Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration.

BMP and Wnt signaling pathways control essential cellular responses through activation of the transcription factors SMAD (BMP) and TCF (Wnt). Here, we show that regeneration of hematopoietic lineages following acute injury depends on the activation of each of these signaling pathways to induce expression of key blood genes. Both SMAD1 and TCF7L2 co-occupy sites with master regulators adjacent to hematopoietic genes. In addition, both SMAD1 and TCF7L2 follow the binding of the predominant lineage regulator during differentiation from multipotent hematopoietic progenitor cells to erythroid cells. Furthermore, induction of the myeloid lineage regulator C/EBPα in erythroid cells shifts binding of SMAD1 to sites newly occupied by C/EBPα, whereas expression of the erythroid regulator GATA1 directs SMAD1 loss on nonerythroid targets. We conclude that the regenerative response mediated by BMP and Wnt signaling pathways is coupled with the lineage master regulators to control the gene programs defining cellular identity.

Author Correction: Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Clinical Utility of Laser Speckle Contrast Imaging and Real-Time Quantification of Bowel Perfusion in Minimally Invasive Left-Sided Colorectal Resections.

BACKGROUND: Left-sided colorectal surgery demonstrates high anastomotic leak rates, with tissue ischemia thought to influence outcomes. Indocyanine green is commonly used for perfusion assessment, but evidence remains mixed for whether it reduces colorectal anastomotic leaks. Laser speckle contrast imaging provides dye-free perfusion assessment in real-time through perfusion heat maps and quantification. OBJECTIVE: This study investigates the efficacy of advanced visualization (indocyanine green versus laser speckle contrast imaging), perfusion assessment, and utility of laser speckle perfusion quantification in determining ischemic margins. DESIGN: Prospective intervention group using advanced visualization with case-matched, retrospective control group. SETTINGS: Single academic medical center. PATIENTS: Forty adult patients undergoing elective, minimally invasive, left-sided colorectal surgery. INTERVENTIONS: Intraoperative perfusion assessment using white light imaging and advanced visualization at 3 time points: T1-proximal colon after devascularization, before transection, T2-proximal/distal colon before anastomosis, and T3-completed anastomosis. MAIN OUTCOME MEASURES: Intraoperative indication of ischemic line of demarcation before resection under each visualization method, surgical decision change using advanced visualization, post hoc laser speckle perfusion quantification of colorectal tissue, and 30-day postoperative outcomes. RESULTS: Advanced visualization changed surgical decision-making in 17.5% of cases. For cases in which surgeons changed a decision, the average discordance between the line of demarcation in white light imaging and advanced visualization was 3.7 cm, compared to 0.41 cm ( p = 0.01) for cases without decision changes. There was no statistical difference between the line of ischemic demarcation using laser speckle versus indocyanine green ( p = 0.16). Laser speckle quantified lower perfusion values for tissues beyond the line of ischemic demarcation while suggesting an additional 1 cm of perfused tissue beyond this line. One (2.5%) anastomotic leak occurred in the intervention group. LIMITATIONS: This study was not powered to detect differences in anastomotic leak rates. CONCLUSIONS: Advanced visualization using laser speckle and indocyanine green provides valuable perfusion information that impacts surgical decision-making in minimally invasive left-sided colorectal surgeries. See Video Abstract . UTILIDAD CLNICA DE LAS IMGENES DE CONTRASTE MOTEADO CON LSER Y LA CUANTIFICACIN EN TIEMPO REAL DE LA PERFUSIN INTESTINAL EN RESECCIONES COLORRECTALES DEL LADO IZQUIERDO MNIMAMENTE INVASIVAS: ANTECEDENTES:La cirugía colorrectal del lado izquierdo demuestra altas tasas de fuga anastomótica, y se cree que la isquemia tisular influye en los resultados. El verde de indocianina se utiliza habitualmente para evaluar la perfusión, pero la evidencia sobre si reduce las fugas anastomóticas colorrectales sigue siendo contradictoria. Las imágenes de contraste moteado con láser proporcionan una evaluación de la perfusión sin colorantes en tiempo real a través de mapas de calor de perfusión y cuantificación.OBJETIVO:Este estudio investiga la eficacia de la evaluación de la perfusión mediante visualización avanzada (verde de indocianina versus imágenes de contraste moteado con láser) y la utilidad de la cuantificación de la perfusión con moteado láser para determinar los márgenes isquémicos.DISEÑO:Grupo de intervención prospectivo que utiliza visualización avanzada con un grupo de control retrospectivo de casos emparejados.LUGARES:Centro médico académico único.PACIENTES:Cuarenta pacientes adultos sometidos a cirugía colorrectal electiva, mínimamente invasiva, del lado izquierdo.INTERVENCIONES:Evaluación de la perfusión intraoperatoria mediante imágenes con luz blanca y visualización avanzada en tres puntos temporales: T1-colon proximal después de la devascularización, antes de la transección; T2-colon proximal/distal antes de la anastomosis; y T3-anastomosis completa.PRINCIPALES MEDIDAS DE VALORACIÓN:Indicación intraoperatoria de la línea de demarcación isquémica antes de la resección bajo cada método de visualización, cambio de decisión quirúrgica mediante visualización avanzada, cuantificación post-hoc de la perfusión con láser moteado del tejido colorrectal y resultados posoperatorios a los 30 días.RESULTADOS:La visualización avanzada cambió la toma de decisiones quirúrgicas en el 17,5% de los casos. Para los casos en los que los cirujanos cambiaron una decisión, la discordancia promedio entre la línea de demarcación en las imágenes con luz blanca y la visualización avanzada fue de 3,7 cm, en comparación con 0,41 cm (p = 0,01) para los casos sin cambios de decisión. No hubo diferencias estadísticas entre la línea de demarcación isquémica utilizando láser moteado versus verde de indocianina (p = 0,16). El moteado con láser cuantificó valores de perfusión más bajos para los tejidos más allá de la línea de demarcación isquémica y al mismo tiempo sugirió 1 cm adicional de tejido perfundido más allá de esta línea. Se produjo una fuga anastomótica (2,5%) en el grupo de intervención.LIMITACIONES:Este estudio no tuvo el poder estadístico suficiente para detectar diferencias en las tasas de fuga anastomótica.CONCLUSIONES:La visualización avanzada utilizando moteado láser y verde de indocianina proporciona información valiosa sobre la perfusión que impacta la toma de decisiones quirúrgicas en cirugías colorrectales mínimamente invasivas del lado izquierdo. (Traducción-Dr. Ingrid Melo).

