Loeffler's Endocarditis- A cause of endomyocardial fibrosis in a patient of juvenile idiopathic arthritis: A Case Report.

Endomyocardial fibrosis secondary to hyper-eosinophilic syndrome also known as Loeffler's Endocarditis is a rare cause of restrictive cardiomyopathy. If left untreated, it carries a very high morbidity and mortality rate. The case of a 20 years old girl, a known case of polyarticular juvenile idiopathic arthritis since the age of 13 years was reported at Federal Government Polyclinic Hospital, Islamabad on 14th May 2022. She presented with an acute history of shortness of breath and cough for two weeks. Her initial echocardiogram showed suspicion of Loeffler's Endocarditis, which is attributed to be an adverse effect of etanercept- a tumour necrosis factor (TNF) inhibitor, which she had been prescribed for her arthritis. The patient is currently being managed with high doses of steroids, therapeutic anticoagulation with rivaroxaban, carvedilol for tachycardia and mycophenolate mofetil as an immunosuppressant.

Outcomes of a Modified Technique for Deflation of Distal Radial Artery Occlusion Device on Radial Artery Patency After Percutaneous Coronary Intervention.

Objective: This study aimed to compare two protocols of deflation with increased intervals versus late deflation with smaller intervals for distal radial artery occlusion device (DROAD) removal to assess for radial artery occlusion (RAO). Methods: All patients who underwent PCI with distal radial access were enrolled in the study. The DROAD was applied using an occlusive hemostasis method. Patients were assigned to either protocol 1 or protocol 2 at the primary physician's discretion. Protocol 1 involved the removal of 2 ml of air starting 1 h after the sheath removal and then the removal of 2 ml every 30 min until the band came off. Protocol 2 involved the removal of 4 ml of air 2 h after the sheath removal and then a further 4 ml of air every 15 min until the band came off. Results: A total of 446 patients were enrolled in this study (mean age; 61 ± 6 (Group 1) and 60 ± 5 (Group 2); females 45.83% (Group 1) and 46.34% (Group 2)). The baseline characteristics were the same, including mean hemostasis time (256 ± 25 min (Group 1) and 254 ± 28 min (Group 2), P-value = 0.611). Primary and secondary endpoints did not reach significance in either group (RAO; 21 (8.71) Group 1 and 18 (8.78) Group 2 (P-value = 0.932)). Age (OR (95%CI): 1.07 (0.57-1.45); P-value = 0.031), female gender (OR (95%CI): 1.42 (0.93-1.74); P-value = 0.012), distal artery diameter (OR (95%CI): 0.57 (0.21-0.93); P-value = 0.005), procedure time (OR (95%CI): 2.64 (0.95-4.32); P-value = 0.001), and sheath size (OR (95%CI): 2.47 (1.43-3.76); P-value = 0.044) were predictors of RAO in our cohort. Conclusion: This investigation shows no difference in the incidence of RAO with the standard versus accelerated deflation protocol after PCI. However, local vascular complications, including hematoma were increased with the accelerated protocol.

Multimodal MRI radiomic models to predict genomic mutations in diffuse intrinsic pontine glioma with missing imaging modalities.

Purpose: Predicting H3.1, TP53, and ACVR1 mutations in DIPG could aid in the selection of therapeutic options. The contribution of clinical data and multi-modal MRI were studied for these three predictive tasks. To keep the maximum number of subjects, which is essential for a rare disease, missing data were considered. A multi-modal model was proposed, collecting all available data for each patient, without performing any imputation. Methods: A retrospective cohort of 80 patients with confirmed DIPG and at least one of the four MR modalities (T1w, T1c, T2w, and FLAIR), acquired with two different MR scanners was built. A pipeline including standardization of MR data and extraction of radiomic features within the tumor was applied. The values of radiomic features between the two MR scanners were realigned using the ComBat method. For each prediction task, the most robust features were selected based on a recursive feature elimination with cross-validation. Five different models, one based on clinical data and one per MR modality, were developed using logistic regression classifiers. The prediction of the multi-modal model was defined as the average of all possible prediction results among five for each patient. The performances of the models were compared using a leave-one-out approach. Results: The percentage of missing modalities ranged from 6 to 11% across modalities and tasks. The performance of each individual model was dependent on each specific task, with an AUC of the ROC curve ranging from 0.63 to 0.80. The multi-modal model outperformed the clinical model for each prediction tasks, thus demonstrating the added value of MRI. Furthermore, regardless of performance criteria, the multi-modal model came in the first place or second place (very close to first). In the leave-one-out approach, the prediction of H3.1 (resp. ACVR1 and TP53) mutations achieved a balanced accuracy of 87.8% (resp. 82.1 and 78.3%). Conclusion: Compared with a single modality approach, the multi-modal model combining multiple MRI modalities and clinical features was the most powerful to predict H3.1, ACVR1, and TP53 mutations and provided prediction, even in the case of missing modality. It could be proposed in the absence of a conclusive biopsy.

