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Porphyromonas gulae and PPAD antibodies are not related to citrullination in rheumatoid arthritis

Clin Oral Investig. 2023 May 3. doi: 10.1007/s00784-023-04964-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Porphyromonas gulae have the enzyme PPAD, as P. gingivalis, which is responsible for citrullination related to the pathophysiology of rheumatoid arthritis and periodontitis; this implies the presence of two species of PPAD-producing bacteria in the mouth as well as the presence of citrullinated proteins. There are no previous reports or studies investigating an association between P. gulae PPAD in rheumatoid arthritis (RA).

OBJECTIVE: To assess the presence of P. gulae and anti-citrullinated peptide antibodies of P. gulae PAD in patients with RA and their possible relationship with clinical activity markers.

SUBJECTS AND METHODS: A total of 95 patients with RA and 95 controls were included. Erythrocyte sedimentation rate (ESR), C-reactive protein, anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) were measured. Activity index-28 (DAS28) and SCDAI. The periodontal diagnosis was established. Presence of P. gulae and P. gingivalis. An ELISA was used to determine antibodies against citrullinated peptides of P. gulae PAD.

RESULTS: A P. gulae frequency of 15.8% was observed in the RA group and 9.5% in the control group. Higher levels of ACPA were found in the P. gulae-positive patients of the RA group, finding no significant difference, but if in patients positive for P. gingivalis with statistical significance (p = 0.0001). The frequency of anti-VDK-cit and anti-LPQ-cit9 antibodies to PPAD of P. gulae was higher in the RA group than in the control group without significant difference. No relationship was found with the clinical variables despite the presence of P. gulae and anti-citrullinated peptide antibodies of P. gulae PPAD in patients with RA CONCLUSIONS: It was not possible to establish a connection with clinical variables in RA and P. gulae; as a result, the presence of P. gingivalis continues to contribute significantly to the increase in antibodies against citrullinated proteins/peptides from exogenous sources of citrullination in RA and periodontitis.

PMID:37133700 | DOI:10.1007/s00784-023-04964-w

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In vitro fatigue and fracture testing of temporary materials from different manufacturing processes in implant-supported anterior crowns

Clin Oral Investig. 2023 May 3. doi: 10.1007/s00784-023-05038-7. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the in vitro fatigue and fracture force of temporary implant-supported anterior crowns made of different materials with different abutment total occlusal convergence (TOC), with/without a screw channel, and with different types of fabrication.

MATERIALS AND METHODS: One hundred ninety-two implant-supported crowns were manufactured (4° or 8° TOC; with/without screw channel) form 6 materials (n = 8; 2 × additive, 3 × subtractive, 1 × automix; reference). Crowns were temporarily cemented, screw channels were closed (polytetrafluoroethylene, resin composite), and crowns were stored in water (37 °C; 10 days) before thermal cycling and mechanical loading (TCML). Fracture force was determined.

STATISTICS: Kolmogorov-Smirnov, ANOVA; Bonferroni; Kaplan-Meier; log-rank; α = 0.05.

RESULTS: Failure during TCML varied between 0 failures and total failure. Mean survival was between 1.8 × 105 and 4.8 × 105 cycles. The highest impact on survival presented the material (η2 = 0.072, p < .001). Fracture forces varied between 265.7 and 628.6 N. The highest impact on force was found for the material (η2 = 0.084, p < .001).

CONCLUSION: Additively and subtractively manufactured crowns provided similar or higher survival rates and fracture forces compared to automix crowns. The choice of material is decisive for the survival and fracture force. The fabrication is not crucial. A smaller TOC led to higher fracture force. Manually inserted screw channels had negative effects on fatigue testing.

CLINICAL RELEVANCE: The highest stability has been shown for crowns with a low TOC, which are manufactured additively and subtractively. In automix-fabricated crowns, manually inserted screw channels have negative effects.

PMID:37133699 | DOI:10.1007/s00784-023-05038-7

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Patient Management and Clinical Outcomes Associated with a Recorded Diagnosis of Stage 3 Chronic Kidney Disease: The REVEAL-CKD Study

Adv Ther. 2023 May 3. doi: 10.1007/s12325-023-02482-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Guidelines for the treatment of chronic kidney disease (CKD) recommend early intervention and management to slow disease progression. However, associations between diagnosis and CKD progression are not fully understood.

