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BMC Oral Health Nov 2023Early childhood caries (ECC) is the most prevalent chronic health problem in young children, and it can be arrested using professionally applied fluoride such as Sodium... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Early childhood caries (ECC) is the most prevalent chronic health problem in young children, and it can be arrested using professionally applied fluoride such as Sodium fluoride (NaF) varnish and Silver Diamine Fluoride (SDF). This trial compared two interventions to arrest ECC lesions: 38% SDF combined with 5% NaF varnish versus 38% SDF and assessed whether the arrest rate was affected by baseline lesion severity measured by ICDAS.
METHODS
Children aged ≤ 4 years from 4 nurseries in a rural area in Alexandria, Egypt joined the study in March 2022. They were included if they had at least one active carious lesion with ICDAS codes ≥ 3. They were randomized to receive either 38% SDF with 5% NaF varnish or 38% SDF alone. In both groups, the agents were applied at baseline and after 6 months on the caries lesions. NaF was additionally applied on all teeth in the oral cavity, and it was also applied after three months. The primary outcome was lesion arrest status after six months. Parents' satisfaction with their children's appearance was the secondary outcome. Pearson Chi-Square test was used for bivariate comparison and multi-level multiple logistic regression was used to assess the effect of the intervention on caries arrest controlling for confounders. The interaction between the intervention and baseline lesion severity (categorized into moderate and severe lesions) was assessed and the p value was calculated.
RESULTS
The study included 1606 lesions in 220 children, median (IQR) age = 48(9) months. The percentages of arrested lesions after the application of SDF + NaF and SDF only were 77.7% and 73.2% (p = 0.035). In multivariable analysis, SDF + NaF had significantly greater caries arrest effect than SDF alone (AOR = 2.12, p = 0.03) with significant difference (p = 0.03) between moderate (AOR = 4.10, p = 0.005) and advanced (AOR = 1.92, p = 0.08) lesions. Most parents were satisfied with their children's appearance with no significant difference between groups (SDF + NaF = 84.5%, SDF = 78.18%, p = 0.23).
CONCLUSION
SDF + NaF had a higher arrest rate than SDF alone and this difference was significant in moderate but not advanced lesions. The findings have implications for the non-invasive management of ECC.
TRIAL REGISTRATION
This trial was registered in the clinicaltrials.gov registry (#NCT05642494).
Topics: Child; Child, Preschool; Humans; Sodium Fluoride; Fluorides, Topical; Cariostatic Agents; Follow-Up Studies; Dental Caries Susceptibility; Dental Caries; Silver Compounds; Quaternary Ammonium Compounds; Sodium
PubMed: 37978488
DOI: 10.1186/s12903-023-03597-5 -
Journal of Clinical Medicine Oct 2023Fibromyalgia (FM) is characterized by chronic musculoskeletal pain, muscle tension, joint mobility loss, and several psychological symptoms severely affecting patient...
Fibromyalgia (FM) is characterized by chronic musculoskeletal pain, muscle tension, joint mobility loss, and several psychological symptoms severely affecting patient well-being. Histamine is naturally degraded in the small intestine by diamine oxidase (DAO). Hereditary or acquired DAO deficiency causes extracellular histamine accumulation, leading to symptoms similar to those of individuals diagnosed with FM. Thus, this study aimed to assess the efficacy of adding DAO supplementation for 8 weeks to their standard therapy. We randomly assigned 100 women with FM (age: 33-61 years) to the supplementation and control groups. The Fibromyalgia Impact Questionnaire (FIQ), the Pain Catastrophizing Scale (PCS), and intensity scales were applied for a series of clinical symptoms together with the Bristol scale to assess the added value of DAO supplementation. Patients in both groups were receiving complete pharmacological support but some differences in the number of subjects receiving analgesics, antidepressants, and anxiolytics was noted. Patients in both study groups experienced favorable changes during the evaluation period as indicated by their final FIQ and PCS scores, particularly in the DAO group in the latter questionnaire. Qualitatively, the patients assigned to the DAO treatment group had lower scores for fatigue, anxiety, depression, burning and for rumination, magnification, and helplessness.
