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Material and methods
PLAQUE, SECONDARY
In total, 35 young adolescents (14–18 years) under treatment with fixed appliances were consecutively enrolled and randomly allocated to an experimental or a placebo group by opening a computer-generated numbered envelope. The subjects were instructed to rinse twice daily during an intervention period of 8 days with ex...
PMC9912700
Results
In total, 28 adolescents (21 females and 7 males) completed the trial and there were no differences in age, clinical, or microbial findings between the test (
PMC9912700
Harms
nausea
ADVERSE EVENTS
In total, one participant in the test group claimed nausea and abandoned the project. In total, two participants did not like the taste of the mouthwash but used it as instructed. No other adverse events or side effects were reported.
PMC9912700
Limitations
Short-term pilot trials may by nature be sensitive for selection and performance biases and are not designed to unveil persisting effects.
PMC9912700
Conclusion
Daily use of enzyme-containing mouthwash reduced the amount of dental biofilm in adolescents under treatment with the fixed orthodontic appliances, without affecting the composition of the salivary microbiota.
PMC9912700
Ethical approval
Approved by the Regional Ethical Board, Lund, Sweden (Dnr 2020-05221).
PMC9912700
Clinical Trial Registration
NCT05033015.
PMC9912700
Introduction
Caries, caries
DISEASE, CARIES, CARIES
Caries is a biofilm-mediated disease and public health problem with social and economic consequences for individuals, communities, and countries (For many decades, caries was regarded as an infectious transmissible disease with Treatment with fixed orthodontic appliances is associated with impaired oral hygiene and dys...
PMC9912700
Materials and methods
PMC9912700
Study design, ethical approval, and registration
The pilot study employed a randomized, double-blind placebo-controlled design with two parallel arms. The project was approved by the Swedish ethical review authority, Sweden (Dnr 2020-05221) and registered in Clinical Trials.gov Identifier (NCT05033015).
PMC9912700
Subjects
caries lesions, allergy, allergies
ALLERGY, PERIODONTAL DISEASE, ALLERGIES, FOOD ALLERGIES, PATHOLOGY
We invited 60 eligible patients (14–18 years) at the Orthodontic Specialist Clinic in Karlshamn, Sweden to enter the study. The subjects were consecutively enrolled and the inclusion criteria were: 1. being under treatment with fixed orthodontic appliances (uni- or bi-maxillary) for at least 3–6 months and 2. visible b...
PMC9912700
Intervention and test products
tooth brushing from mouth
We provided all the subjects with a standardized enzyme-free toothpaste with 1450 ppm sodium fluoride to be used twice daily during the course of the study. After the baseline clinical registration, we asked the participants to rinse their mouth thoroughly by swishing 10 ml of the assigned liquid around the teeth morni...
PMC9912700
Clinical registrations and endpoints
The primary outcome was the amount of dental biofilm around the orthodontic brackets and one principal examiner (TH) performed the registrations at baseline and after 8 days. To visualize the biofilm, teeth were illuminated with a violet UV light in detection mode (D-Light Pro, GC Europe). The biofilm was then scored a...
PMC9912700
Saliva sampling and analyses
The examiner collected unstimulated whole saliva samples at baseline and after 8 days before the biofilm scoring. The subjects rinsed with tap water, accumulated saliva in their mouth and expectorated in a capped plastic tube (approximately 1.0 ml). The tube was immediately frozen and stored at −18°C until transportati...
PMC9912700
Side effects
All the possible subjectively perceived side effects during the intervention were immediately reported to the clinical investigator and the subjects could discontinue their participation at any time without further motivation.
PMC9912700
Power calculation and statistical methods for clinical data
Due to the lack of previous clinical data with respect to the experimental mouth rinse, we anticipated that a mean difference of 0.5 OPI units (SD 0.4) would be clinically meaningful. A calculation with
PMC9912700
Bioinformatics and statistical analysis of the saliva microbiome samples
A complete description is provided in
PMC9912700
Results
PMC9912700
Baseline data
MAY
The mean age was 15.4 years in the test group and 16.8 years in the placebo group. The most common orthodontic treatment indication was moderate-to-severe crowded dental arches and 18 patients had 2–4 premolars extracted. All the patients had pre-adjusted fixed orthodontic appliances (0.022 slot size, MBT prescription,...
PMC9912700
Clinical findings
PLAQUE
Subjects in the placebo group had a slightly higher mean OPI value at baseline but the difference was not statistically significant compared with the test group (Orthodontic plaque index (OPI) on subject level (Differences were tested with an unpaired two-sided Relative change in orthodontic plaque index (OPI) scores f...
