Rotation-dependent nonlinear absorption of orbital angular momentum beams in ruby.

We investigate the effect of a rotating medium on orbital angular momentum (OAM)-carrying beams by combining a weak probe beam shifted in frequency relative to a strong pump beam. We show how the rotational Doppler effect modifies the light-matter interaction through the external rotation of the medium. This interaction leads to an absorption that increases with the mechanical rotation velocity of the medium and with a rate that depends on the OAM of the light beam.

Spine fracture prevalence in a nationally representative sample of US women and men aged ≥40 years: results from the National Health and Nutrition Examination Survey (NHANES) 2013-2014.

Spine fracture prevalence is similar in men and women, increasing from <5 % in those <60 to 11 % in those 70-79 and 18 % in those ≥80 years. Prevalence was higher with age, lower bone mineral density (BMD), and in those meeting criteria for spine imaging. Most subjects with spine fractures were unaware of them. INTRODUCTION: Spine fractures have substantial medical significance but are seldom recognized. This study collected contemporary nationally representative spine fracture prevalence data. METHODS: Cross-sectional analysis of 3330 US adults aged ≥40 years participating in NHANES 2013-2014 with evaluable Vertebral Fracture Assessment (VFA). VFA was graded by semiquantitative measurement. BMD and an osteoporosis questionnaire were collected. RESULTS: Overall spine fracture prevalence was 5.4 % and similar in men and women. Prevalence increased with age from <5 % in those <60 to 11 % in those 70-79 and 18 % in those ≥80 years. Fractures were more common in non-Hispanic whites and in people with lower body mass index and BMD. Among subjects with spine fracture, 26 % met BMD criteria for osteoporosis. Prevalence was higher in subjects who met National Osteoporosis Foundation (NOF) criteria for spine imaging (14 vs 4.7 %, P < 0.001). Only 8 % of people with a spine fracture diagnosed by VFA had a self-reported fracture, and among those who self-reported a spine fracture, only 21 % were diagnosed with fracture by VFA. CONCLUSION: Spine fracture prevalence is similar in women and men and increases with age and lower BMD, although most subjects with spine fracture do not meet BMD criteria for osteoporosis. Since most (>90 %) individuals were unaware of their spine fractures, lateral spine imaging is needed to identify these women and men. Spine fracture prevalence was threefold higher in individuals meeting NOF criteria for spine imaging (∼1 in 7 undergoing VFA). Identifying spine fractures as part of comprehensive risk assessment may improve clinical decision making.

Pharmacokinetics of firocoxib after intravenous administration of multiple consecutive doses in neonatal foals.

The purpose of this study was to determine the pharmacokinetic profile of intravenous firocoxib in neonatal foals. Six healthy foals were administered 0.09 mg/kg firocoxib intravenously once a day for 7 days. Blood was collected for plasma firocoxib analysis using high-performance liquid chromatography with fluorescence detection at times 0 (day 1 of study only) and 0.08, 0.25, 1, 2, 4, 6, 8, 16 and 24 hr on dose numbers 1, 5 and 7. Blood was also collected immediately prior to doses 3, 4, 5 and 7. Final samples were collected at 36, 48, 72 and 96 hr following the final dose. Noncompartmental analysis using the trapezoidal method with linear interpolation revealed a moderate half-life (15.9 ± 9.1 hr) with a large volume of distribution at steady state (1.79 ± 0.57 L/kg) and a clearance (96.0 ± 59.2 ml h-1  kg-1 ) that was more rapid than that observed in adult horses.

An in vivo comparison of hip structure analysis (HSA) with measurements obtained by QCT.

