Overcoming barriers to levonorgestrel-releasing intrauterine system placement: an evaluation of placement of LNG-IUS 8 using the modified EvoInserter® in a majority nulliparous population.

Objectives: To report placement success rate, and ease and pain associated with placement, of the levonorgestrel-releasing intrauterine system (LNG-IUS) 8 using the modified EvoInserter® placement device.

Study Design: This was a pooled analysis using data from three previously reported Phase III studies in nulliparous (83.3%) or parous (16.

Homo- and heteropolymer self-assembly of recombinant trichocytic keratins.

In the past two decades, keratin biomaterials have shown impressive results as scaffolds for tissue engineering, wound healing, and nerve regeneration. In addition to its intrinsic biocompatibility, keratin interacts with specific cell receptors eliciting beneficial biochemical cues. However, during extraction from natural sources, such as hair and wool fibers, natural keratins are subject to extensive processing conditions that lead to formation of unwanted by-products.

Emergence of robustness in networks of networks.

A model of interdependent networks of networks (NONs) was introduced recently [Proc. Natl. Acad.

Inhibition of Mitochondrial Matrix Chaperones and Antiapoptotic Bcl-2 Family Proteins Empower Antitumor Therapeutic Responses.

Rational therapeutic approaches based on synthetic lethality may improve cancer management. On the basis of a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL, and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and obatoclax) or selective (ABT199, WEHI-539, and A1210477), along with the established mitochondrial matrix chaperone inhibitor gamitrinib-TPP.

The RESPIRE trials: Two phase III, randomized, multicentre, placebo-controlled trials of Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) in non-cystic fibrosis bronchiectasis.

Unlabelled: The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve quality of life. However, currently no therapies are licensed for this. Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients.

Synthesis of Diverse N-Acryloyl Azetidines and Evaluation of Their Enhanced Thiol Reactivities.

Acyl azetidines exhibit nonplanar hybridization, leading to lower amide-like character of the corresponding (O)C-N bonds. This impacts N-acryloyl azetidines by producing enhanced electrophilicy at appended Michael acceptors. Herein, reactivity data are reported in the presence of glutathione (GSH) in phosphate buffer (pH 7.

Factors associated with lingual tonsil hypertrophy in Canadian adults.

Background: Hypertrophy of the lingual tonsil tissue in the adult patient is thought to contribute to the pathophysiology of obstructive sleep apnea. The underlying etiology of lingual tonsil hypertrophy (LTH) in the adult patient is unclear and likely multifactorial. Previous studies have suggested that the lingual tonsils may undergo compensatory hyperplasia post-tonsillectomy in children, although it is unknown if this occurs or persists into adulthood.

Model of brain activation predicts the neural collective influence map of the brain.

Efficient complex systems have a modular structure, but modularity does not guarantee robustness, because efficiency also requires an ingenious interplay of the interacting modular components. The human brain is the elemental paradigm of an efficient robust modular system interconnected as a network of networks (NoN). Understanding the emergence of robustness in such modular architectures from the interconnections of its parts is a longstanding challenge that has concerned many scientists.

LIN28 Zinc Knuckle Domain Is Required and Sufficient to Induce let-7 Oligouridylation.

LIN28 is an RNA binding protein that plays crucial roles in pluripotency, glucose metabolism, tissue regeneration, and tumorigenesis. LIN28 binds to the let-7 primary and precursor microRNAs through bipartite recognition and induces degradation of let-7 precursors (pre-let-7) by promoting oligouridylation by terminal uridylyltransferases (TUTases). Here, we report that the zinc knuckle domain (ZKD) of mouse LIN28 recruits TUT4 to initiate the oligouridylation of let-7 precursors.

Malignant Proliferating Trichilemmal Tumor Treated with Radical Radiotherapy: A Case Report and Literature Review.

Reported here is the first case of a malignant proliferating trichilemmal tumor treated with radical radiotherapy. Complete clinical response was achieved, and this obviated the need for aggressive surgery. These tumors have a tendency to develop in older patients, and have a propensity for affecting women more than men.

Patient perspectives on ipilimumab across the melanoma treatment trajectory.

Purpose: Ipilimumab was the first FDA-approved agent for advanced melanoma to improve survival and represents a paradigm shift in melanoma and cancer treatment. Its unique toxicity profile and kinetics of treatment response raise novel patient education challenges. We assessed patient perceptions of ipilimumab therapy across the treatment trajectory.

Cargo delivery on demand from photodegradable MOF nano-cages.

We report the photo-induced degradation of and cargo release from a nanoscale metal-organic framework (nMOF) incorporating photo-isomerizable 4,4'-azobenzenedicarboxylate (AZB) linkers. The structure matches a UiO-type framework where 12 4,4'-azobenzenedicarboxylate moieties are connected to a ZrO(OH) cluster, referred to as UiO-AZB. Due to the incorporation of photo-isomerizable struts, the degradation of UiO-AZB is accelerated by irradiation with white light (1.