PMC9912700
Microbial findings
We display the baseline composition of the salivary microbiome at Genus level and the most abundant taxa in (A) Stacked bar plot showing the relative abundance in the percentage of the 11 most abundant genera for each baseline sample ((A) Boxplot showing the log2 ratio of the relative abundance of the eight significant...
PMC9912700
Side effects
nausea
ADVERSE EVENTS
One participant in the test group claimed nausea and ‘weird taste’ and abandoned the project after the first day. Two participants did not like the taste of the mouthwash but used it as instructed. No other adverse events, or side effects, were reported to the investigators. All the participants except one returned all...
PMC9912700
Discussion
’, tooth
SECONDARY
Treatment with fixed orthodontic appliances interferes with mechanical tooth cleaning which results in the accumulation of dental biofilm, in particular, among patients with irregular tooth-brushing habits. Our intention with this pilot study was, therefore, to evaluate the possible effects of the enzyme-based mouthwas...
PMC9912700
Strengths and limitations
throat, tooth brushing
The strength of this project was the robust randomized double-blinded placebo-controlled design and the clinical scoring was robust and reliable. The efficacy of tooth brushing has an effect on biofilm formation. However, the two groups were under orthodontic treatment for at least 3 months before the start of the tria...
PMC9912700
Conclusion
orthodontic, tooth
A twice-daily use of an enzyme-containing mouthwash decreased the amount of dental biofilm in adolescents with fixed orthodontic appliances over an 8-day period without significantly affecting the composition of the salivary microbiome. The results of this pilot study indicate that the mouthwash, when applied in adjunc...
PMC9912700
Supplementary Material
Click here for additional data file.
PMC9912700
Acknowledgements
The authors thank Dr. Mette Rose Jørgensen at Novozymes A/S for the excellent cooperation.
PMC9912700
Funding
The project was conducted in accordance with the ethical standards of the Helsinki Declaration and its revisions. This study was funded by the author’s institutions and supported by Novozymes A/S, Denmark (NZ-OHBFC 2020-05).
PMC9912700
Conflict of interest
LBSH is an employee of Novozymes A/S. The other authors have no conflict of interest to declare.
PMC9912700
Data Availability
The data underlying this article were provided by Region Blekinge under license/by permission. Data will be shared on request to the corresponding author with permission of Region Blekinge.
PMC9912700
References
PMC9912700
Subject terms
inflammation
INFLAMMATION
The optimal functioning of the liver is essential for athletic performance. It is necessary to maintain the liver’s enzymes at an optimal level so that liver cells can be protected from inflammation or damage. This study investigated the effects of a 12-week aerobic exercise program on the liver function of adult athle...
PMC10256744
Introduction
Liver malfunction, non-alcoholic fatty liver disease, disbalance of enzymes of the liver, inflammation, muscle movements
INFLAMMATION, ADVERSE EFFECTS, NON-ALCOHOLIC FATTY LIVER DISEASE
The liver carries out the detoxification of various metabolites, the production of digestive enzymes and the synthesis of proteins, which is situated in the right upper quadrant of the body and beneath the diaphragm. In addition, the liver’s functions are the metabolism, control of red blood cells (RBCs), and productio...
PMC10256744
Methods and material
PMC10256744
Participants
non-alcoholic fatty liver
BLIND, NON-ALCOHOLIC FATTY LIVER
This study used a pretest–posttest experimental design. The sample size was estimated as 14 in each group by using the G* power software V 3.1.9.2 based on a previous study which compared the efficacy of aerobic training and resistance training on liver enzyme levels in patients with non-alcoholic fatty liver using the...
PMC10256744
Experimentation
The CG was under rigorous supervision and did not participate in any structured exercise program besides their regular soccer practice. The EG was well-versed in their assigned training program and performed the experimental procedure only for 12 weeks. Both groups were allowed to practice their regular soccer practice...
PMC10256744
Training program
The aerobic exercise program which was given to the EG was a series of treadmill exercises, including slow, medium, and fast walking; walking with a 30° incline (uphill); walking with a 30° declination (downhill); jogging with a 30° incline (uphill); running with a 30° declination (downhill); and cycling
PMC10256744
Outcome measures
BLOOD
Blood levels of the following substances were taken as outcome measures.Bilirubin-total mg/dL,Serum AST/SGOT (U/L),Serum ALT/SGPT (U/L),Alkaline phosphatase (U/L),Protein-total (g/L),Albumin (g/dL),Globulin (Gm/dL).
