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Authors’ contributions
All authors (SA, EH, IJ, LA and AF) contributed to conceptualizing the study. SA wrote the first draft and all authors participated in revising the final draft. SA and AF conducted the initial analyses. EH contributed with the statistical analysis. All authors contributed to validating the analyses and have approved th...
PMC10585814
Funding
ALF
This work was supported by the Swedish Research Council for Health, Working Life and Welfare (reference number 2016–07418, 2017 − 00557 and 2019 − 01726) and was financed by grants from the Swedish state under the ALF agreement between the country councils and the Swedish government (ALFGBG-772191 and ALFGBG-932659).Op...
PMC10585814
Data availability
As dictated by the ethical body that approved the study and the promise to participants in their informed consent, the raw study data cannot be shared publicly as the data contain potentially identifying or sensitive patient information. The datasets used and/or analyzed during the current study are available from the ...
PMC10585814
Declarations
PMC10585814
Ethical approval and patient consent
Ethical approval was obtained from the Regional Ethical Review Board in Gothenburg, Sweden (DNr 497 − 17). Informed consent was obtained from all subjects and/or their legal guardian(s). All methods were carried out in accordance with relevant guidelines and regulations.
PMC10585814
Consent for publication
Not applicable.
PMC10585814
Competing interests
The authors declare no competing interests.
PMC10585814
References
PMC10585814
Objectives
orthodontic
Academic Editor: Vikram Dalal This study aimed to evaluate the effects of different cleaning regimes of acrylic-based removable orthodontic appliances on bacterial biofilm formation and whether the surface modification, i.e., polished acrylic fitting surface, reduces biofilm formation.
PMC10586913
Materials and Methods
thirty-nine orthodontic, denture, orthodontic
This double-blind, parallel, randomized clinical trial involved thirty-nine orthodontic patients indicated for removable orthodontic appliances. The patients were allocated into three groups according to the cleaning method: brushing with a denture brush and chlorhexidine (CHX) toothpaste, Lacalut cleaning tablet, and...
PMC10586913
Results
There was no significant difference among the three cleaning methods on the polished or unpolished tiles. However, in polished tiles, streptococci were significantly reduced in all cleaning methods, whereas staphylococci and
PMC10586913
Conclusions
Polishing the fitting surface of an acrylic-based orthodontic appliance reduced the tested bacterial biofilm formation and may enhance cleaning efficiency. Brushing and combination methods showed superior cleaning effects compared to cleaning tablets. This trial is registered with
PMC10586913
1. Introduction
orthodontic, malocclusions
ADHESION
People seeking orthodontic treatment have increased not only to correct their malocclusions but also to improve mastication, speech, appearance, overall health, comfort, and self-esteem [Maintaining good oral hygiene is integral to successful orthodontic treatment [This clinical trial was designed to compare the effect...
PMC10586913
2. Methods
PMC10586913
2.1. Trial Design
This double-blind, parallel, randomized clinical trial was approved by the Ethical and Board Committee of College of Dentistry, University of Baghdad (issue no. 598/April 2022), and registered under protocol ID ClinicalTrials.gov:
PMC10586913
2.2. Participants
orthodontic
MINOR
Thirty-nine subjects were recruited from the Department of Orthodontics at the College of Dentistry. Those included 24 females and 15 males aged 16–31 (a mean of 23.1 years). Those patients fulfilled the following criteria [Patients who were clinically fit and healthy and had no history of systemic diseasesPatient who ...
PMC10586913
2.3. Randomization
A computer random number generator developed a simple, nonstratified randomization of three groups (
PMC10586913
2.4. Allocation Concealment
It was accomplished using an opaque and sealed pack marked with a treatment allocation code. Each pack contained the allocated cleaning materials and an instruction card that an independent person gave.