Dye-less quantification of tissue perfusion by laser speckle contrast imaging is equivalent to quantified indocyanine green in a porcine model.

INTRODUCTION: Subjective surgeon interpretation of near-infrared perfusion video is limited by low inter-observer agreement and poor correlation to clinical outcomes. In contrast, quantification of indocyanine green fluorescence video (Q-ICG) correlates with histologic level of perfusion as well as clinical outcomes. Measuring dye volume over time, however, has limitations, such as it is not on-demand, has poor spatial resolution, and is not easily repeatable. Laser speckle contrast imaging quantification (Q-LSCI) is a real-time, dye-free alternative, but further validation is needed. We hypothesize that Q-LSCI will distinguish ischemic tissue and correlate over a range of perfusion levels equivalent to Q-ICG. METHODS: Nine sections of intestine in three swine were devascularized. Pairs of indocyanine green fluorescence imaging and laser speckle contrast imaging video were quantified within perfused, watershed, and ischemic regions. Q-ICG used normalized peak inflow slope. Q-LSCI methods were laser speckle perfusion units (LSPU), the base unit of laser speckle imaging, relative perfusion units (RPU), a previously described methodology which utilizes an internal control, and zero-lag normalized cross-correlation (X-Corr), to investigate if the signal deviations convey accurate perfusion information. We determine the ability to distinguish ischemic regions and correlation to Q-ICG over a perfusion gradient. RESULTS: All modalities distinguished ischemic from perfused regions of interest; Q-ICG values of 0.028 and 0.155 (p < 0.001); RPU values of 0.15 and 0.68 (p < 0.001); and X-corr values of 0.73 and 0.24 (p < 0.001). Over a range of perfusion levels, RPU had the best correlation with Q-ICG (r = 0.79, p < 0.001) compared with LSPU (r = 0.74, p < 0.001) and X-Corr (r = 0.46, p < 0.001). CONCLUSION: These results demonstrate that Q-LSCI discriminates ischemic from perfused tissue and represents similar perfusion information over a broad range of perfusion levels comparable to clinically validated Q-ICG. This suggests that Q-LSCI might offer clinically predictive real-time dye-free quantification of tissue perfusion. Further work should include validation in histologic studies and human clinical trials.