METHODS: REVEAL-CKD (NCT04847531) is a retrospective observational study of patients with stage 3 CKD. Data were extracted from the US TriNetX database. Eligible patients had two consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD (≥ 30 and < 60 ml/min/1.73 m2) recorded 91-730 days apart from 2015 to 2020. Diagnosed patients were included if their first CKD diagnosis code was recorded at least 6 months after their second qualifying eGFR measurement. We assessed CKD management and monitoring practices for the 180 days before and after CKD diagnosis, annual eGFR decline in the 2 years before and after CKD diagnosis, and associations between diagnostic delay and post-diagnosis event rates.

RESULTS: The study included 26,851 patients. After diagnosis, we observed significant increases in the prescribing rate of guideline-recommended medications such as angiotensin-converting enzyme inhibitors (rate ratio [95% confidence interval]: 1.87 [1.82, 1.93]), angiotensin receptor blockers (1.91 [1.85, 1.97]) and mineralocorticoid receptor antagonists (2.23 [2.13, 2.34]). Annual eGFR decline was significantly reduced following a CKD diagnosis, from 3.20 ml/min/1.73 m2 before diagnosis to 0.74 ml/min/1.73 m2 after diagnosis. Delayed diagnosis (by 1-year increments) was associated with elevated risk of CKD progression to stage 4/5 (1.40 [1.31-1.49]), kidney failure (hazard ratio [95% confidence interval]: 1.63 [1.23-2.18]) and the composite of myocardial infarction, stroke and hospitalization for heart failure (1.08 [1.04-1.13]).

CONCLUSIONS: A recorded CKD diagnosis was associated with significant improvements in CKD management and monitoring practices and attenuated eGFR decline. Recorded diagnosis of stage 3 CKD is an important first step to reduce the risk of disease progression and minimize adverse clinical outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04847531.

PMID:37133647 | DOI:10.1007/s12325-023-02482-5

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Use of Flash Glucose Monitoring and Glycemic Control in Patients with Type 2 Diabetes Mellitus Not Treated with an Intensive Insulin Regimen: 1-Year Real-Life Retrospective Cohort Study

Adv Ther. 2023 May 3. doi: 10.1007/s12325-023-02508-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Estimation of laboratory-derived glycated hemoglobin (HbA1c) cannot be individually used to monitor clinically significant trends in glucose variability. Hence, clinicians advise use of continuous glucose monitoring (CGM) devices such as the Freestyle Libre™ flash glucose monitoring system (FLASH) to optimize glycemic control by estimating glucose monitoring index (GMI) values, which convert mean glucose into an estimate of simultaneously measured laboratory HbA1c. This study aimed to investigate the sustainability of intermittently scanned continuous glucose monitoring (isCGM) in patients with type 2 diabetes mellitus (T2DM) not on intensive insulin regimen, and correlations between GMI values obtained from isCGM and laboratory-derived HbA1c values.

METHODS: A retrospective review of 93 patients with T2DM not on intensive insulin regimen, using FLASH device, was conducted at a major tertiary hospital in Saudi Arabia, over 1 year of continuous device use. To determine the sustainability of isCGM, various glycemic markers such as average glucose and time in range were evaluated. Paired t test or Wilcoxon signed-rank test was used to assess differences in markers of glycemic control, and Pearson’s correlation was used to determine correlations between HbA1c and GMI values.

RESULTS: Descriptive analysis shows the mean HbA1c value significantly decreased following continued use of isCGM. Pre-isCGM mean HbA1c value of 8.3% improved to 8.1% (p < 0.001) and 7.9% (p < 0.001) in the first 90 and last 90 days of device use, respectively. For both 90-day time periods, correlation analysis revealed a statistically significant positive correlation and linear regression between laboratory-derived HbA1c and GMI values (first 90 days r = 0.7999, p < 0.001; last 90 days r = 0.6651, p < 0.001).

CONCLUSION: Continuous use of isCGM demonstrated reductions in HbA1c levels for patients with T2DM not on an intensive insulin regimen. The GMI values showed high levels of agreement with measured HbA1c, indicating their accuracy in glucose management.

PMID:37133646 | DOI:10.1007/s12325-023-02508-y

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Alternative splicing shapes the transcriptome complexity in blackgram [Vigna mungo (L.) Hepper]

Funct Integr Genomics. 2023 May 3;23(2):144. doi: 10.1007/s10142-023-01066-4.

