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Nevin Manimala Statistics

Effect of Local Corticosteroid Administration on CD8+CD25+Foxp3+ Tregs in Neutrophilic CRSwNP

ORL J Otorhinolaryngol Relat Spec. 2022 Apr 25:1-10. doi: 10.1159/000524385. Online ahead of print.

ABSTRACT

INTRODUCTION: CD8+CD25+Foxp3+ regulatory T cells (Tregs) play an important role in human’s immune tolerance. The study was aimed to assess the influence of budesonide nasal spray on CD8+CD25+Foxp3+ Tregs and to evaluate their cellular functions in neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNPs).

METHODS: Fifteen patients with neutrophilic CRSwNPs were enrolled and received physiological saline or budesonide nasal spray treatment (Saline or Budesonide group) for 3 months. Nasal tissue samples were obtained from normal subjects or those patients and cultured in vitro. CD8+CD25+Foxp3+ Tregs were separated from normal or NP tissues and also cultured in vitro. Then interleukin (IL)-10 and its mRNA were evaluated in the above cell cultures. The cells were applied into NP cultures. Finally, myeloperoxidase (MPO), interferon (IFN)-γ, IL-1β, and tumor necrosis factor (TNF)-α were assessed in the tissue cultures.

RESULTS: CD8+CD25+Foxp3+ Tregs decreased in NP tissues. Budesonide administration did not enhance the percentage of these cells in polypoid tissues. IL-10 and its mRNA were increased in the above cell cultures from NPs. However, there were no statistical differences between the two treatments in the IL-10 expression. Additionally, levels of MPO, IFN-γ, IL-1β, and TNF-α were totally elevated in NP tissue cultures and reduced after the administration of CD8+CD25+Foxp3+ Tregs. However, there were no significant differences in concentrations of these mediators between these two groups of the CD8+CD25+Foxp3+ Tregs treatment in vitro.

CONCLUSION: The findings indicate that CD8+CD25+Foxp3+ Tregs might regulate the neutrophilic inflammation, and budesonide nasal spray therapy could not ameliorate the inflammation in neutrophilic CRSwNPs.

PMID:35468610 | DOI:10.1159/000524385

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Nevin Manimala Statistics

Incidence, risk factors, treatment and outcome of ocular hypertension following intravitreal steroid injections: A comparative study

Ophthalmologica. 2022 Apr 25. doi: 10.1159/000522504. Online ahead of print.

ABSTRACT

PURPOSE: To compare the incidence, risk factors, treatment, and outcomes associated with intravitreal triamcinolone-acetonide (TA) and dexamethasone-implant (Dex) induced ocular hypertension (OHT).

METHODS: This retrospective study reviewed 1549 TA and Dex administrations in 1075 eyes of 897 patients. Intraocular pressure (IOP) values were monitored for a period of 6-months following intravitreal injection(s) and patients were categorized as steroid-responders (SR): IOP ≥ 21mmHg, and non-responders (NR): IOP ≤ 20mmHg. Glaucoma patients, glaucoma suspects, uveitis, trauma, and less than one month IOP follow-up cases were excluded from the study. Incidence of IOP rise, time and magnitude of IOP rise, and its management procedures were studied. Ocular and systemic association with OHT incidence was investigated. Statistical analysis was performed using SPSS.23 and p < 0.05 was considered significant.

RESULT: 28% of TA and 17% of Dex administered eyes developed OHT. Male subjects and elderly people (greater than 40 years) are at higher risk for OHT following steroid treatment. A high percentage of IOP rise was observed at day-1 (41%) for TA-SR, and after 1-month (50%) among Dex-SR. IOP rise was found to be more severe (>30mmHg) for TA-SR compared to Dex-SR (p=0.006). 6% TA-SR required trabeculectomy with medically uncontrollable IOP. Myopia is a risk factor for secondary OHT, whereas diabetes mellitus and hypercholesterolemia were protective of it.

CONCLUSION: 28% of TA and 17% of Dex administrations developed OHT. Early and severe IOP rise was more common in TA than among Dex administrations. Myopia is a risk for Dex-OHT.

PMID:35468616 | DOI:10.1159/000522504

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Comparison between Amplatzer and Watchman left atrial appendage closure devices for stroke prevention in atrial fibrillation:a systematic review and meta-analysis

Cardiology. 2022 Apr 25. doi: 10.1159/000524626. Online ahead of print.

