OBJECTIVES: This study aimed to investigate the genetic architecture of EOPD in a multi-ethnic Malaysian cohort.
METHODS: 161 index patients with PD onset ≤50 years were recruited from multiple centers across Malaysia. A two-step approach to genetic testing was used, combining a next-generation sequencing-based PD gene panel and multiplex ligation-dependent probe amplification (MLPA).
RESULTS: Thirty-five patients (21.7%) carried pathogenic or likely pathogenic variants involving (in decreasing order of frequency): GBA1, PRKN, PINK1, DJ-1, LRRK2, and ATP13A2. Pathogenic/likely pathogenic variants in GBA1 were identified in thirteen patients (8.1%), and were also commonly found in PRKN and PINK1 (11/161 = 6.8% and 6/161 = 3.7%, respectively). The overall detection rate was even higher in those with familial history (48.5%) or age of diagnosis ≤40 years (34.8%). PRKN exon 7 deletion and the PINK1 p.Leu347Pro variant appear to be common among Malay patients. Many novel variants were found across the PD-related genes.
CONCLUSIONS: This study provides novel insights into the genetic architecture of EOPD in Southeast Asians, expands the genetic spectrum in PD-related genes, and highlights the importance of diversifying PD genetic research to include under-represented populations.
PURPOSE: The purpose of this in vitro study was to compare the adherence of Streptococcus spp. and Candida spp. on 3D-printed denture bases prepared at different build orientations with conventional heat-polymerized resin.
MATERIAL AND METHODS: Resin specimens (n=5) with standardized 28.3 mm2 surface area were 3D printed at 0 and 60 degrees, and heat-polymerized (3DP-0, 3DP-60, and HP, respectively). The specimens were placed in a Nordini artificial mouth (NAM) model and exposed to 2 mL of clarified whole saliva to create a pellicle-coated substratum. Suspensions of Streptococcus mitis and Streptococcus sanguinis, Candida albicans and Candida glabrata, and a mixed species, each at 108 cfu/mL were pumped separately into the model for 24 hours to promote microbial adhesion. The resin specimens were then removed, placed in fresh media, and sonicated to dislodge attached microbes. Each suspension (100 μL) was aliquoted and spread on agar plates for colony counting. The resin specimens were also examined under a scanning electron microscope. The interaction between types of specimen and groups of microbes was examined with 2-way ANOVA and then further analysis with Tukey honest significant test and Kruskal-Wallis post hoc tests (α=.05).
RESULTS: A significant interaction was observed between the 3DP-0, 3DP-60, and HP specimen types and the groups of microbes adhering to the corresponding denture resin specimens (P
OBJECTIVE: This study aimed to determine the potential of ascorbic acid alone in inducing differentially expressed osteoblast-related proteins in dental stem cells via the liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) approach.
METHODS: The cells were isolated from deciduous (SHED) and permanent teeth (DPSC) and induced with 10 μg/mL of ascorbic acid. Bone mineralisation and osteoblast gene expression were determined using von Kossa staining and reverse transcriptase-polymerase chain reaction. The label-free protein samples were harvested on days 7 and 21, followed by protein identification and quantification using LC-MS/MS. Based on the similar protein expressed throughout treatment and controls for SHED and DPSC, overall biological processes followed by osteoblast-related protein abundance were determined using the PANTHER database. STRING database was performed to determine differentially expressed proteins as candidates for SHED and DPSC during osteoblast development.
RESULTS: Both cells indicated brownish mineral stain and expression of osteoblast-related genes on day 21. Overall, a total of 700 proteins were similar among all treatments on days 7 and 21, with 482 proteins appearing in the PANTHER database. Osteoblast-related protein abundance indicated 31 and 14 proteins related to SHED and DPSC, respectively. Further analysis by the STRING database identified only 22 and 11 proteins from the respective group. Differential expressed analysis of similar proteins from these two groups revealed ACTN4 and ACTN1 as proteins involved in both SHED and DPSC. In addition, three (PSMD11/RPN11, PLS3, and CLIC1) and one (SYNCRIP) protein were differentially expressed specifically for SHED and DPSC, respectively.
CONCLUSION: Proteome differential expression showed that ascorbic acid alone could induce osteoblastrelated proteins in SHED and DPSC and generate specific differentially expressed protein markers.
METHODS: The titration method was used to prepare LPV-loaded SNEDDS (LPV-SNEDDS). Six different pseudo-ternary phase diagrams were constructed to identify the nanoemulsifying region. The developed formulations were chosen in terms of globule size < 100 nm, dispersity ≤ 0.5, dispersibility (Grade A) and% transmittance > 85. Heating-cooling cycle, freeze-thaw cycle, and centrifugation studies were performed to confirm the stability of the developed SNEDDS.
