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Dermatitis : Contact, Atopic,... Jun 2024Construction workers (CWs) are at risk for occupational contact dermatitis (CD) owing to workplace exposures. Determine the prevalence of occupational allergic CD and...
Construction workers (CWs) are at risk for occupational contact dermatitis (CD) owing to workplace exposures. Determine the prevalence of occupational allergic CD and characterize common occupational allergens in CWs referred for patch testing in the United States and Canada. Retrospective cross-sectional analysis of patients patch tested by the North American Contact Dermatitis Group from 2001 to 2020. Of 47,843 patch-tested patients, 681 (1.4%) were CWs. Compared with non-CWs, CWs were more likely to be male (91.0% vs 30.9%) have occupational skin disease (36.9% vs 11.4%) and have hand involvement (37.2% vs 22.5%) (all < 0.0001). Of 681 CWs, 60.1% (411) had clinically relevant positive patch test reactions, and nearly 1/3 of CWs (128) had occupationally relevant reactions. Most common occupationally relevant allergens were potassium dichromate 0.25% pet. (30.5%, 39/128), bisphenol A epoxy resin 1% pet. (28.1%, 36/128), carba mix 3% pet. (14.8%, 19/128), cobalt (ii) chloride hexahydrate 1% pet. (14.1%, 18/128), and thiuram mix 1% pet. (14.1%, 18/128). Top sources of occupationally relevant allergens were cement/concrete/mortar (20.4%, 46/225), gloves (15.1%, 34/225), and coatings (paint/lacquer/shellac/varnish/stains) (9.8%, 22/225). Occupational CD in North American CWs is common. In this group, frequently identified etiological sources of occupational allergic CD included metals, epoxy resin, and rubber.
PubMed: 38888884
DOI: 10.1089/derm.2024.0018 -
Dermatitis : Contact, Atopic,... Jun 2024Topical minoxidil is generally well tolerated, yet there have been a few reports of allergic contact dermatitis (ACD) confirmed through patch testing. This systematic... (Review)
Review
Topical minoxidil is generally well tolerated, yet there have been a few reports of allergic contact dermatitis (ACD) confirmed through patch testing. This systematic review and individual participant data meta-analysis sought to elucidate the primary allergens in patients exhibiting ACD in response to topical minoxidil formulations and to ascertain the appropriate testing concentrations and vehicles of minoxidil itself. A comprehensive search was conducted across the PubMed, Scopus, and Embase databases utilizing the keywords "minoxidil" and "contact dermatitis," or "contact allergy," or "contact eczema." Studies documenting ACD in patients using topical minoxidil confirmed by patch testing were deemed eligible. Our analysis included 46 studies encompassing 99 patients with patch-test-confirmed ACD to minoxidil-based topical treatments. The majority of these patients (93.9%) were exposed to minoxidil without additional active components. Minoxidil itself was identified as the primary allergen in 74.7% of the patients, with propylene glycol being the next most common allergen at 17.1%. Other allergens identified included estradiol, butylene glycol, methylchloroisothiazolinone/methylisothiazolinone, canrenone, and latanoprost. The most effective concentration was found to be 2% minoxidil in propylene glycol, which yielded a 100% positivity rate. The findings indicate that minoxidil is the predominant allergen in ACD reactions to its topical formulations, followed by propylene glycol. For the accurate diagnosis of ACD related to minoxidil, patch testing with 2% minoxidil in propylene glycol is recommended, as are separate tests for propylene glycol and other potential allergenic ingredients.
PubMed: 38885151
DOI: 10.1089/derm.2024.0092 -
Investigative Ophthalmology & Visual... Jun 2024We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene.
PURPOSE
We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene.
METHODS
Fifty-three patients (mean age, 33.6 ± 16.7 years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed.
RESULTS
At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9 dB; 9.0 ± 10.2 dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0 µm; 250.7 ± 63.3 µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6 µm; 2615.5 ± 2370.4 µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]).
CONCLUSIONS
Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.
