Category: Nevin Manimala

J Stroke Cerebrovasc Dis. 2021 Jul 19;30(9):105992. doi: 10.1016/j.jstrokecerebrovasdis.2021.105992. Online ahead of print.

ABSTRACT

OBJECTIVE: Unruptured intracranial vertebral artery dissection (VAD) generally heals spontaneously. A chronological evaluation of intramural hematoma (IMH) using T1-weighted vessel wall imaging (VWI) may provide a more detailed understanding of the pathophysiology of VAD. We herein investigated the relationship between chronological signal changes in IMH on VWI and the spontaneous healing of VAD.

MATERIALS AND METHODS: We retrospectively investigated 26 patients with 27 unruptured VADs who underwent magnetic resonance (MR) imaging more than three times during the follow-up period. Morphological changes were evaluated using MR angiography (MRA). The relative signal intensity (RSI) of IMH against the posterior cervical muscle on T1-weighted VWI was calculated. The ratio of chronological RSI changes was defined as follows: maximum RSI/minimum RSI (RSI _max/min). Based on the median value of RSI _max/min, 27 VADs were divided into VADs with and without chronological RSI changes. Statistical analyses were performed to compare clinical and radiological findings between the two groups.

RESULTS: Spontaneous healing occurred in 17 out of 27 VADs (63%). The median value of RSI _max/min was 1.48. The RSI of VADs with chronological RSI changes (RSI _max/min ≥ 1.48) increased until three weeks after their onset and decreased over time, while that of VADs without chronological RSI changes (RSI _max/min < 1.48) showed no change. The frequency of healing was significantly higher in VADs with than without chronological RSI changes (100% vs 23%, p < 0.0001).

CONCLUSIONS: Chronological signal changes in IMH on T1-weighted VWI have potential as a diagnostic imaging marker of the spontaneous healing of VAD.

PMID:34293642 | DOI:10.1016/j.jstrokecerebrovasdis.2021.105992

Chemosphere. 2021 Jul 17;286(Pt 1):131566. doi: 10.1016/j.chemosphere.2021.131566. Online ahead of print.

ABSTRACT

It is well documented that fine particles matter (PM_2.5), ozone (O₃), and nitrogen dioxide (NO₂) are associated with a range of adverse health outcomes. However, most epidemiologic studies have focused on understanding their additive effects, despite that individuals are exposed to multiple air pollutants simultaneously that are likely correlated with each other. Therefore, we applied a novel method – Bayesian Kernel machine regression (BKMR) and conducted a population-based cohort study to assess the individual and joint effect of air pollutant mixtures (PM_2.5, O₃, and NO₂) on all-cause mortality among the Medicare population in 15 cities with 656 different ZIP codes in the southeastern US. The results suggest a strong association between pollutant mixture and all-cause mortality, mainly driven by PM_2.5. The positive association of PM_2.5 with mortality appears stronger at lower percentiles of other pollutants. An interquartile range change in PM_2.5 concentration was associated with a significant increase in mortality of 1.7 (95% CI: 0.5, 2.9), 1.6 (95% CI: 0.4, 2.7) and 1.4 (95% CI: 0.1, 2.6) standard deviations (SD) when O₃ and NO₂ were set at the 25th, 50th, and 75th percentiles, respectively. BKMR analysis did not identify statistically significant interactions among PM_2.5, O₃, and NO₂. However, since the small sub-population might weaken the study power, additional studies (in larger sample size and other regions in the US) are in need to reinforce the current finding.

PMID:34293557 | DOI:10.1016/j.chemosphere.2021.131566

J Reprod Immunol. 2021 Jul 19;147:103350. doi: 10.1016/j.jri.2021.103350. Online ahead of print.

