Factors associated with receiving an obesity diagnosis and obesity-related treatment for patients with obesity class II and III within a single integrated health system.

Objectives: The prevalence and associated adverse effects of obesity on health and healthcare cost make it a primary public health concern. However, individuals with the physiological features of obesity may be underdiagnosed and undertreated. We aimed to determine the prevalence of obesity diagnoses and obesity-related treatments in an integrated health system and determine the factors associated with receiving an obesity diagnosis and treatment for this indication.

HDL Phospholipids, but Not Cholesterol Distinguish Acute Coronary Syndrome From Stable Coronary Artery Disease.

Background Although acute coronary syndromes (ACS) are a major cause of morbidity and mortality, relationships with biologically active lipid species potentially associated with plaque disruption/erosion in the context of their lipoprotein carriers are indeterminate. The aim was to characterize lipid species within lipoprotein particles which differentiate ACS from stable coronary artery disease. Methods and Results Venous blood was obtained from 130 individuals with de novo presentation of an ACS (n=47) or stable coronary artery disease (n=83) before coronary catheterization.

Computational analysis of contractility in engineered heart tissue.

Engineered heart tissue (EHT) is a potential therapy for heart failure and the basis of functional in vitro assays of novel cardiovascular treatments. Self-organizing EHT can be generated in fiber form, which makes the assessment of contractile function convenient with a force transducer. Contractile function is a key parameter of EHT performance.

Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly.

Frataxin, a conserved nuclear-encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich's ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone in the assembly pathway.

Solvation response along the reaction coordinate in the active site of ketosteroid isomerase.

A light-activated reaction analog has been developed to mimic the catalytic reaction cycle of Delta(5)-3-ketosteroid isomerase to probe the functionally relevant protein solvation response to the catalytic charge transfer. Delta(5)-3-ketosteroid isomerase from Pseudomonas putida catalyzes a C-H bond cleavage and formation through an enolate intermediate. Conversion of the ketone substrate to the enolate intermediate is simulated by a photoacid bound to the active site oxyanion hole.

Proton affinity of the oxyanion hole in the active site of ketosteroid isomerase.

The absorption spectra of a series of inhibitors bound at the active site of Delta(5)-3-ketosteroid isomerase from Pseudomonas putida were found to exhibit substantial variations in the contributions of the protonated and deprotonated forms. Systematic variation of the inhibitor solution pK(a) combined with a method of quantifying the contributions of each protonation state showed the oxyanion hole in the active site of wild-type Delta(5)-3-ketosteroid isomerase to have a proton affinity equal to a solution pK(a) of 10.05 +/- 0.

Deconstructing green fluorescent protein.

Green fluorescent protein (GFP) has been reassembled from two pieces, a large fragment 214 amino acids in length that is produced recombinantly (GFP 1-10) and a short synthetic peptide corresponding to the 11th stave of the beta-barrel that is 16 amino acids long (synthetic GFP 11), following a system developed by Waldo and co-workers (Cabantous, S.; et al. Nat.

Dynamic Stokes shift in green fluorescent protein variants.

Solvent reorganization around the excited state of a chromophore leads to an emission shift to longer wavelengths during the excited-state lifetime. This solvation response is absent in wild-type green fluorescent protein, and this has been attributed to rigidity in the chromophore's environment necessary to exclude nonradiative transitions to the ground state. The fluorescent protein mPlum was developed via directed evolution by selection for red emission, and we use time-resolved fluorescence to study the dynamic Stokes shift through its evolutionary history.

Anomalous negative fluorescence anisotropy in yellow fluorescent protein (YFP 10C): quantitative analysis of FRET in YFP dimers.

Yellow fluorescent protein (YFP) is widely used as a genetically encoded fluorescent marker in biology. In the course of a comprehensive study of this protein, we observed an unusual, negative fluorescence anisotropy at pH 6.0 (McAnaney, T.

Ultrafast excited-state dynamics in the green fluorescent protein variant S65T/H148D. 2. Unusual photophysical properties.

In the preceding accompanying paper [Shu, X., et al. (2007) Biochemistry 46, 12005-12013], the 1.

Ultrafast excited-state dynamics in the green fluorescent protein variant S65T/H148D. 1. Mutagenesis and structural studies.

Wild type green fluorescent protein (wt-GFP) and the variant S65T/H148D each exhibit two absorption bands, A and B, which are associated with the protonated and deprotonated chromophores, respectively. Excitation of either band leads to green emission. In wt-GFP, excitation of band A ( approximately 395 nm) leads to green emission with a rise time of 10-15 ps, due to excited-state proton transfer (ESPT) from the chromophore hydroxyl group to an acceptor.

Measurement of solvation responses at multiple sites in a globular protein.

Proteins respond to electrostatic perturbations through complex reorganizations of their charged and polar groups, as well as those of the surrounding media. These solvation responses occur both in the protein interior and on its surface, though the exact mechanisms of solvation are not well understood, in part because of limited data on the solvation responses for any given protein. Here, we characterize the solvation kinetics at sites throughout the sequence of a small globular protein, the B1 domain of streptococcal protein G (GB1), using the synthetic fluorescent amino acid Aladan.

Masterless soft lithography: patterning UV/ozone-induced adhesion on poly(dimethylsiloxane) surfaces.

A novel microreactor-based photomask capable of effecting high resolution, large area patterning of UV/ozone (UVO) treatments of poly(dimethylsiloxane) (PDMS) surfaces is described. This tool forms the basis of two new soft lithographic patterning techniques that significantly extend the design rules of decal transfer lithography (DTL). The first technique, photodefined cohesive mechanical failure, fuses the design rules of photolithography with the contact-based adhesive transfer of PDMS in DTL.

Large-area patterning of coinage-metal thin films using decal transfer lithography.

We describe two new procedures that appear to hold significant promise as means for patterning thin-film microstructures of the coinage metals (Cu, Ag, Au). A feature central to both is the modification of their surfaces to promote the adhesive transfer of PDMS thin-film microstructures, a material suitable for use as resist layers in large-area patterning, using Decal Transfer Lithography (DTL). The present work provides a significant extension of the capabilities of DTL patterning, providing general protocols that can be used to transfer decal resists to essentially any substrate surface.

Decal transfer microlithography: a new soft-lithographic patterning method.

A new soft-lithographic method for micropatterning polymeric resists, Decal Transfer Microlithography (DTM), is described. This technique is based on the transfer of elastomeric decal patterns via the engineered adhesion and release properties of a compliant poly(dimethylsiloxane) (PDMS) patterning tool. An important feature of the DTM method is the exceptionally broad spectrum of design rules that it embraces.

Hypodontia: genotype or environment? A case report of monozygotic twins.

A case report is presented of monozygotic twins with variable expression of hypodontia. DNA fingerprinting was used to confirm monozygosity, and this evidence supports the theory that genetic coding is not the sole controlling factor in tooth agenesis. It is suggested that DNA fingerprinting should be considered the gold standard for determination of monozygosity.

The value of routine computed tomography scanning of the chest in patients presenting with supradiaphragmatic Hodgkin's disease.

Six patients presenting with supradiaphragmatic Hodgkin's disease are presented to demonstrate the potential benefits of chest computed tomography (CT) scanning as a routine staging procedure. These cases show that CT scanning can detect mediastinal and lung involvement not readily detected by other investigations, and that such findings can influence the radiotherapy plan, the need for extended radiotherapy fields or the use of chemotherapy. Following treatment, CT scanning can be useful to assess treatment response and may permit earlier detection of relapse.

Primary malignant mediastinal germ cell tumours: improved prognosis with platinum-based chemotherapy and surgery.

A retrospective analysis was performed of 18 patients with primary malignant germ cell tumours of the mediastinum treated with platinum-based chemotherapy between 1977 and 1990. All seven patients with pure seminoma were treated initially with chemotherapy and four of these patients received additional mediastinal radiotherapy. Only one patient relapsed; his initial therapy had included radiotherapy and single-agent carboplatin and he was successfully salvaged with combination chemotherapy.

The optimisation of carboplatin dose in carboplatin, etoposide and bleomycin combination chemotherapy for good prognosis metastatic nonseminomatous germ cell tumours of the testis.

An analysis of carboplatin dose response was performed in 121 patients with good prognosis metastatic nonseminomatous germ cell tumours (NSGCT) of the testis, referred to the Royal Marsden Hospital since 1984, who had been given combination carboplatin, etoposide and bleomycin (CEB) chemotherapy. With a median follow-up of 40 months (range: 7 to 85 months) nine patients (7%) have failed CEB. Carboplatin dose was analysed in all patients using body surface area (BSA) to derive a carboplatin dose per metre squared (mg/m2) and by calculation of a predicted serum concentration chi time (AUC: area under the curve) derived from the glomerular filtration rate (GFR), using the formula; Dose = AUC(GFR + 25).

The management of metastases to eye and orbit from carcinoma of the breast.

This report describes 11 patients who developed visual symptoms due to choroidal or orbital metastases from carcinoma of the breast. All patients were treated using palliative radiotherapy with regression of metastases in five of six patients (83%) having choroidal involvement and three of five patients (60%) having orbital metastases. There were no complications due to radiotherapy.