ABSTRACT

Vigna mungo, a highly consumed crop in the pan-Asian countries, is vulnerable to several biotic and abiotic stresses. Understanding the post-transcriptional gene regulatory cascades, especially alternative splicing (AS), may underpin large-scale genetic improvements to develop stress-resilient varieties. Herein, a transcriptome based approach was undertaken to decipher the genome-wide AS landscape and splicing dynamics in order to establish the intricacies of their functional interactions in various tissues and stresses. RNA sequencing followed by high-throughput computational analyses identified 54,526 AS events involving 15,506 AS genes that generated 57,405 transcripts isoforms. Enrichment analysis revealed their involvement in diverse regulatory functions and demonstrated that transcription factors are splicing-intensive, splice variants of which are expressed differentially across tissues and environmental cues. Increased expression of a splicing regulator NHP2L1/SNU13 was found to co-occur with lower intron retention events. The host transcriptome is significantly impacted by differential isoform expression of 1172 and 765 AS genes that resulted in 1227 (46.8% up and 53.2% downregulated) and 831 (47.5% up and 52.5% downregulated) transcript isoforms under viral pathogenesis and Fe2+ stressed condition, respectively. However, genes experiencing AS operate differently from the differentially expressed genes, suggesting AS is a unique and independent mode of regulatory mechanism. Therefore, it can be inferred that AS mediates a crucial regulatory role across tissues and stressful situations and the results would provide an invaluable resource for future endeavours in V. mungo genomics.

PMID:37133618 | DOI:10.1007/s10142-023-01066-4

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Filled Pauses Produced by Autistic Adults Differ in Prosodic Realisation, but not Rate or Lexical Type

J Autism Dev Disord. 2023 May 3. doi: 10.1007/s10803-023-06000-y. Online ahead of print.

ABSTRACT

We examined the use of filled pauses in conversations between homogeneous pairs of autistic and non-autistic adults. A corpus of semi-spontaneous speech was used to analyse the rate, lexical type (nasal “uhm” or non-nasal “uh”), and prosodic realisation (rising, level or falling) of filled pauses. We used Bayesian modelling for statistical analysis. We found an identical rate of filled pauses and an equivalent preference of “uhm” over “uh” across groups, but also a robust group-level difference regarding the intonational realisation of filled pauses: non-autistic controls produced a considerably higher proportion of filled pause tokens realised with the canonical level pitch contour than autistic speakers. Despite the fact that filled pauses are a frequent and impactful part of speech, previous work on their conversational use in autism spectrum disorder (ASD) is limited. Our account is the first to analyse the intonational realisation of filled pauses in ASD and the first to investigate conversations between autistic adults in this context. Our results on rate and lexical type can help to contextualise previous research, while the novel findings on intonational realisation set the stage for future investigations.

PMID:37133610 | DOI:10.1007/s10803-023-06000-y

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Mapping the photochemistry of cyclopentadiene: from theory to ultrafast X-ray scattering

Faraday Discuss. 2023 May 3. doi: 10.1039/d2fd00176d. Online ahead of print.

ABSTRACT

The photoinduced ring-conversion reaction when cyclopentadiene (CP) is excited at 5.10 eV is simulated using surface-hopping semiclassical trajectories with XMS(3)-CASPT2(4,4)/cc-pVDZ electronic structure theory. In addition, PBE0/def2-SV(P) is employed for ground state propagation of the trajectories. The dynamics is propagated for 10 ps, mapping both the nonadiabatic short-time dynamics (<300 fs) and the increasingly statistical dynamics on the electronic ground state. The short-time dynamics yields a mixture of hot CP and bicyclo[2.1.0]pentene (BP), with the two products reached via different regions of the same conical intersection seam. On the ground state, we observe slow conversion from BP to CP which is modelled by RRKM theory with a transition state determined using PBE0/def2-TZVP. The CP products are furthermore associated with ground state hydrogen shifts and some H-atom dissociation. Finally, the prospects for detailed experimental mapping using novel ultrafast X-ray scattering experiments are discussed and observables for such experiments are predicted. In particular, we assess the possibility of retrieving electronic states and their populations alongside the structural dynamics.

PMID:37132432 | DOI:10.1039/d2fd00176d

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OPTN/SRTR 2021 Annual Data Report: Introduction

Am J Transplant. 2023 Feb;23(2S1):S12-S20. doi: 10.1016/j.ajt.2023.02.003.

ABSTRACT

The OPTN/SRTR 2021 Annual Data Report presents the status of the solid organ transplantation system in the United States from 2010 through 2021. Organ-specific chapters are presented for kidney, pancreas, liver, intestine, heart, and lung transplant. Each organ-specific chapter is organized to present waitlist information, donor information (both deceased and living, as appropriate), transplant information, and patient outcomes. Data pertaining to pediatric patients are generally presented separately from the adult data. In addition to the organ-specific chapters, you will find chapters dedicated to deceased organ donation, vascularized composite allograft, and the COVID-19 pandemic. The data presented in the Annual Data Report are descriptive in nature. In other words, most tables and figures present raw data without statistical adjustment for possible confounding or changes over time. Therefore, the reader should keep in mind the observational nature of the data when attempting to draw inferences before trying to ascribe a cause to any observed patterns or trends. This introduction provides a brief overview of trends in waitlist and transplant activity. More detailed descriptions can be found in the respective organ-specific chapters.

