The Short-Term Effects of 2 Different Cryotherapy Methods on Acute and Subacute, Noncomplicated, Bilateral Neck Pain

Background: Cryotherapy has since long been used by physical therapists and chiropractors in the management of acute pain; more recently, its use has been shown to be effective in managing chronic pain. Multiple studies have shown that both ice and menthol reduce blood flow to the affected area and help control pain; however, there is limited research to determine the form of cryotherapy that works better on individual patients. Purpose: The purpose of this study was to compare the effect of a cold pack and menthol topical gel on reports of pain among individuals with neck pain. Methods: In this randomized study, 51 individuals in the age range of 19–65 years (37 ± 11.2 years) with bilateral, nonradicular, acute neck pain (myalgia) were included. Cold packs and Biofreeze®, a topical analgesic, were applied on either side of the neck (ie, ice on one side and Biofreeze on the other). The patients were asked to rate their pain on a 0–10 visual analog scale for either side of the neck both before and immediately following the 10-minute treatment. In addition, the patients were asked to answer 2 questions about which modality they would prefer to use in the future for pain management and their level of comfort with each modality during its application and to rate their answers on a 5-point scale (1 = very unlikely or very uncomfortable and 5 = very likely or very comfortable). On the next day of treatment with cold packs and Biofreeze, patients were asked to choose their preferred mode of treatment among the two and the modality that had a longer-lasting effect. Results: Overall, when asked to rate the comfort and preference, patients preferred Biofreeze 8:1 (P = .000). The average score on the 5-point Likert scale was 4.20 and 2.57 for Biofreeze and cold pack, respectively. In addition, 9 out of 10 patients reported that the effect of Biofreeze lasted longer than that of ice (P = .000). Further, the average score for Biofreeze and ice was 4.47 to 2.63, respectively. For actual levels of pain relief, the average pretreatment visual analog scale score decreased from 6.24 to 3.65 for Biofreeze and from 6.31 to 5.00 for ice. A paired t test showed that both cold packs and Biofreeze significantly reduced pain (P = .000). However, the pain reduction was 2-fold with the Biofreeze treatment. Conclusions: Both cold packs and Biofreeze significantly reduced pain; however, there was a 2-fold reduction in pain with Biofreeze. Biofreeze was rated as substantially more comfortable; patients preferred it, and its effect lasted longer in 9 out of 10 trials. This study was the first to evaluate the immediate effects of 2 different cryotherapy methods. It is not unexpected that the results of this study would differ slightly from other published studies evaluating menthol products. Conservative care specialists are often looking for methods to improve patient satisfaction and compliance. The present study indicates that Biofreeze is the preferred method of cryotherapy application by many neck pain patients on their first visit to the clinic

Resistance studies of erythromycin and rifampin for Rhodococcus equi over a 10-year period

This study sought to determine whether an increase in resistance of Rhodococcus equi to the antibiotics rifampin and erythromycin occurred over a 10-year period. This was carried out by the use of E test strips for rifampin and erythromycin to determine the MIC (minimum inhibitory concentration) values of Rhodococcus equi to this combination of antibiotics

A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis

Extracellular matrix interactions play essential roles in normal physiology and many pathological processes. While the importance of ECM interactions in metastasis is well documented, systematic approaches to identify their roles in distinct stages of tumorigenesis have not been described. Here we report a novel screening platform capable of measuring phenotypic responses to combinations of ECM molecules. Using a genetic mouse model of lung adenocarcinoma, we measure the ECM-dependent adhesion of tumor-derived cells. Hierarchical clustering of the adhesion profiles differentiates metastatic cell lines from primary tumor lines. Furthermore, we uncovered that metastatic cells selectively associate with fibronectin when in combination with galectin-3, galectin-8, or laminin. We show that these molecules correlate with human disease and that their interactions are mediated in part by α3β1 integrin. Thus, our platform allowed us to interrogate interactions between metastatic cells and their microenvironments, and identified ECM and integrin interactions that could serve as therapeutic targets

