Category: Nevin Manimala

BJU Int. 2021 Jun 26. doi: 10.1111/bju.15527. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the role of music in reducing the pain and anxiety associated with flexible cystoscopy using a blinded trial design.

PATIENTS AND METHODS: A patient blinded randomised control trial of music during flexible cystoscopy was performed comparing the pain, measured by visual analogue scale (VAS), anxiety, measured by the state trait anxiety inventory (STAI), and vital signs of 109 patients across two public hospitals in New South Wales, Australia. The purpose and hypothesis of the study was concealed from patients until after results had been collected.

RESULTS: No statistically significant differences were detected between the Non-Music and Music groups in VAS pain score (2.04±1.94 vs 2.10±1.90, P=0.86), change in STAI anxiety score (4.87±9.87 vs 6.8±11.07, P=0.33) or post procedural vital signs (HR 74±14 vs 72±13, P=0.66, SBP 144±20 vs 141±19, P=0.47) between the two groups.

CONCLUSION: Music does not appear to decrease perceived pain or anxiety when used during flexible cystoscopy. These findings may differ from the literature due to a number of factors, most significantly blinding of participants, but also potentially due to the ethnic makeup of the study population or lack of choice of music.

PMID:34174137 | DOI:10.1111/bju.15527

Int J Clin Pract. 2021 Jun 26:e14577. doi: 10.1111/ijcp.14577. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: Subclinical hypothyroidism (SCH) is defined as high thyroid-stimulating hormone (TSH) and normal thyroxine (T4) levels. Data on the effects of early substitution with levothyroxine on psychophysical health in SCH are not consistent enough to support its general administration. The aim of this study was to examine the effect of 3-month levothyroxine (LT4) treatment on cardiovascular function in symptomatic SCH with TSH <10 mIU/L.

METHODS: Anthropometric, biochemical, electro- and echocardiographic indices were measured in 35 patients with persistent symptomatic SCH (4 mIU/L < TSH <10 mIU/L; mean ± SD: 7.0 ± 2.1 mIU/L) and 40 healthy controls at baseline and three months after the euthyroid state had been achieved on LT4 for SCH group, or three months of follow-up for controls.

RESULTS: The analyses showed a significant reduction in body weight (p=0.030), systolic and diastolic blood pressure (p=0.024, p=0.019), TSH (p<0.001), and thyroid peroxidase antibodies (TPO Ab) (p<0.001) on LT4 in the SCH group. There was a statistically significant decrease in end-systolic (ESV) and end-diastolic volumes (EDV) (p<0.001, p<0.001, respectively) after LT4 treatment. LT4 therapy significantly increased values of ejection fraction (EF), global longitudinal, circumferential and radial strains (p<0.001, p<0.001, p<0.001, respectively).

CONCLUSIONS: Our study confirmed an echocardiographic improvement of cardiac structure and function in treated individuals. Findings suggest the role of electrocardiographic and echocardiographic examination in objective monitoring for LT4 therapeutic effects.

PMID:34174124 | DOI:10.1111/ijcp.14577

Clin Oral Implants Res. 2021 Jun 26. doi: 10.1111/clr.13803. Online ahead of print.

ABSTRACT

OBJECTIVES: Purpose of this experimental in-vivo investigation was to evaluate the influence of modifying the implant surface by adding a monolayer of multi-phosphonate molecules on the de novo bone formation and osseointegration.

MATERIAL AND METHODS: The study was designed as an animal pre-clinical trial with intra-animal control and two healing periods, 2 and 8 weeks, to compare implants with an identical macro-design but with two different surfaces. Eight female Beagle dogs participated in the study. Control implants had a moderately rough surface combining sandblasting and acid etching; test implants had an additional monophosphonate layer covalently bonded to titanium. Histologic and radiographic (microCT) outcome variables were evaluated.

RESULTS: The first bone to implant contact (fBIC) was located more coronally for the test implants at the first (0.065 mm (95%CI = -0.82, 0.60)) and second healing milestones (0.17 mm (95%CI = -0.9, 0.55)). Most coronal BIC of the test implants displayed a higher percentage of osseointegration, + 6.33% and + 13.38% after 2 and 8 weeks, respectively; however the differences were not statistically significant. The microCT examination did not show any BIC difference.

