Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment.

Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs.

Comparison of the biomechanical stability of transverse and oblique screw trajectories in retrograde intramedullary nailing of supracondylar femur fractures.

Background: The goal was to determine the effect of addition of oblique trajectory distal interlock screws to a retrograde intramedullary femoral nail on implant stability (stiffness), cycles to failure and mode of failure. The hypothesis was that addition of oblique screws would increase implant stability and number of loading cycles to failure.

Methods: Eight matched pairs were tested; one femur implanted with a femoral nail with only transverse distal interlock screws and the other with transverse and oblique interlock screws.

Team Approach: Preoperative Management of Metabolic Conditions in Total Joint Replacement.

»: Total joint arthroplasties (TJAs) of the knee and hip have been considered 2 of the most successful surgical procedures performed to date.

»: Frailty is defined as increased vulnerability to adverse outcomes with physiologic stress.

»: Preoperative optimization of frailty and metabolic bone conditions, including osteoporosis, vitamin D deficiency, and diabetes, through a multidisciplinary approach can help improve outcomes and minimize costs after TJA.

Custom total knee: understanding the indication and process.

Patient-specific total knee arthroplasty (TKA) is a copy of the bony knee morphology based on a pre-op computer tomography (CT). The images are segmented in 3D and software is utilized through a proprietary process to generate individual total knee implants to recreate the articulating surfaces. The distal condylar valgus angle of the prosthesis is matched anatomically to the distal femur and reversely matched on the tibia with a thicker lateral insert.

The ACS-NSQIP surgical risk calculator is a poor predictor of postoperative complications in patients undergoing oncologic distal femoral replacement.

Background: Distal femur replacement (DFR) has become a preferred reconstruction for tumors involving the femur but is associated with known complications. The ACS-NSQIP surgical risk calculator is an online tool developed to estimate postoperative complications in the first 30-days, however, has not been used in patients undergoing DFR. The purpose of this study was determining the utility of the ACS-NSQIP calculator to predict postoperative complications.

Utility of the ACS-NSQIP surgical risk calculator in predicting postoperative complications in patients undergoing oncologic proximal femoral replacement.

Introduction: Proximal femur replacement (PFR) in the setting of tumor resection is associated with a high rate of postoperative complication. The online American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculator is approved by the Center of Medicare and Medicaid services to estimate 30-day postoperative complications. This study was to determine if the ACS-NSQIP can predict postoperative complications following PFR.

Investigating cytosolic 5'-nucleotidase II family genes as candidates for neuropsychiatric disorders in Drosophila (114/150 chr).

Cytosolic 5'-nucleotidases II (cNT5-II) are an evolutionary conserved family of 5'-nucleotidases that catalyze the intracellular hydrolysis of nucleotides. In humans, the family is encoded by five genes, namely NT5C2, NT5DC1, NT5DC2, NT5DC3, and NT5DC4. While very little is known about the role of these genes in the nervous system, several of them have been associated with neuropsychiatric disorders.

Extremity Soft Tissue Sarcoma: Role of Local Control.

For localized extremity soft tissue sarcoma (eSTS), treatment is individualized and each patient needs to be evaluated by a multidisciplinary team at a referral sarcoma center specialized in the care of sarcoma. For a majority of patients, treatment for eSTS involves limb-salvage surgery, with or without the addition of radiation therapy. Surgery should only be performed by surgeons specifically fellowship trained in the resection of eSTS.

Psychometric evaluation of a screening question for persistent depressive disorder.

Background: About one in five patients with depression experiences a chronic course. Despite the great burden associated with this disease, there is no current screening instrument for Persistent Depressive Disorder (PDD). In the present study, we examine a short screening test, the persistent depression screener (PDS), that we developed for DSM-5 PDD.

Distal Nail Target and Alignment of Distal Tibia Fractures.

Objectives: To assess the relationship between the distal nail target and postoperative alignment for distal tibia fractures treated with intramedullary nailing.

Design: Retrospective cohort study.

Setting: A single level 1 trauma center.

C-X-C Motif Chemokine Receptor 4 Blockade Promotes Tissue Repair After Myocardial Infarction by Enhancing Regulatory T Cell Mobilization and Immune-Regulatory Function.

Background: Acute myocardial infarction (MI) elicits an inflammatory response that drives tissue repair and adverse cardiac remodeling. Inflammatory cell trafficking after MI is controlled by C-X-C motif chemokine ligand 12 (CXCL12) and its receptor, C-X-C motif chemokine receptor 4 (CXCR4). CXCR4 antagonists mobilize inflammatory cells and promote infarct repair, but the cellular mechanisms are unclear.

EMC10 (Endoplasmic Reticulum Membrane Protein Complex Subunit 10) Is a Bone Marrow-Derived Angiogenic Growth Factor Promoting Tissue Repair After Myocardial Infarction.

Background: Clinical trials of bone marrow cell-based therapies after acute myocardial infarction (MI) have produced mostly neutral results. Treatment with specific bone marrow cell-derived secreted proteins may provide an alternative biological approach to improving tissue repair and heart function after MI. We recently performed a bioinformatic secretome analysis in bone marrow cells from patients with acute MI and discovered a poorly characterized secreted protein, EMC10 (endoplasmic reticulum membrane protein complex subunit 10), showing activity in an angiogenic screen.