Firm characteristics, governance mechanisms, and ESG disclosure: how caring about sustainable concerns?

Environmental, social, and governance (ESG) pillars help determine the business organizations' sustainable business practices. Considering the same, this research examines the association between firm characteristics, governance mechanisms, and ESG for a sample of 564 firms from fifteen developed economies. For empirical analysis, ordinary least square, fixed effect, and random effect estimations techniques were applied using annual data from 2010 to 2019. The overall findings reveal that the governance structure of firms (board size, board independence, and cross-listing) play a significant role in ESG disclosure. Moreover, low corruption perception reflects higher ESG disclosure among the targeted firms. Additionally, firm characteristics; such as liquidity position shows a better reporting of ESG during the study period. When accounting for the ESG disclosure individually, the findings confirm the productive role of board size, current ratio, and low corruption towards environmental exposure. Lastly, the results demonstrate that board size and ESG disclosure promote better financial performance. These results offer valuable policy recommendations.

Impact of ComBat and a Multi-Model approach to deal with multi-scanner and missing MRI data in a small cohort study. Application to H3K27M mutation prediction in patients with DIPG.

Radiomics was proposed to identify tumor phenotypes non-invasively from quantitative imaging features. Calculating a large amount of information on images, allows the development of reliable classification models. In multi-modal imaging protocols, the question arises of adding an imaging modality to improve model performance. In addition, in the implementation of clinical protocols, some modalities are not acquired or are of insufficient quality and cannot be reliably taken into account. Furthermore, multi-scanner studies generate some variability in the acquisition and data. Some methodological solutions using ComBat and a multi-model approach were tested to take these two issues into account. It was applied to a cohort of 88 patients with Diffuse Intrinsic Pontine Glioma (DIPG). Sixteen models using radiomic features computed using 0, 1, 2, 3 or 4 MRI modalities were proposed. Based on Leave-One-Out Cross-Validation, F1 weighted scores ranged from 0.66 to 0.85. A model of majority voting using the prediction of all the models available for one given patient was finally applied, reducing drastically the number of unclassified patients.Clinical relevance- In case of patients with DIPG, the prediction of H3 mutation is of prime importance in case of inconclusive biopsy or in the absence of it. It could suggest orientations for new chemotherapy drugs associated with the radiation therapy.

A radiomics pipeline dedicated to Breast MRI: validation on a multi-scanner phantom study.

OBJECTIVE: Quantitative analysis in MRI is challenging due to variabilities in intensity distributions across patients, acquisitions and scanners and suffers from bias field inhomogeneity. Radiomic studies are impacted by these effects that affect radiomic feature values. This paper describes a dedicated pipeline to increase reproducibility in breast MRI radiomic studies. MATERIALS AND METHODS: T1, T2, and T1-DCE MR images of two breast phantoms were acquired using two scanners and three dual breast coils. Images were retrospectively corrected for bias field inhomogeneity and further normalised using Z score or histogram matching. Extracted radiomic features were harmonised between coils by the ComBat method. The whole pipeline was assessed qualitatively and quantitatively using statistical comparisons on two series of radiomic feature values computed in the gel mimicking the normal breast tissue or in dense lesions. RESULTS: Intra and inter-acquisition variabilities were strongly reduced by the standardisation pipeline. Harmonisation by ComBat lowered the percentage of radiomic features significantly different between the three coils from 87% after bias field correction and MR normalisation to 3% in the gel, while preserving or improving performance of lesion classification in the phantoms. DISCUSSION: A dedicated standardisation pipeline was developed to reduce variabilities in breast MRI, which paves the way for robust multi-scanner radiomic studies but needs to be assessed on patient data.

