Quinone-mediated hydrogen anode for non-aqueous reductive electrosynthesis.

Electrochemical synthesis can provide more sustainable routes to industrial chemicals1-3. Electrosynthetic oxidations may often be performed 'reagent-free', generating hydrogen (H2) derived from the substrate as the sole by-product at the counter electrode. Electrosynthetic reductions, however, require an external source of electrons. Sacrificial metal anodes are commonly used for small-scale applications4, but more sustainable options are needed at larger scale. Anodic water oxidation is an especially appealing option1,5,6, but many reductions require anhydrous, air-free reaction conditions. In such cases, H2 represents an ideal alternative, motivating the growing interest in the electrochemical hydrogen oxidation reaction (HOR) under non-aqueous conditions7-12. Here we report a mediated H2 anode that achieves indirect electrochemical oxidation of H2 by pairing thermal catalytic hydrogenation of an anthraquinone mediator with electrochemical oxidation of the anthrahydroquinone. This quinone-mediated H2 anode is used to support nickel-catalysed cross-electrophile coupling (XEC), a reaction class gaining widespread adoption in the pharmaceutical industry13-15. Initial validation of this method in small-scale batch reactions is followed by adaptation to a recirculating flow reactor that enables hectogram-scale synthesis of a pharmaceutical intermediate. The mediated H2 anode technology disclosed here offers a general strategy to support H2-driven electrosynthetic reductions.

Benzoquinone Cocatalyst Contributions to DAF/Pd(OAc)2-Catalyzed Aerobic Allylic Acetoxylation in the Absence and Presence of a Co(salophen) Cocatalyst.

Palladium(II)-catalyzed allylic acetoxylation has been the focus of extensive development and investigation. Methods that use molecular oxygen (O2) as the terminal oxidant typically benefit from the use of benzoquinone (BQ) and a transition-metal (TM) cocatalyst, such as Co(salophen), to support oxidation of Pd0 during catalytic turnover. We previously showed that Pd(OAc)2 and 4,5-diazafluoren-9-one (DAF) as an ancillary ligand catalyze allylic oxidation with O2 in the absence of cocatalysts. Herein, we show that BQ enhances DAF/Pd(OAc)2 catalytic activity, nearly matching the performance of reactions that include both BQ and Co(salophen). These observations are complemented by mechanistic studies of DAF/Pd(OAc)2 catalyst systems under three different oxidation conditions: (1) O2 alone, (2) O2 with cocatalytic BQ, and (3) O2 with cocatalytic BQ and Co(salophen). The beneficial effect of BQ in the absence of Co(salophen) is traced to synergistic roles of O2 and BQ, both of which are capable of oxidizing Pd0 to PdII The reaction of O2 generates H2O2 as a byproduct, which can oxidize hydroquinone to quinone in the presence of PdII NMR spectroscopic studies, however, show that hydroquinone is the predominant redox state of the quinone cocatalyst in the absence of Co(salophen), while inclusion of Co(salophen) maintains oxidized quinone throughout the reaction, resulting in better reaction performance.

Multichannel gas-uptake/evolution reactor for monitoring liquid-phase chemical reactions.

The design of a headspace pressure-monitoring reactor for measuring the uptake/evolution of gas in gas-liquid chemical transformations is described. The reactor features a parallel setup with ten-reactor cells, each featuring a low working volume of 0.2-2 ml, a pressure capacity from 0 to 150 PSIa, and a high sensitivity pressure transducer. The reactor cells are composed of commercially available disposable thick-walled glassware and compact monolithic weld assemblies. The software interface controls the reactor temperature while monitoring pressure in each of the parallel reactor cells. Reactions are easy to set up and yield high-density gas uptake/evolution data. This instrument is especially well suited to acquire quantitative time-course data for reactions with small quantities of gas consumed or produced.

Filling the Gap - Improving Awareness and Practice in Hyponatraemia and the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in the Older Patient: A European Consensus View.

Introduction: Causes of hyponatraemia in older patients are multivariate and in the case of SIADH may often be drug induced. Diagnostic and treatment algorithms are unclear for this important age group. Methods: The author group identified 6 broad themes for consensus and formulated 42 separate consensus statements within these 6 themes. Statements were then circulated to geriatricians, general practitioners and other doctors to test agreement at the European level. Results: 64 responses were evaluated from around Europe. Agreement was achieved in 86% of the statements following amendment and redistribution of 6 of the statements. The survey and its feedback prompted the development of 13 recommendations related to the diagnosis and treatment of hyponatraemia including SIADH. Conclusion: The series of 13 recommendations developed here is intended to increase clarity for clinicians managing older patients with hyponatraemia and SIADH. Surprisingly, despite the lack of clear guidelines or recommendations for this age group consensus levels for the author-based statements were high among the respondents.

