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Effect of nanodiamonds surface deposition on hydrophilicity, bulk degradation and in-vitro cell adhesion of 3D-printed polycaprolactone scaffolds for bone tissue engineering

Biomed Mater. 2024 Jun 25. doi: 10.1088/1748-605X/ad5bac. Online ahead of print.

ABSTRACT

This study was designed to deposit nanodiamonds on 3D-printed PCL scaffolds and evaluate their effect on the surface topography, hydrophilicity, degradation, and in-vitro cell adhesion compared to untreated PCL scaffolds. The PCL scaffold specimens were 3D-printed by fused deposition molding (FDM) technique with specific porosity parameters. The 3D-printed specimens’ surfaces were modified by nanodiamonds deposition followed by oxygen plasma post-treatment using a plasma focus (PF) device and a non-thermal atmospheric plasma jet (NTAPJ), respectively. Specimens were evaluated through morphological characterization by field emission scanning electron microscope (FESEM), microstructure characterization by Raman spectroscopy, chemical characterization by Fourier transform infrared (FTIR) spectroscopy, hydrophilicity degree by contact angle and water uptake measurements, and in-vitro degradation measurements (n=6). In addition, in-vitro bone marrow mesenchymal stem cells (BMSCs) adhesion was evaluated quantitatively by Confocal microscopy and qualitatively by FESEM at different time intervals after cell seeding (n=6). The statistical significance level was set at p ≤0.05. The FESEM micrographs, the Raman, and FTIR spectra confirmed the successful surface deposition of nanodiamonds on scaffold specimens. The nanodiamonds treated specimens showed nano-scale features distributed homogeneously across the surface compared to the untreated ones. Also, the nanodiamonds treated specimens revealed a statistically significant smaller contact angle (17.45 ±1.34 degrees), higher water uptake percentage after 24 h immersion in phosphate buffer saline (PBS) (21.56% ±1.73), and higher degradation rate after six months of immersion in PBS (43.92% ±0.77). Moreover, enhanced cell adhesion at all different time intervals was observed in nanodiamonds treated specimens with higher nuclei area fraction percentage (69.87% ±3.97) compared to the untreated specimens (11.46% ±1.34). Surface deposition of nanodiamonds with oxygen-containing functional groups on 3D-printed PCL scaffolds increased their hydrophilicity and degradation rate with significant enhancement of the in-vitro cell adhesion compared to untreated PCL scaffolds.

PMID:38917826 | DOI:10.1088/1748-605X/ad5bac

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Brainstem raphe hypoechogenicity is an independent predictor of post-stroke depression

Ultraschall Med. 2024 Jun 25. doi: 10.1055/a-2296-3484. Online ahead of print.

ABSTRACT

PURPOSE: Post-stroke depression (PSD) is a common complication after stroke and has a substantial effect on the quality of life of patients. Nevertheless, reliable individual prediction of PSD is not possible. As depressive symptoms have been associated with brainstem raphe (BR) hypoechogenicity on transcranial sonography (TCS), we aimed to explore the association of BR hypoechogenicity and the occurrence of PSD.

MATERIALS AND METHODS: The Prognostic Markers of Post-Stroke Depression (PROMoSD) study is a prospective, observational, single-center, investigator-initiated study that included patients with acute ischemic stroke (AIS) to investigate the presence of BR hypoechogenicity by TCS early after symptom onset. The primary outcome was the presence of PSD assessed at the three-month follow-up investigation by a blinded psychiatrist and defined according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V criteria).

RESULTS: From 105 included AIS patients, 99 patients completed the study. AIS patients with a hypoechogenic BR developed a PSD at three months more frequently compared to patients with normal echogenicity (48.0% versus 4.1%, P <0.001). After adjustment for confounders (sex, mRS at follow-up, previous depressive episode), a hypoechogenic BR remained independently associated with a substantial increase in the appearance of PSD (adjusted OR: 6.371, 95%-CI: 1.181-34.362).

CONCLUSION: A hypoechogenic BR is a strong and independent predictor of PSD at three months after AIS. TCS could be a routine tool to assess PSD risk in clinical practice, thereby streamlining diagnostic and therapeutic algorithms.

PMID:38917825 | DOI:10.1055/a-2296-3484

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Detecting gene-environment interactions from multiple continuous traits

Bioinformatics. 2024 Jun 25:btae419. doi: 10.1093/bioinformatics/btae419. Online ahead of print.

