Sunday, July 31, 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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Incidence, risk factors, outcomes, and clinical management of BK viremia in the modern era of kidney transplantation

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ABSTRACT

Background

: BK viremia is endemic among kidney transplant recipients (KTR). Incidence, risk factors, outcomes, and clinical management of detectable versus high BK viremia have not been considered previously in KTR in the modern era.

Methods

: This observational study examined KTR transplanted between January 1, 2009 and December 31, 2016. Any BK viral load in the serum constituted detectable BK viremia and ≥103 copies/mL constituted high viremia.

Results

: Among 1,193 KTR, the cumulative probability of developing detectable and high BK viremia within two years post-transplant were 27.8% and 19.6%, respectively. Significant risk factors for detectable BK viremia included recipient age (HR 1.02 [95% CI: 1.01, 1.03]) and donor age (HR 1.01 [95% CI: 1.00, 1.02]). Recipient age also predicted high BK viremia (HR 1.02 [95% CI: 1.01, 1.03]), whereas White race (HR 0.70 [95% CI: 0.52, 0.95]), non-depleting induction therapy (HR 0.61 [95% CI: 0.42, 0.89]), and delayed graft function (HR 0.61 [95% CI: 0.42, 0.88]) were protective. Mean estimated glomerular filtration rates were 4.28 mL/min/1.72 m2 (95% CI: 2.71, 5.84) lower with detectable BK viremia. Although low viral load was usually not acted upon at first presentation, anti-proliferative dose reductions were the most common initial management.

Conclusion

: BK viremia remains a common early complication in a modern cohort of KTR. These findings highlight the benefit of early BKV monitoring in addition to intensive clinical management. Clinical responses beyond first positive BK viremia tests, and their implications for graft outcomes, merit further investigation.

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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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Genomic Annotation and Molecular Evolution of Monkeypox Virus Outbreak in 2022

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ABSTRACT

Monkeypox virus (MPXV) has generally circulated in West and Central Africa since its emergence. Recently, sporadic MPXV infections in several non-endemic countries have attracted widespread attention. Here, we conducted a systematic analysis of the recent outbreak of MPXV-2022, including its genomic annotation and molecular evolution. The phylogenetic analysis indicated that the MPXV-2022 strains belong to the same lineage of the MPXV strain isolated in 2018. However, compared with the MPXV strain in 2018, in total 46 new consensus mutations were observed in the MPXV-2022 strains, including 24 non-synonymous mutations. By assigning mutations to 187 proteins encoded by the MPXV genome, we found that ten proteins in the monkeypox virus are more prone to mutation, including D2L-like, OPG023, OPG047, OPG071, OPG105, OPG109, A27L-like, OPG153, OPG188, and OPG210 proteins. In the MPXV-2022 strains, 4 and 3 nucleotide substitutions are observed in OPG105 and OPG210 , respectively. Overall, our studies illustrated the genome evolution of the ongoing MPXV outbreak and pointed out novel mutations as a reference for further studies.

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Case volume regionalization and volume‐based outcome differences in cutaneous head and neck melanoma

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Abstract

Background

Hospital volume has emerged as a prognostic factor in oncology but is not currently known whether volume is associated with improved outcomes for cutaneous head and neck (HN) melanoma.

Methods

A total of 556 079 cutaneous melanoma cases reported by the 2004–2016 National Cancer Database were separated into two cohorts (HN and non-HN) and facilities within each cohort were classified by case volume. Analysis employed chi-square, analysis of variance, Kaplan–Meier, and Cox proportional hazards models.

Results

Only 41 facilities (3.1% of 1326) treating HN melanoma and 50 facilities (3.7% of 1344) treating non-HN melanoma were classified as high-volume facilities (HVFs). The estimated 5-year overall survival (OS) was 62.7% (standard error [SE]: 0.4%) for patients with HN at low-volume facilities (LVFs), 69.3% (SE: 0.4%) at IVFs, and 71.8% (SE 0.4%) at HVFs (p < 0.001). Differences in OS remained significant between HVFs versus LVFs after adjusting for confounders.

Conclusion

Volume is independently associated with OS and improved surgical outcomes for HN melanoma.
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Menopausal hormone therapy and subclinical cardiovascular disease in women with and without HIV

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with HIV who have heightened immune activation and cardiovascular risks.
Methods
Among 609 post-menopausal women (1,234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis – carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors.
Results
Women (mean age = 51, 80% HIV+) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio = 0.57; 95% CI = [0.40, 0.80]; p < 0.01), 2.51 µm less progression of CIMT per year (95% CI = [-4.60, -0.41]; p = 0.02), and marginally lower incidence of plaque over ∼7 years (risk ratio = 0.38; 95% CI = [0.14, 1.03]; p = 0.06), compared with never users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment.
Conclusions
HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.
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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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Empiric versus pre-emptive antifungal strategy in high-risk neutropenic patients on fluconazole prophylaxis: a randomized trial of the European organization for Research and Treatment of cancer (EORTC 65091)

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Abstract
Background
Empiric antifungal therapy is considered the standard-of-care for high-risk neutropenic patients with persistent fever. The impact of a pre-emptive, diagnostic-driven approach based on galactomannan (GM) screening and chest CT-scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown.
Methods
Patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (Arm A) or pre-emptively (Arm B). All patients received fluconazole 400 mg daily as prophylaxis. The primary endpoint of this non-inferiority study was overall survival (OS) 42 days after randomization.
Results
Of 556 patients recruited, 549 were eligible: 275 in Arm A, 274 in Arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemothe rapy and 93% of them were in first induction phase. At day 42, the OS was not inferior in Arm B (96.7%; 95% confidence interval (CI), 93.8 - 98.3%) when compared to Arm A (93.1%; 95% CI, 89.3 - 95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95%CI, 4.5–10.8%) in Arm B versus 6.6% (95%CI, 3.6–9.5%) in Arm A, respectively. The rate of patients receiving caspofungin was significantly lower in Arm B (27%) than in Arm A (63%) (p < 0.001).
Conclusions
The pre-emptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs.
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Cytocompatibility and bioactive potential of AH Plus Bioceramic Sealer: an in vitro study

alexandrossfakianakis shared this article with you from Inoreader

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

alexandrossfakianakis shared this article with you from Inoreader
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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