Synechocystis PCC6803 and PCC6906 dnaK2 expression confers salt and oxidative stress tolerance in Arabidopsis via reduction of hydrogen peroxide accumulation.

Abiotic stress slows plant growth and development. Because salt stress, particularly from NaCl, acts as an important limiting factor in agricultural productivity, the identification and manipulation of genes related to salt tolerance could improve crop productivity. Prokaryotic, heat shock protein (Hsp), DnaK from the ubiquitous Hsp70 family is upregulated in cells that are under abiotic stress. Synechocystis spp. cyanobacteria encode at least three potential DnaK proteins in their genome. Here, expressions of dnaK1s and dnaK2s from two Synechocystis spp. PCC6803 (Sy6803) and PCC6906 (Sy6906), enhanced salt tolerance in a dnaK-defective Escherichia coli strain. In contrast, dnaK3s in both strains were ineffective, indicating that dnaK3 is functionally different from dnaK1 and dnaK2 in Synechocystis spp. under salt stress. Ectopic expression of dnaK2s from Sy6803 and Sy6906 conferred salt tolerance in transgenic Arabidopsis plants, which exhibited greater root length, chlorophyll content, fresh weight, and survival rate than wild type plants, all in the presence of NaCl. In transgenic plants, hydrogen peroxide (H2O2) accumulation was reduced under NaCl stress and loss of chlorophyll content was reduced under H2O2 stress. Overall results suggest that dnaK2s from Sy6803 and Sy6906 confer salt and oxidative tolerance in transgenic plants by reduction of H2O2 accumulation.

Phase I trial of alpelisib in combination with concurrent cisplatin-based chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Deregulation of the PI3K signalling pathway is frequent in squamous cell carcinoma of the head and neck (SCCHN) and may be implicated in radioresistance. We report on the results from a phase I 3 + 3 dose escalation study of alpelisib, a class I α-specific PI3K inhibitor in combination with concurrent cisplatin-based chemoradiation (CRT) in patients with locoregionally advanced SCCHN (LA-SCCHN). METHODS: Eligible patients had previously untreated LA-SCCHN and were candidates for CRT. The primary objective was to evaluate safety and determine the recommended phase II dose (RP2D). Alpelisib was given orally once daily at two dose levels: 200 mg and 250 mg. CRT consisted of cisplatin 100 mg/m2 IV every three weeks and standard fractionation radiotherapy (IMRT) 70 Gy in 35 fractions. RESULTS: Nine patients were enrolled (six alpelisib 200 mg, three 250 mg). Oropharynx was the primary site in all patients (seven p16-positive; five T1-2N2M0, four T3-4N2-3M0 [AJCC 7th edition]). All patients completed CRT within seven weeks. Grade 3 alpelisib-related toxicities occurred in four patients. No dose-limiting toxicity (DLT) was observed at 200 mg among three DLT-evaluable patients. Two of two DLT-evaluable patients treated at 250 mg experienced DLTs (inability to complete ≥75% alpelisib secondary to radiation dermatitis and febrile neutropenia). Thus, RP2D was declared at 200 mg. After median follow-up of 39.7 months, two patients developed pulmonary metastases despite locoregional control. Three-year overall survival was 77.8% (95% CI 36.5%-93.9%). CONCLUSION: Alpelisib at 200 mg has a manageable safety profile in combination with cisplatin-based CRT in LA-SCCHN.

Outcomes by treatment modality in elderly patients with localized gastric and esophageal cancer.

Background: We aimed to assess current treatment patterns and outcomes in elderly patients with localized gastric and esophageal (ge) cancers. Methods: This retrospective analysis considered patients 75 years of age or older with ge cancers treated during 2012-2014. Patient demographics and tumour characteristics were collected. Overall survival (os) and disease-free survival were assessed by univariable and multivariable Cox proportional hazards regression, adjusting for demographics. Logistic regression analyses were used to examine factors affecting treatment choices. Results: The 110 patients in the study cohort had a median age of 81 years (range: 75-99 years). Primary disease sites were esophageal (55%) and gastric (45%). Treatment received included radiation therapy alone (29%), surgery alone (26%), surgery plus perioperative therapy (14%), chemoradiation alone (10%), and supportive care alone (14%). In multivariable analyses, surgery (hazard ratio: 0.48; 95% confidence interval: 0.26 to 0.90; p = 0.02) was the only independent predictor for improved os. Patients with a good Eastern Cooperative Oncology Group performance status (p = 0.008), gastric disease site (p = 0.02), and adenocarcinoma histology (p = 0.01) were more likely to undergo surgery. Conclusions: At our institution, few patients 75 years of age and older received multimodality therapy for localized ge cancers. Outcomes were better for patients who underwent surgery than for those who did not. To ensure optimal treatment selection, comprehensive geriatric assessment should be considered for patients 75 years of age and older with localized ge cancers.

