Targeted Protein Localization by Covalent 14-3-3 Recruitment.

14-3-3 proteins have a unique ability to bind and sequester a multitude of diverse phosphorylated signaling proteins and transcription factors. Many previous studies have shown that interactions of 14-3-3 with specific phosphorylated substrate proteins can be enhanced through small-molecule natural products or fully synthetic molecular glue interactions. However, enhancing 14-3-3 interactions with both therapeutically intractable transcription factor substrates and potential neo-substrates to sequester and inhibit their function remains elusive.

DCAF16-Based Covalent Handle for the Rational Design of Monovalent Degraders.

Targeted protein degradation with monovalent molecular glue degraders is a powerful therapeutic modality for eliminating disease causing proteins. However, rational design of molecular glue degraders remains challenging. In this study, we sought to identify a transplantable and linker-less covalent handle that could be appended onto the exit vector of various protein-targeting ligands to induce the degradation of their respective targets.

Induction of labor versus expectant management in patients with idiopathic polyhydramnios.

Objective: To evaluate whether induction of labor is associated with lower risk of cesarean section compared to expectant management in patients with isolated polyhydramnios.

Study Design: This is a single-center, retrospective cohort study of patients with pregnancies complicated by idiopathic polyhydramnios, documented between 34 and 38 weeks gestation, who were delivered between July 2012 and February 2020. The primary outcome was cesarean delivery.

BTN3A3 evasion promotes the zoonotic potential of influenza A viruses.

Spillover events of avian influenza A viruses (IAVs) to humans could represent the first step in a future pandemic. Several factors that limit the transmission and replication of avian IAVs in mammals have been identified. There are several gaps in our understanding to predict which virus lineages are more likely to cross the species barrier and cause disease in humans.

Comparison of intrapartum glycemic management strategies in pregnant women with type 1 diabetes mellitus.

Background: Achieving intrapartum maternal euglycemia in women with type 1 diabetes mellitus (T1DM) is critical to reducing the risk of neonatal hypoglycemia.

Objective: This study sought to compare the maternal and neonatal outcomes among women with T1DM by different intrapartum glycemic control strategies of continuation of subcutaneous insulin pumps versus intravenous insulin infusion.

Methods: A retrospective cohort study was performed to identify all women with type 1 diabetes mellitus in pregnancy between 1 October 2017 and 1 August 2020 at our tertiary medical center.

Standardization of thyroid ultrasound reporting in the community setting decreases biopsy rates.

Objective: With the rising incidence of thyroid cancer, a standardized approach to the evaluation of thyroid nodules is essential. Despite the presence of multiple national guidelines detailing evaluation and management of these nodules, significant variability exists in the information that is collected and reported to clinicians from diagnostic imaging. The aim of this study was to evaluate the impact of thyroid ultrasound standardization on thyroid cancer detection in a community practice setting.

Trends in the Surgical Management of Known or Suspected Differentiated Thyroid Cancer at a Single Institution, 2010-2018.

The surgical management of nodular thyroid disease has been influenced by the advent of molecular diagnostics and recent guidelines recommending a more conservative approach to low-risk thyroid tumors. The purpose of this study was to assess practice changes arising from the early adoption of current literature within a single high-volume center. A retrospective cohort study of all patients evaluated or surgically treated for known or suspected thyroid cancer at a single institution was performed (2010-2018).

Management of acute limb ischemia related to underlying pheochromocytoma.

Acute limb ischemia (ALI) related to pheochromocytoma is rare. We describe a 69-year-old woman who presented with ALI due to a thromboembolic phenomenon from new-onset atrial fibrillation that was successfully treated with intra-arterial catheter-directed lysis and systemic anticoagulation. Further workup revealed a left adrenal mass and biochemical test results consistent with pheochromocytoma.

Combination of Foley and prostaglandins versus Foley and oxytocin for cervical ripening: a network meta-analysis.

