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Introduction: Chronic limb-threatening ischemia (CLTI) represents the most severe form of peripheral artery disease. While previous studies have focused on gender and racial disparities, there is lack of evidence regarding the impact of housing status. The aim of this analysis was to identify disparities in inpatient management and outcomes of CLTI based on housing status., Methods: In this retrospective, descriptive study, we analyzed patients admitted with CLTI who underwent revascularization, as identified by ICD-10 codes, between 2016-2021, using the National Inpatient Sample database. The patients were stratified by their housing status and a detailed, propensity-matched analysis was conducted to compare the demographics, comorbidities, mortality rates, types of intervention, resource utilization, and inpatient outcomes., Results: During the study, 2,667,294 patients were admitted with CLTI, and 17% (463,435) underwent revascularization. Among these, 0.4% (1,790) were unhoused. Males were overrepresented in the unhoused group (83.5% vs. 62.5%, p<0.001). Unhoused patients were more likely to receive endovascular revascularization (AOR 1.77, 0.45-0.90, p=0.003) but less likely to undergo open surgical intervention (AOR 0.64, 0.45-0.90, p=0.010). They were also more likely to undergo aortoiliac interventions, while housed patients underwent more distal interventions. The mean adjusted length of stay was four days longer and inflation-adjusted costs were $8,501 higher for unhoused patients (p<0.001). Unhoused patients were also more likely to leave against medical advice and be transferred to skilled nursing facilities., Conclusion: This study highlights significant disparities in CLTI management and outcomes between housed and unhoused patients, underscoring the need for targeted interventions to address these inequities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Delayed stent grafting for blunt thoracic aortic injuries (BTAI) is current standard of care. However, given the heterogeneity of pseudoaneurysm presentations, it is currently unclear which severe BTAIs require more urgent intervention. We hypothesize that a Traumatic Aortic Disruption Index (TADI) calculation based on sagittal computed tomography angiography (CTA) imaging measurements would correlate with urgency of stent grafting., Methods: All patients at a level-1 trauma center with BTAIs over a 12-year period were identified. A TADI score was then calculated using the length of pseudoaneurysm (L), maximum width of pseudoaneurysm (W), and normal adjacent aortic diameter (NA) (Figure1). Patient presentation, injury characteristics, timing of stent grafting, and outcomes were then evaluated., Results: Forty-two patients were diagnosed with BTAIs. Mean age was 37.6 years, with a median injury severity score (ISS) of 29. Overall mortality was 11.9%. TADI scores ranged from 3.6 to 158.6. Compared to patients with a TADI<28, patients with TADI>28 had similar median ISS scores (34 vs 29, p=0.16), and rates of both traumatic brain injury (33.3% vs 42.0%, p=0.53) and non-aortic hemorrhage control procedures (44.4% vs 33.3%, p=0.3). TADI>28 patients had a lower initial mean systolic BP (98.5 vs 121.9, p=.003), more severe hypotension (lowest systolic 77.0 vs 91.2, p=.034), lower initial GCS (6 vs 13, p=.039), higher mean admission lactate (4.6 vs 3.3, p=.036), and higher overall mortality (23.8% vs 0%, p=.048). Patients with TADI>28 received stent grafting at significantly shorter median time intervals from injury identification (median 4 hrs vs 14 hrs, p=.001). Overall causes of mortality were aortic hemorrhage related (n=3, 60%) and traumatic brain injury (n=2, 40%)., Conclusion: This simple-to-calculate index is independently correlated with mortality and urgency of stent grafting in blunt trauma patients with similar ISS. Patients with TADI scores >28 were more likely to undergo urgent stent grafting, thereby suggesting a trend in practice patterns with higher scores representing injuries that should be considered for expedited operative management. The TADI score should be validated in a larger sample of blunt trauma patients as an injury prioritization tool in the multi-system injured patient., (Copyright © 2024. Published by Elsevier Inc.)

Background/objectives: Oncolytic virotherapy is a promising approach in cancer immunotherapy. We have previously described a recombinant hybrid oncolytic virus (OV), VSV-NDV, which has a favorable safety profile and therapeutic immunogenicity, leading to direct oncolysis, abscopal effects, and prolonged survival in syngeneic in vivo tumor models. While OVs are known to mediate systemic anti-tumor immune responses, the detailed characterization of local and systemic immune responses to fusogenic oncolytic virotherapy remains unexplored., Methods and Results: We analyzed immune cell compartments in the spleen, blood, tumor-draining lymph nodes (TDLNs), and tumors over the course of VSV-NDV therapy in a bilateral syngeneic melanoma mouse model. Our results revealed significant local infiltration and activation of T lymphocytes in tumors and globally in the blood and spleen. Notably, in vivo CD8 + T cell depletion led to complete abrogation of the tumor response, highlighting the crucial role of T cells in promoting the therapeutic effects of oncolytic VSV-NDV. In vitro co-culture experiments enabled the interrogation of human immune cell responses to VSV-NDV-mediated oncolysis. Human peripheral blood mononuclear cells (PBMCs) were efficiently stimulated by exposure to VSV-NDV-infected cancer cells, which recapitulates the in vivo murine findings., Conclusions: Taken together, these data characterize a broad anti-tumor immune cell response to oncolytic VSV-NDV therapy and suggest that CD8 + T cells play a decisive role in therapeutic outcome, which supports the further development of this chimeric vector as a multimechanistic immunotherapy for solid cancers.

