Late Follow-up for a Randomized Trial of Surgical Treatment of Tricuspid Valve Regurgitation in Patients Undergoing Left Ventricular Assist Device Implantation.

OBJECTIVES: We previously reported that concurrent tricuspid valve surgery (TVS) was not associated with a lower incidence of early RHF among patients undergoing durable LVAD implantation. This is a follow-up analysis to further define the clinical impact of concurrent TVS within 12-months of follow-up. METHODS: Patients with moderate or severe TR on pre-operative echocardiography (n=71) were randomized to either LVAD implantation alone (No TVS, n=34) or with concurrent TVS (TVS, n=37). Randomization was stratified by pre-operative right ventricular dysfunction. Patients were followed for at least 12-months after surgery. The incidence of RHF was determined using INTERMACS criteria by an adjudication committee. Functional studies and repeat echocardiography were performed at 12-months. RESULTS: Demographics were similar between the two arms. At 12-months, the rate of moderate or severe RHF was 50.0% (No TVS) versus 51.4% (TVS). No patients developed RHF between 6- and 12-months following the procedure. Death from RHF was 5.4% (TVS) versus 8.8% (No TVS). At 12-months, there was no significant difference in TR severity between the two arms due to improvement in TR severity in the No TVS arm. On cardiopulmonary exercise testing at 12+ months, there was no significant difference in peak oxygen consumption. CONCLUSIONS: In patients with significant pre-implant TR, the severity of TR improved over time in the LVAD implantation alone arm. By 12-months, there is no significant difference in TR severity between the two arms. This may account for the lack of difference in late clinical or functional parameters.

Evaluation of the Therapeutic Potential of Traditionally-Used Natural Plant Extracts to Inhibit Proliferation of a HeLa Cell Cancer Line and Replication of Human Respiratory Syncytial Virus (hRSV).

Traditional approaches employing natural plant products to treat a wide array of ailments have been documented and described for thousands of years. However, there remains limited scientific study of the therapeutic potential or effectiveness of ethnobotanical applications. Increases in the incidence of cancer and emerging infectious diseases demonstrate a growing need for advances in the development of therapeutic options. In this study, we evaluate the therapeutic potential of aqueous extracts prepared from four plants, purple aster (Symphyotrichum novae-angliae (L.) Nemsom), common sage (Salvia lyrata (L.)), northern spicebush (Lindera benzoin (L.) Blume), and lamb's ear (Stachys byzantina (K.) Koch)) traditionally used in Native American medicine in Indiana, USA. Using a combination of cytotoxicity assays, immunofluorescence microscopy, and antiviral assays, we found that sage and spicebush extracts exhibit cytotoxic and antiproliferative effects on HeLa cell proliferation and that sage, spicebush, and aster extracts were capable of significantly inhibiting human respiratory syncytial virus (hRSV), a major respiratory pathogen of infants and the elderly. Chemical analysis of the four extracts identified four major compounds which were subsequently evaluated to identify the responsible constituents in the extracts. While none of the identified compounds were shown to induce significant impacts on HeLa cell proliferation, two of the compounds, (1S)-(-)-Borneol and 5-(hydroxymethyl)-furfural, identified in sage and spicebush, respectively, were shown to have antiviral activities. Our data suggest that several of the extracts tested exhibited either anti-proliferative or antiviral activity supporting future further analysis.

Comparison of diagnostic tools to assess the feasibility of programmatic use of rapid diagnostic tests for onchocerciasis: A dataset from Gabon.

