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Introduction: Costochondral cells may be isolated with minimal donor site morbidity and are unaffected by pathologies of the diarthrodial joints. Identification of optimal exogenous stimuli will allow abundant and robust hyaline articular cartilage to be formed from this cell source.Methods: In a three factor, two level full factorial design, the effects of hydrostatic pressure (HP), transforming growth factor β1 (TGF-β1), and chondroitinase ABC (C-ABC), and all resulting combinations, were assessed in third passage expanded, redifferentiated costochondral cells. After 4 wks, the new cartilage was assessed for matrix content, superficial zone protein (SZP), and mechanical properties.Results: Hyaline articular cartilage was generated, demonstrating the presence of type II collagen and SZP, and the absence of type I collagen. TGF-β1 upregulated collagen synthesis by 175% and glycosaminoglycan synthesis by 75%, resulting in a nearly 200% increase in tensile and compressive moduli. C-ABC significantly increased collagen content, and fibril density and diameter, leading to a 125% increase in tensile modulus. Hydrostatic pressure increased fibril diameter by 30% and tensile modulus by 45%. Combining TGF-β1 with C-ABC synergistically increased collagen content by 300% and tensile strength by 320%, over control. No significant differences were observed between C-ABC/TGF-β1 dual treatment and HP/C-ABC/TGF-β1.Conclusions: Employing biochemical, biophysical, and mechanical stimuli generated robust hyaline articular cartilage with a tensile modulus of 2 MPa and a compressive instantaneous modulus of 650 kPa. Using expanded, redifferentiated costochondral cells in the self-assembling process allows for recapitulation of robust mechanical properties, and induced SZP expression, key characteristics of functional articular cartilage. © 2013 Murphy et al.; licensee BioMed Central Ltd.

The articulation of the temporomandibular joint (TMJ) is composed of the temporal bone dorsally, the mandibular condyle ventrally and a fibrous articular disc. The TMJ disc plays an essential role in distributing load between the two articular surfaces. Degeneration of the disc in the presence of joint pathology has been shown in man; however, TMJ pathology has not been documented previously in tigers (Panthera tigris). The mandibular condyle and TMJ disc of a Bengal tiger (P. tigris tigris) and a Siberian tiger (P. tigris altaica) were evaluated grossly and the TMJ disc was characterized biochemically and mechanically. Characterization of the TMJ disc verified region- and direction-dependent biochemical and mechanical properties, reflective of the functional demands on the joint. Degenerative joint disease was observed in both cases and this was more severe in the Siberian tiger. Simultaneous evaluation of joint pathology, biochemical composition and mechanical properties of the TMJ disc revealed a loss in functional properties (tensile anisotropy) of the disc as joint pathology advanced from moderate to severe. TMJ degeneration may compromise the ability of the animal to eat and thrive and may be a factor contributing to the endangered status of these species.

STUDY OBJECTIVE: We evaluate the safety and efficacy of a pain protocol using 1 mg intravenous (IV) hydromorphone followed by an optional dose of 1 mg IV hydromorphone 15 minutes later. METHODS: Prospective interventional study at an urban academic emergency department (ED). One milligram of IV hydromorphone was administered to adults 21 to 64 years of age who had acute severe pain. Fifteen minutes later, patients were asked whether they wanted more pain medication. If they answered yes, they received another 1 mg of IV hydromorphone and were again asked 15 minutes later whether they wanted more pain medication. The primary efficacy outcome was the proportion of patients who had adequate analgesia, defined as declining additional hydromorphone within 1 hour of entering the protocol. The primary safety outcome was incidence of oxygen desaturation less than 95%. Secondary outcomes included numeric rating scale pain scores and adverse events. RESULTS: Of the 223 patients with complete data, 1 mg IV hydromorphone provided adequate analgesia for 77% (95% confidence interval 71% to 82%) within 15 minutes and 96% (95% confidence interval 92% to 98%) within 1 hour of entering the protocol. Eighty-six percent of patients reported pain scores that decreased by 2 or more numeric rating scale units. Five percent experienced transient oxygen desaturation below 95%, which was corrected promptly with oxygen. CONCLUSION: A rapid titration protocol using IV hydromorphone (1 mg hydromorphone followed by an optional 1 mg 15 minutes later) is efficacious in nonelderly ED patients with acute severe pain. There were no serious adverse events. [ABSTRACT FROM AUTHOR]

Background: Twin pregnancies are associated with higher risks of adverse neonatal outcomes compared to singleton pregnancies. The choice of delivery mode, when twin A presents cephalic, remains a subject of debate. In low- and middle-income countries, where healthcare resources are limited, the decision on the mode of delivery is even more critical., Objective: To evaluate the neonatal outcomes and the hospital costs of planned vaginal delivery compared to cesarean section (CS) in twin pregnancies with twin A presenting cephalic at Tenwek Hospital, Kenya., Study Design: This retrospective cohort study analyzed data from all twin deliveries at Tenwek Hospital, Kenya from, April 1, 2017, to March 30, 2023. Maternal data, mode of delivery, and neonatal data were collected from delivery logs, electronic health records, and neonatal records. Neonatal outcomes were a composite of either Appearance, Pulse, Grimace, Activity, and Respiration score less than seven at 5 minutes, neonatal intensive care unit admission, resuscitation, birth trauma, or neonatal complications, including death before discharge from the hospital. A logistic regression model was created to assess the impact of the planned mode of delivery on neonatal outcomes, controlling for antenatal care clinic visits, noncephalic presentation of twin B, and birth weight category., Results: The study included 177 twin deliveries: 129 (72.9%) were planned as vaginal deliveries and 48 (27.1%) were planned for CS. Among the planned vaginal deliveries, 66 (51.2%) experienced adverse outcomes, compared to 14 (29.2%) in the CS group ( P =.009). Logistic regression showed that the odds of adverse outcomes were 0.35 times lower in the CS group compared to the planned vaginal delivery group (95% CI: 0.15-0.83; P =.017). The average total hospital costs for planned vaginal delivery were 104,608 Kenya Shillings (standard deviation 111,761) compared to 100,708 Kenya Shillings (standard deviation 75,468) for CS ( P =.82)., Conclusion: Planned cesarean deliveries in twin pregnancies with twin A presenting cephalic at Tenwek Hospital were associated with fewer adverse neonatal outcomes compared to planned vaginal deliveries. There was no significant difference in hospital costs. These findings raise the question of the safest mode of delivery for patients in a resource-constrained setting., (© 2024 The Authors.)