Since the discovery of antimicrobial agents, the misuse of antibiotics has led to the emergence of bacterial strains resistant to both antibiotics and common disinfectants like quaternary ammonium compounds (QACs). A new class, 'gemini' QACs, which contain two polar heads, has shown promise. Octenidine (OCT), a representative of this group, is effective against resistant microorganisms but has limitations such as low solubility and high cytotoxicity. In this study, we developed 16 novel OCT derivatives. These compounds were subjected to in silico screening to predict their membrane permeation. Testing against nosocomial bacterial strains (G + and G - ) and their biofilms revealed that most compounds were highly effective against G + bacteria, while compounds 7, 8, and 10-12 were effective against G - bacteria. Notably, compounds 6-8 were significantly more effective than OCT and BAC standards across the bacterial panel. Compound 12 stood out due to its low cytotoxicity and broad-spectrum antimicrobial activity, comparable to OCT. It also demonstrated impressive antifungal activity. Compound 1 was highly selective to fungi and four times more effective than OCT without its cytotoxicity. Several compounds, including 4, 6, 8, 9, 10, and 12, showed strong virucidal activity against murine cytomegalovirus and herpes simplex virus 1. In conclusion, these gemini QACs, especially compound 12, offer a promising alternative to current disinfectants, addressing emerging resistances with their enhanced antimicrobial, antifungal, and virucidal properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jan Marek reports financial support was provided by Ministry of Health of the Czech Republic. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Radiographic adjacent segment disease (ASD) ranges from 10% to 84%, depending on technique. Occurrence of symptomatic ASD is lower, with a range of 1.9% to 13%. ASD can be very debilitating and necessitate further procedures, leading to high morbidity. Herein, we explore the occurrence of adjacent segment disease when performing anterior column release in lateral interbody fusion., Methods: After institutional review board approval, 120 total patients who underwent lateral lumbar interbody fusion (LLIF) at our facility from 2013 to 2020 were retrospectively reviewed, allowing for a minimum of 3 years for follow-up time. Surgical variables and spinopelvic parameters were measured and collected by our team. Statistical measures of significance were calculated using IBM SPSS Statistics Version 29., Results: One hundred twenty total patients were included. 73.3% of patients had percutaneous screws, and 11.7% had open. Thirteen patients underwent LLIF with anterior column release (ACR). The mean lumbar lordosis (LL) was 50.1 ± 12.9, pelvic incidence (PI) was 52.8 ± 11.2, sacral slope was 33.6 ± 9.2, pelvic tilt was 18.1 ± 6.8, and sagittal vertical axis was 6.8 mm ± 30.5.Twenty four total patients had ASD after LLIF. In univariable analysis, ACR (P < 0.001) and PI-LL Mismatch (P < 0.035) were risk factors for developing ASD. In multivariable analysis, greater PI-LL mismatch was predictive of ASD (P < 0.005, OR = 1.097, and 95% confidence interval = 1.029-1.171), as was ACR (P < 0.001, OR = 9.667, and 95% confidence interval = 2.669-35.09)., Conclusions: Higher PI-LL mismatch after lumbar interbody fusion, and performance of an ACR during LLIF increased the likelihood of developing symptomatic ASD in our patients. Considering ACR to achieve the goal of correcting spinopelvic parameters should be carefully evaluated when undertaking a lateral approach., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The increasing threat of nuclear incidents and the widespread use of ionizing radiation (IR) in medical treatments underscore the urgent need for effective radiation countermeasures. Despite the availability of compounds such as amifostine, their clinical utility is significantly limited by adverse side effects and logistical challenges in administration. This study focuses on the synthesis and evaluation of novel piperazine derivatives as potential radioprotective agents, with the aim of overcoming the limitations associated with current countermeasures. We designed, synthesized, and evaluated a series of 1-(2-hydroxyethyl)piperazine derivatives. The compounds were assessed for cytotoxicity across a panel of human cell lines, and for their radioprotective effects in the MOLT-4 lymphoblastic leukemia cell line and in peripheral blood mononuclear cells (PBMCs) exposed to gamma radiation. The radioprotective efficacy was further quantified using the dicentric chromosome assay (DCA) to measure DNA damage mitigation. Among the synthesized derivatives, compound 6 demonstrated the most significant radioprotective effects in vitro , with minimal cytotoxicity across the tested cell lines. Compound 3 also showed notable efficacy, particularly in reducing dicentric chromosomes, thus indicating its potential to mitigate DNA damage from IR. Both compounds exhibited superior safety profiles and effectiveness compared to amifostine, suggesting their potential as more viable radioprotective agents. This study highlights the development of novel piperazine derivatives with promising radioprotective properties. Compound 6 emerged as the leading candidate, offering an optimal balance between efficacy and safety, with compound 3 also displaying significant potential. These findings support the further development and clinical evaluation of these compounds as safer, and more effective radiation countermeasures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Background: This study explored long-term outcome and functional status of patients born with critical aortic stenosis (CAS) following neonatal surgical or catheter interventions., Methods: A 40-year retrospective review of all consecutive patients within a large, single-center referral unit who required neonatal (<30 days) intervention for CAS. Additional detailed evaluation of surviving patients >7 years age was performed, with clinical assessment, objective cardiopulmonary exercise testing and state-of-the-art characterization of myocardial function (advanced echocardiography and cardiac MRI)., Results: Between 1970 and 2010, ninety-six neonates underwent CAS intervention (mean age 9 ± 7.5 days). Early death occurred in 19 (19.8%) and late death in 10 patients. Overall survival at 10 and 30 years was 70.1% and 68.5%, freedom from reintervention was 41.8% and 32.9% respectively. Among the 25 long-term survivors available for detailed assessment (median age 15.7 ± 6.4 years), 55% exhibited impaired peak oxygen uptake. Mean left ventricle (LV) ejection fraction was 65 ± 11.2%, with a mean LV end-diastolic volume z-score of 0.02 ± 1.4. Mean LV outflow tract Vmax was 2.3 ± 1.02 m/s. CAS patients had reduced LV longitudinal and increased radial strain (p = 0.003, p < 0.001 respectively). Five patients had severe LV diastolic dysfunction associated with endocardial fibroelastosis (EFE) (p = 0.0014)., Conclusion: Despite high early mortality rate, long-term survival of patients with CAS is reasonable at the expense of high reintervention rate. With successful intervention, there remained long-term clinical and subclinical LV myocardial impairment, of which EFE was one marker. Long-term follow-up of all CAS patients is crucial, involving detailed myocardial functional assessment to help elucidate physiology and optimise management., Competing Interests: Declaration of competing interest No grant support, no conflict of interest relating to this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intraoperative positioning system (IOPS; Centerline Biomedical, Inc) is a novel technology that allows for real-time intravascular navigation of endovascular devices using an electromagnetic field. In this report, we describe the use of IOPS for effective treatment of bilateral common iliac artery aneurysms with endovascular aortoiliac repair using iliac branch endoprostheses. Our experience suggests that this technology has the potential to reduce radiation and contrast use in endovascular procedures, although its application is currently limited. To the best of our knowledge, this is the first reported case of bilateral internal iliac cannulations for iliac branch endoprosthesis placement using IOPS., Competing Interests: None., (© 2024 The Authors.)

Hypergranulation is the abnormal accumulation of granulation tissue in a wound and is commonly seen in burns. It impairs wound healing and can predispose patients to infection. There is no gold standard treatment for hypergranulation tissue, but some options include surgical debridement, chemical cautery with silver nitrate, and topical steroids. Silver nitrate treatment is painful and can lead to scarring, so topical steroid use is on the rise. A retrospective review, between January 1, 2017 and August 30, 2021, at a tertiary burn center was performed to analyze outcomes of hypergranulation tissue after treatment with a topical 50/50 mixture of triamcinolone (Perrigo, Dublin, Ireland) and Polysporin (Johnson & Johnson, New Brunswick, NJ). One hundred and sixteen patients were treated with triamcinolone and Polysporin for hypergranulation tissue, although 24 did not meet inclusion criteria. Eighty-eight out of 92 patients were successfully treated until hypergranulation resolution, while 4/92(4.3%) required silver nitrate or surgery despite the topical cream to achieve resolution. In the 88 patients successfully treated until hypergranulation resolution, 99 areas of hypergranulation were treated. Forty-one of 99 (41.4%) hypergranulation areas resolved within 2 weeks. The average time to hypergranulation resolution was 27.5 ± 2.5 days. We found that a novel 50/50 mixture of triamcinolone and Polysporin topical ointment is an effective and safe treatment for hypergranulation tissue in burn wounds. Further prospective studies are needed to determine its efficacy and safety profile., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: There is limited data on the organisation of paediatric echocardiography laboratories in Europe., Methods: A structured and approved questionnaire was circulated across all 95 Association for European Paediatric and Congenital Cardiology affiliated centres. The aims were to evaluate: (1) facilities in paediatric echocardiography laboratories across Europe, (2) accredited laboratories, (3) medical/paramedical staff employed, (4) time for echocardiographic studies and reporting, and (5) training, teaching, quality improvement, and research programs., Results: Respondents from forty-three centres (45%) in 22 countries completed the survey. Thirty-six centres (84%) have a dedicated paediatric echocardiography laboratory, only five (12%) of which reported they were European Association of Cardiovascular Imaging accredited. The median number of echocardiography rooms was three (range 1-12), and echocardiography machines was four (range 1-12). Only half of all the centres have dedicated imaging physiologists and/or nursing staff, while the majority (79%) have specialist imaging cardiologist(s). The median (range) duration of time for a new examination was 45 (20-60) minutes, and for repeat examination was 20 (5-30) minutes. More than half of respondents (58%) have dedicated time for reporting. An organised training program was present in most centres (78%), 44% undertake quality assurance, and 79% perform research. Guidelines for performing echocardiography were available in 32 centres (74%)., Conclusion: Facilities, staffing levels, study times, standards in teaching/training, and quality assurance vary widely across paediatric echocardiography laboratories in Europe. Greater support and investment to facilitate improvements in staffing levels, equipment, and governance would potentially improve European paediatric echocardiography laboratories.