Due to the success of large-scale ivermectin mass drug administration (MDA), the aim of onchocerciasis intervention efforts have shifted from control of the disease to elimination of transmission. This has necessitated a greater understanding and comparison of the performance of diagnostic tools in hypoendemic (low prevalence) settings which had not been incorporated into large-scale MDA programmes before the goal switched from onchocerciasis elimination as a public health problem to elimination (interruption) of transmission (EOT). Data on age, sex and duration of residence were collected, prior to ivermectin treatment, across Gabon in 2015 from 5,829 participants in 67 communities from 14 districts. Skin-snip samples (for detection of Onchocerca volvulus microfilariae) were obtained from 4,350 (75 %) and blood samples (for detection of presence of IgG4 antibodies against the O. volvulus Ov16 antigen) from 4,257 of those skin-snip tested (98 %). Whole blood was tested in the field using the SD Ov16 Rapid Diagnostic Test Prototype (Ov16 RDT). Dried blood spots (DBS) were prepared for all blood-sampled individuals. After assessing DBS quality, 2,990 (70 %) samples underwent valid analysis in the lab using horseradish peroxidase (HRP) Ov16 enzyme-linked immunosorbent assay (Ov16 ELISA). The number of positive individuals varied between diagnostic tools with skin-snip microscopy, Ov16 RDT and Ov16 ELISA detecting 337/4,350 (8 %, 95 % CI =7 %-9 %), 383/4,257 (9 %, 8 %-10 %) and 348/2,990 (12 %, 10 %-13 %), respectively. Data were analysed to understand the age profiles of microfilarial and IgG4 antibody prevalence by diagnostic and mapped across Gabon. These data have reuse potential for policy makers, test manufacturers and country programmes when making determinations at community level of the suitability of using Ov16 RDT for conducting delineation mapping or evaluating the current stage of a community or, more generally, an evaluation unit along the EOT path. Further, these data are of use to transmission dynamics modellers who can fit models to these data to better understand the stage(s) in the O. volvulus lifecycle likely responsible for IgG4 antibody seroconversion in the presence of Ov16 antigen. This is crucial for incorporation of antibody prevalence as an output of onchocerciasis transmission models to permit evaluation of currently proposed serological thresholds to inform decisions about Start- or Stop-MDA in the context of onchocerciasis elimination mapping (OEM) and verification of EOT, respectively.

Efficient CRISPR/Cas9-mediated genome editing in the European corn borer, Ostrinia nubilalis.

The European corn borer (Ostrinia nubilalis) is an agricultural pest and burgeoning model for research on speciation, seasonal adaptation and insect resistance management. Although previous work in O. nubilalis has identified genes associated with differences in life cycle, reproduction, and resistance to Bt toxins, the general lack of a robust gene-editing protocol for O. nubilalis has been a barrier to functional validation of candidate genes. Here, we demonstrate an efficient and practical methodology for heritable gene mutagenesis in O. nubilalis using the CRISPR/Cas9 genome editing system. Precise loss-of-function (LOF) mutations were generated at two circadian clock genes, period (per) and pigment-dispersing factor receptor (pdfr), and a developmental gene, prothoracicotropic hormone (ptth). Precluding the need for a visible genetic marker, gene-editing efficiency remained high across different single guide RNAs (sgRNA) and germline transmission of mutations to F1 offspring approached 100%. When single or dual sgRNAs were injected at a high concentration, gene-specific phenotypic differences in behaviour and development were identified in F0 mutants. Specifically, F0 gene mutants demonstrated that PER, but not PDFR, is essential for normal timing of eclosion. PTTH F0 mutants were significantly heavier and exhibited a higher incidence of diapause. This work will accelerate future studies of gene function in O. nubilalis and facilitate the development of similar screens in other Lepidopteran and non-model insects.

Gestational SARS-CoV-2 Infection in a Ugandan Birth Cohort: High Incidence, Mild Maternal Disease, and Evidence of Association with Transient Infant Stunting.

Many questions remain about the prevalence and effects of SARS-CoV-2 infection in malaria-endemic African countries like Uganda, particularly in vulnerable groups such as pregnant women. We describe SARS-CoV-2 immunoglobulin (Ig)G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. From December 2020-February 2022, among 400 unvaccinated pregnant women enrolled at 12-20 weeks gestation and followed through delivery, 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time, consistent with affinity maturation of the antibody response in the cohort. No women experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infect (-1.54 versus -0.37 and -0.51, P = 0.009). These findings suggest that pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with transient shorter stature in early infancy. Further research should explore the significance of this finding and define targeted measures to prevent infection in pregnancy.

All the king's men (and women): Fluoro-less leadless pacemaker implant in a severely obese patient.

INTRODUCTION: Severe obesity presents significant challenges in imaging and delivery of therapy, including pacemaker implant. METHODS AND RESULT: We present our experience implanting a leadless pacemaker (LP) in a severely obese man presenting with heart block. We describe our multidisciplinary approach using right internal jugular venous access and transesophageal imaging in lieu of fluoroscopy which failed to provide workable images in this instance. CONCLUSION: Ultrasound guided LP placement may have wider application in the midst of an ongoing obesity epidemic where fluoroscopy imaging is both limited and unsafe.

Early U.S. Heart Transplant Experience With Normothermic Regional Perfusion Following Donation After Circulatory Death.