A proposed framework for the description of plant metabolomics experiments and their results.

The study of the metabolite complement of biological samples, known as metabolomics, is creating large amounts of data, and support for handling these data sets is required to facilitate meaningful analyses that will answer biological questions. We present a data model for plant metabolomics known as ArMet (architecture for metabolomics). It encompasses the entire experimental time line from experiment definition and description of biological source material, through sample growth and preparation to the results of chemical analysis. Such formal data descriptions, which specify the full experimental context, enable principled comparison of data sets, allow proper interpretation of experimental results, permit the repetition of experiments and provide a basis for the design of systems for data storage and transmission. The current design and example implementations are freely available (http://www.armet.org/). We seek to advance discussion and community adoption of a standard for metabolomics, which would promote principled collection, storage and transmission of experiment data.

Fast determination of the ripeness stage of strawberries using infrared spectroscopy combined with principal component analysis.

The utility of infrared (IR) spectroscopy for the determination of strawberry ripeness has been successfully demonstrated. Transmission IR spectra were collected using dried liquid extracts from strawberry flesh. The overall IR feature provided fairly noticeable differences, and the ripeness stage was clearly identified using principal component analysis (PCA). Although all of the extracted components contributed to the resulting spectral features for discrimination, the variation of carbohydrate and amide residues played a major role for providing the selective spectral feature. Additionally, NMR spectra were also collected to quantify the concentrations of three small sugars (alpha-glucose, beta-glucose and sucrose) as well as to evaluate the NMR spectral features at each ripeness step. The concentrations of three sugars increased from early to late growth stages. Both IR and NMR spectroscopies were valuable to elucidate the metabolic signatures for the determining of ripeness stage; however, IR spectroscopy could be more advantageous when fast and high throughput analysis is essential.

Re-engineering a pharmacy work system and layout to facilitate patient counseling.

The development and evaluation of a new work system and facility design for a chain of community pharmacies are described. A new work system was developed to optimize utilization of pharmacist and technician time and allow the pharmacy to increase patient counseling without adding personnel. In the new system, pharmacists would review prescriptions, check technicians' work, and dispense prescriptions, counseling patients as needed; technicians would enter prescriptions into the pharmacy computer and fill them. The existing work system and design were evaluated in June and July of 1992 by observing, classifying, and recording activities of pharmacy personnel three days per week at six pharmacies in the chain. Pharmacy designs that would work with the new work system were created by a university design class after consultation with representatives of the pharmacy chain and the university's college of pharmacy. The pharmacy chain selected one design, and a detailed floor plan and specifications were created. To test how the new design and system would work at each of the six test pharmacies, a computer simulation program was developed and verified by using the data collected on the existing pharmacy operations. Computer simulation showed that, with the new design and system, increasing patient counseling would increase patient waiting time slightly but would not require additional personnel. The layout and work system in a chain of community pharmacies were redesigned to facilitate patient counseling and make the best use of employee time.

Biochemical measurement in cord blood as an indicator of neonatal maturity.

Neonates were categorized by gestational scoring (G. Score) using physical and neurological signs, into two groups: TERM and preterm (PRE) using a score corresponding to approximately 38 weeks of gestation as the dividing point. Cord blood concentrations of alphafetoprotein (AFP), fetal hemoglobin (HGF), prealbumin (PALB), creatinine (CRE), and pseudocholinesterase (PC) were determined. The CRE, AFP, and HGF were divided by birthweight in grams (WT) to give three additional markers: CRE/WT, AFP/WT and HGF/WT. Strong Pearsonian correlations between CRE/WT, AFP/WT, and HGF/WT, and G. Scores in the PRE group were obtained. Histograms of AFP/WT and HGF/WT values gave non-Gaussian distributions and resulted in the clear separation of a group of extremely premature infants from the rest of the population. The plots also revealed substantial separation between the TERM and PRE groups. The CRE/WT was predominantly Gaussian, with separation of a group of neonates including the six very preterm infants. It is concluded that CRE/WT, AFP/WT, and HGF/WT have the greatest potential as maturity markers, while PC and PALB have little if any potential.

Hemoglobin F: relationship to maturity measures in the neonate.

The maturity of organ functioning is a key to predicting neonatal prognosis, particularly in preterm babies, and laboratory tests have the potential for providing better information than external exams. This approach was examined utilizing the fetal protein, HGB F. While HGB F itself does not correlate well with current measures of maturity, HGB F/WT was found to correlate very strongly, in a linear relationship with the gestational score (G. Score) obtained from a physical and neurological assessment of the neonate. This relationship was not affected by sex or race in our population. A cut-off value for HGB F/WT of 0.025 was chosen as the difference between mature and immature neonates and the value of the test using that cut-off was determined. Infants were classified as preterm or term based upon G. Score and gestational age (from the mother's last menstrual period) and were further classified depending upon whether the HGB F/WT value indicated a mature or premature infant. Utilizing predictive theory, the test was found to have a predictive value of 0.914 with an overall test efficiency of 0.967. These results indicate that this measurement has potential as a maturity marker in neonates.