ABSTRACT

Synergistic interplay of immune endocrine interaction is prerequisite for an effective maternal fetal tolerance. Pre-term birth (PTB) may be a consequence of altered immune-endocrine crosstalk during third trimester resulting in early breakdown of this tolerance. Myeloid derived suppressor cells (MDSCs), a heterogenous population of immature immune cells are increased in pregnant women and healthy newborns, but their role in PTB still remains obscure. We now report that granulocytic MDSCs (G-MDSCs) is decreased in women delivering prematurely, suggesting their potential role in maintaining maternal fetal tolerance. Interestingly, in contrast statistically significant increase in MDSCs and monocytic MDSCs (M-MDSCs) along with positive correlation with cord serum estradiol (E2), and overexpressed ER-α in placental tissue suggested E2 mediated accumulation of M-MDSCs in PTB babies. MDSCs mediated immune suppression is accompanied with subsequent decline in total T cells and its subtypes: Th and Tc in PTB babies, which signifies their potential contribution towards the impaired immune system of PTB babies.

PMID:34293589 | DOI:10.1016/j.jri.2021.103350

Eur J Paediatr Neurol. 2021 Jul 7;34:14-20. doi: 10.1016/j.ejpn.2021.06.006. Online ahead of print.

ABSTRACT

PURPOSE: To compare Melatonin with Triclofos for efficacy (proportion of successful EEG, need of augmentation, sleep onset latency (SOL), yield of discharges, duration of sleep, presence and grade of artifacts) and tolerability (adverse effect profile).

METHODS: A randomized trial was performed (block randomization). All children were advised regarding sleep deprivation, EEG technician administered the drug. EEG was labelled successful if at least 30 min of record could be obtained (sleep with or without awake state). Pediatric neurologist reported the EEG findings-sleep onset latency, epileptiform abnormalities and graded the artifacts (excess beta activity and movement artifacts if present). The parents were interviewed telephonically next day by a pediatric resident for any adverse effects. The parents, pediatric neurologist and pediatric resident were blinded for the drug given.

RESULTS: 228 children were randomized (114 each received Melatonin and Triclofos). Both the groups were comparable at baseline for age group and demographic data. The proportion of successful EEG was 89.4% in Melatonin and 91.2% in Triclofos. First dose was effective in 64% in Melatonin and 63.15% in Triclofos group. Augmentation dose was needed in 25.4% in Melatonin and 28% in Triclofos group. Mean total sleep duration was 80 min after Melatonin and 82.39 after Triclofos administration. Adverse effects were observed in 6.14% of Melatonin and 8.65% of Triclofos group. None of the results were statistically significant.

CONCLUSION: There was no significant difference between efficacy and tolerability of Melatonin and Triclofos. Melatonin can be safely used to achieve sleep for EEG in children.

PMID:34293628 | DOI:10.1016/j.ejpn.2021.06.006

Hear Res. 2021 Jul 10;408:108310. doi: 10.1016/j.heares.2021.108310. Online ahead of print.

ABSTRACT

Animal studies have demonstrated that noise exposure can lead to the loss of the synapses between the inner hair cells and their afferent auditory nerve fiber targets without impacting auditory thresholds. Although several non-invasive physiological measures appear to be sensitive to cochlear synaptopathy in animal models, including auditory brainstem response (ABR) wave I amplitude, the envelope following response (EFR), and the middle ear muscle reflex (MEMR), human studies of these measures in samples that are expected to vary in terms of the degree of noise-induced synaptopathy have resulted in mixed findings. One possible explanation for the differing results is that synaptopathy risk is lower for recreational noise exposure than for occupational or military noise exposure. The goal of this analysis was to determine if EFR magnitude and ABR wave I amplitude are reduced among young Veterans with a history of military noise exposure compared with non-Veteran controls with minimal noise exposure. EFRs and ABRs were obtained in a sample of young (19-35 years) Veterans and non-Veterans with normal audiograms and robust distortion product otoacoustic emissions (DPOAEs). The statistical analysis is consistent with a reduction in mean EFR magnitude and ABR wave I amplitude (at 90 dB peSPL) for Veterans with a significant history of noise exposure compared with non-Veteran controls. These findings are in agreement with previous ABR wave I amplitude findings in young Veterans and are consistent with animal models of noise-induced cochlear synaptopathy.

PMID:34293505 | DOI:10.1016/j.heares.2021.108310

Med Image Anal. 2021 Jul 9;73:102157. doi: 10.1016/j.media.2021.102157. Online ahead of print.

