Efficient Total Chemical Synthesis of (13) C=(18) O Isotopomers of Human Insulin for Isotope-Edited FTIR.

Isotope-edited two-dimensional Fourier transform infrared spectroscopy (2 D FTIR) can potentially provide a unique probe of protein structure and dynamics. However, general methods for the site-specific incorporation of stable (13) C=(18) O labels into the polypeptide backbone of the protein molecule have not yet been established. Here we describe, as a prototype for the incorporation of specific arrays of isotope labels, the total chemical synthesis-via a key ester insulin intermediate-of 97 % enriched [(1-(13) C=(18) O)Phe(B24) ] human insulin: stable-isotope labeled at a single backbone amide carbonyl.

Critically re-evaluating a common technique: Accuracy, reliability, and confirmation bias of EMG.

Objectives: (1) To assess the diagnostic accuracy of EMG in radiculopathy. (2) To evaluate the intrarater reliability and interrater reliability of EMG in radiculopathy. (3) To assess the presence of confirmation bias in EMG.

Human insulin dynamics in women: a physiologically based model.

Currently available models of insulin dynamics are mostly based on the classical compartmental structure and, thus, their physiological utility is limited. In this work, we describe the development of a physiologically based model and its application to data from 154 patients who underwent an insulin-modified intravenous glucose tolerance test (IM-IVGTT). To determine the time profile of endogenous insulin delivery without using C-peptide data and to evaluate the transcapillary transport of insulin, the hepatosplanchnic, renal, and peripheral beds were incorporated into the circulatory model as separate subsystems.

Novel Report of Phosphoserine Phosphatase Deficiency in an Adult with Myeloneuropathy and Limb Contractures.

Serine is a nonessential amino acid that plays a vital role in proper development and functioning of the central nervous system (CNS). Serine deficiency leads to microcephaly, intellectual disability, seizures, and psychomotor retardation in children and severe axonal neuropathy in adults. Serine deficiency syndrome is due to a deficiency of one of three enzymes in the endogenous serine biosynthesis pathway: phosphoglycerate dehydrogenase, phosphoserine transaminase, or, most rarely, phosphoserine phosphatase.

Utility of Paraneoplastic Antibody Testing in the Diagnosis of Motor Neuron Disease.

Objective: To evaluate the role of paraneoplastic autoantibody testing in the diagnosis of motor neuron disease (MND).

Background: There have been rare case reports of paraneoplastic MND that have prompted many physicians to test for paraneoplastic autoantibodies in patients with MND. Our study is the first to determine the utility of such testing.

ADCY5-related dyskinesia: Broader spectrum and genotype-phenotype correlations.

Objective: To investigate the clinical spectrum and distinguishing features of adenylate cyclase 5 (ADCY5)-related dyskinesia and genotype-phenotype relationship.

Methods: We analyzed ADCY5 in patients with choreiform or dystonic movements by exome or targeted sequencing. Suspected mosaicism was confirmed by allele-specific amplification.

Inline radiofrequency pre-coagulation simplifies single-incision laparoscopic minor liver resection.

Background: Single-incision laparoscopy (SIL) has been developed to reduce surgical trauma, whereas technical difficulties in bleeding control limit the broad acceptance for hepatectomy. A novel minimized invasive strategy combining inline radiofrequency pre-coagulation and transumbilical SIL is presented herein.

Methods: A cohort of 21 selected patients underwent transumbilical SIL hepatectomies (segmentectomies II-VI) utilizing inline radiofrequency pre-coagulation for hepatic transection (Habib 4X).

Competitive Inhibition of the Endoplasmic Reticulum Signal Peptidase by Non-cleavable Mutant Preprotein Cargos.

Upon translocation across the endoplasmic reticulum (ER) membrane, secretory proteins are proteolytically processed to remove their signal peptide by signal peptidase (SPase). This process is critical for subsequent folding, intracellular trafficking, and maturation of secretory proteins. Prokaryotic SPase has been shown to be a promising antibiotic target.

Beta blockade increases pulmonary and systemic transit time heterogeneity: evaluation based on indocyanine green kinetics in healthy volunteers.

Knowledge of factors influencing the heterogeneity of blood transit times is important in cardiovascular physiology. The aim of the study was to investigate the effect of beta-adrenergic blockade on blood transit time dispersion in awake, anxious volunteers. Recirculatory modelling of the disposition of intravascular markers using parametric forms for transit time distributions, such as the inverse Gaussian distribution, provides the opportunity to estimate the systemic and pulmonary transit time dispersion in vivo.

Recurrent Isolated Sixth Nerve Palsy in Relapsing-Remitting Chronic Inflammatory Demyelinating Polyneuropathy.

