assigned to perform abdominal exercises using the sprinter pattern (
PMC10744921
2.5. Intervention
muscle fatigue
ADVERSE EVENTS
Both groups initially underwent a pre-test in which the root of the mean square reference values was assessed using electromyography (EMG), and radiographic imaging was employed to measure the lordotic curve. Subsequently, the participants performed three sets of exercises according to their group: sprinter-pattern exe...
PMC10744921
2.5.1. Sprinter-Pattern Exercise
For the SPE, the participants lay on their backs with their knees bent at a 45° angle and their arms resting beside them on the floor. Upon receiving a given signal, they raised their heads off the mat and simultaneously performed a series of coordinated arm and leg movements: flexing, adducting, and externally rotatin...
PMC10744921
2.5.2. Crunch Exercise
For the CE, the participants lay on their backs with their knees bent at a 45° angle and placed their hands behind their heads. When given the start signal, they lifted their heads and shoulders, elevating the inferior angle of the scapula from the mat [
PMC10744921
2.6. Outcomes
LLA
The LLA and SHA were measured before and after the intervention, while abdominal muscle activity was measured during the intervention period.
PMC10744921
2.6.1. Lordotic Curve
LLA
The LLA and SHA were measured using an Accuray-525R diagnostic X-ray machine (Don Kang Medical System, Seoul, Republic of Korea). Radiographs were captured at distances of 2 m and 50 cm, with the following settings: exposure time, 0.8 s; tube voltage, 90 kVp; and tube current, 200 mA. Images were taken from the sagitta...
PMC10744921
2.6.2. Abdominal Muscle Activity
RA
CONTRACTION
Muscle activity was measured using surface EMG (Mini-wave Infinity Waterproof, Cometa Systems, Italy). The EMG signals were converted from analog to digital, and an EMG analysis software (Myoresearch XP Master ver. 1.07, Noraxon, Scottsdale, AZ, USA) was utilized, with the sampling rate set to 2000 Hz. The raw EMG data...
PMC10744921
2.7. Data Analysis
Statistical analyses of the collected data were performed using SPSS Statistics 22 (IBM, New York, NY, USA). All participants underwent the Shapiro–Wilk normality test, and all variables were confirmed to follow a normal distribution. Descriptive statistics were used to assess participants’ general characteristics, whi...
PMC10744921
3. Results
PMC10744921
3.1. General Characteristics
RECRUITMENT
Based on the study recruitment documents, a total of 40 individuals who voluntarily expressed interest and met the inclusion and exclusion criteria participated in the study (
PMC10744921
3.2. Changes in the Lumbar Lordotic Angle by Exercise Method
The changes in the LLA between the groups according to the exercise method are shown in
PMC10744921
3.3. Changes in Sacrohorizontal Angle by Exercise Method
The changes in the SHA between the groups according to the exercise method are shown in
PMC10744921
3.4. Changes in Muscle Activity by Exercise Method
The differences in the muscle activity between the groups are based on the exercise methods and are shown in
PMC10744921
4. Discussion
hyperlordosis, pain
LORDOSIS
In this study, we examined the immediate effects of the SPE and CE on patients with hyperlordosis. Based on the research results, both LLA and SHA significantly decreased in both groups after the completion of the interventions (The present study emphasized the significance of abdominal exercises in reducing lumbar lor...
PMC10744921
Author Contributions
Conceptualization, S.L. (Sangbong Lee), J.J. and S.L. (Seungwon Lee); methodology, S.L. (Sangbong Lee) and S.L. (Seungwon Lee); software, S.L. (Sangbong Lee) and H.K.; validation, S.L. (Sangbong Lee), J.J. and S.L. (Seungwon Lee); formal analysis, S.L. (Sangbong Lee) and S.L. (Seungwon Lee); investigation, S.L. (Sangbo...
PMC10744921
Institutional Review Board Statement
This study was conducted in accordance with the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board (IRB) of Sahmyook University (No. 2-7001793-AB-N012019086HR, 29 October 2019).
PMC10744921
Informed Consent Statement
Informed consent was obtained from all the participants involved in this study.
