Category: Nevin Manimala

PLoS One. 2022 Jan 28;17(1):e0261691. doi: 10.1371/journal.pone.0261691. eCollection 2022.

ABSTRACT

Conduct Disorder (CD) is an impairing psychiatric disorder of childhood and adolescence characterized by aggressive and dissocial behavior. Environmental factors such as maternal smoking during pregnancy, socio-economic status, trauma, or early life stress are associated with CD. Although the number of females with CD is rising in Western societies, CD is under-researched in female cohorts. We aimed at exploring the epigenetic signature of females with CD and its relation to psychosocial and environmental risk factors. We performed HpaII sensitive genome-wide methylation sequencing of 49 CD girls and 50 matched typically developing controls and linear regression models to identify differentially methylated CpG loci (tags) and regions. Significant tags and regions were mapped to the respective genes and tested for enrichment in pathways and brain developmental processes. Finally, epigenetic signatures were tested as mediators for CD-associated risk factors. We identified a 12% increased methylation 5′ of the neurite modulator SLITRK5 (FDR = 0.0046) in cases within a glucocorticoid receptor binding site. Functionally, methylation positively correlated with gene expression in lymphoblastoid cell lines. At systems-level, genes (uncorr. P < 0.01) were associated with development of neurons, neurite outgrowth or neuronal developmental processes. At gene expression level, the associated gene-networks are activated perinatally and during early childhood in neocortical regions, thalamus and striatum, and expressed in amygdala and hippocampus. Specifically, the epigenetic signatures of the gene network activated in the thalamus during early childhood correlated with the effect of parental education on CD status possibly mediating its protective effect. The differential methylation patterns identified in females with CD are likely to affect genes that are expressed in brain regions previously indicated in CD. We provide suggestive evidence that protective effects are likely mediated by epigenetic mechanisms impairing specific brain developmental networks and therefore exerting a long-term effect on neural functions in CD. Our results are exploratory and thus, further replication is needed.

PMID:35089926 | DOI:10.1371/journal.pone.0261691

PLoS Negl Trop Dis. 2022 Jan 28;16(1):e0010103. doi: 10.1371/journal.pntd.0010103. eCollection 2022 Jan.

ABSTRACT

BACKGROUND: Mass vaccination campaigns have significantly reduced the COVID-19 burden. However, vaccine hesitancy has posed significant global concerns. The purpose of this study was to determine the characteristics that influence perceptions of COVID-19 vaccine efficacy, acceptability, hesitancy and decision making to take vaccine among general adult populations in a variety of socioeconomic and cultural contexts.

METHODS: Using a snowball sampling approach, we conducted an online cross-sectional study in 20 countries across four continents from February to May 2021.

RESULTS: A total of 10,477 participants were included in the analyses with a mean age of 36±14.3 years. The findings revealed the prevalence of perceptions towards COVID-19 vaccine’s effectiveness (78.8%), acceptance (81.8%), hesitancy (47.2%), and drivers of vaccination decision-making (convenience [73.3%], health providers’ advice [81.8%], and costs [57.0%]). The county-wise distribution included effectiveness (67.8-95.9%; 67.8% in Egypt to 95.9% in Malaysia), acceptance (64.7-96.0%; 64.7% in Australia to 96.0% in Malaysia), hesitancy (31.5-86.0%; 31.5% in Egypt to 86.0% in Vietnam), convenience (49.7-95.7%; 49.7% in Austria to 95.7% in Malaysia), advice (66.1-97.3%; 66.1% in Austria to 97.3% in Malaysia), and costs (16.0-91.3%; 16.0% in Vietnam to 91.3% in Malaysia). In multivariable regression analysis, several socio-demographic characteristics were identified as associated factors of outcome variables including, i) vaccine effectiveness: younger age, male, urban residence, higher education, and higher income; ii) acceptance: younger age, male, urban residence, higher education, married, and higher income; and iii) hesitancy: male, higher education, employed, unmarried, and lower income. Likewise, the factors associated with vaccination decision-making including i) convenience: younger age, urban residence, higher education, married, and lower income; ii) advice: younger age, urban residence, higher education, unemployed/student, married, and medium income; and iii) costs: younger age, higher education, unemployed/student, and lower income.

