Electrodeposited MoxSyOz/Ni Tribological Coatings.

Deposition of molybdenum disulfide (MoS2) coatings using physical vapor deposition (PVD) and mechanical burnishing has been widely assessed for solid lubricants in space applications but still suffers from line-of-sight constraints on complex geometries. Here, we highlight one of the first demonstrations of electrodeposited MoxSyOz and MoxSyOz/Ni thin-film coatings from aqueous solutions of ammonium tetrathiomolybdate for solid lubricant applications and their remarkable ability to provide low coefficients of friction and high wear resistance. Characterization of the coating morphology shows amorphous microstructures with a high oxygen content and cracking upon drying. Even so, electrodeposited MoxSyOz can achieve low steady-state coefficients of friction (µ ∼ 0.05-0.06) and wear rates (2.6 × 10-7 mm3/(N m)) approaching those of physical vapor deposited coatings (2.3 × 10-7 mm3/(N m)). Additionally, we show that adding dopants such as nickel increased the wear rate (7.5 × 10-7 mm3/(N m)) and initial coefficient of friction (µi = 0.23) due to compositional modifications such as dramatic sub-stoichiometry (S/Mo ∼ 1) and expression of a NiOx surface layer, although doping did reduce the degree of cracking upon drying.

Resilience as a moderator of depression and anxiety: a bidimensional approach to predictors of subjective cognition in older adults.

OBJECTIVES: Subjective cognitive complaints (SCCs) have shown to be useful predictors of objective cognitive decline in older adults. Though psychopathology symptoms (e.g. depression, anxiety) have been linked to SCCs, little is known about the influence of positive psychology factors (e.g. resilience) on these complaints. The current study aimed to determine whether resilience predicts SCCs, and whether greater resilience moderates (or lessens) the effect of negative mental health symptoms on SCCs. METHODS: Four hundred twenty-eight adults aged 60 years or older (M = 67.6, SD = 5.9) were recruited to participate in an online Qualtrics survey study. Surveys included assessed psychological resilience [University of Washington Resilience Scale 8-item short form (UWRS-8)], depression [Geriatric Depression Scale (GDS-15)], anxiety [Geriatric Anxiety Scale (GAS-30)], and SCCs [Perceived Deficits Questionnaire-Depression (PDQ-D); Barkley Deficits in Executive Functioning Scale-Short Form (BDEFS-SF)]. RESULTS: Although greater resilience was only independently associated with less complaints on BDEFS total scores, resilience moderated (i.e. reduced) the negative effects of depression and anxiety on PDQ-D retrospective memory and planning subscales as well as BDEFS-SF total scores. Resilience also moderated (i.e. reduced) the negative effect of anxiety on PDQ-D total scores. CONCLUSION: With resilience lessening the effect of depression and anxiety on SCCS, our findings suggest positive psychological factors may be useful for understanding the prevalence of complaints. Future research should seek to replicate these findings and investigate relationships between additional positive psychological factors and cognitive health in old age including the use of both objective and subjective assessments of cognition.

Value-consistent rehabilitation is associated with long-term psychological flexibility and quality of life after traumatic brain injury.

Meaningful steps have been taken toward using holistic approaches in outpatient rehabilitation for traumatic brain injury (TBI) (i.e., treating the whole individual); however, research and practice continue to disproportionately focus on adapting to physical and cognitive changes. Research suggests treatment focusing on individual values may be important for psychological adjustment after TBI. The current study sought to explore individual values across multiple life domains in those with TBI as well as what values outpatient rehabilitation was helpful for, and to examine discrepancies between these factors (i.e., value-consistent rehabilitation) in relation to important long-term treatment outcomes. 215 adults with a history of TBI who had participated in outpatient rehabilitation completed online surveys assessing how consistent outpatient rehabilitation was with individual values, psychological flexibility, and quality of life. The life domains with the greatest discrepancies between individual importance and rehabilitation helpfulness were spirituality, intimate relations, and family relations. Greater value-consistent rehabilitation was associated with higher levels of psychological flexibility and quality of life beyond demographics and injury characteristics. Our findings provide further support in favour of holistic, client-centred approaches that are facilitated by neurological rehabilitation programs.