PMC10744921
Data Availability Statement
The data presented in this study are available on request from the corresponding author.
PMC10744921
Conflicts of Interest
The authors declare no conflict of interest.
PMC10744921
References
Interventions. (The lumbar lordotic angle (LLA) and sacrohorizontal angle (SHA).CONSORT (Consolidated Standards for Reporting of Trials) study flow.Effect size by exercise method. CE: crunch exercise, EO: external oblique, IO: internal oblique, LLA: lumbar lordotic angle, RA: rectus abdominis, SHA: sacrohorizontal angl...
PMC10744921
Introduction
DEGENERATIVE CHANGE
Edited by: Michael V. Volin, Midwestern University, United StatesReviewed by: Nirmal Banda, University of Colorado Hospital, United States; Anne E. C. Nichols, University of Rochester Medical Center, United States†These authors share last authorshipDense connective tissues (DCTs) such as tendon, ligament, and cartilage...
PMC10512081
Methods
PROLIFERATIVE
Quantitative mass spectrometry (QMS) profiling of tissue biopsies from the inflammatory phase of healing (n = 40 patients) and microdialysates from the proliferative phase of healing (n = 28 patients) were used to identify specific biomarkers for tendon healing. Further bioinformatic and experimental investigations bas...
PMC10512081
Results
rupture
PROLIFERATIVE
The QMS profiling of tissue biopsies from the inflammatory phase of healing identified 769 unique proteins, and microdialysates from the proliferative phase of healing identified 1423 unique proteins in Achilles tendon rupture patients. QMS-profiling showed that CFD expression was higher during the inflammatory- and lo...
PMC10512081
Discussion
DCT injuries
PROLIFERATIVE
The results of the current studies characterized underlying inflammatory- and proliferative healing mechanisms by which CFD potentially improved tendon repair. These findings may lead to improved individualized treatment options, as well the development of effective therapies to promote good long-term clinical outcomes...
PMC10512081
Trial registration
PMC10512081
Introduction
pain
DEGENERATIVE CHANGE, PROLIFERATIVE
Dense connective tissues (DCTs) provide a matrix, which support and protect other tissues and organs in the human body, as well as acting as force transmitters in the musculoskeletal system. The healing process after an injury to DCTs such as tendon, ligament and meniscus, however, often leads to compromised healing wi...
PMC10512081
Materials and methods
PMC10512081
Clinical samples and data collection
PMC10512081
Patient eligibility criteria and randomization
allergic, malignancy, pitting oedema, Rupture, acute ATR, rupture, thrombophlebitis, heart failure
THROMBOPHLEBITIS, HEART FAILURE, RENAL FAILURE, COAGULATION DISORDER
The database included patients diagnosed with acute ATR and surgically repaired at the Karolinska University Hospital. A total of 55 patients were randomly selected from 2 previously conducted randomized control trials (RCT) and were dichotomized into two clinical cohorts according to their outcome based on Achilles Te...
PMC10512081
Surgery and biopsy collection
The same anesthetic and surgical techniques were used for all patients using a predefined study protocol, as described earlier (
PMC10512081
Microdialysate collection
Microdialysates were collected at 2-week post-surgery from the operated and non-operated healthy leg as described previously (
PMC10512081
Patient-reported outcome
pain, tiredness, Rupture
Patient-reported outcomes were assessed by the validated questionnaire, Achilles Tendon Total Rupture Score (ATRS), at one-year post-surgery during the follow up. The ATRS consists of 10 specific sub-scales which includes strength of tendon, tiredness in the tendon, stiffness in tendon, pain in tendon, as well as limit...
PMC10512081
Functional outcome
At 1-year post-surgery, functional outcomes of all patients were evaluated by using the heel-rise test (HRT), a validated method which has been used previously (The HRT was performed on one leg at time with patient standing on a box with 10° incline wearing standardized footwear connected to a linear encounter, with th...