The retina is an intricately organized neural tissue built on cone and rod pathways for color and night vision. Genetic mutations that disrupt the proper function of the rod circuit contribute to blinding diseases including retinitis pigmentosa and congenital stationary night blindness (CSNB). Down Syndrome cell adhesion molecule like 1 (Dscaml1) is expressed by rods, rod bipolar cells (RBCs), and sub-populations of amacrine cells, and has been linked to a middle age onset of CSNB in humans. However, how Dscaml1 contributes to this visual deficit remains unexplored. Here, we probed Dscaml1's role in the maintenance of the rod-to-RBC synapse using a loss of function mouse model. We used immunohistochemistry to investigate the anatomical formation and maintenance of the rod-to-RBC synapse in the young, adult, and aging retina. We generated 3D reconstructions, using serial electron micrographs, of rod spherules and RBCs to measure the number of invaginating neurites, RBC dendritic tip number, and RBC mitochondrial morphology. We find that while rod-to-RBC synapses form and are maintained, similar to wildtype, that there is an increase in the number of invaginating neurites in rod spherules, a reduction in RBC dendritic tips, and reduced mitochondrial volume and complexity in the Dscaml1 mutant retina compared to controls. We also observed precocious sprouting of RBC dendrites into the outer nuclear layer (ONL) of the Dscaml1 mutant retina compared to controls. These results contribute to our knowledge of Dscaml1's role in rod circuit development and maintenance and give additional insight into possible genetic therapy targets for blinding diseases and disorders like CSNB., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2023 Clemons et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Laryngotracheal stenosis (LTS) is pathologic fibrotic narrowing of the larynx and trachea characterized by hypermetabolic fibroblasts and CD4+ T cell-mediated inflammation. However, the role of CD4+ T cells in promoting LTS fibrosis is unknown. The mTOR signaling pathways have been shown to regulate the T cell phenotype. Here we investigated the influence of mTOR signaling in CD4+ T cells on LTS pathogenesis. In this study, human LTS specimens revealed a higher population of CD4+ T cells expressing the activated isoform of mTOR. In a murine LTS model, targeting mTOR with systemic sirolimus and a sirolimus-eluting airway stent reduced fibrosis and Th17 cells. Selective deletion of mTOR in CD4+ cells reduced Th17 cells and attenuated fibrosis, demonstrating CD4+ T cells' pathologic role in LTS. Multispectral immunofluorescence of human LTS revealed increased Th17 cells. In vitro, Th17 cells increased collagen-1 production by LTS fibroblasts, which was prevented with sirolimus pretreatment of Th17 cells. Collectively, mTOR signaling drove pathologic CD4+ T cell phenotypes in LTS, and targeting mTOR with sirolimus was effective at treating LTS through inhibition of profibrotic Th17 cells. Finally, sirolimus may be delivered locally with a drug-eluting stent, transforming clinical therapy for LTS.

This in-depth critical review investigates the impact of COVID-19 on personal relationships from the start of the pandemic in early 2020 to September 2021. Research examining six themes are identified and described in detail: the impact of COVID-19 on (1) family and intimate relationships; (2) LGBTQ+ relationships; (3) how COVID-19 is linked to technologically mediated communication and personal relationships; (4) potential shifts in sexual behaviors and desire; (5) potential shifts in relational conflict and intimate partner violence; and (6) constructive aspects of personal relationships, which is a broad theme that includes outcomes such as resilience, relational quality, coping, and social support. Findings for overarching patterns are offered to highlight implications for current research and identify future directions to consider when continuing to study personal relationships during the COVID-19 pandemic and similar future crises., (© The Author(s) 2022.)

Undergraduate student engagement in research increases retention and degree completion, especially for students who are underrepresented in science. Several approaches have been adopted to increase research opportunities including curriculum based undergraduate research opportunities (CUREs), in which research is embedded into course content. Here we report on efforts to tackle a different challenge: providing research opportunities to students engaged in remote learning or who are learning at satellite campuses or community colleges with limited research infrastructure. In our project we engaged students learning remotely or at regional centers to map gene expression in the mouse brain. In this project we mapped expression of the Down syndrome cell adhesion molecule like 1 (Dscaml1) gene in mouse brain using a LacZ expression reporter line. Identifying where Dscaml1 is expressed in the brain is an important next step in determining if its roles in development and function in the retina are conserved in the rest of the brain. Students working remotely reconstruct brain montages and annotated Dscaml1 expression in the brain of mice carrying one or two copies of the gene trap. We built on these findings by further characterizing Dscaml1 expression in inhibitory neurons of the visual pathway. These results build on and extend previous findings and demonstrate the utility of including distance learners in an active research group for both the student learners and the research team. We conclude with best practices we have developed based on this and other distance learner focused projects., (© 2022 Wiley-VCH GmbH.)

RNA binding proteins are important regulators of T cell activation, proliferation, and cytokine production. The zinc finger protein 36 (ZFP36) family genes ( Zfp36 , Zfp36l1 , and Zfp36l2 ) encode RNA binding proteins that promote the degradation of transcripts containing AU-rich elements. Numerous studies have demonstrated both individual and shared functions of the ZFP36 family in immune cells, but their collective function in T cells remains unclear. Here, we found a redundant and critical role for the ZFP36 proteins in regulating T cell quiescence. T cell-specific deletion of all three ZFP36 family members in mice resulted in early lethality, immune cell activation, and multiorgan pathology characterized by inflammation of the eyes, central nervous system, kidneys, and liver. Mice with T cell-specific deletion of any two Zfp36 genes were protected from this spontaneous syndrome. Triply deficient T cells overproduced proinflammatory cytokines, including IFN-γ, TNF, and GM-CSF, due to increased mRNA stability of these transcripts. Unexpectedly, T cell-specific deletion of both Zfp36l1 and Zfp36l2 rendered mice resistant to experimental autoimmune encephalomyelitits due to failed priming of antigen-specific CD4 + T cells. ZFP36L1 and ZFP36L2 double-deficient CD4 + T cells had poor proliferation during in vitro T helper cell polarization. Thus, the ZFP36 family redundantly regulates T cell quiescence at homeostasis, but ZFP36L1 and ZFP36L2 are specifically required for antigen-specific T cell clonal expansion.

Gamma-ray irradiation, using the cobalt-60 isotope, is the most common radiation modality used for medical device and biopharmaceutical products sterilization. Although X-ray and electron-beam (e-beam) sterilization technologies are mature and have been in use for decades, impediments remain to switching to these sterilization modalities because of lack of data on the resulting radiation effects for the associated polymers, as well as a lack of education for manufacturers and regulators on the viability of these sterilization alternatives. For this study, the compatibility of ethylene vinyl acetate (EVA) multilayer films with different ionizing radiation sterilization (X-ray, e-beam, and gamma irradiation) is determined by measuring chemical and physical film properties using high performance liquid chromatography, differential scanning calorimetry, Fourier-Transform InfraRed spectroscopy (FTIR), surface energy measurement, and electron spin resonance techniques. The results indicate that the three irradiation modalities induce no differences in thermal properties in the investigated dose range. Gamma and X-Ray irradiations generate the same level of reactive species in the EVA multilayer film, whereas e-beam generates a reduced quantity of reactive species., Competing Interests: NG-P, FG, SD are employed by Sartorius Stedim FMT S. A. S. LN is employed by Steri-Tek. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Sartorius. The funder had the following involvement in the study: study design, data collection and analysis, decision to publish, and preparation of the manuscript. The study also received funding from PNNL, TAMU and Steri-Tek. These funders had the following involvement in the study: irradiation and additional analysis (which was supported by the U.S. Department of Energy National Nuclear Security Administration Office of Radiological Security), study design, data collection and analysis, decision to publish, and preparation of the manuscript., (Copyright © 2022 Girard-Perier, Marque, Dupuy, Claeys-Bruno, Gaston, Dorey, Fifield, Ni, Li, Fuchs, Murphy, Pillai, Pharr and Nichols.)

