Emergency Medical Planning for an Ultramarathon Open Water Swim: A Case Review of "Swim Tuff".

ABSTRACT: Ultramarathon open water swimming (OWS) events are one of the toughest endurance challenges in the world. The sport has gained notoriety with athletes swimming across the English Channel, Diana Nyad swimming from Cuba to Florida, and the 5- and 10-km OWS in the Olympic schedule. The athletes who participate are exposed to dangerous conditions that expose risks inherent to the sport. The optimal time to prepare for an emergency is before it happens. The aim of this paper is to present an emergency action plan (EAP) designed for the "Swim Tuff" event, a record-breaking ultramarathon swim that took place in Rhode Island, United States. This article identifies an overview of Swim Tuff, the challenges experienced, and how the team designed and implemented risk mitigation strategies. The professionals looking over athletes completing an OWS should be educated and aware of the unique circumstances inherent to the sport.

A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis.

BACKGROUND: The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF­06835375, a potent selective afucosyl immunoglobulin G1 antibody targeting C-X-C chemokine receptor type 5 (CXCR5) that potentially depletes B cells, follicular T helper (Tfh) cells, and circulating Tfh-like (cTfh) cells, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: This first-in-human, multicenter, double-blind, sponsor-open, placebo-controlled Phase 1 study recruited patients aged 18-70 years with SLE or RA. In Part A, patients received single doses of intravenous PF-06835375 (dose range: 0.03-6 mg) or placebo in six sequential single ascending dose (SAD) cohorts. In Part B, patients received repeat doses of subcutaneous PF-06835375 (dose range: 0.3-10 mg) or placebo on Days 1 and 29 in five multiple ascending dose (MAD) cohorts. Tetanus/Diphtheria (Td) and Meningococcal B (MenB/Trumenba™) vaccines were administered at Day 4 (Td and MenB) and Week 8 (MenB only) to assess PF-06835375 functional effects. Endpoints included treatment-emergent adverse events (TEAEs), pharmacokinetic parameters, pharmacodynamic effects on B and cTfh cells, and biomarker counts, vaccine response, and exploratory differential gene expression analysis. Safety, pharmacokinetic, and pharmacodynamic endpoints are summarized descriptively. The change from baseline of B and Tfh cell-specific genes over time was calculated using a prespecified mixed-effects model, with a false discovery rate < 0.05 considered statistically significant. RESULTS: In total, 73 patients were treated (SAD cohorts: SLE, n = 17; RA, n = 14; MAD cohorts: SLE, n = 22; RA, n = 20). Mean age was 53.3 years. Sixty-two (84.9%) patients experienced TEAEs (placebo n = 17; PF-06835375 n = 45); most were mild or moderate. Three (9.7%) patients experienced serious adverse events. Mean t1/2 ranged from 3.4-121.4 h (SAD cohorts) and 162.0-234.0 h (MAD cohorts, Day 29). B and cTfh cell counts generally showed dose-dependent reductions across cohorts (range of mean maximum depletion: 67.3-99.3%/62.4-98.7% [SAD] and 91.1-99.6%/89.5-98.1% [MAD], respectively). B cell-related genes and pathways were significantly downregulated in patients treated with PF-06835375. CONCLUSIONS: These data support further development of PF-06835375 to assess the clinical potential for B and Tfh cell depletion as a treatment for autoimmune diseases. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03334851.

Comparison of outcomes and required tools between transvenous extraction of pacemaker and implantable cardioverter defibrillator leads: Insight from single high-volume center experience.