Characterization of a novel pulse normalization technology for beam scanning of small fields without a reference chamber.

PURPOSE: A novel pulse normalization technology enabling the acquisition of low noise beam data without the use of a physical reference chamber has recently been commercially released. The purpose of this study was to characterize the use of this technology for beam scanning of small fields required in the commissioning of a stereotactic radiotherapy program. METHODS: Three detectors (Edge diode, microDiamond, PinPoint) were used to acquire beam data under three conditions: with a reference chamber, with pulse normalization and no reference chamber (PN), and without pulse normalization and no reference chamber (nPN). Percent depth dose (PDD) scans were acquired for 0.5, 1.0, 2.0, and 3.0 cm2 field sizes and profiles were acquired at 1.4, 10, and 30 cm depths using continuous scanning. The coefficient of variation (CoV) was calculated for all beam data to compare signal-to-noise and gamma comparisons (1%, 1 mm) were calculated of the PN and nPN scans compared to the reference data. RESULTS: Average 95th percentile CoV values were similar for all detectors across conditions, with PN data being comparable to reference data and minor increases observed for nPN data. Mean gamma pass rates for PN PDD scans exceeded 98% for all detectors. Profile gamma pass rates were 100% for all detectors at 1.4 and 10 cm depth. At 30 cm depth, profiles acquired with the PinPoint and microDiamond detectors had lower mean gamma pass rates than the Edge, at 95% and 95.7%, respectively. CONCLUSIONS: A novel pulse normalization technology was demonstrated to be effective for acquiring beam profiles and PDDs for small fields without the use of a physical reference chamber. Limitations in how the method is implemented led to some errors in data acquired using lower sensitivity detectors. When used with a diode, pulse normalization produced equivalent scans to those acquired with a reference chamber.

Importin-9 regulates chromosome segregation and packaging in Drosophila germ cells.

Germ cells undergo distinct nuclear processes as they differentiate into gametes. Although these events must be coordinated to ensure proper maturation, the stage-specific transport of proteins in and out of germ cell nuclei remains incompletely understood. Our efforts to genetically characterize Drosophila genes that exhibit enriched expression in germ cells led to the finding that loss of the highly conserved Importin ß/karyopherin family member Importin-9 (Ipo9, herein referring to Ranbp9) results in female and male sterility. Immunofluorescence and fluorescent in situ hybridization revealed that Ipo9KO mutants display chromosome condensation and segregation defects during meiosis. In addition, Ipo9KO mutant males form abnormally structured sperm and fail to properly exchange histones for protamines. Ipo9 physically interacts with proteasome proteins, and Ipo9 mutant males exhibit disruption of the nuclear localization of several proteasome components. Thus, Ipo9 coordinates the nuclear import of functionally related factors necessary for the completion of gametogenesis. This article has an associated First Person interview with the first author of the paper.

Mycosynthesis of Zinc Oxide Nanoparticles Exhibits Fungal Species Dependent Morphological Preference.

Filamentous fungi can synthesize a variety of nanoparticles (NPs), a process referred to as mycosynthesis that requires little energy input, do not require the use of harsh chemicals, occurs at near neutral pH, and do not produce toxic byproducts. While NP synthesis involves reactions between metal ions and exudates produced by the fungi, the chemical and biochemical parameters underlying this process remain poorly understood. Here, the role of fungal species and precursor salt on the mycosynthesis of zinc oxide (ZnO) NPs is investigated. This data demonstrates that all five fungal species tested are able to produce ZnO structures that can be morphologically classified into i) well-defined NPs, ii) coalesced/dissolving NPs, and iii) micron-sized square plates. Further, species-dependent preferences for these morphologies are observed, suggesting potential differences in the profile or concentration of the biochemical constituents in their individual exudates. This data also demonstrates that mycosynthesis of ZnO NPs is independent of the anion species, with nitrate, sulfate, and chloride showing no effect on NP production. These results enhance the understanding of factors controlling the mycosynthesis of ceramic NPs, supporting future studies that can enable control over the physical and chemical properties of NPs formed through this "green" synthesis method.

