Cold storage for Iowa apples

Under present conditions of apple growing in Iowa temporary gluts are common in very many local markets from the time the earliest fruits begin to ripen till early autumn or mid autumn followed usually by an immediate shortage as soon as the early fruit passes out of season. This holds true to a constantly increasing extent from south central Iowa to the north boundary of the State. The result is low prices locally for much of the early fruit with high prices usually prevailing from mid autumn to the end of the season. Even though prices are high very often the available supply of winter apples is not first-class fruit. The experiments demonstrate that certain desirable fall apples which are hardy enough to be grown sucessfully even in northern Iowa, can be held in good market condition through the winter months if handled carefully and stored quickly. This makes it possible to maintain a supply of home-grown fruit till late winter or early spring even in those parts of Iowa where practically none but early apples are now grown

Imaging Modalities for Cervical Spondylotic Stenosis and Myelopathy

Cervical spondylosis is a spectrum of pathology presenting as neck pain, radiculopathy, and myelopathy or all in combination. Diagnostic imaging is essential to diagnosis and preoperative planning. We discuss the modalities of imaging in common practice. We examine the use of imaging to differentiate among central, subarticular, and lateral stenosis and in the assessment of myelopathy

In vitro development of chemotherapy and targeted therapy drug-resistant cancer cell lines: a practical guide with case studies

The development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical drug resistance

Syndecan-3 is selectively pro-inflammatory in the joint and contributes to antigen-induced arthritis in mice

INTRODUCTION: Syndecans are heparan sulphate proteoglycans expressed by endothelial cells. Syndecan-3 is expressed by synovial endothelial cells of rheumatoid arthritis (RA) patients where it binds chemokines, suggesting a role in leukocyte trafficking. The objective of the current study was to examine the function of syndecan-3 in joint inflammation by genetic deletion in mice and compare with other tissues. METHODS: Chemokine C-X-C ligand 1 (CXCL1) was injected in the joints of syndecan-3-/-and wild-type mice and antigen-induced arthritis performed. For comparison chemokine was administered in the skin and cremaster muscle. Intravital microscopy was performed in the cremaster muscle. RESULTS: Administration of CXCL1 in knee joints of syndecan-3-/-mice resulted in reduced neutrophil accumulation compared to wild type. This was associated with diminished presence of CXCL1 at the luminal surface of synovial endothelial cells where this chemokine clustered and bound to heparan sulphate. Furthermore, in the arthritis model syndecan-3 deletion led to reduced joint swelling, leukocyte accumulation, cartilage degradation and overall disease severity. Conversely, CXCL1 administration in the skin of syndecan-3 null mice provoked increased neutrophil recruitment and was associated with elevated luminal expression of E-selectin by dermal endothelial cells. Similarly in the cremaster, intravital microscopy showed increased numbers of leukocytes adhering and rolling in venules in syndecan-3-/-mice in response to CXCL1 or tumour necrosis factor alpha. CONCLUSIONS: This study shows a novel role for syndecan-3 in inflammation. In the joint it is selectively pro-inflammatory, functioning in endothelial chemokine presentation and leukocyte recruitment and cartilage damage in an RA model. Conversely, in skin and cremaster it is anti-inflammatory

