Metabolic cost for isometric force scales nonlinearly and predicts how humans distribute forces across limbs.

Muscles consume metabolic energy for force production and movement. A mathematical model of metabolic energy cost will be useful in predicting instantaneous costs during human exercise and in computing effort-minimizing movements via simulations. Previous in vivo data-derived models usually assumed either zero or linearly increasing cost with force, but a nonlinear relation could have significant metabolic or behavioural implications.

SNAT7 regulates mTORC1 via macropinocytosis.

Mammalian target of rapamycin complex 1 (mTORC1) senses amino acids to control cell growth, metabolism, and autophagy. Some amino acids signal to mTORC1 through the Rag GTPase, whereas glutamine and asparagine activate mTORC1 through a Rag GTPase-independent pathway. Here, we show that the lysosomal glutamine and asparagine transporter SNAT7 activates mTORC1 after extracellular protein, such as albumin, is macropinocytosed.

G-Protein Coupled Receptor Signaling and Mammalian Target of Rapamycin Complex 1 Regulation.

The mammalian target of rapamycin (mTOR) senses upstream stimuli to regulate numerous cellular functions such as metabolism, growth, and autophagy. Increased activation of mTOR complex 1 (mTORC1) is typically observed in human disease and continues to be an important therapeutic target. Understanding the upstream regulators of mTORC1 will provide a crucial link in targeting hyperactivated mTORC1 in human disease.

AKAP13 couples GPCR signaling to mTORC1 inhibition.

The mammalian target of rapamycin complex 1 (mTORC1) senses multiple stimuli to regulate anabolic and catabolic processes. mTORC1 is typically hyperactivated in multiple human diseases such as cancer and type 2 diabetes. Extensive research has focused on signaling pathways that can activate mTORC1 such as growth factors and amino acids.

ArfGAP1 inhibits mTORC1 lysosomal localization and activation.

The mammalian target of rapamycin complex 1 (mTORC1) integrates nutrients, growth factors, stress, and energy status to regulate cell growth and metabolism. Amino acids promote mTORC1 lysosomal localization and subsequent activation. However, the subcellular location or interacting proteins of mTORC1 under amino acid-deficient conditions is not completely understood.

Regulation of mTORC1 by Upstream Stimuli.

The mammalian target of rapamycin (mTOR) is an evolutionary conserved Ser/Thr protein kinase that senses multiple upstream stimuli to control cell growth, metabolism, and autophagy. mTOR is the catalytic subunit of mTOR complex 1 (mTORC1). A significant amount of research has uncovered the signaling pathways regulated by mTORC1, and the involvement of these signaling cascades in human diseases like cancer, diabetes, and ageing.

Small molecule H89 renders the phosphorylation of S6K1 and AKT resistant to mTOR inhibitors.

The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr kinase that comprises two complexes, termed mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1 phosphorylates S6K1 at Thr 389, whereas mTORC2 phosphorylates AKT at Ser 473 to promote cell growth. As the mTOR name implies it is the target of natural product called rapamycin, a clinically approved drug used to treat human disease.

A-kinase anchoring protein 8L interacts with mTORC1 and promotes cell growth.

mTOR complex 1 (mTORC1) senses nutrients to mediate anabolic processes within the cell. Exactly how mTORC1 promotes cell growth remains unclear. Here, we identified a novel mTORC1-interacting protein called protein kinase A anchoring protein 8L (AKAP8L).

Glutamine and asparagine activate mTORC1 independently of Rag GTPases.

Nutrient sensing by cells is crucial, and when this sensing mechanism is disturbed, human disease can occur. mTOR complex 1 (mTORC1) senses amino acids to control cell growth, metabolism, and autophagy. Leucine, arginine, and methionine signal to mTORC1 through the well-characterized Rag GTPase signaling pathway.

GPCR signaling inhibits mTORC1 via PKA phosphorylation of Raptor.

The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth, metabolism, and autophagy. Extensive research has focused on pathways that activate mTORC1 like growth factors and amino acids; however, much less is known about signaling cues that directly inhibit mTORC1 activity. Here, we report that G-protein coupled receptors (GPCRs) paired to Gα proteins increase cyclic adenosine 3'5' monophosphate (cAMP) to activate protein kinase A (PKA) and inhibit mTORC1.

Growth Differentiation Factor 6 Promotes Vascular Stability by Restraining Vascular Endothelial Growth Factor Signaling.

Objective: The assembly of a functional vascular system requires a coordinated and dynamic transition from activation to maturation. High vascular endothelial growth factor activity promotes activation, including junction destabilization and cell motility. Maturation involves junctional stabilization and formation of a functional endothelial barrier.

Incidence of successful voiding and predictors of early voiding dysfunction after retropubic sling.

Introduction And Hypothesis: There is a paucity of literature on resumption of normal voiding predictors after synthetic retropubic sling insertion and lack of a standardized method of determination. Our goals were to determine the incidence of a successful voiding trial; whether clinical, operative, or urodynamic variables predict discharge with a catheter; and incidence of later retention in those who were initially successful.

Methods: We performed an internal-review-board (IRB)-approved retrospective chart review of 229 consecutive patients who underwent retropubic sling (TVT, Boston Scientific, Natick, MA, USA)) from 2001 to 2010.

Discrete Notch signaling requirements in the specification of hematopoietic stem cells.

Hematopoietic stem cells (HSCs) require multiple molecular inputs for proper specification, including activity of the Notch signaling pathway. A requirement for the Notch1 and dispensability of the Notch2 receptor has been demonstrated in mice, but the role of the remaining Notch receptors has not been investigated. Here, we demonstrate that three of the four Notch receptors are independently required for the specification of HSCs in the zebrafish.