Objectives: To evaluate histologic changes in middle ear and eustachian tube (ET) mucosa of mice after exposure to tobacco or electronic cigarette (e-cigarette) smoke. To determine whether there were any mitigating effects of middle ear application of anti-IL-13 or the epidermal growth factor receptor antagonist AG1478 on noted changes within ET mucosa., Study Design: Controlled animal study., Methods: Fifty BALB/cJ mice were randomly assigned to one of five groups: A control group with no smoke exposure, two groups exposed to tobacco smoke, and two groups exposed to e-cigarette vapor. Within the exposed groups after 4 weeks of exposure, one ear was infiltrated with a saline hydrogel and the other ear with hydrogel of either Anti-IL-13 or AG1478. After four more weeks of exposure, the animals were euthanized and the ETs were evaluated for mucosal changes., Results: Compared to control animals with no smoke exposure, there were significant decreases in the numbers of goblet cells within the ET mucosa of mice exposed to tobacco smoke and e-cigarette vapor. No significant differences in cilia, mucin, or squamous metaplasia were noted. Neither anti-IL-13 nor AG178 significantly altered goblet cell count in the ET mucosa of mice exposed to tobacco smoke; however, both agents significantly increased goblet cells within the ET mucosa of mice exposed to e-cigarette vapor., Conclusion: Short-term tobacco smoke and e-cigarette vapor significantly decrease goblet cell count in mouse ET mucosa. Middle ear application of both anti-IL-13 and AG1478 resulted in an increase in goblet cell count among mice exposed to e-cigarette vapor, but not to tobacco smoke., Level of Evidence: NA Laryngoscope, 132:648-654, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Regulation of BCR signaling has important consequences for generating effective Ab responses to pathogens and preventing production of autoreactive B cells during development. Currently defined functions of Fc receptor-like (FCRL) 1 include positive regulation of BCR-induced calcium flux, proliferation, and Ab production; however, the mechanistic basis of FCRL1 signaling and its contributions to B cell development remain undefined. Molecular characterization of FCRL1 signaling shows phosphotyrosine-dependent associations with GRB2, GRAP, SHIP-1, and SOS1, all of which can profoundly influence MAPK signaling. In contrast with previous characterizations of FCRL1 as a strictly activating receptor, we discover a role for FCRL1 in suppressing ERK activation under homeostatic and BCR-stimulated conditions in a GRB2-dependent manner. Our analysis of B cells in Fcrl1 -/- mice shows that ERK suppression by FCRL1 is associated with a restriction in the number of cells surviving splenic maturation in vivo. The capacity of FCRL1 to modulate ERK activation presents a potential for FCRL1 to be a regulator of peripheral B cell tolerance, homeostasis, and activation., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Using a recombinant protein antigen for antibody testing shows a sum of antibody responses to multiple different immune epitopes existing in the protein antigen. In contrast, the antibody testing to an immunogenic peptide epitope reflects a singular antibody response to the individual peptide epitope. Therefore, using a panel of peptide epitopes provides an advantage for profiling multiple singular antibody responses with potential to estimate recent malaria exposure in human infections. However, transitioning from malaria immune epitope peptide-based ELISA to an all peptide bead-based multiplex Luminex assay presents some challenges including variation in the ability of different peptides to bind beads. The aim of this study was to develop a peptide coupling method while demonstrating the utility of these peptide epitopes from multiple stage antigens of Plasmodium falciparum for measuring antibodies. Successful coupling of peptide epitopes to beads followed three steps: 1) development of a peptide tag appended to the C-terminus of each peptide epitope consisting of beta-alanine-lysine (x 4)--cysteine, 2) bead modification with a high concentration of adipic acid dihydrazide, and 3) use of the peptide epitope as a blocker in place of the traditional choice, bovine serum albumin (BSA). This new method was used to couple 12 peptide epitopes from multiple stage specific antigens of P. falciparum, 1 Anopheles mosquito salivary gland peptide, and 1 Epstein-Barr virus peptide as an assay control. The new method was applied to testing of IgG in pooled samples from 30 individuals with previously repeated malaria exposure in western Kenya and IgM and IgG in samples from 37 U.S. travelers with recent exposure to malaria. The new peptide-bead coupling method and subsequent multiplex Luminex assay showed reliable detection of IgG to all 14 peptides in Kenyan samples. Among 37 samples from U.S. travelers recently diagnosed with malaria, IgM and IgG to the peptide epitopes were detected with high sensitivity and variation. Overall, the U.S. travelers had a much lower positivity rates of IgM than IgG to different peptide epitopes, ranging from a high of 62.2% positive for one epitope to a low of only 5.4% positive for another epitope. In contrast, the travelers had IgG positive rates from 97.3% to 91.9% to various peptide epitopes. Based on the different distribution in IgM and IgG positivity to overall number of peptide epitopes and to the number of pre-erythrocytic, erythrocytic, gametocytic, and salivary stage epitopes at the individual level, four distinct patterns of IgM and IgG responses among the 37 samples from US travelers were observed. Independent peptide-bead coupling and antibody level readout between two different instruments also showed comparable results. Overall, this new coupling method resolves the peptide-bead coupling challenge, is reproducible, and can be applied to any other immunogenic peptide epitopes. The resulting all peptide bead-based multiplex Luminex assay can be expanded to include other peptide epitopes of P. falciparum, different malaria species, or other diseases for surveillance, either in US travelers or endemic areas., (Published by Elsevier B.V.)

Understanding radiation-induced chemical and physical transformations at material interfaces is important across diverse fields, but experimental approaches are often limited to either ex situ observations or in situ electron microscopy or synchrotron-based methods, in which cases the radiation type and dose are inextricably tied to the imaging basis itself. In this work, we overcome this limitation by demonstrating integration of an x-ray source with an atomic force microscope to directly monitor radiolytically driven interfacial chemistry at the nanoscale. We illustrate the value of in situ observations by examining effects of radiolysis on material adhesion forces in aqueous solution as well as examining the production of alkali nitrates at the interface between an alkali halide crystal surface and air. For the examined salt-air interface, direct visualization under flexible experimental conditions greatly extends prior observations by enabling the transformation process to be followed comprehensively from source-to-sink with mass balance quantitation. Our novel rad-atomic force microscope opens doors into understanding the dynamics of radiolytically driven mass transfer and surface alteration at the nanoscale in real-time.