Ultra-high resolution Fourier domain optical coherence tomography for old master paintings.

In the last 10 years, Optical Coherence Tomography (OCT) has been successfully applied to art conservation, history and archaeology. OCT has the potential to become a routine non-invasive tool in museums allowing cross-section imaging anywhere on an intact object where there are no other methods of obtaining subsurface information. While current commercial OCTs have shown potential in this field, they are still limited in depth resolution (> 4 µm in paint and varnish) compared to conventional microscopic examination of sampled paint cross-sections (~1 µm). An ultra-high resolution fiber-based Fourier domain optical coherence tomography system with a constant axial resolution of 1.2 µm in varnish or paint throughout a depth range of 1.5 mm has been developed. While Fourier domain OCT of similar resolution has been demonstrated recently, the sensitivity roll-off of some of these systems are still significant. In contrast, this current system achieved a sensitivity roll-off that is less than 2 dB over a 1.2 mm depth range with an incident power of ~1 mW on the sample. The high resolution and sensitivity of the system makes it convenient to image thin varnish and glaze layers with unprecedented contrast. The non-invasive 'virtual' cross-section images obtained with the system show the thin varnish layers with similar resolution in the depth direction but superior clarity in the layer interfaces when compared with conventional optical microscope images of actual paint sample cross-sections obtained micro-destructively.

Validating a refractometer to evaluate immunoglobulin G concentration in Jersey colostrum and the effect of multiple freeze-thaw cycles on evaluating colostrum quality.

The objectives of this study were to (1) validate a method using refractometry to rapidly and accurately determine immunoglobulin (IgG) concentration in Jersey colostrum, (2) determine whether there should be different refractive index (nD) and %Brix cut points for Jersey colostrum, and (3) evaluate the effect of multiple freeze-thaw (FT) cycles on radial immunodiffusion (RID) and a digital refractometer to determine IgG concentration in Jersey colostrum. Samples (n=58; 3L) of colostrum were collected from a dairy in northwestern Iowa. Samples were analyzed within 2h of collection for IgG concentration by RID, %Brix, and nD by refractometer and an estimate of IgG by colostrometer. Samples were frozen, placed on dry ice, and transported to the laboratory at Iowa State University (Ames). Samples arrived frozen and were placed in a -20°C manual-defrost freezer until further analysis. On d 7 (1FT), d 14 (2FT), and 1yr (3FT) all samples were thawed, analyzed for IgG by RID, %Brix, nD by refractometer, and IgG estimate by colostrometer, and frozen until reanalysis at the next time point. Fresh colostrum had a mean (±SD) IgG concentration of 72.91 (±33.53) mg/mL, 21.24% (±4.43) Brix, and nD 1.3669 (±0.0074). Multiple FT cycles did affect IgG as determined by RID and colostrometer reading. The IgG concentrations were greater in fresh and 1FT samples as compared with 2FT and 3FT samples (72.91, 75.38, 67.20, and 67.31mg of IgG/mL, respectively). The colostrometer reading was lower in 1FT samples compared with fresh and 2FT samples. Multiple FT cycles had no effect on nD or %Brix reading. In fresh samples, IgG concentration was moderately correlated with nD (r=0.79), %Brix (r=0.79), and colostrometer reading (r=0.79). Diagnostic test characteristics using the recommended cut point of 1.35966 nD resulted in similar sensitivities for 1FT and 2 FT samples (94.87 and 94.74%, respectively). Cut points of 18 and 19% Brix resulted in the greatest sensitivities (92.31 and 84.62%) and specificity (94.74 and 94.74%, respectively). The 18% Brix cut point resulted in 94.83% of the samples being correctly classified based on IgG concentration. These data support the use of digital refractometer to accurately and rapidly determine IgG concentration in fresh Jersey colostrum. Additionally, these data suggest that IgG concentration determined by RID is affected by multiple FT cycles, whereas estimates obtained by refractometer are not affected by multiple FT cycles.

Dichlorido(η(6)-p-cymene)(eth-oxy-diphenyl-phosphane)ruthenium(II).

The title compound, [RuCl2(C10H14)(C14H15OP)], is an Ru(II) complex in which an η(6)-p-cymene ligand, two chloride anions and the P atom of an ethoxydiphenylphosphane ligand form a piano-stool coordination environment about the central Ru(II) atom.