PubMed: 37892588
DOI: 10.3390/jcm12206449 -
Science Advances Oct 2023Spermidine, a ubiquitous polyamine, is known to be required for critical physiological functions in bacteria. Two principal pathways are known for spermidine...
Spermidine, a ubiquitous polyamine, is known to be required for critical physiological functions in bacteria. Two principal pathways are known for spermidine biosynthesis, both of which involve aminopropylation of putrescine. Here, we identified a spermidine biosynthetic pathway via a previously unknown metabolite, carboxyaminopropylagmatine (CAPA), in a model cyanobacterium sp. PCC 6803 through an approach combining C and N tracers, metabolomics, and genetic and biochemical characterization. The CAPA pathway starts with reductive condensation of agmatine and l-aspartate-β-semialdehyde into CAPA by a previously unknown CAPA dehydrogenase, followed by decarboxylation of CAPA to form aminopropylagmatine, and ends with conversion of aminopropylagmatine to spermidine by an aminopropylagmatine ureohydrolase. Thus, the pathway does not involve putrescine and depends on l-aspartate-β-semialdehyde as the aminopropyl group donor. Genomic, biochemical, and metagenomic analyses showed that the CAPA-pathway genes are widespread in 15 different phyla of bacteria distributed in marine, freshwater, and other ecosystems.
Topics: Spermidine; Putrescine; Biosynthetic Pathways; Aspartic Acid; Ecosystem; Cyanobacteria
PubMed: 37878710
DOI: 10.1126/sciadv.adj9075 -
European Journal of Nuclear Medicine... Aug 2023We aimed to compare the diagnostic performance and biodistribution of two similar PET agents, [Ga]Ga-P16-093 and [Ga]Ga-PSMA-11, in the same group of primary prostate... (Clinical Trial)
Clinical Trial
PURPOSE
We aimed to compare the diagnostic performance and biodistribution of two similar PET agents, [Ga]Ga-P16-093 and [Ga]Ga-PSMA-11, in the same group of primary prostate cancer (PCa) patients.
METHODS
Fifty patients with untreated, histologically confirmed PCa by needle biopsy were enrolled. Each patient underwent [Ga]Ga-P16-093 and [Ga]Ga-PSMA-11 PET/CT within a week. In addition to visual analysis, the standardized uptake value (SUV) was measured for semiquantitative comparison and correlation analysis.
RESULTS
[Ga]Ga-P16-093 PET/CT detected more positive tumors than [Ga]Ga-PSMA-11 PET/CT (202 vs. 190, P = 0.002), both for intraprostatic lesions (48 vs. 41, P = 0.016) and metastatic lesions (154 vs. 149, P = 0.125), especially for intraprostatic lesions in low- and intermediate-risk PCa patients (21/23 vs. 15/23, P = 0.031). Furthermore, [Ga]Ga-P16-093 PET/CT exhibited a significantly higher SUVmax for most matched tumors (13.7 ± 10.2 vs. 11.4 ± 8.3, P < 0.001). For normal organs, [Ga]Ga-P16-093 PET/CT showed significantly lower activity in the kidney (SUVmean: 20.1 ± 6.1 vs. 29.3 ± 9.1, P < 0.001) and urinary bladder (SUVmean: 6.5 ± 7.1 vs. 20.9 ± 17.4, P < 0.001), but displayed a higher uptake in the parotid gland (SUVmean: 8.7 ± 2.6 vs. 7.6 ± 2.1, P < 0.001), liver (SUVmean: 7.0 ± 1.9 vs. 3.7 ± 1.3, P < 0.001), and spleen (SUVmean: 8.2 ± 3.0 vs. 5.2 ± 2.2, P < 0.001) than [Ga]Ga-PSMA-11 PET/CT.
