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Τρίτη 26 Απριλίου 2022

Disclosure of suicidal thoughts and behaviors: The impact of suicide event type

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Abstract

Objectives

Despite its importance, limited work has investigated the nuances of suicidal thoughts and behavior self-disclosure. The present study aimed to examine potential differences in self-disclosure based on whether an individual has disclosed suicidal thinking versus behavior.

Methods

Two hundred and four participants having disclosed their suicidal thoughts or behaviors completed a battery of online questionnaires assessing several key aspects of disclosure (i.e., disclosure recipient, perceived helpfulness of disclosure, impact on treatment seeking), as it pertained to both one's first and overall disclosure experiences.

Results

Individuals who disclosed a suicide attempt, versus ideation, were more likely to have disclosed to a formal support (i.e., health professional) and to seek professional help following disclosure. No significant group differences in perceived helpfulness of experiences were found.

Conclusion

It may be beneficial to increase opportunities for disclosure of suicidal thinking. Overall, disclosures were perceived as helpful and may not impede future help-seeking behavior.

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The response of dual‐species bacterial biofilm to 2% and 5% NaOCl mixed with etidronic acid: a laboratory real‐time evaluation using optical coherence tomography.

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Abstract

Aim

The addition of etidronic acid (HEDP) to sodium hypochlorite (NaOCl) could increase the antibiofilm potency of the irrigant, while maintaining the benefits of continuous chelation. Studies conducted so far have shown that mixing HEDP with NaOCl solutions of relatively low concentration does not compromise the antibiofilm efficacy of the irrigant. However, the working lifespan of NaOCl may decrease resulting in a reduction of its antibiofilm efficacy over time (efficiency). In this regard, continuous irrigant replenishment needs to be examined. This study investigated the response of a dual-species biofilm when challenged with 2% and 5% NaOCl mixed with HEDP for a prolonged timespan and under steady laminar flow.

Methodology

Dual-species biofilms comprised of Streptococcus oralis J22 and Actinomyces naeslundii T14V-J1 were grown on human dentine discs in a constant depth film fermenter (CDFF) for 96 h. Biofilms were treated with 2% and 5% NaOCl, alone or mixed with HEDP. Irrigants were applied under steady laminar flow for 8 min. Biofilm response was evaluated by means of optical coherence tomography (OCT). Biofilm removal, biofilm disruption, rate of biofilm loss and disruption as well as bubble formation were assessed. One-way ANOVA, Wilcoxon's signed-rank test and Kruskal-Wallis H test were performed for statistical analysis of the data. The level of significance was set at a ≤ 0.05.

Results

Increasing NaOCl concentration resulted in increased biofilm removal and disruption, higher rate of biofilm loss and disruption and increased bubble formation. Mixing HEDP with NaOCl caused a delay in the antibiofilm action of the latter, without compromising its antibiofilm efficacy.

Conclusions

NaOCl concentration dictates the biofilm response irrespective of the presence of HEDP. The addition of HEDP resulted in a delay in the antibiofilm action of NaOCl. This delay affects the efficiency, but not the efficacy of the irrigant over time.

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Edaravone dexborneol protects cerebral ischemia reperfusion injury through activating Nrf2/HO‐1 signaling pathway in mice

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Abstract

Stroke is the leading cause of disability and death. When blood flow is restored after prolonged ischemia and hypoxia, it leads to excessive production of reactive oxygen species (ROS), increased local inflammation and apoptosis, which are the cause of most cerebral ischemia reperfusion injury (CIRI), leading to secondary brain tissue damage. Edaravone dexborneol is a novel neuroprotective agent consisting of edaravone and borneol. Studies have shown that it has synergistic antioxidant and anti-inflammatory effects. However, whether Edaravone dexborneol stimulates the Nrf2/HO-1 pathway to regulate NADPH oxidase 2 (NOX2) remains unclear. In this study, wild type (WT) mice and Nrf2 knockout (KO) mice were used to investigate the antioxidant, anti-inflammatory and anti-apoptotic effects of Edaravone dexborneol on CIRI and its mechanism. The cognitive function of mice was evaluated with the Morris Water Maze (MWM) test and the cell structures of hippocampus were observed by HE stainin g. Nrf2, HO-1 and NOX2 proteins and apoptosis-related proteins Bcl-2, Bax and Caspase 3 were detected by Western blotting. Nrf2, HO-1, NOX2 and inflammatory factors TNF-α, IL-1β, IL-4 and IL-10 were detected by real time polymerase chain reaction. The results showed that Edaravone dexborneol treatment improved learning and memory performance, neuronal damage, and enhanced antioxidant, inflammation, and apoptosis in CIRI mice. In addition, Edaravone dexborneol induced the activation Nrf2/HO-1 signaling pathway activation while inhibiting NOX2 expression. Overall, these results indicate that Edaravone dexborneol ameliorates CIRI-induced memory impairments by activating Nrf2/HO-1 signaling pathway and inhibiting NOX2.

