Saint Louis Science Center

ABSTRACT During lunge feeding, rorquals depress their lower jaw to fill the buccal pouch, which can produce a downward pitch on the body from a drag force below the center of mass. It is hypothesized that without flippers the raised upper jaw could produce a counteracting lift to trim the body. Upper jaws of the blue whale and humpback whale have triangular shapes that resemble delta wings. Such wings generate lift without stalling at high angles of attack. To test whether the upper jaw is acting like a delta wing, planform shapes of jaws were tested with multiaxis force transducer in a flow tank at angles of attack. These 2‐dimensional models performed like delta wings without stalling. A CFD model of an inflated buccal pouch indicated that pouch drag could be modeled as a flat plate. Comparison of flume and CFD data, on the other hand, showed pouch lift as more dependent on its degree of streamlining. Three‐dimensional models of whale bodies with the lower jaw angled down at 90 o and the upper jaw angled at 0 o , 15 o , and 30 o were tested in a flow tank. Without the flippers, increasing the angle of the raised upper jaw acted as a delta wing that produces most of the lift needed to negate downward pitching due to the drag of the depressed lower jaw and inflated buccal pouch.

Abstract Following a live discharge from hospice, patients and their caregivers often need to re-establish or transition to community resources as hospice services are no longer available. Although patients may no longer qualify for hospice, they often continue to experience complex medical and psychosocial needs. Therefore, coordinated service utilization following live discharge is critical to ensuring continuity of care, minimizing emergency room visits or caregiver burnout, and supporting quality of life (QOL) for both patients and caregivers. This study surveyed patient-caregiver dyads (n = 24) approximately 3 months following a live discharge due to extended prognosis, to better understand the services utilized and their QOL post-hospice care. Participants were an average age of 86 (SD 12.1), 83% female, and 79% White with 50% of participating living at home, while 42% were in long-term care. Within the first 3 months post discharge, 12.5% reported visiting an urgent care at least once, 8% reported at least one ER visit, and 8% reported at least one hospitalization. Further, 62% reported an established primary care provider while only 33% reported using home health, and less than half (46%) reported use of paid caregivers. Lastly, only 25% of patients reported “Good” QOL in the immediate post-discharge period. Results demonstrate that in the initial post-discharge period, medical service utilization is relatively low as is reported QOL. Research, clinical, and policy implications will be discussed.

New and persistent left bundle branch block (NP-LBBB) following Transcatheter Aortic Valve Replacement (TAVR) is an ongoing concern with incidence ranging from as low as 4% to up to 65% (varying for different types of valves). Such patients are at risk of developing high-grade atrioventricular block (HAVB) warranting permanent pacemaker (PPM) implantation. However, currently, there are no consensus guidelines or large prospective studies to risk stratify these patients for safer discharge after TAVR. To provide insight from a single center study on using modified electrophysiology (EP) study to risk stratify post-TAVR patients to outpatient monitoring for low-risk versus pacemaker implantation for high-risk patients. Between June 2020 and March 2023, all patients who underwent a TAVR procedure (324 patients) at our institution were screened for development of NP-LBBB post-operatively. Out of 26 patients who developed NP-LBBB, after a pre-specified period of observation, 18 patients were deemed eligible for a modified EP study to assess His-Ventricular (HV) interval. 11 out of 18 patients (61.1%) had normal HV interval (HV<55ms). Three out of 18 patients (16.7%) had HV prolongation (55ms<HV<70ms) without significant HV prolongation (defined as an increase in HV interval>30%) with intra-procedural procainamide challenge. Four out of 18 patients (22.2%) had significant HV prolongation (HV>70ms) warranting PPM implantation based on a multidisciplinary approach and shared decision-making with the patients. Total of 50% of patients discharged with PPM (two out of four patients) were noted to be pacemaker dependent based on serial device interrogations. All patients who did not receive PPM were discharged with ambulatory monitoring with 30-day event monitor and did not develop HAVB on serial follow-up. Normal HV interval up to 55ms on modified EP study after TAVR and development of NP-LBBB can be utilized as a threshold for risk stratification to facilitate safe discharge. The optimal upper limit of HV interval threshold remains unclear in determining appropriate candidacy for PPM.

Aging is a complex, multifaceted process that affects all organisms, characterized by functional decline and increased risk of death. Although the molecular and cellular basis of aging has been extensively studied, the roles of bioelectricity, biochemical gradients, and biomechanical gradients in this process remain less understood. This review investigates the current knowledge concerning these factors and their influence on aging at molecular, cellular, and whole organism levels. I examine the connection between steady-state membrane voltage (Vmem) and mitotic division, the relationship between mitochondrial membrane potential and aging, the role of epigenetic modifications in regulating gene expression, and the deliberate manipulation of bioelectric gradients to achieve desired outcomes in aging. This review emphasizes the need for further research to better comprehend the role of bioelectricity and chemical gradients in aging, and to identify potential targets for interventions to delay or alleviate the effects of aging.