INTRODUCTION: Reports of comparison with procedural outcomes for implantable cardioverter defibrillator (ICD) and pacemaker (PM) transvenous lead extraction (TLE) are old and limited. We sought to compare the safety, efficacy, and procedural properties of ICD and PM TLE and assess the impact of lead age. METHODS: The study cohort included all consecutive patients with ICD and PM TLE in the Cleveland Clinic Prospective TLE Registry between 2013 and 2022. Extraction success, complications, and failure employed the definitions described in the HRS 2017 TLE guidelines. RESULTS: A total of 885 ICD leads, a median implant duration of 8 (5-11) years in 810 patients, and 1352 PM leads of 7 (3-13) years in 807 patients were included. Procedural success rates in ICD patients were superior to those of PM in >20 years leads but similar in ≤20 years leads. In the PM group, the complete success rate of TLE decreased significantly according to the increase of lead age, but not in the ICD group. ICD TLE required more extraction tools compared with PM TLE but cases with older leads required non-laser sheath extraction tools in both groups. The most common injury site in major complication cases differed between ICD and PM TLE, although major complication rates showed no difference in both groups (2.7% vs. 1.6%, p = .12). CONCLUSION: The procedural success rate by TLE is greater for ICD patients than PM patients with leads >20 years old but requires more extraction tools. Common vascular complication sites and the impact of lead age on procedural outcomes and required tools differed between ICD and PM TLE.

FeverApp for Parents: A Multilingual and Socially Accountable Approach to Paediatric Fever Management in Germany.

Policymakers and practitioners are increasingly focused on achieving health equity and meeting the specific health needs of diverse populations, including vulnerable groups such as children. To address these challenges, the Fever App for Parents has emerged as a solution to guide parents through the complexities of managing fever in their children by improving fever management in children through real-time data collection and comprehensive educational support. This systematic approach aims to reduce unnecessary medical interventions and overuse of antibiotics, thereby improving the overall quality of pediatric care and reducing parental anxiety. In Germany, almost every second child aged 0-10 is a child with migration status and/or migration experience. This means that the parents of these children also need to be targeted in fever management and informed about the correct behavior in case of fever. This information will also be monitored anonymously to provide a feedback loop on the parent's experience with the menu navigation and information design. The FeverApp provides parents with a structured, step-by-step guide to accurately track their child's temperature and medication intake to encourage adherence to established fever management protocols. This study examines how the FeverApp embodies the principles of social responsibility through its multilingualism and digital development stages that incorporate user feedback. It shows why this app can be a resource to promote health equity through social responsibility in medical education and practice for parents, but also what barriers need to be considered at different stages of app development for parents from different cultural backgrounds to enable informal medical learning through apps.

Intracerebral Hemorrhage in a Patient With Newly Diagnosed Immune Thrombocytopenic Purpura Precipitated by a Viral Illness.

Intracerebral hemorrhage (ICH) is a rare and severe complication of immune thrombocytopenic purpura (ITP) that can be spontaneous. Viral illnesses, other infections, autoimmune disorders, and medications can cause ITP. ITP causes a significant decrease in platelet levels, increasing bleeding risk. ITP can be treated by steroids, intravenous immunoglobulin, plasmapheresis, platelet transfusion, biological agents, and splenectomy. ICH treatment involves the treatment of underlying ITP, as well as any neuro-interventional procedures needed. In this case report, we look at the presenting symptoms and treatment course of an interesting case of ICH in a patient who developed ITP after a viral upper respiratory infection.

Evolution and Prognosis of Tricuspid and Mitral Regurgitation Following Cardiac Implantable Electronic Devices. A Systematic Review and Meta-analysis.