The current study imposes a new class of organophosphorus (OP)-inhibited cholinesterase reactivators by conceptualizing a family of asymmetric bisoximes with various reactivating scaffolds. Several novel nucleophilic warheads were investigated, putting forward 29 novel reactivating options, by evaluating their nucleophilicity and ability to directly decompose OP compounds. Adopting the so-called zwitterionic strategy, 17 mono-oxime and nine bisoxime reactivators were discovered with major emphasis on the bifunctional-moiety approach. Compounds were compared with clinically used standards and other known experimentally highlighted reactivators. Our results clearly favor the concept of asymmetric bisoximes as leading reactivators in terms of efficacy and versatility. These top-ranked compounds were characterized in detail by reactivation kinetics parameters and evaluated for potential CNS availability. The highlighted molecules 55, 57, and 58 with various reactivating warheads, surpassed the reactivating potency of pralidoxime and several notable uncharged reactivators. The versatility of lead drug candidate 55 was also inspected on OP-inhibited butyrylcholinesterase, revealing a much higher rate compared to existing clinical antidotes., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: In patients with recently diagnosed non-ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short-term follow-up. The aim of our study was to assess the long-term clinical course and stability of LVRR in these patients., Methods and Results: We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6 months and LV ejection fraction <40% persisting after at least 1 week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow-up over 5 years. LVRR was defined as the combined presence of (1) LVEF ≥ 50% or increase in LVEF ≥ 10% points and (2) decrease in LV end-diastolic diameter index (LVEDDi) ≥ 10% or (3) LVEDDi ≤ 33 mm/m 2 . LVRR was observed in 46% patients at 1 year, in 60% at 2 years and 50% at 5 years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5-year follow-up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007-1.196), logBNP level (OR 2.02, CI 1.14-3.56), and PR interval (OR 1.02, CI 1.006-1.035) (P < 0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1 year of follow-up was associated with a lower rate of mortality and heart failure hospitalization (P = 0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end-diastolic volume index (OR 0.97, CI 0.946-0.988), LVEF (OR 0.89, CI 0.83-0.96), and diastolic blood pressure (OR 1.04, CI 1.01-1.08) (P < 0.05 for all)., Conclusions: LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2 years of optimally guided heart failure therapy and then remains relatively stable during 5-year follow-up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long-term follow-up., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The lack of preventive and disease modifying therapies for temporal lobe epilepsy (TLE) is a major unmet medical need. Search for such therapies utilize mouse models and require detection of seizures in electroencephalography (EEG) recordings. The labor-intensive nature of reviewing EEGs spanning many weeks underscores the need for a method of automated detection. Here we report a simple automated method of detecting seizures in long term EEG recordings from electrodes implanted in the hippocampus in animal models of TLE. We utilize a 2-pronged approach that relies on the increase in power within the gamma band range (20-50hz) during the seizure followed by suppression of activity following the seizure (post-ictal suppression [PIS]). We demonstrate the utility of this method for detecting seizures in hippocampal and amygdala EEG recordings from multiple models of TLE., Competing Interests: Conflict of interest None of the authors has any conflict of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Fabry disease (FD) is a multisystemic lysosomal storage disorder caused by a defect in the alpha-galactosidase A gene that manifests as a phenocopy of hypertrophic cardiomyopathy. We assessed the echocardiographic 3D left ventricular (LV) strain of patients with FD in relation to heart failure severity using natriuretic peptides, the presence of a cardiovascular magnetic resonance (CMR) late gadolinium enhancement scar, and long-term prognosis., Methods and Results: 3D echocardiography was feasible in 75/99 patients with FD [aged 47 ± 14 years, 44% males, LV ejection fraction (EF) 65 ± 6% and 51% with hypertrophy or concentric remodelling of the LV]. Long-term prognosis (death, heart failure decompensation, or cardiovascular hospitalization) was assessed over a median follow-up of 3.1 years. A stronger correlation was observed for N-terminal pro-brain natriuretic peptide levels with 3D LV global longitudinal strain (GLS, r = -0.49, P < 0.0001) than with 3D LV global circumferential strain (GCS, r = -0.38, P < 0.001) or 3D LVEF (r = -0.25, P = 0.036). Individuals with posterolateral scar on CMR had lower posterolateral 3D circumferential strain (CS; P = 0.009). 3D LV-GLS was associated with long-term prognosis [adjusted hazard ratio 0.85 (confidence interval 0.75-0.95), P = 0.004], while 3D LV-GCS and 3D LVEF were not (P = 0.284 and P = 0.324)., Conclusion: 3D LV-GLS is associated with both heart failure severity measured by natriuretic peptide levels and long-term prognosis. Decreased posterolateral 3D CS reflects typical posterolateral scarring in FD. Where feasible, 3D-strain echocardiography can be used for a comprehensive mechanical assessment of the LV in patients with FD., Competing Interests: Conflict of interest: D.R. reports consulting honoraria from Sanofi Genzyme. J.M. reports consulting honoraria from Sanofi Genzyme, Takeda, Amicus. G.D. reports consulting honoraria from Sanofi Genzyme, Takeda, Amicus, Protalix. A.L. reports consulting honoraria from Sanofi Genzyme, Takeda, Amicus, Avrobio., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Arterial axillosubclavian injuries (ASIs) are currently managed with open repair (OR) and endovascular stenting (ES). The long-term prognosis of patients with these and associated brachial plexus injuries is poorly understood. We hypothesize that OR and ES for ASI have similar long-term patency rates and that brachial plexus injuries would confer high long-term morbidity., Methods: All patients at a level-1 trauma center who underwent procedures for ASI over a 12-year period (2010 to 2022) were identified. Long-term outcomes of patency rates, types of reintervention, rates of brachial plexus injury, and functional outcomes were then investigated., Results: Thirty-three patients underwent operations for ASI. OR was performed in 72.7% (n = 24) and ES in 27.3% (n = 9). ES patency was 85.7% (n = 6/7) and OR patency was 75% (n = 12/16), at a median follow-up of 20 and 5.5 months respectively. In subclavian artery injuries, ES patency was 100% (n = 4/4) and OR patency was 50% (n = 4/8) at a median follow-up of 24 and 12 months respectively. Long-term patency rates were similar between OR and ES (P = 1.0). Brachial plexus injuries occurred in 42.9% (n = 12/28) of patients. Ninety percent (n = 9/10) of patients with brachial plexus injuries who were followed postdischarge had persistent motor deficits at median follow-up of 12 months, occurring at significantly higher rates in patients with brachial plexus injuries (90%) compared to those without brachial plexus injuries (14.3%) (P = 0.0005)., Conclusions: Multiyear follow-up demonstrates similar OR and ES patency rates for ASI. Subclavian ES patency was excellent (100%) and prosthetic subclavian bypass patency was poor (25%). brachial plexus injuries were common (42.9%) and devastating, with a significant portion of patients having persistent limb motor deficits (45.8%) on long-term follow-up. Algorithms to optimize brachial plexus injuries management for patients with ASI are high-yield, and likely to influence long-term outcomes more than the technique of initial revascularization., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We report a green chemistry approach for preparation of oxime-functionalized ILs as AChE reactivators: amide/ester linked IL, l-alanine, and l-phenylalanine derived salts bearing pyridinium aldoxime moiety. The reactivation capacities of the novel oximes were evaluated towards AChE inhibited by typical toxic organophosphates, sarin (GB), VX, and paraoxon (PON). The studied compounds are mostly non-toxic up to the highest concentrations screened (2 mM) towards Gram-negative and Gram-positive bacteria cell lines and both filamentous fungi and yeasts in the in vitro screening experiments as well as towards the eukaryotic cell (CHO-K1 cell line). Introduction of the oxime moiety in initially biodegradable structure decreases its ability to biodegradation. The compound 3d was shown to reveal remarkable activity against the AChE inhibited by VX, exceeding conventional reactivators 2-PAM and obidoxime. The regularities on antidotal activity, cell viability, plasma stability, biodegradability as well as molecular docking study of the newly synthesized oximes will be used for further improvement of their structures., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yevgen Karpichev reports was provided by Tallinn University of Technology., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Phenotypic screening of an in-house library of small molecule purine derivatives against Mycobacterium tuberculosis (Mtb) led to the identification of 2-morpholino-7-(naphthalen-2-ylmethyl)-1,7-dihydro-6H-purin-6-one 10 as a potent antimycobacterial agent with MIC 99 of 4 μM. Thorough structure-activity relationship studies revealed the importance of 7-(naphthalen-2-ylmethyl) substitution for antimycobacterial activity, yet opened the possibility of structural modifications at positions 2 and 6 of the purine core. As the result, optimized analogues with 6-amino or ethylamino substitution 56 and 64, respectively, were developed. These compounds showed strong in vitro antimycobacterial activity with MIC of 1 μM against Mtb H 37 Rv and against several clinically isolated drug-resistant strains, had limited toxicity to mammalian cell lines, medium clearance with respect to phase I metabolic deactivation (27 and 16.8 μL/min/mg), sufficient aqueous solubility (>90 μM) and high plasma stability. Interestingly, investigated purines, including compounds 56 and 64, lacked activity against a panel of Gram-negative and Gram-positive bacterial strains, indicating a specific mycobacterial molecular target. To investigate the mechanism of action, Mtb mutants resistant to hit compound 10 were isolated and their genomes were sequenced. Mutations were found in dprE1 (Rv3790), which encodes decaprenylphosphoryl-β-d-ribose oxidase DprE1, enzyme essential for the biosynthesis of arabinose, a vital component of the mycobacterial cell wall. Inhibition of DprE1 by 2,6-disubstituted 7-(naphthalen-2-ylmethyl)-7H-purines was proved using radiolabelling experiments in Mtb H 37 Rv in vitro. Finally, structure-binding relationships between selected purines and DprE1 using molecular modeling studies in tandem with molecular dynamic simulations revealed the key structural features for effective drug-target interaction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Importance: Prenatal cardiac screening of the first and second trimesters has had a major impact on postnatal prevalence of congenital heart defects (CHDs), rates of termination of pregnancy (TOP), and outcomes among children born alive with CHDs., Objective: To examine the prenatal and postnatal incidence of major CHDs (ie, necessitating intervention within the first year of life), detection rate trends, rates of TOP, and the association of cardiac screening with postnatal outcomes., Design, Settings, and Participants: In this cross-sectional study, 3827 fetuses with antenatally diagnosed major CHDs in the Czech Republic (population 10.7 million) between 1991 and 2021 were prospectively evaluated with known outcomes and associated comorbidities. Prenatal and postnatal prevalence of CHD in an unselected population was assessed by comparison with a retrospective analysis of all children born alive with major CHDs in the same period (5454 children), using national data registry. Data analysis was conducted from January 1991 to December 2021., Main Outcomes and Measures: Prenatal detection and postnatal prevalence of major CHDs and rate of TOPs in a setting with a centralized health care system over 31 years., Results: A total of 3 300 068 children were born alive during the study period. Major CHD was diagnosed in 3827 fetuses, of whom 1646 (43.0%) were born, 2069 (54.1%) resulted in TOP, and 112 (2.9%) died prenatally. The prenatal detection rate increased from 6.2% in 1991 to 82.8% in 2021 (P < .001). Termination of pregnancy decreased from 70% in 1991 to 43% (P < .001) in 2021. Of 627 fetuses diagnosed in the first trimester (introduced in 2007), 460 were terminated (73.3%). Since 2007, of 2066 fetuses diagnosed in the second trimester, 880 (42.6%) were terminated, resulting in an odds ratio of 3.6 (95% CI, 2.8-4.6; P < .001) for TOP in the first trimester compared with the second trimester. Postnatal prevalence of major CHDs declined from 0.21% to 0.14% (P < .001). The total incidence (combining prenatal detection of terminated fetuses with postnatal prevalence) of major CHD remained at 0.23% during the study period., Conclusions and Relevance: In this cross-sectional study, the total incidence of major CHD did not change significantly during the 31-year study period. The prenatal detection of major CHD approached 83% in the current era. Postnatal prevalence of major CHD decreased significantly due to early TOPs and intrauterine deaths. The introduction of first trimester screening resulted in a higher termination rate in the first trimester but did not revert the overall decreasing trend of termination for CHDs in general.

