Κυριακή 31 Ιουλίου 2022

A modified dentin infection model with Fluorescent Lipopolysaccharide and LPS sampling technique to compare XP‐Endo finisher and passive ultrasonic irrigation

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Abstract

Aim

The LPS-dentine-infection models and sampling techniques frequently used to evaluate LPS disinfection have limitations. In this study, a lipopolysaccharides-dentine-infection (LPS-dentine-infection) model was devised using fluorescent conjugate LPS. Secondly, a sampling technique using cryogenic grinding for intraradicular LPS analysis was evaluated. Thirdly, the effectiveness of the XP-endo Finisher (XP-EF) was compared with passive ultrasonic irrigation (PUI) in removing LPS from root canal system.

Methodology

Sixty-nine mandibular premolars was submitted to dentine pretreatment and inoculated with fluorescent LPS conjugate (Alexa Fluor® 594). Twenty-three teeth were analysed under confocal laser scanning microscopy (CLSM) to validate this modified LPS-dentine-infection model. Forty-six teeth were randomly divided into two experimental groups: XP-EF (n = 23) and PUI (n = 23). All teeth were instrumented with XP-endo shaper (XPS; FKG Dentaire, La Chaux-de-Fonds, Switzerland) and 2.5% NaOCl. The root canals were sampled with paper points before (s1) and after (s2) instrumentation and after supplemental treatment (s3) with XP-EF and PUI. After s3, all roots were cryogenically ground for intraradicular LPS analysis (s4). Limulus amebocyte lysate (LAL) assay was used for LPS quantification. The Friedman test was used for differences in LPS among four timepoints (s1, s2, s3, and s4). Dunn's test was used for pairwise testing of timepoints. The significance level wa s set at 5% (P < .05).

Results

Fluorescent LPS conjugate was detected in 100% of the samples under CLSM with a penetration depth of approximately 400 μm into dentine. Chemo-mechanical preparation using XPS files significantly reduced LPS levels (p < .05). Both the XPS and PUI improved the LPS disinfection (p < .05), with no difference between them (p > .05). LPS was recovered from all samples after cryogenic grinding. The residual amount of LPS detected using the cryogenically sampling technique at s4 was approximately 3 times greater than with the paper point sampling technique at s3.

Conclusion

This study established a modified LPS-dentine-infection model using fluorescent conjugate LPS, and validated a LPS sampling technique for using cryopulverization intraradicular LPS analysis. Moreover, both the XP-EF and PUI further improved LPS disinfection from the root canals, and the innovative XP-EF was as effective as PUI.

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No Reduction in the 226-Hz Probe Tone Acoustic Reflex Amplitude Following Severe Inner Hair Cell Loss in Chinchillas

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AbstractThe relationship between the middle ear acoustic reflex (AR) and inner hair cell (IHC) loss is currently unknown. Given that IHC are believed to convey nearly all acoustic information to the central auditory nervous system, it has been assumed that loss of IHC would significantly impact the AR. To evaluate this relationship, we assessed the presence and amplitude of the AR in chinchillas before and after treatment with carboplatin, an anticancer drug that reliably and selectively destroys IHC in this species. Baseline measures of hearing sensitivity, including auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAE), were assessed and then re-evaluated following carboplatin treatment. Post-carboplatin ABR thresholds and DPOAE were found to b...
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Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe COVID-19: The PANCOVID Randomized Clinical Trial

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Abstract
Background
This study was designed to evaluate if patients with high risk for severe COVID-19 would benefit from treatment with TDF/FTC followed by baricitinib in case of hypoxemia and systemic inflammation.
Methods
PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥ 2 comorbidities or older than 60 years conducted between 10 October 2020 and 23 September 2021. In the first randomization patients received TDF/FTC or not TDF/FTC. In the second randomization patients with room-air O2 saturation <95% and at least one increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in th e number of cases and a mortality rate substantially lower than expected EudraCT registration number: 2020-001156-18.
Results
Of the 355 included participants 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% CI 0.52-5.91; p= 0.379); it was 0.42 (95% CI 0.11-1.59; p= 0.201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI 0.66-1.40; p = 0.774); it was 0.90 (95%CI 0.61-1.33; p = 0.687) for those treated with baricitinib.
Conclusions
Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials.
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Cytocompatibility and bioactive potential of AH Plus Bioceramic Sealer: an in vitro study

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Abstract

Abstract

Aim

To assess the cytocompatibility and bioactive potential of the new calcium silicate cement-based sealer AH Plus Bioceramic Sealer (AHPbcs) on human periodontal ligament stem cells (hPDLSCs) compared to the epoxy resin-based sealer AH Plus (AHP) and the calcium silicate cement-based sealer Endosequence BC Sealer (ESbcs).

Methodology

Standardized sample discs and 1:1, 1:2, and 1:4 eluates of the tested materials were prepared. The following assays were performed: surface element distribution via SEM-EDX, cell attachment and morphology via SEM, cell viability via a MTT assay, cell migration/proliferation via a wound-healing assay, osteo/cemento/odontogenic marker expression via RT-qPCR, and cell mineralized nodule formation via Alizarin Red S staining. HPDLSCs were isolated from extracted third molars. Comparisons were made with hPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media. Statistical significance was established at p<0.05.