Anesthetic management of a parturient with fetal sacrococcygeal teratoma and mirror syndrome complicated by elevated hCG and subsequent hyperthyroidism.

Mirror syndrome is a condition in which the mother "mirrors" her hydropic fetus and/or hydropic placenta. Physical and laboratory findings of mirror syndrome include generalized edema, hypertension, and proteinuria similar to preeclampsia. However, unlike preeclampsia, mirror syndrome is associated with hemodilutional anemia and fluid overload, which may progress to pulmonary edema. The anesthetic management of a parturient with fetal sacrococcygeal teratoma, hydrops fetalis, and mirror syndrome complicated by markedly elevated maternal serum human chorionic gonadotropin and subsequent clinical hyperthyroidism, is presented.

The Influence of prolonged beta-blockers treatment on male rabbit's sexual behavior and penile microcirculation.

The aim of the study was to assess the effect of the prolonged intake of three beta-blocking drugs (propranolol, metoprolol and nebivolol) on the sexual behavior and penile microcirculation of rabbits. Drugs were administered p.o. for 9 weeks and every three weeks in each group (n=13) one subgroup (n=7) performed behavioral tests, whereas in the second subgroup (n=6) penile microcirculation was measured with a laser Doppler flowmeter. The copulation studies revealed significant impairment of sexual function only in the propranolol treated group. The measured behavioral parameters suggest that at a given dose propranolol affects more performance rather than arousal aspects of rabbits' sexual behavior. In the course of the whole study no significant difference was observed among groups in penile blood flow. The data indicate that among the beta-blockers given only propranolol interferes with sexual behavior, and that beta-blockers do not appear to have a negative effect on penile microcirculation.

18Flurodeoxyglucose positron emission tomography in the localization of ectopic ACTH-secreting neuroendocrine tumours.

OBJECTIVE: Neuroendocrine tumours (NET) are a rare cause of Cushing's syndrome. These tumours can be very small and therefore difficult to identify. Current localization techniques include CT, MRI and radioisotope scanning, but in a proportion of cases the NET remains occult. Positron emission tomography (PET) scanning, is a relatively new imaging modality that is increasingly used to detect and monitor lesions with high metabolic activity. We report on the use of PET scanning in the evaluation of the ectopic ACTH syndrome. PATIENTS: Three patients with ectopic ACTH-dependent Cushing's syndrome with varying difficulty in NET localization are included in the report. MEASUREMENT: Positron emission tomography scanning using 18flurodeoxyglucose (FDG) identifies tissue with high metabolic activity. 18FDG-PET scanning was used in each of these patients and the imaging is presented along with biochemical data. RESULTS: In each case the NET was easily identified using 18FDG-PET, aiding clinical decision making and therapeutic outcome. A cure was identified by clinical resolution of symptoms and undetectable ACTH levels postsurgery. CONCLUSIONS: 18FDG-PET assisted in localizing small metabolically active NETs, suggesting this imaging modality may have a useful role in identifying NET causing Cushing's syndrome as a result of ectopic ACTH production.

Reduction of Escherichia coli O157 in finishing beef cattle by various doses of Lactobacillus acidophilus in direct-fed microbials.

Our objective was to evaluate the effects of three doses of Lactobacillus acidophilus strain NP51 and a combination treatment of strains NP51 and NP45 on prevalence of Escherichia coli O157 in cattle. Three hundred steers were assigned randomly to 60 pens (five steers per pen) and received one of five treatments: (i) control, no added direct-fed microbial; (ii) HNP51, high dose of NP51 at 10(9) CFU per steer daily; (iii) MNP51, NP51 at 10(8) CFU per steer daily; (iv) LNP51, low dose of NP51 at 10(7) CFU per steer daily; and (v) NP51+45, NP51 at 10(9) CFU per steer daily and NP45 at 106 CFU per steer daily. All direct-fed microbial treatments included Propionibacterium freudenreichii at 10(9) CFU per steer. Individual rectal fecal samples were collected on arrival and every 28 days throughout the feeding period. Fecal and hide samples were collected on the day of harvest. Samples were analyzed for presence of E. coli O157 using immunomagnetic separation methods. Cattle receiving HNP51, MNP51, and LNP51 had a lower prevalence (P < 0.01) of E. coli O157 throughout the feeding period compared with the controls, and the dose response for NP51 was a linear decrease in prevalence with increasing dose (P < 0.01). No decrease in prevalence for cattle receiving the combination NP51+45 was detected compared with controls (P = 0.15). E. coli O157 prevalences averaged across collection times were 23.9, 10.5, 9.9, 6.8, and 17.3% for cattle in the control, LNP51, MNP51, HNP51, and NP51 +45 groups, respectively. Least squares mean estimates of fecal prevalence at harvest of E. coli O157 were 31.7, 12.5, 17.4, 8.2, and 41.6% among cattle in the control, LNP51, MNP51, HNP51, and NP51+45 groups, respectively. Least squares mean estimates of the percentage of positive hide samples at harvest were 8.7, 5.9, 4.8, 3.4, and 8.6% among cattle in the control, LNP51, MNP51, HNP51, and NP51+45 groups, respectively. The greatest decrease in E. coli O157 carriage was achieved using NP51 at 10(9) CFU per steer.