CONCLUSIONS: The monophosphonate layer coating demonstrated clinical, histological and radiographic results similar to the control surface.

PMID:34174121 | DOI:10.1111/clr.13803

Reprod Domest Anim. 2021 Jun 26. doi: 10.1111/rda.13983. Online ahead of print.

ABSTRACT

Retention of fetal membranes (RFM) is a major reproductive disorder in dairy cows. An appropriate immune response is important for a physiological expulsion of the fetal membranes at parturition. Our study aims to provide a deeper insight into characteristics of fetal and maternal macrophages in bovine term placenta. We used transmission electron microscopy (TEM), immunohistochemistry and semi-quantitative RT-PCR to provide a deeper insight into characteristics of fetal and maternal macrophages in bovine term placenta. Semi-quantitative RT-PCR was used to define macrophage polarization in fetal and maternal compartments of normal term placenta. Gene expression of factors involved in M1-polarization [interferon regulatory factor-5 (IRF5), interleukin (IL)-12A, IL12B] and in M2-polarization (IL10) were studied. Ultrastructurally, fetal macrophages showed an irregular shape and large vacuoles, whereas the maternal macrophages were spindle shaped. By immunohistochemistry macrophages were identified by a strong staining with the lysosomal marker Lysosome-associated membrane glycoprotein 1 (LAMP-1), while myofibroblast in the maternal stroma were positive for alpha-smooth muscle actin. We used the LAMP-1 marker to compare the density of fetal stromal macrophages in placentas of cows with RFM and in controls, but no statistically significant difference was observed. RT-PCR showed a higher expression of all studied genes in the maternal compartment of the placenta and generally a higher expression of M1-, compared to M2-associated genes. Our results indicated that at parturition placental macrophages predominantly show the pro-inflammatory M1-polarization. The higher expression of all the target genes in the maternal compartment may denote that maternal macrophages in bovine term placenta are more frequent than fetal macrophages.

PMID:34174122 | DOI:10.1111/rda.13983

Scand J Med Sci Sports. 2021 Jun 26. doi: 10.1111/sms.14002. Online ahead of print.

ABSTRACT

The current study tested the effects of an intervention based on the trans-contextual model (TCM) on secondary school PE students’ sport injury prevention behaviour, and on theory-based motivational and social cognition mediators. Participants were PE students (N=1,168; M_age =13.322±1.045, range=12 to 16; female=51.721%) who participated in a 3-month cluster-randomised controlled trial. Schools were randomly assigned to a treatment group, in which PE teachers received training to be more supportive of psychological needs in teaching sport injury prevention, or a control group, in which PE teachers received no training. Participants completed survey measures of TCM variables and self-reported sport injury prevention behaviour at baseline and at 3-month post-intervention follow-up. The proposed TCM model exhibited adequate fit with the data, χ² =143.080 (df=19), CFI=.956, TLI=.916, RMSEA=.078 [90% CI=.066 to .090], and SRMR=.058. We found positive, statistically significant direct intervention effects on changes in perceived psychological need support (β=.064, p=.020). We also found positive, significant direct (β=.086 to .599, p<.001) and indirect (β=.002 to .027, p=.020 to .032) intervention effects on changes in TCM variables and behaviours to prevent sport injuries. Our findings support the TCM as a useful framework for building an intervention for promoting sport injury prevention behaviours among secondary school students.

PMID:34174104 | DOI:10.1111/sms.14002

Proteins. 2021 Jun 26. doi: 10.1002/prot.26165. Online ahead of print.