Coagulation Abnormalities and Clinical Complications in Children With SARS-CoV-2: A Systematic Review of 48,322 Patients.

Given the limited information on the coagulation abnormalities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in pediatric patients, we designed a systematic review to evaluate this topic. A comprehensive literature search was conducted for "SARS-CoV-2," "coagulopathy," and "pediatrics." Two authors independently screened the articles that the search returned for bleeding, thrombosis, anticoagulant and/or antiplatelet usage, and abnormal laboratory markers in pediatric patients with SARS-CoV-2, and the authors then extracted the relevant data. One hundred twenty-six publications were included. Thirty-four (27%) studies reported thrombotic complications in 504 patients. Thirty-one (25%) studies reported bleeding complications in 410 patients. Ninety-eight (78%) studies reported abnormal laboratory values in 6580 patients. Finally, 56 (44%) studies reported anticoagulant and/or antiplatelet usage in 3124 patients. The variety of laboratory abnormalities and coagulation complications associated with SARS-CoV-2 presented in this review highlights the complexity and variability of the disease presentation in infants and children.

Molecular understanding of heteronuclear active sites in heme-copper oxidases, nitric oxide reductases, and sulfite reductases through biomimetic modelling.

Heme-copper oxidases (HCO), nitric oxide reductases (NOR), and sulfite reductases (SiR) catalyze the multi-electron and multi-proton reductions of O2, NO, and SO32-, respectively. Each of these reactions is important to drive cellular energy production through respiratory metabolism and HCO, NOR, and SiR evolved to contain heteronuclear active sites containing heme/copper, heme/nonheme iron, and heme-[4Fe-4S] centers, respectively. The complexity of the structures and reactions of these native enzymes, along with their large sizes and/or membrane associations, make it challenging to fully understand the crucial structural features responsible for the catalytic properties of these active sites. In this review, we summarize progress that has been made to better understand these heteronuclear metalloenzymes at the molecular level though study of the native enzymes along with insights gained from biomimetic models comprising either small molecules or proteins. Further understanding the reaction selectivity of these enzymes is discussed through comparisons of their similar heteronuclear active sites, and we offer outlook for further investigations.

Emergency Department-Based Human Immunodeficiency Virus Preexposure Prophylaxis Referral Program-Using Emergency Departments as a Portal for Preexposure Prophylaxis Services.

ABSTRACT: A pilot program was implemented to assess the feasibility of emergency department (ED) preexposure prophylaxis (PrEP) referral. Of 119 eligible patients approached and assessed, 39 (33%) expressed interest and were referred to peer navigators. Of these, 16 (41%) scheduled for appointments; four (10%) initiated PrEP, which demonstrated ED-based PrEP referral was feasible.

Hepatic vascular malignancies in children are associated with increased rates of surgical resection and improved overall survival compared with adults.

BACKGROUND: Hepatic vascular malignancies (HVMs) are rare malignancies, with no standardized treatment regimens. The most common HVMs, angiosarcoma and malignant epithelioid hemangioendothelioma (EHE), are often grouped together in the literature complicating our ability to achieve reliable survival data and treatment strategies. OBJECTIVE: To compare the disease characteristics of HVMs, with a subanalysis on pediatric patients. METHODS: The 2016 National Cancer Database was queried for patients with HVMs using international classification of diseases-oncology-3 (ICD-O-3) codes yielding 699 patients. Descriptive statistics, chi-square, Kaplan-Meier, and log-rank analyses were performed. RESULTS: We found 478 patients (68%) with angiosarcoma and 221 (32%) with EHE. The median (Q1, Q3) age for angiosarcoma patients was 65 years (56, 75) versus 54 years (37, 65) in EHE patients (P < .001). The rate of resection was lower in patients with angiosarcoma than EHE (13% vs 32%, P < .001). The mean 1-, 3-, and 5-year overall survival for angiosarcoma patients was 17%, 8%, and 6%, respectively, versus 80%, 65%, and 62% in EHE patients (P < .0001). A subgroup analysis was performed on pediatric patients demonstrating six with angiosarcoma and 10 with EHE. The mean 1-, 3-, and 5-year overall survival for pediatric angiosarcoma patients was 67%, 50%, and 50%, respectively, and 90%, 90%, and 90% for pediatric EHE patients. CONCLUSION: In the largest study of HVMs to date, we found angiosarcoma has significantly worse overall survival than EHE. Pediatric patients appear to have improved survival and higher rates of resection. Larger studies of HVMs are needed to clearly differentiate tumor types, standardize care, and improve survivorship.