PMC10256744
Analysis of data
LIVER
The data of 30 participants (15 in each group) were analyzed using the SPSS statistical software version 20 (SPSS Inc., Chicago, IL, USA). Liver function was analyzed for both pre-test and post-test of all the participants. For 12 weeks, the EG did their assigned activities, which were designed as an aerobic training p...
PMC10256744
Results
PMC10256744
Discussion
hemolysis
HEMOLYSIS
The training effect is the physiological changes that occur due to frequent involvement in exercise programs. The nature of training programs has its effects, which means different training programs produce different kinds of effects on physiological and biochemical parameters. The optimal training programs are one tha...
PMC10256744
Conclusion
In conclusion, the current study shows that a selected aerobic training program has a good impact on some biochemical variables of the liver, such as bilirubin and globulin, in a healthy adult male athlete. The 12 weeks of aerobic training used in the study can potentially improve the liver function of adult athletes.
PMC10256744
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-36361-4.
PMC10256744
Acknowledgements
The authors are grateful to the Researchers Supporting Project number (RSP2023R382), King Saud University, Riyadh, Saudi Arabia for funding this research.
PMC10256744
Author contributions
M.A.B., M.A.M., H.A.A., J.A.P., and A.A. conceptualized the study and its methodology. M.A.B., M.A.M., H.A.A., J.A.P., and A.A. were involved in data collection and curation. M.A.B., M.A.M., H.A.A., J.A.P., A.A., and M.K. wrote the original draft and final version. M.A.B., M.A.M., H.A.A., J.A.P., and A.A. did data anal...
PMC10256744
Funding
Researchers Supporting Project number (RSP2023R382), King Saud University, Riyadh, Saudi Arabia.
PMC10256744
Data availability
The data associated with the paper are not publicly available but are available from the corresponding author on reasonable request.
PMC10256744
Competing interests
The authors declare no competing interests.
PMC10256744
References
PMC10256744
Subject terms
TNBC
TRIPLE-NEGATIVE BREAST CANCER
Immunotherapy combined with chemotherapy has been demonstrated to be effective in early triple-negative breast cancer (TNBC). In this single-arm, phase II study with Simon’s two-stage design, we investigated the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy in patients with early TNBC (NCT04213898)....
PMC10589334
Introduction
heterogeneous disease, TNBC, death, breast cancer
TRIPLE-NEGATIVE BREAST CANCER, RECURRENCE, METASTASES, BREAST CANCER
Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by lack of or minimal expression of estrogen receptor (ER) and progesterone receptor (PR) and lack of overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2). It accounts for almost 15%−20% of all breast cancer ...
PMC10589334
Results
PMC10589334
Patient characteristics
Between January 3, 2020 and October 25, 2021, 97 patients were screened for eligibility, and 39 were enrolled (Fig. 
PMC10589334
Efficacy
DISEASE
In the first stage, eight (88.9%) of the nine patients initially enrolled achieved a pCR, exceeding the threshold required for proceeding to the second stage of enrollment. Among 39 patients finally enrolled, 25 (64.1%, 95%CI: 47.2, 78.8) achieved a pCR (ypT0/Tis ypN0). A total of 35 patients achieved a partial respons...
PMC10589334
Subgroup analysis of pCR.
Data are presented as percentage and 95% confidential interval (CI). The
PMC10589334
Discussion
death, tumor, HR-low tumors, breast cancer, toxicity, cancer, triple-negative tumors, TNBC, tumors, TNBCBreast cancer
TUMOR, BREAST CANCER, ADVERSE EVENTS, CANCER, RESIDUAL DISEASE, HAND PRESENTATION, TUMORS
In this single-arm phase II trial, neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin achieved a pCR rate of 64.1% in patients with early TNBC. Treatment-related adverse events of grade 3 or 4 occurred in 76.9% of patients. No grade 5 treatment-related adverse events occurred. Our study meets the primary endpo...
PMC10589334
Methods
PMC10589334
Study design and patients
basal cell carcinoma of the skin), tumor, Tumor, non-metastatic (stage IIA-IIIC, TNBC, malignant diseases, Cancer
TUMOR, METASTASIS, TUMOR, MALIGNANT DISEASE, CERVICAL CARCINOMA IN SITU, ONCOLOGY, METASTATIC BREAST CANCER, CANCER
This investigator-initiated single-arm, open-label, phase II trial was conducted at the Affiliated Cancer Hospital of Zhengzhou University in China. The study was performed in compliance with the Good Clinical Practice guideline and Declaration of Helsinki (revised in 2013). The study protocol and any amendments were a...