ABSTRACT

Crystallographic B-factors provide direct dynamical information on the internal mobility of proteins that is closely linked to function, and are also widely used as a benchmark in assessing elastic network models. A significant question in the field is: what is the exact amount of thermal vibrations in protein crystallographic B-factors? This work sets out to answer this question. First, we carry out a thorough, statistically sound analysis of crystallographic B-factors of over 10,000 structures. Second, by employing a highly accurate all-atom model based on the well-known CHARMM force field, we obtain computationally the magnitudes of thermal vibrations of nearly 1,000 structures. Our key findings are: (i) the magnitude of thermal vibrations, surprisingly, is nearly protein-independent, as a corollary to the universality for the vibrational spectra of globular proteins established earlier; (ii) the magnitude of thermal vibrations is small, less than 0.1 å² at 100 K; (iii) the percentage of thermal vibrations in B-factors is the lowest at low resolution and low temperature (<10%) but increases to as high as 60% for structures determined at high resolution and at room temperature. The significance of this work is that it provides for the first time, using an extremely large dataset, a thorough analysis of B-factors and their thermal and static disorder components. The results clearly demonstrate that structures determined at high resolution and at room temperature have the richest dynamics information. Since such structures are relatively rare in the PDB database, the work naturally calls for more such structures to be determined experimentally. This article is protected by copyright. All rights reserved.

PMID:34174110 | DOI:10.1002/prot.26165

Genet Epidemiol. 2021 Jun 26. doi: 10.1002/gepi.22419. Online ahead of print.

ABSTRACT

In the analysis of gene expression data, when there are two or more disease conditions/groups (e.g., diseased and normal, responder and nonresponder, and multiple stages/subtypes), differential analysis has been extensively conducted to identify key differences and has important implications. Network analysis takes a system perspective and can be more informative than that limited to simple statistics such as mean and variance. In differential network analysis, a common practice is to first estimate a gene expression network for each condition/group, and then spectral clustering can be applied to the network difference(s) to identify key genes and biological mechanisms that lead to the differences. Compared to “simple” analysis such as regression, differential network analysis can be more challenging with the significantly larger number of parameters. In this study, taking advantage of the increasing popularity of multidimensional profiling data, we develop an assisted analysis strategy and propose incorporating regulator information to improve the identification of key genes (that lead to the differences in gene expression networks). An effective computational algorithm is developed. Comprehensive simulation is conducted, showing that the proposed approach can outperform the benchmark alternatives in identification accuracy. With the The Cancer Genome Atlas lung adenocarcinoma data, we analyze the expressions of genes in the KEGG cell cycle pathway, assisted by copy number variation data. The proposed assisted analysis leads to identification results similar to the alternatives but different estimations. Overall, this study can deliver an efficient and cost-effective way of improving differential network analysis.

PMID:34174112 | DOI:10.1002/gepi.22419

Med Phys. 2021 Jun 26. doi: 10.1002/mp.15054. Online ahead of print.

ABSTRACT

PURPOSE: This study develops a viscous damping model (VDM) based on Rayleigh Damping (RD) with potential use in low cost, non-invasive breast cancer diagnostics using Digital Image Elasto Tomography (DIET).

METHODS: A clinical trial involving 13 subjects, each with a tumor in one breast, resulted in 13 cancerous and 13 healthy breasts. Displacement data following actuator induced steady state vibration in the breast tissue was captured using the DIET system. Over 14,000 reference points on the breast surface were split into four segments and viscous damping constant calculated for each reference point. The VDM was fit to median filtered data for each breast segment and VDM coefficients compared within each breast. One model coefficient, relating to stiffness, was hypothesised to differ in breast segments containing a tumor. Comparison of ‘b’ coefficients in different breast segments using percentage tolerances provided an unbiased, generalizable diagnostic method. Bootstrapping with replacement was used to up-sample the data and create smooth receiver operator characteristic (ROC) curves. A total of 12 breast segmentation configurations were used to demonstrate the robustness of the method.

RESULTS: Fitting the VDM to median filtered data gave consistent results for one VDM coefficient (‘a’) across all breasts. The second VDM coefficient (‘b’) showed diagnostic potential with breast segments having consistent coefficients in healthy breasts. In cancerous breasts ‘b’ coefficients were found to be statistically different in segments containing and adjacent to the tumor compared with the segment furthest from the tumor with p<0.02 using the Student t-Test. Large discrepancies in ‘b’ coefficients were found to be indicative of a tumor with a 14.5% tolerance resulting in sensitivity and specificity of 76.9%. The optimal breast configuration resulted in an area under the ROC curve (AUC) of 0.81 with sensitivity and specificity at 77% and 72%, respectively.