Thrombocytosis in children at one medical center of southern Taiwan.

Thrombocytosis in children is common, but usually without symptoms. The causes of thrombocytosis in children are considered to be mostly due to infection, trauma, surgery, blood disease, prematurity, renal disease and chronic inflammation. To evaluate the incidence and etiology of thrombocytosis of the hospitalized patients, patients who were admitted to the Pediatric Department of Kaohsiung Medical College Hospital (KMCH) from October 1996 to November 1997 were studied. There were 2910 cases studied and 220 cases (127 male and 93 female) had thrombocytosis (> or = 500 x 10(9)/L) with a rate of 7.6%. The causes of thrombocytosis are infections (49.5%), Kawasaki disease (6.4%), postsplenectomy (7.8%), blood diseases (3.7%), malignancies (3.2%), renal disorders (3.2%), prematurity (3.2%), tissue damage (4.5%), chronic inflammation (1.8%), recovery from marrow suppression (1.3%), immunologic disturbances (2.2%), essential thrombocythemia (0.5%), and miscellaneous factors (3.7%). Thrombocytosis associated with multiple, simultaneous causative factors was found in 9.0% of these cases. Thrombocytosis secondary to infectious diseases or Kawasaki disease was significantly more common in children under 2 years old. The most commonly associated infectious disease was respiratory tract infection (61.1%). There were 29 children (13.2%) presenting a platelet count of more than 800,000/mm3. However, no thrombotic complications were seen in any of the children. By far, the major cause of thrombocytosis in our cases was reactive in character. Most of the thrombocytosis cases were due to infections, inflammatory diseases, or Kawasaki disease.

A rapid, simple method for the genetic discrimination of intact Arabidopsis thaliana mutant seeds using metabolic profiling by direct analysis in real-time mass spectrometry.

BACKGROUND: Efficient high throughput screening systems of useful mutants are prerequisite for study of plant functional genomics and lots of application fields. Advance in such screening tools, thanks to the development of analytic instruments. Direct analysis in real-time (DART)-mass spectrometry (MS) by ionization of complex materials at atmospheric pressure is a rapid, simple, high-resolution analytical technique. Here we describe a rapid, simple method for the genetic discrimination of intact Arabidopsis thaliana mutant seeds using metabolic profiling by DART-MS. RESULTS: To determine whether this DART-MS combined by multivariate analysis can perform genetic discrimination based on global metabolic profiling, intact Arabidopsis thaliana mutant seeds were subjected to DART-MS without any sample preparation. Partial least squares-discriminant analysis (PLS-DA) of DART-MS spectral data from intact seeds classified 14 different lines of seeds into two distinct groups: Columbia (Col-0) and Landsberg erecta (Ler) ecotype backgrounds. A hierarchical dendrogram based on partial least squares-discriminant analysis (PLS-DA) subdivided the Col-0 ecotype into two groups: mutant lines harboring defects in the phenylpropanoid biosynthetic pathway and mutants without these defects. These results indicated that metabolic profiling with DART-MS could discriminate intact Arabidopsis seeds at least ecotype level and metabolic pathway level within same ecotype. CONCLUSION: The described DART-MS combined by multivariate analysis allows for rapid screening and metabolic characterization of lots of Arabidopsis mutant seeds without complex metabolic preparation steps. Moreover, potential novel metabolic markers can be detected and used to clarify the genetic relationship between Arabidopsis cultivars. Furthermore this technique can be applied to predict the novel gene function of metabolic mutants regardless of morphological phenotypes.

Biomechanical evaluation of nursing tasks in a hospital setting.

A field study was conducted to investigate spinal kinematics and loading in the nursing profession using objective and subjective measurements of selected nursing tasks observed in a hospital setting. Spinal loading was estimated using trunk motion dynamics measured by the lumbar motion monitor (LMM) and lower back compressive and shear forces were estimated using the three-dimensional (3D) Static Strength Prediction Program. Subjective measures included the rate of perceived physical effort and the perceived risk of low back pain. A multiple logistic regression model, reported in the literature for predicting low back injury based on defined risk groups, was tested. The study results concluded that the major risk factors for low back injury in nurses were the weight of patients handled, trunk moment, and trunk axial rotation. The activities that required long time exposure to awkward postures were perceived by nurses as a high physical effort. This study also concluded that self-reported perceived exertion could be used as a tool to identify nursing activities with a high risk of low-back injury.