Preliminary evidence that misalignment between sleep and circadian timing alters risk-taking preferences.

Decision-making has been shown to suffer when circadian preference is misaligned with time of assessment; however, little is known about how misalignment between sleep timing and the central circadian clock impacts decision-making. This study captured naturally occurring variation in circadian alignment (i.e., alignment of sleep-wake timing with the central circadian clock) to examine if greater misalignment predicts worse decision-making. Over the course of 2 weeks, 32 late adolescent drinkers (aged 18-22 years; 61% female; 69% White) continuously wore actigraphs and completed two overnight in-laboratory visits (Thursday and Sunday) in which both dim-light melatonin onset (DLMO) and behavioural decision-making (risk taking, framing, and strategic reasoning tasks) were assessed. Sleep-wake timing was assessed by actigraphic midsleep from the 2 nights prior to each in-laboratory visit. Alignment was operationalised as the phase angle (interval) between average DLMO and average midsleep. Multilevel modelling was used to predict performance on decision-making tasks from circadian alignment during each in-laboratory visit; non-linear associations were also examined. Shorter DLMO-midsleep phase angle predicted greater risk-taking under conditions of potential loss (B = -0.11, p = 0.06), but less risk-taking under conditions of potential reward (B = 0.14, p = 0.03) in a curvilinear fashion. Misalignment did not predict outcomes in the framing and strategic reasoning tasks. Findings suggest that shorter alignment in timing of sleep with the central circadian clock (e.g., phase-delayed misalignment) may impact risky decision-making, further extending accumulating evidence that sleep/circadian factors are tied to risk-taking. Future studies will need to replicate findings and experimentally probe whether manipulating alignment influences decision-making.

The Biologically Relevant Coordination Chemistry of Iron and Nitric Oxide: Electronic Structure and Reactivity.

Nitric oxide (NO) is an important signaling molecule that is involved in a wide range of physiological and pathological events in biology. Metal coordination chemistry, especially with iron, is at the heart of many biological transformations involving NO. A series of heme proteins, nitric oxide synthases (NOS), soluble guanylate cyclase (sGC), and nitrophorins, are responsible for the biosynthesis, sensing, and transport of NO. Alternatively, NO can be generated from nitrite by heme- and copper-containing nitrite reductases (NIRs). The NO-bearing small molecules such as nitrosothiols and dinitrosyl iron complexes (DNICs) can serve as an alternative vehicle for NO storage and transport. Once NO is formed, the rich reaction chemistry of NO leads to a wide variety of biological activities including reduction of NO by heme or non-heme iron-containing NO reductases and protein post-translational modifications by DNICs. Much of our understanding of the reactivity of metal sites in biology with NO and the mechanisms of these transformations has come from the elucidation of the geometric and electronic structures and chemical reactivity of synthetic model systems, in synergy with biochemical and biophysical studies on the relevant proteins themselves. This review focuses on recent advancements from studies on proteins and model complexes that not only have improved our understanding of the biological roles of NO but also have provided foundations for biomedical research and for bio-inspired catalyst design in energy science.

Technical note: Commissioning of a low-cost system for directly 3D printed flexible bolus.

