Therapeutic inhibition of Mcl-1 blocks cell survival in estrogen receptor-positive breast cancers.

Cancers often overexpress anti-apoptotic Bcl-2 proteins for cell death evasion, a recognized hallmark of cancer progression. While estrogen receptor (ER)-α+ breast cancers express high levels of three anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL, and Mcl-1), pharmacological inhibition of Bcl-2 and/or Bcl-xL fails to induce cell death in ERα+ breast cancer cell lines, due to rapid and robust Mcl-1 upregulation. The mechanisms of acute Mcl-1 upregulation in response to Bcl-2/Bcl-xL inhibition remain undefined in in ERα+ breast cancers.

Aortic Complications in Marfan Syndrome: Should We Anticipate Preventive Aortic Root Surgery?

Background: The purpose of this study was to analyze the risk of aortic events (death, dissection, or aortic rupture) associated with Marfan syndrome and decide on the optimal timing for preventive surgery on the aortic root.

Methods: From January 2004 to June 2015, 397 patients from Marfan Units were studied by echocardiographic and computed tomography and magnetic resonance imaging of aorta and periodic annual monitoring. Mean follow-up was 5.

Efficient ADCC killing of meningioma by avelumab and a high-affinity natural killer cell line, haNK.

Meningiomas are the most common adult primary tumor of the central nervous system, but there are no known effective medical therapies for recurrent meningioma, particularly for World Health Organization grade II and III tumors. Meningiomas arise from the meninges, located outside the blood-brain barrier, and therefore may be directly targeted by antibody-mediated immunotherapy. We found that programmed cell death ligand 1 (PD-L1) was highly expressed in multiple human malignant meningioma cell lines and patient tumor samples.

Forced expression of microRNA-146b reduces TRAF6-dependent inflammation and improves ischemia-induced neovascularization in hypercholesterolemic conditions.

Background And Aims: MicroRNA (miR)-146 is a key regulator of inflammation, endothelial activation and atherosclerosis. This study sought to define its potential role for the modulation of ischemia-induced neovascularization in atherosclerotic conditions.

Methods: Next generation sequencing and qRT-PCR analyses were used to compare microRNA expression in the ischemic muscles of hypercholesterolemic ApoE-deficient (ApoE) mice vs.

A case report of clonal EBV-like memory CD4 T cell activation in fatal checkpoint inhibitor-induced encephalitis.

Checkpoint inhibitors produce durable responses in numerous metastatic cancers, but immune-related adverse events (irAEs) complicate and limit their benefit. IrAEs can affect organ systems idiosyncratically; presentations range from mild and self-limited to fulminant and fatal. The molecular mechanisms underlying irAEs are poorly understood.

Bilateral Internuclear Ophthalmoplegia in a Young Woman with Vertebral Artery Dissection.

Background: Internuclear ophthalmoplegia (INO) is an eye movement disorder caused by a lesion in the medial longitudinal fasciculus (MLF) located in the midbrain. Adduction paralysis of both eyes and bilateral abduction nystagmus are the main features of INO.

Case Presentation: A 29-year-old Hispanic woman was admitted to the emergency department complaining of an intense holocranial headache lasting 9 days, associated with nausea and vomiting.

Compact and Low-Complexity Binary Feature Descriptor and Fisher Vectors for Video Analytics.

In this paper, we propose a compact and low-complexity binary feature descriptor for video analytics. Our binary descriptor encodes the motion information of a spatio-temporal support region into a low-dimensional binary string. The descriptor is based on a binning strategy and a construction that binarizes separately the horizontal and vertical motion components of the spatio-temporal support region.

Implementation of an Intraoperative Instructional Timeout Just Prior to Stapler Use Improves Proficiency of Surgical Stapler Usage by Surgery Residents.

Introduction: With the fragmented rotational structure of training, exposure to surgical staplers is not uniform across surgical residents. Traditionally, educational sessions dedicated to instruction in surgical staplers have taken place outside the operating room. This study implemented and evaluated an intraoperative timeout immediately prior to stapler use in cases with surgical residents.

A soft ring oscillator.

Periodic actuation of multiple soft, pneumatic actuators requires coordinated function of multiple, separate components. This work demonstrates a soft, pneumatic ring oscillator that induces temporally coordinated periodic motion in soft actuators using a single, constant-pressure source, without hard valves or electronic controls. The fundamental unit of this ring oscillator is a soft, pneumatic inverter (an inverting Schmitt trigger) that switches between its two states ("on" and "off") using two instabilities in elastomeric structures: buckling of internal tubing and snap-through of a hemispherical membrane.

Phenotype of haptoglobin and presence of subclinical vascular disease: Population study.

Introduction And Objectives: Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications.

Methylmercury, cadmium and arsenic(III)-induced toxicity, oxidative stress and apoptosis in Pacific red snapper leukocytes.

Methylmercury (MeHg), cadmium (Cd) and arsenic (As(III)) are among the most toxic metals in aquatic systems that have been associated with multiple animal and human health problems. This study investigated cytotoxic, oxidative stress, and apoptosis effects on fish leukocytes following their exposure to metals. A preliminary study indicated that leukocytes exposed to MeHg at a concentration of 0.

Identification of Targetable Recurrent MAP3K8 Rearrangements in Melanomas Lacking Known Driver Mutations.

