Health Care Resource Use and Total Mortality After Hospital Admission for Severe COVID-19 Infections During the Initial Pandemic Wave in France: Descriptive Study.

BACKGROUND: Little is known about post-hospital health care resource use (HRU) of patients admitted for severe COVID-19, specifically for the care of patients with postacute COVID-19 syndrome (PACS). OBJECTIVE: A list of HRU domains and items potentially related to PACS was defined, and potential PACS-related HRU (PPRH) was compared between the pre- and post-COVID-19 periods, to identify new outpatient care likely related to PACS. METHODS: A retrospective cohort study was conducted with the French National Health System claims data (SNDS). All patients hospitalized for COVID-19 between February 1, 2020, and June 30, 2020 were described and investigated for 6 months, using discharge date as index date. Patients who died during index stay or within 30 days after discharge were excluded. PPRH was assessed over the 5 months from day 31 after index date to end of follow-up, that is, for the post-COVID-19 period. For each patient, a pre-COVID-19 period was defined that covered the same calendar time in 2019, and pre-COVID-19 PPRH was assessed. Post- or pre- ratios (PP ratios) of the percentage of users were computed with their 95% CIs, and PP ratios>1.2 were considered as "major HRU change." RESULTS: The final study population included 68,822 patients (median age 64.8 years, 47% women, median follow-up duration 179.3 days). Altogether, 23% of the patients admitted due to severe COVID-19 died during the hospital stay or within the 6 months following discharge. A total of 8 HRU domains were selected to study PPRH: medical visits, technical procedures, dispensed medications, biological analyses, oxygen therapy, rehabilitation, rehospitalizations, and nurse visits. PPRs showed novel outpatient care in all domains and in most items, without specificity, with the highest ratios observed for the care of thoracic conditions. CONCLUSIONS: Patients hospitalized for severe COVID-19 during the initial pandemic wave had high morbi-mortality. The analysis of HRU domains and items most likely to be related to PACS showed that new care was commonly initiated after discharge but with no specificity, potentially suggesting that any impact of PACS was part of the overall high HRU of this population after hospital discharge. These purely descriptive results need to be completed with methods for controlling for confusion bias through subgroup analyses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05073328; https://clinicaltrials.gov/ct2/show/NCT05073328.

Antecedent and persistent symptoms in COVID-19 and other respiratory illnesses: Insights from prospectively collected data in the BRACE trial.

BACKGROUND: Some individuals have a persistence of symptoms following both COVID-19 (post-acute COVID-19 syndrome; PACS) and other viral infections. This study used prospectively collected data from an international trial to compare symptoms following COVID-19 and non-COVID-19 respiratory illness, to identify factors associated with the risk of PACS, and to explore symptom patterns before and after COVID-19 and non-COVID-19 respiratory illnesses. METHODS: Data from a multicentre randomised controlled trial (BRACE trial) involving healthcare workers across four countries were analysed. Symptom data were prospectively collected over 12 months, allowing detailed characterisation of symptom patterns. Participants with COVID-19 and non-COVID-19 respiratory illness episodes were compared, focussing on symptom severity, duration (including PACS using NICE and WHO definitions), and pre-existing symptoms. FINDINGS: Compared to those with a non-COVID-19 illness, participants with COVID-19 had significantly more severe illness (OR 7·4, 95%CI 5·6-9·7). Symptom duration meeting PACS definitions occurred in a higher proportion of COVID-19 cases than non-COVID-19 respiratory controls using both the NICE definition (2·5% vs 0·5%, OR 6·6, 95%CI 2·4-18·3) and the WHO definition (8·8% vs 3·7%, OR 2·5, 95%CI 1·4-4·3). When considering only participants with COVID-19, age 40-59 years (aOR 2·8, 95%CI 1·3-6·2), chronic respiratory disease (aOR 5·5, 95%CI 1·3-23·1), and pre-existing symptoms (aOR 3·0, 95%CI 1·4-6·3) were associated with an increased risk of developing PACS. Symptoms associated with PACS were also reported by participants in the months preceding their COVID-19 or non-COVID-19 respiratory illnesses (32% fatigue and muscle ache, 11% intermittent cough and shortness of breath). INTERPRETATION: Healthcare workers with COVID-19 were more likely to have severe and longer-lasting symptoms than those with a non-COVID-19 respiratory illness, with a higher proportion meeting the WHO or NICE definitions of PACS. Age, chronic respiratory disease, and pre-existing symptoms increased the risk of developing PACS following COVID-19.

Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution.

BACKGROUND: High priority efforts are underway to support the development of novel mucosal COVID-19 vaccines, such as the US Government's Project NextGen and the Center for Epidemic Preparedness Innovations' goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration. METHODS: Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022. RESULTS: High and moderate oral fluid anti-spike (S) secretory IgA (SIgA) post infection was associated with significantly faster viral clearance and symptom resolution across age groups with effect sizes equivalent to having COVID-19 vaccine immunity at the time of infection. Those with high and moderate anti-S SIgA cleared the virus 14 days (95% CI: 10-18) and recovered 9-10 days (95% CI: 6-14) earlier. Delayed and higher anti-S IgG was associated with significantly longer time to clearance and recovery. Experiencing symptoms longer than four weeks was associated with lower anti-RBD SIgA 15-30 days after infection onset (p<0.001). CONCLUSION: Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new mucosal vaccines.

Novel Clinical, Immunological, and Metabolic Features Associated with Persistent Post-Acute COVID-19 Syndrome.

The coronavirus disease 2019 (COVID-19) survivors are frequently observed to present persistent symptoms constituting what has been called "post-acute COVID-19 syndrome" (PACS) or "long COVID-19". Some clinical risk factors have been identified to be associated with PACS development; however, specific mechanisms responsible for PACS pathology remain unknown. This study investigates clinical, immunological, and metabolomic risk factors associated with post-acute COVID-19 syndrome (PACS) in 51 patients, assessed 7-19 months after acute infection. Among the participants, 62.7% were male and 37.2% were female, with an average age of 47.8 years. At the follow-up, 37.2% met the criteria for PACS, revealing significant differences in immunological and metabolomic profiles at the time of acute infection. Patients with PACS were characterized by elevated levels of mature low-density granulocytes (LDGs), interleukin-8 (IL-8), pyruvate, pseudouridine, and cystine. Baseline multivariate analysis showed increased pyruvate and decreased alpha tocopherol levels. At follow-up, there was a decrease in absolute B lymphocytes and an increase in non-classical monocytes and 3-hydroxyisovaleric acid levels. These findings suggest that specific immunological and metabolomic markers during acute infection can help identify patients at higher risk of developing persistent PACS.

Renal denervation improves mitochondrial oxidative stress and cardiac hypertrophy through inactivating SP1/BACH1-PACS2 signaling.