Results

A higher peak of Ca2+ was detected from ESbcs compared with AHPbcs and AHP in SEM-EDX. Both AHPbcs and ESbcs showed significantly positive results in the cytocompatibility assays (cell viability, migration/proliferation, attachment, and morphology) compared with a negative control group, while AHP showed significant negative results. Both AHPbcs and ESbcs exhibited an upregulation of at least one osteo/odonto/cementogenic marker compared to the negative and positive control groups. Both ESbcs and AHPbcs showed a significantly higher calcified nodule formation than the negative and positive control groups, indicative of their biomineralization potential, and were also significantly higher than AHP group.

Conclusion

AH Plus Bioceramic Sealer exhibited a significantly higher cytocompatibility and bioactive potential than AH Plus, and a similar cytocompatibility to that of Endosequence BC Sealer. Endosequence BC Sealer exhibited a significantly higher mineralization potential than the other tested sealers. The results from this in vitro study act as supporting evidence for the use of AH Plus bioceramic sealer in root canal treatment.

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Newborn body composition and child cardiovascular risk markers: a prospective multi-ethnic Asian cohort study

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Abstract
Background
Early epidemiological studies have associated low birthweight with increased cardiovascular risk. We aimed to examine whether the fat and fat-free components of birthweight have differing relationships with childhood cardiovascular risk markers.
Methods
In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, air displacement plethysmography was conducted within 24 h after delivery in 290 naturally conceived singletons. We investigated associations of newborn cohort-specific standardized z-score of fat mass, fat-free mass, body fat percentage and birthweight on child (at 6 years of age) carotid intima-media thickness, pulse wave velocity, blood pressure, prehypertension/hypertension (>110/70 mmHg) and standardized systolic and diastolic blood pressure (SBP and DBP) trajectories (at 3–6 years of age), taking account of maternal education, height, tobacco exposure, parity, ethnicity, child� �s sex, gestational age, age at follow-up, and other maternal factors.
Results
Clear inverse associations were seen for blood pressure with z-score of fat mass [SBP, β (95% CI): −1.31 mmHg (−2.57, −0.06); DBP: −0.79 mmHg (−1.74, 0.15)] and body fat percentage [SBP: −1.46 mmHg (−2.73, −0.19); DBP: −0.80 mmHg (−1.75, 0.16)], but not with fat-free mass [SBP: 0.27 mmHg (−1.29, 1.83)]; DBP: −0.14 mmHg (−1.30, 1.03)]. Being in the lowest tertile of fat mass or body fat percentage was associated with higher blood pressure trajectories and prehypertension/hypertension risk [OR (95% CI), fat mass: 4.23 (1.41, 12.68); body fat percentage: 3.22 (1.09, 9.53)] without concomitantly higher overweight/obesity risk.
Conclusions
At birth, low adiposity was associated with increased childhood blood pressure. Low newborn adiposity might serve as a marker of poor fetal growth or suboptimal intrauterine conditions associated with hypertension risk later in life.
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Long-term wellbeing and neurocognitive functioning of diffuse low-grade glioma patients and their caregivers: a longitudinal study spanning two decades

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Abstract
Background
While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumour progression which may impact on patients' long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQOL investigations (T1, M=7 and T2 M=13 years after diagnosis).
Methods
Participants completed HRQOL (SF-36; EORTC-BN20), fatigue (Checklist Individual Strength (CIS)), and depression (Center for Epidemiological Studies-Depression (CES-D)) questionnaires and underwent NCF assessments. T3 scores were compared with matched controls. Change over time (T1-T2-T3) on group and participant level were assessed. Where available, histology of the initial tumour was revised and immunohistochemical staining for IDH1 R 132H mutant protein was performed.
Results
Thirty patients and nineteen caregivers participated. Of N=11 with tissue available, 3 patients had confirmed diffuse LGG. At T3, patients (M=26 years after diagnosis) had HRQOL and NCF similar to, or better than controls, yet 23.3% and 53.3% scored above the cut-off for depression (≥16 CES-D) and fatigue (≥35 CIS), respectively. Caregivers' HRQOL was similar to controls, but reported high rates of fatigue (63.2%). Over time, patients' mental health improved (p<.05). Minimal detectable change in HRQOL over time was observed in individual patients (30% improvement; 23.3% decline; 20% both improvement and decline) with 23.3% remaining stable. NCF remained stable or improved in 82.8% of patients.
Conclusions
While HRQOL and NCF do not appear greatly impacted during long-term survivorship in LGG, d epressive symptoms and fatigue are persistent.
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Πέμπτη 28 Ιουλίου 2022