CONCLUSION
[Ga]Ga-P16-093 PET/CT demonstrated higher tumor uptake and better tumor detectability than [Ga]Ga-PSMA-11 PET/CT, especially in low- and intermediate-risk PCa patients, which indicated that [Ga]Ga-P16-093 may serve as an alternative agent for detection of PCa.
TRIAL REGISTRATION
Ga-P16-093 and Ga-PSMA-11 PET/CT Imaging in the Same Group of Primary Prostate Cancer Patients (NCT05324332, Registered 12 April 2022, retrospectively registered). URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT05324332 .
Topics: Humans; Male; Edetic Acid; Gallium Radioisotopes; Positron Emission Tomography Computed Tomography; Prospective Studies; Prostatic Neoplasms; Tissue Distribution
PubMed: 37233785
DOI: 10.1007/s00259-023-06283-4 -
Journal of Nuclear Medicine : Official... Jan 2024Functional imaging with prostate-specific membrane antigen (PSMA) ligands has emerged as the standard imaging method for prostate cancer (PCA). In parallel, the analysis...
Examining the Relationship and Prognostic Significance of Cell-Free DNA Levels and the PSMA-Positive Tumor Volume in Men with Prostate Cancer: A Retrospective-Prospective [Ga]Ga-PSMA-11 PET/CT Study.
Functional imaging with prostate-specific membrane antigen (PSMA) ligands has emerged as the standard imaging method for prostate cancer (PCA). In parallel, the analysis of blood-derived, cell-free DNA (cfDNA) has been shown to be a promising quantitative biomarker of PCA aggressiveness and patient outcome. This study aimed to evaluate the relationship and prognostic value of cfDNA concentrations and the PSMA-positive tumor volume (PSMA-TV) in men with PCA undergoing [Ga]Ga-PSMA-11 PET/CT imaging. We recruited 148 men with histologically proven PCA (mean age, 70.7 ± 7.7 y) who underwent [Ga]Ga-PSMA-11 PET/CT (184.9 ± 18.9 MBq) and blood sampling between March 2019 and August 2021. Among these, 74 (50.0%) had hormone-sensitive PCA and 74 (50.0%) had castration-resistant PCA (CRPC). All patients provided written informed consent before blood sample collection and imaging. The cfDNA was extracted and quantified, and PSMA-expressing tumor lesions were delineated to extract the PSMA-TVs. The Spearman coefficient assessed correlations between PSMA-TV and cfDNA concentrations and cfDNA's relation with clinical parameters. The Kruskal-Wallis test examined the mean cfDNA concentration differences based on PSMA-TV quartiles for significantly correlated patient groups. Log-rank and multivariate Cox regression analyses evaluated the prognostic significance of high and low cfDNA and PSMA-TV levels for overall survival. Weak positive correlations were found between cfDNA concentration and PSMA-TV in the overall group ( = 0.16, = 0.049) and the CRPC group ( = 0.31, = 0.007) but not in hormone-sensitive PCA patients ( = -0.024, = 0.837). In the CRPC cohort, cfDNA concentrations significantly differed between PSMA-TV quartiles 4 and 1 ( = 0.002) and between quartiles 4 and 2 ( = 0.016). Survival outcomes were associated with PSMA-TV ( < 0.0001, = 0.004) but not cfDNA ( = 0.174, = 0.12), as per the log-rank and Cox regression analysis. These findings suggest that cfDNA might serve as a biomarker of advanced, aggressive CRPC but does not reliably reflect total tumor burden or prognosis. In comparison, [Ga]Ga-PSMA-11 PET/CT provides a highly granular and prognostic assessment of tumor burden across the spectrum of PCA disease progression.