PURPOSE: To present the commissioning process of a low-cost solution for directly 3D printed flexible patient specific bolus. METHODS: The 3D printing solution used in this study consisted of a resin stereolithography 3D printer and a flexible curing resin. To test the dimensional accuracy of the 3D printer, rectangular cuboids with varying dimensions were 3D printed and their measured dimensions were compared to the designed dimensions. Percent Depth Dose (PDD) profiles were measured by irradiating film embedded in a 3D printed phantom made of the flexible material. A CT of the phantom was acquired and used to replicate the irradiation setup in the treatment planning system. PDDs were calculated for both the native HU of the phantom, and with the phantom HU overridden to 300 HU to match its physical density. Dosimetric agreement was characterized by comparing calculated to measured depths of R90, R80, and R50. Upon completion of the commissioning process, a bolus was 3D printed for a clinical case study for treatment of the nose. RESULTS: Dimensional accuracy of the printer and material combination was found to be good, with all measured dimensions of test cuboids within 0.5 mm of designed. PDD measurements demonstrated the best dosimetric agreement when the material was overridden to 300 HU, corresponding to the measured physical density of the material of 1.18 g/cc. Calculated and measured depths of R90, R80, and R50 all agreed within 1 mm. The bolus printed for the clinical case was free from defects, highly conformal, and led to a clinically acceptable plan. CONCLUSION: The results of the commissioning measurements performed indicate that the 3D printer and material solution are suitable for clinical use. The 3D printer and material combination can provide a low-cost solution a clinic can implement in-house to directly 3D print flexible bolus.

A hybrid method to improve efficiency of patient specific SRS and SBRT QA using 3D secondary dose verification.

PURPOSE: Patient Specific QA (PSQA) by direct phantom measurement for all intensity modulated radiation therapy (IMRT) cases is labor intensive and an inefficient use of the Medical Physicist's time. The purpose of this work was to develop a hybrid quality assurance (QA) technique utilizing 3D dose verification as a screening tool to determine if a measurement is necessary. METHODS: This study utilized Sun Nuclear DoseCHECK (DC), a 3D secondary verification software, and Fraction 0, a trajectory log IMRT QA software. Twenty-two Lung stereotactic body radiation therapy (SBRT) and thirty single isocentre multi-lesion SRS (MLSRS) plans were retrospectively analysed in DC. Agreement of DC and the TPS dose for selected dosimetric criteria was recorded. Calculated 95% confidence limits (CL) were used to establish action limits. All cases were delivered and measured using the Sun Nuclear stereotactic radiosurgery (SRS) MapCheck. Trajectory logs of the delivery were used to calculate Fraction 0 results for the same criteria calculated by DC. Correlation of DC and Fraction 0 results were calculated. Phantom measured QA was compared to Fraction 0 QA results for the cases which had DC criteria action limits exceeded. RESULTS: Correlation of DC and Fraction 0 results were excellent, demonstrating the same action limits could be used for both and DC can predict Fraction 0 results. Based on the calculated action limits, zero lung SBRT cases and six MLSRS cases were identified as requiring a measurement. All plans that passed the DC screening had a passing measurement based PSQA and agreed with Fraction 0 results. CONCLUSION: Using 95% CL action limits of dosimetric criteria, a 3D secondary dose verification can be used to determine if a measurement is required for PSQA. This method is efficient for it is part of the normal clinical workflow when verifying any clinical treatment. In addition, it can drastically reduce the number of measurements needed for PSQA.

HEMATOLOGIC AND BIOCHEMICAL VALUES OF FREE-RANGING HAWKSBILL SEA TURTLES (ERETMOCHELYS IMBRICATA) IN GLOVER'S REEF, BELIZE.

Blood samples were obtained from the dorsal cervical sinus of free-ranging hawksbill sea turtles (Eretmochelys imbricata) collected at Glover's Reef Marine Reserve, 42 km east of the coast of Belize, for hematology and plasma biochemistry analysis. Unknown sex, subadult turtles (N = 32) were sampled in 2013 (n = 22) and 2017 (n = 10). To provide a more robust data set, parameters that did not have statistically significant differences were pooled and treated as a single population. Eleven hematologic parameters were evaluated; of these, five were pooled. Twenty-three plasma biochemical parameters were evaluated; of these, 15 were pooled. The PCV observed in this study (mean 33.44%) was double that observed in two studies of juvenile hawksbills in Dubai (means 17% and 16%), whereas the total WBC count was half that observed in immature and adult hawksbills sampled in the Galápagos (mean 2.91 × 103 versus 5.3 × 103/µl). Total protein and albumin were lower than regionally similar, adult female hawksbills in Brazil (means 3.36 versus 5.45 g/dl and 0.93 versus 2.11 g/dl, respectively). Globulins were higher (mean 2.43 versus 1.06 and 0.5 g/dl), driving the albumin:globulin ratio lower than that observed in two studies of juvenile hawksbills in Dubai (0.4:1 versus 1.1:1 and 1:1, respectively). These findings represent a geographically distinct population from previous reports, highlight the variability in blood parameters from disparate populations, and reaffirm the vital importance of considering a multitude of variables when interpreting reptilian blood values. The similarities in the majority of values observed in 2013 and 2017 provide confidence in the stability of these parameters in this population.

