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Metal polymer composites combining low density, high strength composites with highly ductile and tough metals have gained traction over the last few decades as lightweight and high-performance materials for industrial applications. However, the mechanical properties are limited by the interfacial bonding strength between metals and polymers achieved through adhesives, welding, and surface treatment processes. In this paper, a novel manufacturing process combining additive manufacturing and compression molding to obtain hybrid metal polymer composites with enhanced mechanical properties is presented. Additive manufacturing enabled deposition of polymeric material with fibers in a predetermined pattern to form tailored charge or preform for compression molding. A grade 300 maraging steel triangular lattice is first fabricated using AddUp FormUp350 laser powder bed system and compression overmolded with additively manufactured long carbon fiber-reinforced polyamide-6,6 (40% wt. CF/PA66) preform. The fabricated hybrid metal polymer composites showed high stiffness and tensile strength. The stiffness and failure characteristics determined from the uniaxial tensile tests were correlated to a finite element model within 20% deviation. Fractographic analyses was performed using microscopy to investigate failure mechanisms of the hybrid structures.

Summary: Retinal bipolar cells are second-order neurons that transmit basic features of the visual scene to postsynaptic partners. However, their contribution to motion detection has not been fully appreciated. Here, we demonstrate that cholinergic feedback from starburst amacrine cells (SACs) to certain presynaptic bipolar cells via alpha-7 nicotinic acetylcholine receptors (α7-nAChRs) promotes direction-selective signaling. Patch clamp recordings reveal that distinct bipolar cell types making synapses at proximal SAC dendrites also express α7-nAChRs, producing directionally skewed excitatory inputs. Asymmetric SAC excitation contributes to motion detection in On-Off direction-selective ganglion cells (On-Off DSGCs), predicted by computational modeling of SAC dendrites and supported by patch clamp recordings from On-Off DSGCs when bipolar cell α7-nAChRs is eliminated pharmacologically or by conditional knockout. Altogether, these results show that cholinergic feedback to bipolar cells enhances direction-selective signaling in postsynaptic SACs and DSGCs, illustrating how bipolar cells provide a scaffold for postsynaptic microcircuits to cooperatively enhance retinal motion detection.

Globally, coastal human population density is approximately three times than that of inland areas. Such development threatens the integrity of coastal ecosystems. Coastal dune systems contain unique sets of terrestrial invertebrates and native plants, and represent some of the last remaining areas of semi-natural habitats along the coasts. In our study, we monitored bee and flowering plant abundance and diversity within coastal dune systems located within protected lands and developed sites throughout South and Central Florida. Our aim was to assess the potential impacts dune degradation and development could have on these economically and ecologically important insects. A total of 5419 bees from 5 families and 56 taxa were captured using bowl traps. Halictidae accounted for 70% of all bees collected, followed by Apidae (28%), Megachilidae (2%), Andrenidae (0.1%) and Colletidae (0.07%). Both species richness and Shannon-Wiener diversity indices were higher in protected lands when compared with developed sites. A majority of the commonly collected bee species showed higher abundances in protected lands compared with developed sites. Protected lands also supported higher abundances of ground, wood, and tunnel-nesting bees when compared with developed sites. Bee species richness and Shannon-Wiener indices were lower in sites with greater percentages of development occurring within close proximity to the dune systems, and higher in sites with greater availability of dune coverage. We observed higher abundance and flowering plant species richness within protected lands when compared with developed sites; protected lands also supported more federally endangered/threatened or state protected plant species compared with developed sites. Overall, coastal dune systems are ecologically important bee sanctuaries and should be conserved to help sustain native bee communities and the flowering plants that occur within them. Keywords: native bees, Land use, Urban development, Coastal dunes, Diversity