Hard-to-heal wounds do not heal spontaneously and need long-term care provided by specialists. That burdens the patients as well as the healthcare systems. Such wounds arise from several pathologies, which result in venous leg ulcers (VLU), diabetic foot ulcers (DFU), pressure ulcers (PU), or ulcers originating from post-surgical wounds (pSW). Given the complex nature of hard-to-heal wounds, novel treatments are sought to enable wound healing. We tested the clinical efficacy and applicability of fluid comprising hyaluronic acid and iodine complex (HA-I) in the treatment of hard-to-heal wounds. Patients ( n = 56) with VLU, DFU, PU, or pSW hospitalised in multiple wound-care centres in the Czech Republic were treated with HA-I. Wound size, classically visible signs of infection, exudation, pain, and wound bed appearance were monitored for 12 weeks. The highest healing rate was in DFU (71.4%), followed by pSW (62.5%), VLU (55.6%), and PU (44.4%). Classical visible signs of infection were resolved within 8 weeks in all types of wounds. Wound bed appearance improved most noticeably in pSW and then in VLU. Exudation was lowered most significantly in DFU and pSW. The highest decrease in pain was in pSW and DFU. The treatment with HA-I successfully led to either complete closure or significant improvement in the wound's healing. Therefore, the complex of hyaluronic acid and iodine is suitable for the treatment of hard-to-heal wounds of various aetiologies.

Unraveling the complexities of the tumor microenvironment (TME) and its correlation with responsiveness to immunotherapy has become a main focus in overcoming resistance to such treatments. Targeting tumor-intrinsic retinoic acid-inducible gene-I (RIG-I), a sensor for viral RNA, was shown to transform the TME from an immunogenically "cold" state to an inflamed, "hot" lesion, which we demonstrated previously to be a crucial mediator of the efficacy of immune checkpoint inhibition with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). In this study, we focus on the chimeric oncolytic virus vesicular stomatitis virus (VSV)-Newcastle disease virus (NDV), comprised of genetic components of VSV and NDV, and we investigate its utility to support tumor-intrinsic RIG-I-dependent therapy with anti-CTLA-4. Overall, we demonstrate that treatment with VSV-NDV efficiently delays tumor growth and significantly prolongs survival in a murine model of malignant melanoma, which was further enhanced in combination with anti-CTLA-4. Although the direct oncolytic and pro-inflammatory effects of VSV-NDV therapy were independent of RIG-I activation, the synergism with anti-CTLA-4 therapy and associated activation of tumor-specific T cells was critically dependent on active RIG-I signaling in tumor cells. This work highlights the therapeutic value of utilizing an immune-stimulatory oncolytic virus to sensitize tumors to immune checkpoint inhibition., Competing Interests: J.A. holds a patent for the development and use of rVSV-NDV as an oncolytic therapy of cancer and is co-founder of Fusix Biotech GmbH, which is developing the rVSV-NDV technology for clinical use. S.H. has been a consultant for Bristol Myers-Squibb (BMS), Novartis, Merck, Abbvie, and Roche, has received research funding from BMS and Novartis, and is an employee of and holds equity interest in Roche/Genentech., (© 2023 The Authors.)

Background: More studies using cobalt complexes as drugs are needed. Results: The drug action of two cobalt salicylaldimines was determined. The complexes and amphotericin B (20 mg/ml) inhibited Candida albicans at 9-15 and 21 mm. This concentration of both ligands inhibited Staphylococcus aureus at 10 mm and one ligand inhibited Escherichia coli at 9 mm, but the complexes and ampicillin inhibited four bacteria at 9-20 and 21-26 mm. The ligands were inactive against cancer and normal cells, but the complexes and doxorubicin provided IC 50  values of 28.18-54.19 and 9.66 μM against MCF-7 cells and 15.76-20.49 and 36.42 μM against BHK cells. Conclusion: The ligands' activity was much improved by complexation, although they remained substandard.