ABSTRACT

In current biological and medical research, statistical shape modeling (SSM) provides an essential framework for the characterization of anatomy/morphology. Such analysis is often driven by the identification of a relatively small number of geometrically consistent features found across the samples of a population. These features can subsequently provide information about the population shape variation. Dense correspondence models can provide ease of computation and yield an interpretable low-dimensional shape descriptor when followed by dimensionality reduction. However, automatic methods for obtaining such correspondences usually require image segmentation followed by significant preprocessing, which is taxing in terms of both computation as well as human resources. In many cases, the segmentation and subsequent processing require manual guidance and anatomy specific domain expertise. This paper proposes a self-supervised deep learning approach for discovering landmarks from images that can directly be used as a shape descriptor for subsequent analysis. We use landmark-driven image registration as the primary task to force the neural network to discover landmarks that register the images well. We also propose a regularization term that allows for robust optimization of the neural network and ensures that the landmarks uniformly span the image domain. The proposed method circumvents segmentation and preprocessing and directly produces a usable shape descriptor using just 2D or 3D images. In addition, we also propose two variants on the training loss function that allows for prior shape information to be integrated into the model. We apply this framework on several 2D and 3D datasets to obtain their shape descriptors. We analyze these shape descriptors in their efficacy of capturing shape information by performing different shape-driven applications depending on the data ranging from shape clustering to severity prediction to outcome diagnosis.

PMID:34293535 | DOI:10.1016/j.media.2021.102157

Child Abuse Negl. 2021 Jul 19;120:105217. doi: 10.1016/j.chiabu.2021.105217. Online ahead of print.

ABSTRACT

BACKGROUND: A robust literature-base on adverse childhood experiences (ACEs) provides strong evidence on the relationships between social adversity in childhood and the health and well-being of individuals across the lifespan. One form of social adversity, exposure to violence in childhood, is not only harmful to a child’s health and well-being, but detrimental to their performance in school. Poor performance in school may affect educational attainment later in life and hinder a child’s upward social mobility. We focus on the impact of violence-related ACEs on school success factors to add new evidence on how violence in childhood affects a child’s educational progress.

OBJECTIVE: To examine the impact of violence-related ACEs on school success factors, including grade repetition, school absence, and school-home contact.

PARTICIPANTS AND SETTINGS: This study uses secondary data analysis of a nationally representative survey, the National Survey of Children’s Health (NSCH), to study a sample of non-institutionalized children aged 6-17 in the US (n = 35,122).

METHODS: We employed binary logistic regression and multinomial logistic regression using 95% confidence intervals to analyze the effect of violence in childhood on three school success factors, controlling for socio-demographic and health status characteristics.

RESULTS: We found that violence in childhood increases the likelihood of grade repetition (OR = 1.47, 95% CI, 1.12-1.92), school-home contact (OR = 2.20, 95% CI, 1.86-2.60), and school absence greater than one week (OR=1.4, 95%CI,1.08-2.00; OR=1.86, 95%CI, 1.36-2.60), controlling for socio-demographic and health status characteristics.

CONCLUSIONS: Violence in childhood has a statistically significant negative impact on each of the school success factors included in this study.

PMID:34293551 | DOI:10.1016/j.chiabu.2021.105217

Depress Anxiety. 2021 Jul 22. doi: 10.1002/da.23193. Online ahead of print.

ABSTRACT

BACKGROUND: Comorbid anxiety is generally associated with poorer response to antidepressant treatment. This post hoc analysis explored the efficacy of esketamine plus an antidepressant in patients with treatment-resistant depression (TRD) with or without comorbid anxiety.

METHODS: TRANSFORM-2, a double-blind, flexible-dose, 4-week study (NCT02418585), randomized adults with TRD to placebo or esketamine nasal spray, each with a newly-initiated oral antidepressant. Comorbid anxiety was defined as clinically noteworthy anxiety symptoms (7-item Generalized Anxiety Disorder scale [GAD-7] score ≥10) at screening and baseline or comorbid anxiety disorder diagnosis at screening. Treatment effect based on change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, and response and remission were examined by presence/absence of comorbid anxiety using analysis of covariance and logistic regression models.

