Farleyziegler1478

Resolving the genetic architecture of painful neuropathy will lead to better disease management strategies. We aimed to develop a reliable method to re-sequence multiple genes in a large cohort of painful neuropathy patients at low cost. In this study, we compared sensitivity, specificity, targeting efficiency, performance and cost effectiveness of Molecular Inversion Probes-Next generation sequencing (MIPs-NGS) and TruSeq® Custom Amplicon-Next generation sequencing (TSCA-NGS). Capture probes were designed to target nine sodium channel genes (SCN3A, SCN8A-SCN11A, and SCN1B-SCN4B). One hundred sixty-six patients with diabetic and idiopathic neuropathy were tested by both methods, 70 patients were validated by Sanger sequencing. Sensitivity, specificity and performance of both techniques were comparable, and in agreement with Sanger sequencing. The average targeted regions coverage for MIPs-NGS was 97.3% versus 93.9% for TSCA-NGS. MIPs-NGS has a more versatile assay design and is more flexible than TSCA-NGS. The cost of MIPs-NGS is >5 times cheaper than TSCA-NGS when 500 or more samples are tested. In conclusion, MIPs-NGS is a reliable, flexible, and relatively inexpensive method to detect genetic variations in a large cohort of patients. In our centers, MIPs-NGS is currently implemented as a routine diagnostic tool for screening of sodium channel genes in painful neuropathy patients.Sugars are commonly supplemented into vitrification solution to dehydrate cells in order to reduce the formation of fatal intracellular ice crystals. Natural honey is a mixture of 25 sugars (mainly fructose and glucose) that have different biological and pharmacological benefits. The present study was designed to determine if honey can be used as a nonpermeating cryoprotectant in vitrification of bovine oocytes. In the first experiment, denuded-MII oocytes were exposed to 0.25, 0.5, 1.0, 1.5 or 2.0 M of honey or sucrose. Natural honey and sucrose caused similar ooplasm dehydration. A significant relationship existed between time and ooplasm volume change (P less then 0.05), during dehydration and rehydration phases, in both honey and sucrose solutions. In the second experiment, the immature cumulus-oocyte complexes (COCs) were vitrified in an EG/DMSO-based vitrification solution containing honey (0.5, 1 or 1.5 M) or sucrose (0.5 M) as a gold standard. The vitrified-warmed COCs were matured in vitro and evaluated for nuclear maturation. The maturation (MII) rate was greater in nonvitrified control (81%) than vitrified groups (54%, P less then 0.05). In the third experiment, COCs were either remained nonvitrified (control) or vitrified in 1.0 M honey or 0.5 M sucrose, followed by IVM, IVF and IVC (for 9 days). Cleavage rate was greater in control (74%) than in vitrified groups (47%, P less then 0.05), without significant difference between sugars. Blastocyst rate was 34, 13 and 3% in control, honey and sucrose groups respectively (P less then 0.05). In conclusion, natural honey acted as a nonpermeating cryoprotectant in vitrification solution and improved the embryonic development in vitrified bovine COCs.[This corrects the article DOI 10.1371/journal.pone.0235607.].Somatic copy number alterations (CNA) are common in endometrial serous carcinoma (ESC). We used the Tumor Cancer Genome Atlas Pan Cancer dataset (TCGA Pan Can) to explore the impact of somatic CNA and gene expression levels (mRNA) of cancer-related genes in ESC. Results were correlated with clinico-pathologic parameters such as age of onset, disease stage, progression-free survival (PFS) and overall survival (OS) (n = 108). 1,449 genes with recurrent somatic CNA were identified, observed in 10% or more tumor samples. Somatic CNA and mRNA expression levels were highly correlated (r> = 0.6) for 383 genes. Among these, 45 genes were classified in the Tier 1 category of Cancer Genome Census-Catalogue of Somatic Mutations in Cancer. Eighteen of 45 Tier 1 genes had highly correlated somatic CNA and mRNA expression levels including ARNT, PIK3CA, TBLXR1, ASXL1, EIF4A2, HOOK3, IKBKB, KAT6A, TCEA1, KAT6B, ERBB2, BRD4, KEAP1, PRKACA, DNM2, SMARCA4, AKT2, SS18L1. Our results are in agreement with previously reported somatic CNA for ERBB2, BRD4 and PIK3C in ESC. In addition, AKT2 (p = 0.002) and KAT6A (p = 0.015) amplifications were more frequent in tumor samples from younger patients ( less then 60), and CEBPA (p = 0.028) and MYC (p = 0.023) amplifications were more common with advanced (stage III and IV) disease stage. Patients with tumors carrying KAT6A and MYC amplifications had shorter PFS and OS. selleck chemical The hazard ratio (HR) of KAT6A was 2.82 [95 CI 1.12-7.07] for PFS and 3.87 [95 CI 1.28-11.68] for OS. The HR of MYC was 2.25 [95 CI 1.05-4.81] and 2.62[95 CI 1.07-6.41] for PFS and OS, respectively.

Uncomplicated urinary tract infections (UTIs) can often be diagnosed based solely on symptoms and should be treated with a short course of narrow spectrum antibiotics. However, clinicians often order urine analyses and prescribe long courses of broad spectrum antibiotics.

The objectives of our study are 1) Understand how primary care providers and residents clinically approach UTIs and 2) to understand specific opportunities, based on provider type, to target future antibiotic stewardship interventions.

We conducted semi-structured qualitative interviews of community primary care providers (n = 15) and internal medicine residents (n = 15) in St. Louis, Missouri from 2018-2019. A 5-point Likert scale was used to evaluate participant preferences for possible interventions. Interviews were transcribed, de-identified, and coded by two independent researchers using a combination inductive and deductive approach.

Several common themes emerged. Both providers and residents ordered urine tests to "confirm" pridelines, and pragmatic clinical decision support systems are needed to improve antibiotic prescribing and diagnostic testing; optimal interventions to improve UTI management may vary based on provider training level.

Significant opportunities exist to optimize urinary tract infection management among residents and community providers. Multifaceted interventions that include provider education, synthesis of guidelines, and pragmatic clinical decision support systems are needed to improve antibiotic prescribing and diagnostic testing; optimal interventions to improve UTI management may vary based on provider training level.