Topics: Male; Humans; Middle Aged; Aged; Gallium Radioisotopes; Positron Emission Tomography Computed Tomography; Prognosis; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Tumor Burden; Prospective Studies; Gallium Isotopes; Prostatic Neoplasms; Biomarkers; Cell-Free Nucleic Acids; Hormones; Edetic Acid
PubMed: 38050125
DOI: 10.2967/jnumed.123.266158 -
Journal of the American Dental... Oct 2023Evidence-based noninvasive caries therapies for initial caries lesions are available in the United States. Fundamental differences between noninvasive therapies and the...
BACKGROUND
Evidence-based noninvasive caries therapies for initial caries lesions are available in the United States. Fundamental differences between noninvasive therapies and the traditional surgical dental approach warrant a study of the financial scalability.
METHODS
The financial costs and benefits of fee-for-service clinics and payors were compared across 11 scenarios simulating the treatment of 1,000 initial caries lesions during a 3-year period. The scenarios included varying combinations of noninvasive therapies (that is, silver diamine fluoride, self-assembling peptide P-4, and glass ionomer therapeutic sealants), no treatment, and various rates of 1- through 3-surface restorations to an estimated 2022 practice model. We used a decision tree microsimulation model for deterministic and probabilistic sensitivity analyses. We derived assumptions from an initial lesion and noninvasive therapy-focused cohort study with operations data from 16 sites accepting Medicaid in Alabama as a case study and clinical data from all 92 sites.
RESULTS
In comparison with the 2022 practice model assumed for this study, scenarios that produce mutually beneficial results for payors' savings and clinics' net profits and profit margins include self-assembling peptide P-4, silver diamine fluoride on nonesthetic surfaces, and a mix of 3 noninvasive therapies. When considering the limited resources of chair and clinician time, the same scenarios, as well as silver diamine fluoride with restorations, emerged with substantially higher clinic net profit.
CONCLUSIONS
Hypothetical scenarios that include noninvasive therapies and minimize restorations achieve improved outcomes for all parties.
PRACTICAL IMPLICATIONS
Payors and clinicians should explore and implement noninvasive caries therapies to improve oral health for all. This study was registered at ClinicalTrials.gov. The registration number is NCT04933331.
Topics: Humans; Cohort Studies; Dental Caries Susceptibility; Dental Caries; Fluorides, Topical
PubMed: 37770132
DOI: 10.1016/j.adaj.2023.07.007 -
Cell Death & Disease Sep 2023Intracellular Ca signals control several physiological and pathophysiological processes. The main tool to chelate intracellular Ca is intracellular BAPTA (BAPTA),...
Intracellular Ca signals control several physiological and pathophysiological processes. The main tool to chelate intracellular Ca is intracellular BAPTA (BAPTA), usually introduced into cells as a membrane-permeant acetoxymethyl ester (BAPTA-AM). Previously, we demonstrated that BAPTA enhanced apoptosis induced by venetoclax, a BCL-2 antagonist, in diffuse large B-cell lymphoma (DLBCL). This finding implied a novel interplay between intracellular Ca signaling and anti-apoptotic BCL-2 function. Hence, we set out to identify the underlying mechanisms by which BAPTA enhances cell death in B-cell cancers. In this study, we discovered that BAPTA alone induced apoptosis in hematological cancer cell lines that were highly sensitive to S63845, an MCL-1 antagonist. BAPTA provoked a rapid decline in MCL-1-protein levels by inhibiting mTORC1-driven Mcl-1 translation. These events were not a consequence of cell death, as BAX/BAK-deficient cancer cells exhibited similar downregulation of mTORC1 activity and MCL-1-protein levels. Next, we investigated how BAPTA diminished mTORC1 activity and identified its ability to impair glycolysis by directly inhibiting 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) activity, a previously unknown effect of BAPTA. Notably, these effects were also induced by a BAPTA analog with low affinity for Ca. Consequently, our findings uncover PFKFB3 inhibition as an Ca-independent mechanism through which BAPTA impairs cellular metabolism and ultimately compromises the survival of MCL-1-dependent cancer cells. These findings hold two important implications. Firstly, the direct inhibition of PFKFB3 emerges as a key regulator of mTORC1 activity and a promising target in MCL-1-dependent cancers. Secondly, cellular effects caused by BAPTA are not necessarily related to Ca signaling. Our data support the need for a reassessment of the role of Ca in cellular processes when findings were based on the use of BAPTA.