The 24-hour rhythm in alcohol craving and individual differences in sleep characteristics and alcohol use frequency.

BACKGROUND: Evidence implicates sleep/circadian factors in alcohol use, suggesting the existence of a 24-h rhythm in alcohol craving, which may vary by individual differences in sleep factors and alcohol use frequency. This study sought to (1) replicate prior findings of a 24-h rhythm in alcohol craving, and (2) examine whether individual differences in sleep timing, sleep duration, or alcohol use frequency are related to differences in the timing of the peak of the craving rhythm (i.e., the acrophase) or magnitude of fluctuation of the rhythm (i.e., amplitude). Finally, whether such associations varied by sex or racial identity was explored. METHODS: Two-hundred fifteen adult drinkers (21 to 35 years of age, 72% male, 66% self-identified as White) completed a baseline assessment of alcohol use frequency and then smartphone reports of alcohol craving intensity six times a day across 10 days. Sleep timing was also recorded each morning of the 10-day period. Multilevel cosinor analysis was used to test the presence of a 24-h rhythm and to estimate acrophase and amplitude. RESULTS: Multilevel cosinor analysis revealed a 24-h rhythm in alcohol craving. Individual differences in sleep timing or sleep duration did not predict rhythm acrophase or amplitude. However, alcohol use frequency moderated this rhythm wherein individuals who used alcohol more frequently in the 30 days prior to beginning the study had higher mean levels of craving and greater rhythm amplitudes (i.e., greater rhythmic fluctuations). Associations did not vary by sex or racial identity. CONCLUSIONS: Results show that alcohol craving exhibits a systematic rhythm over the course of the 24 h and that the frequency of alcohol use may be relevant to the shape of this rhythm. Consideration of daily rhythms in alcohol craving may further our understanding of the mechanisms that drive alcohol use.

Cubic Crystal Structure Formation and Optical Properties within the Ag-BII-MIV-X (BII = Sr, Pb; MIV = Si, Ge, Sn; X = S, Se) Family of Semiconductors.

Quaternary chalcogenide semiconductors are promising materials for energy conversion and nonlinear optical applications, with properties tunable primarily by varying the elemental composition and crystal structure. Here, we first analyze the connections among several cubic crystal structure types, as well as the orthorhombic Ag2PbGeS4-type structure, reported for select members within the Ag-BII-MIV-X (BII = Sr, Pb; MIV = Si, Ge, Sn; X = S, Se) compositional space. Focusing on the Ag-Pb-Si-S and Ag-Sr-Sn-S systems, we show that one structure type, with the formulas Ag2Pb3Si2S8 and Ag2Sr3Sn2S8, is favored. We have prepared powder and single-crystal samples of Ag2Pb3Si2S8 and Ag2Sr3Sn2S8, showing that each takes on the noncentrosymmetric cubic space group I4̅3d and is isostructural to the previously reported compound Ag2Sr3Ge2Se8. Through hybrid density functional theory calculations, these cubic compounds are demonstrated to be (quasi-)direct band gap semiconductors with high densities of states at the band maxima. The band-gap energies are measured by reflectance spectroscopy as 1.95(3) and 2.66(4) eV for Ag2Pb3Si2S8 and Ag2Sr3Sn2S8, respectively. We further measure the optical properties and show the electronic band structures of three other isostructural AI-BII-MIV-X-type materials, i.e., Ag2Sr3Si2S8, Ag2Sr3Ge2S8, and Ag2Sr3Ge2Se8, showing that the band gaps can be predictably tuned by element substitution. Detailed visual analyses of the different structures and of their relationships with other members of the Ag-BII-MIV-X compositional family provide a basis for a broader understanding of the structure formation and optoelectronic properties within the quaternary chalcogenide semiconductor family.

