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Microarray expression results of VEGF, YAP1 and PTEN immunostains in preeclampsia cases

J Immunoassay Immunochem. 2023 Feb 23:1-9. doi: 10.1080/15321819.2023.2182219. Online ahead of print.

ABSTRACT

We aimed to evaluate the expression of YAP1, PTEN, VEGF in the placentas of patients with preeclampsia and placentas of healthy pregnant women for trophoblast invasion, which is similar to cancer etiopathogenesis. The placentas of 70 women who gave birth, including 30 preeclampsia and 40 healthy controls, were evaluated. YAP1, PTEN and VEGF immunohistochemical staining were performed using the microarray method on placental tissue. The mean ± standard deviation for YAP1, PTEN and VEGF intensity were; 1.57 ± 0.71,2.59 ± 0.80, 1.61 ± 0.59, respectively. PTEN intensity was statistically significantly lower in the preeclampsia group than in the control group (2.37 ± 0.99 vs 2.75 ± 0.58, p = .049). There was no difference between the groups in terms of YAP1 and VEGF staining (p > .05). The etiopathogenesis of preeclampsia is still unclear. However, since trophoblast invasion and endothelial repair have similar aspects with cancer mechanisms, both preeclampsia and cancer studies are progressing by supporting each other. Our study is a prototype study showing that large-participation studies can be carried out easily by using the microarray method as an economic model.

PMID:36815553 | DOI:10.1080/15321819.2023.2182219

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Association between hepatic angiosarcoma and end-stage renal disease: nationwide population-based evidence and enriched mutational signature of aristolochic acid exposure

J Pathol. 2023 Feb 23. doi: 10.1002/path.6072. Online ahead of print.

ABSTRACT

Hepatic angiosarcoma (HAS) is an aggressive mesenchymal malignancy that remains underexplored in its etiology and mutational landscapes. To clarify the association between HAS and end stage end-stage renal disease (ESRD), we exploited nationwide data of the National Health Insurance Research Database (NHIRD) in Taiwan, covering ~99% of the population, from 2001 to 2016. To investigate molecular signatures, we performed whole-exome sequencing (WES) in 27 surgical specimens, including 9 ESRD-associated cases. The NHIRD analysis demonstrated that HAS ranked 2nd among all angiosarcomas in Taiwan, with the incidence rates of HAS being 0.08, 2.49, and 5.71 per 100,000 person-years in the general population, chronic kidney disease (CKD), and ESRD patients, respectively. The standardized incidence ratios of HAS in CKD and ESRD patients were 29.99 and 68.77, respectively. In comparison with nonhepatic angiosarcoma, the multivariate regression analysis of our institutional cohort validated CKD/ESRD as an independent risk factor for HAS (odds ratio: 9.521, 95% confidence interval: 2.995-30.261, P < 0.001). WES identified a high tumor mutation burden (TMB; median: 8.66 variants per megabase) and dominant A:T-to-T:A transversion in HAS with frequent TP53 (81%) and ATRX (41%) mutations, KDR amplifications/gains (56%), and CDKN2A/B deletions (48%). Notably, ESRD-associated HAS had a significantly higher TMB (17.62 variants per megabase, P = 0.01) and enriched mutational signatures of aristolochic acid exposure (COSMIC SBS22, P < 0.001). In summary, a significant proportion of HAS in Taiwan is associated with ESRD and harbors a distinctive mutational signature, which concomitantly links nephrotoxicity and mutagenesis resulting from the exposure to aristolochic acid or related compounds. High TMB may support the eligibility for immunotherapy in treating ESRD-associated HAS. This article is protected by copyright. All rights reserved.

PMID:36815532 | DOI:10.1002/path.6072

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Is a new COVID-19 wave coming from China due to an unknown variant of concern? Keep calm and look at the data

J Med Virol. 2023 Feb 23. doi: 10.1002/jmv.28601. Online ahead of print.

ABSTRACT

Supported by the GISAID data, we discuss on the more or less probable increase in the number of COVID-19 cases in the very next future. Currently, all the sequenced case in Europe, USA and Asia refer to Omicron-related variants and recombinations. Accordingly, the increasing in the attention to the Covid situation is currently not justified by looking at the available indicators and at the current variants of concern recorded worldwide This article is protected by copyright. All rights reserved.

PMID:36815498 | DOI:10.1002/jmv.28601

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Investigating the impact of music therapy on two in-patient psychiatric wards for people living with dementia: retrospective observational study

BJPsych Open. 2023 Feb 23;9(2):e42. doi: 10.1192/bjo.2023.20.

ABSTRACT

BACKGROUND: Music therapy can lift mood and reduce agitation for people living with dementia (PwD) in community and residential care settings, potentially reducing the prevalence of distress behaviours. However, less is known about the impact of music therapy on in-patient psychiatric wards for PwD.

AIMS: To investigate the impact of music therapy on two in-patient psychiatric wards for PwD.