Melanomas are characterized by driver and loss-of-function mutations that promote mitogen-activated protein kinase (MAPK) signaling. MEK inhibitors are approved for use in BRAF-mutated melanoma; however, early-phase clinical trials show occasional responses in driver-negative melanoma, suggesting other alterations conferring MAPK/ERK dependency. To identify additional structural alterations in melanoma, we evaluated RNA-Seq from a set of known MAPK/ERK regulators using a novel population-based algorithm in The Cancer Genome Atlas (TCGA).

Seasonal and geographic variation in insecticide resistance in Aedes aegypti in southern Ecuador.

Insecticide resistance (IR) can undermine efforts to control vectors of public health importance. Aedes aegypti is the main vector of resurging diseases in the Americas such as yellow fever and dengue, and recently emerging chikungunya and Zika fever, which have caused unprecedented epidemics in the region. Vector control remains the primary intervention to prevent outbreaks of Aedes-transmitted diseases.

Enhancing the removal of atrazine from soils by electrokinetic-assisted phytoremediation using ryegrass (Lolium perenne L.).

Atrazine (ATR) continues being one of the most frequently detected pesticides in natural waters and soils. In this work, an electrokinetic-assisted phytoremediation pot test (EKPR) was performed for the remediation of an atrazine-spiked soil; a low electric voltage gradient (1 V cm) with two different electric field operation times (6 and 24 h per day) was used in combination with ryegrass (Lolium perenne L.).

Risk Of Recurrence After Withdrawal Of Anticoagulation In Patients With Unprovoked Venous Thromboembolism: External Validation Of The Vienna Nomogram And The Dash Prediction Score.

Introduction: Scales for predicting venous thromboembolism (VTE) recurrence are useful for deciding the duration of the anticoagulant treatment. Although there are several scales, the most appropriate for our setting has not been identified. For this reason, we aimed to validate the DASH prediction score and the Vienna nomogram at 12 months.

Differential detoxifying responses to crude oil water-accommodated fraction in Hyallela curvispina individuals from unpolluted and contaminated sites.

Sublethal effects of water-accommodated fraction (WAF) from crude oil of Neuquén basin, Northern Patagonia-Argentina, were examined on both antioxidant and detoxification system of Hyalella curvispina adults collected in Los Barreales (LB) lake and in an oil-polluted stream (DS). The effects of WAF exposure during 6, 24 and 48 h were evaluated in the glutathione content (GSH) and glutathione S-transferase (GST), catalase (CAT) and cytochrome P450 (CYP450) activities. Populations from DS and LB showed not only different basal GSH content and enzyme activities but also different behavior to WAF exposure.

The transcription factor CBFB suppresses breast cancer through orchestrating translation and transcription.

Translation and transcription are frequently dysregulated in cancer. These two processes are generally regulated by distinct sets of factors. The CBFB gene, which encodes a transcription factor, has recently emerged as a highly mutated driver in a variety of human cancers including breast cancer.

Metformin attenuates the onset of non-alcoholic fatty liver disease and affects intestinal microbiota and barrier in small intestine.

The antidiabetic drug metformin has been proposed to affect non-alcoholic fatty liver disease (NAFLD) through its effects on intestinal microbiota and barrier function. However, so far most studies focused on long-term effects and more progressed disease stages. The aim of this study was to assess in two experimental settings, if the onset of NAFLD is associated with changes of intestinal microbiota and barrier function and to determine effects of metformin herein.

Proximal aorta longitudinal strain predicts aortic root dilation rate and aortic events in Marfan syndrome.

Aims: Life expectancy in Marfan syndrome patients has improved thanks to the early detection of aortic dilation and prophylactic aortic root surgery. Current international clinical guidelines support the use of aortic root diameter as a predictor of complications. However, other imaging markers are needed to improve risk stratification.

Evaluation of the Impact of 2 Disposable Diapers in the "Natural" Diaper Category on Diapered Skin Condition.

The demand for natural infant care products, including diapers, has increased. However, few disposable diapers have been able to provide the performance caregivers desire while also incorporating ingredients consistent with the "natural" category. In an examiner-blinded clinical study, the performance of a new cotton-enhanced diaper with high-performance materials was compared with an existing natural diaper offering.

Mapping Bromodomains in breast cancer and association with clinical outcome.

A specific family of proteins that participate in epigenetic regulation is the bromodomain (BRD) family of proteins. In this work, we aimed to explore the expression of the BRD family at a transcriptomic level in breast cancer, and its association with patient survival. mRNA level data from normal breast and tumor tissues were extracted from public datasets.

Exercise during abstinence normalizes ultrastructural synaptic plasticity associated with nicotine-seeking following extended access self-administration.

Nicotine-craving progressively increases, or incubates, over abstinence following extended access self-administration. While not yet examined for nicotine, the incubation of cocaine-seeking is accompanied by changes in synaptic plasticity in the nucleus accumbens. Here, we determined whether such changes also accompany enhanced nicotine-seeking following extended access self-administration and abstinence, and whether exercise, a potential intervention for nicotine addiction, may exert its efficacy by normalizing these changes.

Glycosylation of Staphylococcus aureus cell wall teichoic acid is influenced by environmental conditions.

Wall teichoic acid (WTA) are major constituents of Staphylococcus aureus (S. aureus) cell envelopes with important roles in the bacteria's physiology, resistance to antimicrobial molecules, host interaction, virulence and biofilm formation. They consist of ribitol phosphate repeat units in which the ribitol residue is substituted with D-alanine (D-Ala) and N-acetyl-D-glucosamine (GlcNAc).