BH3 mimetics suppress CXCL12 expression in human malignant peripheral nerve sheath tumor cells.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, Schwann cell-derived neoplasms of the peripheral nervous system that have recently been shown to possess an autocrine CXCL12/CXCR4 signaling loop that promotes tumor cell proliferation and survival. Importantly, the CXCL12/CXCR4 signaling axis is driven by availability of the CXCL12 ligand rather than CXCR4 receptor levels alone. Therefore, pharmacological reduction of CXCL12 expression could be a potential chemotherapeutic target for patients with MPNSTs or other pathologies wherein the CXCL12/CXCR4 signaling axis is active.

Design principles for effective video-based professional development.

Background: Most studies of teacher professional development (PD) do not rigorously test impact on teaching practice and student learning. This makes it difficult to define what is truly "effective." The (STeLLA) PD program, in contrast, was studied in a cluster randomized experimental design that examined impact on teaching practice and student learning.

Vitamin D Deficiency: The Missing Etiological Factor in the Development of Juvenile Osteochondrosis Dissecans?

Background: Vitamin D deficiency can result in rickets and hypocalcemia during infant and childhood growth. There is an increasing interest in the role of vitamin D with regards to childhood bone health. Osteochondrosis dissecans (OD) is a common disease affecting different joints.

Applications of patient-specific 3D printing in medicine.

Already three decades ago, the potential of medical 3D printing (3DP) or rapid prototyping for improved patient treatment began to be recognized. Since then, more and more medical indications in different surgical disciplines have been improved by using this new technique. Numerous examples have demonstrated the enormous benefit of 3DP in the medical care of patients by, for example, planning complex surgical interventions preoperatively, reducing implantation steps and anesthesia times, and helping with intraoperative orientation.

The American Journal of Pathology, Value Beyond Simple Metrics.

This Editorial highlights the value of The American Journal of Pathology beyond normal metrics.

Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer.

Background: Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer.

A single-arm phase III study exploring the efficacy and safety of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg), in an Asia-Pacific population.

Objective: The objective was to evaluate the efficacy and safety of a low-dose levonorgestrel intrauterine system with total content 13.5 mg (average approximately 8 μg/24 h over the first year; LNG-IUS 8; Jaydess®) in an Asia-Pacific population.

Study Design: An open-label, single-arm phase III study conducted at 25 centers in China, Australia and Korea assessed LNG-IUS 8 use over 3 years in nulliparous and parous women (N=1114) aged 18-40 years with regular menstrual cycles (21-35 days).

Dairy farmers' perceptions toward the implementation of on-farm Johne's disease prevention and control strategies.

Implementation of specific management strategies on dairy farms is currently the most effective way to reduce the prevalence of Johne's disease (JD), an infectious chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). However, dairy farmers often fail to implement recommended strategies. The objective of this study was to assess perceptions of farmers participating in a JD prevention and control program toward recommended practices, and explore factors that influence whether or not a farmer adopts risk-reducing measures for MAP transmission.

Is there an association between low serum 25-OH-D levels and the length of hospital stay in orthopaedic patients after arthroplasty?

Background: The purpose of this observational study was to evaluate serum levels of 25-OH-D in patients scheduled to undergo elective hip or knee arthroplasty. We hypothesised that 25-OH-D level is an independent risk factor for length of stay in orthopaedic patients after elective hip or knee arthoplasty.

Materials And Methods: 25-OH-D levels were measured in 1083 patients admitted to an orthopaedic surgery department to undergo elective hip or knee arthroplasty.

Understanding Lung Development, Injury, and Repair.

This Editorial introduces the Lung Ontogeny and Injury Theme Issue, which provides critical insights into lung development, injury, and repair as well as key pulmonary diseases.

Tamoxifen Induces Cytotoxic Autophagy in Glioblastoma.

Glioblastomas (GBMs) are the most common and aggressive primary human malignant brain tumors. 4-Hydroxy tamoxifen (OHT) is an active metabolite of the tamoxifen (TMX) prodrug and a well-established estrogen receptor (ER) and estrogen-related receptor antagonist. A recent study from our laboratory demonstrated that OHT induced ER-independent malignant peripheral nerve sheath tumor (MPNST) cell death by autophagic degradation of the prosurvival protein Kirsten rat sarcoma viral oncogene homolog.

A multicentre, open-label, randomised phase III study comparing a new levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral contraception in young women of reproductive age.

Objectives: To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 μg/24 h over the first year [total content 13.5 mg]) and a 30 μg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women.

Methods: Nulliparous and parous women (aged 18-29 years) with regular menstrual cycles (21-35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months.

COSTS OF DEPRESSION FROM CLAIMS DATA FOR MEDICARE RECIPIENTS IN A POPULATION-BASED SAMPLE.

Background: Many persons with depressive disorder are not treated and associated costs are not recorded.

Aims Of The Study: To determine whether major depressive disorder (MDD) is associated with higher medical cost among Medicare recipients.

Methods: Four waves of the Baltimore-Epidemiologic Catchment Area (Baltimore ECA) Study conducted between 1981 and 2004 were linked to Medicare claims data for the years 1999 to 2004 from the Centers for Medicare and Medicaid Services (CMS).