Immune mediated necrotizing myopathy: A rare complication of statin therapy.

Immune mediated necrotizing myopathy (IMNM) is part of the inflammatory myopathies group of diseases and presents with muscle weakness, myalgias and elevated serum creatine phosphokinase (CPK). Statin-induced IMNM is a rare complication. We present a patient with IMNM secondary to simvastatin use. The patient presented with proximal myopathy, dysphagia, and elevated creatinine kinase levels, and was subsequently found to have anti-3- hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies with a necrotizing process on muscle biopsy. This patient's case was further complicated by sequelae of multiple disease processes, ultimately leading to deterioration of his health.

Asymmetric effects of energy efficiency and renewable energy on carbon emissions of BRICS economies: evidence from nonlinear panel autoregressive distributed lag model.

Embracing energy efficiency (EE) and renewable energy (RE) is essential for improving environmental quality. This research investigates the asymmetric impacts of EE, RE, and other factors on CO2 emissions in BRICS (i.e., Brazil, Russia, India, China, and South Africa) countries from 1990 to 2014. In contrast to previous studies, the present study considers EE as a major cause of CO2 emissions in BRICS countries. By using the new hidden panel cointegration and nonlinear panel autoregressive distributive lag model, this study is the first of its kind that unfolds the asymmetric links among EE, RE, and CO2 emissions. Findings clearly explain that the impact of the selected variables on CO2 emissions is asymmetric, and both EE and RE help to lower CO2 emissions in BRICS countries. In the long run, positive shocks in EE and RE can significantly mitigate CO2 emissions in BRICS economies. In particular, a 1% fluctuation in the positive sum of EE reduces CO2 emissions by 0.783% in the long run. On the other hand, a 1% fluctuation in the positive component of RE reduces CO2 emissions by 0.733%. Moreover, individual country estimates suggest the heterogeneous effects among BRICS countries. Based on the empirical findings, policymakers should consider the asymmetric behavior of the EE, RE, and economic growth while formulating, energy, environment, and growth policies of BRICS countries. Graphical abstract.

Anti-IgE therapy for asthma: an audit at atertiary care centre in Saudi Arabia.

BACKGROUND: Although anti-IgE therapy has been shown to offer numerous benefits, we suspect it is underutilized locally. To date, there are no studies on any aspect of its use in the Arab region. There is also no information on whether physicians follow current guidelines nor on patient response to this form of therapy. OBJECTIVE: Assess the use of omalizumab for patients with difficult asthma at a tertiary care center. DESIGN: Retrospective, descriptive. SETTING: Tertiary care hospital. PATIENTS AND METHODS: Information was collected from medical records and interviews of all patients who received a minimum of 6 months of omalizumab, including data on practices of the prescribing physician (pulmonary versus allergy), indications, dose, subjective response, number of emergency room visits and hospitalizations, changes in asthma medications, adverse effects, and the setting for delivery of therapy. MAIN OUTCOME MEASURES: Extent to which current guidelines for prescribing omalizumab were followed. Patient subjective and objective responses to treatment as reflected by changes in the use of medications and lung function before and after therapy. SAMPLE SIZE: 50 patients. RESULTS: Of the 50 consecutive patients, 35 were female and the mean (SD) age was 46.3 (9.2) years. Only 28 patients (56 %) met all the criteria for the prescription of omalizumab as per current guidelines; 18 (64%) by pulmonary and 10 (36%) by allergy physicians (P less than .05). Pulmonary physicians performed more tests for conditions complicating or simulating asthma (P less than .05). The mean (SD) duration of treatment by omalizumab of 35 (22) months was longer in patients managed by allergists (42 [24] months) than pulmonary physicians (30 [21] months) (P greater than .05). Both physician groups prescribed a lower initial dose than recommended (P less than .05 recommended vs. prescribed). Patients reported a significant improvement in symptoms, reduction in the use of broncho-dilators and oral steroids and in the use of healthcare services (from 16.28 [7.9] to 2.08 [1.78], P less than .0001) mean values from sum of hospitalizations/year, ER visits/year, exacerbations/year, but not in other medications or pulmonary function tests (P greater than .05). CONCLUSION: Despite several benefits, notably a reduction in utilization of health services and asthma medication, anti-IgE therapy is probably underutilized locally. Pulmonary physicians are more likely to follow the guidelines than allergy physicians. This study suggests that there is room for improvement in the prescription practices, particularly in dosing and the setting for delivery. Further multicenter prospective studies are required to identify gaps in the current practices and improve asthma management. LIMITATIONS: Too few patients met inclusion criteria, lack of control group, and use of a subjective assessment for patient symptoms as opposed to validated questionnaires. CONFLICT OF INTEREST: None.