ABSTRACT

MOTIVATION: Genetic variants present differential effects on humans according to various environmental exposures, the so-called “gene-environment interactions” (GxE). Many diseases can be diagnosed with multiple traits, such as obesity, diabetes, and dyslipidemia. I developed a multivariate scale test (MST) for detecting the GxE of a disease with several continuous traits. Given a significant MST result, I continued to search for which trait and which E enriched the GxE signals. Simulation studies were performed to compare MST with the univariate scale test (UST).

RESULTS: MST can gain more power than UST because of (1) integrating more traits with GxE information and (2) the less harsh penalty on multiple testing. However, if only few traits account for GxE, MST may lose power due to aggregating non-informative traits into the test statistic. As an example, MST was applied to a discovery set of 93,708 Taiwan Biobank (TWB) individuals and a replication set of 25,200 TWB individuals. From among 2,570,487 SNPs with minor allele frequencies ≥ 5%, MST identified 18 independent variance quantitative trait loci (p < 2.4E-9 in the discovery cohort and p < 2.8E-5 in the replication cohort) and 41 GxE signals (p < 0.00027) based on eight trait domains (including 29 traits).

AVAILABILITY: https://github.com/WanYuLin/Multivariate-scale-test-MST.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:38917408 | DOI:10.1093/bioinformatics/btae419

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Evaluation of Long-Term Posterior Segment Parameters in Children Who Had Recovered From Multisystem Inflammatory Syndrome

Ophthalmic Surg Lasers Imaging Retina. 2024 Jun 1:1-9. doi: 10.3928/23258160-20240415-01. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: To evaluate long-term posterior segment findings in children recovering from multisystemic inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.

PATIENTS AND METHODS: Our study included 22 patients who were admitted to an intensive care unit with a diagnosis of MIS-C between November 2021 and March 2022, and 25 healthy controls. The study included pediatric patients who had an eye examination an average of 12.35 ± 2.18 months after recovery from MIS-C. Detailed eye examinations and measurements of all participants were obtained retrospectively from patient files. Posterior segment parameters were measured using swept-source optical coherence tomography (OCT) and OCT-angiography (OCT-A); these parameters included peripapillary retinal nerve fiber layer (pRNFL) thickness, central macular thickness (CMT), subfoveal choroidal thickness (SCT), macular vascular densities (VD), and foveal avascular zone (FAZ) area.

RESULTS: Mean age was 9.7 ± 3.6 years in the MIS-C group and 10.6 ± 2.8 years in the healthy control group (P = 0.316). There were no statistically significant differences between the MIS-C group and the healthy control group in terms of pRNFL thickness, CMT, and SCT. However, in the MIS-C group, the macular superficial vascular plexus and deep vascular plexus showed significantly lower VD in the superior, inferior, nasal, and temporal quadrants compared to the healthy controls (P < 0.05 for all). A comparison of the superficial and deep FAZ area parameters of both groups showed no statistically significant difference (P > 0.05).

CONCLUSIONS: We showed that patients who had recovered from MIS-C had retinal vascular damage at the long-term follow-up. Following up with these patients after recovery with OCT and OCT-A, which are noninvasive methods commonly used in the detailed evaluation of the posterior segment of the eye, could be beneficial for understanding the long-term effects of MIS-C on retinal microvasculature. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

PMID:38917398 | DOI:10.3928/23258160-20240415-01

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Factors associated with suicide risk and attempts in healthcare students: A cross-sectional study

Medwave. 2024 Jun 25;24(5):e2756. doi: 10.5867/medwave.2024.05.2756.

ABSTRACT

INTRODUCTION: Suicide deaths in young people have been increasing in recent decades and are considered a major public health problem worldwide, being a partially preventable event. The prevalence of suicidal ideation is high among university students, especially in health careers. The objective of this study was to measure the prevalence of high suicidal risk in this specific group and to identify associated factors, aiming to provide empirical evidence for the construction of effective suicide prevention strategies.

METHODS: A cross-sectional study was conducted based on an online survey directed to healthcare students near the end of the first year of the COVID-19 pandemic to learn about the frequency of suicidal risk and its associated factors. The sample consisted of 477 students (70.8% female, mean age 21.7 ± 2.5 years) from eight healthcare majors. The data were collected in January 2021.