PMC10512081
Quantitative mass spectrometry
PMC10512081
Protein extraction from tissue biopsies and microdialysate
Tissue samples were solubilized in urea and NaCl with ProteaseMAX (Promega) in ammonium bicarbonate (AmBic) and mixed vigorously. Furthermore, samples were quickly frozen on block and subjected to disruption with a Vortex Genie disruptor before additional NaCl, urea and AmBic were mixed in. The supernatant fraction was...
PMC10512081
Reversed-phase liquid chromatography-mass spectrometry/MS analysis
HF mass spectrometer
Briefly, a C18 EASY-spray and C18 trap columns linked to an Ultimate 3000 UPLC system (Thermo Scientific) were used for the reversed phase liquid chromatographic separations of peptides. An Q Exactive HF mass spectrometer (Thermo Scientific) was used for the subsequent mass spectra, followed by data-dependent higher-en...
PMC10512081
Protein identification and quantification
The raw data were analyzed using the Mascot v2.5.1 (MatrixScience Ltd., UK) search engine. The Human Uniport database (last modified: 3 September 2020; ID: UP000005640; 75,777 proteins) was matched with the MS/MS spectra using the MSFragger database engine (
PMC10512081
Cell culture
In order to evaluate the healing mechanisms of CFD in dense connective tissue repair fibroblast cells were used. The use of fibroblast cells for tendon research has been previously reported (
PMC10512081
Inflammatory fibroblast model creation
TUMOR NECROSIS
Recombinant human tumor necrosis factor (TNF) (Pepro Tech) was used to establish an inflammation-induced injury model after transfection of cells. Model creation used TNF in 0.2% BSA at a concentration of 10 ng TNF/ml (
PMC10512081
Cell transfection
Cells were seed in 12-well plates and incubated with CFD silencing RNA (siRNA CFD) to detect whether CFD impacts Col1a1 production. Fibroblasts were incubated with a final concentration of 100 nM siRNA CFD mixed with Lipofectamine™ 3000 transfection reagent (Thermo Fisher Scientific), Opti-MEM reagent was used for dilu...
PMC10512081
Western blot analysis
MP
LYSED, SECONDARY
Briefly, 5μg protein lysed from fibroblasts were loaded into each well of the gel. Proteins were separated using 4-12% Bis-Tris gel electrophoresis (Invitrogen), and then transferred to nitrocellulose membranes. Nonspecific binding was blocked by incubating the membranes using 5% nonfat milk diluted in 1x tris-buffered...
PMC10512081
Statistical analysis
SPSS (IBM SPSS, v26.0), GraphPad Prism 8.0 and R were used for statistical analysis and data plotting. All the variables were checked for skewness. Standard descriptive statistics were used to summarize clinical variables as means and standard deviations. Mann-Whitney
PMC10512081
Results
PMC10512081
Patient cohort
To establish a tissue atlas relating to good and poor patient outcome, tendon biopsies were collected from 40 ATR patients at the time of surgery during the inflammatory healing phase which represented 2-7 days after injury. Among these patients, 20 patients were assessed with good clinical outcomes and the other 20 wi...
PMC10512081
Bioinformatic and prognostic detection of complement factor D during tendon repair
inflammation
INFLAMMATION, PROLIFERATIVE
In total, 769 unique proteins were identified from the biopsies as representative of the inflammatory stage of healing, whereas 1423 proteins were detected from microdialysates representing the proliferative healing phase of DCT repair. After combining proteomic profiles from both phases, CFD was detected to be signifi...
PMC10512081
Association between CFD and healing related biomarker Col1a1 in patient samples
inflammation, CFD
REGRESSION, INFLAMMATION
Our stepwise regression analysis identified a correlation between CFD with other healing-related markers, especially with different collagens. This is of interest as collagens are some of the most vital cellular components for maintaining and remodeling of the AT matrix. Interestingly, we observed opposite associations...
PMC10512081
Association between CFD and Col1a1 expression in inflammatory and proliferative
inflammation
PROLIFERATION, INFLAMMATION
After tendon injury, inflammation is the first phase of tissue repair, subsequently followed by the proliferation phase. To confirm and investigate the effect of CFD on Col1a1 expression during healing, inflammation-induced and unchallenged fibroblast injury models based on human primary fibroblasts and a fibroblast ce...
