Millennial-scale variability of the Antarctic ice sheet during the early Miocene.

Millennial-scale ice sheet variability (1-15 kyr periods) is well documented in the Quaternary, providing insight into critical atmosphere-ocean-cryosphere interactions that can inform the mechanism and pace of future climate change. Ice sheet variability at similar frequencies is comparatively less known and understood prior to the Quaternary during times, where higher atmospheric CO and warmer climates prevailed, and continental-scale ice sheets were largely restricted to Antarctica. In this study, we evaluate a high-resolution clast abundance dataset (ice-rafted debris) that captures East Antarctic ice sheet variability in the western Ross Sea during the early Miocene.

Development and Evaluation of an Innovative Neurology E-learning Didactic Curriculum for Psychiatry Residents.

Objective: This article describes the development, implementation, and piloting of an e-learning neuropsychiatry curriculum for psychiatry residents. The primary outcome of interest was feasibility. Secondary outcomes were interest and confidence caring for patients with neuropsychiatric disorders, and knowledge about neuropsychiatry.

A Novel Pulsed Stimulation Pattern in Spinal Cord Stimulation: Clinical Results and Postulated Mechanisms of Action in the Treatment of Chronic Low Back and Leg Pain.

Objectives: The aim of this article is to discuss the possible mechanisms of action (MOAs) and results of a pilot study of a novel, anatomically placed, and paresthesia-independent, neurostimulation waveform for the management of chronic intractable pain.

Materials And Methods: A novel, multilayered pulsed stimulation pattern (PSP) that comprises three temporal layers, a Pulse Pattern layer, Train layer, and Dosage layer, was developed for the treatment of chronic intractable pain. During preliminary development, the utility was evaluated of anatomical PSP (aPSP) in human subjects with chronic intractable pain of the leg(s) and/or low back, compared with that of traditional spinal cord stimulation (T-SCS) and physiological PSP.

Fully displaced pediatric supracondylar humerus fractures: Which ones need to go at night?

Background: Challenges remain in determining which displaced supracondylar humerus fractures are safe to postpone surgical treatment until daylight hours. The purpose of this study is to determine which characteristics can be identified to guide the timing of treatment of supracondylar humerus fractures.

Methods: 225 completely displaced Gartland extension type 3/4 supracondylar humerus fractures in healthy patients that presented between 6 am and 7 am were identified.

8 out of 10 patients do well after surgery for tarsal coalitions: A systematic review on 1284 coalitions.

Background: The primary aim was to determine the clinical success rate after treatment for talocalcaneal (TCC) and calcaneonavicular coalitions (CNC). The secondary aim was to evaluate the complication, recurrence and revision rate.

Methods: A search was carried out in MEDLINE, EMBASE and Cochrane Library.

Retrospective study of patterns of vitamin D testing and status at a single institution paediatric orthopaedics and sports clinics.

Objectives: There has been a recent increase in awareness of the importance of bone health in children treated by paediatric orthopaedic and sports medicine providers. The purpose of this study was to assess our utilisation of 25 hydroxy vitamin D (25(OH)Vit D) testing in the past 10 years, and to evaluate the level of 25(OH)Vit D sufficiency in various populations of patients seen.

Design: This is a single site, retrospective medical record review study.

Toddlers learn and flexibly apply multiple possibilities.

The ability to consider multiple possibilities forms the basis for a wide variety of human-unique cognitive capacities. When does this skill develop? Previous studies have narrowly focused on children's ability to prepare for incompatible future outcomes. Here, we investigate this capacity in a causal learning context.

Fast generation and detection of spatial modes of light using an acousto-optic modulator.

Spatial modes of light provide a high-dimensional space that can be used to encode both classical and quantum information. Current approaches for dynamically generating and measuring these modes are slow, due to the need to reconfigure a high-resolution phase mask such as a spatial light modulator or digital micromirror device. The process of updating the spatial mode of light can be greatly accelerated by multiplexing a set of static phase masks with a fast, image-preserving optical switch, such as an acousto-optic modulator (AOM).

Is ward round participation by clinical pharmacists a valuable use of time and money? A time and motion study.

Background: While the benefits of multidisciplinary ward round (WR) participation by clinical pharmacists have been demonstrated, it can be time-consuming. No previous studies have compared the specific benefits of WR participation and other clinical activities.

Objectives: To assess the clinical impact of different clinical pharmacist activities and analyse patterns of practice based on WR involvement and timing and significance of clinical interventions.

A Low-Cost Mechanical Stretching Device for Uniaxial Strain of Cells: A Platform for Pedagogy in Mechanobiology.

Mechanical cues including stretch, compression, and shear stress play a critical role in regulating the behavior of many cell types, particularly those that experience substantial mechanical stress within tissues. Devices that impart mechanical stimulation to cells in vitro have been instrumental in helping to develop a better understanding of how cells respond to mechanical forces. However, these devices often have constraints, such as cost and limited functional capabilities, that restrict their use in research or educational environments.