BACKGROUND: Renal denervation (RDN) has been proved to relieve cardiac hypertrophy; however, its detailed mechanisms remain obscure. This study investigated the detailed protective mechanisms of RDN against cardiac hypertrophy during hypertensive heart failure (HF). METHODS: Male 5-month-old spontaneously hypertension (SHR) rats were used in a HF rat model, and male Wistar-Kyoto (WKY) rats of the same age were used as the baseline control. Myocardial hypertrophy and fibrosis were evaluated by hematoxylin-eosin (HE) staining and Masson staining. The expression of target molecule was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, immunohistochemical and immunofluorescence, respectively. Cardiomyocyte hypertrophy was induced by norepinephrine (NE) in H9c2 cells in vitro and evaluated by brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), ß-myosin heavy chain (ß-MHC), and α-myosin heavy chain (α-MHC) levels. Oxidative stress was determined by malondialdehyde (MDA) level, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) enzyme activities. Mitochondrial function was measured by mitochondrial membrane potential, adenosine triphosphate (ATP) production, mitochondrial DNA (mtDNA) number, and mitochondrial complex I-IV activities. Molecular mechanism was assessed by dual luciferase reporter and chromatin immunoprecipitation (ChIP) assays. RESULTS: RDN decreased sympathetic nerve activity, attenuated myocardial hypertrophy and fibrosis, and improved cardiac function in the rat model of HF. In addition, RDN ameliorated mitochondrial oxidative stress in myocardial tissues as evidenced by reducing MDA and mitochondrial reactive oxygen species (ROS) levels, and enhancing SOD and GSH-Px activities. Moreover, phosphofurin acid cluster sorting protein 2 (PACS-2) and broad-complex, tramtrak and bric à brac (BTB) domain and cap'n'collar (CNC) homolog 1 (BACH1) were down-regulated by RDN. In NE-stimulated H9c2 cells, PACS-2 and BACH1 levels were markedly elevated, and knockdown of them could suppress NE-induced oxidative stress, cardiomyocyte hypertrophy, fibrosis, as well as mitochondrial dysfunction. Transforming growth factor beta1(TGFß1)/SMADs signaling pathway was inactivated by RDN in the HF rats, which sequentially inhibited specificity protein 1 (SP1)-mediated transcription of PACS2 and BACH1. CONCLUSION: Collectively, these data demonstrated that RDN improved cardiac hypertrophy and sympathetic nerve activity of HF rats via repressing BACH1 and PACS-2-mediated mitochondrial oxidative stress by inactivating TGF-ß1/SMADs/SP1 pathway, which shed lights on the cardioprotective mechanism of RDN in HF.

Emerging Applications of Picture Archiving and Communication Systems and Their Impact on Research and Education: A Literature Review.

In recent times, technological advancements have remarkably improved picture archiving and communication system (PACS) capabilities beyond their conventional use in radiology departments. Researchers and instructors have started employing PACS functionalities to improve medical research processes, promote interdisciplinary collaborations, and facilitate learning. To illustrate this point further, the PACS enables researchers to handle and analyze huge amounts of imaging data with superior precision and speed, supporting innovative studies in areas like disease progression, treatment outcomes, and imaging modalities. Moreover, a PACS integrated with artificial intelligence (AI) algorithms leads to significant improvements in image processing, diagnostic accuracy, and personalized treatment, thus marking a new approach to medical imaging. The PACS supported by AI is mostly transformative since they allow for improved early disease detection capabilities as well as automated image processing and decision assistance, which increase diagnostic accuracy and clinical outcomes. Such systems can rapidly process large quantities of visual data with an accuracy rate surpassing earlier endeavors. In medical research, however, combining PACS with AI allows challenging imaging datasets to be examined, thereby making findings that were not previously possible. The capacity to combine imaging outcomes with clinical information is valuable for medical students and professionals in the field of education. They can access extensive medical image collections and case studies using PACS. This link is critical for teaching and learning as it allows students to interact with concrete events and improve their diagnostic accuracy in a controlled environment. This review discusses how the PACS affects educational courses and clinical outcomes based on the available literature. Our aim was not only to outline recent research or developments but also to present a comprehensive overview regarding the growing role played by PACS in the modern healthcare system and academics. Similarly, we look at the challenges and opportunities associated with the wide adoption of PACS, highlighting possible future areas of study or teaching methodologies. Issues such as data security, interoperability, and the need for defined protocols are included to give an exhaustive understanding of what PACS can and cannot do. Through this study, we stress PACS's revolutionary potential in advancing research methodology and educational practices, eventually contributing to enhanced patient care and knowledge dissemination in healthcare areas. The continual growth of PACS technology and its applications is expected to reshape the landscape of medical research and education, making it a vital component in the quest for medical excellence. By knowing the present trends and future potential, stakeholders in healthcare and education may better employ PACS to reach their objectives and boost overall results.