A Clinical Trial to Test the Feasibility of a Telehealth Psychoeducational Intervention for Persons With Schizophrenia and Their Families: Intervention and 3-Month Findings.

OBJECTIVE: To evaluate the feasibility of a telehealth psychoeducation intervention for persons with schizophrenia and their family members. STUDY DESIGN: Randomized controlled trial. PARTICIPANTS: 30 persons with schizophrenia and 21 family members or other informal support persons. INTERVENTIONS: Web-based psychoeducation program that provided online group therapy and education. MAIN OUTCOME MEASURES: Measures for persons with schizophrenia included perceived stress and perceived social support; for family members, they included disease-related distress and perceived social support. RESULTS: At 3 months, participants with schizophrenia in the intervention group reported lower perceived stress (p = .04) and showed a trend for a higher perceived level of social support (p = .06). CONCLUSIONS: The findings demonstrate the feasibility and impact of providing telehealth-based psychosocial treatments, including online therapy groups, to persons with schizophrenia and their families.

A test of four plant species to reduce total nitrogen and total phosphorus from soil leachate in subsurface wetland microcosms.

Four wetland plant species (Scirpus validus, Carex lacustris, Phalaris arundinacea, and Typha latifolia) were grown in monoculture and as a four-species mixture to compare effectiveness of nutrient removal in controlled 18.93-l outdoor subsurface treatment wetland microcosms. A nutrient treatment that mimicked single-resident domestic effluent consisted of two levels of nitrogen (N) and phosphorus (P) [low (56 mg/l N and 31 mg/l P) and high (112 mg/l N and 62 mg/l P)] of nutrient solution applied three times weekly. The plants were established and maintained for one year before the nutrient treatment and monthly water sampling commenced; water sampling began July 31, 2001 and ended October 23, 2001. We tested four hypotheses: (1) vegetated microcosms are more effective at reducing concentrations of total N and total P from soil leachate than unvegetated, (2) there is a differential species effect on the potential to reduce N and P, (3) plant mixtures are more effective than monocultures at reducing N and P, and (4) the microcosms will be least effective at reducing N and P concentrations in October compared to August. We found support for hypotheses 1, 2, and 4, but our results are inconclusive for the third hypothesis. Total N and total P in the soil leachate were significantly higher from unvegetated microcosms compared to vegetated. S. validus was most effective and P. arundinacea was generally least effective at reducing N and P in monocultures, with treatment capabilities similar to unvegetated microcosms. The four-species mixture was generally highly effective at nutrient removal, however the results were not significantly different from the monocultures. At the end of the growing season (October) treatment efficiency was significantly less than earlier months, especially for the unvegetated treatment.

Enhanced cellular immune response and reduced CD8(+) lymphocyte apoptosis in acutely SIV-infected Rhesus macaques after short-term antiretroviral treatment.

Losing the decisive virus-specific functions of both CD4(+) and CD8(+) T lymphocytes in the first weeks after immunodeficiency virus infection ultimately leads to AIDS. The SIV/rhesus monkey model for AIDS was used to demonstrate that a 4-week chemotherapeutic reduction of viral load during acute SIV infection of macaques allowed the development of a competent immune response able to control virus replication after discontinuation of treatment in two of five monkeys. Increasing SIV-specific CD4(+) T-helper-cell proliferation was found in all macaques several weeks after treatment, independent of their viral load. However, only macaques with low viral loads showed persistent T-cell reactivity of lymph node cells. In contrast to animals with higher viral loads, T-helper-cell counts and memory T-helper cells did not decline in the two macaques controlling viral replication. Lymphocyte apoptosis was consistently low in all treated macaques. In contrast, high CD8(+) lymphocyte death but only slightly increased CD4(+) lymphocyte apoptosis were observed during the first weeks after infection in untreated control animals, indicating that early apoptotic death of virus-specific CTL could be an important factor for disease development. Antiretroviral treatment early after infection obviously retained virus-specific and competent T lymphocytes, whereby a virus-specific immune response could develop in two animals able to control the viral replication after cessation of treatment.