Background: Trial and meta-analysis data revealed a reduction in time to delivery for Foley and prostaglandins or Foley and oxytocin vs Foley alone. However, there are limited data for the comparison of the 2 combination methods against each other.

Objective: This study aimed to determine whether Foley and prostaglandins or Foley and oxytocin decrease the time to vaginal delivery using a network meta-analysis.

Skeletal effects of combined medical and surgical management of primary hyperparathyroidism.

Background: Parathyroidectomy (PTX) increases bone mineral density and decreases fracture risk in patients with primary hyperparathyroidism. This study examined the effect of adding bisphosphonates either before or after PTX on skeletal outcomes.

Methods: A retrospective cohort study of bisphosphonate-naïve patients (1995-2016) with osteoporosis and primary hyperparathyroidism (calcium >10.

Surgery for Primary Hyperparathyroidism with Normal Non-suppressed Parathyroid Hormone can be Both Challenging and Successful.

Background: Criteria for diagnosing primary hyperparathyroidism (PHPT) include hypercalcemia in the presence of parathyroid hormone (PTH) levels that are either elevated (classic PHPT) or normal but non-suppressed. However, there is no standard definition of what constitutes normal non-suppressed levels, and data are lacking regarding the potential for surgical cure in these patients.

Methods: A retrospective review of patients undergoing parathyroidectomy for sporadic PHPT between 2012 and 2014 was performed.

Detection of tactile inputs in the rat vibrissa pathway.

The rapid detection of sensory inputs is crucial for survival. Sensory detection explicitly requires the integration of incoming sensory information and the ability to distinguish between relevant information and ongoing neural activity. In this study, head-fixed rats were trained to detect the presence of a brief deflection of their whiskers resulting from a focused puff of air.

Cognitive and functional status after vein of Galen aneurysmal malformation endovascular occlusion.

Aim: To study the clinical outcomes of treating vein of Galen aneurysmal malformations (VGAM), we assessed our patient cohort using standardized cognitive and functional measures.

Methods: A retrospective review of patients with VGAM treated by a single practitioner between 2003 and 2009 was performed for this study. In addition to routine clinical assessment, all patients were evaluated for cognitive and functional impairment using validated measures including the Neurobehavioral Rating Scale-Revised, the Bicêtre outcome score, and the Barthel index.

Contrast-enhanced sonography as a novel tool for assessment of vascular malformations.

Background: Vascular malformations with arteriovenous shunt components can cause significant disability, chronic pain, and functional impairment. Effective treatment may require serial procedures, yet an imaging modality optimized to control cost and reduce radiation exposure in this predominantly pediatric population has not yet been identified.

Methods And Results: We describe the use of contrast-enhanced sonography as a novel tool to define vascular anatomy and localize arteriovenous shunting in a young patient with a symptomatic vascular malformation.

Prefrontal activity predicts monkeys' decisions during an auditory category task.

The neural correlates that relate auditory categorization to aspects of goal-directed behavior, such as decision-making, are not well understood. Since the prefrontal cortex (PFC) plays an important role in executive function and the categorization of auditory objects, we hypothesized that neural activity in the PFC should predict an animal's behavioral reports (decisions) during a category task. To test this hypothesis, we tested PFC activity that was recorded while monkeys categorized human spoken words (Russ et al.

Prefrontal neurons predict choices during an auditory same-different task.

The detection of stimuli is critical for an animal's survival [1]. However, it is not adaptive for an animal to respond automatically to every stimulus that is present in the environment [2-5]. Given that the prefrontal cortex (PFC) plays a key role in executive function [6-8], we hypothesized that PFC activity should be involved in context-dependent responses to uncommon stimuli.

Sex differences in learning and inhibition in spontaneously hypertensive rats.

Few studies have addressed potential differences in the nature of cognitive impairment observed in males and females with ADHD. In Experiment 1, we examined sex differences in conditioned inhibitory behaviour in spontaneously hypertensive rats (SHR strain), a purported animal model of ADHD. Rats were presented with two types of trials during each of the 15 conditioning sessions.