PMC10512081
CFD Enhances tendon repair by improving human fibroblast migration
CFD
The migration of fibroblasts to the site of injury is vital for the initiation of wound healing processes (Protein-protein interactions and association among CFD and highly enriched migration-related proteins. To confirm the role of CFD on fibroblast migration, a gene silencing technique in CFD regulates fibroblast mig...
PMC10512081
Function of Col1a1 in regulating healing outcome
To analyze whether the effect of CFD on fibroblast migration act through a pathway involving Col1a1 further experiments were performed. Previous studies have indicated that Col1a1 and its proteolytic-derived peptides at sites of tissue injury may act as chemotactic factors to attract fibroblast migration and initiate r...
PMC10512081
Discussion
ATR, inflammation, connective tissue injuries, acute ATR
PROLIFERATION, INFLAMMATION, PROLIFERATIVE
In this study, the proteomic composition of good versus poor ATR repair was quantitatively characterized during both the inflammatory and proliferative phases of healing in patients with acute ATR. By combining data from tissue biopsies representing the inflammatory healing stage from the first week after injury and mi...
PMC10512081
Data availability statement
MS proteomic data files are deposited at the ProteomeXchange Consortium (
PMC10512081
Ethics statement
The studies involving humans were approved by Regional Ethical Review Committee in Sweden (Reference no. 2009/2079-31/2: 2013/1791-31/3). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this st...
PMC10512081
Author contributions
DAH
The project organization, training, resources and funding acquisition by PWA and ASA; Data analysis by JW; Data curation by JW, ZZ and JC; Visualization by JW, ZZ, DAH and ASA; Experiment completed by JC; Writing original draft by JC; Manuscript reviewing and editing by ZZ, DAH, PWA and ASA.
PMC10512081
Acknowledgments
We would like to thank LB for the collection of human samples and Dr. AV at the Proteomics Biomedicum, Karolinska Institutet, Sweden for excellent help in MS data analysis and interpretation.
PMC10512081
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.
PMC10512081
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 ...
PMC10512081
Supplementary material
The Supplementary Material for this article can be found online at: Click here for additional data file.Click here for additional data file.Click here for additional data file.
PMC10512081
References
PMC10512081
Background
CHILDHOOD OBESITY
Early childhood obesity interventions supporting parents have the largest effects on child weight status. However, long-term follow-ups are lacking.
PMC10599998
Objective
obesity
OBESITY
To examine weight status 48 months after obesity treatment initiation for 4- to 6-year-olds.
PMC10599998
Methods
177 families were recruited to the More and Less study, a 12-month randomized controlled trial (RCT) conducted in Sweden (2012–2017); 6 children were excluded due to medical diagnoses. Thus, 171 families (non-Swedish origin 59%, university degree 40%) were eligible for this 48-month follow-up with modified intention-to...
PMC10599998
Results
After 48 months (mean 50 months, range 38–67 months) mean (95% CI) BMI-SDS was reduced in all groups: PGB −0.45 (−0.18 to −0.73,
PMC10599998
Conclusion
CHILDHOOD OBESITY
The intensive parent-support early childhood obesity intervention led to better weight status outcomes over time, though BMI-SDS alone did not reflect this. Further research should investigate how to assess weight changes in growing children.
PMC10599998
Clinical trial registration
Clinicaltrials.gov,
PMC10599998
Subject terms
PMC10599998
Introduction
Obesity, obesity
OBESITY, OBESITY, CHILDHOOD OBESITY
Obesity among young children is at unprecedented high levels: in the US, 15% of children under 5 years of age have obesity [The purpose of this study was to follow up the diverse population of children who took part in the ML trial, to examine their weight status after 48 months; this allows us to evaluate the long-ter...