PMID:37132351 | DOI:10.1016/j.ajt.2023.02.003

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Experiences of people with dementia and informal caregivers with post-diagnostic support: Data from the international COGNISANCE study

Int J Geriatr Psychiatry. 2023 May;38(5):e5916. doi: 10.1002/gps.5916.

ABSTRACT

OBJECTIVES: The study aims to describe people with dementia and informal caregivers’ respective experiences of support after diagnosis and compares these experiences. Additionally, we determine how people with dementia and informal caregivers who are satisfied with support differ from those dissatisfied.

METHODS: A cross-sectional survey study in Australia, Canada, the Netherlands, Poland, and United Kingdom was carried out to examine people with dementia and informal caregivers experience with support (satisfaction with information, access to care, health literacy, and confidence in ability to live well with dementia). The separate surveys contained closed questions. Analysis consisted of descriptive statistics and Chi-square tests.

RESULTS: Ninety people with dementia and 300 informal caregivers participated, and 69% of people with dementia and 67% of informal caregivers said support after diagnosis helped them deal more efficiently with their concerns. Up to one-third of people with dementia and informal caregivers were dissatisfied with information about management, prognosis, and strategies for living positively. Few people with dementia (22%) and informal caregivers (35%) received a care plan. People with dementia were more often satisfied with information, had more often confidence in their ability to live well with dementia, and were less often satisfied with access to care compared to informal caregivers. Informal caregivers who were satisfied with support were more satisfied with information and access to care compared to informal caregivers not satisfied with support.

CONCLUSIONS: Experience of dementia support can be improved and people with dementia and informal caregiver differ in their experiences of support.

PMID:37132330 | DOI:10.1002/gps.5916

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Early markers of Sepsis Cardiomyopathy in Murine Models by Echocardiography

Curr Med Imaging. 2023 Apr 28. doi: 10.2174/1573405620666230428123541. Online ahead of print.

ABSTRACT

BACKGROUND: Strain echocardiography (SE) is a procedure for analyzing myocardial dysfunction that is known to be less dependent on preload and afterload of heart function. Unlike dimension-based parameters, like ejection fraction (EF) and fractional shortening (FS), SE measures cardiac function by tracking cardiac tissue deformation and anomalies throughout the cardiac cycle. Although SE is proven to locate myocardial ailments in various heart diseases, few studies exist regarding using SE relevant to sepsis pathophysiology.

OBJECTIVE: The study aimed to calculate the myocardial strain and strain rates, like longitudianl strain (LS), global radial strain (GRS), and global longitudinal strain (GLS), and to show these to be reduced earlier in cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)-induced sepsis in coordination with an elevation of pro-inflammatory cytokines Methodology: Wild-type mice C57BL/6J (WT) were taken in this study and classified as CLP, LPS, and control groups. CLP surgery and LPS injection were given to induce sepsis. Endotoxemic septic shock was induced by intraperitoneal (IP) injection of LPS Escherichia coli. Echocardiography short axis views (SAX), longitudinal strain (LS), global circumferential strain (GCS), and global radial strain (GRS) were measured from the anterior and posterior positions of the septal and lateral walls of the heart. Real-time polymerase chain reaction (RT-PCR) was performed to evaluate post-CLP and LPS to analyze cardiac pro-inflammatory cytokines expressions. Inter- and intra-observer variables were tested by Bland-Altman analyses (BA). All data analysis was performed by GraphPad Prism 6 software. p<0.05 was taken as statistically significant.

RESULT: After 48 hours following CLP and LPS-induced sepsis, a significant declination in both longitudinal strain and strain rate (LS and LSR) was identified in the CLP and LPS groups compared to the control group. Strain depression in sepsis was linked with the up-regulation of pro-inflammatory cytokines in RT-PCR analysis.

CONCLUSION: In the present study, we found myocardial strain and strain rate parameters, like LS, GRS, and GLS, to be reduced after CLP and LPS-induced sepsis in coordination with the elevation of pro-inflammatory cytokines.

PMID:37132319 | DOI:10.2174/1573405620666230428123541