STATIN USE MAY BE ASSOCIATED WITH A LOWER RISK OF INVASIVE ASPERGILLOSIS IN LUNG TRANSPLANT RECIPIENTS

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Abstract
Background
Statins are competitive inhibitors of HMG-CoA reductase that catalyses HMG-CoA conversion to mevalonate, a process involved in synthesizing cholesterol in humans and ergosterol in fungi. The effect of statin use on the risk of development of invasive aspergillosis (IA) in lung transplant recipients (LTRs) is not well documented.
Methods
This retrospective study included LTRs from 2010 to 2017 who were followed for one-year post-transplant. Proven or probable IA was diagnosed as per ISHLT criteria. We performed a multivariable Cox proportional hazards model of the association between IA and statin use (minimum of two weeks duration prior to IA), adjusting for other known IA risk factors.
Results
We identified 785 LTRs, 44% female, mean age 53 years old, the most common underlying disease being pulmonary fibrosis (23.8%). 451 LTRs (57%) received statins post-transplant, atorvastatin was the most commonly used statin (68%). The mean duration of statins post-transplant was 347 days (IQR: 305 to 346). 55 (7%) LTRs developed IA in the first-year post-transplant. Out of these 55 LTRs, 9 (16.3%) had received statin before developing IA. In multivariable analysis, statin use was independently associated with a lower risk of IA (p = 0.002, SHR 0.30, CI 95% 0.14-0.64). Statin use was also associated with a lower incidence of post-transplant Aspergillus colonization, 114 (34%) in the no statin group vs. 123 (27%) in the statin group (p = 0.038).
Conclusions
The use of statin for a minimum of two weeks during the first-year post-transplant was associated with a 70% risk reduction of IA in LTRs.
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Τρίτη 26 Ιουλίου 2022

Reinfection with SARS‐CoV‐2 in general population,

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Abstract

To better understand epidemiology of SARS-CoV-2 reinfections, we analyzed national data from South Korea n who were followed longitudinally from January 2020 to April 2022. We conducted a nationwide retrospective cohort study to estimate possible SARS-CoV-2 reinfection rates in all residents in South Korea, with at least two episodes of laboratory-confirmed SARS-CoV-2 infection by reverse-transcriptase polymerase chain reaction (RT-PCR) or rapid antigen test (RAT) performed at least 45 or more days between both episodes, between January 2020 and April 2022. There were 1,6130,855 laboratory-confirmed SARS-CoV-2 cases in South Korea, with 55,841 (346.2 per 100,000; or 0.3% of all infections) were cases of possible reinfections. Reinfection rate has increased from 6.0 cases per 100,000 during Pre-Delta period to 128.0 cases per 100,000 and 355.1 cases per 100,000 during Delta and Omicron periods, respectively. Persons with one dose of vaccination had the highes t reinfection rate of 642.2 per 100,000, followed by unvaccinated persons (536.2/100,000) and two-dose vaccinated persons (406.3/100,000). Our finding suggests the majority of possible reinfections occurred following emergence of new variants.

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the Incidence and Outcomes of Early-Onset Well-differentiated Neuroendocrine Neoplasms

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imageObjective: The objective of this study was to evaluate the incidence and outcomes of adults with early-onset (20 to 34 y) diagnosis of well-differentiated neuroendocrine neoplasms. Methods: Surveillance, Epidemiology, and End Results (SEER)-18 database was accessed, and patients with well-differentiated lung or digestive tract neuroendocrine neoplasms diagnosed 2000 to 2018 were reviewed. Annual percent changes (APCs) were calculated for the 3 disease subsites (foregut, midgut, and hindgut) stratified by age group. Kaplan-Meier survival estimates/log-rank testing were used to examine differences in overall survival between the 3 age groups. Multivariable Cox regression analyses were used to evaluate factors affecting overall and cancer-specific survivals. Results: Throughout the study period, patients with early-onset disease (20 to 34 y) have experienced the greatest APC (20 to 34 y: 9.7; 35 to 49 y: 5.4; ≥50 y: 4.1). When APCs were stratified by disease subsite, this difference in APCs appears to be driven by midgut tumors (20 to 34 y: 19.2; 35 to 49: 8.4; ≥50 y: 3.8). Using multivariable Cox regression modeling, the following variables were associated with a higher risk of all-cause death (worse overall survival): male sex (hazard ratio [HR] 1.27; 95% confidence interval [CI]: 1.22-1.31), African American race (HR vs. white race: 1.20; 95% CI: 1.15-1.26), nonhindgut primary (HR foregut vs. hindgut primary: 2.02; 95% CI: 1.91-2.13; HR midgut vs. hindgut primary: 2.09; 95% CI: 1.95-2.24), distant disease (HR vs. regional disease: 2.06; 95% CI: 1.96-2.18), no surgery to the primary (HR: 2.34; 95% CI: 2.24-2.46), and older age (HR: 5.80; 95% CI: 4.87-6.91). Conclusion: Cases of early-onset well-differentiated neuroendocrine neoplasms have disproportionately increased over the past 2 decades (compared with other age groups), and this appears to have been driven mainly by midgut tumors.
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