PMC10589334
Treatments
SENTINEL LYMPH NODE
Patients were treated with neoadjuvant camrelizumab plus chemotherapy every three-week for six cycles. Camrelizumab was administered intravenously at 200 mg on day one of every three-week cycle. Chemotherapy consisted of nab-paclitaxel at 125 mg/mPatients who either discontinued or completed the neoadjuvant therapy cou...
PMC10589334
Study endpoints and assessment
tumor, Tumor, toxicity, Tumors, Cancer
ADVERSE EVENT, TUMOR, TUMOR, ADVERSE EVENTS, TUMORS, SECONDARY, CPS, CANCER
The primary endpoint was pCR, defined as the percentage of patients with no evidence of viable tumor cells in both breast and sampled lymph nodes (ypT0/Tis ypN0) (14−15). The secondary endpoints included safety, objective response rate, event-free survival, disease-free survival, and distant disease-free survival.Tumor...
PMC10589334
Statistical analysis
We used Simon’s two-stage design. Previous studies of neoadjuvant anthracycline-taxane-based chemotherapy showed a pCR rate of 30%−40% in TNBCFor the endpoints of pCR and objective response rate, the point estimate and 95% confidential intervals (CIs) were summarized descriptively using the Clopper-Pearson method. Post...
PMC10589334
Reporting summary
Further information on research design is available in the 
PMC10589334
Supplementary information
Supplementary InformationPeer Review FileReporting Summary
PMC10589334
Supplementary information
The online version contains supplementary material available at 10.1038/s41467-023-42479-w.
PMC10589334
Acknowledgements
This study was supported by Jiangsu Hengrui Pharmaceuticals Co., Ltd., which provided camrelizumab free of charge. We thank all the patients, their families, and the medical staff who participated in this study. We also thank Zheng Pang, Yufen Xiang, Yuyu Du, and Jinyun Sun from Jiangsu Hengrui Pharmaceuticals Co., Ltd...
PMC10589334
Author contributions
Z.Lu
PATHOLOGY
All authors verify that this study was done per protocol and vouch for data accuracy and completeness. All authors reviewed and edited the manuscript, provided final approval to publish, and agreed to be accountable for all aspects of the article. C.W. Z.Liu., X.C., J.Q., Z.Lu., L.L. X.S. and C.Z. contributed to the de...
PMC10589334
Peer review
PMC10589334
Data availability
The study protocol is available as Supplementary Note in the
PMC10589334
Competing interests
The authors declare no competing interests.
PMC10589334
References
PMC10589334
Background
weight loss
Both low‐carbohydrate (LC) and calorie-restricted (CR) diets have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a 12-week randomized trial to compare the effects of these diets separately and in combination on both weight loss and metabolic risk factor...
PMC10210464
Methods
A total of 302 participants were randomized to LC diet (
PMC10210464
Results
A total of 298 participants were analyzed. BMI change over 12 weeks was − 0.6 (95% CI, − 0.8 to − 0.3) kg/m
PMC10210464
Conclusions
weight loss, overweight/obese
The reduction of carbohydrate intake without restricting caloric intake is more potent to achieve weight loss over 12 weeks when compared to a calorie-restricted diet in overweight/obese adults. The combination of restricting carbohydrate and total calorie intake may augment the beneficial effects of reducing BMI, body...
PMC10210464
Trial registration
The study was approved by the institutional review board of Zhujiang Hospital of Southern Medical University and registered at the China Clinical Trial Registration Center (registration number: ChiCTR1800015156).
PMC10210464
Supplementary Information
The online version contains supplementary material available at 10.1186/s12916-023-02869-9.
PMC10210464
Keywords
PMC10210464
Background
Obesity, obesity, weight loss, metabolic abnormalities
OBESITY, OBESITY
Obesity and its associated metabolic abnormalities have become a major public health challenge worldwide. From 1993 to 2015, obesity (BMI ≥ 27.5 m/kgDietary interventions have been proven to be an effective method for weight loss [In this study, we aimed to conduct a 12-week randomized controlled trial to compare the c...
PMC10210464
Methods
PMC10210464
Study design and participants
This study was a multicenter, randomized, parallel-group clinical trial with participants allocated in a 1:1:1:1 ratio to normal control (NC) diet, low-carbohydrate (LC) diet, calorie-restricted (CR) diet, or LC + CR diet for 12 weeks. The randomization schedules were generated using a centrally controlled, computer-ge...
PMC10210464
Diet interventions
Participants in the NC group were designed to follow a non-restricted calorie diet with 55–65% of calories from carbohydrates, 30% from fat, and 20% from protein. The CR diet group restricted daily calories to 1200–1500 kcal/day with 55–65% of calories from carbohydrates, 30% from fat, and 20% from protein. Participant...