Background: Adjacent segment disease (ASD) is a common problem after lumbar spinal fusions. Ways to reduce the rates of ASD are highly sought after to reduce the need for reoperation., Objective: To find predisposing factors of ASD after lumbar interbody fusions, especially in mismatch of pelvic incidence and lumbar lordosis (PI-LL)., Methods: We conducted a retrospective cohort study of all patients undergoing lumbar interbody fusions of less than 4 levels from June 2015 to July 2020 with at least 1 year of follow-up and in those who had obtained postoperative standing X-rays., Results: We found 243 patients who fit inclusion and exclusion criteria. Fourteen patients (5.8%) developed ASD, at a median of 24 months. Postoperative lumbar lordosis was significantly higher in the non-ASD cohort (median 46.4° ± 1.4° vs 36.9° ± 3.6°, P < .001), pelvic tilt was significantly lower in the non-ASD cohort (16.0° ± 0.66° vs 20.3° ± 2.4°, P = .002), PI-LL mismatch was significantly lower in the non-ASD cohort (5.28° ± 1.0° vs 17.1° ± 2.0°, P < .001), and age-appropriate PI-LL mismatch was less common in the non-ASD cohort (34 patients [14.8%] vs 13 [92.9%] of patients with high mismatch, P < .001). Using multivariate analysis, greater PI-LL mismatch was predictive of ASD (95% odds ratio CI = 1.393-2.458, P < .001) and age-appropriate PI-LL mismatch was predictive of ASD (95% odds ratio CI = 10.8-970.4, P < .001)., Conclusion: Higher PI-LL mismatch, both age-independent and when adjusted for age, after lumbar interbody fusion was predictive for developing ASD. In lumbar degenerative disease, correction of spinopelvic parameters should be a main goal of surgical correction., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Amyloidoses represent a group of pathological conditions characterized by amyloid fibrils accumulating in the form of deposits in intra- or extracellular space, leading to tissue damage. The lysozyme from hen egg-white (HEWL) is often used as a universal model protein to study the anti-amyloid effects of small molecules. The in vitro anti-amyloid activity and mutual interactions of green tea leaf constituents: (-)-epigallocatechin gallate (EGCG), (-)-epicatechin (EC), gallic acid (GA), caffeine (CF) and their equimolar mixtures were studied. The inhibition of HEWL amyloid aggregation was monitored by a Thioflavin T fluorescence assay and atomic force microscopy (AFM). The interactions of the analyzed molecules with HEWL were interpreted by ATR-FTIR and protein-small ligand docking studies. EGCG was the only substance efficiently inhibiting amyloid formation (IC 50  ∼193 μM), slowing the aggregation process, reducing the number of fibrils and partially stabilizing the secondary structure of HEWL. Compared to EGCG alone, EGCG-containing mixtures displayed lower overall anti-amyloid efficacy. The decrease in efficiency results from (a) the spatial interference of GA, CF and EC with EGCG while binding to HEWL, (b) the propensity of CF to form a less active adduct with EGCG, which participates in interactions with HEWL in parallel with pure EGCG. This study confirms the importance of interaction studies, revealing the possible antagonistic behavior of molecules when combined., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate the prenatal characteristics of double aortic arch (DAA), assess the relative size of the arches and their growth during pregnancy, describe associated cardiac, extracardiac and chromosomal/genetic abnormalities and review postnatal presentation and clinical outcome., Methods: This was a retrospective cohort study of all fetuses with a confirmed diagnosis of DAA seen in five specialized referral centers in London, UK, between October 2012 and November 2019. Cases were identified from the hospitals' fetal databases. Fetal echocardiographic findings, intracardiac and extracardiac abnormalities, genetic defects, computed tomography (CT) findings and postnatal clinical presentation and outcome were evaluated., Results: A total of 79 fetuses with DAA were included. Of those assessed postnatally, 48.6% had an atretic left aortic arch (LAA), while 5.1% had an atretic LAA at the first fetal scan and were misdiagnosed antenatally with right aortic arch (RAA). The LAA was atretic in 55.8% of those who underwent CT. DAA was an isolated abnormality in 91.1% of cases; 8.9% of patients had an additional intracardiac abnormality and 2.5% had both intra- and extracardiac abnormalities. Among the 52 cases that underwent genetic testing, 11.5% had genetic abnormalities and, specifically, the 22q11 microdeletion was identified in 3.8% of patients. At a median follow-up of 993.5 days, 42.5% of patients had developed symptoms of tracheoesophageal compression (5.5% during the first month after birth) and 56.2% had undergone intervention. Statistical analysis using the χ-square test showed no significant relationship between morphology of DAA (patency of both aortic arches vs atretic LAA) and the need for intervention (P = 0.134), development of vascular ring symptoms (P = 0.350) or evidence of airway compression on CT (P = 0.193)., Conclusions: Most cases of DAA can be diagnosed easily at midgestation, as typically both arches are patent with a dominant RAA at this stage. However, we found that the LAA had become atretic in approximately half of the cases postnatally, supporting the theory of differential growth of the arches during pregnancy. DAA is usually an isolated abnormality; however, thorough assessment is required to exclude associated intra- and extracardiac anomalies and to determine the need for invasive prenatal genetic testing. Postnatally, early clinical assessment is needed and CT scan should be considered, irrespective of the presence of symptoms. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Background. Diabetic foot osteomyelitis may precede major limb amputations and lengthy hospital admission. These complications impact patients' morbidity and mortality. Healthcare institutions with dedicated limb-preservation teams realize reduced amputation rates and improved quality of care. This study evaluates the outcomes following the implementation of a rigorous diabetic limb-preservation program at an academic institution. Methods. Patients with diabetes admitted for osteomyelitis occurring below the knee were identified by ICD-10 codes and included for retrospective review. The number and type of amputations, bone biopsies, revascularizations, and hospital length of stay (LOS) were evaluated. Outcomes were compared using the high-low (Hi-Lo) amputation ratio for the 24 months preceding and the 24 months after the integration of a diabetic limb-preservation service. Results . The authors identified and included 337 patients admitted for diabetic foot osteomyelitis. In the 24-month period prior to program implementation, 140 patients were evaluated. In the 24-month period after program implementation, 197 patients were evaluated. The overall amputation rate decreased from 67.1% (n = 94) to 59.9% (n = 118) ( P  = .214). Major limb amputation rates significantly decreased from 32.9% (n = 46) to 12.7% (n = 25) ( P  = .001). Minor amputation rates significantly increased from 34.2% (n = 48) to 47.2% (n = 93) ( P  = .024). The Hi-Lo amputation ratio decreased from 0.96 to 0.27 ( P  < .001). The rate of obtaining bone biopsies increased from 32.1% (n = 45) to 72.1% ( P  < .001). The rate of revascularization increased from 10.7% (n = 15) to 15.2% (n = 30) ( P  = .299). Average hospital LOS decreased significantly from 11.6 days to 9.8 days ( P  = .044). Conclusion . After the implementation of a limb-preservation team, there was a precipitous drop in major limb amputations in favor of minor amputations. The average hospital LOS decreased. These findings demonstrated improved clinical care and outcomes in patients with lower extremity osteomyelitis and reinforce the importance of a diabetic foot-preservation service within healthcare institutions.

Background and Objectives : PolDrugs is the largest Polish naturalistic nationwide survey to present basic demographic and epidemiological data that could potentially prevent harm from illicit substances intake in drugs users. The most recent results were presented in 2021. The goal of this year's edition was to re-present the above data and compare it to the previous edition's data to identify and describe the differences. Materials and Methods : The survey included original questions about basic demographics, substance use, and psychiatric treatment. The survey was administered via the Google Forms platform and promoted via social media. The data was collected from 1117 respondents. Results : People of all ages use a variety of psychoactive substances in many situations. The three most commonly used drugs are marijuana, 3,4-methylenedioxymethamphetamine, and hallucinogenic mushrooms. The most common reason for seeking professional medical help was amphetamine use. A total of 41.7 percent of respondents were receiving psychiatric treatment. The three most common psychiatric diagnoses among the respondents were depressive disorders, anxiety disorders, and ADHD. Conclusions : Key findings include increases in the use of psilocybin and DMT, increases in the use of heated tobacco products, and a near doubling in the percentage of individuals receiving psychiatric help in the past two years. These issues are discussed in the discussion section of this paper, which also addresses the limitations to the article.

Competing Interests: Conflict of interest: J.M. reports consulting honoraria from Sanofi Genzyme, Takeda, and Amicus. A.L. reports consulting honoraria from Sanofi Genzyme, Takeda, Amicus, and AVROBIO.