Objective/hypothesis: Glutamine inhibition has been demonstrated an antifibrotic effect in iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts in vitro. We hypothesize that broadly active glutamine antagonist, DON will reduce collagen formation and fibrosis-associated gene expression in iLTS mice., Study Design: Prospective controlled animal study., Methods: iLTS in mice were induced by chemomechanical injury of the trachea using a bleomycin-coated wire brush. PBS or DON (1.3 mg/kg) were administered by intraperitoneal injection (i.p.) every other day. Laryngotracheal complexes were harvested at days 7 and 14 after the initiation of DON treatment for the measurement of lamina propria thickness, trichrome stain, immunofluorescence staining of collagen 1, and fibrosis-associated gene expression., Results: The study demonstrated that DON treatment reduced lamina propria thickness (P = .025) and collagen formation in trichrome stain and immunofluorescence staining of collagen 1. In addition, DON decreased fibrosis-associated gene expression in iLTS mice. At day 7, DON inhibited Col1a1 (P < .0001), Col3a1 (P = .0046), Col5a1 (P < .0001), and Tgfβ (P = .023) expression. At day 14, DON reduced Co1a1 (P = .0076) and Tgfβ (P = .023) expression., Conclusions: Broadly active glutamine antagonist, DON, significantly reduces fibrosis in iLTS mice. These results suggest that the concept of glutamine inhibition may be a therapeutic option to reduce fibrosis in the laryngotracheal stenosis., Level of Evidence: N/A Laryngoscope, 131:E2125-E2130, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Signaling lymphocyte activation molecule family member 9 (SLAMF9) is a cell surface protein of the CD2/SLAM family of leukocyte surface receptors. It is conserved throughout mammals and has roles in the initiation of inflammatory responses and regulation of plasmacytoid dendritic cell function. Through comparison of reference sequences encoding SLAMF9 in human, mouse, and primate sequences, we have determined that the SLAMF9 gene underwent successive mutation events, resulting in the loss of the protein and subsequent recovery of a less stable version. The mutations included a single base pair deletion in the second exon and a change in the splice acceptor site of that same exon. These changes would have had the effect of creating and later repairing a frameshift in the coding sequence. These events took place since the divergence of the human lineage from the chimpanzee-human last common ancestor and represent the first known case of the functional loss and recovery of a gene within the human lineage.

Reproductive hardship is highly stigmatized, which leads to such struggles being relegated to the private sphere. At the same time, numerous studies show links between toxic chemicals and reproductive hardship including miscarriage, infertility, and birth defects. There thus exists a disconnection between structural contributors to reproductive challenges and the fact that such hardship is frequently viewed as a personal problem. Considering this tension, this qualitative study sought to examine how women who had both experienced reproductive difficulty and lived proximal to hydraulic fracturing operations made sense of their experiences. Analysis revealed that participants emphasized hydraulic fracturing as economically essential at the same time that they tended to minimize fracking as a potential contributor to reproductive hardship., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Murphy, Soyer, Ziyanak and Godfrey.)

Radiation driven reactions at mineral/air interfaces are important to the chemistry of the atmosphere, but experimental constraints (e.g. simultaneous irradiation, in situ observation, and environmental control) leave process understanding incomplete. Using a custom atomic force microscope equipped with an integrated X-ray source, transformation of potassium bromide surfaces to potassium nitrate by air radiolysis species was followed directly in situ at the nanoscale. Radiolysis initiates dynamic step edge dissolution, surface composition evolution, and ultimately nucleation and heteroepitaxial growth of potassium nitrate crystallites mediated by surface diffusion at rates controlled by adsorbed water. In contrast to in situ electron microscopy and synchrotron-based imaging techniques where high radiation doses are intrinsic, our approach illustrates the value of decoupling irradiation and the basis of observation., (© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: Idiopathic subglottic stenosis (iSGS) is an inflammatory process leading to fibrosis and narrowing of the laryngotracheal airway. There is variability in patient response to surgical intervention, but the mechanisms underlying this variability are unknown. In this pilot study, we measure expression of candidate targets at the mucosal surface of the subglottis in iSGS patients. We aim to identify putative biomarkers for iSGS that provide insights into the molecular basis of disease progression, yield a gene signature for the disease, and/or predict a response to therapy., Study Design: In vitro comparative study of human cells., Methods: Levels of candidate transcripts and proteins were measured in healthy and stenotic laryngotracheal tissue specimens taken from the mucosal surface in 16 iSGS patients undergoing endoscopic balloon dilation. Pre- and post-operative pulmonary function test and patient reported voice and breathing outcomes were also assessed. Unsupervised clustering was used to define patient subgroups based on expression profile., Results: Pulmonary function and voice and breathing outcome metrics demonstrated significant post-operative improvement. Transcript levels of αSMA, CCL2, COL1A1, COL3A1, FN1, IFNG, and TGFB1 and protein levels of CCL2, IFNG, and IL-6 were significantly upregulated in stenotic as compared to healthy tissues. Marked heterogeneity was observed in the patterns of expression of candidate markers across individuals and tissue types. Patient subgroups defined by expression profile did not show a statistically significant difference in dilation interval., Conclusion: Pro-inflammatory and pro-fibrotic pathways are significantly upregulated along the mucosal surface of stenotic laryngotracheal tissues, and CCL2 and IFNG merit further investigation as potential iSGS biomarkers., Level of Evidence: 4 Laryngoscope, 131:342-349, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Macrophages exhibit distinct phenotypes and are dysregulated in a model of iatrogenic laryngotracheal stenosis (iLTS). Increased populations of alternatively activated or M2 macrophages have been demonstrated. However, the role of these macrophages is unknown. The aims of this study are: 1) define the macrophage population in iLTS in the context of classically activated or M1 and M2 macrophage phenotypes, and 2) characterize the effect of monocyte-derived M1 and M2 macrophages on normal airway and LTS-derived fibroblasts (FBs) in vitro., Study Design: Comparative analysis; in vitro controlled study., Methods: Immunohistochemical analysis of human iLTS and control specimens was performed to define the macrophage population. In vitro, M1, and M2 macrophages were polarized using M-CSF + Interferon-gamma and lipopolysaccharide or Interleukin-4, respectively. FBs isolated from laryngotracheal scar (LTS-FBs) and normal tracheal airway (NA-FBs) in eight patients with iLTS were cocultured with polarized macrophages. Fibrosis gene expression, soluble collagen production, and proliferation were assessed., Results: Immunohistochemical analysis revealed increased CD11b + cells (macrophage marker) in laryngotracheal scar specimens (18.3% vs. 8.5%, P = .03) and predominant CD206 (M2) costaining versus CD86 (M1) (51.5% vs. 9.8%, n = 10, P = .001). In vitro, NA-FBs cultured with M2 macrophages demonstrated a 2.41-fold increase in collagen-1 expression (P = .05, n = 8) and an increase in soluble collagen (9.98 vs. 8.875, mean difference: 1.11 95%, confidence interval 0.024-2.192, n = 8, P = .015)., Conclusion: Increased populations of CD11b cells are present in iLTS specimens and are predominantly CD206+, indicating an M2 phenotype. In vitro, M2 macrophages promoted collagen expression in airway FBs. Targeting macrophages may represent a therapeutic strategy for attenuating fibrosis in iLTS., Level of Evidence: NA Laryngoscope, 131:E346-E353, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, The Triological Society and American Laryngological Association (ALA).)