Cellular prion protein (PrPC) protects neurons against oxidative stress damage. This role is lost upon its misfolding into insoluble prions in prion diseases, and correlated with cytoskeletal breakdown and neurophysiological deficits. Here we used mouse neuronal models to assess how PrPC protects the neuronal cytoskeleton, and its role in network communication, from oxidative stress damage. Oxidative stress was induced extrinsically by potassium superoxide (KO2) or intrinsically by Mito-Paraquat (MtPQ), targeting the mitochondria. In mouse neural lineage cells, KO2 was damaging to the cytoskeleton, with cells lacking PrPC (PrP-/-) damaged more than wild-type (WT) cells. In hippocampal slices, KO2 acutely inhibited neuronal communication in WT controls without damaging the cytoskeleton. This inhibition was not observed in PrP-/- slices. Neuronal communication and the cytoskeleton of PrP-/- slices became progressively disrupted and degenerated post-recovery, whereas the dysfunction in WT slices recovered in 5 days. This suggests that the acute inhibition of neuronal activity in WT slices in response to KO2 was a neuroprotective role of PrPC, which PrP-/- slices lacked. Heterozygous expression of PrPC was sufficient for this neuroprotection. Further, hippocampal slices from mice expressing PrPC without its GPI anchor (PrPGPI-/-) displayed acute inhibition of neuronal activity by KO2. However, they failed to restore normal activity and cytoskeletal formation post-recovery. This suggests that PrPC facilitates the depressive response to KO2 and its GPI anchoring is required to restore KO2-induced damages. Immuno spin-trapping showed increased radicals formed on the filamentous actin of PrP-/- and PrPGPI-/- slices, but not WT and PrP+/- slices, post-recovery suggesting ongoing dysregulation of redox balance in the slices lacking GPI-anchored PrPC. The MtPQ treatment of hippocampal slices temporarily inhibited neuronal communication independent of PrPC expression. Overall, GPI-anchored PrPC alters synapses and neurotransmission to protect and repair the neuronal cytoskeleton, and neuronal communication, from extrinsically induced oxidative stress damages.

Strongyloides stercoralis is a soil-transmitted helminth endemic to tropical and subtropical regions and can be acquired due to parasite penetration through the skin. It can remain dormant in the gastrointestinal system for decades after the primary infection. In immunocompromised patients, this parasite can cause autoinfection with progression to hyperinfection syndrome. Here we report a unique case of pulmonary strongyloidiasis in a 32-year-old female, originally from Guatemala, with a significant clinical history of Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia diagnosed in 2019. The patient is status post chemotherapy with tyrosine kinase inhibitor plus hyper-CVAD regimen (Cyclophosphamide, Vincristine sulfate, Doxorubicin hydrochloride (Adriamycin), and Dexamethasone). History of drug-induced hyperglycemia and obesity was also noted. Her current chief complaint included dyspnea, tachycardia, and chest pain. Chest computerized tomography (CT) scan showed diffuse interstitial pulmonary edema with septal thickening, scattered ground-glass opacities, and small pericardial effusion. Due to normal ejection fraction, the differential diagnosis included non-cardiogenic pulmonary edema, pneumonitis secondary to chemotoxicity, and infection. She rapidly progressed to acute hypoxic respiratory failure, and a bronchoalveolar lavage study revealed numerous larvae consistent with Strongyloides hyperinfection. Further workup revealed eosinophilia with negative Strongyloides IgG antibody. Given the rarity of this infection in the United States and the patient’s place of birth, acquired latent Strongyloides infection is favored as the initial source of infection. The reactivation of the infection process was most likely secondary to her chemotherapy treatment. Strongyloides hyperinfection diagnosis can be challenging to establish and entails a high level of suspicion. Cytology evaluation is an essential factor for diagnosis.