BACKGROUND: Heart transplantation following donation after circulatory death (DCD HT) has short-term survival outcomes comparable to donation after brain death and has led to a significant increase in transplantation volume. The U.S. experience with the normothermic regional perfusion (NRP) DCD HT procurement method has not been evaluated. OBJECTIVES: The aim of this study was to examine short-term outcomes associated with NRP vs direct procurement and perfusion (DPP) methods used during DCD HT in the United States. METHODS: The UNOS (United Network for Organ Sharing) registry was queried for all adult (age ≥18 years) heart recipients and corresponding donors of controlled DCD HT from January 2019-December 2023. Transplantations were stratified by NRP or DPP reperfusion methods. The primary outcome was overall survival. RESULTS: A total of 918 heart donors and recipients met inclusion criteria, including 622 (68%) DPP and 296 (32%) NRP transplantations. Unadjusted Kaplan-Meier survival analysis demonstrated improved short-term survival associated with NRP (log-rank P = 0.005). After adjustment, DCD HT with NRP was independently associated with improved survival (HR: 0.39 [95% CI: 0.22-0.70]; P = 0.002). A propensity-matched analysis similarly demonstrated a cumulative survival benefit to NRP (log-rank P = 0.006). CONCLUSIONS: In this largest national series of DCD HT procurement perfusion strategies, NRP is associated with improved short-term survival as compared with DPP. This study evaluates the U.S. early experience with DCD HT, and longer-term follow-up data are needed to further assess the impact of DPP and NRP methods on post-heart transplantation outcomes.

Erosive toe-web intertrigo: Clinical features and management.

BACKGROUND: Toe-web (TW) intertrigo is a common disease of fungal or bacterial origin. Gram-negative bacterial (GNB) TW intertrigo consists of weeping, erosive, painful lesions that may be recurrent, leading to functional disability. Eczema is often associated with this condition. The management of intertrigo is poorly codified. OBJECTIVE: To evaluate the efficacy and safety of a standardized treatment plan using topical steroids in relation to the course and the frequency of recurrence of GNB-TW intertrigo. METHODS: We conducted a prospective open interventional multicentre study from June 2020 to June 2021. Standardised treatment using TCS together with follow-up via phone calls were performed over a 6-month period. In addition, a retrospective historical monocentric study was performed for patients with suspected TW-GNB intertrigo treated without standardized management. The primary endpoint was disease duration. We performed a Wilcoxon test to compare the median duration of GNB-TW intertrigo in both series. RESULTS: We included 13 patients in the prospective cohort and 14 in the retrospective cohort. In both cohorts, most patients were male with a median age of 59 years. The most frequent signs were fissures and exudates. Eczema was often associated (51.8%). Identified risk factors were psoriasis, local humidity, fungal intertrigo, vascular disease (arterial or venous insufficiency), and a history of multiple local treatments prior to diagnosis. Pseudomonas aeruginosa was the predominant pathogen (48.1%). Median durations of TW-GNB intertrigo were 56 days and 61 days. There was no significant difference in the median duration of the disease between the prospective and the retrospective cohorts (respectively61 days and 56 days; p > 0.58). Relapses were more frequent in the retrospective cohort (respectively 7.7% and 21.4%). CONCLUSION: GNB-TW intertrigo is a difficult-to-treat disease often associated with eczema. While topical corticosteroids (TCS) seem to be an effective and well-tolerated treatment they do not appear to reduce disease duration compared to other treatments.

Mitochondrial structural alterations in fibromyalgia: a pilot electron microscopy study.

OBJECTIVES: The pathogenesis of fibromyalgia (FM), characterised by chronic widespread pain and fatigue, remains notoriously elusive, hampering attempts to develop disease modifying treatments. Mitochondria are the headquarters of cellular energy metabolism, and their malfunction has been proposed to contribute to both FM and chronic fatigue. Thus, the aim of the current pilot study, was to detect structural changes in mitochondria of peripheral blood mononuclear cells (PBMCs) of FM patients, using transmission electron microscopy (TEM). METHODS: To detect structural mitochondrial alterations in FM, we analysed PBMCs from seven patients and seven healthy controls, using TEM. Patients were recruited from a specialised Fibromyalgia Clinic at a tertiary medical centre. After providing informed consent, participants completed questionnaires including the widespread pain index (WPI), symptoms severity score (SSS), fibromyalgia impact questionnaire (FIQ), beck depression inventory (BDI), and visual analogue scale (VAS), to verify a diagnosis of FM according to ACR criteria. Subsequently, blood samples were drawn and PBMCs were collected for EM analysis. RESULTS: TEM analysis of PBMCs showed several distinct mitochondrial cristae patterns, including total loss of cristae in FM patients. The number of mitochondria with intact cristae morphology was reduced in FM patients and the percentage of mitochondria that completely lacked cristae was increased. These results correlated with the WPI severity. Moreover, in the FM patient samples we observed a high percentage of cells containing electron dense aggregates, which are possibly ribosome aggregates. Cristae loss and possible ribosome aggregation were intercorrelated, and thus may represent reactions to a shared cellular stress condition. The changes in mitochondrial morphology suggest that mitochondrial dysfunction, resulting in inefficient oxidative phosphorylation and ATP production, metabolic and redox disorders, and increased reactive oxygen species (ROS) levels, may play a pathogenetic role in FM. CONCLUSIONS: We describe novel morphological changes in mitochondria of FM patients, including loss of mitochondrial cristae. While these observations cannot determine whether the changes are pathogenetic or represent an epiphenomenon, they highlight the possibility that mitochondrial malfunction may play a causative role in the cascade of events leading to chronic pain and fatigue in FM. Moreover, the results offer the possibility of utilising changes in mitochondrial morphology as an objective biomarker in FM. Further understanding the connection between FM and dysfunction of mitochondria physiology, may assist in developing both novel diagnostic tools as well as specific treatments for FM, such as approaches to improve/strengthen mitochondria function.