Objectives/hypothesis: Glutamine metabolism is a critical energy source for iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts, and glutaminase (GLS) is an essential enzyme converting glutamine to glutamate. We hypothesize that the GLS-specific inhibitor BPTES will block glutaminolysis and reduce iLTS scar fibroblast proliferation, collagen deposition, and fibroblast metabolism in vitro., Study Design: Test-tube Lab Research., Methods: Immunohistochemistry of a cricotracheal resection (n = 1) and a normal airway specimen (n = 1) were assessed for GLS expression. GLS expression was assessed in brush biopsies of subglottic/tracheal fibrosis and normal airway from patients with iLTS (n = 6). Fibroblasts were isolated and cultured from biopsies of subglottic/tracheal fibrosis (n = 6). Fibroblast were treated with BPTES and BPTES + dimethyl α-ketoglutarate (DMK), an analogue of the downstream product of GLS. Fibroblast proliferation, gene expression, protein production, and metabolism were assessed in all treatment conditions and compared to control., Results: GLS was overexpressed in brush biopsies of iLTS scar specimens (P = .029) compared to normal controls. In vitro, BPTES inhibited iLTS scar fibroblast proliferation (P = .007), collagen I (Col I) (P < .0001), collagen III (P = .004), and α-smooth muscle actin (P = .0025) gene expression and protein production (P = .031). Metabolic analysis demonstrated that BPTES reduced glycolytic reserve (P = .007) but had no effects on mitochondrial oxidative phosphorylation. DMK rescued BPTES inhibition of Col I gene expression (P = .0018) and protein production (P = .021)., Conclusions: GLS is overexpressed in iLTS scar. Blockage of GLS with BPTES significantly inhibits iLTS scar fibroblasts proliferation and function, demonstrating a critical role for GLS in iLTS. Targeting GLS to inhibit glutaminolysis may be a successful strategy to reverse scar formation in the airway., Level of Evidence: NA Laryngoscope, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

There is a growing population of ageing individuals living with acquired immunodeficiency syndrome (HIV). Older adults living with HIV often contend with intersecting stigmas including HIV stigma, ageism, and for some, homonegativity and/or racism. Although the HIV stigma literature is quite robust, research on the relationship between HIV stigma, social support, and mental well-being among older adults living with HIV is limited. This study begins to address this gap by examining how intersectional stigma affects social support and mental wellbeing among rural-dwelling older adults living with HIV. Qualitative interviews were conducted by phone with 29 older adults living with HIV, over the age of 50, living in rural areas of the United States. Interviews were transcribed verbatim and analyzed using thematic content analysis in MAXQDA qualitative analysis software. Analysis revealed three primary themes. The first had to do with gossip and non-disclosure of HIV status, which intersected with ageism and homonegativity to exacerbate experiences that fell within the remaining themes of experiences of physical and psychological isolation and loneliness, and shame and silence surrounding depression. The prevalence of social isolation and the effects of limited social support among older adults living with HIV are prominent and indicate a need for tailored interventions within the HIV care continuum for older adults living with HIV.

Strong school-based vision and eye health systems include 12 key components to be implemented before, during, and after the actual vision screening event. The National Center for Children's Vision and Eye Health (NCCVEH) at Prevent Blindness partnered with the National Association of School Nurses (NASN) to provide guidance for school nurses for each of the 12 key components via a Vision and Eye Health webpage on the NASN website ( https://www.nasn.org/nasn-resources/practice-topics/vision-health ). This online resource is designed to support school nurses accountable for vision screening and maintaining the eye health of preschool- and school-age children. This NCCVEH/NASN webpage addresses key activities that provide overall support for a child's vision and eye health-beginning with parent/caregiver education and ending with an annual evaluation of the school's vision and eye health system. NASN School Nurse is publishing information about each of these 12 components. The May 2019 installment provided details about the 12 Components approach as a whole and Components 1 and 2: Family Education and a Comprehensive Communication/Approval Process. The July 2019 edition described Components 3 and 4: Vision Screening Tools and Procedures and Vision Health for Children With Special Health Care Needs. This article describes Component 5: Standardized Approach for Rescreening.

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aim to help nurses provide caregivers with the tools they need to manage their family member's health care at home.The articles in this new installment of the series provide simple and useful instructions that nurses should reinforce with family caregivers. This article is the second of two that explain the nutritional principles nurses should consider and reinforce with caregivers. Each article includes an informational tear sheet-Information for Family Caregivers-that contains links to the instructional videos. To use this series, nurses should read the article first, so they understand how best to help family caregivers, and then encourage caregivers to watch the videos and ask questions. For additional information, see Resources for Nurses.

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home.The articles in this new installment of the series provide simple and useful instructions regarding nutritional principles that nurses should reinforce with family caregivers. Most articles include an informational tear sheet-Information for Family Caregivers-that contains links to the instructional videos. To use this series, nurses should read the article first, so they understand how best to help family caregivers, and then encourage caregivers to watch the videos and ask questions. For additional information, see Resources for Nurses and Resources for Family Caregivers.

Irradiators utilizing radioactive cesium-137 ( 137 Cs) or cobalt-60 ( 60 Co) gamma-ray sources have been used for biological applications for many decades. These applications include irradiation of much of the nation's blood supply and radiation biology research. In 2005, the U.S. Nuclear Regulatory Commission was assigned the task of preventing the misuse of radioactive materials by persons with malicious intentions; gamma-ray sources, in particular, were given high priority. This resulted in increased security requirements, including constant surveillance, controlled access and personnel background checks. As a result of such regulations being introduced, organizations considering the purchase of a gamma-ray irradiator for the first time or as a replacement to an existing one due to radioactive decay, are now looking into alternative technologies, primarily an X-ray irradiator. To make an educated decision on whether a particular type of X-ray irradiator is of sufficient equivalency to a particular type of 137 Cs irradiator for specific applications, one must rely on relevant published comparison studies from other researchers, or perform the comparison studies on their own. This work focuses on the comparison of the radiation physics aspects of two 137 Cs irradiator models and three X-ray irradiator models, for the purpose of determining whether the X-ray irradiator models could validly replace the 137 Cs irradiator models for certain applications. Although evaluating the influence of relative biological effectiveness (RBE) differences among irradiators could be part of this study, that has been left for a related publication focused on the theoretical aspects of this topic. These evaluations were performed utilizing 47-g and 120-g tissue-equivalent rodent dosimetry phantoms. Our results indicate that, depending upon the user's dose uncertainty budget and maximum areal density of specimens to be irradiated, the RS 2000 160 kVp X-ray irradiator, X-RAD160 X-ray irradiator or X-RAD320 X-ray irradiator could successfully replace a 137 Cs irradiator. Technically, any X-ray irradiator model providing similar irradiation geometry, and average energy similar to or higher than these three X-ray models, could also successfully replace a 137 Cs irradiator. The results also reveal that differences in inherent source geometry, field geometry and irradiation geometry can counter some of the influence due to differences in energy spectrum. Our goal is that this publication be used as a guide for other similar studies, providing investigators with information on important details that can make the difference between strong and weak comparison conclusions.

Successful vision screening efforts require the implementation of 12 key components of a strong vision health system of care. The National Center for Children's Vision and Eye Health (NCCVEH) at Prevent Blindness partnered with the National Association of School Nurses (NASN) to provide guidance around these 12 components via a Vision and Eye Health webpage on the NASN website ( https://www.nasn.org/nasn-resources/practice-topics/vision-health ). This online resource is organized according to the 12 Components of a Strong Vison Health System of Care to support school nurses accountable for screening the vision of preschool and K-12 students. This NCCVEH/NASN webpage addresses key activities that support a child's vision health-beginning with parent/caregiver education and ending with an annual evaluation of the school's vision health system. Each of these 12 components will be described in NASN School Nurse . The May 2019 installment provided information about the 12 components approach as a whole and details on Family Education and a Comprehensive Communication/Approval Process. This installment describes Components 3 and 4: Vision Screening Tools and Procedures and Vision Health for Children with Special Health Care Needs.

