Development of a Controlled-Ventilation Box for Modified-Atmosphere Storage of Fresh Produce.

Adjusting beneficial gas concentrations in real time in response to changing storage conditions is important for fresh produce, especially throughout the supply chain when temperature abuse occurs frequently. In this study, a controlled-ventilated box for bulk transportation of fresh produce was demonstrated and tested under variable temperatures. The presented system comprised a rigid container with a miniature blower installed in the opening of its wall for facilitating the gas exchange and an additional wall opening with a metal tube protruding into the inner container's space. The in-package atmosphere was formed by the balance between the respiratory activity of the produce and the influx of fresh air through the wall openings, regulated by switching the blower ON or OFF. The mass transfer coefficient for metal tubes of different dimensions was measured under modified atmosphere featuring 15% CO2 and 5% O2 at 10 °C. The addition of an air blower increased the mass transfer coefficient by at least 100 times. A further storage trial with cherries was successfully performed at 10 °C and 20 °C. The demonstrated trial featured some significant inputs to increase the knowledge about better storage of fresh produce throughout the supply chain and storage.

Integrative programming for simulation of packaging headspace and shelf life of fresh produce.

Fresh horticultural products are exposed to different environmental conditions from farm to fork. Barrier properties of packaging and physiological behaviour of produce, namely respiration and transpiration can affect headspace conditions surrounding produce and consequently remaining shelf life. Packaging material also plays a role in heat and mass transfer, such as thermal conduction and permeation of O2, CO2 and water vapour. All of these behaviours are integrated together in the form of ordinary differential equations and solved using numerical methods in MATLAB. • The simulation program is useful for designing the size and number of perforations to achieve equilibrium modified atmosphere alone or in combination with packaging material having a higher water transmission rate or active moisture absorber. • The simulation program is also useful for predicting the shelf life of fresh produce under the actual supply chain conditions. • The simulation program provides a flexible system to input predefined supply chain conditions and the properties of fresh produce and packaging material, thus, minimizing the costly and time consuming experimental procedures for selecting the optimum packaging material for fresh produce.

A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease.

Systemic inflammation in pregnant obese women is associated with 1.5- to 2-fold increase in serum Interleukin-6 (IL-6) and newborns with lower kidney/body weight ratio but the role of IL-6 in increased susceptibility to chronic kidney (CKD) in adult progeny is not known. Since IL-6 crosses the placental barrier, we administered recombinant IL-6 (10 pg/g) to pregnant mice starting at mid-gestation yielded newborns with lower body (p < 0.001) and kidney (p < 0.001) weights. Histomorphometry indicated decreased nephrogenic zone width (p = 0.039) with increased numbers of mature glomeruli (p = 0.002) and pre-tubular aggregates (p = 0.041). Accelerated maturation in IL-6 newborns was suggested by early expression of podocyte-specific protein podocin in glomeruli, increased 5-methyl-cytosine (LC-MS analysis for CpG DNA methylation) and altered expression of certain genes of cell-cycle and apoptosis (RT-qPCR array-analysis). Western blotting showed upregulated pJAK2/pSTAT3. Thus, treating dams with IL-6 as a surrogate provides newborns to study effects of maternal systemic inflammation on future susceptibility to CKD in adulthood.

Color analysis of horticultural produces using hue spectra fingerprinting.

Color has great importance in agriculture due to its relationship with plant pigments and therefore, plant development and biochemical changes. Due to the trichromatic vision, instruments equipped with CCD or CMOS sensor represent color with the mixture of red, green and blue signals. These values are often transformed into HSL (hue, saturation, luminance) color space. Beyond average color of the visible surface area, histograms can represent color distribution. Interpretation of distribution can be challenging due to the information shared among histograms. Hue spectra fingerprinting offers color information suitable for analysis with common chemometric methods and easy to understand. Algorithm is presented with GNU Octave code.•Hue spectra is a histogram of hue angle over the captured scene but summarizes saturation instead of number of pixels. There are peaks of important colors, while others of low saturation disappear. Neutral backgrounds such as white, black or gray, are removed without the need of segmentation.•Color changes of fruits and vegetables are represented by displacement of color peaks. Since saturation is usually changing during ripening, storage and shelf life, peaks also change their shape by means of peak value and width.

In-Situ Measurement of Fresh Produce Respiration Using a Modular Sensor-Based System.

