A Novel Method for Quantifying Total Thoracic Tumor Burden in Mice.

Mouse models are powerful tools to study lung cancer initiation and progression in vivo and have contributed significantly to recent advances in therapy. Using micro-computed tomography to monitor and study parenchymal and extra-parenchymal metastases in existing murine models of lung cancer is challenging owing to a lack of radiographic contrast and difficulty in achieving respiratory gating. To facilitate the analysis of these in vivo imaging studies and study of tumor progression in murine models we developed a novel, rapid, semi-automated method of calculating thoracic tumor burden from computed tomography images.

Tissue-susceptibility matched carbon nanotube electrodes for magnetic resonance imaging.

Test disk electrodes were fabricated from carbon nanotubes (CNT) using the Carbon Nanotube Templated Microfabrication (CNT-M) technique. The CNT-M process uses patterned growth of carbon nanotube forests from surfaces to form complex patterns, enabling electrode sizing and shaping. The additional carbon infiltration process stabilizes these structures for further processing and handling.

Necrotizing epiglottitis treated with early surgical debridement: A case report.

Objective: Necrotizing supraglottitis is a rare but potentially morbid infection most often seen in immunocompromised patients. All reported cases have utilized intravenous antibiotic therapy as the mainstay of treatment and many have had associated morbidities.

Methods: We describe a case of a 50-year-old previously healthy female who presented with necrotizing epiglottis and was treated with immediate surgical debridement followed by directed antibiotic therapy.

Diagnostic lymph node extirpation in CUP syndrome - useful or damaging?

Objective: In a proportion of patients with cervical lymph node metastasis no primary can be found even with modern imaging and careful clinical examination (cancer of unknown primary syndrome = CUP syndrome). The ideal diagnostic approach is still debated on.

Methods: The clinical data of 75 patients (median age: 61.

Facing the facts on prophylactic antibiotics for facial fractures: 1 day or less.

Background: To evaluate the role of initial prophylactic antibiotics on facial fractures, outcomes were compared between a short course (≤24 hours) of antibiotics to those who received an extended course (>24 hours).

Methods: Adults admitted (2010-2015) to a Level I trauma center intensive care unit with at least one facial bone fracture and major injuries isolated to the head and neck were included. Our primary analysis compared infectious complications of the head or neck (H/N infection) between patients given short or extended courses of antibiotic prophylaxis.

Value of sample information in dynamic, structurally uncertain resource systems.

Few if any natural resource systems are completely understood and fully observed. Instead, there almost always is uncertainty about the way a system works and its status at any given time, which can limit effective management. A natural approach to uncertainty is to allocate time and effort to the collection of additional data, on the reasonable assumption that more information will facilitate better understanding and lead to better management.

The role of oral anticoagulants in epistaxis.

Purpose: The purpose of this retrospective study was to identify the impact of oral anticoagulants on epistaxis with the focus on new oral anticoagulants.

Methods: The study was conducted at the Department  for Ear- Nose- and Throat (ENT), Head and Neck Surgery, Technical University Munich, Germany. All patients presenting in 2014 with the diagnosis of epistaxis to a specialized ENT accident and emergency department were identified and analyzed in clinical data and medication.

Interhemispheric dominance switching in a neural network model for birdsong.

Male zebra finches produce a sequence-invariant set of syllables, separated by short inspiratory gaps. These songs are learned from an adult tutor and maintained throughout life, making them a tractable model system for learned, sequentially ordered behaviors, particularly speech production. Moreover, much is known about the cortical, thalamic, and brain stem areas involved in producing this behavior, with the premotor cortical nucleus HVC (proper name) being of primary importance.

Phase 1/1b dose escalation and expansion study of BEZ235, a dual PI3K/mTOR inhibitor, in patients with advanced solid tumors including patients with advanced breast cancer.

Purpose: To determine the maximum tolerated dose (MTD) of BEZ235, an oral inhibitor of class I PI3K and mTOR complexes 1 and 2.

Methods: We performed a phase I/Ib, multicenter, open-label study of oral BEZ235 administered in a continuous daily schedule. The study consisted of two parts: dose-escalation part and safety-expansion part.

Comprehensive pharmacogenomic profiling of human papillomavirus-positive and -negative squamous cell carcinoma identifies sensitivity to aurora kinase inhibition in KMT2D mutants.

To address the unmet need for effective biomarker-driven targeted therapy for human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) and cervical cancer, we conducted a high-throughput drug screen using 1122 compounds in 13 HPV-positive and 11 matched HPV-negative cell lines. The most effective drug classes were inhibitors of polo-like kinase, proteasomes, histone deacetylase, and Aurora kinases. Treatment with a pan-Aurora inhibitor, danusertib, led to G2M arrest and apoptosis in vitro.

A regulatory loop connecting WNT signaling and telomere capping: possible therapeutic implications for dyskeratosis congenita.

The consequences of telomere dysfunction are most apparent in rare inherited syndromes caused by genetic deficiencies in factors that normally maintain telomeres. The principal disease is known as dyskeratosis congenita (DC), but other syndromes with similar underlying genetic defects share some clinical aspects with this disease. Currently, there are no curative therapies for these diseases of telomere dysfunction.