Phosphofurin Acidic Cluster Sorting Protein 1 Syndrome: Insights Gained on the Multisystem Involvement Reviewing Encoded Protein Interactions?

Mutations in PACS1 cause moderate-to-severe intellectual disability. Very few cases of PACS1 neurodevelopment disorder have been described in the literature that were identified using whole exome sequencing (WES). We report a case of de novo PACS1 mutation identified through WES after an initial workup for mucopolysaccharidosis. Through this case, we wish to emphasize that most important clinical clue in the facial gestalt is a downturned angle of mouth, thin lips, and wide mouth, giving characteristic wavy appearance of face that can distinguish these cases and can prevent unnecessary workup for the patients.

Post-SARS-CoV-2 infection and post-vaccine-related neurological complications share clinical features and the same positivity to anti-ACE2 antibodies.

Introduction: A potential overlap in symptoms between post-acute COVID-19 syndrome and post-COVID-19 vaccination syndrome has been noted. We report a paired description of patients presenting with similar manifestations involving the central (CNS) or peripheral nervous system (PNS) following SARS-CoV-2 infection or vaccination, suggesting that both may have triggered similar immune-mediated neurological disorders in the presence of anti-idiotype antibodies directed against the ACE2 protein. Patients and methods: Four patients exhibited overlapping neurological manifestations following SARS-CoV-2 infection or vaccination: radiculitis, Guillain-Barré syndrome, and MRI-negative myelitis, respectively, sharing positivity for anti-ACE2 antibodies. Autoantibodies against AQP-4, MOG, GlyR, GAD, and amphiphysin, onconeural antibodies for CNS syndromes, and anti-ganglioside antibodies for PNS syndromes tested negative in all patients. Discussion: Anti-idiotype antibodies against ACE2 have been detected in patients who recovered from COVID-19 infection, and it has been hypothesized that such antibodies may mediate adverse events following SARS-CoV-2 infection or vaccination, resulting in the activation of the immune system against cells expressing ACE2, such as neurons. Our data reveal clinically overlapping syndromes triggered by SARS-CoV-2 infection or vaccination, sharing positivity for anti-ACE2 antibodies. Their presence, in the absence of other classic autoimmune markers of CNS or PNS involvement, suggests that they might play an active role in the context of an aberrant immune response. Conclusion: Anti-idiotype antibodies directed against ACE2 may be triggered by both SARS-CoV-2 infection and vaccination, possibly contributing to neurological autoimmune manifestations. Their pathogenic role, however, remains to be demonstrated in large-scale, more structured studies.

Post-acute CoVid-19 syndrome (PACS) linked cardiovascular symptoms.

Officials have marked the end of the CoVid-19 pandemic, yet we continue to learn more about the SARS-CoV2 virus itself and its lasting multidimensional effects after acute infection. Long COVID, or the post-acute CoViD-19 syndrome (PACS), manifests as a wide range of prolonged physical, mental, and emotional symptoms over at least 1 to 12 months after SARS-CoV2 infection. Here, we describe certain pervasive clinical consequences of PACS on the cardiovascular system, and insight on the potentially improved prognoses in heart failure patients.

Using PACS for teaching radiology to undergraduate medical students.