ABSTRACT

INTRODUCTION: The Amplatzer and Watchman left atrial appendage closure (LAAC) devices are the two most frequently used devices for left atrial appendage closure devices worldwide. This meta-analysis aims to compare the safety and efficacy of the two devices.

METHODS: We searched the PubMed, EMBASE and the Cochrane Library for studies up to 6 February 2022 that compared the safety and efficacy of the Amplatzer and Watchman devices.

RESULTS: Fifteen studies including 2,150 patients in randomized controlled trials (RCTs) and 2,526 patients in observational studies were included in the meta-analysis. Amplatzer device was associated with higher rates of major procedure-related complications (odds ratio [OR]: 1.99, 95% confidence interval [CI]: 1.45-2.74, P <0.0001) and device embolization (OR: 1.99, 95% CI: 1.09-3.64, P =0.03). However, Amplatzer device had lower rates of total peridevice leak (PDL) (OR:0.48, 95% CI: 0.27-0.83, P =0.009), significant PDL (OR:0.27, 95% CI: 0.12-0.57, P =0.0007) and device-related thrombus (DRT) (OR:0.67, 95% CI: 0.48-0.95, P =0.02). No statistical differences were observed between the two devices in other safety and efficacy endpoints, such as pericardial effusion, cardiac tamponade, air embolism, vascular complications, ischemic stroke/ transient ischemic attack (TIA), hemorrhagic stroke, all-cause death, cardiovascular death and bleeding.

CONCLUSIONS: Amplatzer LAAC device was associated with higher rates of major procedure-related complications, especially in device embolization. Watchman LAAC device was associated with higher rates of PDL and DRT. There were no significant differences between two devices in ischemic stroke/TIA, hemorrhagic stroke, all-cause death, cardiovascular death and bleeding.

PMID:35468598 | DOI:10.1159/000524626

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Nevin Manimala Statistics

A brief overview of current approaches for underwater sound analysis and reporting

Mar Pollut Bull. 2022 Apr 22;178:113610. doi: 10.1016/j.marpolbul.2022.113610. Online ahead of print.

ABSTRACT

Soundscapes have substantially changed since the industrial revolution and in response to biodiversity loss and climate change. Human activities such as shipping, resource exploration and offshore construction alter natural ecosystems through sound, which can impact marine species in complex ways. The study of underwater sound is multi-disciplinary, spanning the fields of acoustics, physics, animal physiology and behaviour to marine ecology and conservation. These different backgrounds have led to the use of various disparate terms, metrics, and summary statistics, which can hamper comparisons between studies. Different types of equipment, analytical pathways, and reporting can lead to different results for the same sound source, with implications for impact assessments. For meaningful comparisons and derivation of appropriate thresholds, mitigation, and management approaches, it is necessary to develop common standards. This paper presents a brief overview of acoustic metrics, analysis approaches and reporting standards used in the context of long-term monitoring of soundscapes.

PMID:35468578 | DOI:10.1016/j.marpolbul.2022.113610

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Phase differentiation based on x-ray energy spectrum correlation with an energy dispersive spectrometer (EDS)

Ultramicroscopy. 2022 Apr 19;238:113534. doi: 10.1016/j.ultramic.2022.113534. Online ahead of print.

ABSTRACT

Generating quantitative phase maps is unvaluable to access the phase distribution in a material. X-ray hyperspectral mapping using an energy dispersive spectrometer (EDS) attached to a scanning electron microscope (SEM) is the most practical way to collect these data, mainly due to its relatively ease of operation and availability around the world. In this work, we demonstrate an innovative technique to produce high-quality phase maps based on the correlation between each hyperspectral image pixel spectrum and a set of standards spectra. The standards spectra can be obtained experimentally from bulk specimens of known materials but also via analytical computations. The method is not only robust against electron beam current and spectrometer instabilities but also to statistical noise in the standards as well as in the hyperspectral image spectra. Equally, the method is reliable to produce phase distribution maps at low operating voltage where SEM-EDS quantitative x-ray microscopy is limited by many factors like peak overlapping, continuous background approximations and produces inaccurate phase maps. The results presented in this study will certainly open a new path to produce useful x-ray quantitative data and potentially break the locks of conventional x-ray microanalysis using EDS.

PMID:35468564 | DOI:10.1016/j.ultramic.2022.113534

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Could routine forensic STR genotyping data leak personal phenotypic information?

Forensic Sci Int. 2022 Apr 18;335:111311. doi: 10.1016/j.forsciint.2022.111311. Online ahead of print.