Topics: Myeloid Cell Leukemia Sequence 1 Protein; Phosphoric Monoester Hydrolases; Egtazic Acid; Phosphofructokinase-2; Neoplasms
PubMed: 37684238
DOI: 10.1038/s41419-023-06120-4 -
Medicine Oct 2023Our aim was to determine the laboratory parameters that distinguish pseudothrombocytopenia from true thrombocytopenia. A total of 107 patients who were referred to the...
Our aim was to determine the laboratory parameters that distinguish pseudothrombocytopenia from true thrombocytopenia. A total of 107 patients who were referred to the adult hematology outpatient clinic with thrombocytopenia and subsequently diagnosed with acute myeloid leukaemia, immune thrombocytopenia and pseudothrombocytopenia were included in our study. Hemogram parameters on admission, platelet value in the control hemogram and peripheral smear findings were recorded. Forty three (40.2%) males and 64 (59.8%) females, were included in our study. There were 25 patients in the leukaemia group, 39 in the immune thrombocytopenia group and 43 in the pseudothrombocytopenia group. Control platelet value and red cell distribution width/platelet ratio were found to be statistically significantly different between the 3 groups. Receiver operating characteristic analysis based on platelet values showed that platelet value ≤ 38,000/µL (86% sensitivity, 78.1% specificity, P < .001), difference between 2 consecutively measured platelet levels ≤ 11. 000/µL (79.1% sensitivity, 79.7% specificity, P < .001), red cell distribution width/platelet ratio ≥ 0.413 (90.7% sensitivity, 78.1% specificity, P < .001) were found to be in favor of true thrombocytopenia. In the differentiation of pseudothrombocytopenia and true thrombocytopenia, the difference between the hemogram parameters at the time of admission and the platelet count in the control blood count may be guiding. This result may reduce patient and physician anxiety and prevent patient referral.
Topics: Adult; Male; Female; Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Platelet Count; Blood Platelets; Blood Cell Count; Edetic Acid; Platelet Aggregation
PubMed: 37832120
DOI: 10.1097/MD.0000000000035395 -
Scientific Reports Apr 2024Terpenes represent a promising renewable feedstock for the substitution of fossil resources in the synthesis of renewable platform chemicals, like diamines. This work...
Terpenes represent a promising renewable feedstock for the substitution of fossil resources in the synthesis of renewable platform chemicals, like diamines. This work describes the synthesis and full characterization of 1,4-p-menthane diamine (1,4-PMD) obtained from α-terpinene (1). A two-step procedure using dibenzyl azodicarboxylate (DBAD) and H as rather benign reagents was employed under comparatively mild conditions. Both C-N bonds were formed simultaneously during a visible-light mediated Diels-Alder reaction, which was investigated in batch or flow, avoiding regioselectivity issues during the amination steps that are otherwise typical for terpene chemistry. Heterogeneously catalyzed quadruple hydrogenation of the cycloadduct (2a) yielded 1,4‑PMD (3). While the intermediate cycloadduct was shown to be distillable, the target diamine can be sublimed, offering sustainable purification methods.
PubMed: 38580709
DOI: 10.1038/s41598-024-58615-5 -
Journal of Lipid Research Feb 2024Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of...
Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.
Topics: Animals; Mice; Humans; Phospholipids; Phosphorylcholine; Phospholipid Ethers; Ferroptosis; Mice, Inbred C57BL; Atherosclerosis; Human Umbilical Vein Endothelial Cells; Endothelium; Glutathione; Iron; Fatty Acid Binding Protein 3; Cyclohexylamines; Phenylenediamines
PubMed: 38218337
DOI: 10.1016/j.jlr.2024.100499