Mycophenolate mofetil treatment for primary glomerular diseases

Mycophenolate mofetil treatment for primary glomerular diseases.BackgroundTreatment of primary glomerular diseases may be unsuccessful or have potential toxicities. Therefore, we evaluated the use of mycophenolate mofetil (MMF) for empirical treatment of primary glomerulopathies.MethodsForty-six patients with biopsy-proven primary glomerulopathies received MMF for ≥3 months as adjunctive or primary treatment. Median (range) 24-hour urine protein to creatinine ratio (Up/c) and serum creatinine at the start and end of MMF therapy were compared using the Wilcoxon signed-ranks test.ResultsOverall, the median Up/c decreased from 4.7 (range <0.1, 20.3) to 1.1 (<0.1, 14.3; P < 0.001) at the end of MMF treatment with no significant change in median serum creatinine 1.3 (0.6 to 6.1) to 1.2 (0.5 to 6.5) mg/dL. Median serum albumin increased from 3.4 (1.4, 4.6) to 4.1 (1.7, 48) g/dL (P < 0.001) and the median serum cholesterol decreased from 270 (148, 795) to 220 (140, 309) mg/dL (P < 0.001) post-treatment. For those with minimal change disease, a complete steroid withdrawal was accomplished in 5/6 steroid dependent patients. Focal segmental glomerulosclerosis (FSGS) patients had a median Up/c that decreased from 2.7 (0.1, 20.3) to 0.8 (<0.1, 8.2; P = 0.001) in 18 patients. In membranous nephropathy (MN) patients, the median Up/c decreased from 7.3 (0.1, 18.5) to 1.5 (<0.1, 14.3) (P = 0.001) in 17 patients. No significant change in median serum creatinine was detected in FSGS or MN patient groups during treatment.ConclusionsEmpirical MMF therapy in the majority of patients with primary glomerulopathies was well tolerated and achieved the goals of steroid withdrawal, improvement of nephrotic syndrome, and stabilization of renal function

Artificial Neural Networks for Classification in Metabolomic Studies of Whole Cells Using 1H Nuclear Magnetic Resonance

We report the successful classification, by artificial neural networks (ANNs), of 1H NMR spectroscopic data recorded on whole-cell culture samples of four different lung carcinoma cell lines, which display different drug resistance patterns. The robustness of the approach was demonstrated by its ability to classify the cell line correctly in 100% of cases, despite the demonstrated presence of operator-induced sources of variation, and irrespective of which spectra are used for training and for validation. The study demonstrates the potential of ANN for lung carcinoma classification in realistic situations

A preclinical evaluation of the PI3K alpha/delta dominant inhibitor BAY 80-6946 in HER2-positive breast cancer models with acquired resistance to the HER2-targeted therapies trastuzumab and lapatinib.

The PI3K pathway is a key mechanism of trastuzumab resistance, but early attempts to indirectly target this pathway with mTOR inhibitors have had limited success. We present the results of a preclinical study of the selective alpha/delta isoform dominant PI3K inhibitor BAY 80-6946 tested alone and in combination with HER2-targeted therapies in HER2-positive cell lines, including models with acquired resistance to trastuzumab and/or lapatinib. A panel of HER2-positive breast cancer cells were profiled for their mutational status using Sequenom MassARRAY, PTEN status by Western blot, and anti-proliferative response to BAY 80-6946 alone and in combination with the HER2-targeted therapies trastuzumab, lapatinib and afatinib. Reverse phase protein array was used to determine the effect of BAY 80-6946 on expression and phosphorylation of 68 proteins including members of the PI3K and MAPK pathways. The Boyden chamber method was used to determine if BAY 80-6946 affected cellular invasion and migration. BAY 80-6946 has anti-proliferative and anti-invasive effects when used alone in our panel of cell lines (IC50s 3.9-29.4 nM). BAY 80-6946 inhibited PI3K signalling and was effective in cells regardless of their PI3K, P53 or PTEN status. The combination of HER2-targeted therapies and BAY 80-6946 inhibited growth more effectively than either therapy used alone (with clear synergism in many cases), and can restore sensitivity to trastuzumab and lapatinib in cells with acquired resistance to either trastuzumab and/or lapatinib. The addition of BAY 80-6946 to HER2-targeted therapy could represent an improved treatment strategy for patients with refractory metastatic HER2-positive breast cancer, and should be considered for clinical trial evaluation

Radiologic imaging in cystic fibrosis: cumulative effective dose and changing trends over 2 decades