Topics: Humans; Male; Female; Adult; Prospective Studies; Tomography, Optical Coherence; Visual Acuity; Middle Aged; Electroretinography; Myosin VIIa; Visual Fields; Young Adult; Adolescent; Usher Syndromes; Genetic Therapy; Child; Visual Field Tests; Europe; Fluorescein Angiography; Follow-Up Studies; Aged; Longitudinal Studies; Disease Progression; Myosins; Retina
PubMed: 38884554
DOI: 10.1167/iovs.65.6.25 -
European Journal of Pharmacology Aug 2024Voltage-gated potassium (Kv) channel growth is strongly associated with the development of arrhythmia. Salidroside (Sal), an active component from Rhodiola crenulata,...
BACKGROUND
Voltage-gated potassium (Kv) channel growth is strongly associated with the development of arrhythmia. Salidroside (Sal), an active component from Rhodiola crenulata, has been shown to exert protective effects against heart disease. The present study was conducted to investigate the effects of Sal on Kv2.1 channel, and to explore the ionic mechanism of anti-arrhythmic.
METHODS
In this study, we utilized cisapride (Cis., A stimulant that prolongs the QT interval and causes cardiac arrhythmias) by intravenous injection to establish an arrhythmia model, and detected the effects of Sal on electrocardiography (ECG) and pressure volume loop (P-V loop) in SD rats. The effect of Sal on ECG of citalopram (Cit., a Kv2 channel inhibition)-evoked arrhythmia rat models was further evaluated by monitoring the dynamic changes of multiple indicators of ECG. Then, we detected the effect of Sal on the viability of hypoxic H9c2 cells using CCK-8 assay. After that, the effect of Sal on Kv channel currents (I) and Kv2.1 channel currents (I) in H9c2 cells under normal and hypoxic conditions was examined using whole-cell patch clamp technique. In addition, the effect of Sal on I and I in H9c2 cells was determined under the inhibition of Kv and Kv2.1 channels. HEK293 cells stably transfected with Kv2.1 plasmids were also used to investigate the I changes under Sal pre-treated and co-incubated conditions. In addition, potential interactions of Sal with Kv2.1 protein were predicted and tested by molecular docking, molecular dynamics simulation (MDS), localized surface plasmon resonance (LSPR), and cellular thermal shift assay (CETSA) techniques, respectively. Furthermore, gene and protein levels of Kv2.1 in Sal-treated H9c2 cell were estimated by qRT-PCR, Western blot (WB) and immunofluorescence (IF) analysis.
RESULTS
Sal shortened the prolongated QT interval and ameliorated the cardiac impairment associated with arrhythmia in SD rats caused by Cis., as reflected in the ECG and P-V loop data. And Sal was also protective against arrhythmia in rats caused by Kv2 channel inhibition. At the cellular level, Sal increased cell viability after CoCl-induced hypoxic injury in H9c2 cells. Whole-cell patch clamp assay confirmed that Sal inhibited both I and I in normal H9c2 cells, while enhanced I and I in cardiomyocytes after hypoxic injury. And Sal enhanced I inhibited by 1.5 mM 4-AP and upregulated all inhibition of Kv2 channels induced by 20 mM 4-AP administration, antagonized the I inhibitory effect of Cit. Moreover, Sal pre-administration for 24 h and immediate administration increased I in HEK293 cells stably transfected with Kv2.1 plasmids. Molecular docking demonstrated the potential binding of Sal to the Kv2.1 protein, with calculated binding energy of -5.4 kcal/mol. MDS test illustrated that the average hydrogen bonding of the Sal-Kv2.1 complexes was 30.89%. LSPR results verified the potential binding of Sal to Kv2.1 protein with an affinity value of 9.95 × 10 M. CETSA assay confirmed Sal can enhance the expression of Kv2.1 protein in H9c2 cells treated with heat, which suggests that Sal may bind to Kv2.1 protein. The results of WB, qRT-PCR, and IF further argued that Sal pre-administration for 24 h enhanced the levels of the Kv2.1 gene and protein (with no effects on the Kv2.1 gene and protein for H9c2 cells co-incubated with Sal for 6 h and 12 h).
CONCLUSION
Overall, our findings indicate that Sal can resist drug-induced arrhythmias in SD rats, partially by modulating repolarization through stimulating Kv2.1.