METHOD: A mixed-methods design was used. Statistical analysis was conducted on incidents involving behaviours reported as ‘disruptive and aggressive’ in 2020, when music therapy delivery varied because of the COVID-19 pandemic. Semi-structured interviews conducted online with three music therapists and eight ward-based staff were analysed using reflexive thematic analysis.

RESULTS: Quantitative findings showed a significant reduction in the frequency of behaviours reported as disruptive and aggressive on days with in-person music therapy (every 14 days) than on the same weekday with no or online music therapy (every 3.3 or 3.1 days, respectively). Qualitative findings support this, with music therapy reported by music therapists and staff members to be accessible and meaningful, lifting mood and reducing agitation, with benefits potentially lasting throughout the day and affecting the ward environment.

CONCLUSIONS: We identified a significant reduction in the occurrence of distress behaviours on days with in-person music therapy when compared with no music therapy. Music therapy was reported to be a valuable intervention, supporting patient mood and reducing agitation. Interventional studies are needed to investigate the impact of music therapy and its optimum mode of delivery.

PMID:36815454 | DOI:10.1192/bjo.2023.20

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Dissemination and reporting bias of clinical and observational studies conducted in the Local health unit of Verona.

Recenti Prog Med. 2023 Mar;114(3):163-169. doi: 10.1701/3981.39641.

ABSTRACT

INTRODUCTION: Bias in dissemination and reporting of clinical research findings has an impact on the pooled summary utilised to produce clinical-therapeutic guidelines and recommendations. This analysis aims to evaluate the dissemination and reporting biases of interventional and observational studies conducted in the setting of the Local health authority of Verona (Aulss). The possible correlation between both biases and profit versus no-profit sponsors was also evaluated.

METHODS: Verona’s Aulss studies completed in the period 01.01.2014-31.01.2021 were extracted from the Clinical study register of the Veneto Region and any form of results’ dissemination was identified and compared with the original protocol. Identified studies were stratified by profit or no-profit sponsor and results compared using the Chi-Square test.

RESULTS: 67 studies (29 profit; 38 non-profit) were included in this analysis. 58.2% of the studies (n=39/67) reports at least one type of findings’ dissemination, for 22.4% data-analysis or publication is in progress, while 19.4% has not been published. Regarding the evaluation on reporting bias, 36 of the 39 published studies were considered (n=19 profit; n=17 non-profit): 64% (23/36) showed inconsistencies between the results reported in the manuscript and the protocol. The number of non-compliant profit studies (n=15/19; 79%) was statistically higher than the compliant ones [n=8/17; 47%; (p=0.049; χ2=3.845)].

DISCUSSION: This study highlights that findings’ dissemination occurs for the majority of the studies evaluated and that the odds of selective reporting are higher for industry funded studies than for publicly funded studies, affecting the quality of the research.

PMID:36815420 | DOI:10.1701/3981.39641

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Focal adhesion formation of primary human gingival fibroblast on hydrothermally and in-sol-made TiO2 -coated titanium

Clin Implant Dent Relat Res. 2023 Feb 23. doi: 10.1111/cid.13195. Online ahead of print.

ABSTRACT

Optimal cell adhesion of the gingival fibroblasts to dental implants is important for maintaining good implant integration. The aim of this study was to discover, if the nanoporous TiO2 -coating on titanium alloy substrates is able to increase the cell adhesion of the human gingival fibroblasts (HGF). The study consisted of three differently produced titanium groups: hydrothermally produced TiO2 -coating (HT), novel TiO2 -coating made in sol (SOL), and noncoated control group. Primary HGF cells were initiated from gingival biopsies from patients having a third molar extraction. HGF were cultivated on titanium discs for 2 and 24 h to determine the initial attachment with confocal microscope. The cell spreading and adhesion protein signals were measured. In addition, expression of adhesion proteins vinculin, paxillin, and focal adhesion kinase (FAK) were measured after 3 days of cultivation by using Western Blotting. Higher protein levels of paxillin, vinculin, and FAK were induced on both coated discs compared to noncoated discs. The difference was statistically significant (p < 0.05) concerning expression of paxillin. The cell spreading was significantly larger on SOL discs after 2 and 24 h when comparing to noncoated controls. The confocal microscope analyses revealed significantly higher adhesion protein signals on both HT- and SOL-coated titanium compared to control group. This study showed, that both methods to produce TiO2 -coatings are able to increase HGF adhesion protein expression and cell spreading on titanium surface. Accordingly, the coatings can potentially improve the gingival attachment to titanium implant surfaces.

PMID:36815407 | DOI:10.1111/cid.13195

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Impact of vincristine dose reduction on outcomes of patients with aggressive B-cell lymphoma treated with (R) – CHOP

Haematologica. 2023 Feb 23. doi: 10.3324/haematol.2022.282126. Online ahead of print.

ABSTRACT

Not available.

PMID:36815369 | DOI:10.3324/haematol.2022.282126

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Hypometabolism of the left middle/medial frontal lobe on FDG-PET in anti-NMDA receptor encephalitis: Comparison with MRI and EEG findings

CNS Neurosci Ther. 2023 Feb 23. doi: 10.1111/cns.14125. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate changes in brain-glucose metabolism in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, and compare results with MRI and electroencephalography (EEG) findings at different disease stages.