RESULTS: 22.6% of the young people reported a high suicide risk on the Okasha scale, and 3.4% made a suicide attempt in the previous year. Factors associated with high suicidal risk were having a non-heterosexual orientation, an irregular academic trajectory, experiences of physical and/or psychological violence, higher levels of depressive and anxious symptomatology, as well as lower levels of social support from friends and family.

CONCLUSIONS: Suicide risk and attempt levels are high in this group of students, and there is a group of factors that could guide more effective actions, such as support for higher-risk groups and screening to identify and provide support to young people at high suicidal risk and with mental health conditions.

PMID:38917390 | DOI:10.5867/medwave.2024.05.2756

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Clinical Study Report and Individual Participant Data Transparency for US Food and Drug Administration-Approved Anticancer Drugs: A Call for Systematic Data Availability

J Clin Oncol. 2024 Jun 25:JCO2400539. doi: 10.1200/JCO.24.00539. Online ahead of print.

ABSTRACT

Unlocking the full potential of clinical trials through comprehensive CSR and IPD sharing can revolutionize cancer care, enhance safety evaluations, and reduce bias in systematic reviews. It is time for all stakeholders to embrace transparency and advance patient-centered outcomes.

PMID:38917375 | DOI:10.1200/JCO.24.00539

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Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial

J Clin Psychiatry. 2024 Jun 17;85(3):24m15265. doi: 10.4088/JCP.24m15265.

ABSTRACT

Objective: To test esmethadone (REL-1017) as adjunctive treatment in patients with major depressive disorder (MDD) and inadequate response to standard antidepressants.

Methods: In this phase 3, double-blind, placebo-controlled trial, outpatients with MDD (DSM-5) were randomized to daily oral esmethadone (75 mg on day 1, followed by 25 mg daily on days 2 through 28) or placebo between December 2020 and December 2022. The primary efficacy measure was change from baseline (CFB) to day 28 in the Montgomery-Asberg Depression Rating Scale (MADRS) score. The intent-to-treat (ITT) population included all randomized participants. The per-protocol (PP) population included completers without major protocol deviations impacting assessment. Post hoc analyses included participants with severe depression (baseline MADRS score ≥35).

Results: For the ITT analysis (n = 227), mean CFB was 15.1 (SD 11.3) for esmethadone (n = 113) and 12.9 (SD 10.4) for placebo (n = 114), with a mean difference (MD) of 2.3, which was not statistically significant (P = .154; Cohen effect size [ES] = 0.21). Remission rates were 22.1% and 13.2% (P = .076), and response rates were 39.8% and 27.2% (P = .044) with esmethadone and placebo, respectively. For the PP analysis (n = 198), mean CFB was 15.6 (SD 11.2) for esmethadone (n = 101) and 12.5 (SD 9.9) for placebo (n = 97), with an MD of 3.1 (P = .051; ES =0.29). In post hoc analyses of patients with baseline MADRS ≥35 in the ITT population (n = 112), MD was 6.9; P = .0059; ES = 0.57, and for the PP population (n = 98), MD was 7.9; P = .0015; ES = 0.69. Adverse events (AEs) were predominantly mild or moderate and transient, with no significant differences between groups.

Conclusions: The primary end point was not met. Esmethadone showed stronger efficacy in PP than in ITT analyses, with the discrepancy not attributable to AEs impacting treatment adherence. Significant efficacy occurred in post hoc analyses of patients with severe depression. Esmethadone was well tolerated, consistent with prior studies.

Trial Registration: ClinicalTrials.gov identifier: NCT04688164.

PMID:38917366 | DOI:10.4088/JCP.24m15265

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Depression, Rumination, and Suicide Attempts in Adolescents With Mood Disorders: Sex Differences in This Relationship

J Clin Psychiatry. 2024 Jun 19;85(3):23m15136. doi: 10.4088/JCP.23m15136.

ABSTRACT

Abstract.

Background: Sex differences in suicide attempts have been widely recognized across domains such as depression and rumination. The relationship between depression, rumination, and suicide attempts in mood disorders has been studied before; however, how they interact across sexes remains unclear. This study aimed to examine the sex differences in the relationship between depression, rumination, and suicide attempts in Chinese adolescents with mood disorders.

Methods: We recruited 681 adolescents with mood disorders who met ICD-10 criteria for having unipolar or bipolar depression with a current depressive episode at the time of the study and collected demographic and clinical data.