RNA-mediated gene regulation is less evolvable than transcriptional regulation.

Much of gene regulation is carried out by proteins that bind DNA or RNA molecules at specific sequences. One class of such proteins is transcription factors, which bind short DNA sequences to regulate transcription. Another class is RNA binding proteins, which bind short RNA sequences to regulate RNA maturation, transport, and stability. Here, we study the robustness and evolvability of these regulatory mechanisms. To this end, we use experimental binding data from 172 human and fruit fly transcription factors and RNA binding proteins as well as human polymorphism data to study the evolution of binding sites in vivo. We find little difference between the robustness of regulatory protein-RNA interactions and transcription factor-DNA interactions to DNA mutations. In contrast, we find that RNA-mediated regulation is less evolvable than transcriptional regulation, because mutations are less likely to create interactions of an RNA molecule with a new RNA binding protein than they are to create interactions of a gene regulatory region with a new transcription factor. Our observations are consistent with the high level of conservation observed for interactions between RNA binding proteins and their target molecules as well as the evolutionary plasticity of regulatory regions bound by transcription factors. They may help explain why transcriptional regulation is implicated in many more evolutionary adaptations and innovations than RNA-mediated gene regulation.

Co-Circulation of 72bp Duplication Group A and 60bp Duplication Group B Respiratory Syncytial Virus (RSV) Strains in Riyadh, Saudi Arabia during 2014.

Respiratory syncytial virus (RSV) is an important viral pathogen of acute respiratory tract infection (ARI). Limited data are available on molecular epidemiology of RSV from Saudi Arabia. A total of 130 nasopharyngeal aspirates were collected from children less than 5 years of age with ARI symptoms attending the Emergency Department at King Khalid University Hospital and King Fahad Medical City, Riyadh, Saudi Arabia between October and December, 2014. RSV was identified in the 26% of the hospitalized children by reverse transcriptase PCR. Group A RSV (77%) predominated during the study as compared to group B RSV (23%). The phylogenetic analysis of 28 study strains clustered group A RSV in NA1 and ON1 genotypes and group B viruses in BA (BA9) genotype. Interestingly, 26% of the positive samples clustered in genotypes with duplication in the G protein gene (ON1 for group A and BA for group B). Both the genotypes showed enhanced O-linked glycosylation in the duplicated region, with 10 and 2 additional sites in ON1 and BA respectively. Selection pressure analysis revealed purifying selection in both the ON1 and BA genotypes. One codon each in the ON1 (position 274) and BA genotypes (position 219) were positively selected and had high entropy values indicating variations at these amino acid positions. This is the first report describing the presence of ON1 genotype and the first report on co-circulation of two different genotypes of RSV with duplication in the G protein gene from Saudi Arabia. The clinical implications of the simultaneous occurrence of genotypes with duplication in G protein gene in a given population especially in the concurrent infections should be investigated in future. Further, the ongoing surveillance of RSV in this region will reveal the evolutionary trajectory of these two genotypes with duplication in G protein gene from largest country in the Middle East.

Mechanistic insights into the manganese-dependent phosphodiesterase activity of yeast Dbr1 with bis-p-nitrophenylphosphate and branched RNA substrates.