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated sensory and motor demyelinating polyneuropathy that typically presents as a relapsing-remitting or progressive disorder. Cranial neuropathies infrequently occur in association with other more typical symptoms of CIDP.

Case Report: We report a case of CIDP with recurrent isolated sixth nerve palsy.

Diagnosis and Treatment of Work-Related Proximal Median and Radial Nerve Entrapment.

Proximal median (PMNE) and radial (RNE) nerve entrapment syndromes are uncommon. This article provides an evidenced-based treatment guideline for PMNE and RNE based on the available literature. Arriving at an accurate diagnosis must involve an electrodiagnostic (EDx) workup.

Diagnosis and Treatment of Work-Related Ulnar Neuropathy at the Elbow.

Ulnar neuropathy at the elbow (UNE) is the second most common entrapment neuropathy after carpal tunnel syndrome and occurs most commonly at the elbow due to mechanical forces that produce traction or ischemia to the nerve. The primary symptom associated with UNE is diminished sensation or dysesthesias in the fourth or fifth digits, often coupled with pain in the proximal medial aspect of the elbow. Treatment may be conservative or surgical, but optimal management remains controversial.

Identification of Habitat-Specific Biomes of Aquatic Fungal Communities Using a Comprehensive Nearly Full-Length 18S rRNA Dataset Enriched with Contextual Data.

Molecular diversity surveys have demonstrated that aquatic fungi are highly diverse, and that they play fundamental ecological roles in aquatic systems. Unfortunately, comparative studies of aquatic fungal communities are few and far between, due to the scarcity of adequate datasets. We combined all publicly available fungal 18S ribosomal RNA (rRNA) gene sequences with new sequence data from a marine fungi culture collection.

Entorrhizomycota: A New Fungal Phylum Reveals New Perspectives on the Evolution of Fungi.

Entorrhiza is a small fungal genus comprising 14 species that all cause galls on roots of Cyperaceae and Juncaceae. Although this genus was established 130 years ago, crucial questions on the phylogenetic relationships and biology of this enigmatic taxon are still unanswered. In order to infer a robust hypothesis about the phylogenetic position of Entorrhiza and to evaluate evolutionary trends, multiple gene sequences and morphological characteristics of Entorrhiza were analyzed and compared with respective findings in Fungi.

Timing of percutaneous cholecystostomy affects conversion rate of delayed laparoscopic cholecystectomy for severe acute cholecystitis.

Background: Percutaneous cholecystostomy is reserved for very high-operative-risk patients suffering from severe acute cholecystitis, who do not respond to conservative treatment. It is associated with high conversion rate to open surgery, when cholecystectomy is held later on. Our objective was to assess whether early timing of percutaneous cholecystostomy decreases conversion rate of delayed laparoscopic cholecystectomy to open surgery.

Individualized Risk of Surgical Complications: An Application of the Breast Reconstruction Risk Assessment Score.

Background: Risk discussion is a central tenet of the dialogue between surgeon and patient. Risk calculators have recently offered a new way to integrate evidence-based practice into the discussion of individualized patient risk and expectation management. Focusing on the comprehensive Tracking Operations and Outcomes for Plastic Surgeons (TOPS) database, we endeavored to add plastic surgical outcomes to the previously developed Breast Reconstruction Risk Assessment (BRA) score.

Multiple song features are related to paternal effort in common nightingales.

Background: Sexual ornamentation may be related to the degree of paternal care and the 'good-parent' model predicts that male secondary characters honestly advertise paternal investment. In most birds, males are involved in bringing up the young and successful reproduction highly depends on male contribution during breeding. In passerines, male song is indicative of male attributes and for few species it has been shown that song features also signal paternal investment to females.

Therapeutic impact of systemic AAV-mediated RNA interference in a mouse model of myotonic dystrophy.

RNA interference (RNAi) offers a promising therapeutic approach for dominant genetic disorders that involve gain-of-function mechanisms. One candidate disease for RNAi therapy application is myotonic dystrophy type 1 (DM1), which results from toxicity of a mutant mRNA. DM1 is caused by expansion of a CTG repeat in the 3' UTR of the DMPK gene.

Modeling the heterogeneous intestinal absorption of propiverine extended-release.

Propiverine is a widely used antimuscarinic drug with bioavailability that is limited by intestinal first-pass extraction. To study the apparent heterogeneity in intestinal first-pass extraction, we performed a population analysis of oral concentration-time data measured after administration of an extended-release formulation of propiverine in ten healthy subjects. Using an inverse Gaussian function as input model, the assumption that the systemically available fraction increases as a sigmoidal function of time considerably improved the fit.