Oncolytic virotherapy uses replication-competent virus as a means of treating cancer. Whereas this field has shown great promise as a viable treatment method, the limited spread of these viruses throughout the tumor microenvironment remains a major challenge. To overcome this issue, researchers have begun looking at syncytia formation as a novel method of increasing viral spread. Several naturally occurring fusogenic viruses have been shown to possess strong oncolytic potential and have since been studied to gain insight into how this process benefits oncolytic virotherapy. Whereas these naturally fusogenic viruses have been beneficial, there are still challenges associated with their regular use. Because of this, engineered/recombinant fusogenic viruses have also been created that enhance nonfusogenic oncolytic viruses with the beneficial property of syncytia formation. The purpose of this review is to examine the existing body of literature on syncytia formation in oncolytics and offer direction for potential future studies. Keywords: syncytia, oncolytic virotherapy, fusogenic virus, fusion protein

Objective: To identify gaps and opportunities in complex care training for pediatric residents., Methods: Residents in an academic pediatric residency program were surveyed about: training experiences in complex care; self-entrustment in key clinical activities in complex care; educational strategies that would increase preparedness; and recommendations for curriculum development. We used descriptive statistics for quantitative data and content analysis for free-text responses., Results: Of the 160 residents surveyed, 110 (69%) participated. Most participants reported prior clinical exposure to children with medical complexity (CMC; 106, 96%) during both inpatient (82, 75%) and outpatient (88, 80%) clinical rotations. Mean self-entrustment was at or below "somewhat confident" for all clinical activities in complex care, for residents in all postgraduate years. Clinical activities with highest reported self-entrustment included evaluating aspiration into the airway, nutritional issues, care coordination, and evaluating pain. Lowest self-entrustment was reported for facilitating transition to adult care, managing medical technologies, and safety/emergency planning. In terms of educational strategies, participants recommended inpatient encounters with an expert preceptor teaching about evaluating aspiration, pain/irritability and dysmotility (>50%); discussions with patients/families for advocacy, difficult discussions, and transition to adult care (>40%); and hands-on practice for medical technology care (>40%)., Conclusions: Pediatric residents report limited self-entrustment in performing key clinical activities in complex care, including for residents at the end of their last postgraduate year. Future curriculum development should prioritize direct observation of clinical encounters with CMC by expert preceptors, partnership with patients and families of CMC, and hands-on simulation., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Women with a gynecologic cancer tend to be older, obese, and postmenopausal, characteristics that are associated with an increased risk for obstructive sleep apnea. However, there is limited investigation regarding the condition's prevalence in this population or its impact on postoperative outcomes. In other surgical populations, patients with obstructive sleep apnea have been observed to be at increased risk for adverse postoperative events., Objective: We sought to estimate the prevalence of obstructive sleep apnea among gynecologic oncology patients undergoing elective surgery and to investigate for a relationship between obstructive sleep apnea and postoperative outcomes., Study Design: Patients referred to an academic gynecologic oncology practice were approached for enrollment in this prospective, observational study. Patients were considered eligible for study enrollment if they were scheduled for a nonemergent inpatient surgery and could provide informed consent. Enrolled patients were evaluated for a preexisting diagnosis of obstructive sleep apnea. Those without a prior diagnosis were screened using the validated, 4-item STOP questionnaire (ie, Snore loudly, daytime Tiredness, Observed apnea, elevated blood Pressure). All patients who screened positive for obstructive sleep apnea were referred for polysomnography. The primary outcome was the prevalence of women with obstructive sleep apnea or those who screened at high risk for the condition. Secondary outcomes examined the correlation between body mass index (kg/m 2 ) with obstructive sleep apnea and assessed for a relationship between obstructive sleep apnea and postoperative outcomes., Results: Over a 22-month accrual period, 383 eligible patients were consecutively approached to participate in the study. A cohort of 260 patients were enrolled. A total of 33/260 patients (13%) were identified as having a previous diagnosis of obstructive sleep apnea. An additional 66/260 (25%) screened at risk for the condition using the STOP questionnaire. Of the patients who screened positive, 8/66 (12%) completed polysomnography, all of whom (8/8 [100%]) were found to have obstructive sleep apnea. The prevalence of previously diagnosed obstructive sleep apnea or screening at risk for the condition increased as body mass index increased (P < .001). Women with untreated obstructive sleep apnea and those who screened at risk for the condition were found to have an increased risk for postoperative hypoxemia (odds ratio, 3.5; 95% confidence interval, 1.8-4.7; P = .011) and delayed return of bowel function (odds ratio, 2.1; 95% confidence interval, 1.3-4.5; P = .009)., Conclusion: The prevalence of obstructive sleep apnea or screening at risk for the condition is high among women presenting for surgery with a gynecologic oncologist. Providers should consider evaluating a patient's risk for obstructive sleep apnea in the preoperative setting, especially when risk factors for the condition are present., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background/aims: The REAL HEALTH -Diabetes Study is a practice-based clinical trial that adapted the Look AHEAD lifestyle intervention for implementation in primary care settings. The trial will compare the effectiveness and cost-effectiveness of in-person group lifestyle intervention, telephone group lifestyle intervention, and individual medical nutrition therapy (MNT), the current recommended standard of care in type 2 diabetes. The primary outcome is percent weight loss at 6 months with outcomes also measured at 12, 18, 24 (intervention completion), and 36 months. Here, we describe the adaptation, trial design, implementation strategies, and baseline characteristics of enrolled participants., Methods: The study is a three-arm, patient-level, randomized trial conducted in three community health centers (CHCs) and one diabetes practice affiliated with one academic medical center., Results: The study used existing clinical infrastructure to recruit participants from study sites. Strategies for successful conduct of the trial included partnering with health-center based co-investigator clinicians, engaging primary care providers, and accommodating clinical workflows. Of 248 eligible patients who attended a screening visit, 211 enrolled, with 70 randomly assigned to in-person group lifestyle intervention, 72 to telephone group lifestyle intervention, and 69 to MNT. The cohort was 55% female, 29% non-white, with mean age 62 years and mean BMI 35 kg/m 2 . Enrollment rates were higher at CHC sites., Conclusions: A practice-based randomized trial of a complex behavioral lifestyle intervention for type 2 diabetes can be implemented in community health and usual clinical settings. Participant and provider engagement was higher at local CHC sites reflecting the study implementation focus., Clinical Trial Registration: NCT02320253., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Coagulation transglutaminase factor XIII (FXIII) exists in circulation as heterotetrameric proenzyme FXIII-A 2 B 2 Effectively all FXIII-A 2 B 2 circulates bound to fibrinogen, and excess FXIII-B 2 circulates in plasma. The motifs that mediate interaction of FXIII-A 2 B 2 with fibrinogen have been elusive. We recently detected reduced binding of FXIII-A 2 B 2 to murine fibrinogen that has γ-chain residues 390-396 mutated to alanines (Fibγ 390-396A ). Here, we evaluated binding features using human components, including recombinant fibrinogen variants, FXIII-A 2 B 2 , and isolated FXIII-A 2 and -B 2 homodimers. FXIII-A 2 B 2 coprecipitated with wild-type (γA/γA), alternatively-spliced (γ'/γ'), and αC-truncated (Aα251) fibrinogens, whereas coprecipitation with human Fibγ 390-396A was reduced by 75% (P <0001). Surface plasmon resonance showed γA/γA, γ'/γ', and Aα251 fibrinogens bound FXIII-A 2 B 2 with high affinity (nanomolar); however, Fibγ 390-396A did not bind FXIII-A 2 B 2 These data indicate fibrinogen residues γ390-396 comprise the major binding motif for FXIII-A 2 B 2 Compared with γA/γA clots, FXIII-A 2 B 2 activation peptide release was 2.7-fold slower in Fibγ 390-396A clots (P < .02). Conversely, activation of recombinant FXIII-A 2 (lacking FXIII-B 2 ) was similar in γA/γA and Fibγ 390-396A clots, suggesting fibrinogen residues γ390-396 accelerate FXIII-A 2 B 2 activation in a FXIII-B 2 -dependent mechanism. Recombinant FXIII-B 2 bound γA/γA, γ'/γ', and Aα251 with similar affinities as FXIII-A 2 B 2 , but did not bind or coprecipitate with Fibγ 390-396A FXIII-B 2 also coprecipitated with fibrinogen from FXIII-A-deficient mouse and human plasmas. Collectively, these data indicate that FXIII-A 2 B 2 binds fibrinogen residues γ390-396 via the B subunits, and that excess plasma FXIII-B 2 is not free, but rather circulates bound to fibrinogen. These findings provide insight into assembly of the fibrinogen/FXIII-A 2 B 2 complex in both physiologic and therapeutic situations., (© 2016 by The American Society of Hematology.)

