Morphine and P2Y12 Inhibitors in ST-Elevation Myocardial Infarction: An Updated Meta-Analysis.

Background: Morphine is used to control pain in ST-elevation myocardial infarction but reduces P2Y12 inhibition. It is not known if this modulation of platelet inhibition appreciably affects clinical outcomes.

Methods: We screened 979 articles and identified seven studies that met the eligibility criteria for meta-analysis.

Lichen sclerosus of the eyelid involving the eyelash margin.

Lichen sclerosus is a debilitating and chronic disease that typically affects the anogenital area, although it can also be found on extragenital locations such as the shoulders, neck, trunk, breasts, and arms. Facial involvement is rare, but there have been a few reported cases of extragenital lichen sclerosus affecting the infraorbital area. To our knowledge, there are 7 documented cases of extragenital lichen sclerosus affecting the eyelid in medical literature.

Insights into the importance of WPD-loop sequence for activity and structure in protein tyrosine phosphatases.

Protein tyrosine phosphatases (PTPs) possess a conserved mobile catalytic loop, the WPD-loop, which brings an aspartic acid into the active site where it acts as an acid/base catalyst. Prior experimental and computational studies, focused on the human enzyme PTP1B and the PTP from , YopH, suggested that loop conformational dynamics are important in regulating both catalysis and evolvability. We have generated a chimeric protein in which the WPD-loop of YopH is transposed into PTP1B, and eight chimeras that systematically restored the loop sequence back to native PTP1B.

Augmented Cardiac Growth Hormone Signaling Contributes to Cardiomyopathy Following Genetic Disruption of the Cardiomyocyte Circadian Clock.

Circadian clocks regulate numerous biological processes, at whole body, organ, and cellular levels. This includes both hormone secretion and target tissue sensitivity. Although growth hormone (GH) secretion is time-of-day-dependent (increased pulse amplitude during the sleep period), little is known regarding whether circadian clocks modulate GH sensitivity in target tissues.

Isolated Ventricular Septal Aneurysm: A Differential Diagnosis for a Right Sinus of Valsalva Aneurysm.

BACKGROUND A ventricular septal aneurysm (VSA) is rare and almost always an incidental finding on cardiac imaging. It is rarely an isolated phenomenon and is more commonly associated with other forms of congenital heart disease such a ventricular septal defect (VSD). Differentiating a ventricular septal aneurysm from an aneurysm of the right sinus of Valsalva is crucial as the latter usually has a more aggressive course and may require surgical intervention.

Clinical effects of morning and afternoon radiotherapy on high-grade gliomas.

Initial clinical reports comparing the delivery of radiotherapy (RT) at distinct times of the day suggest that this strategy might affect toxicity and oncologic outcomes of radiation for multiple human tissues, but the clinical effects on high-grade gliomas (HGG) are unknown. The present study addresses the hypothesis that radiotherapy treatment time of the day (RT-TTD) influences outcome and/or toxic events in HGG. Patients treated between 2009-2018 were reviewed (n = 109).

Malignant solitary fibrous tumour of the prostate: four cases emphasising significant histological and immunophenotypical overlap with sarcomatoid carcinoma.

Solitary fibrous tumour (SFT) is well-described in the urinary tract, but malignant examples are rare. We studied our experience with high grade malignant SFT of the prostate to address the degree of histological and immunophenotypical overlap with sarcomatoid carcinoma and prostatic stromal sarcoma. Four cases were identified from the surgical pathology consultation archives.

CRTC1-TRIM11 fusion defined melanocytic tumors: A series of four cases.

A cutaneous melanocytic tumor with morphologic overlap with clear cell sarcoma, but defined by CRTC1-TRIM11 gene fusion, was recently described in a series of five adult patients. Here, we expand the clinicopathologic features of this entity by four additional cases which include pediatric presentation, exophytic growth, and propensity to occur on the head. Patients (2F; 2M) had a median age of 41 years (range 11-59).

SATB2 Versus CDX2: A Battle Royale for Diagnostic Supremacy in Mucinous Tumors.

Context.—: Metastatic mucinous tumors present a diagnostic challenge for pathologists as tumor histomorphology is often nonspecific and optimal immunoprofiles are still under investigation.

Objective.

Transition-State Interactions in a Promiscuous Enzyme: Sulfate and Phosphate Monoester Hydrolysis by Pseudomonas aeruginosa Arylsulfatase.

Pseudomonas aeruginosa arylsulfatase (PAS) hydrolyzes sulfate and, promiscuously, phosphate monoesters. Enzyme-catalyzed sulfate transfer is crucial to a wide variety of biological processes, but detailed studies of the mechanistic contributions to its catalysis are lacking. We present linear free energy relationships (LFERs) and kinetic isotope effects (KIEs) of PAS and analyses of active site mutants that suggest a key role for leaving group (LG) stabilization.

Diagnosis of known sarcoma fusions and novel fusion partners by targeted RNA sequencing with identification of a recurrent ACTB-FOSB fusion in pseudomyogenic hemangioendothelioma.

Integration of morphological, immunohistochemical, and molecular methods is often necessary for the precise diagnosis and optimal clinical management of sarcomas. We have validated and implemented a clinical molecular diagnostic assay, MSK- Fusion Solid, for detection of gene fusions in solid tumors, including sarcomas. Starting with RNA extracted from formalin-fixed paraffin-embedded tumor material, this targeted RNA sequencing assay utilizes anchored multiplex PCR to detect oncogenic fusion transcripts involving 62 genes known to be recurrently rearranged in solid tumors including sarcomas without prior knowledge of fusion partners.