RESULTS: The final LPV-SNEDDS (L-14) droplet size was 58.18 ± 0.62 nm, with polydispersity index, zeta potential, and entrapment efficiency (EE%) values of 0.326 ± 0.005, -22.08 ± 1.2 mV, and 98.93 ± 1.18%, respectively. According to high-resolution transmission electron microscopy (HRTEM) analysis, the droplets in the optimised formulation were < 60 nm in size. The selected SNEDDS released nearly 99% of the LPV within 30 min, which was significantly (p < 0.05) higher than the LPV-suspension in methylcellulose (0.5% w/v). It indicates the potential use of SNEDDS to enhance the solubility of LPV, which eventually could help improve the oral bioavailability of LPV. The Caco-2 cellular uptake study showed a significantly (p < 0.05) higher LPV uptake from the SNEEDS (LPV-SNEDDS-L-14) than the free LPV (LPV-suspension).
CONCLUSION: The LPV-SNEDDS could be a potential carrier for LPV oral delivery.
METHODS: In total, 154 patients (wild-type EGFR, 72 patients; Del19 mutation, 45 patients; and L858R mutation, 37 patients) were retrospectively enrolled and randomly divided into 92 training and 62 test cases. Two support vector machine (SVM) models to distinguish between wild-type and mutant EGFR (mutation [M] classification) as well as between the Del19 and L858R subtypes (subtype [S] classification) were trained using 3DBN features. These features were computed from 3DBN maps by using histogram and texture analyses. The 3DBN maps were generated using computed tomography (CT) images based on the Čech complex constructed on sets of points in the images. These points were defined by coordinates of voxels with CT values higher than several threshold values. The M classification model was built using image features and demographic parameters of sex and smoking status. The SVM models were evaluated by determining their classification accuracies. The feasibility of the 3DBN model was compared with those of conventional radiomic models based on pseudo-3D BN (p3DBN), two-dimensional BN (2DBN), and CT and wavelet-decomposition (WD) images. The validation of the model was repeated with 100 times random sampling.
RESULTS: The mean test accuracies for M classification with 3DBN, p3DBN, 2DBN, CT, and WD images were 0.810, 0.733, 0.838, 0.782, and 0.799, respectively. The mean test accuracies for S classification with 3DBN, p3DBN, 2DBN, CT, and WD images were 0.773, 0.694, 0.657, 0.581, and 0.696, respectively.
CONCLUSION: 3DBN features, which showed a radiogenomic association with the characteristics of the EGFR Del19/L858R mutation subtypes, yielded higher accuracy for subtype classifications in comparison with conventional features.
METHODS: 18 voluntarily participants were recruited from the Canterbury and Otago region of New Zealand to take part in a Dynamic Insulin Sensitivity and Secretion Test (DISST) clinical trial. A total of 46 DISST data were collected. However, due to ambiguous and inconsistency, 4 data had to be removed. Analysis was done using MATLAB 2020a.
RESULTS AND DISCUSSION: Results show that, with 42 gathered dataset, the ANN generates higher gains, ∅P = 20.73 [12.21, 28.57] mU·L·mmol-1·min-1 and ∅D = 60.42 [26.85, 131.38] mU·L·mmol-1 as compared to the linear least square method, ∅P = 19.67 [11.81, 28.02] mU·L·mmol-1 ·min-1 and ∅D = 46.21 [7.25, 116.71] mU·L·mmol-1. The average value of the insulin sensitivity (SI) of ANN is lower with, SI = 16 × 10-4 L·mU-1 ·min-1 than the linear least square, SI = 17 × 10-4 L·mU-1 ·min-1.
CONCLUSION: Although the ANN analysis provided a lower SI value, the results were more dependable than the linear least square model because the ANN approach yielded a better model fitting accuracy than the linear least square method with a lower residual error of less than 5%. With the implementation of this ANN architecture, it shows that ANN able to produce minimal error during optimization process particularly when dealing with outlying data. The findings may provide extra information to clinicians, allowing them to gain a better knowledge of the heterogenous aetiology of diabetes and therapeutic intervention options.
MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases (date: 15 February 2023) to identify original studies on QOL and PROs following PT for OC. We employed a fluid strategy in the search strategy by tracking citations of the initially selected studies. Reports were extracted for information on demographics, main results, and clinical and dose factor correlates. Quality assessment was performed using the NIH's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The PRISMA guidelines were followed in the preparation of this report.
RESULTS: Seven reports were selected, including one from a recently published paper captured from citation tracking. Five compared PT and photon-based therapy, although none were randomized controlled trials. Most endpoints with significant differences favored PT, including xerostomia, cough, need for nutritional supplements, dysgeusia, food taste, appetite, and general symptoms. However, some endpoints favored photon-based therapy (sexual symptoms) or showed no significant difference (e.g., fatigue, pain, sleep, mouth sores). The PROs and QOL improve following PT but do not appear to return to baseline.
CONCLUSION: Evidence suggests that PT causes less QOL and PRO deterioration than photon-based therapy. Biases due to the non-randomized study design remain obstacles to a firm conclusion. Whether or not PT is cost-effective should be the subject of further investigation.
METHODS AND RESULTS: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management.
CONCULSIONS: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.