SUMMARY: In a population of elderly women, bone cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), femoral neck axis length (FNAL), and width measured with hip structure analysis (HSA) on dual-energy x-ray absorptiometry (DXA) images in the femoral neck and trochanteric regions are highly correlated to quantitative computed tomography (QCT) measurements. INTRODUCTION: HSA is a method of obtaining measurements of proximal femur structure using 2D DXA technology. This study was designed to examine the correlations between HSA measurements and 3D QCT. METHODS: Forty-one women (mean age, 82.8 ± 2.5 years) were measured using DXA and a 64-slice CT scanner (1 mm slice thickness, 0.29 mm in plane resolution). HSA parameters were calculated at the narrow neck (NN) and trochanteric (IT) regions on the DXA image. These regions were then translated to anatomically equivalent regions on the QCT dataset by co-registering the DXA image and QCT dataset using four DXA images acquired at different angles. RESULTS: At the NN and IT regions, high linear correlations were measured between HSA and QCT for CSA r = 0.95 and 0.93, CSMI r = 0.94 and 0.93, and Z r = 0.93 and 0.89, respectively. All correlations were highly significant (p < 0.001), but there were differences in slope and offset between the two techniques, at least in part due to differences in calibration between the two techniques. FNAL and width of the bone at the NN and IT regions, physical measurements independent of the calibration, were highly correlated (r = 0.90-0.95, p < 0.001) and had slopes close to 1.0 (range, 0.978 to 1.003). CONCLUSION: CSA, CSMI, Z, FNAL, and width measured by HSA correlate highly to high-resolution QCT.

Differences in structural geometrical outcomes at the neck of the proximal femur using two-dimensional DXA-derived projection (APEX) and three-dimensional QCT-derived (BIT QCT) techniques.

UNLABELLED: Structural geometric parameters at neck of the proximal femur were obtained using DXA-derived hip structural analysis (APEX 3) and quantitative computed tomography-derived (BIT QCT) techniques in 237 elderly females. Linear correlations for parameters ranged from 0.45 to 0.90. The average value of the subperiosteal width, as determined by the two techniques, was the same; variables dependent on mass measurements were different. INTRODUCTION: There has been increasing interest in using bone structural geometry to assess bone fragility to complement bone mineral mass. The objective of this study is to compare structural geometrical differences between "2D" DXA-derived and "3D" QCT-derived techniques in unselected clinical cases. METHODS: All 237 females had both DXA and QCT assessments of femoral neck structural geometry. Variables compared were areal bone mineral density, cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), averaged cortical thickness (Ct), endosteal width (ESW), subperiosteal width (W), and buckling ratio (BR). RESULTS: Correlation of femoral neck variables ranged from 0.45 for ESW to 0.90 for CSA. APEX 3 and BIT QCT-derived femoral neck W values were numerically similar. However CSA, CSMI, Z and Ct values measured by APEX 3 were higher and ESW and BR values were lower than corresponding BIT QCT. CONCLUSIONS: 2D DXA structural analysis of neck of femur is related to but different from same parameters calculated from true 3D images obtained by CT. Femoral neck size values are similar for DXA and QCT, but structural geometrical variables dependent on mass calibration standards, location of neck ROI and mathematical derivation techniques are different.

Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses.

BACKGROUND: There are no published studies on the pharmacokinetics of acetaminophen at the dosage used clinically (20 mg/kg), nor has the safety of multiple doses in horses been investigated. OBJECTIVE: Define the pharmacokinetic parameters of oral acetaminophen at 20 mg/kg in adult horses as a single dose, and twice daily for 14 days to assess the safety of multiple dosing. STUDY DESIGN: Pharmacokinetic study, multiple dose safety study. METHODS: Eight healthy Thoroughbred geldings were given acetaminophen (20 mg/kg; 500 mg tablets) orally as a single dose followed by doses every 12 h for 14 days. Serial blood samples were collected for determination of plasma acetaminophen concentrations using high performance liquid chromatography with ultraviolet detection. Serum biochemical analysis, gastroscopy and liver biopsy were examined during the safety study. RESULTS: Following a single dose, mean maximum concentration (Cmax ) was 16.61 µg/mL at 1.35 h (Tmax ), and drug concentration was below the lower limit of detection in most horses by 24 h. Elimination half-life (T1/2 ) was 2.78 h. No significant accumulation was noted following multiple doses. Average Cmax of acetaminophen following multiple oral dosing was 15.85 µg/mL, with a Tmax of 0.99 h and T1/2 of 4 h. Serum activities of sorbitol dehydrogenase were significantly decreased and total bilirubin concentrations were significantly increased following the last dose. No statistically significant changes were noted in gastroscopy scores. MAIN LIMITATIONS: Only one dose level (20 mg/kg) was studied, sample size was small and only a single breed and sex was used, with no pretreatment liver biopsies. CONCLUSION: This study described the pharmacokinetics of acetaminophen following single and multiple 20 mg/kg oral doses in adult horses and demonstrated the safety of acetaminophen with multiple oral dosing over 14 days. The summary is available in Portuguese - see Supporting information.