Creating a Three-Dimensional Reconstruction of the Glenohumeral Joint From Magnetic Resonance Imaging to Assist in Surgical Decision-Making.

Understanding the anatomical structure of a patient's shoulder joint is essential in surgical decision-making, especially regarding glenohumeral bone loss. The use of various imaging techniques, such as magnetic resonance imaging (MRI) and computed tomography (CT), bring certain advantages and disadvantages in assessing joint structure. Before a surgical procedure, bone loss can be observed and measured using these imaging techniques in both 2-dimensional and 3-dimensional (3D) views. The ability to visualize the shoulder joint in a 3D manner, as commonly done with CT scans, is helpful in assessing bone loss; however, CT involves exposure to radiation, additional time, and greater costs. The process of obtaining a 3D view of the shoulder joint from an MRI, although less common, can be completed effectively to assess bone loss while also solving some issues surrounding CT scans. By loading MRI datasets into an image-reformation program, such as 3D Slicer, the anatomical structures can be segmented to create realistic 3D models of the shoulder joint. Surgical direction can be determined after bone loss measurements and structural assessment of these models, without the need for CT scans. This technique can also be applied to other skeletal joints, in addition to the shoulder.

Transgenerational phenotypic responses to herbicide stress are more rapid than to shade and simulated herbivory in Arabidopsis.

Weeds in agricultural settings continually adapt to stresses from ecological and anthropogenic sources, in some cases leading to resistant populations. However, consequences of repeated sub-lethal exposure of these stressors on fitness and stress "memory" over generations remain poorly understood. We measured plant performance over a transgenerational experiment with Arabidopsis thaliana where plants were exposed to sub-lethal stress induced by the herbicides glyphosate or trifloxysulfuron, stresses from clipping or shading in either one (G1) or four successive generations (G1-G4), and control plants that never received stress. We found that fourth-generation (G4) plants that had been subjected to three generations of glyphosate or trifloxysulfuron stress produced higher post-stress biomass, seed weight, and rosette area as compared to that produced by plants that experienced stress only in the first generation (G1). By the same measure, clipping and shade were more influential on floral development time (shade) and seed weight (clipping) but did not show responsive phenotypes for vegetative metrics after multiple generations. Overall, we found that plants exhibited more rapid transgenerational vegetative "stress memory" to herbicides while reproductive plasticity was stressor dependent and similar between clipping/shade and anthropogenic stressors. Our study suggests that maternal plant stress memory aids next-generation plants to respond and survive better under the same stressors.

Modelling onchocerciasis-associated epilepsy and the impact of ivermectin treatment on its prevalence and incidence.

Retrospective cohort studies in Cameroon found an association between Onchocerca volvulus microfilarial load in childhood (measured in 1991-1993) and risk of developing epilepsy later in life (measured in 2017). We parameterised and integrated this relationship (across children aged 3-15 years) into the previously published, stochastic transmission model, EPIONCHO-IBM, for Simulium damnosum sensu lato-transmitted onchocerciasis. We simulated 19 years (1998-2017) of annual ivermectin mass drug administration (MDA) reflecting coverage in the study area, and modelled epilepsy prevalence and incidence. Scenario-based simulations of 25 years of (annual and biannual) MDA in hyper- and holoendemic settings, with 65% and 80% therapeutic coverage, were also conducted. EPIONCHO-IBM predicted 7.6% epilepsy prevalence (compared to 8.2% in the Cameroon study) and incidence of 317 cases/100,000 person-years (compared to 350). In hyperendemic areas, 25 years of biannual MDA (80% coverage) eliminated onchocerciasis-associated epilepsy (OAE) and protected untreated under-fives from its development. Strengthening onchocerciasis programmes, implementing alternative strategies, and evaluating treatment for under-fives and school-age children are crucial to prevent OAE in highly-endemic settings.