Objective: With the increasing life expectancy for patients with cystic fibrosis (CF), and a known predisposition to certain cancers, cumulative radiation exposure from radiologic imaging is of increasing significance. This study explores the estimated cumulative effective radiation dose over a 17-year period from radiologic procedures and changing trends of imaging modalities over this period. Methods: Estimated cumulative effective dose (CED) from all thoracic and extrathoracic imaging modalities and interventional radiology procedures for both adult and pediatric patients with CF, exclusively attending a nationally designated CF center between 1992-2009 for > 1 year, was determined. The study period was divided into three equal tertiles, and estimated CED attributable to all radiologic procedures was estimated for each tertile. Results: Two hundred thirty patients met inclusion criteria (2,240 person-years of follow-up; 5,596 radiologic procedures). CED was > 75 mSv for one patient (0.43%), 36 patients (15.6%) had a CED between 20 and 75 mSv, 56 patients (24.3%) had a CED between 5 and 20 mSv, and in 138 patients (60%) the CED was estimated to be between 0 and 5 mSv over the study period. The mean annual CED per patient increased consecutively from 0.39 mSv/y to 0.47 mSv/y to 1.67 mSv/y over the tertiles one to three of the study period, respectively (P < .001). Thoracic imaging accounted for 46.9% of the total CED and abdominopelvic imaging accounted for 42.9% of the CED, respectively. There was an associated 5.9-fold increase in the use of all CT scanning per patient (P < .001). Conclusions: This study highlights the increasing exposure to ionizing radiation to patients with CF as a result of diagnostic imaging, primarily attributable to CT scanning. Increased awareness of CED and strategies to reduce this exposure are needed

Sexuality and intimacy among people with serious mental illness: a qualitative systematic review

OBJECTIVE: The aim of this systematic review was to synthesize the best available qualitative evidence on the experiences and support needs of people with serious mental illness (SMI) regarding sexuality and intimacy within hospital and community settings. The objectives were to explore intimate relationship experiences of people with SMI, to uncover potential obstacles to the expression of sexuality and to present recommendations for mental health policy, education, research and practice. INTRODUCTION: Mental health services worldwide have seen major transformations in recent years through deinstitutionalization programs and more enlightened ways of organizing and providing mental health care. However, in terms of social and emotional wellbeing, issues persist for people with SMI, particularly relating to intimacy and the expression of sexuality. This systematic review may assist service providers to determine ways that they may better support people in establishing and maintaining satisfying intimate relationships and the full expression of their sexuality. INCLUSION CRITERIA: This review explored the intimacy and sexuality experiences, perceptions and concerns of people over the age of 18 years who were living with a SMI in hospital or community settings. This review considered studies that focused on qualitative data including, but not limited to, designs such as phenomenology, grounded theory, ethnography, action research and feminist research. METHODS: The databases MEDLINE, CINAHL, PsycINFO, Embase and Web of Science were utilised in the review. The search included studies published from 1995 up to and including February 6, 2018 and were limited to those in the English language. Each paper was assessed by two independent reviewers for methodological quality using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research. Any disagreements that arose between the reviewers were resolved through discussion. Data extraction was conducted by two independent reviewers using the standardized qualitative data extraction tool from JBI. The qualitative research findings were pooled using JBI methodology. The JBI process of meta-aggregation was used to identify categories and synthesized findings. RESULTS: Based on the thematic findings from the 21 studies, three synthesized findings were extracted from 10 categories and 83 findings: 1) the complexity of individual sexual experiences, 2) the clinical constructs of sexuality and 3) family and partner involvement. CONCLUSIONS: Having fulfilling and satisfying sexual and relationship experiences is a fundamental human right that can enhance an individual's quality of life. Being aware of the potential stresses and challenges that having a SMI can have on a relationship and involving partners in the treatment, may help to promote intimacy and recovery. Practitioners can use these findings to guide future policy, education and developments in practice. Further research is required to develop and evaluate interventions that target the identified barriers and help people with SMI to fulfil their unmet sexuality and intimacy needs