CONCLUSIONS: Most participants believed that vaccination would effectively control and prevent COVID-19, and they would take vaccinations upon availability. Determinant factors found in this study are critical and should be considered as essential elements in developing COVID-19 vaccination campaigns to boost vaccination uptake in the populations.

PMID:35089917 | DOI:10.1371/journal.pntd.0010103

PLoS Comput Biol. 2022 Jan 28;18(1):e1009799. doi: 10.1371/journal.pcbi.1009799. Online ahead of print.

ABSTRACT

One of the main goals of current systems neuroscience is to understand how neuronal populations integrate sensory information to inform behavior. However, estimating stimulus or behavioral information that is encoded in high-dimensional neuronal populations is challenging. We propose a method based on parametric copulas which allows modeling joint distributions of neuronal and behavioral variables characterized by different statistics and timescales. To account for temporal or spatial changes in dependencies between variables, we model varying copula parameters by means of Gaussian Processes (GP). We validate the resulting Copula-GP framework on synthetic data and on neuronal and behavioral recordings obtained in awake mice. We show that the use of a parametric description of the high-dimensional dependence structure in our method provides better accuracy in mutual information estimation in higher dimensions compared to other non-parametric methods. Moreover, by quantifying the redundancy between neuronal and behavioral variables, our model exposed the location of the reward zone in an unsupervised manner (i.e., without using any explicit cues about the task structure). These results demonstrate that the Copula-GP framework is particularly useful for the analysis of complex multidimensional relationships between neuronal, sensory and behavioral variables.

PMID:35089913 | DOI:10.1371/journal.pcbi.1009799

Clin Chem Lab Med. 2022 Jan 31. doi: 10.1515/cclm-2022-0035. Online ahead of print.

NO ABSTRACT

PMID:35089658 | DOI:10.1515/cclm-2022-0035

Pharmacol Res Perspect. 2022 Feb;10(1):e00915. doi: 10.1002/prp2.915.

ABSTRACT

Although relapse is an important outcome to measure the effectiveness of schizophrenia treatment, no standard definition exists. This review aimed at identifying definitions and measurements of schizophrenia relapse in observational studies of long-acting injectables (LAIs) versus oral antipsychotics (OAPs) and at determining their impact on heterogeneity of comparative effectiveness estimates. A systematic review was conducted using MEDLINE and Embase (01 January 2010-11 November 2019 [date last searched]). Pragmatic searches of gray literature and snowballing were also conducted. Search outputs were screened independently by two assessors at first stage, and full-text of potentially eligible sources at second stage. For each retained source, definition and measurement of relapse, study methods, and comparative effectiveness estimates were extracted. Heterogeneity of estimates was assessed using I² statistic with a threshold of 50% for substantial heterogeneity. Literature search yielded 543 sources and pragmatic searches, 21, of which 35 were eligible. Twelve definitions of relapse were found based on hospitalization/emergency department (ED) data (28 studies) or clinical assessment (5 studies). No definition was provided in five studies. According to quantitative analyses, in studies defining relapse as schizophrenia-related hospitalization and/or ED visits over 1-year follow-up, LAIs were significantly more effective than OAPs. For studies measuring relapse based on all-cause hospitalization, heterogeneity was too high for pooling; yet this definition is the most frequently found in pooled estimates published in the literature. Schizophrenia relapse definitions led to substantial heterogeneity of comparative effectiveness estimates of LAIs versus OAPs. Creating study subgroups based on relapse definition effectively reduces statistical heterogeneity.

PMID:35089656 | DOI:10.1002/prp2.915

J Eval Clin Pract. 2022 Jan 28. doi: 10.1111/jep.13657. Online ahead of print.

ABSTRACT

RATIONALE, AIMS, AND OBJECTIVES: It is generally believed that evidence from low quality of evidence generate inaccurate estimates about treatment effects more often than evidence from high (certainty) quality evidence (CoE). As a result, we would expect that (a) estimates of effects of health interventions initially based on high CoE change less frequently than the effects estimated by lower CoE (b) the estimates of magnitude of effect size differ between high and low CoE. Empirical assessment of these foundational principles of evidence-based medicine has been lacking.