BACKGROUND: Significant changes in tricuspid regurgitation (TR) and mitral regurgitation (MR) post-cardiac implantable electronic devices (CIED) are increasingly recognized. However, uncertainty remains as to whether risk of CIED-associated TR and MR differs with right ventricular pacing (RVP) via CIED with trans-tricuspid RV leads, compared to cardiac resynchronization therapy (CRT), conduction system pacing (CSP), and leadless pacing (LP). AIMS: Synthesize extant data on risk and prognosis of significant post-CIED TR and MR across pacing strategies. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases published until October 31st, 2023. Significant post-CIED TR and MR were defined as ≥ moderate. RESULTS: Fifty-seven TR studies (N=13,723 patients) and 90 MR studies (N =14,387 patients) were included. For all CIED, risk of post-CIED TR increased (pooled odds ratio (OR)=2.46 and 95% CI=1.88-3.22), while risk of post-CIED MR reduced (OR=0.74, 95% CI=0.58-0.94) after 12 and 6 months of median follow-up respectively. RVP via CIED with trans-tricuspid RV leads was associated with increased risk of post-CIED TR (OR=4.54, 95% CI=3.14-6.57) and post-CIED MR (OR=2.24, 95% CI=1.18-4.26). Binarily, CSP did not alter TR risk (OR=0.37, 95% CI=0.13-1.02), but significantly reduced MR (OR =0.15, 95% CI=0.03-0.62). CRT did not significantly change TR risk (OR=1.09, 95% CI=0.55-2.17), but significantly reduced MR with prevalence pre-CRT of 43%, decreasing post-CRT to 22% (OR =0.49, 95% CI=0.40-0.61). There was no significant association of LP with post-CIED TR (OR=1.15, 95% CI=0.83-1.59) or MR (OR=1.31, 95% CI=0.72-2.39). CIED-associated TR was independently predictive of all-cause mortality (pooled hazard ratio (HR)=1.64, 95% CI=1.40-1.90) after median of 53 months. MR persisting post-CRT independently predicted all-cause mortality (HR=2.00, 95% CI=1.57-2.55) after 38 months. CONCLUSIONS: Our findings suggest that, when possible, adoption of pacing strategies which avoid isolated trans-tricuspid RV leads may be beneficial in preventing incident or deteriorating atrioventricular valvular regurgitation and might reduce mortality.

Sparse Spiking Neural-Like Membrane Systems on Graphics Processing Units.

The parallel simulation of Spiking Neural P systems is mainly based on a matrix representation, where the graph inherent to the neural model is encoded in an adjacency matrix. The simulation algorithm is based on a matrix-vector multiplication, which is an operation efficiently implemented on parallel devices. However, when the graph of a Spiking Neural P system is not fully connected, the adjacency matrix is sparse and hence, lots of computing resources are wasted in both time and memory domains. For this reason, two compression methods for the matrix representation were proposed in a previous work, but they were not implemented nor parallelized on a simulator. In this paper, they are implemented and parallelized on GPUs as part of a new Spiking Neural P system with delays simulator. Extensive experiments are conducted on high-end GPUs (RTX2080 and A100 80GB), and it is concluded that they outperform other solutions based on state-of-the-art GPU libraries when simulating Spiking Neural P systems.

Eye-movement desensitisation and reprocessing therapy (EMDR) to prevent transition to psychosis in people with an at-risk mental state (ARMS): mixed method feasibility study.

BACKGROUND: Trauma plays an important role in the development of psychosis, but no studies have investigated whether a trauma-focused therapy could prevent psychosis. AIMS: This study aimed to establish whether it would be feasible to conduct a multicentre randomised controlled trial (RCT) to prevent psychosis in people with an at-risk mental state (ARMS), using eye-movement desensitisation and reprocessing therapy (EMDR). METHOD: This started as a mixed-method randomised study comparing EMDR to treatment as usual but, as a result of low participant recruitment, was changed to a single-arm feasibility study. The proposed primary outcome for an RCT was transition to psychosis at 12-month follow-up. Data on secondary outcomes were also collected. Qualitative interviews were conducted with patients and therapists. RESULTS: Fourteen participants were recruited from the Early Intervention teams. Most people who expressed an interest in taking part attended an assessment to determine eligibility. All those eligible consented to take part. A total of 64% (7 of 11) of participants who were offered EMDR were followed up at 12 months. Of the 11 participants offered EMDR, one (11%, 95% CI: 0.2%, 48%) transitioned to psychosis. Nine patients and three therapists were interviewed. Participants who completed therapy (n = 4; mean 10.5 sessions) found EMDR helpful, but those who discontinued (n = 6; mean 5.2 sessions) said it had not benefitted them overall. Therapists said EMDR could be effective, although not for all patients. CONCLUSIONS: Future studies recruiting people with an ARMS to an RCT may need to extend recruitment beyond Early Intervention teams. Although some individuals found EMDR helpful, reasons for discontinuing need to be addressed in future studies.