Successful treatment of recurrent small bowel adenocarcinoma by cytoreductive surgery and chemotherapy: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Small bowel adenocarcinoma is a rare malignancy associated with a poor prognosis and there is little evidence of effective treatment. Recurrent small bowel adenocarcinoma is an intractable disease for which there is little information available regarding its treatment by palliative therapy. We present a case of recurrent small bowel adenocarcinoma successfully treated by cytoreductive surgery and palliative chemotherapy.</p> <p>Case presentation</p> <p>We report the case of a 72-year-old Japanese female who developed a peritoneal metastasis from recurrent small bowel adenocarcinoma after curative resection and adjuvant chemotherapy with S-1 and polysaccharide K. She underwent cytoreductive surgery followed by chemotherapy with folinic acid/fluorouracil/oxaliplatin and folinic acid/fluorouracil/irinotecan with polysaccharide K. Subsequently, no sign of a recurrence was observed 42 months after the second operation.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first case report of the successful treatment of peritoneal metastasis from small bowel adenocarcinoma by cytoreductive surgery and combination chemotherapy (folinic acid/fluorouracil/oxaliplatin and folinic acid/fluorouracil/irinotecan with polysaccharide K).</p

Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma

Genetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC proto-oncogene. Tumors from EGFR- and Kras-driven models exhibited, respectively, 0.02 and 0.07 nonsynonymous mutations per megabase, a dramatically lower average mutational frequency than observed in human lung adenocarcinomas. Tumors from models driven by strong cancer drivers (mutant EGFR and Kras) harbored few mutations in known cancer genes, whereas tumors driven by MYC, a weaker initiating oncogene in the murine lung, acquired recurrent clonal oncogenic Kras mutations. In addition, although EGFR- and Kras-driven models both exhibited recurrent whole-chromosome DNA copy number alterations, the specific chromosomes altered by gain or loss were different in each model. These data demonstrate that GEMM tumors exhibit relatively simple somatic genotypes compared with human cancers of a similar type, making these autochthonous model systems useful for additive engineering approaches to assess the potential of novel mutations on tumorigenesis, cancer progression, and drug sensitivity

Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers

Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non-small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-chain amino acids (BCAAs) differently. NSCLC tumors incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen source, whereas PDAC tumors have decreased BCAA uptake. These differences are reflected in expression levels of BCAA catabolic enzymes in both mice and humans. Loss of Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor formation, but these enzymes are not required for PDAC tumor formation, arguing that tissue of origin is an important determinant of how cancers satisfy their metabolic requirements.National Institutes of Health (U.S.) (Grant F30CA183474)National Institutes of Health (U.S.) (Grant T32GM007753

European Financial Market Integration: A Closer Look at Government Bonds in Eurozone Countries

The European Union made a number of steps not least of them the introduction of a common currency to foster the integration of the European financial markets. A number of papers have tried to gauge the degree of integration for various financial markets looking at the convergence of interest rates. A common finding is that government bond markets are quite well integrated. In this paper stochastic Kernel density estimates are used to take a closer look at the dynamics that drive the process of interest rate convergence. The main finding is that countries with large initial deviations from the mean interest rate do indeed converge. Interestingly the candidates least suspected namely the countries initially with interest rates at the mean level show a pattern of slight divergence

Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma.

Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells. To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used to assess differences between cancer cell and fibroblast metabolism in murine pancreatic cancer organoid-fibroblast co-cultures and tumors. Pancreatic cancer cells exhibited increased pyruvate carboxylation relative to fibroblasts, and this flux depended on both pyruvate carboxylase and malic enzyme 1 activity. Consequently, expression of both enzymes in cancer cells was necessary for organoid and tumor growth, demonstrating that dissecting the metabolism of specific cell populations within heterogeneous systems can identify dependencies that may not be evident from studying isolated cells in culture or bulk tissue

Expression of tumour-specific antigens underlies cancer immunoediting

Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack1, 2. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is thereby enhanced in immune-compromised mice, whereas the capacity for such tumours to grow after transplantation into wild-type mice is reduced2, 3. However, many questions about the process of cancer immunoediting remain unanswered, in part because of the known antigenic complexity and heterogeneity of carcinogen-induced tumours4. Here we adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allows us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbour identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice with their development in mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or presentation on major histocompatibility complex I was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of tumour-specific-antigen expression in immune surveillance, and potentially, immunotherapy.National Institutes of Health (U.S.) (Grant 1 U54 CA126515-01)National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051)Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship AwardJohnD. Proctor FoundationDaniel K. Ludwig Schola