The National Center for Children's Vision and Eye Health (NCCVEH) at Prevent Blindness partnered with the National Association of School Nurses (NASN) to provide guidance for school nurses responsible for screening the vision of preschool and K-12 students. Goals of this national partnership are to (1) standardize approaches to vision health, (2) facilitate follow up to eye care for students who do not pass vision screening, (3) provide family/caregiver friendly educational information, and (4) consult with leading pediatric eye care experts to promote evidence-based best practices. The NCCVEH/NASN partnership created a Vision and Eye Health page on the NASN website ( https://www.nasn.org/nasn-resources/practice-topics/vision-health ). This resource is organized according to the 12 Components of a Strong Vision Health System of Care. The 12 components emerged as the NCCVEH considered vision screening from a systems perspective. This systems perspective addresses key activities along the entire spectrum of care that supports a child's vision health-beginning with parent/caregiver education and ending with an annual evaluation of the school's vision health system. Each of these 12 components will be described in 4 installments of NASN School Nurse in 2019. This installment describes the first two components: Family Education and a Comprehensive Communication/Approval Process.

Objective/hypothesis: This prospective controlled human and murine study assessed the presence of inflammatory cells and cytokines to test the hypothesis that immune cells are associated with fibroproliferation in iatrogenic laryngotracheal stenosis (iLTS)., Methods: Inflammation was assessed by histology and immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), and flow cytometry of cricotracheal resections of iLTS patients compared to normal controls. An iLTS murine model assessed the temporal relationship between inflammation and fibrosis., Results: iLTS specimens showed increased inflammation versus normal controls (159/high power field [hpf] vs. 119/hpf, P = 0.038), and increased CD3 + T-cells, CD4 + cells, and CD3+/CD4 + T-helper (T H ) cells (all P < 0.05). The inflammatory infiltrate was located immediately adjacent to the epithelial surface in the superficial aspect of the thickened lamina propria. Human flow cytometry and qRT-PCR showed a significant increase in interleukin (IL)-4 gene expression, indicating a T H 2 phenotype. Murine IF revealed a dense CD4 + T-cell inflammatory infiltrate on day 4 to 7 postinjury, which preceded the development of fibrosis. Murine flow cytometry and qRT-PCR studies mirrored the human ones, with increased T-helper cells and IL-4 in iLTS versus normal controls., Conclusion: CD3/CD4 + T-helper lymphocytes and the proinflammatory cytokine IL-4 are associated with iLTS. The association of a T H 2 immunophenotype with iLTS is consistent with findings in other fibroinflammatory disorders. The murine results reveal that the inflammatory infiltrate precedes the development of fibrosis. However, human iLTS specimens with well-developed fibrosis also contain a marked chronic inflammatory infiltrate, suggesting that the continued release of IL-4 by T-helper lymphocytes may continue to propagate iLTS., Level of Evidence: NA Laryngoscope, 129:177-186, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Home parenteral nutrition (HPN) is a life-sustaining therapy for short bowel syndrome (SBS) and other severe digestive diseases, but complications are common. We evaluated a predischarge HPN hands-on training course to reduce complications in children with SBS, including hospital readmissions., Methods: We conducted a prospective, nonrandomized controlled research study between April 1, 2014, and April 30, 2017. Eligible participants were children aged <18 years old with SBS and anticipated HPN dependence duration ≥6 months. Excluded participants had a previous history of discharge with a central venous catheter (CVC), HPN, or intravenous fluids or strictly palliative goals of care. An intervention group practiced hands-on HPN within the hospital room for 24 hours using infusion equipment. The groups received standard teaching (CVC care, home infusion pump operation, HPN preparation and administration)., Results: Nine children were assigned to the intervention group and 12 served as controls. The median age was 8.4 months, and length of stay (LOS) was 82 days. All participants experienced ≥1 event, with a total of 47 issues related to HPN. There were no significant associations between group assignment and 30-day postdischarge events. Each additional week of LOS was associated with 11% increase in the odds of an emergency department visit (OR 1.11; 95% CI, 1.01-1.26) and 16% increase in the odds of readmission (OR 1.16; 95% CI, 1.04-1.37)., Conclusions: Postdischarge events remained widespread despite HPN bedside interventions offered by this pilot intervention. With refinement of HPN discharge processes, quality benchmarks are needed., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Objective: Management of laryngotracheal stenosis (LTS) remains primarily surgical, with a critical need to identify targets for adjuvant therapy. Laryngotracheal stenosis scar fibroblasts exhibit a profibrotic phenotype with distinct metabolic shifts, including an increased glycolysis/oxidative phosphorylation ratio. This study examines the effects of the glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) on collagen production, gene expression, proliferation, and metabolism of human LTS-derived fibroblasts in vitro., Method: Paired normal and scar-derived fibroblasts isolated from subglottic and proximal tracheal tissue in patients with iatrogenic laryngotracheal stenosis (iLTS) were cultured. Proliferation rate, gene expression, protein production, and cellular metabolism were assessed in two conditions: 1) fibroblast growth medium, and 2) fibroblast growth medium with 1 × 10 -4 M DON., Results: DON treatment reduced cellular proliferation rate (n = 7, P =  0.0150). Expression of genes collagen 1 and collagen 3 both were reduced (n = 7, P =  0.0102, 0.0143, respectively). Soluble collagen production decreased (n = 7, P =  0.0056). As measured by the rate of extracellular acidification, glycolysis and glycolytic capacity decreased (n = 7, P =  0.0082, 0.0003, respectively). adenosine triphosphate (ATP) production and basal respiration decreased (n = 7, P = 0.0045, 0.0258, respectively), determined by measuring the cellular rate of oxygen consumption., Conclusion: The glutamine antagonist DON reverses profibrotic changes by inhibiting both glycolysis and oxidative phosphorylation in iLTS scar fibroblasts. In contrast to untreated iLTS scar fibroblasts, collagen gene expression, protein production, metabolic rate, and proliferation were significantly reduced. These results suggest DON and/or its derivatives as strong candidates for adjuvant therapy in the management of iatrogenic laryngotracheal stenosis. Enzymes involved in glutamine metabolism inhibited by DON offer targets for future investigation., Level of Evidence: NA. Laryngoscope, 128:E59-E67, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Home parenteral nutrition (HPN) and home intravenous (IV) hydration are complex, high-risk life-sustaining therapies for children and adults with severe digestive disorders. HPN compounding errors have the potential to cause serious patient harm. Here we present a retrospective case series at an interdisciplinary pediatric HPN program that includes specialized pharmacists reconciling prescriptions against commercial compounding records. Seven HPN or IV hydration patients were affected by significant errors in anion balance, copper, potassium, sodium, and infusion volume. Outpatient pharmacists' or other clinicians' review of compounding records as part of routine quality assurance process is critical for identifying and preventing errors.