Tumour lysis syndrome developing during an operation.

We describe an unusual case of tumour lysis syndrome in a child with a high-grade lymphoma undergoing a staging laparotomy. The patient presented with a refractory ventricular arrhythmia, which required continuous resuscitation in the operating room and continuous venous-venous haemodialysis in the intensive care unit. This case report suggests that surgery is a possible trigger for developing tumour lysis syndrome, so anaesthetists should be alert to this possibility during surgery in patients with pre-existing high tumour burdens.

Impact of school-based health centers on children with asthma.

PURPOSE: To quantitatively assess the impact of school-based health centers (SBHCs) on hospitalization and emergency department (ED) visits for children with asthma. METHODS: The study was conducted at four SBHC intervention school districts and two comparable non-SBHC school districts in Greater Cincinnati, Ohio. A longitudinal quasi-experimental time-series repeated measures design was used with a study period from 1997 to 2003. Children with asthma with at least 2 years of continuous enrollment who had medical claims for asthma diagnosis and antiasthmatic medications were selected. The primary data sources were student enrollment data from the schools and the Ohio Medicaid claims database. Generalized estimating equation (GEE) analysis and analysis of covariance were used to assess the intervention effect before and after the SBHC program. RESULTS: Asthma was one of the major diseases for SBHC encounters. Major prescription drugs that SBHC staff managed for children with asthma included albuterol, montelukast, fluticasone, budesonide, and triamcinolone. Of 273 children (196 in SBHC schools and 77 in non-SBHC schools), 42% were female, 41.7% African-Americans, and the average age was 8.2 years. After the opening of the SBHC, relative risks of hospitalization and ED visits in the SBHC group decreased 2.4-fold and 33.5%, respectively. The cost of hospitalization per child decreased significantly over time for children in SBHC schools (F = 4.115, p = .044). After SBHCs opened, cost of hospitalization decreased for African-American children (F = 5.198, p = .023). Costs of ED visits for children in SBHC schools were significantly lower than children in non-SBHC schools (F = 19.8, p < .0001). CONCLUSIONS: The risk of hospitalization and ED visits for children with asthma decreased significantly with SBHC programs. The potential cost-savings for hospitalization was estimated as 970 dollars per child.

General purpose of research designs.

The purposes and criteria for formulating a design of research, conditions for judging causality, and use of research design as a control of variance are discussed. The purpose of a research design is to provide a plan of study that permits accurate assessment of cause and effect relationships between independent and dependent variables. The classic controlled experiment is an ideal example of good research design. Factors that jeopardize the evaluation of the effect of experimental treatment (internal validity) and the generalizations derived from it (external validity) are identified. Sources of variance can be controlled by eliminating a variable, randomization, matching, or including a variable as part of the design. A research project should be so designed that (1) it answers the questions being investigated, (2) extraneous factors are controlled, and (3) the degree of generalization that can be made is valid.

Medicaid formularies: a critical review of the literature.

Studies on the impact of restricted Medicaid formularies were reviewed to assess whether other drugs on the formulary were substituted for restricted drugs, the cost of the substitutes, whether the substitutes were therapeutically appropriate, whether restricted drugs continued to be prescribed, what incremental administrative costs accompanied restrictions, what indirect costs occurred and how the cost-effectiveness of pharmaceuticals impinged on the total cost of illness. The assumption that restriction of specific drugs results in savings in the drug costs proportional to prior usage was shown to be questionable, numerous studies found alternate formulary drugs to the restricted drugs being prescribed, or patients were paying out-of-pocket for denied drugs. There was a tendency for alternate drugs to be more expensive. Little information exists as to the incremental administrative costs of restricted formularies or the therapeutic appropriateness of substituted drugs. One study suggests that major shifts in costs occur due to restrictive formularies through substitution of more expensive services such as hospitalization in lieu of pharmaceuticals. It is concluded that restricting formularies leads to dynamic changes in the total Medicaid program of a complex and often costly nature. Plans to implement formulary restrictions require considerable careful thought.

Tapping employee insights with the Nominal Group Technique.

In our scenario, we brought together the manager, pharmacist, full-time and part-time sales people, the delivery person, and the stock person, to give a perspective from every possible area of operation. We have found that input from all employees often generates ideas that they would not have thought of on their own. We suggest that NGT, used on a quarterly basis, for instance, would be an excellent means of developing team spirit, employee participation, and meaningful and effective solutions to problems. NGT is much better than trying to "go it alone," especially in today's competitive environment. NGT helps us realize that the potential contribution of employees is great, but generally untapped. The process requires planning but little time; yet it can produce astounding results, both in encouraging team spirit and in protecting profitability. The process fosters effective use of a participative style of management. It forces us, in effect, to use our most valuable resource: the people we manage.