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Indian Journal of Dental Research :... Jan 2024Wet oral environment may have deleterious effects on performance of the composites due to influences of water sorption and solubility. The study evaluated the hydrolytic...
INTRODUCTION
Wet oral environment may have deleterious effects on performance of the composites due to influences of water sorption and solubility. The study evaluated the hydrolytic degradation caused because of water sorption and solubility of silorane and methacrylate-based dental composites.
METHODS
Ten disc samples (2 mm × 10 mm) were prepared. Samples were analyzed for water solubility and sorption according to ISO 4049:2000 regulations and tested for mass gain or loss following immersion in water or in artificial saliva at 1 day, 15 days, and 30 days period. Student's 't' test, repeated measures analysis of variance (ANOVA), and Tukey's post-hoc tests determined statistical significance of the experimental results with global significance set at P = 0.05.
RESULTS
Considerable sorption and solubility was observed with time in both materials on immersion. Silorane composites showed lower water sorption and solubility than methacrylate-based composite (MBC). Artificial saliva demonstrated higher sorption and solubility compared to distilled water.
CONCLUSION
Silorane composites display enhanced hydrolytic stability even after a month of immersion in contrast to conventional methacrylate-based composites (MBCs), making it a better alternative to MBC resins clinically.
Topics: Solubility; Methacrylates; Composite Resins; Water; Silorane Resins; Saliva, Artificial; Materials Testing; Hydrolysis; Dental Materials
PubMed: 38934754
DOI: 10.4103/ijdr.ijdr_195_23 -
Medycyna Pracy Jun 2024Voivodeship Occupational Medicine Centres (VOMC), being higher-level units towards basic units providing preventive care for employees in Poland, play a consultative,...
BACKGROUND
Voivodeship Occupational Medicine Centres (VOMC), being higher-level units towards basic units providing preventive care for employees in Poland, play a consultative, appeal, supervisory and registration role towards them. Additionally, they perform many other tasks specified in the Occupational Medicine Service Act, including conducting diagnostic and jurisprudential activities related to occupational diseases and postgraduate education in occupational medicine.
MATERIAL AND METHODS
The analysis covers data from 2017-2022 on VOMCs activities, derived from mandatory MZ-35 reporting.
RESULTS
Over 6 years, the number of employed physicians at VOMCs decreased from 830 in 2017 to 820 in 2022, with >20% of employment contracts transitioning to other forms of cooperation. The number of employed nurses decreased from 375 to 342, and the number of psychologists from 86 to 82. During the 3 years of the pandemic (2020-2022), compared to 2017-2019, the consultative activity of VOMCs for basic units of occupational health service decreased by nearly 30%, while appeal and supervisory activities decreased by 15.2% and 15.8%, respectively. The number of individuals receiving outpatient medical rehabilitation for occupational pathology decreased by >32%, and the number of services provided for established occupational pathology decreased by >14%. The number of certifications for occupational diseases decreased from 3963 in 2019 to 3518 in the first year of the pandemic, then increased to 4145 in 2021 and 3990 in 2022.
CONCLUSIONS
The COVID-19 pandemic had a significant impact on the functioning of VOMCs. Changes in specific areas of their judicial, consultative, appeal, supervisory, training and rehabilitation activities corresponded with the socio-legal changes observed between 2020-2022. The structure of employment at VOMCs and the scope of their tasks remained stable during the pandemic. The observed changes in employment of medical staff were in line with general trends in healthcare institutions and regional conditions. Med Pr Work Health Saf. 2024;75(4).
PubMed: 38934657
DOI: 10.13075/mp.5893.01502 -
Archivio Italiano Di Urologia,... Jun 2024Single sperm cryopreservation (SSC) is a specific technique especially used in individuals with small numbers of sperm who suffered from non-obstructive azoospermia...
Pentoxifylline treatment as a safe method for selecting viable testicular spermatozoa before cryopreservation of a small numbers of spermatozoa in azoospermia individuals.
BACKGROUND
Single sperm cryopreservation (SSC) is a specific technique especially used in individuals with small numbers of sperm who suffered from non-obstructive azoospermia (NOA). Testicular specimens possess poor motility and low population of viable spermatozoa. Therefore, sperm selection methods such as applying pentoxifylline (PTX) may improve motility in these cases. The main aim of this study was to evaluate the protective effects of PTX on testicular spermatozoa before and after performing SSC.
