American Radium Society Appropriate Use Criteria for the Workup and Treatment of Local Intraprostatic Recurrence of Prostate Cancer Following Definitive Radiotherapy.

Background And Objective: Local intraprostatic radiorecurrence of prostate cancer (IPR-PC) can be associated with an aggressive natural history and impact long-term disease-specific survival. While appropriate local salvage intervention can be curative, best practices for workup and local salvage of intraprostatic recurrence are poorly defined. The American Radium Society (ARS) Genitourinary Appropriate Use Criteria Committee sought to develop evidence-based recommendations to address this gap.

Financing Policy Considerations From Texas to Optimize Care for Children With Medical Complexity.

Texas has a tremendous opportunity and momentum to build a more effective system of care for children with medical complexity (CMC) and their families. This is evidenced by growing collaboration among many committed partners since implementation of the Medicaid STAR Kids managed care program in 2016 and Texas' participation in a US Health Resources and Services Administration-funded, 10-state Collaborative Improvement and Innovation Network to Advance Care for CMC from 2017 to 2022. Texas has several comprehensive health homes for CMC that position the state to serve as a national model of integrated, family-centered care for CMC and ensure high-quality care to an exceedingly vulnerable population.

Divergent metabolic phenotypes in two genetic syndromes of low insulin secretion.

Aims: We examined the effect of growth hormone (GH) counter-regulation on carbohydrate metabolism in individuals with life-long diminished insulin secretion (DIS).

Methods: Adults homozygous for the E180 splice site mutation of GHR [Laron syndrome (LS)], adults with a gain-of-function mutation in CDKN1c [Guevara-Rosenbloom syndrome (GRS)], and controls were evaluated for body composition, leptin, total and high molecular weight (HMW) adiponectin, insulin-like growth factor (IGF) axis molecules, and a 5-hour oral glucose tolerance test (OGTT), with measurements of glucose, insulin, glucagon, ghrelin, pancreatic polypeptide, gastric inhibitory peptide, glucagon-like peptide-1, peptide YY, and islet amyloid polypeptide (IAPP).

Results: Both syndromic cohorts displayed DIS during OGTT.

High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging.

Resolving the spatial distribution of RNA and protein in tissues at subcellular resolution is a challenge in the field of spatial biology. We describe spatial molecular imaging, a system that measures RNAs and proteins in intact biological samples at subcellular resolution by performing multiple cycles of nucleic acid hybridization of fluorescent molecular barcodes. We demonstrate that spatial molecular imaging has high sensitivity (one or two copies per cell) and very low error rate (0.

Mechanism of actin filament nucleation.

We used computational methods to analyze the mechanism of actin filament nucleation. We assumed a pathway where monomers form dimers, trimers, and tetramers that then elongate to form filaments but also considered other pathways. We aimed to identify the rate constants for these reactions that best fit experimental measurements of polymerization time courses.

β-Catenin signaling dynamics regulate cell fate in differentiating neural stem cells.

Stem cells undergo differentiation in complex and dynamic environments wherein instructive signals fluctuate on various timescales. Thus, cells must be equipped to properly respond to the timing of signals, for example, to distinguish sustained signaling from transient noise. However, how stem cells respond to dynamic variations in differentiation cues is not well characterized.

Comparative Proteomics Enables Identification of Nonannotated Cold Shock Proteins in E. coli.

Recent advances in mass spectrometry-based proteomics have revealed translation of previously nonannotated microproteins from thousands of small open reading frames (smORFs) in prokaryotic and eukaryotic genomes. Facile methods to determine cellular functions of these newly discovered microproteins are now needed. Here, we couple semiquantitative comparative proteomics with whole-genome database searching to identify two nonannotated, homologous cold shock-regulated microproteins in Escherichia coli K12 substr.

At Light Speed: Advances in Optogenetic Systems for Regulating Cell Signaling and Behavior.