BACKGROUND: Traditional radiology education for medical students predominantly uses textbooks, PowerPoint files, and hard-copy radiographic images, which often lack student interaction. PACS (Picture Archiving and Communication System) is a crucial tool for radiologists in viewing and reporting images, but its use in medical student training remains limited. OBJECTIVE: This study investigates the effectiveness of using PACS (Picture Archiving and Communication System) for teaching radiology to undergraduate medical students compared to traditional methods. METHODS: Fifty-three medical students were divided into a control group (25 students) receiving traditional slide-based training and an intervention group (28 students) using PACS software to view complete patient images. Pre- and post-course tests and satisfaction surveys were conducted for both groups, along with self-evaluation by the intervention group. The validity and reliability of the assessment tools were confirmed through expert review and pilot testing. RESULTS: No significant difference was found between the control and intervention groups regarding, gender, age, and GPA. Final multiple-choice test scores were similar (intervention: 10.89 ± 2.9; control: 10.76 ± 3.5; p = 0.883). However, the intervention group demonstrated significantly higher improvement in the short answer test for image interpretation (intervention: 8.8 ± 2.28; control: 5.35 ± 2.39; p = 0.001). Satisfaction with the learning method did not significantly differ between groups (intervention: 36.54 ± 5.87; control: 39.44 ± 7.76; p = 0.129). The intervention group reported high familiarity with PACS capabilities (75%), CT principles (71.4%), interpretation (64.3%), appropriate window selection (75%), and anatomical relationships (85.7%). CONCLUSION: PACS-based training enhances medical students' diagnostic and analytical skills in radiology. Further research with larger sample sizes and robust assessment methods is recommended to confirm and expand upon theses results.

A Global Industry Survey on Post-Approval Change Management and Use of Reliance.

Post-approval changes (PACs) to the control and manufacturing processes of medicines and vaccines are routinely undertaken and critical to enable both innovation and secure sustained supply. In a world of global supply chains, the existence of divergent national PAC requirements (with additional countries introducing new requirements with potential differences) and other factors including document preparation and response timelines, can lead to long delays in approval (of up to 3-5 years) increasing the risk of disruption and shortages.We undertook an Industry survey in 2023 to assess implementation of ICH Q12, PAC procedures (change categorisation and review timelines) and use of reliance mechanisms across different countries (9 selected ICH Members and 19 Observers). Although this survey revealed limited implementation of Q12 in ICH Member countries, when comparing the data collected with those of a previous survey performed in 2020, we observed a broader adoption of risk-based approaches to variation categorisation (in all countries). This, however, was not reflected in improved timelines for approval.With regards to ICH Q12 adoption, the uptake of Post-Approval Change Management Protocols (PACMPs) was unchanged (with only one country reporting in-use) and implementation gaps were evident for Established Conditions (EC) and the Product Life Cycle Management document (PLCM). The survey found greater awareness of ICH Q12 and its tools compared to 2020, potentially illustrating the positive impact of training efforts. This illustrates the challenges being faced to broaden its implementation and use globally.In the same Industry survey, we also assessed PAC processes across different international countries. Long unpredictable timelines were the major concern across the countries surveyed together with limited capacity of the regulators. Four different CMC changes were selected and categorized by the respondents according to current knowledge of national classifications and timelines in the selected countries and compared with a reference classification and timeline from the European Medicines Agency and the World Health Organisation. This highlighted the lack of harmonisation of many countries with EU/WHO requirements, especially within the ICH Observer group.Last, this survey showed that some use of unilateral forms of reliance to Reference Authorities for PACs is starting. This is a mechanism all countries can employ, regardless of convergence of requirements and expertise, to enhance capacity building and reduce duplication of reviews, streamline variations approval, whilst accelerating patient access to innovation and securing supply.

Aliphatic and polycyclic aromatic compounds in coal and coal-based solid wastes: Relationship with coal-forming paleoenvironment and implications for environmental pollution.