METHODS
Thirty testicular samples were obtained from men with azoospermia. This study was conducted in two phases. Phase 1 evaluated the effect of PTX for sperm selection before SSC. Twenty testicular samples were divided to two experimental groups: SSC without (I) and with PTX treatment (II). For PTX treatment spermatozoa were incubated with PTX at 37°C for 30 min and only motile spermatozoa were selected for SSC. In phase 2, ten testicular samples were cryopreserved with SSC and warming procedure was carried out in droplet with and without PTX. Motility and viability rates, morphology by motile sperm organelle morphology examination (MSOME), DNA fragmentation by sperm chromatin dispersion test (SCD) and mitochondrial membrane potential (MMP) were evaluated.
RESULTS
In phase 1, post warm motility rate was higher in PTX exposed group compared to the unexposed group (25.6 ± 8.13 vs. 0.85 ± 2.1) (p > 0.00). Recovery rate, viability and morphology were not significantly different between groups. DNA integrity and MMP were also similar between both groups. In phase 2 although motility increased in PTX group compared to without PTX group (29.30 ± 12.73 vs. 1.90 ± 2.64) (p > 0.00), the viability rate was not different (70.40 ± 12.12 vs. 65.30 ± 11.87). All above mentioned parameters were similar between the two SSC groups.
CONCLUSIONS
Supplementation of testicular spermatozoa with PTX before cryopreservation increases motility and did not have adverse effects on viability, morphology, DNA integrity and MMP. PTX could be used as sperm selection method before single sperm cryopreservation, but PTX could not maintain motile the most of viable testicular sperms.
Topics: Male; Humans; Pentoxifylline; Cryopreservation; Azoospermia; Spermatozoa; Sperm Motility; Semen Preservation; DNA Fragmentation; Testis; Adult; Cell Survival; Membrane Potential, Mitochondrial
PubMed: 38934523
DOI: 10.4081/aiua.2024.12525 -
Emerging Microbes & Infections Jun 2024, a group of multi-drug resistant, Gram-positive, aerobic and partially acid-fast bacteria, are emerging causes of bacterial conjunctivitis and keratitis. However, the...
, a group of multi-drug resistant, Gram-positive, aerobic and partially acid-fast bacteria, are emerging causes of bacterial conjunctivitis and keratitis. However, the pathogenesis of keratitis is largely unknown. To address this, we used New Zealand White rabbits to develop the first eye infection model and conducted tests to study the pathogenesis mechanisms of . There is increasing evidence that biofilms play a significant role in ocular infections, leading us to hypothesize that biofilm formation is crucial for effective infection. In order to look for potential candidate genes which are important in biofilm formation and keratitis. We performed genome sequencing of two ocular isolates, -PW1004 and -PW899, to identify potential virulence factors. Through and studies, we characterized their biological roles in mediating keratitis. Our findings confirmed that is an ocular pathogen by fulfilling the Koch's postulates, and using genome sequence data, we identified encoding a mycolyltransferase, as a crucial gene in biofilm formation and causing keratitis in the rabbit model. This is the first report demonstrating the novel role of mycolyltransferase in causing ocular infections. Overall, our findings contribute to a better understanding of pathogenesis and provide a potential target for treatment. Specific inhibitors targeting TmytC could serve as an effective treatment option for infections.
PubMed: 38934251
DOI: 10.1080/22221751.2024.2373317 -
Haematologica Jun 2024Chromosomal translocations in non-Hodgkin lymphoma (NHL) result in activation of oncogenes by placing them under the regulation of immunoglobulin heavy chain (IGH)...
Chromosomal translocations in non-Hodgkin lymphoma (NHL) result in activation of oncogenes by placing them under the regulation of immunoglobulin heavy chain (IGH) super-enhancers. Aberrant expression of translocated oncogenes induced by enhancer activity can contribute to lymphomagenesis. The role of the IGH enhancers in normal B-cell development is well established, but knowledge regarding the precise mechanisms of their involvement in control of the translocated oncogenes is limited. The goal of this project was to define the critical regions in the IGH regulatory elements and identify enhancer RNAs (eRNA). We designed a sgRNA library densely covering the IGH enhancers and performed tiling CRISPR interference screens in three NHL cell lines. This revealed three regions crucial for NHL cell growth. With chromatin-enriched RNA-Seq we showed transcription from the core enhancer regions and subsequently validated expression of the eRNAs in a panel of NHL cell lines and tissue samples. Inhibition of the essential IGH enhancer regions decreased expression of eRNAs and translocated oncogenes in several NHL cell lines. The observed expression and growth patterns were consistent with the breakpoints in the IGH locus. Moreover, targeting the Eμ enhancer resulted in loss of B-cell receptor expression. In a Burkitt lymphoma cell line, MYC overexpression partially rescued the phenotype induced by IGH enhancer inhibition. Our results indicated the most critical regions in the IGH enhancers and provided new insights into the current understanding of the role of IGH enhancers in B-cell NHL. As such, this study forms a basis for development of potential therapeutic approaches.
