Scope and Limitations of Reductive Amination Catalyzed by Half-Sandwich Iridium Complexes Under Mild Reaction Conditions.

The conversion of aldehydes and ketones to 1° amines could be promoted by half-sandwich iridium complexes using ammonium formate as both the nitrogen and hydride source. To optimize this method for green chemical synthesis, we tested various carbonyl substrates in common polar solvents at physiological temperature (37 °C) and ambient pressure. We found that in methanol, excellent selectivity for the amine over alcohol/amide products could be achieved for a broad assortment of carbonyl-containing compounds. In aqueous media, selective reduction of carbonyls to 1° amines was achieved in the absence of acids. Unfortunately, at Ir catalyst concentrations of <1 mM in water, reductive amination efficiency dropped significantly, which suggest that this catalytic methodology might be not suitable for aqueous applications where very low catalyst concentration is required (e.g., inside living cells).

Clean, robust alkali sources by intercalation within highly oriented pyrolytic graphite.

We report the fabrication, characterization, and use of rubidium vapor dispensers based on highly oriented pyrolytic graphite (HOPG) intercalated with metallic rubidium. Compared to commercial chromate salt dispensers, these intercalated HOPG (IHOPG) dispensers hold an order of magnitude more rubidium in a similar volume, require less than one-fourth the heating power, and emit less than one-half as many impurities. Appropriate processing permits exposure of the IHOPG to atmosphere for over ninety minutes without any adverse effects. Intercalation of cesium, potassium, and lithium into HOPG has also been demonstrated in the literature, which suggests that IHOPG dispensers may also be made for those metals.

Rapid Discovery of De Novo Deleterious Mutations in Cattle Enhances the Value of Livestock as Model Species.

In humans, the clinical and molecular characterization of sporadic syndromes is often hindered by the small number of patients and the difficulty in developing animal models for severe dominant conditions. Here we show that the availability of large data sets of whole-genome sequences, high-density SNP chip genotypes and extensive recording of phenotype offers an unprecedented opportunity to quickly dissect the genetic architecture of severe dominant conditions in livestock. We report on the identification of seven dominant de novo mutations in CHD7, COL1A1, COL2A1, COPA, and MITF and exploit the structure of cattle populations to describe their clinical consequences and map modifier loci. Moreover, we demonstrate that the emergence of recessive genetic defects can be monitored by detecting de novo deleterious mutations in the genome of bulls used for artificial insemination. These results demonstrate the attractiveness of cattle as a model species in the post genomic era, particularly to confirm the genetic aetiology of isolated clinical case reports in humans.

Facets of Clinical Appearance and Aetiology in an Unusual Bovine Amorphus Globosus.

Amorphus globosus is a rare entity, more common in the cow but also reported in mares, buffaloes and goats. In respect of both development and clinical presentation, this abnormity can be evolved very variably. Previously, it has been discussed whether it is a form of twin pregnancy or placental teratoma. This case report deals with morphology and genetic observations in an unusual bovine amorphus globosus exhibiting a rudimentary clitoris and vulva, gut-like structures and rudimentary bones. The amorphus globosus was shown to be dizygotic to the normal male twin using the BovineSNP50 v2 BeadChip and had a genetical female sex. Aspects of aetiology and pathogenesis as well as the possible impact of amorphus globosus in the emergence of freemartinism are discussed.

Partial Thyroidectomy for Papillary Thyroid Microcarcinoma: Is Completion Total Thyroidectomy Indicated?