METHODS: We reviewed the Cochrane Database of Systematic Reviews from January 2016 through May 2021 for pairs of original and updated reviews for change in CoE assessments based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We assessed the difference in effect sizes between the original versus updated reviews as a function of change in CoE, which we report as a ratio of odds ratio (ROR). We compared ROR generated in the studies in which CoE changed from very low/low (VL/L) to moderate/high (M/H) versus M/H to VL/L. Heterogeneity and inconsistency were assessed using the tau and I² statistic. We also assessed the change in precision of effect estimates (by calculating the ratio of standard errors) (seR), and the absolute deviation in estimates of treatment effects (aROR).

RESULTS: Four hundred and nineteen pairs of reviews were included of which 414 (207 × 2) informed the CoE appraisal and 384 (192 × 2) the assessment of effect size. We found that CoE originally appraised as VL/L had 2.1 [95% confidence interval (CI): 1.19-4.12; p = 0.0091] times higher odds to be changed in the future studies than M/H CoE. However, the effect size was not different (p = 1) when CoE changed from VL/L → M/H [ROR = 1.02 (95% CI: 0.74-1.39)] compared with M/H → VL/L (ROR = 1.02 [95% CI: 0.44-2.37]). Similar overlap in aROR between the VL/L → M/H versus M/H → VL/L subgroups was observed [median (IQR): 1.12 (1.07-1.57) vs. 1.21 (1.12-2.43)]. We observed large inconsistency across ROR estimates (I² = 99%). There was larger imprecision in treatment effects when CoE changed from VL/L → M/H (seR = 1.46) than when it changed from M/H → VL/L (seR = 0.72).

CONCLUSIONS: We found that low-quality evidence changes more often than high CoE. However, the effect size did not systematically differ between the studies with low versus high CoE. The finding that the effect size did not differ between low and high CoE indicate urgent need to refine current EBM critical appraisal methods.

PMID:35089627 | DOI:10.1111/jep.13657

Int J Med Robot. 2022 Jan 28:e2370. doi: 10.1002/rcs.2370. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to compare the bone resection thickness, rate of minimal thickness insert usage, and postoperative range of motion (ROM) between robotic and navigated TKA.

METHODS: Fifty consecutive posterior-stabilized (PS) robotic TKA and 50 case-controlled PS navigated TKA were enrolled. Bone resection thickness, rate of minimal thickness insert usage, and postoperative flexion contracture over 5X00B0; were statistically compared.

RESULTS: The tibial bone resection thickness was significantly thinner in robotic TKA. The insert thickness was significantly lower, and the rate of minimal thickness insert usage was significantly higher in robotic TKA. The ROM at 3 months postoperatively and the rate of postoperative flexion contracture were comparable between the two groups.

CONCLUSION: Robotic TKA can reduce the tibial bone resection thickness and increase the rate of minimal thickness insert usage without increasing postoperative flexion contracture as compared with navigated TKA. This article is protected by copyright. All rights reserved.

PMID:35089642 | DOI:10.1002/rcs.2370

Med Vet Entomol. 2022 Jan 28. doi: 10.1111/mve.12564. Online ahead of print.

ABSTRACT

The study aimed to develop a multiplex qPCR to detect Leishmania infantum load in different sandfly sample settings using Leishmania kDNA and sandfly vacuolar ATPase (VATP) subunit C as internal control gene. The amplification of Lutzomyia longipalpis VATP gene was evaluated together with Leishmania infantum kDNA in a multiplex reaction. The concentration of VATP gene oligonucleotides was adjusted until no statistically significant difference was observed between all multiplex standard curves and singleplex curves, that is, only kDNA amplification. Limit of detection (LoD) was measured using a probit model and a cut-off defined by receiver operating characteristic analysis. Limit of quantification (LoQ) was assessed by a linear model using the coefficient of variation threshold of 25%. After assuring VATP gene amplification, its primer-probe concentrations were best at 100 nM/10 nM, respectively. The cut-off C_q value for L. infantum kDNA was defined as 35.46 with 100% of sensitivity and specificity. A total of 95% LoD was determined to be of 0.162 parasites while LoQ was 5.858. Our VATP/kDNA multiplex qPCR assay shows that it can be used to evaluate both DNA integrity and determine L. infantum load in L. longipalpis even for low yielded samples, that is, individual midguts.