PubMed: 38934080
DOI: 10.3324/haematol.2023.284672 -
Frontiers in Aging Neuroscience 2024Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday...
Amyloid and tau burden relate to longitudinal changes in the performance of complex everyday activities among cognitively unimpaired older adults: results from the performance-based Harvard Automated Phone Task.
BACKGROUND
Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed to investigate how changes over time in everyday functioning relate to tau and amyloid in cognitively unimpaired older adults.
METHODS
Seventy-six cognitively unimpaired participants (72 ± 6 years old, 61% female) completed multiple Harvard Automated Phone Task (APT) assessments over 2.0 ± 0.9 years. The Harvard APT consists of three tasks, performed through an automated phone system, in which participants refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and transfer money to pay a bill (APT-Bank). Participants underwent Pittsburgh compound-B and flortaucipir positron emission tomography scans at baseline. We computed distribution volume ratios for a cortical amyloid aggregate and standardized uptake volume ratios for medial temporal and neocortical tau regions. In separate linear mixed models, baseline amyloid by time and tau by time interactions were used to predict longitudinal changes in performance on the Harvard APT tasks. Three-way amyloid by tau by time interactions were also investigated. Lastly, we examined associations between tau and change in Harvard APT scores in exploratory voxel-wise whole-brain analyses. All models were adjusted for age, sex, and education.
RESULTS
Amyloid [unstandardized partial regression coefficient estimate (β) = -0.007, 95% confidence interval (95% CI) = (-0.013, -0.001)], and medial temporal tau [β = -0.013, 95% CI = (-0.022, -0.004)] were associated with change over time in years on APT-PCP only, i.e., higher baseline amyloid and higher baseline tau were associated with steeper rate of decline of APT-PCP. Voxel-wise analyses showed widespread associations between tau and change in APT-PCP scores over time.
CONCLUSION
Even among cognitively unimpaired older adults, changes over time in the performance of cognitively complex everyday activities relate to cortical amyloid and widespread cerebral tau burden at baseline. These findings support the link between Alzheimer's disease pathology and function and highlight the importance of measuring everyday functioning in preclinical disease stages.
PubMed: 38934017
DOI: 10.3389/fnagi.2024.1420290 -
Frontiers in Endocrinology 2024Radiofrequency ablation (RFA) is an emerging non-surgical treatment for benign thyroid nodules (BTN). Despite its proven safety profile, data on the learning curve (LC)...
OBJECTIVE
Radiofrequency ablation (RFA) is an emerging non-surgical treatment for benign thyroid nodules (BTN). Despite its proven safety profile, data on the learning curve (LC) required to achieve proficiency are still lacking.
MATERIALS AND METHODS
The first 179 RFA procedures performed by a single operator in patients with non-functioning BTN were retrospectively analyzed. Six-month nodule volume reduction rate (VRR) ≥ 50% was regarded as reflection of proficiency. Multiple linear regression analysis has been performed to determine the relationship between the VRR and clinical variables. Cumulative sum (CUSUM) charts were plotted to assess LCs for all consecutive procedures and in relation to basal nodule size. In details, Group 1 (G1): 57 patients with small nodules (<10 ml); Group 2 (G2): 87 patients with intermediate nodules (10 - 25 ml); Group 3 (G3): 35 patients with large size (> 25 ml).
RESULTS
LC of all 179 procedures showed 3 phases: initial learning (1-39 procedures); consolidation (40-145 procedures); and experienced period (146-179 procedures). For G1 and G2 proficiency is achieved starting from the 10th procedure within the group (or 37th considering consecutively all procedures) and from the 59th procedure within the group (or 116th considering consecutively all procedures), respectively. LC of G3 did not detect operator proficiency.
CONCLUSION
Specific LCs exist concerning the basal size of the nodule treated with RFA. In nodules with baseline volume > 25 ml suboptimal VRR has to be expected. Previously achieved experience on small-intermediate nodules does not seem to provide advantages in terms of higher VRR in the treatment of large nodules. Other potential and non-modifiable factors likely play a key role in the final volume reduction independently from the increased skill of the operator.
Topics: Humans; Thyroid Nodule; Female; Male; Radiofrequency Ablation; Retrospective Studies; Middle Aged; Adult; Learning Curve; Clinical Competence; Aged; Treatment Outcome
PubMed: 38933827
DOI: 10.3389/fendo.2024.1399912 -
Frontiers in Endocrinology 2024The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective...