PMC10599998
Methods
PMC10599998
Design
CHILDHOOD OBESITY
The ML study was a 12-month open-label, non-blinded, childhood obesity RCT assessing the effects of a 10-week parent support program, with and without telephone-based booster sessions, compared to standard treatment [
PMC10599998
Participants
obesity, Obesity
OBESITY, OBESITY
Families enrolled in the ML study were recruited from 68 primary healthcare centers in the Stockholm region, and some self-referred through advertisements in local newspapers and bulletin boards. Families were eligible for participation if the child was 4-6 years old, had obesity according to the International Obesity ...
PMC10599998
Randomization
Families were randomized in a 1:1:2 scheme to the parent support treatment group with (PGB) and without booster sessions (PGNB) and standard treatment (ST), enabling comparison between two groups, parent program (PGB, PGNB) and ST, and between three groups, PGB, PGNB and ST. To reduce possible bias, families and group ...
PMC10599998
Treatment approaches and settings
PMC10599998
Intervention
Families in the PGB and PGNB received the ML parent support program. The ML program is based on the Keeping Foster and Kinship Parents Supported and Trained (KEEP) program from Oregon Social Learning Center, US. Details about KEEP [
PMC10599998
Standard treatment
obesity
OBESITY, CHILDHOOD OBESITY
Families randomized to ST were referred to one of 14 pediatric outpatient clinics for obesity treatment. Both the parent(s) and the child attended treatment based on the action plan for childhood obesity treatment in Stockholm [
PMC10599998
Statistical analysis
SECONDARY
Modified intention-to-treat analysis with linear mixed model compared the effects of treatment on the primary outcome of BMI-SDS, secondary outcomes BMI and WC, and post-hoc outcome %IOTF25 from baseline to 48 months. Data were approximately normally distributed as assessed by histograms. Based on marked differences fo...
PMC10599998
Results
From the original sample of 177 children, 6 children were excluded due to developing medical diagnoses incompatible with inclusion criteria. Thus, 171 qualified for the modified intention-to-treat-analysis, 19% (Study participant flow chart.Baseline characteristics are presented in Table Graphical presentation of indiv...
PMC10599998
Attendance of clinical visits between 12 and 48 months
Of the 114 children with BMI data (i.e., without imputation), between 12–48 months after treatment initiation, 62% (
PMC10599998
Change in weight status (baseline to 48 months)
In all groups, BMI-SDS, mean (95% CI), decreased over time (baseline to 48 months), for PGB −0.45 (−0.73 to −0.18), PGNB −0.34 (−0.55 to −0.13) and ST −0.25 (−0.40 to −0.10), Fig.
PMC10599998
Clinical significance
At 48 months, the probability (95% CI) of a clinically significant ≥0.5 BM-SDS reduction was twice as likely, RR = 2.03 (1.27 to 3.27,
PMC10599998
Sensitivity analysis
We investigated if variability in attendance had an effect on the overall findings by including number of visits as a covariate to the primary model; however, no significant effect on the results was found (data not shown). Additionally, we separately analysed the timeframe 12 to 48 months; the results were in the same...
PMC10599998
Discussion
obesity
OBESITY, CHILDHOOD OBESITY
This study is the first to report on the long-term follow-up of a 12-month obesity treatment among a diverse population of preschool-age children. Weight change was analyzed with four different metrics: BMI-SDS, BMI, WC and %IOTF25. We observed that all groups of children, independently of randomization, reduced their ...
PMC10599998
Strengths and limitations
obesity
OBESITY
This is the largest RCT assessing a parent program for preschool-aged children with obesity. The sample is heterogenous, with most families reporting low or median incomes and diverse ethnic origin, which strengthens the generalizability of our results. A unique feature of this study is the long-term follow-up, which p...
PMC10599998
Future studies
eating behavior
SECONDARY
We will examine the other secondary outcomes of ML at 48 months, including child eating behavior, metabolic health, blood chemistry and parental feeding practices and mental wellbeing, to better understand the mechanisms leading from treatment to outcomes. Furthermore, the heterogeneity of treatment response, as shown ...