Multimodality Cardiac Imaging Assessment of a Large Metastatic Pericardial Leiomyosarcoma.

• Cardiac metastases from ULMS are very rare. • This is the first case report of a metastatic leiomyosarcoma to the pericardium. • Multimodality imaging is important in assessing an undifferentiated cardiac tumor.

Differential tissue response to growth hormone in mice.

Growth hormone (GH) has been shown to act directly on multiple tissues throughout the body. Historically, it was believed that GH acted directly in the liver and only indirectly in other tissues via insulin-like growth hormone 1 (IGF-1). Despite extensive work to describe GH action in individual tissues, a comparative analysis of acute GH signaling in key metabolic tissues has not been performed.

EWSR1-SMAD3-rearranged Fibroblastic Tumor: An Emerging Entity in an Increasingly More Complex Group of Fibroblastic/Myofibroblastic Neoplasms.

Three cases of superficial acral fibroblastic spindle cell neoplasms with EWSR1-SMAD3 fusion have been recently reported. Their differential diagnosis is broad, primarily comprising rare tumors from the fibroblastic/myofibroblastic category. The aim of this report is to present 4 new cases of this entity and to discuss the appropriate differential diagnosis.

Temporal partitioning of adaptive responses of the murine heart to fasting.

Recent studies suggest that the time of day at which food is consumed dramatically influences clinically-relevant cardiometabolic parameters (e.g., adiposity, insulin sensitivity, and cardiac function).

A Comprehensive Evaluation of Special AT-rich Sequence-binding Protein 2 (SATB2) Immunohistochemical Staining in Mucinous Tumors From Gastrointestinal and Nongastrointestinal Sites.

Special AT-rich sequence-binding protein 2 (SATB2) is an accurate marker for conventional colorectal carcinoma (CRC), although its sensitivity and specificity in mucinous tumors from the colon and other sites remains unknown. The objective of this study is to evaluate the accuracy of SATB2 expression detected by immunohistochemical assay, as a marker of primary CRC in mucinous adenocarcinomas. SATB2 immunohistochemical stains were performed on whole sections from 63 conventional CRCs (controls), 47 mucinous CRCs (mCRC), and 182 noncolorectal mucinous tumors.

High levels of tumor-associated neutrophils are associated with improved overall survival in patients with stage II colorectal cancer.

Conflicting reports regarding whether high tumor-associated neutrophils (TAN) are associated with outcomes in colorectal cancer (CRC) exist. Previous investigators have counted TAN using non-neutrophil-specific immunohistochemistry (IHC) stains. We examined whether TAN levels as determined by multi-field manual counting would predict prognosis.

Bone marrow adipocytes.

Adipocytes were identified in human bone marrow more than a century ago, yet until recently little has been known about their origin, development, function or interactions with other cells in the bone marrow. Little functional significance has been attributed to these cells, a paradigm that still persists today. However, we now know that marrow adipose tissue increases with age and in response to a variety of physiologic induction signals.

Puberty is an important developmental period for the establishment of adipose tissue mass and metabolic homeostasis.

Over the past 2 decades, the incidence of childhood obesity has risen dramatically. This recent rise in childhood obesity is particularly concerning as adults who were obese during childhood develop type II diabetes that is intractable to current forms of treatment compared with individuals who develop obesity in adulthood. While the mechanisms responsible for the exacerbated diabetic phenotype associated with childhood obesity is not clear, it is well known that childhood is an important time period for the establishment of normal white adipose tissue in humans.

A savanna response to precipitation intensity.

As the atmosphere warms, precipitation events are becoming less frequent but more intense. A three-year experiment in Kruger National Park, South Africa, found that fewer, more intense precipitation events encouraged woody plant encroachment. To test whether or not these treatment responses persisted over time, here, we report results from all five years of that experiment.

The Adipose Tissue Microenvironment Regulates Depot-Specific Adipogenesis in Obesity.

The sexually dimorphic distribution of adipose tissue influences the development of obesity-associated pathologies. The accumulation of visceral white adipose tissue (VWAT) that occurs in males is detrimental to metabolic health, while accumulation of subcutaneous adipose tissue (SWAT) seen in females may be protective. Here, we show that adipocyte hyperplasia contributes directly to the differential fat distribution between the sexes.

Synapse Loss and Dendrite Remodeling in a Mouse Model of Glaucoma.

It has been hypothesized that synaptic pruning precedes retinal ganglion cell degeneration in glaucoma, causing early dysfunction to retinal ganglion cells. To begin to assess this, we studied the excitatory synaptic inputs to individual ganglion cells in normal mouse retinas and in retinas with ganglion cell degeneration from glaucoma (DBA/2J), or following an optic nerve crush. Excitatory synapses were labeled by AAV2-mediated transfection of ganglion cells with PSD-95-GFP.

The Emergence of Zoonotic Onchocerca lupi Infection in the United States--A Case-Series.

This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test.

Adipose Tissue Residing Progenitors (Adipocyte Lineage Progenitors and Adipose Derived Stem Cells (ADSC).

The formation of brown, white and beige adipocytes have been a subject of intense scientific interest in recent years due to the growing obesity epidemic in the United States and around the world. This interest has led to the identification and characterization of specific tissue resident progenitor cells that give rise to each adipocyte population in vivo. However, much still remains to be discovered about each progenitor population in terms of their "niche" within each tissue and how they are regulated at the cellular and molecular level during healthy and diseased states.