Regulation of distinct branches of the non-canonical Wnt-signaling network in Xenopus dorsal marginal zone explants.

Background: A tight regulation of the Wnt-signaling network, activated by 19 Wnt molecules and numerous receptors and co-receptors, is required for the establishment of a complex organism. Different branches of this Wnt-signaling network, including the canonical Wnt/β-catenin and the non-canonical Wnt/PCP, Wnt/Ror2 and Wnt/Ca(2+) pathways, are assigned to distinct developmental processes and are triggered by certain ligand/receptor complexes. The Wnt-signaling molecules are closely related and it is still on debate whether the information for activating a specific branch is encoded by specific sequence motifs within a particular Wnt protein.

Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation.

Convergent extension movements during vertebrate gastrulation require a balanced activity of non-canonical Wnt signaling pathways, but the factors regulating this interplay on the molecular level are poorly characterized. Here we show that sFRP2, a member of the secreted frizzled-related protein (sFRP) family, is required for morphogenesis and papc expression during Xenopus gastrulation. We further provide evidence that sFRP2 redirects non-canonical Wnt signaling from Frizzled 7 (Fz7) to the receptor tyrosine kinase-like orphan receptor 2 (Ror2).

Comparison Between Various Color Spectra and Conventional Grayscale Imaging for Detection of Parenchymal Liver Lesions With B-Mode Sonography.

Objectives: The electronic colorization of grayscale B-mode sonograms using various color schemes aims to enhance the adaptability and practicability of B-mode sonography in daylight conditions. The purpose of this study was to determine the diagnostic effectiveness and importance of colorized B-mode sonography.

Methods: Fifty-three video sequences of sonographic examinations of the liver were digitized and subsequently colorized in 2 different color combinations (yellow-brown and blue-white).

In situ cooling with ice water for the easier removal of self-expanding nitinol stents.

Background: It is yet to be determined what effects temperature has on the properties of nitinol in order to simplify the process of removing nitinol self-expanding metal stents (SEMS).

Materials And Methods: We describe the procedure for removal of SEMS in a total of 11 cases with 9 patients. A study involving cooling of nitinol stents in situ with ice water just before their removal was attempted.

Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction.

Paracrine-acting proteins are emerging as a central mechanism by which bone marrow cell-based therapies improve tissue repair and heart function after myocardial infarction (MI). We carried out a bioinformatic secretome analysis in bone marrow cells from patients with acute MI to identify novel secreted proteins with therapeutic potential. Functional screens revealed a secreted protein encoded by an open reading frame on chromosome 19 (C19orf10) that promotes cardiac myocyte survival and angiogenesis.

Caenorhabditis elegans PIG-1/MELK acts in a conserved PAR-4/LKB1 polarity pathway to promote asymmetric neuroblast divisions.

Asymmetric cell divisions produce daughter cells with distinct sizes and fates, a process important for generating cell diversity during development. Many Caenorhabditis elegans neuroblasts, including the posterior daughter of the Q cell (Q.p), divide to produce a larger neuron or neuronal precursor and a smaller cell that dies.

Symptoms, spirometry, and serum antibody concentrations among compost workers exposed to organic dust.

Work-related symptoms and diseases of 190 currently exposed compost workers, 59 former compost workers, and 38 nonexposed control subjects were investigated in a cross-sectional study. Using a standardized questionnaire, participants were asked for work-related symptoms, exposures to bioaerosols, atopic diseases, and smoking habits. The subjects underwent a physical examination and a lung function test.

The suitability of human adipose-derived stem cells for the engineering of ligament tissue.

Rupture of the anterior cruciate ligament (ACL) is the one of the most common sports-related injuries. With its poor healing capacity, surgical reconstruction using either autografts or allografts is currently required to restore function. However, serious complications are associated with graft reconstructions and the number of such reconstructions has steadily risen over the years, necessitating the search for an alternative approach to ACL repair.

Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction.

Aims: Results from clinical trials suggest that cardiac function after acute myocardial infarction (AMI) can be enhanced by an intracoronary infusion of autologous unselected nucleated bone marrow cells (BMCs). Release of paracrine factors has been proposed as a mechanism for these therapeutic effects; however, this hypothesis has not been tested in humans.

Methods And Results: BMCs and peripheral blood leucocytes (PBLs) were obtained from 15 patients with AMI and cultured in serum-free medium to obtain conditioned supernatants (SN).

Pseudomonas exotoxin antisense RNA selectively kills hepatitis B virus infected cells.

Aim: To present an approach for selectively killing retrovirus-infected cells that combines the toxicity of Pseudomonas exotoxin (PE) and the presence of reverse transcriptase (RT) in infected cells.

Methods: PE antisense toxin RNA has palindromic stem loops at its 5' and 3' ends enabling self-primed generation of cDNA in the presence of RT. The RT activity expressed in retrovirus-infected cells converts "antisense-toxin-RNA" into a lethal toxin gene exclusively in these cells.

Analysis and evaluation of environmental tobacco smoke exposure as a risk factor for chronic cough.

Exposure to environmental tobacco smoke (ETS) and active tobacco smoking has been shown to increase symptoms of bronchial asthma such as bronchoconstriction but effects on other respiratory symptoms remain poorly assessed. Current levels of exposure to tobacco smoke may also be responsible for the development of chronic cough in both children and adults. The present study analyses the effects of tobacco smoke exposure as potential causes of chronic cough.