Background Transthoracic echocardiography is part of the regular follow-up protocol at most pediatric pulmonary arterial hypertension (PAH) centers. We aimed to develop a comprehensive and simple echocardiographic risk stratification for children with PAH. Methods and Results We included 63 children with PAH and a biventricular cardiac anatomy without relevant shunt lesions (60% female patients; mean age, 9.0 years; 42 idiopathic PAH and 21 associated PAH) undergoing a standardized transthoracic echocardiographic assessment. The prognostic value of echocardiographic parameters was assessed using Cox proportional hazards survival analysis and recursive partitioning for classification tree methods. Over a median follow-up period of 4.0 years, 17 patients died and 4 underwent lung transplantation. Various echocardiographic parameters were associated with the combined endpoint of death and transplantation on univariate analysis. On further analysis, right atrial area ( z score) and left ventricular diastolic eccentricity index (LVEId) emerged as robust and independent predictors of transplant-free survival. Considering mortality alone as an end point, a combination of right atrial area, left ventricular diastolic eccentricity index, and tricuspid annular plane systolic excursion were identified as independent predictors of outcome. Based on these parameters, we propose simple risk scores that can be applied at the bedside without computer assistance. CONCLUSIONS Echocardiographic parameters predict prognosis in children with pulmonary hypertension. A combination of widely available parameters including right atrial area, left ventricular eccentricity index, and tricuspid annular plane systolic excursion emerged as risk stratifiers that await external validation but may assist clinicians determining the prognosis of children with PAH.

Background: Secondary prevention of recurrent rheumatic fever in individuals with rheumatic heart disease (RHD) requires continuous antibiotic prophylaxis. However, the impact of antibiotic prophylaxis on the outcome of patients with severe RHD who underwent heart valve replacement is unknown. The objective of the study was to assess the relationship between the use of antibiotics as secondary prophylaxis in RHD patients who underwent valve replacement and clinical outcomes including mortality, reoperation, and valve-related hospitalization., Methods: We retrospectively compared outcomes of adult patients who underwent heart valve replacement for RHD at our institution from 1990 through 2014 and who received secondary antibiotic prophylaxis (prophylaxis group) with those who did not receive prophylaxis (nonprophylaxis group) using propensity score matching analysis., Results: A total of 1094 patients (56% females, median age 40 years, range 31-53 years) were included with a median follow-up of 9.6 years (range 2.9-12.6 years). Antibiotic prophylaxis was prescribed in 201 patients (18%). Propensity score matching analysis demonstrated no significant difference in overall survival (95% [92%-98%] vs 97% [95%-99%], respectively; P  = .7), valve-related hospitalization-independent survival (72% [range 65%-78%] vs 81% [range 76%-88%]; P  = .25), and redo valve surgery-independent survival [76% [range 70%-83%] vs 75% [range 72%-79%]; P  = .41) at 10-year follow-up in the nonantibiotic prophylaxis versus the antibiotic prophylaxis group., Conclusion: Secondary antibiotic prophylaxis among adult RHD patients following valve replacement is not associated with improved clinical outcomes.

Purpose: The hippocampus forms part of the limbic system and is involved in the learning process; it is responsible for transferring information from short-term to long-term memory. The aim of our study was to assess the effect of intensive studying on hippocampal volume and whether this correlates with exam results., Material and Methods: The analysis included volunteer final-year medical students who underwent 2 volumetric 3D T1 magnetic resonance imaging scans with an interval of 20 weeks: 19 weeks before and one week after the Final Medi-cal Examination. FreeSurfer software was used to compare the volumes of the whole hippocampus and its subfields between the 2 measurements. We assessed correlations between changes in hippocampal volume and the time students spent studying, between changes in hippocampal volume and the results of the exam, and between time spent studying and exam results., Results: Forty participants (25 women and 15 men; mean age 25 years) were included in the analysis. The right hippocampus presubiculum area increased significantly over the study period ( p = 0.029), whereas the volume of the left hippocampus remained unchanged. An increase in the volume of the right hippocampus correlated with longer study time ( r = 0.371 in percentage and r = 0.397 in mm 3 ) and better LEK exam results ( r = 0.441 in percentage and r = 0.456 in mm 3 )., Conclusions: Our research confirms the role of the hippocampus, particularly the subicular complex, in the process of learning and remembering, and suggest that the plastic abilities of the hippocampus depend on the intensity of learning and translate into better skills., Competing Interests: The authors report no conflict of interest., (© Pol J Radiol 2023.)

As COVID-19 is spreading, national agencies need to monitor and track several metrics. Since we do not have perfect testing programs on the hand, one needs to develop an advanced sampling strategies for prevalence study, control and management. Here we introduce REDACS: Regional emergency-driven adaptive cluster sampling for effective COVID-19 management and control and justify its usage for COVID-19. We show its advantages over classical massive individual testing sampling plans. We also point out how regional and spatial heterogeneity underlines proper sampling. Fundamental importance of adaptive control parameters from emergency health stations and medical frontline is outlined. Since the Northern hemisphere entered Autumn and Winter season (this paper was originally submitted in November 2020), practical illustration from spatial heterogeneity of Chile (Southern hemisphere, which already experienced COVID-19 winter outbreak peak) is underlying the importance of proper regional heterogeneity of sampling plan. We explain the regional heterogeneity by microbiological backgrounds and link it to behavior of Lyapunov exponents. We also discuss screening by antigen tests from the perspective of "on the fly" biomarker validation, i.e., during the screening.

The impact of atrial fibrillation and atrial tachycardias (AF/AT), and their optimal treatment strategy in PH patients is still being discussed. The goal of this study was to evaluate the effect of AF/AT termination on the hemodynamic parameters in PH patients. We compared patients with pre-capillary pulmonary hypertension (PH group), left ventricular heart failure (LV-HF group), and a Control group. A repeated right heart catheterization was performed during the catheter ablation (CA) procedure. The first measurement was done in arrhythmia, the second after the sinus rhythm (SR) was restored. High frequency atrial stimulation was used to simulate AT in patients without arrhythmia presence at the time of the CA. The variation of pressure parameters in PH patients did not differ significantly from the Controls. There was a significant increase in the right ventricle pressure after the SR restoration in the LV-HF group compared to the Controls and PH group (+4 vs. -2 vs. -3 mmHg, p<0.05). The cardiac index (CI) variation was not significant when compared between the study groups. An increase of the CI after the SR restoration was found in those patients with AF (+0.31 l/min/m2 [IQR 0.18; 0.58]) in contrast to those patients with organized AT/high frequency atrial stimulation ( 0.09 l/min/m2, [IQR - 0.45; 0.19]). This difference was statistically significant (p<0.05). The acute hemodynamic response to arrhythmia termination was not significantly different in the PH patients when compared to the Controls. In contrast to AT/high frequency stimulation, the restoration of SR in AF patients leads to an increased CI, irrespective of the presence or absence of PH.

Aims: Fabry disease (FD) is often associated with heart failure (HF). However, data on HF prevalence, prognosis, and applicability of echocardiographic criteria for HF diagnosis in FD remain uncertain., Methods and Results: We evaluated patients with genetically proven FD for symptoms and natriuretic peptides indicating HF. We then analysed the diagnostic utility of the currently recommended European Society of Cardiology (ESC) echocardiographic criteria for HF diagnosis and their relationship to natriuretic peptides. Finally, we examined the association between HF and echocardiographic criteria with mortality and cardiovascular events during follow-up. Of 116 patients with FD, 48 (41%) had symptomatic HF (mean age 58 ± 11 years, 62% male). HF with preserved ejection fraction (HF-pEF) was diagnosed in 43 (91%) patients, representing the dominant phenotype. Left ventricular mass index (LVMi) had the highest diagnostic utility (sensitivity 71% and specificity 83%) for HF diagnosis in FD, followed by E/e' > 9 (sensitivity 76% and specificity 78%) and global longitudinal strain (GLS) <16% (sensitivity 54% and specificity 88%). Log N-terminal pro-brain natriuretic peptide correlated significantly with LVMi (r = 0.60), E/e' (r = 0.54), and GLS (r = 0.52) (all Ps < 0.001) but not with left ventricular ejection fraction (r = -0.034, P = 0.72). During follow-up (mean 1208 ± 444 days), patients diagnosed with HF had a higher rate of all-cause mortality and worsening HF (33% vs. 1.5%, P < 0.001). Abnormal LVMi, E/e' > 9, and GLS < 16% were all associated with higher all-cause mortality and worsening HF., Conclusions: This study found a high prevalence of symptomatic HF in FD patients. HF-pEF was the dominant phenotype. LVMi, E/e', and GLS yielded the highest diagnostic utility for HF diagnosis and were significantly correlated with natriuretic peptides levels. Echocardiographic criteria proposed by current ESC HF guidelines apply to Fabry patients and predict cardiovascular events. At follow-up, Fabry patients with HF diagnosis had high event rates and significantly worse prognosis than patients without HF., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Silicon carbide (SiC) has been envisioned as an almost ideal material for power electronic devices; however, device reliability is still a great challenge. Here we investigate the reliability of commercial 1.2-kV 4H-SiC MOSFETs under repetitive unclamped inductive switching (UIS). The stress invoked degradation of the device characteristics, including the output and transfer characteristics, drain leakage current, and capacitance characteristics. Besides the shift of steady-state electrical characteristics, a significant change in switching times points out the charge trapping phenomenon. Transient capacitance spectroscopy was applied to investigate charge traps in the virgin device as well as after UIS stress. The intrinsic traps due to metal impurities or Z1,2 transitions were recognized in the virgin device. The UIS stress caused suppression of the second stage of the Z1,2 transition, and only the first stage, Z10, was observed. Hence, the UIS stress is causing the reduction of multiple charging of carbon vacancies in SiC-based devices.