Bladder perforation during tension-free vaginal tape procedures: abdominal versus vaginal approach.

Objective: Bladder perforation rates for the tension-free vaginal tape (TVT) are higher with inexperienced surgeons. The purpose of this study was to examine if surgical approach affects this rate.

Methods: We performed a retrospective cohort study of consecutive patients undergoing a TVT as the sole procedure.

Outcomes of Retropubic Synthetic Midurethral Gynecare TVT Slings When Performed by Urogynecologists, Urologists, and General Gynecologists in a Private Community Hospital.

Objectives: : To compare perioperative outcomes of a retropubic synthetic midurethral Gynecare TVT slings (Gynecare Worldwide, division of Ethicon Inc, NJ) performed by urogynecologists, urologists, and general gynecologists.

Methods: : This is a retrospective, cohort study of retropubic synthetic midurethral Gynecare TVT sling outcomes performed between 2001 and 2007 at a single institution. Other synthetic and nonsynthetic slings, or slings performed with concurrent surgeries were excluded.

Reduction in the incidence of chronic lung disease in very low birth weight infants: results of a quality improvement process in a tertiary level neonatal intensive care unit.

Objective: Our objective was to reduce the incidence of chronic lung disease by introducing potentially better practices in our delivery room and NICU.

Methods: We compared the incidences of chronic lung disease in infants with birth weights of 501 to 1500 g in 2002 and 2005, after implementation of the changes. Medical records for infants of 501 to 1500 g who were born in 2002 and 2005 were reviewed for maternal characteristics, care of the infant in the delivery room and the NICU (including surfactant usage, duration of ventilation, duration of continuous positive airway pressure therapy, and duration of oxygen treatment), length of stay, and short-term clinical outcomes (eg, pneumothorax, severe intracranial hemorrhage, retinopathy of prematurity, and weight gain).

Outcomes of hysterectomies performed by supervised residents vs those performed by attendings alone.

Objective: The objective of the study was to compare the outcomes of hysterectomies performed by residents under supervision of a teaching physician with those performed by attendings alone.

Study Design: This was a retrospective cohort analysis of hysterectomies performed at the Greater Baltimore Medical Center from 2004 to 2006.

Results: Of 159 nonteaching and 265 teaching cases, there was no significant difference in any of the surgical outcomes, except mean operating room time in minutes (94.

Incontinence pads: recommending the best product-based wetback performance and price.

Incontinence pads are available in the USA without a prescription and are commonly the first treatment option a patient with incontinence uses. The goal of this study was to examine the difference in the performance and cost of commercially available incontinence pads with the intention of providing recommendations to women. Ten different urinary incontinence products were selected.

Patients' satisfaction with and attitudes toward vaginal delivery.

Objective: To determine patient satisfaction with delivery mode and whether information on urinary incontinence would modify their decision.

Study Design: Postpartum women completed an anonymous questionnaire regarding their delivery, complications, types of information received during pregnancy, and delivery and satisfaction with their mode of delivery. Various risk scenarios for urinary incontinence ranging from 10-50% were presented.

Bladder perforation during tension-free vaginal tape procedures: analysis of learning curve and risk factors.

Objective: To estimate whether rates of bladder perforation decrease with increasing surgical experience.

Methods: We performed a review of all patients undergoing a tension-free vaginal tape procedure performed by senior resident physicians under the guidance of a single surgeon. Physician experience was assessed by sequentially assigning case numbers to each procedure for each resident.

Patients' knowledge of potential pelvic floor changes associated with pregnancy and delivery.

Physicians cite pelvic floor injury as a major reason for Cesarean section as their personal preferred delivery mode. This study was undertaken to determine whether patients receive information about possible pelvic floor complications of pregnancy/delivery. Day 1 post-partum women completed a 52-item questionnaire assessing information given during routine antenatal care.

Comparison of long-term outcomes of autologous fascia lata slings with Suspend Tutoplast fascia lata allograft slings for stress incontinence.

Objective: This study was undertaken to compare the objective and subjective long-term surgical outcomes in patients receiving Tutoplast fascia lata allograft slings with those receiving autograft slings for the treatment of stress urinary incontinence (SUI).

Study Design: We reviewed all patients (n = 71) undergoing suburethral sling with either autologous fascia lata (n = 39) or Tutoplast fascia lata (n = 32) for urodynamic stress incontinence (USI) from October 1, 1998, to August 1, 2001.

Results: Of the original 71 patients, 47 were evaluated by objective and/or subjective means at a minimum of 2 years after surgery.

Anatomic relationship between the vaginal apex and the bony architecture of the pelvis: a magnetic resonance imaging evaluation.

Objective: This study was undertaken to define anatomic relationships between the vaginal apex and the ischial spines and sacrum for nulliparous women with normal support.

Study Design: We retrospectively evaluated the magnetic resonance images of 11 consecutive women who underwent pelvic imaging at Johns Hopkins. Coordinates were recorded for the posterior fornix, sacrum, ischial spines, and cervical vaginal junctions.

The effects of knowledge management on surgeon behavior.

Knowledge management is an important process for health care researchers and administrators. The way we manage and transfer knowledge in an organization can have a substantial impact on behavior and performance. In this article, we examine the behavioral effects of transferring performance-efficiency knowledge to a group of hospital-based surgeons.

A comparison of anticipatory and postprocedure pain perception in patients who undergo urodynamic procedures.

Objective: The purpose of this study was to compare anticipatory and postprocedure pain perception in female patients who undergo multichannel urodynamic evaluation in an office setting.

Study Design: One hundred consecutive patients completed a visual analogue pain scale before and after urodynamic testing.

Results: The mean postprocedure pain score of 2.