PMC10586913
2.5. Interventions
PMC10586913
2.5.1. Construction of Removable Appliance with Acrylic Tiles of Different Surface Textures
Acrylic tiles (5.5 mm × 1 mm) of two surface textures were made from an acrylic block of 1 mm thickness using a mould of silicone rubber (Rema® Sil silicone duplicating material, Dentaurum, Ispringen, Germany) [After obtaining the consent form, an impression was taken on the maxillary arch using alginate impression mat...
PMC10586913
2.5.2. Patient Grouping
denture
The patients were randomly divided into three groups:Lacalut cleaning tablet group: Patients were instructed to use one tablet (LacalutDent, Lacalut, Germany) dissolved in 150 ml of tap water. The appliance was soaked for 20 minutes and then washed with tap water.Brushing with CHX toothpaste group: Patients were instru...
PMC10586913
2.5.3. Sample Collection
STERILE
A CONSORT flow diagram illustrating subjects' flow during the clinical trial was followed (After seven days of wearing the appliance, three acrylic tiles of each roughness category were gently removed from their wells using a metal pin through the chimney-like structure without disturbing the biofilm. The tiles were he...
PMC10586913
2.5.4. Scanning Electron Microscope (SEM)
The fourth acrylic tile (of each roughness category) was removed from the appliance aseptically and immersed carefully in a Petri dish containing PBS (Sigma-Aldrich). The sample was prepared for SEM using a previously suggested protocol [
PMC10586913
2.6. Statistical Analysis
Data from the colony-forming unit (CFU) using different cleansing methods were compared, following log transformation, using one-way analysis of variance (ANOVA). The polished and unpolished tiles were compared for biofilm formation on each cleansing method using independent
PMC10586913
3. Results
The results showed no significant difference among different cleaning methods regarding staphylococci, streptococci, and total anaerobic bacterial biofilm on polished tiles (Similarly, there was no significant difference among different cleaning methods regarding the tested bacterial biofilm on unpolished tiles ( The S...
PMC10586913
4. Discussion
cleft lip, MPS, orthodontic, palate
ADHESION
This randomized clinical trial was designed to compare the effects of mechanical and chemical cleansing methods on bacterial biofilm attached to acrylic-based removable orthodontic appliances. It was reported that the prevalence of opportunistic pathogens was higher in PMMA-based intraoral devices such as feeding appli...
PMC10586913
4.1. Study Limitations
diabetes
DIABETES
There are limitations encountered in the current study. These include the microbial diversity between individuals and the response of bacterial species to individual cleaning methods.Furthermore, this study was conducted on clinically fit and healthy patients, and further investigation may widen the scope of its novelt...
PMC10586913
5. Conclusion
The study found that polishing the acrylic surface significantly reduced bacterial biofilm, regardless of the cleansing method used. Furthermore, brushing and the combination cleaning methods showed superior cleaning efficacy compared to the Lacalut cleaning tablet for all tested bacteria in polished acrylic samples.
PMC10586913
Acknowledgments
The authors would like to thank Ms. Samar Qahtan, the technical manager at the Orthodontic Department/College of Dentistry, University of Baghdad, for her help with the appliance fabrication. The authors would also like to thank ClinicalTrials.gov for providing a valuable platform for the registration and dissemination...
PMC10586913
Data Availability
The data used to support the findings of this study are available from the corresponding author upon request.
PMC10586913
Conflicts of Interest
The authors declare that they have no conflicts of interest.
PMC10586913
Authors' Contributions
orthodontic
DHA conceptualized and designed the study, interpreted the results, contributed to critical revision, and finally approved the manuscript. SIK collected data, analysed the study, performed statistics, and wrote the manuscript. All authors have approved the final version of the manuscript.Acrylic tiles made from polishe...
PMC10586913
Results
PMC10077489
Development of albuminuria and increased glomerular permeability in early DN is ameliorated by MR antagonism.
After receiving streptozotocin (STZ), rats were hyperglycemic at week 3 (
PMC10077489
The effect of MR antagonism in preventing the diabetes-induced increase in glomerular permeability is dependent on the GEnGlx.