BACKGROUND: Total thyroidectomy is a well-established surgical approach for the management of papillary thyroid cancer (PTC). However, the best surgical approach for papillary microcarcinoma is nowadays still debated. Both total thyroidectomy and simple lobectomy are used. We report the experience of a single University center in the treatment of thyroid microcarcinoma. METHODS: A retrospective analysis on all patients who underwent thyroid surgery at our institution over a 24-year period (1991-2015) was performed. Patients were grouped according to whether they received total thyroidectomy (Group 1) or lobectomy (Group 2). Follow-up was made by routine clinical and ultrasound examination. Specific outcomes such as recurrence and need for reoperation as well as complications (transient vocal cord paralysis and hypocalcemia) were analyzed. RESULTS: During the study period 880 patients underwent surgery for PTC. Group 1 and 2 consisted, respectively, of 756 and 124 patients. A micro PTC (<10 mm) was present in 251 and 69 specimen of Group 1 and 2. No evidence of disease recurrence in the follow-up was reported in patients with microPTC in Group 1 and in 57 patients of Group 2. In the remaining 12 patients completion thyroidectomy was carried out due to ultrasound findings of contralateral nodules (10), lymphadenopathy (1), and capsular invasion (1). Five of these patients had a contralateral papillary carcinoma on final histopathologic examination. Thus recurrence rate for patients of Group 2 was 7.3%. Morbidity rates were, respectively, for Group 1 and 2: transient nerve palsy 81 and 5 (11 vs. 7.3%, p = ns), transient hypoparathyroidism (Calcium <2.00 mmol/L) 137 (18.6%) and 0 (p < 0.0001). Three of the 12 patients of Group 2 undergoing further surgery had a transient hypoparathyroidism. CONCLUSIONS: Thyroid lobectomy is an effective surgical strategy to manage papillary microcarcinomas with low complications. Routine completion thyroidectomy is not mandatory. Appropriate selection excluding high-risk patients is of paramount importance in order to achieve the best results.

Effects of walnut consumption on cognitive performance in young adults.

Walnuts contain a number of potentially neuroprotective compounds like vitamin E, folate, melatonin, several antioxidative polyphenols and significant amounts of n-3 α-linolenic fatty acid. The present study sought to determine the effect of walnuts on verbal and non-verbal reasoning, memory and mood. A total of sixty-four college students were randomly assigned to two treatment sequences in a crossover fashion: walnuts-placebo or placebo-walnuts. Baseline data were collected for non-verbal reasoning, verbal reasoning, memory and mood states. Data were collected again after 8 weeks of intervention. After 6 weeks of washout, the intervention groups followed the diets in reverse order. Data were collected once more at the end of the 8-week intervention period. No significant increases were detected for mood, non-verbal reasoning or memory on the walnut-supplemented diet. However, inferential verbal reasoning increased significantly by 11.2 %, indicating a medium effect size (P = 0.009; d = 0.567). In young, healthy, normal adults, walnuts do not appear to improve memory, mood or non-verbal reasoning abilities. However, walnuts may have the ability to increase inferential reasoning.

High-precision laser beam shaping using a binary-amplitude spatial light modulator.

We have achieved high-precision laser beam shaping by using a binary-amplitude spatial light modulator, a digital micromirror device (DMD), followed by an imaging telescope that contains a pinhole low-pass filter (LPF). An error diffusion algorithm was used to design the initial DMD pixel pattern based on the measured input beam profile. This pattern was iteratively refined by simulating the optically low-pass filtered DMD image and changing DMD pixels to lift valleys and suppress peaks. We noted the gap between the experimental result of 1.4% root-mean-square (RMS) error and the simulated result for the same DMD pattern of 0.3% RMS error. Therefore, we deemed it necessary to introduce iterative refinement based on actual measurements of the output image to further improve the uniformity of the beam. Using this method, we have demonstrated the ability to shape raw, non-spatially filtered laser beams (quasi-Gaussian beams) into beams with precisely controlled profiles that have an unprecedented level of RMS error with respect to the target profile. We have shown that our iterative refinement process is able to improve the light intensity uniformity to around 1% RMS error in a raw camera image for both 633 and 1064 nm laser beams. The use of a digital LPF on the camera image is justified in that it matches the performance of the pinhole filter in the experimental setup. The digital low-pass filtered results reveal that the actual optical beam profiles have RMS error down to 0.23%. Our approach has also demonstrated the ability to produce a range of target profiles as long as they have similar spatial-frequency content (i.e., a slowly varying beam profile). Circular and square cross-section flat-top beams and beams with a linear intensity variation within a circular and square cross section were produced with similarly low RMS errors. The measured errors were about twice the ultimate limit of 0.1% RMS error based on the number of binary DMD pixels that participate in the beam-formation process.

1.5% root-mean-square flat-intensity laser beam formed using a binary-amplitude spatial light modulator.