Myeloid NCOA4 sequesters KEAP1 to reduce ferroptosis for protection against salmonellosis in mice.

Salmonellosis, caused by Salmonella enterica serovar Typhimurium, is a significant global threat. Host immunity limits bacterial replication by inducing hepcidin, which degrades ferroportin, reducing iron transfer. However, this boosts macrophage iron storage, aiding intracellular pathogens like Salmonella. Mice lacking ferritin heavy chain (FTH1) in myeloid cells suffer worsened Salmonella infection. Nuclear receptor co-activator 4 (NCOA4) regulates iron release via FTH1 degradation during low iron, but its role in salmonellosis is unclear. Here, we reveal that myeloid NCOA4 deficiency augments spleen iron levels and increases cellular iron accumulation, oxidative stress, and ferroptosis in bone marrow-derived macrophages. This deficiency also increases susceptibility to Salmonella-induced colitis in mice. Mechanistically, NCOA4 suppresses oxidative stress by directly binding to the E3 ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1) and stabilizing the antioxidant transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2). Activation of NRF2 protects myeloid NCOA4 knockout mice from Salmonella-induced colitis. Antioxidant Tempol and myeloid cell-targeted curcumin offer protection against colitis in myeloid NCOA4-deficient mice. A low iron diet and ferroptosis inhibition also mitigate the heightened colitis in these mice. Overexpression of myeloid cell-specific NCOA4 confers protection against Salmonella-induced colitis via upregulating NRF2 signaling. Serum iron was reduced in myeloid NCOA4-overexpressing mice, but not in NCOA4-deficient mice. Targeted serum metabolomics analysis revealed that many lipids were decreased in myeloid NCOA4-deficient mice, while several of them were increased in myeloid NCOA4-overexpressing mice. Together, this study not only advances our understanding of NCOA4/KEAP1/NRF2/ferroptosis axis but also paves the way for novel myeloid cell-targeted therapies to combat salmonellosis.

Effect of a diabetes-specific formula in non-diabetic inpatients with stroke: a randomized controlled trial.

BACKGROUND/OBJECTIVES: In patients with acute stroke, the presence of hyperglycaemia has been associated with higher morbidity and less neurological recovery. The aim of the study was to evaluate the impact of a diabetes specific enteral nutrition (EN) formula on glycaemia, comorbidities and mortality in patients admitted with a first episode of stroke who received complete EN. METHODS: This was a prospective randomised controlled trial. Patients with acute stroke did not have diagnosis of diabetes mellitus and required nasogastric tube feeding. This study has been registered with code NCT03422900. The patients were randomised into two arms: an isocaloric isoprotein formula (control group (CG), 27 patients) vs a diabetes-specific formula (low glycaemic index carbohydrates, fibre (80% soluble) and higher lipid content) (experimental group (EG), 25 patients). Pre-EN blood glucose, hyperglycaemia during EN treatment, HbA1c, insulin use, oral route recovery, length of stay (LOS) and mortality at 30 days were collected. The complications of enteral nutrition during admission were collected as well. RESULTS: 52 patients were included, 50% females, with an age of 77.44(11.48) years; 34 (65.4%) had ischaemic stroke, with a Rankin score of 0(0-2), and a National Institute of Health Stroke Scale (NIHSS) of 19 (15-22). In CG, there were more cases of hyperglycaemia on the 5th day post-NE (13(65%) vs7(35%), p < 0.01). CG showed an OR of 7.58(1.49-39.16) (p = 0.02) for the development of hyperglycaemia. There were no differences in LOS between groups (12(8.5) days vs 14(23) days, p = 0.19) or in the death rate (10(37%) vs 10(40%), p = 0.8), although differences were found in terms of oral route recovery (EG: 11(44%) patients vs CG: 5(18.5%) patients, p = 0.04) (OR (EG): 5.53(1.25-24.47); p = 0.02). CONCLUSIONS: The use of a diabetes-specific enteral formula in non-diabetic patients admitted with acute stroke reduced the risk of developing hyperglycaemia and improved the rate of oral route recovery. Registered under ClinicalTrials.gov Identifier no. NCT03422900.