Laparoscopic experience and attitudes toward a low-cost laparoscopic system among surgeons in East, Central, and Southern Africa: a survey study.

BACKGROUND: Laparoscopic surgery has become standard of care in high-income countries but is rarely accessible in low- and middle-income countries (LMICs). This study assessed experience with laparoscopy and attitudes toward a low-cost laparoscopic system among surgeons in sub-Saharan Africa. METHODS: A survey assessing current laparoscopic practice and feedback on a low-cost laparoscopic system was administered to attendees of the College of Surgeons of East, Central, and Southern Africa (COSECSA) Scientific Conference between December 4 and December 6, 2019 in Kampala, Uganda. RESULTS: Fifty-six surgeons from 14 countries participated. A majority were male (n = 46, 82%) general surgeons (n = 37, 66%) from tertiary/teaching hospitals (n = 36, 64%). For those with training in laparoscopy (n = 33, 59%), 22 (67%) reported less than 1 year of training and over half (n = 17, 52%) reported 1 month or less. Overall, a minority (n = 21, 38%) used laparoscopy in current practice, with 57% (n = 12) of those performing laparoscopy less than once per week. The most common laparoscopic surgeries performed were cholecystectomy (n = 15), diagnostic laparoscopy (n = 14), and appendectomy (n = 12). Few surgeons were performing more complex cases (n = 5). Barriers to laparoscopy included poor access to training equipment (n = 34, 61%), mentors (n = 33, 59%), laparoscopic equipment (n = 31, 55%), equipment maintenance (n = 25, 45%), access to consumable supplies (n = 21, 38%), and cost (n = 31, 55%). Fifty-two participants (93%) were interested in increasing their use of laparoscopy; the majority felt that a low-cost laparoscope (n = 52, 93%) and lift retractor for gasless laparoscopy (n = 46, 82%) would serve an unmet need in their practice. CONCLUSIONS: While the use of laparoscopy is currently limited in COSECSA countries, there is a significant interest among surgeons to increase implementation. A low-cost, durable laparoscopic system was viewed as a potential solution to the current barriers and could improve implementation in LMICs.

Death Attitudes, Palliative Care Self-efficacy, and Attitudes Toward Care of the Dying Among Hospice Nurses.

Previous research has linked death attitudes, palliative care self-efficacy, and attitudes toward care of the dying among nursing students and other nursing samples, but not among hospice nurses. The purpose of this study was to investigate these relationships among hospice nurses (N = 90). More positive attitudes toward care of the dying were associated with lower fear of death and death avoidance as well as higher neutral acceptance and escape acceptance, but not with approach acceptance. More positive attitudes toward care of the dying was associated with perceived capability to answer end-of-life concerns, but not with perceived capability to respond to end-of-life symptoms. Clinical interventions seeking to improve attitudes toward care of the dying among hospice nurses may be most effective by targeting death attitudes and improving self-efficacy in the area of discussing end-of-life concerns with patients.

Reactivity of Diarylnitrenium Ions.

Hydride abstraction from diarylamines with the trityl ion is explored in an attempt to generate a stable diarylnitrenium ion, Ar2 N+ . Sequential H-atom abstraction reactions ensue. The first H-atom abstraction leads to intensely colored aminium radical cations, Ar2 NH.+ , some of which are quite stable. However, most undergo a second H-atom abstraction leading to ammonium ions, Ar2 NH2 + . In the absence of a ready source of H-atoms, a unique self-abstraction reaction occurs when Ar=Me5 C6 , leading to a novel iminium radical cation, Ar=N.+ Ar, which decays via a second self H-atom abstraction reaction to give a stable iminium ion, Ar=N+ HAr. These products differ substantially from those derived via photochemically produced diarylnitrenium ions.

Proteomic Analysis of Infants Undergoing Cardiopulmonary Bypass Using Contemporary Ontological Tools.