Importance: Laryngotracheal stenosis (LTS) is a fibroproliferative disorder of the glottis, subglottis, and trachea. In models of fibrosis from other organ systems, the CD4+ T-cell response has been shown to regulate extracellular matrix deposition. Specifically, helper T cell 2 (TH2) promotes fibrosis, whereas TH1 and associated cytokines have been shown to be antifibrotic. However, this antifibrotic effect of the TH1 response has not been demonstrated in LTS., Objective: To determine whether the TH1 cytokine interferon-γ inhibits the function of LTS-derived fibroblasts in vitro., Design, Setting, and Participants: This in vitro controlled study included 6 patients with iatrogenic LTS undergoing routine surgical subglottic and tracheal dilation at a single institution. Fibroblasts were isolated from biopsy specimens of laryngotracheal scar and normal-appearing trachea. The presence of fibroblasts was confirmed by an immunohistochemical analysis. Laryngotracheal stenosis-derived fibroblasts were treated with interferon-γ and compared with untreated controls (2 sets of untreated, LTS-derived fibroblasts [media did not contain interferon-γ]) and normal airway fibroblasts (fibroblasts isolated from normal trachea). Data were collected from August 2015 through June 2016., Interventions: Treatment with interferon-γ, 10 ng/mL., Main Outcomes and Measures: Cellular proliferation, fibrosis gene expression (using quantitative reverse transcription polymerase chain reaction analysis), soluble collagen, and cellular histologic features were assessed., Results: Among the 6 patients (6 women; mean [SD] age, 38.3 [17.2] years), LTS-derived fibroblast proliferation was reduced in patients who received interferon-γ treatment compared with untreated controls on days 3 (mean difference, -6515 cells; 95% CI, -10 630 to -2600 cells) to 6 (mean difference, -47 521 cells; 95% CI, -81 285 to -13 757 cells). Interferon-γ treatment reduced collagen types I and III gene expression by 86% and 68%, respectively, and resulted in lower total collagen production (10.94 vs 14.89 μg/mL). In addition, interferon-γ treatment resulted in a 32% reduction in expression of transforming growth factor β in LTS-derived fibroblasts., Conclusions and Relevance: Interferon-γ reduced proliferation, soluble collagen production, and collagen expression in LTS-derived fibroblasts while also reducing the expression of the profibrotic cytokine transforming growth factor β. These findings suggest that therapeutics aimed at increasing interferon-γ and the TH1 response could attenuate LTS.

Objectives (1) Develop a novel method for serial assessment of gene and protein expression in laryngotracheal stenosis (LTS). (2) Assess cytokine expression and determine an immunophenotype in LTS. Study Design A matched comparison of endolaryngeal brush biopsy samples from laryngotracheal scar and normal airway. Setting Tertiary care hospital, 2015-2016. Methods Brush biopsy specimens of laryngotracheal scar and normal trachea were obtained from 17 patients with LTS at the time of operating room dilation and were used for protein and RNA extraction. Gene expression of the T H 1 cytokine interferon γ (INF-γ), T H 2 cytokine interleukin 4 (IL-4), transforming growth factor β, and collagen 1 (Coll1) was quantified with quantitative real-time polymerase chain reaction. Cytokine analysis was performed with flow cytometry with a cytometric bead array. Results LTS specimens demonstrated a 13.68-fold increase in Coll1 gene expression versus normal ( P < .001, N = 17). Additionally, IL-4 gene expression showed a 3.76-fold increase ( P < .001, N = 17) in LTS scar. When stratified into iatrogenic LTS and idiopathic subglottic stenosis cohorts, INF-γ gene expression was significantly increased in idiopathic subglottic stenosis ( P = .011). Soluble cytokine measurements were below the limit of detection for reliable quantification and thus could not be assessed. Conclusions Brush biopsies from LTS samples can be successfully utilized for RNA extraction and demonstrate the expected increase in Coll1 gene expression associated with LTS. Preliminary gene expression suggests that abnormal collagen production may be mediated by the T H 2 cytokine IL-4 and that increased INF-γ expression may represent a key difference between iatrogenic LTS and idiopathic subglottic stenosis. Further analysis of soluble cytokines is needed to confirm these findings.

Evaluations of neutron survey instruments, area monitors, and personal dosimeters rely on reference neutron radiations, which have evolved from the heavy reliance on (α,n) sources to a shared reliance on (α,n) and the spontaneous fission neutrons of californium-252 (Cf). Capable of producing high dose equivalent rates from an almost point source geometry, the characteristics of Cf are generally more favorable when compared to the use of (α,n) and (γ,n) sources or reactor-produced reference neutron radiations. Californium-252 is typically used in two standardized configurations: unmoderated, to yield a fission energy spectrum; or with the capsule placed within a heavy-water moderating sphere to produce a softened spectrum that is generally considered more appropriate for evaluating devices used in nuclear power plant work environments. The U.S. Department of Energy Cf Loan/Lease Program, a longtime origin of affordable Cf sources for research, testing and calibration, was terminated in 2009. Since then, high-activity sources have become increasingly cost-prohibitive for laboratories that formerly benefited from that program. Neutron generators, based on the D-T and D-D fusion reactions, have become economically competitive with Cf and are recognized internationally as important calibration and test standards. Researchers from the National Institute of Standards and Technology and the Pacific Northwest National Laboratory are jointly considering the practicality and technical challenges of implementing neutron generators as calibration standards in the U.S. This article reviews the characteristics of isotope-based neutron sources, possible isotope alternatives to Cf, and the rationale behind the increasing favor of electronically generated neutron options. The evaluation of a D-T system at PNNL has revealed characteristics that must be considered in adapting generators to the task of calibration and testing where accurate determination of a dosimetric quantity is necessary. Finally, concepts are presented for modifying the generated neutron spectra to achieve particular targeted spectra, simulating Cf or workplace environments.