Topics: Animals; Shab Potassium Channels; Phenols; Rats; Glucosides; Male; Rats, Sprague-Dawley; Arrhythmias, Cardiac; Cell Line; Molecular Docking Simulation; Humans; Anti-Arrhythmia Agents; HEK293 Cells; Myocytes, Cardiac; Electrocardiography; Cell Survival; Action Potentials
PubMed: 38880221
DOI: 10.1016/j.ejphar.2024.176741 -
Proceedings. Biological Sciences Jun 2024Understanding the drivers of community stability has been a central goal in ecology. Traditionally, emphasis has been placed on studying the effects of biotic...
Understanding the drivers of community stability has been a central goal in ecology. Traditionally, emphasis has been placed on studying the effects of biotic interactions on community variability, and less is understood about how the spatial configuration of habitats promotes or hinders metacommunity stability. To test the effects of contrasting spatial configurations on metacommunity stability, I designed metacommunities with patches connected as random or scale-free networks. In these microcosms, two prey and one protist predator dispersed, and I evaluated community persistence, tracked biomass variations, and measured synchrony between local communities and the whole metacommunity. After 30 generations, scale-free metacommunities had lower global biomass variability and higher persistence, suggesting higher stability. Synchrony between patches was lower in scale-free metacommunities. Patches in scale-free metacommunities showed a positive relationship between variability and patch connectivity, indicating higher stability in isolated communities. No clear relationship between variability and patch connectivity was observed in random networks. These results suggest the increased heterogeneity in connectivity of scale-free networks favours the prevalence of isolated patches of the metacommunity, which likely act as refugia against competition-the dominant interaction in this system-resulting in higher global stability. These results highlight the importance of accounting for network topology in the study of spatial dynamics.
Topics: Ecosystem; Animals; Population Dynamics; Biomass; Food Chain; Biota; Models, Biological
PubMed: 38864323
DOI: 10.1098/rspb.2024.0567 -
JAMA Jun 2024Whether β-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain.
IMPORTANCE
Whether β-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain.
OBJECTIVE
To evaluate whether continuous vs intermittent infusion of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis.
DESIGN, SETTING, AND PARTICIPANTS
An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis.
INTERVENTION
Eligible patients were randomized to receive an equivalent 24-hour dose of a β-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality.
RESULTS
Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, -1.9% [95% CI, -4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P = .08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different.
CONCLUSIONS AND RELEVANCE
The observed difference in 90-day mortality between continuous vs intermittent infusions of β-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03213990.
PubMed: 38864155
DOI: 10.1001/jama.2024.9779 -
Cureus May 2024Coronary artery aneurysms (CAAs) due to an immunoglobulin G4 (IgG4)-related disease (IgG4-RD) are relatively rare, and there is no consensus on the choice of treatment...
Coronary artery aneurysms (CAAs) due to an immunoglobulin G4 (IgG4)-related disease (IgG4-RD) are relatively rare, and there is no consensus on the choice of treatment method. In the present study, we report the results of the surgical treatment for multiple giant CAAs caused by IgG4-RD. A 71-year-old man was diagnosed with severe aortic regurgitation and CAAs. A blood test showed high IgG4 levels, and computed tomography revealed four giant coronary artery aneurysms: two in the right coronary artery (RCA) (proximal RCA and posterior descending artery (PDA)), one in the left anterior descending (LAD), and one in the diagonal branch (Dx). We planned aortic valve replacement, coronary aneurysm resection, and coronary artery bypass grafting (CABG). After finishing aortic valve replacement, the CAAs in proximal RCA, LAD, and Dx were resected. The proximal and distal tracts of the aneurysm were closed with a pericardial bovine patch and ligation. However, since the distal PDA was too calcified to be anastomosed, and the PDA aneurysm was smaller than the others, it was decided to leave the PDA aneurysm. The anastomoses of SVG-RCA and Dx, as well as the left internal thoracic artery to LAD, were performed. Histopathological examination of the aneurysm wall showed a high IgG4-positive cell/IgG-positive cell ratio, and a diagnosis of IgG4-RD was made. In the treatment of CAAs due to IgG4-RD, it is essential to select a procedure that takes into account the size, location, and nature of the aneurysm, and comorbidities. To ensure resection of the aneurysm and blockade of blood flow, closure of the inflow and outflow tracts with a pericardial bovine patch and CABG are effective.