BACKGROUND: Cardiopulmonary bypass (CPB) is essential for the repair of many congenital cardiac defects in infants but is associated with significant derangements in hemostasis and systemic inflammation. As a result, hemorrhagic complications and thrombosis are major challenges in the management of children requiring CPB or extracorporeal membrane oxygenation. Conventional clinical laboratory tests capture individual hemostatic derangements (low platelets, elevated fibrinogen) but fail to describe the complex, overlapping interactions among the various components of coagulation, including cellular interactions, contact activation, fibrinolysis, and inflammation. Given recent advances in analytic tools for identifying protein-protein interactions in the plasma proteome, we hypothesized that an unbiased proteomic analysis would help identify networks of interacting proteins for further investigation in pediatric CPB. MATERIALS AND METHODS: Infants up to 1 y of age were enrolled. Plasma samples were collected at 0, 1, 4, and 24 h after CPB. Mass spectrometry was used to identify proteins undergoing changes in concentration after CPB, and STRING and ToppGene tools were used to identify biological networks. Two-dimensional difference gel electrophoresis identified changes in protein concentrations. Inflammatory markers were assessed by enzyme-linked immunosorbent assay at the same time points. RESULTS: Ten infants with cardiac anomalies requiring surgery and CPB were enrolled; no major complications were recorded (median age, 127.5 d; interquartile range, 181.25 d). Using two-dimensional difference gel electrophoresis, >1400 individual protein spots were observed, and 89 proteins demonstrated change in concentration >30% with P < 0.02 when comparing 1, 4, or 24 h to baseline. Among protein spots with significant changes in concentration after CPB, 29 were identified with mass spectrometry (33%). In our interrogation of functional associations among these differentially expressed proteins, our results were dominated by the acute phase response, coagulation, and cell signaling functional categories. Among cytokines analyzed by enzyme-linked immunosorbent assay, IL-2, IL-8, and IL-10 were elevated at 4 h but normalized by 24 h, whereas IL-6 was persistently elevated. CONCLUSIONS: Infants manifest a robust response to CPB that includes overlapping, complex pathways. Further investigation of interactions among immune, coagulation, and cell signaling systems may lead to novel therapeutics or biomarkers useful in the management of infants requiring CPB.

Intraluminal indocyanine green for intraoperative staple line leak testing in bariatric surgery.

BACKGROUND: Bariatric surgical procedures have recognized benefits for morbidly obese patients. Unfortunately, staple line leaks remain a profound complication after these procedures. Currently available intraoperative surveillance modalities have multiple drawbacks, such as requiring an available upper endoscope and experienced endoscopist. Additionally, increased procedure time and resources are needed to perform intraoperative endoscopy and maintain equipment. METHODS: This is a retrospective cohort study of all bariatric patients undergoing Roux-en-Y gastric bypass or sleeve gastrectomy procedures performed by one attending surgeon at a tertiary care facility designated as a bariatric surgical center of excellence. Patients were grouped based on procedure date being before (September 2016 to mid-October 2018) or after (mid-October 2018 to March 2019) implementation of a novel intraluminal indocyanine green leak testing protocol. Diluted indocyanine green was injected via orogastric bougie intraluminally at the location of the gastric staple line and observed with near-infrared imaging from the intraperitoneal perspective for evidence of immunofluorescence extravasation. Data from the electronic medical record and bariatric surgical outcomes database were gathered to analyze the sensitivity and specificity of this new intraoperative diagnostic modality. RESULTS: Total of 196 patients underwent bariatric surgery with intraoperative leak testing using the gastroscopy method; of these, there were 3 false negatives and 193 true negatives. Total of 59 patients underwent bariatric surgery with intraoperative leak testing using the intraluminal ICG method; of these, there was 1 true positive, 1 false positive, 0 false negatives, and 57 true negatives. Indocyanine green leak testing had a sensitivity of 100.00% and specificity of 98.28%. CONCLUSIONS: Intraluminal indocyanine green is an alternative for intraoperative detection of staple line integrity during bariatric surgical procedures with comparable specificity to intraoperative gastroscopy.