RESULTS: Approximately 72% (162/223) of patients had baseline comorbid anxiety. Esketamine-treated patients with and without anxiety demonstrated significant reductions in MADRS (mean [SD] change from baseline at day 28: -21.0 [12.51] and -22.7 [11.98], respectively). Higher rates of response and remission, and a significantly greater decrease in MADRS score at day 28 were observed compared to antidepressant/placebo, regardless of comorbid anxiety (with anxiety: difference in LS means [95% CI] -4.2 [-8.1, -0.3]; without anxiety: -7.5 [-13.7, -1.3]). There was no significant interaction of treatment and comorbid anxiety (p = .371). Notably, in the antidepressant/placebo group improvement was similar in those with and without comorbid anxiety.

CONCLUSION: Post hoc data support efficacy of esketamine plus an oral antidepressant in patients with TRD, regardless of comorbid anxiety.

PMID:34293233 | DOI:10.1002/da.23193

Proteins. 2021 Jul 22. doi: 10.1002/prot.26184. Online ahead of print.

ABSTRACT

MOTIVATION: Deep mutational scanning provides unprecedented wealth of quantitative data regarding the functional outcome of mutations in proteins. A single experiment may measure properties (e.g., structural stability) of numerous protein variants. Leveraging the experimental data to gain insights about unexplored regions of the mutational landscape is a major computational challenge. Such insights may facilitate further experimental work and accelerate the development of novel protein variants with beneficial therapeutic or industrially relevant properties. Here we present a novel, machine learning approach for the prediction of functional mutation outcome in the context of deep mutational screens.

RESULTS: Using sequence (one-hot) features of variants with known properties, as well as structural features derived from models thereof, we train predictive statistical models to estimate the unknown properties of other variants. The utility of the new computational scheme is demonstrated using five sets of mutational scanning data, denoted “targets”: (a) protease specificity of APPI (amyloid precursor protein inhibitor) variants; (b – d) three stability related properties of IGBPG (immunoglobulin G-binding β1 domain of streptococcal protein G) variants; and (e) fluorescence of GFP (green fluorescent protein) variants. Performance is measured by the overall correlation of the predicted and observed properties, and enrichment – the ability to predict the most potent variants and presumably guide further experiments. Despite the diversity of the targets the statistical models can generalize variant examples thereof and predict the properties of test variants with both single and multiple mutations. This article is protected by copyright. All rights reserved.

PMID:34293212 | DOI:10.1002/prot.26184

Mol Carcinog. 2021 Jul 22. doi: 10.1002/mc.23334. Online ahead of print.

ABSTRACT

Insulin-like growth factors (IGF) play important roles in carcinogenesis. The associations of circulating IGF-1 and insulin-like growth factor-binding protein-3 (IGFBP-3) with the risks of bladder cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy controls, we assessed the associations of circulating IGF-1 and IGFBP-3 with bladder cancer risks using a Mendelian randomization approach, which uses genetic variants as instruments to study causal relationship between risk factors and diseases. We first constructed a weighted genetic risk score (GRS) predictive of circulating IGF-1 and IGFBP-3 using 413 genome-wide association study-identified single nucleotide polymorphisms (SNPs) associated with IGF-1 and four SNPs with IGFBP-3, respectively. We found that higher GRS for IGF-1 was associated with a significantly reduced bladder cancer risk (odds ratio [OR] = 0.66 per SD increase, 95% confidence interval [CI], 0.54-0.82, p < 0.001). We then used a summary statistics-based MR method, inverse-variance weighting (IVW), and found a similar risk estimate (OR = 0.67 per SD increase, 95% CI = 0.54-0.83, p < 0.001). When we categorized individuals into high and low IGF-1 groups using the median GRS value in the controls, the high GRS group had a 21% reduced bladder cancer risk (OR = 0.79, 95% CI = 0.70-0.89) compared to the low GRS group. Genetically predicted circulating IGFBP-3 was not associated with bladder cancer risk. In conclusion, our data demonstrated for the first time a strong inverse relationship between circulating IGF-1 level and bladder cancer risk.

PMID:34293213 | DOI:10.1002/mc.23334