Rheumatoid arthritis synovial T cells regulate transcription of several genes associated with antigen-induced anergy.

Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis whose pathogenesis may involve autoimmune mechanisms. Anergy is a state of T-cell nonresponsiveness characterized by downregulated IL-2 production. Paradoxically, RA T cells are hyporesponsive and proliferate poorly to antigens and mitogens, thus sharing some characteristics with anergic T cells. We analyzed the molecular basis of anergy in cloned human CD4+ T cells using differential display RT-PCR and subsequently examined the levels of differentially expressed transcripts in RA and, as control, reactive arthritis (ReA) synovium. Several transcriptional events were common to anergic T cells and RA synovium. These included downregulation of CALMODULIN:, which is critical to T-cell activation, and of cellular apoptosis susceptibility protein, which may mediate resistance to apoptosis in RA. Transcription of CALMODULIN: in RA synovium was less than 1% of that in ReA and was lower in RA synovial fluid mononuclear cells than in paired PBMCs. Following anti-TNF-alpha therapy in vivo, RA PBMC CALMODULIN: transcripts increased five- to tenfold. Pharmacological calmodulin blockade in vitro impaired antigen-specific proliferation. These data provide a link between reduced CALMODULIN: transcription and impaired T-cell responsiveness in RA. The identification of transcriptional changes common to anergic and RA synovial T cells should help interpret some of the characteristic RA cellular defects.

Can intravenous conscious sedation with midazolam be effective at facilitating surgical dentistry in adolescent orthodontic patients? A service evaluation.

Background Surgical dentistry during orthodontic care often occurs in adolescence and may involve surgical removal or exposure of teeth. The invasive nature of treatment, combined with dental anxiety, means care can often be provided under general anaesthesia (GA). Best-practice guidelines however endorse conscious sedation as an alternative, where appropriate. Although a limited number of studies have shown safe and effective use of intravenous conscious sedation (IVCS) with midazolam in this cohort, robust evidence to support routine use is lacking. Aim To assess whether IVCS with midazolam can effectively facilitate surgical dentistry in adolescent orthodontic patients in primary care.Method A retrospective service evaluation was undertaken reviewing clinical records of adolescents (aged 12-15 years) undergoing surgical exposure and/or surgical removal of teeth under IVCS with midazolam.Results A total of 174 adolescents (mean age 14.2 years) attended for treatment between 2009 and 2015. Of these adolescents, 98.9% (N = 172) allowed cannulation, with all surgical dentistry completed during a single visit. Midazolam dose ranged from 2-7 mg with 79.1% of patients having good or excellent cooperation and three minor adverse events occurring.Conclusion This service evaluation shows IVCS with midazolam can effectively facilitate surgical orthodontics in carefully selected adolescents. There is however a distinct need to further explore potential for this technique to provide a viable alternative to GA.

A study of dental students' clinical knowledge acquisition and experiences in conscious sedation.

AIM: To evaluate final year dental students' knowledge acquisition and experiences during their intravenous sedation (IVS) clinical attachment within the sedation department at Newcastle School of Dental Sciences (NSDS). METHODS: Students attending IVS clinical attachments in the period September 2012 - April 2013 completed a novel clinical knowledge test at the beginning and end of their one week attachment; a feedback questionnaire was also completed. RESULTS: A total of 70 students attended the attachment. Clinical knowledge tests were completed by 71.4% (n = 50) of students. The average test result improved from 75.1% in the pre-attachment test to 92.1% in the post-attachment test. Feedback questionnaires were returned by 65.7% (n = 46) of students. All students attained clinical experience of administering sedation and treating sedated patients. 'Teaching and Clinical Support' was rated highest, with 97.8% (n = 45) rating it as excellent. Students commented that hands-on clinical experience and clinical teaching were the most valuable parts of the attachment. Patients failing to attend appointments were considered the least useful part of the attachment. CONCLUSION: This pilot study provides an insight into undergraduate clinical sedation, which is often under reported in the literature. The clinical experience gained at NSDS exceeds GDC recommendations for undergraduate sedation. The clinical knowledge test results suggest that clinical knowledge may be better retained after direct clinical experience.

Ligand binding properties of human cellular retinoic acid binding protein II expressed in E. coli as a glutathione-S-transferase fusion protein.