OBJECTIVES
The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective diagnostic imaging tools to predict the non-iodine-avid status of lung metastasis (LMs) in differentiated thyroid cancer (DTC) patients is underscored to prevent unnecessary radioactive iodine treatment (RAI).
METHODS
Primary cohort consisted 1962 pretreated LMs of 496 consecutive DTC patients with pretreated initially diagnosed LMs who underwent chest CT and subsequent post-treatment radioiodine SPECT. After automatic lesion segmentation by SE V-Net, SE Net deep learning was trained to predict non-iodine-avid status of LMs. External validation cohort contained 123 pretreated LMs of 24 consecutive patients from other two hospitals. Stepwise validation was further performed according to the nodule's largest diameter.
RESULTS
The SE-Net deep learning network yielded area under the receiver operating characteristic curve (AUC) values of 0.879 (95% confidence interval: 0.852-0.906) and 0.713 (95% confidence interval: 0.613-0.813) for internal and external validation. With the LM diameter decreasing from ≥10mm to ≤4mm, the AUCs remained relatively stable, for smallest nodules (≤4mm), the model yielded an AUC of 0.783. Decision curve analysis showed that most patients benefited using deep learning to decide radioactive I treatment.
CONCLUSION
This study presents a noninvasive, less radioactive and fully automatic approach that can facilitate suitable DTC patient selection for RAI therapy of LMs. Further prospective multicenter studies with larger study cohorts and related metabolic factors should address the possibility of comprehensive clinical transformation.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Lung Neoplasms; Female; Male; Middle Aged; Adult; Aged; Deep Learning; Retrospective Studies; Tomography, Emission-Computed, Single-Photon; Cohort Studies
PubMed: 38933823
DOI: 10.3389/fendo.2024.1429115 -
Frontiers in Oncology 2024Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human...
INTRODUCTION
Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human monoclonal antibody targeting nectin-4. No validated biomarker predictive of or correlated with response exists for EV. Cutaneous toxicity is among the most common EV-related toxicities and typically emerges in early cycles. This retrospective experience of patients with urothelial cancer treated with EV monotherapy evaluated whether EV-related cutaneous toxicity correlated with improved outcomes including progression-free (PFS) and overall (OS) survival and overall response rate (ORR).
PATIENTS AND METHODS
Patients treated with EV monotherapy at Johns Hopkins were identified, and baseline characteristics, treatment, and toxicity details were extracted through chart review. Univariable Cox hazard ratios (HRs) were calculated for assessing the effect of baseline patient characteristics and cutaneous toxicity in PFS and OS. Based on the univariable analysis and known risk factors, all subsequent analyses were adjusted for: Eastern Cooperative Oncology Group performance status, visceral metastases at baseline, gender as well as EV dose, and weight to account for dosing differences. Multivariable Cox proportional HRs were used for comparing PFS and OS between patients with and without cutaneous toxicity, assessing toxicity and EV dose as a time-dependent variables. Adjusted p-values were calculated to compare ORR and disease control rate (DCR) between groups using the Poisson regression model.
RESULTS
Of the 78 patients analyzed, 42 (53.8%) experienced EV-related cutaneous toxicity that appeared early during treatment (median time to occurrence 0.5 months from EV initiation). Cutaneous toxicity correlated with significantly improved OS [HR, 0.48; 95% confidence interval (CI), 0.25, 0.9; P = 0.0235], ORR (68.3% vs. 20.7%, P = 0.0033) and DCR (82.9% vs. 48.3%, P = 0.0122). Median PFS was numerically longer in the cutaneous toxicity group (6.3 vs. 1.7 months), although no significance was achieved in the multivariable analysis (HR, 0.62; 95% CI: 0.35, 0.108; P = 0.0925).
CONCLUSION
In this retrospective study, EV-related cutaneous toxicity was associated with improved patient outcomes. Confirming this observation and understanding its mechanism could lead to discovery of a new clinical biomarker of EV response that can emerge in the first cycle.
PubMed: 38933451
DOI: 10.3389/fonc.2024.1377842 -
European Heart Journal Open May 2024Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and...
AIMS
Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed.
METHODS AND RESULTS
To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38-0.51, = 2.6e-28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39-0.76, = 4.2e-04) but not with bleeding (OR = 1.13, 95% CI = 0.93-1.36, = 2.2e-01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58-0.64, = 4.1e-85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69-0.86, = 4.1e-06) but not with bleeding (OR = 1.01, 95% CI = 0.95-1.08, = 7.5e-01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses.
CONCLUSION
These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.
PubMed: 38933427
DOI: 10.1093/ehjopen/oeae043