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Immunosuppressants contribute to a reduced risk of Parkinson’s disease in rheumatoid arthritis

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Abstract
Background
Observational studies have suggested a decreased risk of Parkinson's disease (PD) in patients with rheumatoid arthritis (RA). However, the results are controversial and the biological mechanism underlying this effect remains largely unknown.
Methods
T he effect sizes of five observational studies were summarized to determine the association between RA and PD. A two-step Mendelian randomization (TSMR) analysis was conducted using genome-wide association studies data sets of RA, PD and prescription of non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants (IS) and glucocorticoids (GC). A multivariable MR (MVMR) was also performed to verify the impact of prescription history on PD risk.
Results
Integrated data from observational studies showed that RA was associated with a decreased risk of PD in the European population (effect size = –0.38, P = 0.004). We found that genetically predicted RA was correlated with a decreased risk of PD [odds ratio (OR)=0.91, P = 0.007]. In the TSMR, RA patients tended to have an increased prescription of GC (OR = 1.16, P = 2.96e − 07) and IS (OR = 1.77, P = 5.58e − 64), which reduced the risk of PD (GC: OR = 0.86, P = 0.0270; IS: OR = 0.82, P = 0.0277), respectively. Further MVMR analysis demonstrated that only IS was linked to a decreased risk of PD (OR = 0.86, P = 0.004).
Conclusion
This work clarified that patients with RA had a decreased risk of PD, which was partially attributed to the use of IS in RA patients but not GC or NSAIDs.
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Investigation of the potential association between the use of fluoxetine and occurrence of acute pancreatitis: a Danish register-based cohort study

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Abstract
BackgroundThere is currently conflicting evidence of the association between the use of selective serotonin reuptake inhibitors (SSRIs) and acute pancreatitis. The SSRI fluoxetine has been suspected to be the driver of this serious outcome. Therefore, this study aims to investigate the potential association between fluoxetine use and the occurrence of acute pancreatitis.
Methods
We conducted a nationwide cohort study using Danish register-based data from 1996 to 2016. The exposed group were new users of fluoxetine (1-year washout). The control subjects were new users of citalopram or SSRIs, excluding fluoxetine. The outcome was an incident diagnosis of acute pancreatitis with a 5-year washout. We used an intention-to-treat approach following patients for a maximum of 6 months. Cox regression analyses were performed, estimating hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age/sex, comorbidities and co-medications, using propensity score adjustment and matchi ng.
Results
In the propensity score-matched analyses, 61 783 fluoxetine users were included. The incidence rates among users of fluoxetine and other SSRIs were 5.33 (3.05–8.66) and 5.36 (3.06–8.70) per 10 000 person-years, respectively. No increased risk of acute pancreatitis was identified following fluoxetine exposure compared with either citalopram [HR 1.00, 95% CI 0.50–2.00) or other SSRIs (0.76, 0.40–1.46).
Conclusions
Fluoxetine use was not associated with an increased risk of acute pancreatitis compared with citalopram or other SSRIs. The absolute risk of acute pancreatitis was low and did not vary between different SSRIs. Further research is needed to determine whether there is a class effect on the risk of acute pancreatitis.
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Developing a Multimodal Monitoring System for Geriatric Depression: A Feasibility Study

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imageThe Internet of Medical Things is promising for monitoring depression symptoms. Therefore, it is necessary to develop multimodal monitoring systems tailored for elderly individuals with high feasibility and usability for further research and practice. This study comprised two phases: (1) methodological development of the system; and (2) system validation to evaluate its feasibility. We developed a system that includes a smartphone for facial and verbal expressions, a smartwatch for activity and heart rate monitoring, and an ecological momentary assessment application. A sample of 21 older Koreans aged 65 years and more was r ecruited from a community center. The 4-week data were collected for each participant (n = 19) using self-report questionnaires, wearable devices, and interviews and were analyzed using mixed methods. The depressive group (n = 6) indicated lower user acceptance relative to the nondepressive group (n = 13). Both groups experienced positive emotions, had regular life patterns, increased their self-interest, and stated that a system could disturb their daily activities. However, they were interested in learning new technologies and actively monitored their mental health status. Our multimodal monitoring system shows potential as a feasible and useful measure for acquiring mental health information about geriatric depression.
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MEOX2 homeobox gene promotes growth of malignant gliomas

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Abstract
Background
Glioblastoma (GBM) is an aggressive tumor that frequently exhibits gain of chromosome 7, loss of chromosome 10 and aberrantly activated receptor tyrosine kinase signaling pathways. Previously, we identified Mesenchyme Homeobox 2 (MEOX2), a gene located on chromosome 7, as an upregulated transcription factor in GBM. Overexpressed transcription factors can be involved in driving GBM. Here, we aimed to address the role of MEOX2 in GBM.
Methods
Patient-derived GBM tumorspheres were used to constitutively knockdown or overexpress MEOX2 and subjected to in vitro assays including western blot to assess ERK phosphorylation. Cerebral organoid models were used to investigate the role of MEOX2 in growth initiation. Intracranial mouse implantation models were used to assess the tumorigenic potential of MEOX2. RNA-sequencing, ACT-seq and CUT&Tag w ere used to identify MEOX2 target genes.
Results
MEOX2 enhanced ERK signaling through a feed-forward mechanism. We identified Ser 155 as a putative ERK-dependent phosphorylation site upstream of the homeobox-domain of MEOX2. S155A substitution had a major effect on MEOX2 protein levels and altered its subnuclear localization. MEOX2 overexpression cooperated with p53 and PTEN loss in cerebral organoid models of human malignant gliomas to induce cell proliferation. Using high-throughput genomics, we identified putative transcriptional target genes of MEOX2 in patient-derived GBM tumorsphere models and a fresh frozen GBM tumor.
Conclusions
We identified MEOX2 as an oncogenic transcription regulator in GBM. MEOX2 increases proliferation in cerebral organoid models of GBM and feeds into ERK signaling that represents a core signaling pathway in GBM.
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Optimization of vonoprazan‐amoxicillin dual therapy for eradicating Helicobacter pyloriinfection in China: A prospective, randomized clinical pilot study