Abstract Cryo‐electron microscopy (cryo‐EM) has become a major experimental technique to determine the structures of large protein complexes and molecular assemblies, as evidenced by the 2017 Nobel Prize. Although cryo‐EM has been drastically improved to generate high‐resolution three‐dimensional maps that contain detailed structural information about macromolecules, the computational methods for using the data to automatically build structure models are lagging far behind. The traditional cryo‐EM model building approach is template‐based homology modeling. Manual de novo modeling is very time‐consuming when no template model is found in the database. In recent years, de novo cryo‐EM modeling using machine learning (ML) and deep learning (DL) has ranked among the top‐performing methods in macromolecular structure modeling. DL‐based de novo cryo‐EM modeling is an important application of artificial intelligence, with impressive results and great potential for the next generation of molecular biomedicine. Accordingly, we systematically review the representative ML/DL‐based de novo cryo‐EM modeling methods. Their significances are discussed from both practical and methodological viewpoints. We also briefly describe the background of cryo‐EM data processing workflow. Overall, this review provides an introductory guide to modern research on artificial intelligence for de novo molecular structure modeling and future directions in this emerging field.This article is categorized under: Structure and Mechanism &gt; Molecular Structures Structure and Mechanism &gt; Computational Biochemistry and Biophysics Data Science &gt; Artificial Intelligence/Machine Learning

Parasol cells are one of the major types of primate retinal ganglion cells. The goal of this study was to describe the synaptic inputs that shape the light responses of the ON type of parasol cells, which are excited by increments in light intensity. A connectome from central macaque retina was generated by serial blockface scanning electron microscopy. Six neighboring ON parasol cells were reconstructed, and their synaptic inputs were analyzed. On average, they received 21% of their input from bipolar cells, excitatory local circuit neurons receiving input from cones. The majority of their input was from amacrine cells, local circuit neurons of the inner retina that are typically inhibitory. Their contributions to the neural circuit providing input to parasol cells are not well-understood, and the focus of this study was on the presynaptic wide-field amacrine cells, which provided 17% of the input to ON parasol cells. These are GABAergic amacrine cells with long, relatively straight dendrites, and sometimes also axons, that run in a single, narrow stratum of the inner plexiform layer. The presynaptic wide-field amacrine cells were reconstructed, and two types were identified based on their characteristic morphology. One presynaptic amacrine cell was identified as semilunar type 2, a polyaxonal cell that is electrically coupled to ON parasol cells. A second amacrine was identified as wiry type 2, a type known to be sensitive to motion. These inputs likely make ON parasol cells more sensitive to stimuli that are rapidly changing outside their classical receptive fields.

Manuka honey is an ancient remedy to improve wound healing; however, an effective delivery system is needed to facilitate extended release of honey into wounds. We developed an electrospun dermal regeneration template consisting of a poly (ε-caprolactone) (PCL) scaffold embedded with 1%, 5%, 10%, or 20% manuka honey. In vitro studies demonstrated that honey PCL scaffolds were not toxic to macrophages, and they allowed for macrophage infiltration into the scaffolds. Vascular endothelial growth factor (VEGF), a marker of angiogenesis, was released by macrophages cultured with scaffolds and macrophage/scaffold conditioned media promoted endothelial cell tube formation in an angiogenesis assay. In a full thickness murine wound model, the scaffolds prevented rapid wound contraction. In vivo, cells infiltrated the scaffolds by post-wounding day 7, but the honey scaffolds did not affect collagen deposition at that time. In summary, preliminary studies investigating the effect of honey on tissue repair show that scaffolds prevent rapid wound contraction, allow for cell infiltration, and promote angiogenesis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2620-2628, 2019.

ObjectiveTo examine correlations between blood levels of complement splitproduct iC3b and serum component C3 with clinically meaningful changes indisease activity in patients with systemic lupus erythematosus (SLE).Methods159 consecutive subjects with American College of Rheumatology orSystemic Lupus International Collaborating Clinics classified SLE wereenrolled into CASTLE (Complement ActivationSignatures in Systemic LupusErythematosus), a prospective observational study. Patientswith 1–7 study visits were included in this longitudinal analysis. 48healthy volunteers were enrolled to establish the normal reference iC3b/C3ratio. Serum C3 and C4 were measured by nephelometry and blood iC3b levelsby a lateral flow assay. SLE disease activity was monitored utilizing theSystemic Lupus Erythematosus Disease Activity Index 2K Responder Index-50instrument.ResultsiC3b/C3 ratio, double-stranded (ds)DNA antibodies (Abs), andsupraphysiologic prednisone dose (>7.5 mg/day) each independentlycorrelated with SLE disease activity, employing multilevel multiple logisticregression analysis. Only the iC3b/C3 ratio was significantly associatedwith clinically meaningful improvements in disease activity among subjectsreceiving supraphysiologic doses of prednisone. iC3b/C3 outperformed C3 andC4 levels discriminating both active versus inactive SLE disease and majorflares versus no disease activity. iC3/C3, dsDNA Abs, ESR, andsupraphysiologic prednisone dose were independently associated with lupusnephritis, while none were associated with SLE rash. The association ofiC3b/C3 with nephritis was independent of other observed clinicalmanifestations.ConclusionBlood iC3b/C3 correlates with SLE disease activity and clinicallymeaningful changes. Furthermore, it discriminates between active versusinactive SLE, and major flares compared to those patients without activedisease.

Gangliogliomas are rare neoplasms of the central nervous system that mostly originate in the temporal lobe and are associated with seizures. Literature mentions that BRAF mutations are most commonly associated with gangliogliomas. We discuss a unique case of ganglioglioma originating in the posterior fossa that showed multiple losses and a unique interstitial deletion at 9q21 by an array-comparative genome hybridization (array-CGH). The deletion led to a novel molecular fusion (TLE4-NTRK2) which was confirmed by next generation sequencing and provides a potential for a gene-targeted therapy.