The Impact of Spliceosome Inhibition in SF3B1-Mutated Uveal Melanoma.

Purpose: Unfortunately, treatment of patients with uveal melanoma (UM) with metastatic disease is limited. Twenty percent of patients with UM harbor a mutation in the splicing factor gene SF3B1, suggesting that aberrant spliceosome function plays a vital role in tumorigenesis. Splicing inhibitors exploit the preferential sensitivity of spliceosome-compromised leukemic cells to these compounds.

8q Gain Has No Additional Predictive Value in Uveal Melanoma but Is Predictive for a Worse Prognosis in Patients with Uveal Melanoma.

Purpose: Gain of chromosome 8q has been associated with poor prognosis in uveal melanoma (UM), and an increase in the absolute number of 8q-copies correlated with an even shorter survival. Splicing factor 3b subunit 1 ()-mutated () tumors display structural chromosomal anomalies and frequently show a partial gain of chromosome 8qter. A recent subset of UM with early-onset metastases has been identified, prompting the investigation of the relationship between survival, 8q gain, and UM.

Disparities of Cutaneous Malignancies in the US Military.

Occupational sun exposure is a well-known risk factor for the development of melanoma and nonmelanoma skin cancer (NMSC), especially among US military personnel who may have inadequate access to sun protection, are located in geographic regions with increased sun exposure, and work with potential carcinogens. Herein, we describe a case of a military service member who developed skin cancer at an early age potentially due to occupational sun exposure. We also provide a review of the literature to examine the risk factors and incidence of melanoma and NMSC in US military personnel and veterans, as well as provide recommendations for skin cancer prevention, screening, and intervention in the military population.

Is a Transcription Factor Important for Uveal Melanocyte Development and Associated with High-Risk Uveal Melanoma.

Uveal melanoma (UM) is a deadly ocular malignancy, originating from uveal melanocytes. Although much is known regarding prognostication in UM, the exact mechanism of metastasis is mostly unknown. Metastatic tumor cells are known to express a more stem-like RNA profile which is seen often in cell-specific embryonic development to induce tumor progression.

Identification of Early-Onset Metastasis in SF3B1 Mutated Uveal Melanoma.

Approximately 25% of all uveal melanoma (UM) contain driver mutations in the gene encoding the spliceosome factor , and whilst patients with such mutations generally have an intermediate risk on developing metastatic disease, a third of these patients develop early metastasis within 5 years after diagnosis. We therefore investigated whether clinical and/or genetic variables could be indicative of short progression-free survival (PFS < 60 months) or long PFS (PFS ≥ 60 months) for -mutated () UM patients. We collected 146 UM from our Rotterdam Ocular Melanoma Studygroup (ROMS) database and external published datasets.

Lipidation of Class IV CdiA Effector Proteins Promotes Target Cell Recognition during Contact-Dependent Growth Inhibition.

Contact-dependent growth inhibition (CDI) systems enable the direct transfer of protein toxins between competing Gram-negative bacteria. CDI strains produce cell surface CdiA effector proteins that bind specific receptors on neighboring bacteria to initiate toxin delivery. Three classes of CdiA effectors that recognize different outer membrane protein receptors have been characterized in Escherichia coli to date.

Spliceosome Mutations in Uveal Melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy of the eye. It has a high metastatic potential and mainly spreads to the liver. Genetics play a vital role in tumor classification and prognostication of UM metastatic disease.

Can Robin Sequence Be Predicted From Prenatal Ultrasonography?

Purpose: Prenatal diagnosis of Robin sequence (RS) could promote safe delivery and improve perinatal care. The purpose of this study was to evaluate the correlation between prenatal ultrasonography (US) and magnetic resonance imaging (MRI) studies for assessing micrognathia to determine if US alone can be used to reliably screen for RS.

Materials And Methods: This was a retrospective case-control study of fetuses evaluated in the Advanced Fetal Care Center at Boston Children's Hospital from 2002 to 2017.

Convergent Evolution of the Barnase/EndoU/Colicin/RelE (BECR) Fold in Antibacterial tRNase Toxins.

Contact-dependent growth inhibition (CDI) is a form of interbacterial competition mediated by CdiB-CdiA two-partner secretion systems. CdiA effector proteins carry polymorphic C-terminal toxin domains (CdiA-CT), which are neutralized by specific CdiI immunity proteins to prevent self-inhibition. Here, we present the crystal structures of CdiA-CT⋅CdiI complexes from Klebsiella pneumoniae 342 and Escherichia coli 3006.

Impact of Obstructive Sleep Apnea on Optic Nerve Function in Patients With Craniosynostosis and Recurrent Intracranial Hypertension.

Purpose: Assessment of combined impact of intracranial hypertension (ICH) and obstructive sleep apnea (OSA) on optic nerve function in children with craniosynostosis (CS).

Design: Retrospective cross-sectional study.

Methods: Patients treated at Boston Children's Hospital for CS who had an ophthalmic examination that included pattern reversal (pr)VEP (2013-2014) and history of ICH based on direct measurement, papilledema, or classic features on neuroimaging and during cranial vault expansion were included.