To test the hypothesis that 9-cis-retinoic acid is a ligand for cellular retinoic acid binding protein II (CRABP II), human CRABP II was expressed as a glutathione-S-transferase fusion protein (GST-CRABP II) and a single affinity purification step used to extract it from bacterial lysates. GST-CRABP II bound all trans-retinoic acid with high affinity (Kd 14.2 +/- 6.5 nM), but 9-cis-retinoic acid bound poorly. These studies suggest that 9-cis-retinoic acid is not a ligand for CRABP II. Their ease of purification makes GST-CRABP fusion proteins useful tools for ligand binding studies with different retinoids.

Bacterial and plant glycoconjugates at the Rhizobium-legume interface.

Many classes of bacterial and plant glycoconjugate have been shown to be involved in establishing the Rhizobium root nodule symbiosis with peas (Pisum sativum). It was demonstrated, using techniques of molecular genetics, that a group of Rhizobium nodulation genes (nod genes) co-operate to synthesize a lipo-oligosaccharide signal molecule that specifically initiates nodule development on legume hosts. An additional gene function, encoded by nodX, has been found to extend the host range of Rhizobium leguminosarum bv. viciae to include nodulation of a pea mutant, cultivar Afghanistan; the nodX gene product specifies the addition of an acetyl group to the terminal N-acetylglucosamine residue at the reducing end of the pentasaccharide core of this signal molecule. Several other classes of bacterial glycoconjugate have also been shown by genetic analysis to be essential for normal nodule development and function: these include a capsular extracellular polysaccharide; lipopolysaccharide in the outer membrane; and cyclic glucans present in the periplasmic space. Potential functions for these glycoconjugates are discussed in the context of tissue and cell invasion by Rhizobium. Some plant components involved in symbiotic interactions have been identified by the analysis of nodule-specific gene expression (early nodulins). Several of the cDNA clones encoding these early nodulins specify proline-rich proteins that presumably correspond to cell wall glycoproteins or membrane arabinogalactan proteins. Other plant glycoconjugates have been identified using monoclonal antibodies as probes. A plant glycoprotein present in intercellular spaces has been identified as a component of the luminal matrix of infection threads. Because it attaches to the surface of bacteria and is itself susceptible to oxidative cross-linking, this glycoprotein may be involved in limiting the progress of microbial infections. Endocytosis of bacteria into the plant cytoplasm is apparently driven by direct interactions between the bacterial surface and the plasma membrane that is exposed within an unwalled infection droplet; glycoprotein and glycolipid components of the plant membrane glycocalyx have been defined using monoclonal antibodies. Differentiation of endosymbiotic bacteroids is preceded by differentiation of the plant-derived peribacteroid membrane which encloses the symbiosome compartment. Using a monoclonal antibody that identifies a group of plant membrane-associated, inositol-containing glycolipids, we have identified a very early marker for the differentiation of peribacteroid membrane from plasma membrane.

Selective protection and relative importance of the carboxylic acid groups of zaragozic acid A for squalene synthase inhibition.

Chemistry that allows selective modification of the carboxylic acid groups of the squalene synthase inhibitor zaragozic acid A (1) was developed and applied to the synthesis of compounds modified at the 3-,4-,5-,3,4-,3,5-, and 4,5-positions. A key step in this procedure is the selective debenzylation by transfer hydrogenolysis in the presence of other olefinic groups. These compounds were tested in the rat squalene synthase assay and in vivo mouse model. Modification at C3 retains significant enzyme potency and enhances oral activity, indicating that C3 is not essential for squalene synthase activity. Modification at C4 and C5 results in significant loss in enzyme activity. In contrast, substitution at C3 or C4 enhances in vivo activity. Furthermore, disubstitution at the C3 and C4 positions results in additive in vivo potency.

High throughput approaches in neuroscience.

Traditional approaches to understanding biological problems are now being advanced with the use of high throughput technologies, which analyse multiple samples simultaneously, or thousands of analytes in a single sample. The application of these technologies in neurochemistry and neuroscience is beginning to be explored and is assisting in the development of new models of drug action, neuroanatomical investigations, and in identifying molecular pathways involved in neurological and psychiatric disease. Tools such as microarray-based gene expression profiling and 2D and multidimensional proteomic methods are uncovering functional components to a wide variety of neuroscience paradigms and the application of these technologies is set to become standard in analysis.