We demonstrate a digital micromirror device (DMD)-based optical system that converts a spatially noisy quasi-Gaussian to an eighth-order super-Lorentzian flat-top beam. We use an error-diffusion algorithm to design the binary pattern for the Texas Instruments DLP device. Following the DMD, a telescope with a pinhole low-pass filters the beam and scales it to the desired sized image. Experimental measurements show a 1% root-mean-square (RMS) flatness over a diameter of 0.28 mm in the center of the flat-top beam and better than 1.5% RMS flatness over its entire 1.43 mm diameter. The power conversion efficiency is 37%. We develop an alignment technique to ensure that the DMD pattern is correctly positioned on the incident beam. An interferometric measurement of the DMD surface flatness shows that phase uniformity is maintained in the output beam. Our approach is highly flexible and is able to produce not only flat-top beams with different parameters, but also any slowly varying target beam shape. It can be used to generate the homogeneous optical lattice required for Bose-Einstein condensate cold atom experiments.

Impaired niacin sensitivity in acute first-episode but not in multi-episode schizophrenia.

Niacin (vitamin B3) flushing--a marker of altered prostaglandin signaling--is indirectly linked to the phospholipid-prostaglandin metabolism. Diminished skin flushing was repeatedly found in schizophrenia, but has not been systematically investigated at different stages of disorder as yet. We compared niacin sensitivity of 32 first-episode and 32 multi-episode patients (mainly on stable medication) with age and gender matched healthy controls. Methylnicotinate was applied in three concentrations onto the inner forearm skin. Flush response was assessed in 3 min intervals over 15 min using optical reflection spectroscopy. Whereas first-episode patients showed significantly diminished flush response as compared to controls, comparable differences were not found between multi-episode patients and controls. Comparison of niacin sensitivity at different stages of schizophrenia support the notion of altered prostaglandin signaling primarily at the onset of disorder. Longitudinal studies have to rule out possible long-term effects of neuroleptic medication.

Biopharmaceutical production in transgenic livestock.

The production of recombinant human proteins in the milk of transgenic dairy animals offers a safe, renewable source of commercially important proteins that cannot be produced as efficiently in adequate quantities by other methods. A decade of success in expressing a variety of proteins in livestock has brought three human recombinant proteins to human clinical trials. Recent progress has drawn on molecular biology and reproductive physiology to improve the efficiency of producing and reproducing useful transgenic founder animals, and to improve the expression of heterologous proteins in their milk.

Capitated payment approaches for Medicaid-financed long-term care services.

In the following analysis, the authors examine the capitated payment approaches for long-term care (LTC) services of five programs: the Program of All-Inclusive Care for the Elderly (PACE), the Arizona Long-Term Care System (ALTCS), the Texas STAR + PLUS, the Minnesota Senior Health Option (MSHO), and the Monroe County Continuing Care Networks (CCNs) in New York. The authors describe key aspects in the design of these programs, with an emphasis on Medicaid reimbursement, and discuss differences and commonalities in the approaches taken by the programs in setting capitation rates.

Experimental comparative study of various mouthguards.

The aim of this study was to evaluate the mechanical and physical properties of several standard size commercially available mouthguards. For the purpose of objective testing, a special study model, which the various gum shield devices could be fitted onto, was developed to record tooth deflection caused by impact forces induced by a pendulum ram impact testing machine. The data measured on teeth provided with various gum shield devices were correlated with those of unprotected teeth; this enabled the individual cushioning effects of the respective devices and their specific force conduction to be evaluated. Using mouthguards considerably diminishes the deflection of the teeth subjected to stress in comparison with the row of unprotected teeth. In addition, force is transmitted to the adjacent teeth all the way to the distal regions of the row of teeth. The individual cushioning effects are directly correlated to the thickness of the material; the force distribution is determined by the rigidity of the gum shield device. The devices examined showed considerable differences with regard to force distribution and dimensioning. The study showed that this was due to the thickness of the materials, the manufacturing process and the composition of the materials of the devices examined. In comparison to laboratory-produced devices of similar material thickness, the devices that were designed to be fitted by the user achieved significantly poorer results as regards both cushioning properties and dissipation of exerted forces.

The effect of age on the level of human ABO blood group antibodies.

It is generally assumed that cellular and humoral immunity decline in aging humans. Although there have been reports that the naturally-occurring ABO antibodies also decline with age, some of the data are incomplete and others contradictory. Our study involved only healthy women of various ages and included assays of anti-A and anti-B titers in A, B, and O subjects. Statistical analyses of the data showed that while the antibody titers decreased with age, the amount of change was very small relative to the amount of variability among individuals and the variability attributable to blood type and season of the year. Comparisons with a previous study (1) from our laboratory showed that the changes due to aging were also small relative to the variability in titer scores within an individual over the course of a year. Based on this study, we conclude that the decrease in antibody titers with age is of doubtful clinical significance.