Coagulopathy Characterized by Rotational Thromboelastometry in a Porcine Pediatric ECMO Model.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to support patients with reversible cardiopulmonary insufficiency. Although it is a lifesaving technology, bleeding, inflammation, and thrombosis are well-described complications of ECMO. Adult porcine models of ECMO have been used to recapitulate the physiology and hemostatic consequences of ECMO cannulation in adults. However, these models lack the unique physiology and persistence of fetal forms of coagulation factors and fibrinogen as in human infants. We aimed to describe physiologic and coagulation parameters of piglets cannulated and supported with VA-ECMO. Four healthy piglets (5.7-6.4 kg) were cannulated via jugular vein and carotid artery by cutdown and supported for a maximum of 20 hours. Heparin was used with a goal activated clotting time of 180-220 seconds. Arterial blood gas (ABG) was performed hourly, and blood was transfused from an adult donor to maintain hematocrit (Hct) > 24%. Rotational thromboelastometry (ROTEM) was performed at seven time points. All animals achieved adequate flow with a patent circuit throughout the run (pre- and post-oxygenator pressure gradient <10 mmHg). There was slow but significant hemorrhage at cannulation, arterial line, and bladder catheter sites. All animals required the maximum blood transfusion volume available. All animals became anemic after exhaustion of blood for transfusion. ABG showed progressively declining Hct and adequate oxygenation. ROTEM demonstrated decreasing fibrin-only ROTEM (FIBTEM) clot firmness. Histology was overall unremarkable. Pediatric swine are an important model for the study of pediatric ECMO. We have demonstrated the feasibility of such a model while providing descriptions of physiologic, hematologic, and coagulation parameters throughout. Weak whole-blood clot firmness by ROTEM suggested defects in fibrinogen, and there was a clinical bleeding tendency in all animals studied. This model serves as an important means to study the complex derangements in hemostasis during ECMO.

A Terminal FeIII-Oxo in a Tetranuclear Cluster: Effects of Distal Metal Centers on Structure and Reactivity.

Tetranuclear Fe clusters have been synthesized bearing a terminal FeIII-oxo center stabilized by hydrogen-bonding interactions from pendant ( tert-butylamino)pyrazolate ligands. This motif was supported in multiple Fe oxidation states, ranging from [FeII2FeIII2] to [FeIII4]; two oxidation states were structurally characterized by single-crystal X-ray diffraction. The reactivity of the FeIII-oxo center in proton-coupled electron transfer with X-H (X = C, O) bonds of various strengths was studied in conjunction with analysis of thermodynamic square schemes of the cluster oxidation states. These results demonstrate the important role of distal metal centers in modulating the reactivity of a terminal metal-oxo.

Thermodynamics of Proton and Electron Transfer in Tetranuclear Clusters with Mn-OH2/OH Motifs Relevant to H2O Activation by the Oxygen Evolving Complex in Photosystem II.

We report the synthesis of site-differentiated heterometallic clusters with three Fe centers and a single Mn site that binds water and hydroxide in multiple cluster oxidation states. Deprotonation of FeIII/II3MnII-OH2 clusters leads to internal reorganization resulting in formal oxidation at Mn to generate FeIII/II3MnIII-OH. 57Fe Mössbauer spectroscopy reveals that oxidation state changes (three for FeIII/II3Mn-OH2 and four for FeIII/II3Mn-OH clusters) occur exclusively at the Fe centers; the Mn center is formally MnII when water is bound and MnIII when hydroxide is bound. Experimentally determined p Ka (17.4) of the [FeIII2FeIIMnII-OH2] cluster and the reduction potentials of the [Fe3Mn-OH2] and [Fe3Mn-OH] clusters were used to analyze the O-H bond dissociation enthalpies (BDEO-H) for multiple cluster oxidation states. BDEO-H increases from 69 to 78 and 85 kcal/mol for the [FeIIIFeII2MnII-OH2], [FeIII2FeIIMnII-OH2], and [FeIII3MnII-OH2] clusters, respectively. Further insight of the proton and electron transfer thermodynamics of the [Fe3Mn-OH x] system was obtained by constructing a potential-p Ka diagram; the shift in reduction potentials of the [Fe3Mn-OH x] clusters in the presence of different bases supports the BDEO-H values reported for the [Fe3Mn-OH2] clusters. A lower limit of the p Ka for the hydroxide ligand of the [Fe3Mn-OH] clusters was estimated for two oxidation states. These data suggest BDEO-H values for the [FeIII2FeIIMnIII-OH] and [FeIII3MnIII-OH] clusters are greater than 93 and 103 kcal/mol, which hints to the high reactivity expected of the resulting [Fe3Mn═O] in this and related multinuclear systems.