PMC10599998
Conclusion
obesity
OBESITY, CHILDHOOD OBESITY
To strengthen the evidence-base for early childhood obesity treatment, long-term results from RCTs are needed. In this study, the long-term development of weight status 48 months after an obesity treatment intervention was analyzed through four different metrics. In three out of the four, the most intensive treatment –...
PMC10599998
Supplementary information
The online version contains supplementary material available at 10.1038/s41366-023-01373-7.
PMC10599998
Acknowledgements
We thank all participating families, child health care and school nurses, and all personnel who contributed to data collection in pediatric outpatient clinics. We would also like to acknowledge the previous members and collaborators in the More and Less study for their valuable contributions.
PMC10599998
Author contributions
AE obtained funding, conceptualized, and designed the study, supervised data collection, drafted, revised, and critically reviewed the manuscript for important intellectual content. MB carried out the initial analyses, drafted, revised, and critically reviewed the manuscript for important intellectual content. AE and M...
PMC10599998
Funding
This study was supported by the Frimurare Barnhuset Foundation and Center for Medical Innovation (CIMED) funding (SLL20190383). Open access funding provided by Karolinska Institute.
PMC10599998
Data availability
Data will not be made publicly available but shared upon request by qualified researchers in accordance with approval by regulatory body.
PMC10599998
Competing interests
The authors declare no competing interests.
PMC10599998
References
PMC10599998
1. Introduction
inflammation, cancer and neurodegenerative disorders
DISEASE, INFLAMMATION, OXIDATIVE STRESS, CARDIOVASCULAR DISEASE
Grape consumption acts on the immune system to produce antioxidant and anti-inflammatory effects. Since immune activity demonstrates circadian rhythmicity, with peak activity occurring during waking hours, the timing of grape intake may influence the magnitude of its antioxidant effect. This study followed a 2 × 2 fact...
PMC10419126
2. Materials and Methods
PMC10419126
2.1. Materials and Reagents
EMD
Resveratrol, L-(+)-tartaric acid, quercetin, (+)-catechin hydrate sulfatase (Helix pomatia, Type H-1, sulfatase ≥ 10,000 units/g), and β-glucuronidase (Helix pomatia, Type HP-2, ≥100,000 units/mL) were purchased from Sigma-Aldrich (St. Louis, MO, USA). 8-iso prostaglandin F2α and 8-iso prostaglandin F2α-d4 were purchas...
PMC10419126
2.2. Study Design
MAY, OXIDATIVE STRESS
The Idaho State University Institutional Review Board, Human Subjects Committee approved the study protocol IRB-FY2021-264. Participants provided written informed consent. Enrollment occurred between September 2021 and May 2022. The study’s clinical trials registry identification is IRB-FY2021-264 at ClinicalTrials.gov...
PMC10419126
2.3. Participants
OXIDATIVE STRESS
Healthy men (Potential participants completed a scripted telephone screening questionnaire to assess eligibility. Those who passed the telephone screening then completed an in-person lab visit with the principal investigator that included a detailed study description, the informed consent process, and instruction on fo...
PMC10419126
2.4. Dietary Assessment
Cancer
CANCER
During the laboratory visit, after the meal was completed, participants answered a diet history questionnaire to provide data on usual dietary intake. A research staff member administered to participants the National Cancer Institute’s online Diet History Questionnaire version III (DHQ III, National Institutes of Healt...
PMC10419126
2.5. Intervention
inflammation
INFLAMMATION, OXIDATIVE STRESS
The intervention was composed of two factors: treatment and time. The treatment factor served as the antioxidant agent and was a grape drink or placebo. The time factor served as the modulator of the effect of the agent on the oxidative stress challenge (high-fat meal) and was morning or evening. The grape drink consis...
PMC10419126
2.6. Anthropometric Measurements, Urine Collection and Biomarker/Metabolite Analysis
OXIDATIVE STRESS
Upon arrival at the laboratory visit, height was measured to the nearest 0.1 cm using a stadiometer and weight was measured to the nearest 0.1 kg using a beam scale. Body mass index was calculated as (weight in kg)/(height in meters)A baseline urine sample was collected during the laboratory visit before test meal cons...
PMC10419126