Sweet syndrome: a sweet disease with a bitter diagnosis

Sweet syndrome is an acute febrile neutrophilic dermatosis first described by Robert Douglas Sweet in 1964. Sweet syndrome presents in three clinical settings: classical (or idiopathic), malignancy-associated, and drug-induced. It has been associated with hematopoietic malignancies and myelodysplastic disorders. A-28-years married woman presented to us with chief complaints of Fever and Multiple swellings over the body since 2 months. At presentation she has Pallor; venous hum present. Multiple, tender, erythematous subcutaneous swellings, firm in consistency noted in both forearms. Skin over the swellings is pinchable; superficial skin is normal. Sweet syndrome can occasionally cause an intense systemic response involving the lungs, liver and musculoskeletal system. The skin lesions in Sweet syndrome typically start as erythematous papules, plaques, and nodules. The lesions can take on pseudovesicular or pseudopustular appearance, and sometimes fully formed vesicles or pustules develop. The lesions can be subcutaneous mimicking erythema nodosum which can’t be differentiated unless a biopsy is taken. Because the diagnosis of Sweet syndrome can be challenging, particularly when associated with other connective tissue disorders such as SLE, a set of diagnostic criteria were proposed initially by Su and Liu and then revised by Von den Driesch. The diagnosis is based upon the presence of two major and two of the four minor criteria. Concurrent Sweet syndrome and SLE are exceedingly rare. Twelve patients with both Sweet syndrome and systemic lupus erythematosus (SLE) have been previously reported. We report a case of sweet syndrome associated with SLE diagnosed in our hospital. In our patient, diagnostic criteria are satisfied for Sweet syndrome as well as for SLE (ACR criteria-patient had polyarthralgia, anemia, thrombocytopenia, ANA and Ds DNA positive. Four out of 11 are fulfilled for SLE). Patient responded to corticosteroids

Effect of Structural Relaxation on the Indentation Size Effect and Deformation Behavior of Cu–Zr–Based Nanoglasses

In this work, the deformation behavior of as-prepared (AP) and structurally relaxed (SR) Cu–Zr–based nanoglasses (NGs) are investigated using nano- and micro-indentation. The NGs are subjected to structural relaxation by annealing them close to the glass transition temperature without altering their amorphous nature. The indentation load, p, vs. displacement, h, curves of SR samples are characterized by discrete displacement bursts, while the AP samples do not show any of them, suggesting that annealing has caused a local change in the amorphous structure. In both the samples, hardness (at nano- and micro-indentation) decreases with increasing p, demonstrating the indentation size effect. The micro-indentation imprints of SR NGs show evidence of shear bands at the periphery, indicating a heterogeneous plastic flow, while AP NG does not display any shear bands. Interestingly, the shear band density decreases with p, highlighting the fact that plastic strain is accommodated entirely by the shear bands in the subsurface deformation zone. The results are explained by the differences in the amorphous structure of the two NGs

Carotid-cavernous fistula as a mimicker of myasthenia gravis

BACKGROUND: A carotid-cavernous fistula (CCF) is an abnormal communication between the carotid arterial system and the cavernous sinus. Common symptoms of CCFs include proptosis and ophthalmoplegia, but fluctuating diplopia and presence of ptosis are not typical. CASE DESCRIPTION: We present an unusual case of CCF with fluctuating binocular diplopia and ptosis, mimicking myasthenia gravis. Electrodiagnostic testing, which included repetitive nerve stimulation and single-fiber electromyography, was normal. Magnetic resonance imaging of the brain and orbits was initially normal, but later magnetic resonance angiography revealed enlargement of the left superior ophthalmic vein along with a left CCF. Patient underwent a successful left cavernous sinus embolization. CONCLUSION: Fluctuating ophthalmic symptoms are a typical presentation of myasthenia gravis; however, there may be an association of these symptoms with a CCF. Repetitive nerve stimulation and single-fiber electromyography played a key role in diagnosis of this case, as the normal result led to further investigations revealing a CCF

MODBASE, a database of annotated comparative protein structure models and associated resources.

MODBASE (http://salilab.org/modbase) is a database of annotated comparative protein structure models. The models are calculated by MODPIPE, an automated modeling pipeline that relies primarily on MODELLER for fold assignment, sequence-structure alignment, model building and model assessment (http:/salilab.org/modeller). MODBASE currently contains 5,152,695 reliable models for domains in 1,593,209 unique protein sequences; only models based on statistically significant alignments and/or models assessed to have the correct fold are included. MODBASE also allows users to calculate comparative models on demand, through an interface to the MODWEB modeling server (http://salilab.org/modweb). Other resources integrated with MODBASE include databases of multiple protein structure alignments (DBAli), structurally defined ligand binding sites (LIGBASE), predicted ligand binding sites (AnnoLyze), structurally defined binary domain interfaces (PIBASE) and annotated single nucleotide polymorphisms and somatic mutations found in human proteins (LS-SNP, LS-Mut). MODBASE models are also available through the Protein Model Portal (http://www.proteinmodelportal.org/)