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Abstract

Background

Vonoprazan-amoxicillin (VA) dual therapy has been shown to achieve acceptable cure rates for treatment of Helicobacter pylori(H. pylori) in Japan. Its effectiveness in other regions is unknown. We aimed to explore the efficacy of VA dual therapy as first-line treatment for H. pyloriinfection in China.

Methods

This was a single center, prospective, randomized clinical pilot study conducted in China. Treatment naive H. pyloriinfected patients were randomized to receive either low- or high-dose amoxicillin-vonoprazan consisting of amoxicillin 1 g either b.i.d. or t.i.d plus VPZ 20 mg b.i.d for 7 or 10 days. 13C-urea breath tests were used to access the cure rate at least 4 weeks after treatment.

Results

Three hundred and twenty-three patients were assessed, and 119 subjects were randomized. The eradication rates of b.i.d. amoxicillin for 7 and 10 days, t.i.d. amoxicillin for 7 and 10 days were 66.7% (16/24), 89.2% (33/37), 81.0% (17/21), and 81.1% (30/37) (p = .191) by intention-to-treat analysis, respectively, and 72.7% (16/22), 89.2% (33/37), 81.0% (17/21), and 81.1% (30/37) (p = .454) by per-protocol analysis, respectively.

Conclusion

Neither 7- or 10-day VA dual therapy with b.i.d. or t.i.d. amoxicillin provides satisfied efficacy as the first-line treatment for H. pyloriinfection in China. Further optimization is needed.

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Cardiovascular Risk and Sudden Sensorineural Hearing Loss: A Systematic Review and Meta‐Analysis

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Objectives/Hypothesis

It was previously suggested that patients with idiopathic sudden sensorineural hearing loss (ISSNHL) have a higher risk of cardiovascular disease. The aim of this study is to determine if ISSNHL patients have an increased cardiovascular risk by means of a systematic review and meta-analysis.

Methods

A systematic literature review was performed using PubMed, Embase, Cochrane Libraries and Web of Science. Studies with a clear definition of ISSNHL, investigating an association between traditional vascular risk factors and ISSNHL were included. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, two reviewers extracted the data, assessed the risk of bias and performed the analysis of the collected evidence.

Results

Nineteen case–control studies and two cohort studies were included (102,292 patients). Individual studies argued for higher prevalence of hypercholesterolemia, diabetes mellitus (DM) and higher blood pressure (HBP) in ISSNHL patients with a range of odds ratios (ORs) from 1.03 to 19. Pooled analysis of adjusted ORs revealed a significantly increased risk of ISSNHL for patients with hypertriglyceridemia (OR 1.54; 95% confidence interval [CI] 1.18–2.02) and high levels of total cholesterol (TC) (OR 2.09; 95% CI 1.52–2.87 after sensitivity analysis), but not for HBP, DM, or high levels of low- and high-density lipoproteins.

Conclusion

An association between higher vascular risk profile and ISSNHL seems apparent in high levels of triglycerides (TG) and TC, but more studies are needed to confirm this hypothesis due to the high levels of data heterogeneity in the literature.

Level of Evidence

N/A Laryngoscope, 2022

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JGI at 25: The Human Genome Project, or the JGI’s Origin Story

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JGI at 25 revisits our contributions to the Human Genome Project, and our origins in DOE bringing together the people and resources from three national labs.
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Effect of obesity on the associations of 25-hydroxyvitamin D with prevalent and incident distal sensorimotor polyneuropathy: population-based KORA F4/FF4 study

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Development of a targeted gene panel for the diagnosis of Gorlin syndrome

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Message:

A rare, inherited disorder that affects many organs and tissues in the body. People with this disorder have a very high risk of developing basal cell skin cancer during adolescence or early adulthood. They are also at risk of developing medulloblastoma (a type of brain cancer) and other types of cancer.

In this study, a gene panel was developed to overcome the challenges in the diagnosis of Gorlin syndrome and allow diagnosis using a single test. A custom panel was generated for four genes associated with Gorlin syndrome: PTCH1, PTCH2, SMO, and SUFU. Twenty-seven samples from 12 patients with Gorlin syndrome and three asymptomatic blood relatives of the patients were examined. (Source: International Journal of Oral and Maxillofacial Surgery)
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