Study Objective: Long-acting reversible contraceptive (LARC) methods are the most effective forms of reversible contraception but adolescents often opt for other, less effective methods. In this study we explored how adolescents viewed LARC as an innovation to be adopted or rejected, and how their assessment of innovation attributes affected their decisions about LARC. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Sexually active adolescents between 15 and 22 years old (n = 22) participated in semistructured qualitative interviews. The data underwent a content analysis informed by constructs of the diffusion of innovations and emergent interview themes., Results: Data analysis indicated 3 subgroups of participants on the basis of their inclination to use LARC and the mutability of that position: positive/persuaded (n = 7), negative/low knowledge (n = 10), and negative/adamant (n = 5). Participants' perceptions of the relative advantage, compatibility, complexity, trialability, and observability of LARC cohered around subgroup membership. Perceived complexity entailed in obtaining LARC and fears about LARC were observed across all participants. All participants believed that one has to try LARC to know how it will work for her, personally. This led the positive/persuaded group to be undeterred by others' negative experiences with LARC and the negative/low knowledge and negative/adamant groups to decide LARC was too risky to try., Conclusion: Adolescents engage in nuanced evaluations of LARC, weighing competing information about LARC while receiving anecdotal and empirical information about LARC from various valid sources. To reduce the uncertainty about LARC that prohibits trying these methods, adolescents require straightforward information about LARC that directly addresses the advantages of LARC over other methods coupled with candid acknowledgement of the potential disadvantages of LARC., (Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Background: Nursing home (NH) residents who require assistance during mealtimes are at risk for malnutrition. Supportive handfeeding is recommended, yet there is limited evidence supporting use of a specific handfeeding technique to increase meal intake., Objectives: To compare efficacy of three handfeeding techniques for assisting NH residents with dementia with meals: Direct Hand (DH), Over Hand (OH), and Under Hand (UH)., Design: A prospective pilot study using a within-subjects experimental Latin square design with randomization to one of three handfeeding technique sequences., Setting and Participants: 30 residents living with advanced dementia in 11 U.S. NHs., Measurements: Time required for assistance; meal intake (% eaten); and feeding behaviors, measured by the Edinburgh Feeding Evaluation in Dementia (EdFED) scale., Intervention: Research Assistants provided feeding assistance for 18 video-recorded meals per resident (N = 540 meals). Residents were assisted with one designated technique for 6 consecutive meals, changing technique every 2 days., Results: Mean time spent providing meal assistance did not differ significantly between techniques. Mean meal intake was greater for DH (67 ± 15.2%) and UH (65 ± 15.0%) with both significantly greater than OH (60 ± 15.1%). Feeding behaviors were more frequent with OH (8.3 ± 1.8%), relative to DH (8.0 ± 1.8) and UH (7.7 ± 1.8)., Conclusion: All three techniques are time neutral. UH and DH are viable options to increase meal intake among NH residents with advanced dementia and reduce feeding behaviors relative to OH feeding., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Study Objective: Long-acting reversible contraceptive (LARC) methods are the most effective form of reversible contraception but are underutilized by adolescents. The purpose of this study was to identify the context-specific barriers to providing adolescents with LARC that are experienced by pediatricians, family medicine physicians, and advanced practice nurses (APNs)., Design, Setting, Participants, and Interventions: Pediatricians, family medicine providers, and APNs (n = 16) who care for adolescents participated in semistructured qualitative interviews. Interview data were analyzed using a modified grounded theory approach., Main Outcome Measures: Pediatricians, family medicine physicians, and APNs self-reported attitudes and practices regarding LARC provision to adolescents., Results: Provider confidence in LARC, patient-centered counseling on LARC, and instrumental supports for LARC all work interdependently either in support of or in opposition to provision of LARC to adolescents. Low provider confidence in LARC for adolescents was characterized by confusion about LARC eligibility criteria and perceptions of LARC insertion as traumatic for adolescents. Patient-centered counseling on LARC required providers' ability to elicit patient priorities, highlight the advantages of LARC over other methods, and address patients' concerns about these methods. Instrumental support for LARC included provider training on LARC, access to and financial support for LARC devices, and opportunity to practice LARC insertion and counseling skills., Conclusion: Although none of the identified essential components of LARC provision to adolescents exist in isolation, instrumental support like provider training on LARC and access to LARC devices have the most fundamental effect on the other components and on providers' attitudes and practices regarding LARC for adolescents., Competing Interests: None of the authors have any conflicts of interest to report., (Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

A sudden cardiac arrest in school or at a school event is potentially devastating to families and communities. An appropriate response to such an event-as promoted by developing, implementing, and practicing a cardiac emergency response plan (CERP)-can increase survival rates. Understanding that a trained lay-responder team within the school can make a difference in the crucial minutes between the time when the victim collapses and when emergency medical services arrive empowers school staff and can save lives. In 2015, the American Heart Association convened a group of stakeholders to develop tools to assist schools in developing CERPs. This article reviews the critical components of a CERP and a CERP team, the factors that should be taken into account when implementing the CERP, and recommendations for policy makers to support CERPs in schools., (© 2016 The Author(s).)

Objective: To test the hypothesis that a substantial proportion of laryngoscopes exhibit substandard illuminance by comparing laryngoscope illuminance in a tertiary-level medical center to established standards and identifying features associated with poor illuminance., Study Design: Cross-sectional observational study., Setting: Academic tertiary care medical center (level 1 trauma center, specialty cardiac hospital, and general hospital)., Subjects and Methods: Laryngoscopes from main, cardiac, and outpatient operating rooms; emergency department; and code carts were tested using a standard technique. Illuminance (lux) was chosen as the outcome measure. Benchmarks were derived from the International Standards Organization and medical literature. Light types included incandescent bulb, light-emitting diode, and xenon. Personnel were surveyed regarding maintenance practices., Results: Across all hospitals, 691 laryngoscopes were tested. Mean (SD) illuminance was 810 (700) lux for incandescent bulb-on-blade designs (n = 237), 1860 (1220) lux for incandescent bulb in-handle designs (n = 79), 4730 (3210) lux for LED (n = 354), and 28,800 (34,500) lux for xenon (n = 21). Seven percent of units failed to turn on (n = 45). Using an established threshold of 867 lux, 28% of devices (47% of incandescent, 12% of LED, and 10% of xenon) were substandard. All laryngoscopes were cleaned according to standard protocols following use; no preventive maintenance was reported., Conclusion: Twenty-eight percent of laryngoscopes in a tertiary care hospital exhibit substandard illuminance; these results corroborate the findings of our inaugural study on this subject. Consequently, our hospital is instituting changes to reduce the likelihood of substandard performance by laryngoscopes in circulation., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Unlabelled: Antibodies that can neutralize diverse viral strains are likely to be an important component of a protective human immunodeficiency virus type 1 (HIV-1) vaccine. To this end, preclinical simian immunodeficiency virus (SIV)-based nonhuman primate immunization regimens have been designed to evaluate and enhance antibody-mediated protection. However, these trials often rely on a limited selection of SIV strains with extreme neutralization phenotypes to assess vaccine-elicited antibody activity. To mirror the viral panels used to assess HIV-1 antibody breadth, we created and characterized a novel panel of 14 genetically and phenotypically diverse SIVsm envelope (Env) glycoproteins. To assess the utility of this panel, we characterized the neutralizing activity elicited by four SIVmac239 envelope-expressing DNA/modified vaccinia virus Ankara vector- and protein-based vaccination regimens that included the immunomodulatory adjuvants granulocyte-macrophage colony-stimulating factor, Toll-like receptor (TLR) ligands, and CD40 ligand. The SIVsm Env panel exhibited a spectrum of neutralization sensitivity to SIV-infected plasma pools and monoclonal antibodies, allowing categorization into three tiers. Pooled sera from 91 rhesus macaques immunized in the four trials consistently neutralized only the highly sensitive tier 1a SIVsm Envs, regardless of the immunization regimen. The inability of vaccine-mediated antibodies to neutralize the moderately resistant tier 1b and tier 2 SIVsm Envs defined here suggests that those antibodies were directed toward epitopes that are not accessible on most SIVsm Envs. To achieve a broader and more effective neutralization profile in preclinical vaccine studies that is relevant to known features of HIV-1 neutralization, more emphasis should be placed on optimizing the Env immunogen, as the neutralization profile achieved by the addition of adjuvants does not appear to supersede the neutralizing antibody profile determined by the immunogen., Importance: Many in the HIV/AIDS vaccine field believe that the ability to elicit broadly neutralizing antibodies capable of blocking genetically diverse HIV-1 variants is a critical component of a protective vaccine. Various SIV-based nonhuman primate vaccine studies have investigated ways to improve antibody-mediated protection against a heterologous SIV challenge, including administering adjuvants that might stimulate a greater neutralization breadth. Using a novel SIV neutralization panel and samples from four rhesus macaque vaccine trials designed for cross comparison, we show that different regimens expressing the same SIV envelope immunogen consistently elicit antibodies that neutralize only the very sensitive tier 1a SIV variants. The results argue that the neutralizing antibody profile elicited by a vaccine is primarily determined by the envelope immunogen and is not substantially broadened by including adjuvants, resulting in the conclusion that the envelope immunogen itself should be the primary consideration in efforts to elicit antibodies with greater neutralization breadth., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)