Scanning probe microscopy is a useful tool in nanoscience. The effective application of nanotechnologies in various fields requires a knowledge of the characteristic attributes of nanoparticles such as shape, dimensions and statistical distribution, and a wide spectrum of experimental and theoretical methods based on various principles have been developed to determine these characteristics. Image histograms offer a global overview of the characteristics of an image. Their shape can encode specific statistical properties of displayed objects such as the distribution function in the case of similar and scalable objects. The model of height histogram presented here proposes a method which solves the long-term problem of processing images of extremely dense particle distributions. The method is based on the principle of the superposition of histograms of individual particles whose topographic surface is described by a parametric model. The resulting height histogram is defined by a convolution of the model of the particle histogram with the distribution function of particle size, with this construction forming the basis of the regression model. The parameters of the distribution function can be obtained via the optimization of the model. The method has been tested on artificially generated configurations of particles of various shapes and size distributions. Each of these configurations creates a topographic surface which is transformed into an image, and the heights obtained from the image allow a histogram to be calculated. Firstly, various configurations of particles are simulated without the presence of any disruptive influences. Next, several experimental effects are evaluated separately (for example, the background, particle shape irregularity and particle overlap). The decomposition of the histogram by the regression model on artificially generated images shows the robustness of the method with respect to particle density, partial horizontal overlap, randomly generated backgrounds and random fluctuations in particle shape. However, the method is sensitive to uniform changes in particle shape, a factor which limits its use to particles with known parametric models of their shape which allow the means of their parameters to be estimated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Transient spectroscopies are sensitive to charge carriers released from trapping centres in semiconducting devices. Even though these spectroscopies are mostly applied to reveal defects causing states that are localised in the energy gap, these methods also sense-charge from quantum wells in heterostructures. However, proper evaluation of material response to external stimuli requires knowledge of material properties such as electron effective mass in complex structures. Here we propose a method for precise evaluation of effective mass in quantum well heterostructures. The infinite well model is successfully applied to the InGaAsN/GaAs quantum well structure and used to evaluate electron effective mass in the conduction and valence bands. The effective mass m / m 0 of charges from the conduction band was 0.093 ± 0.006, while the charges from the valence band exhibited an effective mass of 0.122 ± 0.018.

There is limited knowledge regarding α-lactalbumin amyloid aggregation and its mechanism. We examined the formation of α-lactalbumin amyloid fibrils (α-LAF) in the presence of cations (Mg&lt;sup&gt;2+&lt;/sup&gt;, Ca&lt;sup&gt;2+&lt;/sup&gt;, Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;, NH&lt;sub&gt;4&lt;/sub&gt;&lt;sup&gt;+&lt;/sup&gt;, and Cs&lt;sup&gt;+&lt;/sup&gt;) in the form of chloride salts at two concentrations. We have shown that studied cations affect the conformation of α-lactalbumin, the kinetics of its amyloid formation, morphology, and secondary structure of α-LAF in a different manner. The higher salts concentration significantly accelerated the aggregation process. Both salt concentrations stabilized α-lactalbumin's secondary structure. However, the presence of divalent cations resulted in shorter fibrils with less β-sheet content. Moreover, strongly hydrated Mg&lt;sup&gt;2+&lt;/sup&gt; significantly altered α-lactalbumin's tertiary structure, followed by Na&lt;sup&gt;+&lt;/sup&gt;, NH&lt;sub&gt;4&lt;/sub&gt;&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;, and weakly hydrated Cs&lt;sup&gt;+&lt;/sup&gt;. On the other hand, Ca&lt;sup&gt;2+&lt;/sup&gt;, despite being also strongly hydrated, stabilized the tertiary structure, supposedly due to its high affinity towards α-lactalbumin. Yet, Ca&lt;sup&gt;2+&lt;/sup&gt; was not able to inhibit α-lactalbumin amyloid aggregation., (© 2022. The Author(s).)

This paper presents a case of double murder in which different mechanisms of suffocation, involving smothering, burking, and manual strangulation, were used. The victims are usually elderly people with disabilities and social isolation. The cases described here involve two women who were disabled and were murdered through blockage of the airway. Even though similar suffocating mechanisms were used in the murders, the autopsy findings differed between the two cases. This difference between the two can be explained by a preexisting medical condition that the younger victim had, which was quadriplegia resulting from cerebral hemorrhage, which limited herself-defense ability.

Streptococcus mutans is one of the bacteria that initiates the colonization of the pellicle at the tooth surface. It forms a plaque, together with other bacteria, which gradually dissolves the pellicle and leaves the tooth surface unprotected against the acidic oral environment. Calcium phosphate ceramics are excellent synthetic materials for the study of biofilm formation in dentistry because they are comparable to teeth in chemical composition and structure. Calcium phosphates can be processed to achieve a variety of crystalline compounds with biologically relevant ionic substitutions and structures that allow study of the effect of the surface chemistry and the topography independently. In this article, we describe the preparation and characterization of three types of calcium phosphate-based materials as a suitable surface for the formation of the S. mutans biofilm: beta-tricalcium phosphate (β-TCP); sintered hydroxyapatite (SHA); and calcium-deficient hydroxyapatite (CDHA). The densest biofilms were formed on the surfaces of SHA and CDHA, with no significant differences due to the stoichiometry or microstructure. In contrast, β-TCP showed a lower susceptibility to S. mutans biofilm formation, suggesting that the crystalline structure is the controlling parameter. Subsequently, SHA was selected to develop a dental biofilm model that allowed study of S. mutans biofilm susceptibility to chlorhexidine and ethanol., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Vascular rings are rare congenital abnormalities of the aortic arch. There are many embryological variants including a double aortic arch. In symptomatic children, division of ring and release of airway structures may be sufficient. Persistence of symptoms can be related to an anterior angle formed between the two arches. The aim of this study is to evaluate the clinical efficacy in improving symptoms and on changing this angle at the primary surgery., Methods: All children who had surgery for double aortic arch between 2005 and 2020, were studied. Relevant factors were analyzed for persistent symptoms including anatomical substrates and surgical details., Results: A total of 87 out of 224 children had surgery for a double aortic arch. At presentation, airway symptoms ( n = 74/87) were more common than esophageal symptoms ( n = 27/87). Early onset symptoms within 1 year were seen in 49 children. In addition to division of one arch, surgical steps also included realigning the anterior left arch, thereby eliminating the acute angle in 36 children (after 2014). After surgery, symptom relief within 12 months following surgery was seen in 64% of children (56 out of 87) but in 27 out of 36 children (75%) with additional surgical modification, as against 29 out of 51 (57%) in those with division of the arch. Symptoms persisted beyond 1 year needing reintervention in eight children., Conclusion: Anterior arch angulation plays an important role in double aortic arch by causing a "nutcracker" phenomenon. Repair in double aortic arch should consider this aspect and include modification of surgical steps by realigning the corresponding aortic arch branches and an anterior pexy in selected cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Beeman, Ramaswamy, Srinivasan, Rudrappa, Christov, Marek, Derrick and Muthialu.)