Implications of germination tolerances on invasion potential of Arthraxon hispidus.

Arthraxon hispidus is an introduced, rapidly spreading, and newly invasive grass in the eastern United States, yet little is known about the foundational biology of this aggressive invader. Germination responses to environmental factors including salinity, pH, osmotic potential, temperature, and burial depth were investigated to better understand its germination niche. Seeds from six populations in the Mid-Atlantic US germinated 95% with an average mean time to germination of 3.42 days of imbibition in the dark at 23°C. Germination occurred across a temperature range of 8-37°C and a pH range of 5-10 (≥83%), suggesting that neither pH nor temperature will limit germination in many environments. Arthraxon hispidus germination occurred in high salinity (342 mM NaCl) and osmotic potentials as low as -0.83MPa. The NaCl concentration required to reduce germination by 50% exceeded salinity concentrations found in soil and some brackish water saltmarsh systems. While drought adversely affects A. hispidus, 50% germination occurred at osmotic potentials ranging from -0.25 to -0.67 MPa. Given the climatic conditions of North America, drought stress is unlikely to restrict germination in large regions. Finally, emergence greatly decreased with burial depth. Emergence was reduced to 45% at 1-2 cm burial depths, and 0% at 8 cm. Emergence depths in concert with adequate moisture, germination across a range of temperatures, and rapid germination suggests A. hispidus' seed bank may be short-lived in moist environments, but further investigation is warranted. Given the broad abiotic tolerances of A. hispidus and a widespread native range, A. hispidus has the potential to germinate in novel territories beyond its currently observed invaded range.

Severe obesity among patients with left ventricular assist devices.

BACKGROUND: Patients with obesity and advanced heart failure requiring left ventricular assist device (LVAD) support are more likely to experience LVAD complications and may be disproportionately Black and/or female when compared to patients without obesity. Among these patients, obesity may represent a barrier to transplant eligibility and a marker of inequity in heart transplantation and health outcomes in advanced heart failure. METHODS: To better understand this issue at our institution, we examined our active LVAD cohort and found that almost one-third of all patients had severe obesity with BMI ≥ 35 kg/m2. RESULTS: Patients with LVADs and severe obesity were significantly younger and more likely to self-identify as Black, and numerically more likely to be female. CONCLUSION: Weight management in this group represents a vital area for improved equity in health outcomes and barriers to heart transplantation. TRIAL REGISTRATION: NA.

Trends in the use of immunotherapy to treat soft tissue sarcoma.

BACKGROUND: The role of immune-oncology (IO) therapy in soft tissue sarcoma (STS) is underexplored. This study characterized IO use in STS. METHODS: This is a retrospective analysis of patients with a soft tissue mass in the National Cancer Database, 2011-2021. Patients were categorized by IO receipt status. Groupwise testing and proportional trend tests were performed with Chi-squared tests. Multivariate logistic regression was performed to assess factors associated with IO receipt. RESULTS: Of the 103,092 patients with STS, 1935 (1.9 â€‹%) received or were recommended IO therapy. IO use increased 10-fold (0.24 â€‹%-2.5 â€‹% from 2011 to 2021; p â€‹< â€‹0.0001). Patients had higher odds of receiving IO when having higher grade tumors and metastatic disease, and when treated at an academic research center (all p â€‹< â€‹0.001). CONCLUSIONS: IO use in STS is low but increasing and primarily used in the metastatic setting. Future studies should identify biomarkers of IO response and facilitators for treatment receipt.

Hyperbaric oxygen therapy vs. pharmacological intervention in adults with fibromyalgia related to childhood sexual abuse: prospective, randomized clinical trial.

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = - 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.

Exploratory factor analysis yields grouping of brain injury biomarkers significantly associated with outcomes in neonatal and pediatric ECMO.

In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100ß, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRß, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments.

A Three-Step Catalytic Asymmetric Sequence from Alkynes to α-Silyloxyaldehydes and Its Application to a C22-C41 Fragment of Bastimolide A.

1,5-Polyol structures present challenges in stereocontrol, configurational assignment, and diastereomer separation; these are all compromised by remote stereochemical relationships. A configuration-encoded approach with alcohol configurations previously established within enantiopure building blocks offers a versatile solution to these issues. The iterative construction begins with α-silyloxyaldehydes; here, we introduce an enantioselective and step-economical route from alkynes to α-silyloxyaldehydes via silyl cation-induced ring opening of enol ester epoxides. This development enables an efficient configuration-encoded synthesis of the C22-C41 fragment of the bastimolides.