ABSTRACT

The application of forensic genetic markers must comply with privacy rights and legal policies on a premise that the markers do not expose phenotypic information. The most widely-used short tandem repeats (STRs) are generally viewed as ‘junk’ DNA because most STRs are located in non-coding regions and therefore refrain from leaking phenotypic traits. But with a deepening understanding of phenotypes and underlying genetic structure, whether STRs could potentially reflect any phenotypic information may need re-examining. Therefore, we performed the following analyses. First, we analyzed the association between 15 STRs and three facial characteristics (single or double eyelid, with or without epicanthus, unattached or attached earlobe) on 721 unrelated Han Chinese individuals. Then, we collected 27199 individuals’ STRs and geographic data from the literature to investigate the association between STRs and bio-geographic information, and predict geographic information by STRs on additional 1993 unrelated individuals. We found that there was scarcely any association between STRs with studied facial characteristics. Although allele19 in D2S1338 and allele 18 in FGA (P = 0.0032, P = 0.0030, respectively after Bonferroni correction) showed statistical significance, the prediction effectiveness was very low. For the STRs and bio-geographic information, the principal component analysis showed the first three components could explain 87.7% of the variance, but the prediction accuracy only reached 25.2%. We demonstrated that the forensic phenotypes are usually complex traits, it is hardly possible to uncover phenotypic information by testing only dozens of STR loci.

PMID:35468577 | DOI:10.1016/j.forsciint.2022.111311

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Nevin Manimala Statistics

Techniques for digital histological morphometry of the pineal gland

Acta Histochem. 2022 Apr 22;124(4):151897. doi: 10.1016/j.acthis.2022.151897. Online ahead of print.

ABSTRACT

INTRODUCTION: The pineal gland is a small photo-neuro-endocrine organ. This study used human post-mortem pineal glands to microscopically assess immunohistochemical marker intensity and percentage of positivity using known and novel digital techniques.

MATERIALS AND METHODS: An experimental non-inferiority study has been performed on 72 pineal glands harvested from post-mortem examinations. The glands have been stained with glial fibrillary acidic protein (GFAP), synaptophysin (SYN), neuron-specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using optical analysis, CaseViewer, ImageJ, and MorphoRGB RESULTS: Strong and statistically significant correlations were found and plotted using Bland-Altman diagrams between the two image analysis software in the case of mean percentage and intensity of GFAP, NSE, NF, and SYN.

DISCUSSIONS: Software such as SlideViewer and ImageJ, with our novel software MorphoRGB were used to perform histological morphometry of the pineal gland. Digital morphometry of a small organ such as the pineal gland is easy to do by using whole slide imaging (WSI) and digital image analysis software, with potential use in clinical settings. MorphoRGB provides slightly more accurate data than ImageJ and is more user-friendly regarding measurements of parenchyma percentage stained by immunohistochemistry. The results show that MorphoRGB is not inferior in functionality.

CONCLUSIONS: The described morphometric techniques have potential value in current practice, experimental small animal models and human pineal glands, or other small endocrine organs that can be fully included in a whole slide image. The software we used has applications in quantifying immunohistochemical stains.

PMID:35468563 | DOI:10.1016/j.acthis.2022.151897

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Modeling the population-level impact of treatment on COVID-19 disease and SARS-CoV-2 transmission

Epidemics. 2022 Apr 16;39:100567. doi: 10.1016/j.epidem.2022.100567. Online ahead of print.

ABSTRACT

Different COVID-19 treatment candidates are under development, and some are becoming available including two promising drugs from Merck and Pfizer. This study provides conceptual frameworks for the effects of three types of treatments, both therapeutic and prophylactic, and to investigate their population-level impact, to inform drug development, licensure, decision-making, and implementation. Different drug efficacies were assessed using an age-structured mathematical model describing SARS-CoV-2 transmission and disease progression, with application to the United States as an illustrative example. Severe and critical infection treatment reduces progression to COVID-19 severe and critical disease and death with small number of treatments needed to avert one disease or death. Post-exposure prophylaxis treatment had a large impact on flattening the epidemic curve, with large reductions in infection, disease, and death, but the impact was strongly age dependent. Pre-exposure prophylaxis treatment had the best impact and effectiveness, with immense reductions in infection, disease, and death, driven by the robust control of infection transmission. Effectiveness of both pre-exposure and post-exposure prophylaxis treatments was disproportionally larger when a larger segment of the population was targeted than a specific age group. Additional downstream potential effects of treatment, beyond the primary outcome, enhance the population-level impact of both treatments. COVID-19 treatments are an important modality in controlling SARS-CoV-2 disease burden. Different types of treatment act synergistically for a larger impact, for these treatments and vaccination.