Chronic kidney disease in gout in a managed care setting

<p>Abstract</p> <p>Background</p> <p>To study the prevalence of chronic kidney disease (CKD) and its impact on allopurinol dosing and uric acid control among patients with gout.</p> <p>Methods</p> <p>This was a retrospective study using data from a large US health plan. Claims and laboratory data were analyzed for enrollees from the health plan database from January 2002 through December 2005. Patients with gout were identified from pharmacy and medical claims data based on the presence of codes for gout medication or gout diagnosis. Severity of CKD was determined using the estimated glomerular filtration rate (eGFR). Allopurinol titration was defined as a change in average daily dose from first prescription to last prescription of ≥ 50 mg.</p> <p>Results</p> <p>A total of 3,929 patients were identified for inclusion in this study, 39% of whom had CKD (based on having an eGFR < 90 mL/min/1.73 m²). Subjects with CKD were older (p < 0.01) and more likely to be women (p < 0.01), had a greater number of comorbid conditions (p < 0.01), and were more likely to be prescribed allopurinol (p < 0.01) compared to those with no CKD. The average starting dose of allopurinol was lower among those with CKD, and it decreased with worsening kidney function. Among the 3,122 gout patients who used allopurinol, only 25.6% without CKD and 22.2% with CKD achieved a serum uric acid concentration of < 6.0 mg/dL (p = 0.0409). Also, only 15% of allopurinol users had an upward dose titration (by ≥50 mg), but the average increase in dose did not differ significantly between those with and without CKD.</p> <p>Conclusions</p> <p>About two out of every five patients with gout in this population had CKD. Allopurinol doses were not adjusted in the majority of CKD patients. Serum uric acid control in gout was poor among patients without CKD and even worse among those with CKD.</p

Structure of the 80S Ribosome from Saccharomyces cerevisiae—tRNA-Ribosome and Subunit-Subunit Interactions

AbstractA cryo-EM reconstruction of the translating yeast 80S ribosome was analyzed. Computationally separated rRNA and protein densities were used for docking of appropriately modified rRNA models and homology models of yeast ribosomal proteins. The core of the ribosome shows a remarkable degree of conservation. However, some significant differences in functionally important regions and dramatic changes in the periphery due to expansion segments and additional ribosomal proteins are evident. As in the bacterial ribosome, bridges between the subunits are mainly formed by RNA contacts. Four new bridges are present at the periphery. The position of the P site tRNA coincides precisely with its prokaryotic counterpart, with mainly rRNA contributing to its molecular environment. This analysis presents an exhaustive inventory of an eukaryotic ribosome at the molecular level

Prediction of enzyme function by combining sequence similarity and protein interactions

<p>Abstract</p> <p>Background</p> <p>A number of studies have used protein interaction data alone for protein function prediction. Here, we introduce a computational approach for annotation of enzymes, based on the observation that similar protein sequences are more likely to perform the same function if they share similar interacting partners.</p> <p>Results</p> <p>The method has been tested against the PSI-BLAST program using a set of 3,890 protein sequences from which interaction data was available. For protein sequences that align with at least 40% sequence identity to a known enzyme, the specificity of our method in predicting the first three EC digits increased from 80% to 90% at 80% coverage when compared to PSI-BLAST.</p> <p>Conclusion</p> <p>Our method can also be used in proteins for which homologous sequences with known interacting partners can be detected. Thus, our method could increase 10% the specificity of genome-wide enzyme predictions based on sequence matching by PSI-BLAST alone.</p

A road map for the generation of a near-infrared guide star catalog for thirty meter telescope observations

The near-infrared instruments in the upcoming Thirty Meter Telescope (TMT) will be assisted by a multi conjugate Adaptive Optics (AO) system. For the efficient operation of the AO system, during observations, a near-infrared guide star catalog which goes as faint as 22 mag in JVega band is essential and such a catalog does not exist. A methodology, based on stellar atmospheric models, to compute the expected near-infrared magnitudes of stellar sources from their optical magnitudes is developed. The method is applied and validated in JHKs bands for a magnitude range of JVega 16–22 mag. The methodology is also applied and validated using the reference catalog of PAN STARRS. We verified that the properties of the final PAN STARRS optical catalog will satisfy the requirements of TMT IRGSC and will be one of the potential sources for the generation of the final catalog. In a broader context, this methodology is applicable for the generation of a guide star catalog for any existing/upcoming near-infrared telescopes

The cohesin ring concatenates sister DNA molecules

Sister chromatid cohesion, which is essential for mitosis, is mediated by a multi-subunit protein complex called cohesin whose Scc1, Smc1, and Smc3 subunits form a tripartite ring structure. It has been proposed that cohesin holds sister DNAs together by trapping them inside its ring. To test this, we used site-specific cross-linking to create chemical connections at the three interfaces between the ring’s three constituent polypeptides, thereby creating covalently closed cohesin rings. As predicted by the ring entrapment model, this procedure produces dimeric DNA/cohesin structures that are resistant to protein denaturation. We conclude that cohesin rings concatenate individual sister minichromosome DNAs