Blood serum was used to identify protein biomarkers for diagnosis of Parkinson's disease (PD) using analytically validated quantitative 2D-gel electrophoresis, and single variable and multivariate statistics. Using banked samples from a first medical center, we identified 57 specific protein spot biomarkers with disease-specific abnormal levels in serum of patients with PD, Alzheimer's disease, amyotrophic lateral sclerosis and similar neurodegenerative conditions (337 samples), when compared to age-matched normal controls (132 samples). To further assess their clinical usefulness in Parkinson's disease, we obtained prospective newly drawn blood serum samples from a second (56 PD, 30 controls) and third (6 PD, 48 controls) medical center. The protein concentrations of the 57 biomarkers were assessed by 2D-gel electrophoresis. Stepwise linear discriminant analysis selected a combination of 21 of the 57 as optimal to distinguish PD patients from controls. When applied to the samples from the second site, the 21 proteins had sensitivity of 93.3% (52 of 56 PD correctly classified), specificity of 92.9% (28 of 30 controls correctly classified); 15 of 15 patients with mild, 28 of 30 with moderate to severe symptoms, and all of the 6 PD patients from the third site were correctly classified. Eleven of the 21 proteins showed statistically significant abnormal concentrations in patients with mild symptoms, and 14 in patients with moderate-severe symptoms. The protein identities reflect the heterogeneity of Parkinson's disease, and thus may provide the capability of monitoring the blood for a diverse range of PD pathophysiological mechanisms: cellular degeneration, oxidative stress, inflammation, and transport.

The effects of endogenous and exogenous opioid substances on feline colonic transit were evaluated using colonic transit scintigraphy. Naloxone (0.3 mg/kg, i.m.) accelerated emptying of the cecum and ascending colon, and filling of the transverse colon. Endogenous opioid peptides thus appear to play a significant role in the regulation of colonic transit. At a moderate dose of morphine (0.1 mg/kg, i.m.), cecum and ascending colon transit was accelerated, while at a larger dose (1.0 mg/kg, i.m.) morphine had no effect. Since naloxone, a relatively nonspecific opioid antagonist, and morphine, a principally mu opioid receptor agonist, both accelerate proximal colonic transit, a decelerating role for at least one of the other opioid receptors is inferred.

We have examined the requirement for normal acetylcholine metabolism in the formation and maintenance of the larval and adult central nervous system in Drosophila melanogaster. By using mutations at the Ace and Cha loci, which respectively encode the degradative and synthetic enzymes for acetylcholine (ACh), acetylcholinesterase (AChE), and choline acetyltransferase (ChAT), we have been able to disrupt acetylcholine metabolism in situ. An ultrastructural analysis of embryonic nervous tissue lacking either enzymatic function has indicated that while neither function is required for the formation of the larval central nervous system, each is required for the subsequent maintenance of its structural integrity and function. Using temperature sensitive mutations at the Cha locus, the normal developmental profile of ChAT activity during the late larval and pupal stages was disrupted. Subsequent examination of the morphology and behavior of the treated animals has indicated that normal acetylcholine metabolism is not required for the initial formation of the adult nervous system, but is required for the subsequent maintenance of its structural integrity and function. The results obtained in these studies are discussed with respect to data presented on the adult distribution of the cholinergic markers' AChE activity and ChAT immunoreactivity. The projections of adult peripheral neurons innervating Ace+ tissue from Ace cuticular clones has been examined to address the nature of the structure of Ace neuropil. Normal projections are apparently achieved and maintained, suggesting that the defects seen in adult Ace mosaics arise as an aberrant intracellular organization of morphologically normal cells.