PubMed: 38864041
DOI: 10.7759/cureus.60115 -
Frontiers in Oncology 2024The ability to dynamically adjust target contours, derived Boolean structures, and ultimately, the optimized fluence is the end goal of online adaptive radiotherapy...
INTRODUCTION
The ability to dynamically adjust target contours, derived Boolean structures, and ultimately, the optimized fluence is the end goal of online adaptive radiotherapy (ART). The purpose of this work is to describe the necessary tests to perform after a software patch installation and/or upgrade for an established online ART program.
METHODS
A patch upgrade on a low-field MR Linac system was evaluated for post-software upgrade quality assurance (QA) with current infrastructure of ART workflow on (1) the treatment planning system (TPS) during the initial planning stage and (2) the treatment delivery system (TDS), which is a TPS integrated into the delivery console for online ART planning. Online ART QA procedures recommended for post-software upgrade include: (1) user interface (UI) configuration; (2) TPS beam model consistency; (3) segmentation consistency; (4) dose calculation consistency; (5) optimizer robustness consistency; (6) CT density table consistency; and (7) end-to-end absolute ART dose and predicted dose measured including interruption testing. Differences of calculated doses were evaluated through DVH and/or 3D gamma comparisons. The measured dose was assessed using an MR-compatible A26 ionization chamber in a motion phantom. Segmentation differences were assessed through absolute volume and visual inspection.
RESULTS
(1) No UI configuration discrepancies were observed. (2) Dose differences on TPS pre-/post-software upgrade were within 1% for DVH metrics. (3) Differences in segmentation when observed were small in general, with the largest change noted for small-volume regions of interest (ROIs) due to partial volume impact. (4) Agreement between TPS and TDS calculated doses was 99.9% using a 2%/2-mm gamma criteria. (5) Comparison between TPS and online ART plans for a given patient plan showed agreement within 2% for targets and 0.6 cc for organs at risk. (6) Relative electron densities demonstrated comparable agreement between TPS and TDS. (7) ART absolute and predicted measured end-to-end doses were within 1% of calculated TDS.
DISCUSSION
An online ART QA program for post-software upgrade has been developed and implemented on an MR Linac system. Testing mechanics and their respective baselines may vary across institutions, but all necessary components for a post-software upgrade QA have been outlined and detailed. These outlined tests were demonstrated feasible for a low-field MR Linac system; however, the scope of this work may be applied and adapted more broadly to other online ART platforms.
PubMed: 38863634
DOI: 10.3389/fonc.2024.1358487 -
IEEE Transactions on Medical Imaging Jun 2024Data-driven methods have shown tremendous progress in medical image analysis. In this context, deep learning-based supervised methods are widely popular. However, they...
Data-driven methods have shown tremendous progress in medical image analysis. In this context, deep learning-based supervised methods are widely popular. However, they require a large amount of training data and face issues in generalisability to unseen datasets that hinder clinical translation. Endoscopic imaging data is characterised by large inter- and intra-patient variability that makes these models more challenging to learn representative features for downstream tasks. Thus, despite the publicly available datasets and datasets that can be generated within hospitals, most supervised models still underperform. While self-supervised learning has addressed this problem to some extent in natural scene data, there is a considerable performance gap in the medical image domain. In this paper, we propose to explore patch-level instance-group discrimination and penalisation of inter-class variation using additive angular margin within the cosine similarity metrics. Our novel approach enables models to learn to cluster similar representations, thereby improving their ability to provide better separation between different classes. Our results demonstrate significant improvement on all metrics over the state-of-the-art (SOTA) methods on the test set from the same and diverse datasets. We evaluated our approach for classification, detection, and segmentation. SSL-CPCD attains notable Top 1 accuracy of 79.77% in ulcerative colitis classification, an 88.62% mean average precision (mAP) for detection, and an 82.32% dice similarity coefficient for segmentation tasks. These represent improvements of over 4%, 2%, and 3%, respectively, compared to the baseline architectures. We demonstrate that our method generalises better than all SOTA methods to unseen datasets, reporting over 7% improvement.
PubMed: 38857149
DOI: 10.1109/TMI.2024.3411933 -
Patch test positive results in patients with biopsy-proven central centrifugal cicatricial alopecia.Journal of the European Academy of... Jun 2024
PubMed: 38856113
DOI: 10.1111/jdv.20158