Syntheses and studies of deuterated Imdiazo[1,2-a]pyridine-3-carboxamides with potent anti-tuberculosis activity and improved metabolic properties.

The imidazo[1,2-a]pyridine-3-carboxyamides (IAPs) are a unique class of compounds endowed with impressive nanomolar in vitro potency against Mycobacterium tuberculosis (Mtb) as exemplified by clinical candidate Telacebec (Q203). These compounds target mycobacterial respiration through inhibition of the QcrB subunit of cytochrome bc1:aa3 super complex resulting in bacteriostatic efficacy in vivo. Our labs have had a long-standing interest in the design and development of IAPs. However, some of these compounds suffer from short in vivo half-lives, requiring multiple daily dosing or the addition of a cytochrome P450 inhibitor for murine efficacy evaluations. Deuteration has been shown to decrease metabolism as the C-D bond is stronger than the CH bond. Herein we describe our efforts on design and synthesis of potent deuterated IAPs and the effect that deuteration has upon metabolism through microsomal stability studies.

Assessment of Pain, Healing Time, and Wound Contraction in Postoperative Auricular Defects Healing Secondarily With and Without the Use of a Porcine Xenograft, a Pilot Study.

BACKGROUND: Postoperative auricular defects heal well with secondary intention healing (SIH); however, potential complications include postoperative pain, perichondritis, and chondritis. OBJECTIVE: To compare postoperative pain and wound healing in auricular defects healing by secondary intention with and without the placement of a porcine xenograft. MATERIALS AND METHODS: Twenty-one subjects were enrolled in the study. The primary outcome was self-reported pain, measured on a 0 to 10 scale for 14 postprocedure days. Secondary outcomes included time to greater than 90% of reepithelialization and degree of wound contraction. RESULTS: There was a 1 to 2 point difference in median pain scores between the porcine graft and control groups during postoperative days 4 to 7, 12, and 13. Time to 90% or greater reepithelialization was not statistically different between groups (p = .94). The average wound contraction was 34.1% for the porcine group and 34.0% for the control group (p = .95). CONCLUSION: In this pilot study, overall pain scores were low in both groups. Placement of a porcine xenograft resulted in a slight reduction of median pain compared with traditional SIH. Patients in the control group were more likely to require analgesics. Similar rates of reepithelialization and degree of wound contracture were observed.

Opioid Prescribing Patterns of Optometrists in the Medicare Part D Database.

SIGNIFICANCE: This study aimed to determine the prescription rates and prescribing trends of opioids by optometrists in the Centers for Medicare & Medicaid Services (CMS) part D database from 2013 to 2017 and to assess opioid prescribing patterns of U.S. optometrists in the CMS part D database. METHODS: With internal review board approval, a retrospective observational cohort study was conducted on optometrists listed in the CMS part D database who prescribed opioids from 2013 to 2017. RESULTS: There was an average of 26,477 optometrists in the CMS database from 2013 to 2017, of which 5.9% prescribed opioids. Of those prescribing opioids, optometrists wrote an average of 5.9 opioid prescriptions per year. Those writing greater than 10 opioid prescriptions averaged 24.2 annually. Overall, of opioid prescribing optometrists, opioid prescriptions comprised 7% of prescriptions written per year. CONCLUSIONS: Most optometrists do not prescribe opioids, and the vast majority of those who do write few opioid prescriptions. The total number of optometrists prescribing opioids and the total number of opioid prescriptions declined from 2013 to 2017. Further investigation into the opioid prescribing practices by optometrists will help better understand specific pain needs, as opioid prescribing patterns may differ depending on patient population.

Long-acting opioid prescribing patterns of ophthalmic plastic surgeons in the medicare Part D database.