PMID:35089617 | DOI:10.1111/mve.12564

J Magn Reson Imaging. 2022 Jan 28. doi: 10.1002/jmri.28078. Online ahead of print.

ABSTRACT

BACKGROUND: Liver shear stiffness measurement using magnetic resonance elastography (MRE) aids in the noninvasive diagnosis and staging of liver fibrosis. Inadequate breath-holds can lead to inaccurate stiffness estimation and/or failed MRE exams.

PURPOSE: To prospectively evaluate the performance of compressed sensitivity encoding (C-SENSE) accelerated rapid MRE measurement of liver shear stiffness using displacement wave polarity-inversion motion encoding.

STUDY TYPE: Retrospective.

SUBJECTS: Eleven with liver disease and 10 asymptomatic subjects.

FIELD STRENGTH/SEQUENCE: 1.5 T; gradient-recalled-echo (GRE) MRE.

ASSESSMENT: All participants underwent: 1) two-dimensional (2D) GRE MRE with inflow saturation using SENSE acceleration factor (R) of 2 (standard of care [SC]); 2) 2D rapid MRE with (RwS); and 3) without (RnS) inflow saturation using C-SENSE R = 3; and 4) spatial three-dimensional (3D) rapid MRE with inflow saturation (R3D) using C-SENSE R = 4; with nominally identical spatial resolution and coverage. Image analyst (D.G., 2 years of experience) drew identical and maximal regions of interest (ROIs) in right hepatic lobe.

STATISTICAL TESTS: Linear regression, intra-class correlation coefficients (ICC), Bland-Altman analyses, and the Wilcoxon signed-rank test were used to assess consistency and agreement of liver stiffness measurements for manually drawn identical and maximal ROIs.

RESULTS: In 21 participants (37 ± 14 years) with liver stiffness (2.3 ± 0.7 kPa), body mass index (BMI 27 ± 7 kg/m² ), proton density fat fraction (PDFF 9 ± 9%), and T₂ * (27 ± 4 msec); rapid MRE sequences showed excellent agreement (ICC > 0.95) with SC MRE and no correlation (r² < 0.1) of the differences (mean difference <0.2 kPa, <6%; limits of agreement <0.4 kPa, <16%) with BMI, PDFF, and T₂ *. Breath-hold times were: 14 seconds (SC), 5 seconds (RnS), 7 seconds (RwS) per slice, and 16 seconds for the R3D acquisition.

DATA CONCLUSIONS: C-SENSE accelerated GRE MRE sequences, using displacement wave polarity-inversion motion encoding, produce equivalent measurements of liver stiffness and have potential clinical benefit in patients with limited breath-holding capacity.

LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

PMID:35089614 | DOI:10.1002/jmri.28078

Acta Neurol Scand. 2022 Jan 28. doi: 10.1111/ane.13584. Online ahead of print.

ABSTRACT

OBJECTIVE: Uncertainty exists for the absolute risk of ischemic and hemorrhagic stroke in users of oral contraceptives (OCs). Estimates greatly vary between countries. In Denmark, absolute risk of ischemic stroke (IS) is estimated to be 21 per 100,000 person-years. Risk of cerebral hemorrhage (CH) is unknown. Using the Danish Stroke Registry, we investigated absolute risk of IS and CH in users of OC.

MATERIAL AND METHODS: For the Danish female population aged 15-49 years during 2003-2011, we obtained information on hospital admission for IS and CH and current use of OC from Danish nationwide registries. We defined current use of OC as redeeming at least two OC prescriptions within the previous year.

RESULTS: The Danish female population years 2003-2011 consisted mean of 1,246,142 women per year. Of these, 29.6% were OC users. In the study period, OC users had 291 IS and 14 CH. Absolute risk of IS in OC users was 8.8 per 100,000 person-years and of CH it was 0.4 per 100,000 person-years.

CONCLUSIONS: In OC users, absolute risk of IS was 8.8 per 100,000 person-years. This is more than half that of the risk previously assumed in Denmark. Risk of CH in OC users was very low and 0.4 per 100,000 person-years.

PMID:35089604 | DOI:10.1111/ane.13584