Effects of ultraviolet-A exposure on ultraviolet-B-induced accumulation of specific flavonoids in Brassica napus.

Many plant species are able to acclimate to changes in ultraviolet-B radiation (UVB) (290-320 nm) exposure. Due to the wide range of targets of UVB, plants have evolved diverse repair and protection mechanisms. These include increased biosynthesis of UVB screening compounds, elevated antioxidant activity and increased rates of DNA repair. We have shown previously that Brassica napus L. cv Topas plants can acclimate quite effectively to environmentally relevant increases in UVB through the accumulation of specific flavonoids in the leaf epidermis. However, B. napus was found to lose other flavonoids when plants are exposed to ultraviolet-A radiation (UVA) (320-400 nm) and/or UVB (Wilson et al. [1998] Photochem. Photobiol. 67, 547-553). In this study we demonstrate that the levels of all the extractable flavonoids in the leaves of B. napus plants are decreased in a dose-dependent manner in response to UVA exposure. Additionally, the accumulation of the extractable flavonoids was examined following a shift from photosynthetically active radiation (PAR) + UVA to PAR + UVB to assess if preexposure to UVA affected UVB-induced flavonoid accumulation. UVA preexposures were found to impede UVB-induced accumulation of some flavonoids. This down regulation was particularly evident for quercetin-3-O-sophoroside and quercetin-3-O-sophoroside-7-O-glucoside, which is interesting because quercetins have been demonstrated to be induced by UVB and correlated with UVB tolerance in some plant species. The photobiological nature of these UVA-mediated effects on flavonoid accumulation implies complex interactions between UVA and UVB responses.

L-669,262, a potent HMG-CoA reductase inhibitor.

The microbial transformation of simvastatin (MK-733) by Nocardia autotrophica subspecies amethystina yielded iso-simvastatin-6-one as a minor component. This transformation product is a dienone and is one of the more potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase found to date.

Northienamycin and 8-epi-thienamycin, new carbapenems from Streptomyces cattleya.

Two new carbapenem antibiotics, northienamycin and 8-epi-thienamycin have been isolated from culture broth of Streptomyces cattleya grown under conditions for thienamycin production. The isolation, structure elucidation and in vitro antibacterial spectra of the new carbapenems are reported. In addition, comparison of the in vitro potency of the corresponding formamidine derivatives to that of MK787 is presented.

L-681,217, a new and novel member of the efrotomycin family of antibiotics.

L-681,217 is a new broad spectrum antibiotic isolated from fermentation broth. The compound is a structurally unique member of the efrotomycin family of growth permittant antibiotics.

Pneumocandins from Zalerion arboricola. I. Discovery and isolation.

HPLC bioautography of the directed biosynthesis of Zalerion arboricola led to the discovery of pneumocandin B0 (L-688,786), a new antifungal and anti-Pneumocystis carinii lipopeptide. Isolation techniques were developed to separate this component from pneumocandin A0 (L-671,329) in fermentations of a mutant of Zalerion arboricola. A number of related compounds were also isolated, which differ from pneumocandins A0 and B0 in the hydroxylation patterns on the ornithine, homotyrosine, and proline.

Difficidin and oxydifficidin: novel broad spectrum antibacterial antibiotics produced by Bacillus subtilis. II. Isolation and physico-chemical characterization.

The isolation of difficidin (1) and oxydifficidin (2) from fermentation broth of Bacillus subtilis ATCC 39320 and the physico-chemical characterization of these labile antibiotics are described. The structures of the compounds represent a new class of antibiotics, characterized as highly unsaturated 22-membered macrolide phosphates. Difficidin and oxydifficidin undergo reversible thermal isomerization to 3 and 4 respectively. Biological evaluation of the isomers is presented.

Restricticin, a novel glycine-containing antifungal agent.

Restricticin (1) is a naturally-occurring antifungal agent which contains triene, pyran and glycine ester functionalities and is unrelated to any previously known family of natural products. This unstable compound, as well as its corresponding N,N-dimethyl derivative (2), have been produced and isolated from both solid and liquid fermentations of Penicillium restrictum. The desglycyl hydrolysis product, restrictinol (3), was produced via the hydrolysis of pure restricticin and as an artifact of the isolation of restricticin.