Saccharomyces cerevisiae Dbr1 is a manganese-dependent RNA debranching enzyme that cleaves the 2'-5' phosphodiester bond of the lariat introns formed during pre-mRNA splicing. Dbr1 is a member of the binuclear metallophosphoesterase enzyme superfamily. We showed previously via alanine scanning that RNA debranching in vivo and in vitro depends on conserved active site residues His13, Asp40, Asn85, His86, His179, His231, and His233. Here, by extending the alanine scan, we added Cys11 to the ensemble of essential active site components. We report that Dbr1 has a vigorous manganese-dependent phosphodiesterase activity with the non-RNA substrate bis-p-nitrophenylphosphate. Whereas RNA debranching requires His86, bis-p-nitrophenylphosphatase activity does not. We interpret these and other structure-activity relations reported here in light of the crystal structures of Entamoeba Dbr1 and other homologous binuclear metallophosphodiesterases. Our results suggest that (i) Dbr1 adheres to the two-metal mechanism of the enzyme superfamily, but is distinguished by its reliance on a Cys11-Xaa-His13 motif to engage one of the catalytic metals instead of the Asp-Xaa-His element typical of other clades within the superfamily; (ii) His86 is a general acid catalyst that protonates the O2' leaving group of the RNA 2'-5' phosphodiester; and (iii) the favorable pKa of p-nitrophenol elides the strict need for a general acid during hydrolysis of bis-p-nitrophenylphosphate. The Dbr1 bis-p-nitrophenylphosphatase activity is well suited for high-throughput screening for inhibitors of debranching.

Adenosine triphosphate-binding cassette member A3 gene mutation in children from one family from Saudi Arabia.

Mutation in ABCA3, which is adenosine triphosphate-binding cassette member A3, a member of protein transporter family for phospholipids into the lamellar bodies during synthesis of surfactant, can cause lung disease related to surfactant dysfunction with autosomal recessive pattern. We reported three cases from same family with ABCA3 mutation, their gene, clinical course, and outcomes mentioning that one patient had successful lung transplantation, one started the process of the lung transplantation while the third one died during infancy. We concluded that the patients with ABCA3 gene mutations are increasing in numbers may be due to the availability of the genetic testing and high index of suspicion among physicians. Lung transplantation is the definitive treatment, but availability is limited in our region.

Genonets server-a web server for the construction, analysis and visualization of genotype networks.

A genotype network is a graph in which vertices represent genotypes that have the same phenotype. Edges connect vertices if their corresponding genotypes differ in a single small mutation. Genotype networks are used to study the organization of genotype spaces. They have shed light on the relationship between robustness and evolvability in biological systems as different as RNA macromolecules and transcriptional regulatory circuits. Despite the importance of genotype networks, no tool exists for their automatic construction, analysis and visualization. Here we fill this gap by presenting the Genonets Server, a tool that provides the following features: (i) the construction of genotype networks for categorical and univariate phenotypes from DNA, RNA, amino acid or binary sequences; (ii) analyses of genotype network topology and how it relates to robustness and evolvability, as well as analyses of genotype network topography and how it relates to the navigability of a genotype network via mutation and natural selection; (iii) multiple interactive visualizations that facilitate exploratory research and education. The Genonets Server is freely available at http://ieu-genonets.uzh.ch.

Effects of Reproductive Health Education on Knowledge and Attitudes Among Female Adolescents in Saudi Arabia.

BACKGROUND: For many girls, the onset of puberty that occurs during adolescence marks a time of heightened vulnerability to early pregnancy, with its attendant complications and heightened risk of maternal mortality. National and international forums have recognized the need to address these problems through reproductive health education. PURPOSE: This article assesses the reproductive-health-related knowledge and attitudes of female adolescents aged between 14 and 19 years. In addition, the authors assess the effectiveness of a reproductive health education program in improving the related knowledge of female adolescents. METHODS: The study was conducted on female students in three secondary schools and in the preparatory year at Qassim University (N = 309). A 59-item structured questionnaire was used to test the knowledge and attitudes of all participants regarding reproductive health before and after the intervention program. Data collection was carried out between September and November 2012. RESULTS: A significant increase for the total sample in knowledge regarding puberty and menstruation was observed (p < .001) postintervention. Differences in overall knowledge regarding pregnancy and antenatal care were statistically significant. Knowledge regarding contraceptive intrauterine devices improved from 27.2% preintervention to 67.6% postintervention. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study clearly showed that the reproductive health education program improves knowledge among adolescent girls regarding reproductive health.

The short-sighted perspective of long-term eye health-care.

Eye health-care in Australia encompasses patients with chronic disorders being referred to ophthalmologists for detailed assessment and subsequent management. An increasing case load and relative decrease in ophthalmologists predicted over the next few years portend of an upcoming bottleneck in care delivery. To improve the efficiency and effectiveness of patient care within a rapidly changing health system, we propose that minor adjustments to existing services could improve the proficiency of resources. Such changes will require service providers to rethink their positions and roles and actively collaborate with each other for improved patient outcomes.