Discovery of Stromal Regulatory Networks that Suppress Ras-Sensitized Epithelial Cell Proliferation.

Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation.

Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer.

Substantial evidence has clearly demonstrated the role of the IL-6-NF-κB signaling loop in promoting aggressive phenotypes in breast cancer. However, the exact mechanism by which this inflammatory loop is regulated remains to be defined. Here, we report that integrin-linked kinase (ILK) acts as a molecular switch for this feedback loop.

A New Player in the Spermiogenesis Pathway of Caenorhabditis elegans.

Precise timing of sperm activation ensures the greatest likelihood of fertilization. Precision in Caenorhabditis elegans sperm activation is ensured by external signaling, which induces the spherical spermatid to reorganize and extend a pseudopod for motility. Spermatid activation, also called spermiogenesis, is prevented from occurring prematurely by the activity of SPE-6 and perhaps other proteins, termed "the brake model.

Function of Integrin-Linked Kinase in Modulating the Stemness of IL-6-Abundant Breast Cancer Cells by Regulating γ-Secretase-Mediated Notch1 Activation in Caveolae.

Interleukin-6 (IL-6) and Notch signaling are important regulators of breast cancer stem cells (CSCs), which drive the malignant phenotype through self-renewal, differentiation, and development of therapeutic resistance. We investigated the role of integrin-linked kinase (ILK) in regulating IL-6-driven Notch1 activation and the ability to target breast CSCs through ILK inhibition. Ectopic expression/short hairpin RNA-mediated knockdown of ILK, pharmacological inhibition of ILK with the small molecule T315, Western blot analysis, immunofluorescence, and luciferase reporter assays were used to evaluate the regulation of IL-6-driven Notch1 activation by ILK in IL-6-producing triple-negative breast cancer cell lines (MDA-MB-231, SUM-159) and in MCF-7 and MCF-7(IL-6) cells.

SPE-8, a protein-tyrosine kinase, localizes to the spermatid cell membrane through interaction with other members of the SPE-8 group spermatid activation signaling pathway in C. elegans.

Background: The SPE-8 group gene products transduce the signal for spermatid activation initiated by extracellular zinc in C. elegans. Mutations in the spe-8 group genes result in hermaphrodite-derived spermatids that cannot activate to crawling spermatozoa, although spermatids from mutant males activate through a pathway induced by extracellular TRY-5 protease present in male seminal fluid.

Determination of pesticide residues in cannabis smoke.

The present study was conducted in order to quantify to what extent cannabis consumers may be exposed to pesticide and other chemical residues through inhaled mainstream cannabis smoke. Three different smoking devices were evaluated in order to provide a generalized data set representative of pesticide exposures possible for medical cannabis users. Three different pesticides, bifenthrin, diazinon, and permethrin, along with the plant growth regulator paclobutrazol, which are readily available to cultivators in commercial products, were investigated in the experiment.

UV light B-mediated inhibition of skin catalase activity promotes Gr-1+ CD11b+ myeloid cell expansion.

Skin cancer incidence and mortality are higher in men compared with women, but the causes of this sex discrepancy remain largely unknown. UV light exposure induces cutaneous inflammation and neutralizes cutaneous antioxidants. Gr-1(+)CD11b(+) myeloid cells are heterogeneous bone marrow-derived cells that promote inflammation-associated carcinogenesis.

Routine surveillance of modular PFC TKA shows increasing failures after 10 years.

Background/rationale: A 10-year survivorship of 100% was reported for patients with PFC cruciate-retaining prostheses. Beyond 10 years, we observed additional polyethylene wear likely related to thin liners gamma-irradiated in air and were concerned this wear might predispose to implant construct failure.

Questions/purposes: We therefore determined (1) the functional scores at a minimum of 15 years followup, (2) rates of radiographic failure, (3) overall revision rates, and (4) mode of failure after 10 years and the fate of the revised implants.

Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor).

Purpose: Neuroblastoma is a childhood cancer of the sympathetic nervous system and many patients present with high-risk disease. Risk stratification, based on pathology and tumor-derived biomarkers, has improved prediction of clinical outcomes, but overall survival (OS) rates remain unfavorable and new therapeutic targets are needed. Some studies suggest a link between interleukin (IL)-6 and more aggressive behavior in neuroblastoma tumor cells.

Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer.

Bone is the primary anatomical site of breast cancer metastasis, and bone metastasis is associated with increased morbidity and mortality. Mesenchymal stem cells (MSC) are a predominant fibroblast cell population within the bone marrow, and metastatic breast cancer cells that seed within bone would predictably encounter MSC or their soluble factors. Therefore, we examined the impact of primary human MSC on a panel of estrogen receptor-alpha (ERalpha)-positive (MCF-7, T47D, BT474, and ZR-75-1) and ERalpha-negative (MDA-MB-231 and MDA-MB-468) human breast tumor cell lines.