Novel hepatoselective insulin analog: studies with a covalently linked thyroxyl-insulin complex in humans.

OBJECTIVE: To test whether a thyroxyl-insulin analog with restricted access to receptor sites in peripheral tissues displays relative hepatoselectivity in humans. RESEARCH DESIGN AND METHODS: Five normal human subjects received a subcutaneous bolus injection of either N(alphaBl) L-thyroxyl-insulin (Bl-T4-Ins) or NPH insulin in random order. Insulin kinetics, relative effects on hepatic glucose production, and peripheral glucose uptake were studied using euglycemic clamp and stable isotope [D-6,6-(2)H2]glucose) dilution techniques. Blood samples were taken for the determination of total immunoreactive insulin/analog concentrations and for liquid chromatography to assess the protein binding of the analog in the circulation. RESULTS: After subcutaneous administration, Bl-T4-Ins was well tolerated and rapidly absorbed. The analog had a long serum half-life and was highly protein bound (approximately 86%). Its duration of action, as judged by the duration of infusion of exogenous glucose to maintain euglycemia, was similar to that of NPH insulin. The effect of the analogs on hepatic glucose production was similar to that of NPH insulin, indicating equivalent hepatic potency. The analog demonstrated less effect on peripheral glucose uptake than NPH insulin (P = 0.025), had no effect on metabolic clearance rate of glucose, and exhibited a reduced capacity to inhibit lipolysis (P < 0.05). CONCLUSIONS: When injected subcutaneously into normal human subjects, Bl-T4-Ins is well tolerated, quickly absorbed, and highly protein bound, resulting in a long plasma halflife. This analog appears to have a hepatoselective action, and, therefore, has the potential to provide more physiological insulin action than the insulin preparations currently used.

Homozygosity for a conserved Mhc class II DQ-DRB haplotype is associated with rapid disease progression in simian immunodeficiency virus-infected macaques: results from a prospective study.

In human immunodeficiency virus type 1 (HIV-1)-infected individuals, disease progression varies considerably. This is also observed after experimental infection of macaques with simian immunodeficiency virus (SIV). Major histocompatibility complex (MHC) genes may influence disease progression in both species. Homozygosity for Mhc-Mamu (Macaca mulatta)-DQB1*0601 was previously identified to be associated with rapid disease progression in SIV-infected macaques. To validate the association of this genotype with disease progression, a prospective study was carried out. Six unrelated monkeys homozygous for Mamu-DQB1*0601 and DRB1*0309-DRB*W201 and 6 heterozygous monkeys were infected with SIVmac. Five of the homozygous and only 1 of the heterozygous monkeys died rapidly after infection, with manifestations of AIDS. These results were validated by a retrospective survival analysis of 71 SIV-infected monkeys. The identified DQ-DRB genotype is frequent among monkeys of different breeding colonies and allows a fairly reliable selection before infection of monkeys predisposed for rapid disease progression.

Kinetics of lymphocyte apoptosis in macaques infected with different simian immunodeficiency viruses or simian/human immunodeficiency hybrid viruses.

Increased rates of T-cell apoptosis have been detected in human immunodeficiency virus (HIV)-infected individuals and in the simian immunodeficiency model (SIV) for AIDS research. We have infected macaques with virulent SIV or SIV/HIV hybrid viruses (SHIV) of different pathogenic potentials to study the early kinetics of apoptosis in this model. Animals infected with SIV showed an increased degree of apoptosis in their peripheral blood mononuclear cells as early as 8 weeks after virus inoculation. Apoptotic cells were detected in the CD4 and CD8 cell populations of infected animals. In contrast, apathogenic SHIV did not lead to increased lymphocyte apoptosis and moderately pathogenic SHIV induced only transient apoptosis. T-cell death was temporally linked to viral replication in vivo. Furthermore, lymphocyte apoptosis in infected macaques was associated with impaired proliferative responses of helper T-cells and with CD4 cell depletion. The monkey model described here provides the opportunity for testing early therapeutic interventions to prevent virus-induced programmed cell death and the subsequent onset of AIDS.