Extending surgeon response times in tier 2 traumas does not adversely affect patient outcomes.

BACKGROUND: The presence of a trauma surgeon during patient resuscitations is required at most American College of Surgeons-verified trauma centers despite little evidence showing improved patient outcomes in the less-than-critically injured (Tier 2) trauma patients. This study was designed to identify the impact of extending required surgeon response times on outcomes in tier 2 trauma patients. METHODS: An American College of Surgeons-verified level 2 trauma center extended the maximum allowed surgeon response time for tier 2 activations from 60 min to 120 min on November 1, 2011. Surgeon response time and patient outcomes of the retrospective control group (January 1, 2008-October 31, 2011) were then compared with the prospective test group (November 1, 2011-December 31, 2014). Primary outcomes included mortality and hospital length of stay (HLOS). Secondary outcomes were emergency department length of stay, and time from ED arrival to CT scan. A subset analysis of all patients evaluated by a surgeon within 60 min of arrival versus those evaluated by a surgeon after 60 min was also performed. RESULTS: The control and test groups were composed of 757 and 792 patients, and their mean injury severity score was 9.0 and 6.0, respectively. Emergency department length of stay showed a statistically significant increase of 12 min, whereas HLOS was unchanged throughout the study. Mortality was not significantly different between the groups. Subset analysis revealed a median surgeon arrival time of 15 min in the <60-min group and 85 min in the >60-min group, whereas the injury severity score, HLOS, and mortality were not significantly different between these subsets. No correlation existed between these outcomes and surgeon arrival time. CONCLUSIONS: Doubling required surgeon response time in tier 2 trauma patients does not produce negative outcomes in this patient group. Mandatory surgeon response times in similar patient groups can be re-evaluated to allow for greater flexibility of a limited surgeon workforce while still providing safe care.

Solid Pseudopapillary Neoplasm of the Pancreas in Children and Adults: A National Study of 369 Patients.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor in children, with current evidence limited to single-center studies. We examined treatment and clinical outcomes for pediatric and adult SPN with a national data set. METHODS: The 2004 to 2013 National Cancer Data Base was queried to identify all patients diagnosed with SPN. The cohort was stratified by age (pediatric and adult) defined as below 18 years and 18 years and above, respectively. Baseline characteristics and unadjusted outcomes were compared. RESULTS: We identified 21 pediatric and 348 adult patients with SPN. Both groups displayed similar demographic composition. Patients were commonly female (90.5% [pediatric] vs. 85.9% [adult], P=0.56) and white (66.7% vs. 68.3%, P=0.74). Tumor location was similar between adults and children. Median tumor size was similar between children and adults (5.9 vs. 4.9 cm, P=0.41). Treatment strategies did not vary between groups. Partial pancreatectomy was the most common resection strategy (71.4% vs. 53.1%, P=0.80). Both groups experienced low mortality (0.0% vs. 0.7% at 5 y, P=0.31). CONCLUSIONS: This study provides the largest comparison of pediatric and adult SPN to date. Children with SPN have similar disease severity at presentation, receive similar treatments, and demonstrate equivalent postoperative outcomes compared with their adult counterparts.

Redox Couple Involving NOx in Aerobic Pd-Catalyzed Oxidation of sp3-C-H Bonds: Direct Evidence for Pd-NO3-/NO2- Interactions Involved in Oxidation and Reductive Elimination.