Recommended data elements for health registries: a survey from a German funding initiative.

BACKGROUND: The selection of data elements is a decisive task within the development of a health registry. Having the right metadata is crucial for answering the particular research questions. Furthermore, the set of data elements determines the registries' readiness of interoperability and data reusability to a major extent. Six health registries shared and published their metadata within a German funding initiative. As one step in the direction of a common set of data elements, a selection of those metadata was evaluated with regard to their appropriateness for a broader usage. METHODS: Each registry was asked to contribute a 10%-selection of their data elements to an evaluation sample. The survey was set up with the online survey tool "LimeSurvey Cloud". The registries and an accompanying project participated in the survey with one vote for each project. The data elements were offered in content groups along with the question of whether the data element is appropriate for health registries on a broader scale. The question could be answered using a Likert scale with five options. Furthermore, "no answer" was allowed. The level of agreement was assessed using weighted Cohen's kappa and Kendall's coefficient of concordance. RESULTS: The evaluation sample consisted of 269 data elements. With a grade of "perhaps recommendable" or higher in the mean, 169 data elements were selected. These data elements belong preferably to groups' demography, education/occupation, medication, and nutrition. Half of the registries lost significance compared with their percentage of data elements in the evaluation sample, one remained stable. The level of concordance was adequate. CONCLUSIONS: The survey revealed a set of 169 data elements recommended for health registries. When developing a registry, this set could be valuable help in selecting the metadata appropriate to answer the registry's research questions. However, due to the high specificity of research questions, data elements beyond this set will be needed to cover the whole range of interests of a register. A broader discussion and subsequent surveys are needed to establish a common set of data elements on an international scale.

Use of Muscle Ultrasonography in Morphofunctional Assessment of Amyotrophic Lateral Sclerosis (ALS).

Amyotrophic lateral sclerosis (ALS) is a progressive disease with a high prevalence of malnutrition that can influence prognosis. The main objective of this study is to compare the validity of muscle ultrasonography in the diagnosis of malnutrition and the prognosis of patients with ALS. METHODS: This is a prospective observational study that analyzes the nutritional status of patients at the beginning of nutritional monitoring. The morphofunctional assessment included the examination of anthropometric variables such as weight, height, body mass index (BMI), arm circumference, and calf circumference. Additionally, electrical bioimpedanciometry (BIA) was used to measure electrical parameters and estimate other relevant metrics. Muscle ultrasonography® (quadriceps rectus femoris (QRF)) assessed muscle mass parameters, including muscle area index (MARAI), anteroposterior diameter of the QRF (Y-axis) (cm), transverse diameter of the QRF (X-axis) (cm), and the sum of the quadriceps thickness (RF+VI) (cm), as well as muscle quality parameters such as echogenicity and the Y-X index. RESULTS: A total of 37 patients diagnosed with amyotrophic lateral sclerosis (ALS) were included in this study. Of these patients, 51.4% were men. The mean age was 64.27 (12.59) years. A total of 54.1% of the patients had a bulbar onset of amyotrophic lateral sclerosis, and 45.9% had spinal onset. The percentage of subjects with malnutrition diagnosed by the Global Leadership Initiative on Malnutrition (GLIM) criteria was 45.9% of patients. There was a direct correlation between muscle mass parameters assessed by muscle ultrasonography (RF+VI) and active mass markers measured by bioimpedanciometry (body cellular mass index (BCMI) (r = 0.62; p < 0.01), fat-free mass index (FFMI) (r = 0.75; p < 0.01), and appendicular skeletal mass index (ASMI) (r = 0.69; p < 0.01)). There was a direct correlation between echogenicity and resistance (r = 0.44; p = 0.02), as well as between the fat-free mass index and the Y-X index (r = 0.36; p = 0.14). Additionally, there was a negative correlation between echogenicity and BCMI (r = -0.46; p < 0.01) and ASMI (r = 0.34; p = 0.06). Patients with low quadriceps thickness (male < 2.49 cm; female < 1.84 cm) showed an increased risk of hospital admission adjusted by age, sex, and presence of dysphagia (OR: 7.84 (CI 95%: 1.09-56.07); p-value = 0.04), and patients with low-quality mass (Y-X index < 0.35) had a higher risk of hospital admission adjusted by age, sex, and presence of dysphagia (OR: 19.83 (CI 95%: 1.77-222.46); p-value = 0.02). CONCLUSIONS: In patients with ALS, ultrasonography echogenicity was inversely related to BCMI, FFMI, and ASMI, and the Y-X index was directly related to FFMI. The lowest quartiles of quadriceps thickness and Y-X index are risk factors for hospital admission.

Post-COVID-19 syndrome, inflammation and insulin resistance: a retrospective cohort study.

BACKGROUND: COVID-19-induced diabetes is a novel and enigmatic disease. Our aim was to evaluate a possible relationship between post-COVID-19 syndrome (PCS) and increased insulin resistance (IR) in non-diabetic outpatients after mild COVID-19. METHODS: Repeated measures design. Three evaluations [1E (pre-COVID, baseline), 2E (3 months post-COVID) and 3E (21 months post-COVID)] were performed, directed to PCS+ and PCS- subjects. Triglyceride-glucose (TyG) index ≥8.74 was considered IR, and albumin-to-globulin ratio (AGR) <1.50, inflammation. RESULTS: We analyzed 112 individuals (median [IQR] age=44 [20] years, 58% women, 36 PCS+, 76 PCS-). PCS+ with very low basal IR (TyG <7.78, lowest quartile) showed a reduced inflammatory burden (basal AGR=1.81 [0.4] vs. 1.68 [0.2] in 2E; P=0.23), and increased TyG across evaluations (from basal 7.62 [0.2] to 8.29 [0.5]; P=0.018]. Conversely, PCS+ subjects with high basal TyG (TyG ≥8.65, highest quartile) did not show significant variations in TyG, but a greater inflammatory load (basal AGR=1.69 [0.3] vs. 1.44 [0.3] in 2E; P=0.10). In multivariable models addressing groups with reduced basal IR (TyG <8.01), PCS has been a consistent predictor for TyG, after adjusting for confounders. Partial correlation and multivariable analyses showed similarities involving acute polysymptomatic COVID-19 and PCS regarding IR. CONCLUSIONS: PCS was associated with increased IR, being more evident when the baseline degree of IR was very low. PCS and increased IR were separately associated with inflammation. Acute polysymptomatic COVID-19 and PCS could be clinical expressions of underlying inflammatory state, which in turn may also trigger IR.

Evolution of tissue-specific expression of ancestral genes across vertebrates and insects.

Regulation of gene expression is arguably the main mechanism underlying the phenotypic diversity of tissues within and between species. Here we assembled an extensive transcriptomic dataset covering 8 tissues across 20 bilaterian species and performed analyses using a symmetric phylogeny that allowed the combined and parallel investigation of gene expression evolution between vertebrates and insects. We specifically focused on widely conserved ancestral genes, identifying strong cores of pan-bilaterian tissue-specific genes and even larger groups that diverged to define vertebrate and insect tissues. Systematic inferences of tissue-specificity gains and losses show that nearly half of all ancestral genes have been recruited into tissue-specific transcriptomes. This occurred during both ancient and, especially, recent bilaterian evolution, with several gains being associated with the emergence of unique phenotypes (for example, novel cell types). Such pervasive evolution of tissue specificity was linked to gene duplication coupled with expression specialization of one of the copies, revealing an unappreciated prolonged effect of whole-genome duplications on recent vertebrate evolution.

Influence of Controlled Chirality on the Crystallization of Maleimide-Functionalized 3,4-Ethylenedioxythiophene (EDOT-MA) Monomers.

Conjugated poly(alkoxythiophenes) such as poly(3,4-ethylenedioxythiophene) (PEDOT) have attracted considerable interest for use in a variety of applications such as biomedical devices, energy storage, and chemical sensing. Functionalized versions of the 3,4-ethylenedioxythiophene (EDOT) monomer make it possible to create polymers with properties tailored for specific applications. The maleimide functional group shows particular promise due to the wide variety of chemical modifications that it can undergo. Here, we examine the role that control of the chirality of the maleimide (MA) substituent has on the crystal structure and crystallization of the EDOT-MA monomer. We describe a method for the synthesis of a homochiral (S) variant of EDOT-MA and compare its crystallography, morphology, and thermal properties to that of the (R,S) EDOT-MA racemic compound. The conformation of the EDOT-MA molecule was substantially different, with the molecules adopting an "L" shape in the homochiral crystal, while in the racemic crystals, they were more colinear. The thermal stability of the homochiral crystals (Tm = 128.6 °C) was slightly higher than the racemic ones (Tm = 102.8 °C). We expect these results to be important in better understanding the solid-state assembly of the corresponding polymers prepared from these monomers.

Rapid Blueprinting: An Efficient Method for Designing Content of Assessments.

Problem: Many assessments in medical education involve measuring proficiency in a content area. Thus, proper content development (blueprinting) of tests in this field is of primary importance. Prior efforts to conduct content review as part of assessment development have been time- and resource-intensive, relying on practice analysis and then on linking methods. This monograph explores a "rapid, cost-effective" approach to blueprinting that allows efficient assessment development with rigor. Our investigation seeks to explore an efficient and effective alternate method for creating a content design (blueprint) for medical credentialing and evaluation examinations by focusing directly on assessment requirements. Approach: We employed a two-phase process to propose a rapid blueprinting method. Phase 1 involved a 1-day direct meeting of content experts/practitioners. Phase 2 involved a corroboration survey sent to a wider group of content experts/practitioners. The rapid blueprinting method was applied to developing eleven blueprints (five for medical specialty certification; five for health professions certification; and one for in-training assessment). Outcomes: The methods we used resulted in effective, well-balanced, operational examinations that successfully implemented the resulting blueprints in item writing assignments and test development. Assessments resulting from the use of the rapid blueprinting method also generated psychometrically sound inferences from the scores. For example, the assessments resulting from this methodology of test construction had KR-20 reliability coefficients ranging from .87 to .92. Next Steps: This approach leveraged the effectiveness and feasibility of the rapid blueprinting method and demonstrated successful examination designs (blueprints) that are cost- and time-effective. The rapid blueprinting method may be explored for further implementation in local assessment settings beyond medical credentialing examinations.

Bridges Between Spiking Neural Membrane Systems and Virus Machines.

Spiking Neural P Systems (SNP) are well-established computing models that take inspiration from spikes between biological neurons; these models have been widely used for both theoretical studies and practical applications. Virus machines (VMs) are an emerging computing paradigm inspired by viral transmission and replication. In this work, a novel extension of VMs inspired by SNPs is presented, called Virus Machines with Host Excitation (VMHEs). In addition, the universality and explicit results between SNPs and VMHEs are compared in both generating and computing mode. The VMHEs defined in this work are shown to be more efficient than SNPs, requiring fewer memory units (hosts in VMHEs and neurons in SNPs) in several tasks, such as a universal machine, which was constructed with 18 hosts less than the 84 neurons in SNPs, and less than other spiking models discussed in the work.

Medium-Term Outcomes from a Series of 1000 One Anastomosis Gastric Bypass in Australia: A Case Series.