Cells are bombarded by extrinsic signals that dynamically change in time and space. Such dynamic variations can exert profound effects on behaviors, including cellular signaling, organismal development, stem cell differentiation, normal tissue function, and disease processes such as cancer. Although classical genetic tools are well suited to introduce binary perturbations, new approaches have been necessary to investigate how dynamic signal variation may regulate cell behavior.

A half-century of studies of growth hormone insensitivity/Laron syndrome: A historical perspective.

Unlabelled: A growth hormone (GH) dependent substance responsible for sulfate uptake by costal cartilage of hypophysectomized rats, labeled sulfation factor, was reported in 1957. In 1962 the radioimmunoassay for GH was described. The clinical picture of severe GH deficiency but with high serum concentrations of GH was reported in 3 siblings in 1966 and followed by a 1968 report of 22 patients belonging to 14 consanguineous oriental Jewish families in Israel.

GH Receptor Deficiency in Ecuadorian Adults Is Associated With Obesity and Enhanced Insulin Sensitivity.

Context: Ecuadorian subjects with GH receptor deficiency (GHRD) have not developed diabetes, despite obesity.

Objective: We sought to determine the metabolic associations for this phenomenon.

Design: Four studies were carried out: 1) glucose, lipid, adipocytokine concentrations; 2) metabolomics evaluation; 3) metabolic responses to a high-calorie meal; and 4) oral glucose tolerance tests.

Obesity, diabetes and cancer: insight into the relationship from a cohort with growth hormone receptor deficiency.

Obesity with insulin-resistant diabetes and increased cancer risk is a global problem. We consider the alterations of metabolism attendant on the underlying pathogenic overnutrition and the role of the growth hormone (GH)-IGF-1 axis in this interaction. Obesity-induced insulin resistance is a determinant of diabetes.

Optimized two-color super resolution imaging of Drp1 during mitochondrial fission with a slow-switching Dronpa variant.

We studied the single-molecule photo-switching properties of Dronpa, a green photo-switchable fluorescent protein and a popular marker for photoactivated localization microscopy. We found the excitation light photoactivates as well as deactivates Dronpa single molecules, hindering temporal separation and limiting super resolution. To resolve this limitation, we have developed a slow-switching Dronpa variant, rsKame, featuring a V157L amino acid substitution proximal to the chromophore.

Sudden death of a young woman attributed to diabetic ketoacidosis.

A young woman's death at home was attributed to new onset diabetic ketoacidosis with subsequent litigation supported by several expert consultants, despite a history and postmortem findings inconsistent with this diagnosis. More thorough tissue study of the heart and analysis of the circumstances led to a credible explanation of the entire scenario.

Exploring signatures of positive selection in pigmentation candidate genes in populations of East Asian ancestry.

Background: Currently, there is very limited knowledge about the genes involved in normal pigmentation variation in East Asian populations. We carried out a genome-wide scan of signatures of positive selection using the 1000 Genomes Phase I dataset, in order to identify pigmentation genes showing putative signatures of selective sweeps in East Asia. We applied a broad range of methods to detect signatures of selection including: 1) Tests designed to identify deviations of the Site Frequency Spectrum (SFS) from neutral expectations (Tajima's D, Fay and Wu's H and Fu and Li's D* and F*), 2) Tests focused on the identification of high-frequency haplotypes with extended linkage disequilibrium (iHS and Rsb) and 3) Tests based on genetic differentiation between populations (LSBL).

Recommended IGF-I dosage causes greater fat accumulation and osseous maturation than lower dosage and may compromise long-term growth effects.

Context: The maximum dose of IGF-I recommended for treatment of GH insensitivity is commonly used.

Objective: The aim was to test the hypothesis that a lower dose is as effective as a high dose of IGF-I in growth promotion and has fewer deleterious effects.

Design And Setting: Subjects were treated for 3 years with regular examinations including bone age and dual energy x-ray absorptiometry and for 1 year with abdominal ultrasound studies at a clinical research institute in Quito, Ecuador.