NaNO3 is used in oxidative Pd-catalyzed processes as a complementary co-catalyst to common oxidants, e.g., CuII salts, in C-H bond activation and Wacker oxidation processes. NaNO3 and NaNO2 (with air or O2) assist the sp3-C-H bond acetoxylation of substrates bearing an N-directing group. It has been proposed previously that a redox couple is operative. The role played by NOx anions is examined in this investigation. Evidence for an NOx anion interaction at PdII is presented. Palladacyclic complexes containing NOx anions are competent catalysts for acetoxylation of 8-methylquinoline, with and without exogenous NaNO3. The oxidation of 8-methylquinoline to the corresponding carboxylic acid has also been noted at PdII. 18O-Labeling studies indicate that oxygen derived from nitrate appears in the acetoxylation product, the transfer of which can only occur by interaction of 18O at Pd with a coordinating-acetate ligand. Nitrated organic intermediates are formed under catalytic conditions, which are converted to acetoxylation products, a process that occurs with (50 °C) and without Pd (110 °C). A catalytically competent palladacyclic dimer intermediate has been identified. Head-space analysis measurements show that NO and NO2 gases are formed within minutes on heating catalytic mixtures to 110 °C from room temperature. Measurements by in situ infrared spectroscopy show that N2O is formed in sp3-C-H acetoxylation reactions at 80 °C. Studies confirm that cyclopalladated NO2 complexes are rapidly oxidized to the corresponding NO3 adducts on exposure to NO2(g). The investigation shows that NOx anions act as participating ligands at PdII in aerobic sp3-C-H bond acetoxylation processes and are involved in redox processes.

Tetranuclear Fe Clusters with a Varied Interstitial Ligand: Effects on the Structure, Redox Properties, and Nitric Oxide Activation.

A new series of tetranuclear Fe clusters displaying an interstitial µ4-F ligand was prepared for a comparison to previously reported µ4-O analogues. With a single nitric oxide (NO) coordinated as a reporter of small-molecule activation, the µ4-F clusters were characterized in five redox states, from FeII3{FeNO}8 to FeIII3{FeNO}7, with NO stretching frequencies ranging from 1680 to 1855 cm-1, respectively. Despite accessing more reduced states with an F- bridge, a two-electron reduction of the distal Fe centers is necessary for the µ4-F clusters to activate NO to the same degree as the µ4-O system; consequently, NO reactivity is observed at more positive potentials with µ4-O than µ4-F. Moreover, the µ4-O ligand better translates redox changes of remote metal centers to diatomic ligand activation. The implication for biological active sites is that the higher-charge bridging ligand is more effective in tuning cluster properties, including the involvement of remote metal centers, for small-molecule activation.

Particle-to-PFU ratio of Ebola virus influences disease course and survival in cynomolgus macaques.

UNLABELLED: This study addresses the role of Ebola virus (EBOV) specific infectivity in virulence. Filoviruses are highly lethal, enveloped, single-stranded negative-sense RNA viruses that can cause hemorrhagic fever. No approved vaccines or therapies exist for filovirus infections, and infectious virus must be handled in maximum containment. Efficacy testing of countermeasures, in addition to investigations of pathogenicity and immune response, often requires a well-characterized animal model. For EBOV, an obstacle in performing accurate disease modeling is a poor understanding of what constitutes an infectious dose in animal models. One well-recognized consequence of viral passage in cell culture is a change in specific infectivity, often measured as a particle-to-PFU ratio. Here, we report that serial passages of EBOV in cell culture resulted in a decrease in particle-to-PFU ratio. Notably, this correlated with decreased potency in a lethal cynomolgus macaque (Macaca fascicularis) model of infection; animals were infected with the same viral dose as determined by plaque assay, but animals that received more virus particles exhibited increased disease. This suggests that some particles are unable to form a plaque in a cell culture assay but are able to result in lethal disease in vivo. These results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures. IMPORTANCE: Ebola virus (EBOV) can cause severe hemorrhagic disease with a high case-fatality rate, and there are no approved vaccines or therapies. Specific infectivity can be considered the total number of viral particles per PFU, and its impact on disease is poorly understood. In stocks of most mammalian viruses, there are particles that are unable to complete an infectious cycle or unable to cause cell pathology in cultured cells. We asked if these particles cause disease in nonhuman primates by infecting monkeys with equal infectious doses of genetically identical stocks possessing either high or low specific infectivities. Interestingly, some particles that did not yield plaques in cell culture assays were able to result in lethal disease in vivo. Furthermore, the number of PFU needed to induce lethal disease in animals was very low. Our results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures.