Tourniquetless Total Knee Arthroplasty With Modern Perioperative Protocols Decreases Pain and Opioid Consumption in Women

Background This study examined whether a modern total knee arthroplasty (TKA) protocol without a tourniquet results in less patient-reported pain and in-hospital opioid consumption compared to TKA with a tourniquet. Methods A retrospective study of 203 primary unilateral cemented TKAs consecutively performed with or without tourniquet was performed. Identical perioperative pain and blood loss protocols were used in all cases. In tourniquetless TKAs, the tourniquet was not inflated at any time, and sterile CO2 gas compression maximized cement interdigitation. Results After exclusions for scientific confounds, 184 TKAs (93 with tourniquet; 91 tourniquetless) were analyzed. Controlling for multiple covariates, females with a tourniquet reported significantly more pain (P = .002) and opioid consumption (P < .001) the first 24 hours after surgery compared to females without a tourniquet. There were no differences in pain (P = .192) or amount of opioids consumed (P = .203) among males with and without a tourniquet. Tourniquet use resulted in a significant reduction in blood loss for both females (P ≤ .040) and males (P ≤ .020), although the total blood savings of approximately 200 mL is of unknown clinical significance. Conclusion Avoiding tourniquet use during TKA for females may be a relatively risk-free adjunct to minimize opioid consumption during hospitalization. Further study is warranted to elucidate the factors accounting for different outcomes in females and males

Serum S100A6 Concentration Predicts Peritoneal Tumor Burden in Mice with Epithelial Ovarian Cancer and Is Associated with Advanced Stage in Patients

BACKGROUND:Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved means for early detection and reliable patient monitoring are needed to increase survival. METHODOLOGY AND PRINCIPAL FINDINGS:Applying mass spectrometry-based proteomics, we sought to elucidate an unanswered biomarker research question regarding ability to determine tumor burden detectable by an ovarian cancer biomarker protein emanating directly from the tumor cells. Since aggressive serous epithelial ovarian cancers account for most mortality, a xenograft model using human SKOV-3 serous ovarian cancer cells was established to model progression to disseminated carcinomatosis. Using a method for low molecular weight protein enrichment, followed by liquid chromatography and mass spectrometry analysis, a human-specific peptide sequence of S100A6 was identified in sera from mice with advanced-stage experimental ovarian carcinoma. S100A6 expression was documented in cancer xenografts as well as from ovarian cancer patient tissues. Longitudinal study revealed that serum S100A6 concentration is directly related to tumor burden predictions from an inverse regression calibration analysis of data obtained from a detergent-supplemented antigen capture immunoassay and whole-animal bioluminescent optical imaging. The result from the animal model was confirmed in human clinical material as S100A6 was found to be significantly elevated in the sera from women with advanced stage ovarian cancer compared to those with early stage disease. CONCLUSIONS:S100A6 is expressed in ovarian and other cancer tissues, but has not been documented previously in ovarian cancer disease sera. S100A6 is found in serum in concentrations that correlate with experimental tumor burden and with clinical disease stage. The data signify that S100A6 may prove useful in detecting and/or monitoring ovarian cancer, when used in concert with other biomarkers

The role of diatom nanostructures in biasing diffusion to improve uptake in a patchy nutrient environment

Extent: 9 p.BACKGROUND: Diatoms are important single-celled autotrophs that dominate most lit aquatic environments and are distinguished by surficial frustules with intricate designs of unknown function. PRINCIPAL FINDINGS: We show that some frustule designs constrain diffusion to positively alter nutrient uptake. In nutrient gradients of 4 to 160 times over, 5 cm, the screened-chambered morphology of Coscincodiscus sp. biases the nutrient diffusion towards the cell by at least 3.8 times the diffusion to the seawater. In contrast, the open-chambers of Thalassiosira eccentrica produce at least a 1.3 times diffusion advantage to the membrane over Coscincodiscus sp. when nutrients are homogeneous. SIGNIFICANCE: Diffusion constraint explains the success of particular diatom species at given times and the overall success of diatoms. The results help answer the unresolved question of how adjacent microplankton compete. Furthermore, diffusion constraint by supramembrane nanostructures to alter molecular diffusion suggests that microbes compete via supramembrane topology, a competitive mechanism not considered by the standard smooth-surface equations used for nutrient uptake nor in microbial ecology and cell physiology.James G. Mitchell, Laurent Seuront, Mark J. Doubell, Dusan Losic, Nicolas H. Voelcker, Justin Seymour and Ratnesh La

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Nmp4/CIZ Closes the Parathyroid Hormone Anabolic Window

Chronic degenerative diseases are increasing with the aging U.S. population. One consequence of this phenomenon is the need for long-term osteoporosis therapies. Parathyroid hormone (PTH), the only FDA-approved treatment that adds bone to the aged skeleton, loses its potency within two years of initial treatment but the mechanism regulating its limited “anabolic window” is unknown. We have discovered that disabling the nucleocytoplasmic shuttling transcription factor nuclear matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) in mice extends the PTH bone-forming capacity. Nmp4 was discovered during our search for nuclear matrix transcription factors that couple this hormone’s impact on osteoblast cytoskeletal and nuclear organization with its anabolic capacity. CIZ was independently discovered as a protein that associates with the focal adhesion-associated mechanosensor p130Cas. The Nmp4/CIZ-knockout (KO) skeletal phenotype exhibits a modestly enhanced bone mineral density but manifests an exaggerated response to both PTH and to BMP2 and is resistant to disuse-induced bone loss. The cellular basis of the global Nmp4/CIZ-KO skeletal phenotype remains to be elucidated but may involve an expansion of the bone marrow osteoprogenitor population along with modestly enhanced osteoblast and osteoclast activities supporting anabolic bone turnover. As a shuttling Cys(2)His(2) zinc finger protein, Nmp4/CIZ acts as a repressive transcription factor perhaps associated with epigenetic remodeling complexes, but the functional significance of its interaction with p130Cas is not known. Despite numerous remaining questions, Nmp4/CIZ provides insights into how the anabolic window is regulated, and itself may provide an adjuvant therapy target for the treatment of osteoporosis by extending PTH anabolic efficacy