CONCLUSION: This VDM method enables a computationally simple diagnostic technique using DIET for comfortable breast screening for women of all ages. Regular screening potential allows for tolerance alteration based on age, prior subject-specific results, and other risk factors to manage false positives, reducing psychological harm while optimising early detection for successful treatment and decreased mortality.

PMID:34174093 | DOI:10.1002/mp.15054

Biometrics. 2021 Jun 26. doi: 10.1111/biom.13509. Online ahead of print.

ABSTRACT

The COVID-19 pandemic due to the novel coronavirus SARS CoV-2 has inspired remarkable breakthroughs in the development of vaccines against the virus and the launch of several phase 3 vaccine trials in Summer 2020 to evaluate vaccine efficacy (VE). Trials of vaccine candidates using mRNA delivery systems developed by Pfizer-BioNTech and Moderna have shown substantial VEs of 94-95%, leading the US Food and Drug Administration to issue Emergency Use Authorizations and subsequent widespread administration of the vaccines. As the trials continue, a key issue is the possibility that VE may wane over time. Ethical considerations dictate that trial participants be unblinded and those randomized to placebo be offered study vaccine, leading to trial protocol amendments specifying unblinding strategies. Crossover of placebo subjects to vaccine complicates inference on waning of VE. We focus on the particular features of the Moderna trial and propose a statistical framework based on a potential outcomes formulation within which we develop methods for inference on potential waning of VE over time and estimation of VE at any post-vaccination time. The framework clarifies assumptions made regarding individual- and population-level phenomena and acknowledges the possibility that subjects who are more or less likely to become infected may be crossed over to vaccine differentially over time. The principles of the framework can be adapted straightforwardly to other trials. This article is protected by copyright. All rights reserved.

PMID:34174097 | DOI:10.1111/biom.13509

Med Phys. 2021 Jun 26. doi: 10.1002/mp.15057. Online ahead of print.

ABSTRACT

PURPOSE: MR-Linac integrates an MRI scanner and a linear accelerator to provide adaptive radiation treatment. Superior tissue contrast and real-time imaging can give the clinicians confidence to reduce the margins of the planning target volume (PTV). The purpose of this study was to verify the dosimetric accuracy of an MR-Linac system in treating a moving target and assess the error with different motion patterns and adaptation methods.

METHODS: We performed an end-to-end test for Elekta Unity (Elekta, Crawley, UK) using the 4D Dynamic Thorax Phantom (CIRS MRgRT 008Z), comparing the measured and planned dose. The moving phantom had four measurement locations in the tumor, liver, kidney, and spinal cord regions with a PTW30013 ion chamber (Freiberg, Germany). For seven different motion patterns, we first acquired simulation CT using a slow-scanning protocol, based on which we generated reference plans. The treatment technique was the standard intensity-modulated radiation therapy (IMRT). We tested both adaptation workflows: the Adapt-To-Position (ATP) and the Adapt-To-Shape (ATS). The 3D distribution was measured using a diode array phantom (Sun Nuclear Inc., Melbourne, FL) to check the dose distribution accuracy as part of the routine QA process. We also performed end-to-end tests on a conventional Linac. Finally, we used SPSS Statistics 22.0 (Inc., Chicago, IL, USA) for data analysis.

RESULTS: All pre-treatment reference plans and delivered plans had excellent QA results with a better than 95% passing rate of relative Gamma analysis (2%/2 mm criteria). The adaptive planning for MR-Linac produced quality plans. The measured dose in the target agreed with the calculated dose.

CONCLUSIONS: The adaptive treatment on the MR-Linac system investigated met the expected performance with tumor motions. The outline of the target could be visualized and accurately contoured on the 3D MR for online planning. Under different motion patterns, the difference between the measured and calculated dose was acceptable clinically.

PMID:34174099 | DOI:10.1002/mp.15057