Programmed Secretion Arrest and Receptor-Triggered Toxin Export during Antibacterial Contact-Dependent Growth Inhibition.

Contact-dependent growth inhibition (CDI) entails receptor-mediated delivery of CdiA-derived toxins into Gram-negative target bacteria. Using electron cryotomography, we show that each CdiA effector protein forms a filament extending ∼33 nm from the cell surface. Remarkably, the extracellular filament represents only the N-terminal half of the effector.

Functional plasticity of antibacterial EndoU toxins.

Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CT from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15.

The sensitivity and specificity of touch preparation for rapid diagnosis of invasive fungal sinusitis: A pilot study.

Invasive fungal sinusitis is a morbid pathology that typically affects immunocompromised patients and may quickly progress to fulminant disease. The purpose of this study was to measure the sensitivity and specificity of touch preparation of nasal debridement specimens as a rapid diagnostic tool for invasive fungal sinusitis. A retrospective chart review was performed of 22 patients undergoing nasal debridement due to suspicion for invasive fungal sinusitis over a 10-year period.

CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria.

Contact-dependent growth inhibition (CDI) systems encode CdiA effectors, which bind to specific receptors on neighboring bacteria and deliver C-terminal toxin domains to suppress target cell growth. Two classes of CdiA effectors that bind distinct cell surface receptors have been identified, but the molecular basis of receptor specificity is not understood. Alignment of BamA-specific CdiA from EC93 and OmpC-specific CdiA from 536 suggests that the receptor-binding domain resides within a central region that varies between the two effectors.

CDI Systems Are Stably Maintained by a Cell-Contact Mediated Surveillance Mechanism.

Contact-dependent growth inhibition (CDI) systems are widespread amongst Gram-negative bacteria where they play important roles in inter-cellular competition and biofilm formation. CDI+ bacteria use cell-surface CdiA proteins to bind neighboring bacteria and deliver C-terminal toxin domains. CDI+ cells also express CdiI immunity proteins that specifically neutralize toxins delivered from adjacent siblings.

The proton-motive force is required for translocation of CDI toxins across the inner membrane of target bacteria.

Contact-dependent growth inhibition (CDI) is a mode of bacterial competition orchestrated by the CdiB/CdiA family of two-partner secretion proteins. The CdiA effector extends from the surface of CDI(+) inhibitor cells, binds to receptors on neighbouring bacteria and delivers a toxin domain derived from its C-terminal region (CdiA-CT). Here, we show that CdiA-CT toxin translocation requires the proton-motive force (pmf) within target bacteria.

Effectiveness of a standardized education process for tracheostomy care.

Objectives/hypothesis: Evaluate the effectiveness of an educational curriculum on general tracheostomy care principles and determine the effect of this educational curriculum on the level of provider comfort with tracheostomy care.

Study Design: Cross-sectional questionnaire in an academic medical center.

Materials And Methods: A 25-question multiple choice and true/false quiz was given to nonotolaryngology health care providers (nurses and physicians) who routinely provide tracheostomy care.

Asteatotic eczema in hypoesthetic skin: a case series.

Importance: Asteatotic eczema (eczema craquelé, xerotic eczema) occurs most frequently in areas of dehydrated skin, most often during the winter months when decreased humidity results in increased water loss from the stratum corneum. We present 5 cases in which asteatotic eczema was found outside of its normal distribution, within desensitized skin and scars.

Observations: Five patients with a history of trauma and scar formation presented with erythematous, dry plaques with fine crackling involving hypoesthetic skin.

Delayed lower cranial neuropathies following primary radiotherapy for oropharyngeal squamous cell carcinoma.

Delayed lower cranial neuropathy is a rare complication following primary radiotherapy for head and neck cancer, and has been most associated with nasopharyngeal carcinoma with minimal data regarding this outcome in the treatment of the oropharynx. No reports, to the authors' knowledge, have described this complication following intensity modulated radiation therapy (IMRT) for oropharyngeal primaries. Once encountered, this adverse outcome can have serious impacts on speech and swallowing.

Leclercia adecarboxylata cellulitis in a child with acute lymphoblastic leukemia.

Leclercia adecarboxylata is a rare, gram-negative rod that has been infrequently reported in the literature. The organism has been documented to cause solitary infections in immunocompromised hosts and polymicrobial wound infections in the immunocompetent. We present a case of an 8-year-old boy with significant past medical history of acute lymphoblastic leukemia who developed cellulitis due to local infection by L.

The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: a systematic review and meta-analysis of randomized controlled trials.

Background: There is a need to better understand the safety of tumor necrosis factor (TNF) inhibitors in patients with psoriatic disease in whom TNF inhibitors are frequently used as monotherapy.

Objective: We sought to examine the risks of infection and malignancy with the use of TNF antagonists in adult patients with psoriatic disease.

Methods: We conducted a systematic search for trials of TNF antagonists for adults with plaque psoriasis and psoriatic arthritis.