Results: The prevalence of suicide attempts in female adolescents with mood disorders (64.36%) was significantly higher than that in male adolescents with mood disorders (49.47%), with an odds ratio of 1.84 (95% CI, 1.31-2.59). Regression analysis showed that PHQ-9 was independently associated with suicide attempts among male adolescents with mood disorders, while in female adolescents with mood disorders, total scores of PHQ-9 and RRS-10 were independently associated with suicide attempts. Importantly, in female adolescents with mood disorders, the mediating effect of RRS-10 total score on the relationship between PHQ-9 and suicide attempts was significant (standardized β = 0.005, P = 0.003, 95% CI, 0.002-0.008), the mediating effect accounted for 31.25% of the total effect of depressive symptoms on suicide attempts.

Conclusions: Our study suggests that there are sex differences in depression, rumination, and suicide attempts and in the interaction between them in adolescents with mood disorders. These sex differences may have important clinical implications, both for improving strategies to detect suicidal behaviors and for developing better early intervention programs for this population.

PMID:38917361 | DOI:10.4088/JCP.23m15136

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Effect of proton pump inhibitors compared to histamine-2 receptor antagonists on bleeding management and wound healing after endoscopic mucosal resection or endoscopic submucosal dissection: A meta-analysis of randomized clinical trials

Adv Clin Exp Med. 2024 Jun 25. doi: 10.17219/acem/176892. Online ahead of print.

ABSTRACT

INTRODUCTION: Proton pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs) are generally effective in preventing delayed bleeding and healing artificial wounds after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). This study aimed to review the therapeutic effects of PPIs and H2RAs on damage caused by EMR and ESD.

MATERIAL AND METHODS: Thirteen articles were collected between 2002 and 2022 by searching Medlib, ScienceDirect, PubMed, International Scientific Indexing (ISI), Embase, and Scopus databases using valid keywords. The main inclusion criteria were delayed wound healing, bleeding, epigastric pain, intraoperative bleeding, and perforation. The odds ratio (OR) and 95% confidence interval (95% CI) were evaluated using a random or fixed effects model. Data analysis was performed using Stata v. 14.2.

RESULTS: A total of 13 articles including 1,483 patients were analyzed. The results showed that delayed bleeding was significantly less frequent in the PPI group than in the H2RA group (OR = 0.6; 95% CI: 0.39-0.92). Subgroup analysis showed that PPI was more effective in preventing delayed bleeding than H2RA for ESD wounds (OR = 0.65; 95% CI: 0.44-1.08). There was no statistically significant difference between both groups regarding the incidence of epigastric pain, intraoperative bleeding, wound healing, and perforation after endoscopic treatments.

CONCLUSION: The meta-analysis results reveal that PPI is more effective than H2RA in preventing delayed bleeding after endoscopic treatment, particularly in patients treated with ESD. However, there was no significant difference between PPI and H2RA in terms of intraoperative bleeding, epigastric pain, wound healing, and perforation from endoscopic therapy.

PMID:38917321 | DOI:10.17219/acem/176892

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A Comparison of COVID-19 Associated Hospitalization Rates Among Unvaccinated Versus Vaccinated Residents in Rhode Island, September 2022 to March 2024

R I Med J (2013). 2024 Jul 1;107(7):39-43.

ABSTRACT

While the burden of COVID-19 in Rhode Island has diminished since 2020, Rhode Islanders’ health continues to be severely impacted. We compared COVID-19 hospitalization rates among Rhode Islanders who did and did not receive the latest COVID-19 vaccination for the 2022-2023 and 2023-2024 COVID-19 seasons (November through March). Crude and age-adjusted rate ratios were calculated for each season comparing hospitalization rates of unvaccinated and vaccinated individuals. During the 2022-2023 season, individuals who were not vaccinated with the bivalent COVID-19 vaccine were 3.6 times (95% CI=2.8-4.6) more likely to be hospitalized for COVID-19 than individuals who received the vaccine, whereas during the 2023-2024 season, not receiving the updated vaccine was associated with a 2.4 times (95% CI=1.8-3.3) higher risk of hospitalization. The study provides the first assessment of the protection from hospitalization provided by COVID-19 vaccinations among Rhode Islanders and highlights the importance of continued vaccination for COVID-19.

PMID:38917315