Hyaluronidase, a Glx-degrading enzyme, was infused in a subgroup of spironolactone-treated diabetic rats to remove the EnGlx to confirm the importance of GEnGlx preservation in this model (
PMC10077489
Increased MMP activity in early DN is ameliorated by MR antagonism.
We have previously identified MMP2 and MMP9 as key Glx sheddases (
PMC10077489
Exposing human GEnC to diabetic conditions resulted in MMP upregulation and GEnGlx damage that were both ameliorated by MR antagonism.
Secreted gelatinases MMP2 and MMP9 can be activated by cell membrane–bound membrane type 1 MMP, also known as MMP14 (
PMC10077489
The GEnGlx is damaged in human DN.
Human renal biopsies were obtained from two centers (Bristol, United Kingdom; Bari, Italy) (
PMC10077489
MR antagonism in human diabetes reduces urinary MMP activity.
Previously, Mehdi et al. confirmed that the addition of spironolactone to a regimen including maximal ACE inhibition improved renoprotection in DN (
PMC10077489
Discussion
albuminuria, GEnGlx damage, diabetes, STZ-induced diabetic, diabetic, MR, glomerular dysfunction
DISEASE, DYSFUNCTION, ADVERSE EFFECTS, PEARLY DISEASE, DIABETES
Using a rat model of diabetes, we have demonstrated that upregulation of MMPs, GEnGlx damage, and glomerular dysfunction develop rapidly before other visible markers of DN. MR antagonism preserved the GEnGlx and restored GFB function. In vitro, using human GEnC exposed to a diabetic environment, we also observed upregu...
PMC10077489
Methods
PMC10077489
Animals.
Male Wistar rats (150–200 g, Charles River Laboratories) were maintained by the Animal Services Unit, University of Bristol. Animals were housed in a conventional facility with a controlled environment (21°C–24°C and 12:12 hour light/dark cycle). Timelines of the experimental protocols used are included (
PMC10077489
Type 1 diabetic model.
diabetic rats, diabetic, diabetes
DIABETES
For induction of diabetes, randomized rats were injected i.p. with 50 mg/kg STZ (S0130; Sigma-Aldrich) by adding the appropriate volume of the drug at 25 mg/mL in 10 mM sodium citrate (pH 4.5). Comparisons were made with vehicle-treated rats (10 mM sodium citrate [pH 4.5]). Glycemia, by tail-tip blood droplet analysis ...
PMC10077489
Tissue collection.
For tissue collection, rats were anesthetized with isoflurane in 1 L/min oxygen. A midline laparotomy was performed, and the abdominal aorta was cannulated with PE-10 tubing (427400; Becton Dickinson) to flush both kidneys with Ringer solution (NaCl, 132 mM; KCl, 4.6 mM; MgSO
PMC10077489
Glomerular albumin permeability (Ps’
The glomerular P
PMC10077489
Lectin staining.
FLUOR
MOA, WGA, and UEA-I lectins have binding specificities for carbohydrate sequences present in the glycocalyx. MOA lectin binds to nonreducing terminal galactose-α-1,3-galactose-carbohydrates, WGA lectin binds to the sialyloligosaccharides, N-Acetylglucosamine and N-Acetylneuraminic acid, and UEA-I binds to α-L-fucose. L...
PMC10077489
Fluorescent profile confocal peak-to-peak analysis.
Initially, the fluorescence profile peak-to-peak assessment was carried out, blinded using a manual methodology, as previously described (
PMC10077489
PAS staining.
Rat paraffin-embedded kidney sections from perfused kidneys were stained using a periodic acid–Schiff (PAS) kit according to the manufacturer’s instructions. Images were quantified with ImageJ using the Haematoxylin PAS color deconvolution plug-in. Corrected total cell intensity values were calculated as follows: integ...
PMC10077489
TEM.
TEM
Perfusion-fixed right kidneys were used for TEM, as described previously, to measure GEnC, GBM, and podocyte parameters to identify effects on GFB ultrastructure that could explain changes in glomerular permeability (
PMC10077489
MMP activity.