PURPOSE: This study presents the short- (less than 6 months) and medium-term (6 months to 2 years) outcomes for weight loss and type 2 diabetes mellitus (T2DM) for all patients undergoing one anastomosis gastric bypass (OAGB) across multiple institutions between 2015 and 2021. MATERIALS AND METHODS: A retrospective analysis of prospectively collected databases was performed including 1022 participants who underwent OAGB at multiple institutions by multiple surgeons between 2015 and 2021. Primary outcome was percentage total weight loss (TWL) and secondary outcomes were achieving resolution of T2DM; OAGB specific short- and medium-term complications including bile reflux, marginal ulceration and internal herniation. RESULTS: One thousand and twenty-two patients underwent OAGB (81% primary surgery). A percentage of 34.1% (n = 349) had a preoperative diagnosis of type 2 diabetes mellitus (T2DM). Mean TWL was 33.6 ± 9% with a T2DM remission rate of 74% at 1-year post-op. Rates of bile reflux and marginal ulceration was 1.1% (n = 11) and 1.1% (n = 11). There were no cases of internal herniation during the follow-up period. CONCLUSION: OAGB results has echoed previously published work as being efficacious and safe in a short-medium term. The prevalence of complications, especially bile reflux is overall low in our population and no current evidence exists to support an increased risk of metaplasia or malignancy related to bile within the stomach.

Viscum album Lipophilic Extract in Actinic Keratosis, Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma: A Retrospective Case Series.

Introduction Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) belong to the group of keratinocyte carcinomas (KC). Actinic keratosis (AK) is a precursor lesion of cSCC. The incidences of cSCC, BCC and AK are currently strongly increasing. Different standard therapies exist for these conditions but are not always applicable or successful. Hydrophilic Viscum album extracts have been used in anthroposophic cancer therapy since 1917. Viscum album Lipophilic Extract (VALE) is prepared by means of supercritical CO2 extraction. This retrospective case series assessed the safe-ty and clinical effects of a topical application of 10% VALE in individual cases of cSCC, BCC and AK. Methods For this retrospective case series, a positive vote was obtained from the ethics committee of the University of Witten/Herdecke (No. 146/2020). Eligible patients signed a declaration of consent prior to inclusion in the study. The main outcome parameters were the clinical response to treat-ment with VALE and adverse drug reactions. Risk factors, concomitant therapies and diseases, fur-ther diagnostic and therapeutic information were documented where available. Data analysis was performed on the level of patients and of individual lesions. Results The study population consisted of 55 patients with 74 skin lesions. Individual case analysis accom-panied by photographic documentation revealed typical and promising treatment courses. Clinical response rates (complete + partial remissions) for individual lesions were 78 % for cSCC, 70 % for BCC, and 71 % for AK. Complete remission rates for individual lesions were 56 % for cSCC, 35 % for BCC, and 15 % for AK. In cSCC and BCC, shorter times to best clinical response were observed. Ad-verse drug reactions were reported in five patients including erythema and inflammatory reactions of mostly moderate severity that resolved completely. In one case, therapy was temporarily paused, in four cases it was continued without interruption. Discussion/ Conclusion The results of this study suggest that VALE is a safe and tolerable extract under whose application complete and partial remissions of KC could be observed. To improve and assess the efficacy of VALE, prospective investigations are necessary.

RNA Pol II-dependent transcription efficiency fine-tunes A-to-I editing levels.

A-to-I RNA editing is a widespread epitranscriptomic phenomenon leading to the conversion of adenosines to inosines, which are primarily interpreted as guanosines by cellular machines. Consequently, A-to-I editing can alter splicing or lead to recoding of transcripts. As misregulation of editing can cause a variety of human diseases, A-to-I editing requires tight regulation of the extent of deamination, particularly in protein-coding regions. The bulk of A-to-I editing occurs cotranscriptionally. Thus, we studied A-to-I editing regulation in the context of transcription and pre-mRNA processing. We show that stimulation of transcription impacts editing levels. Activation of the transcription factor MYC leads to an up-regulation of A-to-I editing, particularly in transcripts that are suppressed upon MYC activation. Moreover, low pre-mRNA synthesis rates and low pre-mRNA expression levels support high levels of editing. We also show that editing levels greatly differ between nascent pre-mRNA and mRNA in a cellular system, as well as in mouse tissues. Editing levels can increase or decrease from pre-mRNA to mRNA and can vary across editing targets and across tissues, showing that pre-mRNA processing is an important layer of editing regulation. Several lines of evidence suggest that the differences emerge during pre-mRNA splicing. Moreover, actinomycin D treatment of primary neuronal cells and editing level analysis suggests that regulation of editing levels also depends on transcription.