PURPOSE: To assess extended release/long acting (ER/LA) opioid prescribing patterns among ophthalmic plastic surgeons in the Centers for Medicare and Medicaid Services (CMS) Part D database. METHODS: A retrospective observational cohort study was conducted on oculoplastic surgeons in the CMS Part D database who prescribed ER/LA opioids from 2013 to 2017. American Society of Ophthalmic Plastics and Reconstructive Surgery (ASOPRS) and non-ASOPRS surgeons were analyzed as groups. Prescribers were also analyzed based on gender and practice experience. RESULTS: Oculoplastic surgeons (64 ASOPRS and 78 non-ASOPRS) were responsible for 1,177 ER/LA opioid prescriptions from 2013 to 2017. ASOPRS members accounted for 4.6% and non-ASOPRS members accounted for 7.5% of all ER/LA opioids prescribed by ophthalmologists over the study period (p= .02). The total number of ASOPRS and non-ASOPRS members prescribing ER/LA opioids decreased by 52% (p= .10) and 58% (p= .07) from 2013 to 2017 respectively. CONCLUSION: ER/LA opioids are indicated for treatment of chronic pain and may be appropriately prescribed by the oculoplastic surgeon in certain circumstances, however due to the higher risk of overdose injury, those circumstances must be defined and justified. While a relatively small number of oculoplastic surgeons (10.6% ASOPRS and 19.6% non-ASOPRS) prescribed ER/LA opioids from 2013 to 2017, non-ASOPRS oculoplastic surgeons wrote 23.5% more ER/LA opioid prescriptions over the study period. Over the 5-year study period there was a general decline in the prescribing of ER/LA opioids by oculoplastic surgeons. Reviewing the prescribing practices of oculoplastic specialists, regardless of professional affiliation, is necessary to understand the role of ER/LA opioids for all of ophthalmology.

Evaluating online and tangible interfaces for engaging stakeholders in forecasting and control of biological invasions.

Ecological forecasts will be best suited to inform intervention strategies if they are accessible to a diversity of decision-makers. Researchers are developing intuitive forecasting interfaces to guide stakeholders through the development of intervention strategies and visualization of results. Yet, few studies to date have evaluated how user interface design facilitates the coordinated, cross-boundary management required for controlling biological invasions. We used a participatory approach to develop complementary tangible and online interfaces for collaboratively forecasting biological invasions and devising control strategies. A diverse group of stakeholders evaluated both systems in the real-world context of controlling sudden oak death, an emerging forest disease killing millions of trees in California and Oregon. Our findings suggest that while both interfaces encouraged adaptive experimentation, tangible interfaces are particularly well suited to support collaborative decision-making. Reflecting on the strengths of both systems, we suggest workbench-style interfaces that support simultaneous interactions and dynamic geospatial visualizations.

Structural, Optical, and Electronic Properties of Two Quaternary Chalcogenide Semiconductors: Ag2SrSiS4 and Ag2SrGeS4.

Quaternary chalcogenide materials have long been a source of semiconductors for optoelectronic applications. Recent studies on I2-II-IV-X4 (I = Ag, Cu, Li; II = Ba, Sr, Eu, Pb; IV = Si, Ge, Sn; X = S, Se) materials have shown particular versatility and promise among these compounds. These semiconductors take advantage of a diverse bonding scheme and chemical differences among cations to target a degree of antisite defect resistance. Within this set of compounds, the materials containing both Ag and Sr have not been experimentally studied and leave a gap in the full understanding of the family. Here, we have synthesized powders and single crystals of two Ag- and Sr-containing compounds, Ag2SrSiS4 and Ag2SrGeS4, each found to form in the tetragonal I4̅2m structure of Ag2BaGeS4. During the synthesis targeting the title compounds, two additional materials, Ag2Sr3Si2S8 and Ag2Sr3Ge2S8, have also been identified. These cubic compounds represent impurity phases during the synthesis of Ag2SrSiS4 and Ag2SrGeS4. We show through hybrid density functional theory calculations that Ag2SrSiS4 and Ag2SrGeS4 have highly dispersive band-edge states and indirect band gaps, experimentally measured as 2.08(1) and 1.73(2) eV, respectively. Second-harmonic generation measurements on Ag2SrSiS4 and Ag2SrGeS4 powders show frequency-doubling capabilities in the near-infrared range.