AS-72017
MMP2 activity was studied using the MMP2 Biotrack activity assay (RPN2631; GE Healthcare) and the SensoLyte Plus 520 MMP2 assay (AS-72224; AnaSpec). MMP9 activity was studied using the SensoLyte Plus 520 MMP9 assay (AS-72017; AnaSpec). The manufacturer’s instructions were followed in full. Urinary active MMP2 and MMP9 ...
PMC10077489
Cell culture.
Human CiGEnC (
PMC10077489
Human renal samples.
TBMN
RENAL, EMERGENCY
Renal biopsy samples from 34 patients were obtained from the Histopathology Department of Southmead Hospital (Bristol, United Kingdom) and Aldo Moro University of Bari (Division of Nephrology, Dialysis and Transplantation, Department of Emergency and Organ Transplantation; Bari, Italy). Tissue was immersion fixed in 10...
PMC10077489
Human urine samples.
diabetes
DIABETES
Urine samples from 35 patients were obtained from a double-blind, placebo-controlled trial conducted in patients with diabetes as previously described (
PMC10077489
Statistics.
All statistics were calculated using Prism 8 (GraphPad). Normality was assessed visually and using the Shapiro-Wilk test. Where data was normally distributed, a 1-way ANOVA or Student’s 2-tailed
PMC10077489
Study approval.
All animal protocols were approved by the UK Government Home Office and conformed to the
PMC10077489
Author contributions
HLH, CJD, RDR
CJD
MC, GIW, RRF, SCS, and MJB designed research; MC, JKF, RDR, ASO, LKD, and MJB performed research; JS, CJD, SJH, PP, LG, HLH, and RDT contributed resources; MC, JKF, KLO, ASO, MG, LS, KHW, and MJB analyzed data; MC, SCS, and MJB wrote paper; and all authors approved the final version of the manuscript.
PMC10077489
Supplementary Material
PMC10077489
02/07/2023
In-Press Preview
PMC10077489
03/08/2023
Electronic publication
PMC10077489
Development of albuminuria and increased glomerular permeability in early diabetic nephropathy is ameliorated by MR antagonism.
(
PMC10077489
Fluorescence profile peak-to-peak measurements confirm that glomerular endothelial glycocalyx damage is prevented by MR antagonism and correlates strongly with glomerular albumin permeability.
Rats were perfused with Ringer solution, and the left kidney was removed for lectin staining. (
PMC10077489
The effect of MR antagonism in preventing the diabetes-induced increase in glomerular permeability is dependent on the glomerular endothelial glycocalyx.
(
PMC10077489
Increased matrix metalloproteinase activity in early diabetic nephropathy is ameliorated by MR antagonism.
(
PMC10077489
Exposing human GEnC to diabetic conditions resulted in MMP upregulation and GEnGlx damage, effects ameliorated by MR antagonism.
diabetic
Human conditionally immortalized glomerular endothelial cells (CiGEnC) were maintained in the presence of glucose, insulin, TNF-α, and IL-6 to mimic a diabetic environment. (
PMC10077489
The glomerular endothelial glycocalyx is damaged in human diabetic nephropathy.
(
PMC10077489
Matrix metalloproteinase activity in human diabetes is reduced by MR antagonism.
Matrix metalloproteinase (MMP) activities were measured for the sheddases MMP2 and MMP9. (
PMC10077489
Clinical and analytical data at the time of renal biopsy
PMC10077489
Clinical and analytical data at the time of urine sample
PMC10077489
Keywords
PMC10357344
Introduction
In recent years, improved price transparency of pharmaceuticals has emerged as an important yet highly debated approach to manage medicine prices. This approach is believed to contribute to expanded access to medicines through the reduction of medicine prices The importance of promoting price transparency has also been...