METHODS: The clinical data of 18 patients (median age, 35 years; 11 men) were retrospectively collected. Patients were divided into groups based on the time of symptom onset to examination, (≤1 month, >1 but ≤3 months, >3 months). Two-sample t-test results were compared with age and sex-paired healthy controls using statistical parametric mapping and verified using a NeuroQ software normal database with a discriminating z-score of 2.

RESULTS: Abnormal patterns on FDG-PET differed over time (T = 3.21-8.74, Z = 2.68-4.23, p < 0.005). Regional analysis showed hypometabolic left middle or medial frontal cortex in 4/5, 5/7, and 5/6 patients, respectively. Time-subgroup analysis revealed hypermetabolic supertemporal cortex in 4/5, 5/7, and 2/6, patients, respectively. MRI and EEG abnormalities in any region and stage occurred in 10/18 and 10/16 patients, respectively. MRI and EEG time-subgroup analysis showed abnormalities in 5/9, 4/5, and 1/4, and 1/3, 6/7, and 3/6 patients, respectively. Abnormal temporal lobes were detected most frequently in MRI analyses and occurred in 3/10 patients.

CONCLUSIONS: Decreased left middle/medial frontal metabolism could be common to all stages. Metabolism in other regions, MRI, and EEG results were associated with the progression of anti-NMDAR encephalitis. The sensitivity rate of FDG-PET was superior to that of MRI and EEG.

PMID:36815303 | DOI:10.1111/cns.14125

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Pulmonary important outcomes after extremely preterm birth: parental perspectives

Acta Paediatr. 2023 Feb 23. doi: 10.1111/apa.16723. Online ahead of print.

ABSTRACT

AIM: To describe pulmonary important outcomes (PIO) reported by parents of children born extremely preterm.

METHODS: Over one-year, all parents of children aged 18 months-7-years born <29 weeks’ GA were asked regarding their perspectives. The proportion of parents who described PIO and the themes they invoked were examined. Results were analyzed using mixed methods.

RESULTS: Among parental responses (n=285, 98% participation rate), 44% spoke about PIO, invoking 24 themes pertaining to NICU hospitalization and/or long-term respiratory health. Some themes had an impact primarily on the child (eg: exercise limitation), while the majority had an impact on the whole family (eg: hospital readmissions). None mentioned oxygen at 36 weeks nor bronchopulmonary dysplasia (BPD). The proportion of responses invoking PIO were statistically similar between parents of children with and without BPD, born before or after 25-weeks, or with birthweight < or ≥750g. PIO were more likely to be mentioned in males and among those readmitted for respiratory problems.

CONCLUSION: Parents describe many PIO, most related to the functional impact of lung disease on their child (and family), rather then the diagnosis of BPD itself. Most of these PIO are not primary outcomes in large neonatal trials, nor collected in neonatal databases.

PMID:36815277 | DOI:10.1111/apa.16723

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A pharmacokinetic model of anti-seizure medication load to guide care in the Epilepsy Monitoring Unit

Epilepsia. 2023 Feb 23. doi: 10.1111/epi.17558. Online ahead of print.

ABSTRACT

OBJECTIVE: Evaluating patients with drug-resistant epilepsy often requires inducing seizures by tapering anti-seizure medications (ASMs) in the Epilepsy Monitoring Unit (EMU). The relationship between ASM taper strategy, seizure timing and severity remains unclear. In this study, we developed and validated a pharmacokinetic model of total ASM load and tested its association with seizure occurrence and severity in the EMU.

METHODS: We studied 80 patients who underwent intracranial EEG recording for epilepsy surgery planning. We developed a first-order pharmacokinetic model of the ASMs administered in the EMU to generate a continuous metric of overall ASM load. We then related modeled ASM load to seizure likelihood and severity. We determined the association between the rate of ASM load reduction, the length of hospital stay and the probability of having a severe seizure. Finally, we used modeled ASM load to predict oncoming seizures.

RESULTS: Seizures occurred in the bottom 50th -percentile of sampled ASM loads across the cohort (p < 0.0001, Wilcoxon sign-rank test), and seizures requiring rescue therapy occurred at lower ASM loads than seizures that did not require rescue therapy (logistic regression mixed effects model, odds ratio = 0.27, p = 0.01). Greater ASM decrease early in the EMU was not associated with an increased likelihood of having a severe seizure, nor with a shorter length of stay.

SIGNIFICANCE: A pharmacokinetic model can accurately estimate ASM levels for patients in the EMU. Lower modeled ASM levels are associated with increased seizure likelihood and seizure severity. We show that ASM load, rather than ASM taper speed, is associated with severe seizures. ASM modeling has the potential to help optimize taper strategy to minimize severe seizures while maximizing diagnostic yield.

PMID:36815252 | DOI:10.1111/epi.17558