PMC10210464
Outcomes and follow-up
BLOOD, SECONDARY, INSULIN RESISTANCE
The primary outcome was change in body mass index (BMI). The secondary outcomes included changes in body weight, body fat, waist circumference, waist-to-hip ratio (WHR), and metabolic risk factors. Body fat was quantified using IOI353 Body Composition Analyser (Jawon Medical, Gyeongsansi, South Korea). Blood samples we...
PMC10210464
Statistical analysis
Based on data from previous studies [All analyses were conducted in both the ITT and completer samples. A mixed-effects model was used to assess the effects of diet programs on the change in BMI, and an autoregressive correlation matrix was used to correct within-participant correlation for repeated measurements. In th...
PMC10210464
Results
PMC10210464
Dietary intake and adherence
The four groups reported similar physical activity during 12 weeks (Additional file Energy and nutrition intake during follow-upDuring the 12-week intervention, the mean (± SD) percentage of the days that participants adhered to both the prescribed calories and carbohydrates was 84.9 ± 32.3% in the NC group, 90.3 ± 21....
PMC10210464
Adverse events
deaths
ADVERSE EVENTS, ASYMPTOMATIC HYPOGLYCEMIA
No deaths or serious adverse events were reported throughout the study. One participant in the CR diet group reported asymptomatic hypoglycemia and one in the LC + CR diet group reported gastrointestinal surgery because of small polyps.
PMC10210464
Discussion
obese, weight loss
OBESE
In this multicenter study, we test the hypothesis that a reduction of carbohydrate intake without restricting caloric intake was more effective on weight loss when compared to a calorie-restricted diet in overweight/obese adults. Our findings align with some previous studies. Samaha et al. [Our results indicated that a...
PMC10210464
Conclusions
weight loss, overweight/obese
In this study, we dissect the effects of calories and carbohydrates and highlight the important of carbohydrate restriction, and not solely reduced caloric intake is more important to achieve weight loss over a 12-week period. The combination of restricting carbohydrate and total calorie intake may augment the benefici...
PMC10210464
Supplementary Information
weight loss
Additional file 1. The trial protocol.Additional file 2: Fig. S1. Adherence to the prescribed diets over 12 weeks. Fig. S2. Metabolites changes of LC diet and CR diet at baseline and 12 weeks. Table S1. Food profile of diet interventions. Table S2. Baseline characteristics of study participants included in completer a...
PMC10210464
Acknowledgements
The authors thank the study participants for their cooperation. The authors thank Guangzhou Nanda Fit Nutrition and Health Consulting Co., Ltd., for the donations in support of the nutrition bar.
PMC10210464
Authors’ contributions
The authors read and approved the final manuscript. JS, YTR, NNX, and PLW contributed equally to this work. JS, NNX, YTR, and PLW had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: HC, JS, NNX, YTR, PLW, NL,...
PMC10210464
Funding
This study was partly supported by the National Natural Science Foundation of China (Grant NO: 82170859, 82100860, 81974117, 82074207), the Natural Science Foundation of Guangdong Province (Grant No.: 2021A1515010785, 2019A1515110658, 2019A1515010665), and Guangzhou Science and Technology Project (Grant No.: 2018030100...
PMC10210464
Availability of data and materials
Please contact the corresponding authors to discuss the availability of the datasets used and/or analyzed during the current study.
PMC10210464
Declarations
PMC10210464
Ethics approval and consent to participate
The study was approved by the institutional review board of Zhujiang Hospital of Southern Medical University and registered at the China Clinical Trial Registration Center (registration number: ChiCTR1800015156). All participants provided written informed consent before enrollment.
PMC10210464
Consent for publication
Not applicable.
PMC10210464
Competing interests
The authors declare that they have no competing interests.
PMC10210464
References
PMC10210464
Subject terms
bipolar disorder, cognitive dysfunction
SECONDARY, CORTEX
A more effective and better-tolerated site for repetitive transcranial magnetic stimulation (rTMS) for treating cognitive dysfunction in patients with bipolar disorder (BD) is needed. The primary visual cortex (V1) may represent a suitable site. To investigate the use of the V1, which is functionally linked to the dors...
PMC10250373
Introduction
chronic disorder, Bipolar disorder, mania, bipolar disorder, hypomania, depression
CHRONIC DISORDER, RETINA, CORTEX
Bipolar disorder (BD) is a chronic disorder with recurrent periods of depression and mania or hypomania. It has a lifetime prevalence of 2.4% for the bipolar disorder spectrum and affects over 1% of the global population [Thus, it is useful to focus not only on improvement in the emotional symptoms of BD in interventio...
PMC10250373