PMC10357344
Methods
This systematic review was undertaken according to the principles of systematic reviewing embodied in the Cochrane Handbook and guidance document published by the Centre for Reviews and Dissemination (CRD) [As part of a wider review on ten pharmaceutical pricing policies, this paper only addresses policies promoting pr...
PMC10357344
Search strategy and selection criteria
An extensive literature search was performed between September 5 and October 10, 2019, for relevant articles published from 2004 to the search date in a large number of databases including but not limited to Ovid MEDLINE (Ovid), Embase (Ovid), Social Science Citation Index, EconLit, and the NHS Economic Evaluations Dat...
PMC10357344
Selection criteria
This systematic review only included studies that used robust experimental or observational study designs comparing policies promoting price transparency (see Definition of the policy intervention.
PMC10357344
Study selection
TB
A single researcher assessed all titles and abstracts identified from the database searches and removed the obviously irrelevant records based on titles and abstracts. Two reviewers independently screened the titles and abstracts of potentially eligible records, with disagreements adjudicated by a third reviewer. The f...
PMC10357344
Data extraction and quality assessment
Data from included studies was extracted by one member of the review team (IRJ or LT) using a standardized data extraction form, including information on study design, setting and subjects, interventions including implementation strategies, outcomes, and results including contextual factors. Extracted data was verified...
PMC10357344
Data analysis
Substantial expected differences in the characteristics and contexts of included studies meant we did not aim to undertake a meta-analysis. Instead, we provided a narrative summary describing the quality of the studies, the relationship between interventions and patterns discerned in the data.
PMC10357344
Results
Electronic database and grey literature searches identified 43,693 records for all ten pricing policies combined. The review of relevant reference lists and other sources yielded a further 2,345 records. After removal of duplicates, 32,011 articles were screened by title and abstract, resulting in 1,000 potential artic...
PMC10357344
Discussion
Following extensive searches, we found only two studies assessing an intervention promoting price transparency in a manner sufficiently robust for inclusion in this review. It is worth noting that the SEP, while introducing transparency in the private market, also included aspects of price control other than price tran...
PMC10357344
Conclusion
In conclusion, the lack of quantitative and comparative evidence assessing the impact of policies promoting price transparency is a clear call for further research. Collaborative pilots involving both national governments and researchers could help to align their interests and overcome the current inertia in evidence d...
PMC10357344
Role of the funding source
This systematic review was commissioned and funded by the World Health Organization [HQ/EMP/2019/002, 2019] under a grant from the United Kingdom Department for International Development (DFID). The review was part of the process for developing the 2020 WHO Guideline on Country Pharmaceutical Pricing Policies. The WHO ...
PMC10357344
Declaration of Competing Interest
This systematic review was commissioned and funded by the World Health Organization.
PMC10357344
References
PMC10357344
Supplementary materials
PMC10357344
Acknowledgements
TB
The authors are grateful to the members of the Guideline Development Group (GDG) and the World Health Organization (WHO) secretariat and its advisors for providing technical support while establishing the research protocol: Kiu Tay-Teo, Fatima Suleman, Lisa Bero, Sabine Vogler. Additionally, Zaheer Babar, Jaime Espin a...
PMC10357344
2. Materials and Methods
PMC10536396
2.1. Study Design
arteria, ischaemic stroke
ISCHAEMIC STROKE
A randomised controlled monocentric study was conducted in a population of patients after their first ischaemic stroke in the arteria cerebri media basin who were admitted to a rehabilitation sanatorium. The study was approved by the Ethics Committee of the University of Ostrava Faculty of Medicine. All patients signed...
PMC10536396
2.2. Participants
neurological disease, cardiovascular instability, cognitive impairment, Stroke, ischaemic stroke, epilepsy, dementia, low functional mobility, arteria
NEUROLOGICAL DISEASE, STROKE, EPILEPSY, ISCHAEMIC STROKE, EVENT, SEVERE VISUAL IMPAIRMENT
The study included patients after their first ischaemic stroke in the arteria cerebri media basin (time since the event <6 months) who were referred for rehabilitation for 4 to 5 weeks in a rehabilitation sanatorium in the Czech Republic, between November 2022 and March 2023. Patients were treated according to the Euro...