Amyloid fibrils draw attention as potential novel biomaterials due to their high stability, strength, elasticity or resistance against degradation. Therefore, the controlled and fast fibrillization process is of great interest, which raises the demand for effective tools capable of regulating amyloid fibrillization. Ionic liquids (ILs) were identified as effective modulators of amyloid aggregation. The present work is focused on the study of the effect of 1-ethyl-3-methyl imidazolium-based ILs with kosmotropic anion acetate (EMIM-ac) and chaotropic cation tetrafluoroborate (EMIM-BF 4 ) on the kinetics of lysozyme amyloid aggregation and morphology of formed fibrils using fluorescence and CD spectroscopy, differential scanning calorimetry, AFM with statistical image analysis and docking calculations. We have found that both ILs decrease the thermal stability of lysozyme and significantly accelerate amyloid fibrillization in a dose-dependent manner at concentrations of 0.5%, 1% and 5% ( v / v ) in conditions and time-frames when no fibrils are formed in ILs-free solvent. The effect of EMIM-BF 4 is more prominent than EMIM-ac due to the different specific interactions of the anionic part with the protein surface. Although both ILs induced formation of amyloid fibrils with typical needle-like morphology, a higher variability of fibril morphology consisting of a different number of intertwining protofilaments was identified for EMIM-BF 4.

Platinum-based anticancer drugs are actively developed utilizing lipophilic ligands or drug carriers for the efficient penetration of biomembranes, reduction of side effects, and tumor targeting. We report the development of a supramolecular host-guest system built on cationic platinum(II) compounds bearing ligands anchored in the cavity of the macrocyclic host. The host-guest binding and hydrolysis process on the platinum core were investigated in detail by using NMR, MS, X-ray diffraction, and relativistic DFT calculations. The encapsulation process in cucurbit[7]uril unequivocally promotes the stability of hydrolyzed dicationic cis -[Pt II (NH 3 ) 2 (H 2 O)(NH 2 -R)] 2+ compared to its trans isomer. Biological screening on the ovarian cancer lines A2780 and A2780/CP shows time-dependent toxicity. Notably, the reported complex and its β-cyclodextrin (β-CD) assembly achieve the same cellular uptake as cisplatin and cisplatin@β-CD, respectively, while maintaining a significantly lower toxicity profile.

Aims: We aim to determine any additional benefit of virtual reality (VR) experience if compared to conventional cross-sectional imaging and standard three-dimensional (3D) modelling when deciding on surgical strategy in patients with complex double outlet right ventricle (DORV)., Methods and Results: We retrospectively selected 10 consecutive patients with DORV and complex interventricular communications, who underwent biventricular repair. An arterial switch operation (ASO) was part of the repair in three of those. Computed tomography (CT) or cardiac magnetic resonance imaging images were used to reconstruct patient-specific 3D anatomies, which were then presented using different visualization modalities: 3D pdf, 3D printed models, and VR models. Two experienced paediatric cardiac surgeons, blinded to repair performed, reviewed each case evaluating the suitability of repair following assessment of each visualization modalities. In addition, they had to identify those who had ASO as part of the procedure. Answers of the two surgeons were compared to the actual operations performed. There was no mortality during the follow-up (mean = 2.5 years). Two patients required reoperations. After review of CT/cardiac magnetic resonance images, the evaluators identified the surgical strategy in accordance with the actual surgical plan in 75% of the cases. When using 3D pdf this reached only 70%. Accordance improved to 85% after revision of 3D printed models and to 95% after VR. Use of 3D printed models and VR facilitated the identification of patients who required ASO., Conclusion: Virtual reality can enhance understanding of suitability for biventricular repair in patients with complex DORV if compared to cross-sectional images and other 3D modelling techniques., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Cardiac allograft vasculopathy is one of the leading causes of late graft failure and subsequent death in orthotopic heart transplant. Although invasive coronary angiography is the gold standard modality for detection of cardiac allograft vasculopathy, dobutamine stress echocardiography has been recently frequently used as an alternative. Our aim was to evaluate the diagnostic performance of dobutamine stress echocardiography for detection of cardiac allograft vasculopathy in transplant patients., Methods: A retrospective analysis was conducted using a total of 150 dobutamine stress echocardiographic exams that were performed on 99 patients in our institution, with paired coronary angiogram and no acute rejection, within a median of 538 [interquartile range 371-816] days. Sensitivity and specificity of dobutamine echocardiography to detect allograft vasculopathy was evaluated. Allograft vasculopathy was defined as Grade 1 or higher based on ISHLT criteria. A positive dobutamine stress echo result was defined by new or worsening wall motion abnormality., Results: Median age of the population at transplant was 34 [interquartile range 22-46] years; 76 (77%) patients were male. Allograft vasculopathy was present in 31 (20.6%) out of 150 coronary angiograms. Only 7 (4.6%) of that number were positive on dobutamine stress echocardiography. Sensitivity and specificity for allograft vasculopathy detection was 3% and 94%, respectively. Out of 7 false positive dobutamine stress echocardiograms, two were in patients with myocardial bridging. Two patients with mild acute rejection had both negative dobutamine stress echo., Conclusions: Overall, positivity of dobutamine stress echocardiography in patients after heart transplant is low. It has high specificity, but very low sensitivity for detection of cardiac allograft vasculopathy. Dobutamine stress echocardiography should only be cautiously used as an alternative to coronary angiography., Competing Interests: Conflict of interest None., (© 2021 Saudi Heart Association.)

Far infrared (FIR) textiles are a new category of functional textiles that have presumptive health and well-being functionality and are closely related to human thermo-physiological comfort. FIR exerts strong rotational and vibrational effects at the molecular level, with the potential to be biologically beneficial. In general, after absorbing either sunlight or heat from the human body, FIR textiles are designed to transform the energy into FIR radiation with a wavelength of 4-14 μm and pass it back to the human body. FIR textiles can meet increased demand for light, warm, comfortable, and healthy clothing. The main aim of this research is to describe the procedure for creating the FIR reflective textile layer as part of multilayer textile structures that have enhanced thermal protection. To develop the active FIR reflecting surface, the deposition of copper nanolayer on lightweight polyester nonwoven structure Milife, which has beneficial properties of low fiber diameters, good shape stability and comfort, was used. This FIR reflective layer was used as an active component of sandwiches composed of the outer layer, insulation layer, active layer, and inner layer. The suitable types of individual layers were based on their morphology, air permeability, spectral characteristics in the infra-red region, and thermal properties. Reflectivity, transmittance, and emissivity were evaluated from IR measurements. Human skin thermal behavior and the prediction of radiation from the human body dependent on ambient conditions and metabolic rate are also mentioned. The FIR reflective textile layer created, as part of multilayer textile structures, was observed to have enhanced thermal protection.

Benzoxonium chloride belongs to the group of quaternary ammonium salts, which have been widely used for decades as disinfectants because of their high efficacy, low toxicity, and thermal stability. In this study, we have prepared the C 10 -C 18 set of benzoxonium-like salts to evaluate the effect of their chemical and biological decontamination capabilities. In particular, biocidal activity against a panel of bacterial strains including Staphylococcus aureus in biofilm form was screened. In addition, the most promising compounds were successfully tested against Francisella tularensis as a representative of potential biological warfare agents. From a point of view of chemical warfare protection, the efficiency of BOC-like compounds to degrade the organophosphate simulant fenitrothion was examined. Notwithstanding that no single compound with universal effectiveness was identified, a mixture of only two compounds from this group would be able to satisfactorily cover the proposed decontamination spectrum. In addition, the compounds were evaluated for their cytotoxicity as a basic safety parameter for potential use in practice. In summary, the dual effect on chemical and biological agents of benzoxonium-like salts offer attractive potential as active components of decontamination mixtures in the case of a terrorist threat or chemical or biological accidents.