In this study, coal and coal-based solid wastes (coal gangue, fly ash, bottom ash, desulfurized gypsum and tar residue) were collected from major coal mines, power plants and coking plants in Lianghuai mining area (LH), China, and were analyzed for 76 polycyclic aromatic compounds (PACs), 27 n-alkanes and 2 isoprenoids (phytane and pristane). The total n-alkanes concentrations and ∑76 PACs in raw coals (640 ± 600 and 180 ± 87 µg/g) were higher than those in coal-based solid wastes (47 ± 40 and 24 ± 25 µg/g), but were lower than those in tar residue (3700 and 63,000 µg/g). It was discovered that the depositional paleoenvironment in LH was mostly a lacustrine and freshwater environment with oxidizing conditions and mixed organic matter input, but the Huainan coalfield had stronger oxidizing conditions and more input of terrestrial organic matter than that of the Huaibei coalfield. Alkylated PACs made up 56 ± 12 % of the ∑76PACs in raw coals, whereas solid wastes mainly consisted of 16 EPA PAHs (66 ± 16 %). Coal combustion and gangue weathering altered the structural properties of n-alkanes and PACs, resulting in a significant loss of n-alkanes and PACs, a higher proportion of parent PACs, and an increased abundance of short n-alkanes in the products (No apparent change of n-alkanes composition was observed through gangue weathering). The toxicity of PACs in raw coal and its solid wastes in LH from high to low was tar residue, raw coal, coal gangue, and coal-fired products. This investigation further confirmed that traditional diagnostic ratios may distort source information, and that they should not be used to assess PACs sources from raw coal particles or coal gangues, but rather to identify combustion sources near the point source. In addition, Retene/(Retene + Chrysene) < 0.03 may indicate direct contamination of raw coal particles.

Transforming experimental radiology: Design and implementation of an innovative ePACS image storage system for AI imaging research environments.

INTRODUCTION AND PURPOSE: We present the needs, design, development, implementation, and accessibility of a crafted experimental PACS (ePACS) system to securely store images, ensuring efficiency and ease of use for AI processing, specifically tailored for research scenarios, including phantoms, animal and human studies and quality assurance (QA) exams. The ePACS system plays a crucial role in any medical imaging departments that handle non-care profile studies, such as protocol adjustments and dummy runs. By effectively segregating non-care profile studies from the healthcare assistance, the ePACS usefully prevents errors both in clinical practice and storage security. METHODS AND RESULTS: The developed ePACS system considers the best practices for management, maintenance, access, long-term storage and backups, regulatory audits, and economic aspects. Moreover, key aspects of the ePACS system include the design of data flows with a focus on incorporating data security and privacy, access control and levels based on user profiles, internal data management policies, standardized architecture, infrastructure and application monitorization and traceability, and periodic backup policies. A new tool called DicomStudiesQA has been developed to standardize the analysis of DICOM studies. The tool automatically identifies, extracts, and renames series using a consistent nomenclature. It also detects corrupted images and merges separated dynamic series that were initially split, allowing for streamlined post-processing. DISCUSSION AND CONCLUSIONS: The developed ePACS system encompasses a successful implementation, both in hospital and research environments, showcasing its transformative nature and the challenging yet crucial transfer of knowledge to industry. This underscores the practicality and real-world applicability of our innovative approach, highlighting the significant impact it has on the field of experimental radiology.

Cybersecurity in radiology: Cautionary Tales, Proactive Prevention, and What to do When You Get Hacked.

To improve awareness and understanding of cybersecurity threats to radiology practice and better equip healthcare practices to manage cybersecurity risks associated with medical imaging, this article reviews topics related to cybersecurity in healthcare, with emphasis on common vulnerabilities in radiology operations. This review is intended to assist radiologists and radiology administrators who are not information technology specialists to attain an updated overview of relevant cybersecurity concepts and concerns relevant to safe and effective practice of radiology and provides a succinct reference for individuals interested in learning about imaging-related vulnerabilities in healthcare settings. As cybersecurity incidents have become increasingly common in healthcare, we first review common cybersecurity threats in healthcare and provide updates on incidence of healthcare data breaches, with emphasis on the impact to radiology. Next, we discuss practical considerations on how to respond to a healthcare data breach, including notification and disclosure requirements, and elaborate on a variety of technical, organizational, and individual actions that can be adopted to minimize cybersecurity risks applicable to radiology professionals and administrators. While emphasis is placed on specific vulnerabilities within radiology workflow, many of the preventive or mitigating strategies are also relevant to cybersecurity within the larger digital healthcare arena. We anticipate that readers, upon completing this review article, will gain a better appreciation of cybersecurity issues relevant to radiology practice and be better equipped to mitigate cybersecurity risks associated with medical imaging.