PMC10536396
2.3. Procedures
stroke, BBS, disability, cognitive deficits
STROKE
All patients underwent an initial examination (T0) by a trained occupational therapist on the first day after admission to the rehabilitation sanatorium. The mini-mental state examination (MMSE), the Barthel index (BI), the extended Barthel index (EBI), the Berg balance scale (BBS), and the WHO disability assessment sc...
PMC10536396
2.4. Instruments Used
Oculus Quest 2 (Meta Quest 2) has 6 GB of RAM combined with the ultra-fast Qualcomm Snapdragon XR2 platform. It consists of a projection helmet and two controllers. The helmet houses two screens for the eyes with the ability to adjust focus and the addition of an eyeglass attachment. A fast switchable LCD display with ...
PMC10536396
2.5. Intervention
hand pain, seizure, sudden instability
In addition to conventional therapy, the patients in the intervention group received training using the Oculus Quest 2 VR device. In total, there were a minimum of 10 and a maximum of 15 therapy sessions of 20 min per day, 3 times per week for 4 to 5 weeks. The total volume of active VR therapy averaged 270 min for the...
PMC10536396
2.6. Statistical Methods
Basic descriptive statistics and statistical tests according to the type of data were used for statistical evaluation. The normality of the data was tested using the Shapiro–Wilk test, followed by a two-sample t-test and a non-parametric Mann–Whitney test, paired Wilcoxon test, and Spearman correlation coefficient. For...
PMC10536396
4. Discussion
stroke, comorbidity, post-stroke, ’ illness
EVENTS, STROKE
New sophisticated virtual reality technologies implemented in the therapy of post-stroke patients have gained importance in recent years and are promising forms of technology that have been shown to increase patient satisfaction with post-stroke rehabilitation [In the studied patient group, statistically significant ch...
PMC10536396
5. Conclusions
post-stroke
The application of VR did not lead to significantly different changes compared to conventional therapy. Patients experienced improvements in self-sufficiency and quality of life, but these improvements were not different from the changes seen with conventional therapy. However, more randomised controlled trials are nee...
PMC10536396
Author Contributions
Formal analysis, D.P.; Funding acquisition, M.F.; Investigation, M.D.; Methodology, M.J.; Resources, L.H.; Software, H.T.; Supervision, Š.B.; Writing—review & editing, I.F. All authors have read and agreed to the published version of the manuscript.
PMC10536396
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of the Faculty of Medicine of the University of Ostrava, proceedings number: 12/2022, 12 December 2022.
PMC10536396
Informed Consent Statement
Patients included in the study signed an informed consent to be included in the study and for publication of the results of the study in a peer-reviewed journal.
PMC10536396
Data Availability Statement
All research data was securely stored in digital format and protected from loss and unauthorized access. Data may be shared with other researchers upon request.
PMC10536396
Conflicts of Interest
The authors declare no conflict of interest.
PMC10536396
References
BBS
Flow chart of study participants according to CONSORT.Explanatory notes: WHODAS 2.0—WHO Disability Assessment Schedule 2.0. The Basic sociodemographic and clinical characteristics of the experimental and control groups and their comparison.Explanatory notes: IQR—Interquartile range, Comparison of MMSE, WHODAS 2, BI, EB...
PMC10536396
Aims
hyperglycaemia, GDM, dysglycaemia
GDM, HYPERGLYCAEMIA, GESTATIONAL DIABETES MELLITUS
Gestational diabetes mellitus (GDM) is the most common type of hyperglycaemia in pregnancy. GDM is a risk factor of adverse perinatal outcomes, with the incidence rate increasing proportionally to the level of maternal dysglycaemia. Therefore, glycaemic control plays an important role in management of GDM. The aim of t...
PMC10359198