Developmental patterns of antioxidant defense mechanisms in human erythrocytes.

To obtain a profile of erythrocyte antioxidant defense potential during late fetal development, we studied selected antioxidant parameters in blood samples from 65 neonates with birth wt between 520 and 4210 g and from 12 healthy adults. Erythrocyte superoxide dismutase activity did not change significantly with maturation and no significant differences were observed among preterm infants grouped in increasing birth wt categories, term neonates, and adults. Erythrocyte catalase and glutathione peroxidase, as well as plasma vitamin E levels, showed highly significant positive correlations (p less than 0.001) with increasing fetal wt and gestational age; by term, CAT activity reached a level similar to the adult control group, but glutathione peroxidase activity, as well as plasma vitamin E levels, were markedly lower in all the preterm and in the term groups than in adults (p less than 0.01). Erythrocyte glutathione S-transferase activity showed a negative correlation with increasing gestational age (p less than 0.01) and the adult values were considerably lower than any of the neonatal levels (p less than 0.001). The role of glutathione S-transferase in erythrocyte metabolism remains obscure. Maturational changes in the activity of the red cell enzymes that were studied and in the plasma vitamin E level were apparent from about 31-36 wk of gestation, suggesting that the stimulation for these changes may have commenced from about 28-31 wk.

Identification of ataxia telangiectasia heterozygotes by flow cytometric analysis of X-ray damage.

Flow cytometry was used to identify heterozygotes for the autosomal recessive DNA-repair deficiency disease ataxia telangiectasia (AT). Confluent G0/G1 fibroblasts from 4 homozygotes (at/at), 5 obligate heterozygotes (at/+) and 7 presumed normal controls (+/+) were X-irradiated with 200 Rad and subcultured immediately in medium containing 5-bromodeoxyuridine (BrdU). Cells were harvested 72 h later and stained with fluoresceinated anti-BrdU antibody to identify cells that had entered S phase. They were counterstained with propidium iodide to measure total DNA content. On the basis of relative release from G0/G1, the at/+ strains as a group (33 +/- 3% release) were distinguished from both the presumed +/+ strains (60 +/- 3%) and at/at strains (85 +/- 3%), although the individual values for some strains did show overlap between genotypes. When 10 cell strains were coded and analyzed in 'blind' experiments, all 4 heterozygotes were correctly assigned, although one poorly growing presumed normal line was incorrectly assigned as a heterozygote. By a similar assay in which exponentially growing cultures were pulsed briefly with BrdU 8 h after irradiation with 400 Rad and then harvested immediately, presumed +/+ cells as a group could be distinguished from at/at cells but not from at/- cells. This combination of assays assists in the identification of all 3 AT genotypes. This should be of both basic and diagnostic use, particularly in families known to segregate AT.

Flow cytometric analysis of X-ray sensitivity in ataxia telangiectasia.

Flow cytometric analysis of 5-bromodeoxyuridine (BrdU) incorporation during DNA synthesis was used to characterize the effects of X-rays on cell-cycle kinetics in the DNA-repair deficiency disease ataxia telangiectasia (AT). Cultured fibroblasts from homozygotes (at/at), heterozygotes (at/+) and normal controls (+/+) were either: (1) irradiated, cultured, then pulsed with BrdU and harvested, or (2) pulsed with BrdU, irradiated, cultured and then harvested. Cells were then fixed and stained with both a fluoresceinated monoclonal antibody against BrdU to identify S-phase cells and with propidium diiodide to measure total DNA content. Irradiation of +/+ and at/+ cells induced a similar, transient G2/M arrest detectable within 8 h, which subsequently delayed by 6-8 h the passage of cells into G1 and depleted early S phase. In contrast, at/at cells failed to arrest in G2/M phase and entered the next cell cycle without pausing to repair radiation-induced damage. X-Rays also blocked entry of +/+ G1 cells into S phase, subsequently reducing the total S-phase population. This effect was not observed in at/at cells. These cell-cycle responses to radiation may be of diagnostic use and ultimately may help explain the basic defect in AT.