PMID:35468531 | DOI:10.1016/j.epidem.2022.100567

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Effect of customised preformed foot orthoses on gait parameters in children with juvenile idiopathic arthritis: A multicentre randomised clinical trial

Gait Posture. 2022 Apr 19;95:93-99. doi: 10.1016/j.gaitpost.2022.04.017. Online ahead of print.

ABSTRACT

BACKGROUND: Children with juvenile idiopathic arthritis (JIA) can experience significant physical impairment of the lower extremity. Prolonged joint disease and symptoms may cause gait alterations such as reduced walking speed and increased plantar pressures in diseased areas of their feet. There is limited robust clinical trials investigating the effect of non-invasive mechanical therapies such as foot orthoses (FOs) on improving gait parameters in children with JIA.

RESEARCH QUESTION: Are customised preformed FOs effective in improving gait parameters in children with JIA?

METHODS: A multicentre, parallel design, single-blinded randomised clinical trial was used to assess the gait impacts of customised preformed FOs on children with JIA. Children with a diagnosis of JIA, exhibiting lower limb symptoms and aged 5-18 were eligible. The trial group received a low-density full length, Slimflex Simple device which was customised chair side and the control group received a sham device. Peak pressure and pressure time integrals were used as the main gait outcomes and were measured using portable Tekscan gait analysis technology at baseline, 3 and 6 months. Differences at each follow-up were assessed using the Wilcoxon rank sum test.

RESULTS: 66 participants were recruited. Customised preformed FOs were effective in altering plantar pressures in children with JIA versus a control device. Reductions of peak pressures and pressure time integrals in the heel, forefoot and 5th metatarsophalangeal joint were statistically significant in favour of the trial group. This was associated with statistically significant increased midfoot contact with the trial device at baseline, 3 and 6-month data collections. The trial intervention was safe and well accepted by participants, which is reflected in the high retention rate (92%).

SIGNIFICANCE: Clinicians may prescribe customised preformed FOs in children with JIA to deflect pressure from painful joints and redistribute from high pressure areas such as the rearfoot and forefoot.

PMID:35468489 | DOI:10.1016/j.gaitpost.2022.04.017

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Generative models improve radiomics performance in different tasks and different datasets: An experimental study

Phys Med. 2022 Apr 22;98:11-17. doi: 10.1016/j.ejmp.2022.04.008. Online ahead of print.

ABSTRACT

PURPOSE: Radiomics is an active area of research focusing on high throughput feature extraction from medical images with a wide array of applications in clinical practice, such as clinical decision support in oncology. However, noise in low dose computed tomography (CT) scans can impair the accurate extraction of radiomic features. In this article, we investigate the possibility of using deep learning generative models to improve the performance of radiomics from low dose CTs.

METHODS: We used two datasets of low dose CT scans – NSCLC Radiogenomics and LIDC-IDRI – as test datasets for two tasks – pre-treatment survival prediction and lung cancer diagnosis. We used encoder-decoder networks and conditional generative adversarial networks (CGANs) trained in a previous study as generative models to transform low dose CT images into full dose CT images. Radiomic features extracted from the original and improved CT scans were used to build two classifiers – a support vector machine (SVM) and a deep attention based multiple instance learning model – for survival prediction and lung cancer diagnosis respectively. Finally, we compared the performance of the models derived from the original and improved CT scans.

RESULTS: Denoising with the encoder-decoder network and the CGAN improved the area under the curve (AUC) of survival prediction from 0.52 to 0.57 (p-value < 0.01). On the other hand, the encoder-decoder network and the CGAN improved the AUC of lung cancer diagnosis from 0.84 to 0.88 and 0.89 respectively (p-value < 0.01). Finally, there are no statistically significant improvements in AUC using encoder-decoder networks and CGAN (p-value = 0.34) when networks trained at 75 and 100 epochs.

CONCLUSION: Generative models can improve the performance of low dose CT-based radiomics in different tasks. Hence, denoising using generative models seems to be a necessary pre-processing step for calculating radiomic features from low dose CTs.

PMID:35468494 | DOI:10.1016/j.ejmp.2022.04.008