High throughput spatial immune mapping reveals an innate immune scar in post-COVID-19 brains.

The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine learning methods on brains from initial COVID-19 survivors to identify the biological correlate associated with previous SARS-CoV-2 challenge. Compared to healthy controls, individuals with post-COVID-19 revealed a high percentage of TMEM119+P2RY12+CD68+Iba1+HLA-DR+CD11c+SCAMP2+ microglia assembled in prototypical cellular nodules. In contrast to acute SARS-CoV-2 cases, the frequency of CD8+ parenchymal T cells was reduced, suggesting an immune shift toward innate immune activation that may contribute to neurological alterations in post-COVID-19 patients.

Evaluating solubility, stability, and inclusion complexation of oxyresveratrol with various ß-cyclodextrin derivatives using advanced computational techniques and experimental validation.

Oxyresveratrol (OXY), a natural stilbenoid in mulberry fruits, is known for its diverse pharmacological properties. However, its clinical use is hindered by low water solubility and limited bioavailability. In the present study, the inclusion complexes of OXY with ß-cyclodextrin (ßCD) and its three analogs, dimethyl-ß-cyclodextrin (DMßCD), hydroxypropyl-ß-cyclodextrin (HPßCD) and sulfobutylether-ß-cyclodextrin (SBEßCD), were investigated using in silico and in vitro studies. Molecular docking revealed two binding orientations of OXY, namely, 4',6'-dihydroxyphenyl (A-form) and 5,7-benzenediol ring (B-form). Molecular Dynamics simulations suggested the formation of inclusion complexes with ßCDs through two distinct orientations, with OXY/SBEßCD exhibiting maximum atom contacts and the lowest solvent-exposed area in the hydrophobic cavity. These results corresponded well with the highest binding affinity observed in OXY/SBEßCD when assessed using the MM/GBSA method. Beyond traditional simulation methods, Ligand-binding Parallel Cascade Selection Molecular Dynamics method was employed to investigate how the drug enters and accommodates within the hydrophobic cavity. The in silico results aligned with stability constants: SBEßCD (2060 M-1), HPßCD (1860 M-1), DMßCD (1700 M-1), and ßCD (1420 M-1). All complexes exhibited a 1:1 binding mode (AL type), with SBEßCD enhancing OXY solubility (25-fold). SEM micrographs, DSC thermograms, FT-IR and 1H NMR spectra confirm the inclusion complex formation, revealing novel surface morphologies, distinctive thermal behaviors, and new peaks. Notably, the inhibitory impact on the proliferation of breast cancer cell lines, MCF-7, exhibited by inclusion complexes particularly OXY/DMßCD, OXY/HPßCD, and OXY/SBEßCD were markedly superior compared to that of OXY alone.

Machine learning-based QSAR and LB-PaCS-MD guided design of SARS-CoV-2 main protease inhibitors.

The global outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 virus had led to profound respiratory health implications. This study focused on designing organoselenium-based inhibitors targeting the SARS-CoV-2 main protease (Mpro). The ligand-binding pathway sampling method based on parallel cascade selection molecular dynamics (LB-PaCS-MD) simulations was employed to elucidate plausible paths and conformations of ebselen, a synthetic organoselenium drug, within the Mpro catalytic site. Ebselen effectively engaged the active site, adopting proximity to H41 and interacting through the benzoisoselenazole ring in a π-π T-shaped arrangement, with an additional π-sulfur interaction with C145. In addition, the ligand-based drug design using the QSAR with GFA-MLR, RF, and ANN models were employed for biological activity prediction. The QSAR-ANN model showed robust statistical performance, with an r2training exceeding 0.98 and an RMSEtest of 0.21, indicating its suitability for predicting biological activities. Integration the ANN model with the LB-PaCS-MD insights enabled the rational design of novel compounds anchored in the ebselen core structure, identifying promising candidates with favorable predicted IC50 values. The designed compounds exhibited suitable drug-like characteristics and adopted an active conformation similar to ebselen, inhibiting Mpro function. These findings represent a synergistic approach merging ligand and structure-based drug design; with the potential to guide experimental synthesis and enzyme assay testing.