A score for the differential diagnosis of bradykinin- and histamine-induced head and neck swellings.

Purpose: Acute edema of the head and neck region may lead to life-threatening dyspnea and require quick and targeted treatment. They can be subdivided in bradykinin- and histamine-mediated swellings, which require treatment with different classes of pharmaceuticals. Clinical pathways for differential diagnoses do not exist so far, although it is known that early treatment is decisive for faster symptom relief and reduced expression of the swellings.

Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia.

Tolerance to self-antigens prevents the elimination of cancer by the immune system. We used synthetic chimeric antigen receptors (CARs) to overcome immunological tolerance and mediate tumor rejection in patients with chronic lymphocytic leukemia (CLL). Remission was induced in a subset of subjects, but most did not respond.

Arginase inhibition prevents the development of hypertension and improves insulin resistance in obese rats.

This study investigated the temporal activation of arginase in obese Zucker rats (ZR) and determined if arginase inhibition prevents the development of hypertension and improves insulin resistance in these animals. Arginase activity, plasma arginine and nitric oxide (NO) concentration, blood pressure, and insulin resistance were measured in lean and obese animals. There was a chronological increase in vascular and plasma arginase activity in obese ZR beginning at 8 weeks of age.

A novel tricarbonylmethane agent (CMC2.24) reduces human pancreatic tumor growth in mice by targeting Ras.

Pancreatic Cancer (PC) is a deadly disease in need of new therapeutic options. We recently developed a novel tricarbonylmethane agent (CMC2.24) as a therapeutic agent for PC, and evaluated its efficacy in preclinical models of PC.

Differential effects of natural Curcumin and chemically modified curcumin on inflammation and bone resorption in model of experimental periodontitis.

Objective: The purpose of this study was to compare the effects of the oral administration of natural curcumin and a chemically modified curcumin (CMC2.24) on osteoclast-mediated bone resorption, apoptosis, and inflammation in a murine model of experimental periodontal disease.

Design: Fifty male rats were distributed among the following treatment groups: (i) 2% carboxymethylcellulose, (ii) CMC2.

TERRA and the histone methyltransferase Dot1 cooperate to regulate senescence in budding yeast.

The events underlying senescence induced by critical telomere shortening are not fully understood. Here we provide evidence that TERRA, a non-coding RNA transcribed from subtelomeres, contributes to senescence in yeast lacking telomerase (tlc1Δ). Levels of TERRA expressed from multiple telomere ends appear elevated at senescence, and expression of an artificial RNA complementary to TERRA (anti-TERRA) binds TERRA in vivo and delays senescence.

Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres.

Aging and age-related diseases pose some of the most significant and difficult challenges to modern society as well as to the scientific and medical communities. Biological aging is a complex, and, under normal circumstances, seemingly irreversible collection of processes that involves numerous underlying mechanisms. Among these, chromatin-based processes have emerged as major regulators of cellular and organismal aging.

Erlotinib in the treatment of recurrent or metastatic cutaneous squamous cell carcinoma: A single-arm phase 2 clinical trial.

Background: Cutaneous squamous cell carcinoma (CSCC) is a very common malignancy in which most patients present with localized disease. Recurrent and metastatic disease is rare, and there is no standard therapy. These tumors frequently overexpress the epidermal growth factor receptor (EGFR).

Intentions to Prevent Weight Gain in Older and Younger Adults; The Importance of Perceived Health and Appearance Consequences.

Objectives: This study investigates whether health and appearance consequences predict intentions to prevent weight gain and whether these relationships differ in younger versus older adults and in men versus women.

Methods: UK adults aged 18-26 years (younger adults; n = 584) or >45 years (older adults; n = 107) participated in an online survey. Logistic regression assessed associations between intentions to avoid gaining weight and age, gender as well as perceived negative consequences of weight gain for health and appearance.

Publisher Correction: Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease.

In the version of this article initially published online, the fifth author's name was given as Alexander Amlie-Wolf. The correct name is Alexandre Amlie-Wolf. The error has been corrected in the print, PDF and HTML versions of this article.

Dynamic minimum set problem for reserve design: Heuristic solutions for large problems.

Conversion of wild habitats to human dominated landscape is a major cause of biodiversity loss. An approach to mitigate the impact of habitat loss consists of designating reserves where habitat is preserved and managed. Determining the most valuable areas to preserve in a landscape is called the reserve design problem.

Mortality Following Hospital Admission for US Active Duty Service Members Diagnosed With Penetrating Traumatic Brain Injury, 2004-2014.

Objective: To examine mortality among active duty US military service members (SMs) with the diagnosis of penetrating traumatic brain injury (PTBI) and a hospital admission between 2004 and 2014.

Design: Data on SMs with PTBI and an admission to a military or civilian hospital were obtained from the 2004 to 2014 Military Health System data repository. After applying exclusion criteria, data on 1226 SMs were analyzed.

Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease.

Aging is the strongest risk factor for Alzheimer's disease (AD), although the underlying mechanisms remain unclear. The chromatin state, in particular through the mark H4K16ac, has been implicated in aging and thus may play a pivotal role in age-associated neurodegeneration. Here we compare the genome-wide enrichment of H4K16ac in the lateral temporal lobe of AD individuals against both younger and elderly cognitively normal controls.