Nevin Manimala

Physiol Meas. 2024 Jun 25. doi: 10.1088/1361-6579/ad5bbb. Online ahead of print.

ABSTRACT

The cerebral vasculature is formed of an intricate network of blood vessels over many different length scales. Changes in their structure and connection are implicated in multiple cerebrovascular and neurological disorders. In this study, we present a novel approach to the quantitative analysis of the cerebral macrovasculature using computational and mathematical tools in a large dataset. &#xD;Approach. We analysed a publicly available vessel dataset from a cohort of 56 (32/24 F/M) healthy subjects. This dataset includes digital reconstructions of human brain macrovasculatures. We then propose a new mathematical model to compute blood flow dynamics and pressure distributions within these 56-representative cerebral macrovasculatures and quantify the results across this cohort.&#xD;Main results. Statistical analysis showed that the steady state level of cerebrovascular resistance (CVR) gradually increases with age in both men and women. These age-related changes in CVR are in good agreement with previously reported values. All subjects were found to have only small phase angles (< 6°) between blood pressure and blood flow at the cardiac frequency.&#xD;Significance. These results showed that the dynamic component of blood flow adds very little phase shift at the cardiac frequency, which implies that the cerebral macrocirculation can be regarded as close to steady state in its behaviour, at least in healthy populations, irrespective of age or sex. This implies that the phase shift observed in measurements of blood flow in cerebral vessels is caused by behaviour further down the vascular bed. This behaviour is important for future statistical models of the dynamic maintenance of oxygen and nutrient supply to the brain.

PMID:38917841 | DOI:10.1088/1361-6579/ad5bbb

J Phys Condens Matter. 2024 Jun 25. doi: 10.1088/1361-648X/ad5baf. Online ahead of print.

ABSTRACT

In this manuscript, we undertake an examination of a classical plasma deployed on two finite co-planar surfaces: a circular region $Omega_{in}$ into an annular region $Omega_{out}$ with a gap in between. It is studied both from the point of view of statistical mechanics and the electrostatics of continua media. We employ a dual perspective: the first one is by using Molecular Dynamics (MD) simulations to find the system’s positional correlation functions and velocity distributions. That by modeling the system as a classical two-dimensional Coulomb plasma of point-like charged particles $q_1$ and $q_2$ on the layers $Omega_{in}$ and $Omega_{out}$ respectively with no background density. The second one corresponds to a finite surface electrode composed of planar metallic layers displayed on the regions $Omega_{in}$, $Omega_{out}$ at constant voltages $V_{in}$, $V_{out}$ considering axial symmetry. The surface charge density is calculated by the Method of Moments (MoM) under the electrostatic approximation. Point-like and differential charges elements interact via a $1/r$ – electric potential in both cases. The thermodynamic averages of the number density, and electric potential due to the plasma depend on the coupling and the charge ratio $xi=q_1/q_2$ once the geometry of the layers is fixed. On the other hand, the fields due to the Surface Electrode (SE) depend on the layer’s geometry and their voltage. In the document, is defined a protocol to properly compare the systems. We show that there are values of the coupling parameter, where the thermodynamic averages computed via MD agree with the results of MoM for attractive $xi=-1$ and repulsive layers $xi=1$.

PMID:38917836 | DOI:10.1088/1361-648X/ad5baf

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

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

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

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

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

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

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

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