Rewinding the Clock: Preparing the Next Generation of Radiology Residents for Oral Boards.

The replacement of the ABR in-person oral examination with the DR certifying examination affected approximately 15,000 radiologists, spanning from 2013 to 2027. This decision was motivated by better aligning with the timing of other American Board of Medical Specialty (ABMS) members, more closely reflecting real-world practice of radiology and narrowing training geared towards the trainee's subspecialty preference. However, in retrospect, this change may have subtracted from the quality and value of diagnostic radiology training as a whole with the de-emphasis on competence in general radiology, communication skills, and cognitive reasoning. In this paper, the authors lay out a blueprint necessary in order to rewind the clock of how diagnostic radiology programs can prepare their trainees for the new DR oral examination. Such a change will require substantial redactions affecting all designations, including radiology faculty, education teams, departmental leadership, academic institutions, ACGME, and ABR. The authors believe that implementing these modifications will not only effectively equip radiology candidates for the new DR oral examination but will also augment the significance of radiologists as indispensable members of multidisciplinary teams. The authors also outline the challenges that could emerge from these changes and speculate on the anticipated role of AI in future oral board examinations.

Association between blood pressure levels and premature atrial contractions in patients with hypertension.

BACKGROUND: High blood pressure (BP) induces left atrial structural and functional remodeling that increases susceptibility to atrial arrhythmia. We hypothesized that lower systolic BP (SBP) levels are associated with a lower prevalence of premature atrial contractions (PACs) in patients with hypertension. METHODS: This analysis included 4,697 participants (mean age 62±13.1 years, 50% women, 25.6% blacks) with hypertension from the Third National Health and Nutrition Examination Survey who did not have a prior history of cardiovascular disease (CVD). Multivariable logistic regression was used to examine the cross-sectional association between SBP and prevalence of PACs ascertained from 12-lead resting electrocardiograms. Multivariable Cox proportional hazard analysis was used to examine the association between baseline PACs and CVD mortality. RESULTS: Approximately 1.6% (n=74) of participants had baseline PACs. Patients with SBP ≤140 mmHg had a lower prevalence of PACs than those with SBP ≥140 mmHg (1.1% vs. 1.9%, p-value=0.01). In a multivariable logistic regression model, each 10 mmHg decrease in SBP was associated with a 12% lower odds of PACs (OR (95%CI): 0.88 (0.77-0.99)). During 14 years of follow-up, 645 CVD deaths occurred. In a multivariable-adjusted Cox model, presence of PACs was associated with a 78% increased risk of CVD mortality (HR (95%CI): 1.78 (1.23-2.60)). CONCLUSIONS: In patients with hypertension, lower SBP levels are associated with a lower prevalence of PACs, and presence of PACs is associated with a higher risk of CVD mortality risk. These findings highlight the potential role of BP lowering in the management of cardiac arrhythmias.

Atrial Tachycardia Masquerading as Atrial Fibrillation Following Bi-Atrial MAZE Procedure.

A 34-year-old woman presented with palpitations and paroxysmal atrial fibrillation (AF). Workup revealed anterior mitral valve prolapse with severe mitral regurgitation. She was referred for surgical repair and underwent a mitral valve replacement, tricuspid valve repair, and bi-atrial cryoMAZE procedure with left atrial appendage ligation. Her postoperative course was complicated by inferior wall myocardial infarction. She subsequently presented with palpitations and underwent electrophysiology study and ablation. This case illustrates pitfalls associated with the surgical MAZE procedure and highlights the challenges in postoperative atrial arrhythmias diagnosis and management.