In situ, continuous and real-time monitoring of respiration (R) and respiratory quotient (RQ) are crucial for identifying the optimal conditions for the long-term storage of fresh produce. This study reports the application of a gas sensor (RMS88) and a modular respirometer for in situ real-time monitoring of gas concentrations and respiration rates of strawberries during storage in a lab-scale controlled atmosphere chamber (190 L) and of Pinova apples in a commercial storage facility (170 t). The RMS88 consisted of wireless O2 (0% to 25%) and CO2 sensors (0% to 0.5% and 0% to 5%). The modular respirometer (3.3 L for strawberries and 7.4 L for apples) consisted of a leak-proof arrangement with a water-containing base plate and a glass jar on top. Gas concentrations were continuously recorded by the RMS88 at regular intervals of 1 min for strawberries and 5 min for apples and, in real-time, transferred to a terminal program to calculate respiration rates ( R O 2 and R CO 2 ) and RQ. Respiration measurement was done in cycles of flushing and measurement period. A respiration measurement cycle with a measurement period of 2 h up to 3 h was shown to be useful for strawberries under air at 10 °C. The start of anaerobic respiration of strawberries due to low O2 concentration (1%) could be recorded in real-time. R O 2 and R CO 2 of Pinova apples were recorded every 5 min during storage and mean values of 1.6 and 2.7 mL kg-1 h-1, respectively, were obtained when controlled atmosphere (CA) conditions (2% O2, 1.3% CO2 and 2 °C) were established. The modular respirometer was found to be useful for in situ real-time monitoring of respiration rate during storage of fresh produce and offers great potential to be incorporated into RQ-based dynamic CA storage system.

Application of pharmacogenomics for trauma and critical care patients: A case report.

BACKGROUND: Pharmacogenomics is increasingly becoming a valuable tool for improving health outcomes, reducing health care costs and avoiding adverse drug reactions. While application of pharmacogenomics is quite common in oncology and cardiology, routine use of this technology is rare in certain other fields including Trauma and Critical Care Surgery. We are testing feasibility of applying pharmacogenomic testing to improve therapeutic outcomes of trauma and acute care patients at MercyOne Medical Center in Des Moines, IA. METHODS: Trauma patients admitted to the hospital with projected stay of >5 days, or with admission extended due to failed multiple trials of medication volunteered to participate in this IRB-approved study. Effectiveness of medical therapy was evaluated using standard pain scores recorded prior to admission of any pain medication to conscious and competent patients. Pharmacogenomic results were obtained from commercial providers within 3-5 days and used to alter medical therapy as needed. RESULTS: An 18-year-old African American male, admitted for gunshot wounds to the neck, exhibited an ASIA A spinal cord injury, with no sensation or movement of his extremities, persistent nausea with emesis and a history of depression. He also developed gastritis with hematemesis. In addition to all standard trauma procedures, he received standard doses of tramadol, oxycodone or hydrocodone, ondansetron, citalopram, and intravenous protonix daily. He reported no pain relief. The patient's pharmacogenomic analysis revealed his ultrarapid and rapid genotype for CYP2D6 and CYP2C19 respectively, allowing us to choose dilaudid resulting in immediate improvement of his pain scores. Additionally, using metoclopramide, duloxetine and famotidine led to immediate improvement or complete resolution of symptoms. CONCLUSION: Pharmacogenomics testing is a useful tool for selecting appropriate pain management of trauma patients with expected hospital stay ≥5 days. Additionally, standard pharmacogenomic panels allow tailoring medical therapy to common conditions associated with traumatic injury.

Response of pomegranate arils (cv. Wonderful) to low oxygen stress under active modified atmosphere condition.

BACKGROUND: Successful characterization of the relationship between respiration rate (RR) and low oxygen (O2 ) limit is critical for optimizing the modified atmosphere condition. It is well documented that a low O2 atmosphere reduces the RR of fresh produce, but could also lead to abiotic stress due to the accumulation of glycolysis end products. Therefore, this study investigated the response of pomegranate arils exposed to low O2 atmosphere (composed of 2 kPa O2 , 18 kPa carbon dioxide, and 80 kPa nitrogen) and identified the low O2 limit at 5 °C and 10 °C. The study aim was achieved by using real-time RR and respiration quotient (RQ) data, microbial growth, identifying changes in the fermentative volatile organic compounds profile, and the consumption of respiratory metabolites (organic acids and individual sugars). RESULTS: The gas concentrations changed significantly respective to the storage temperature and resulted in a significant change in the parameters studied. The response of pomegranate arils to low O2 stress involves making alterations to the metabolic composition, especially those involved in anaerobiosis, such as the accumulation of ethanol, and an immediate increase on RQ. CONCLUSION: Pomegranate arils (cv. Wonderful) can tolerate down to 1.9 kPa O2 and 2.3 kPa O2 concentrations at 5 °C and 10 °C respectively. © 2018 Society of Chemical Industry.

Addition of Allopurinol for Altering Thiopurine Metabolism to Optimize Therapy in Patients with Inflammatory Bowel Disease.

Thiopurine drugs, including azathioprine and 6-mercaptopurine, are used commonly in patients with inflammatory bowel disease for maintenance of remission. Although generally well tolerated, adverse effects lead to discontinuation in a significant minority of patients. Pharmacogenomic studies have suggested that metabolic breakdown of azathioprine in an individual is genetically determined. Coupled with the fact that certain thiopurine metabolites, notably 6-thioguanine nucleotide and 6-methylmercaptopurine, are associated with antiinflammatory effects and adverse effects, respectively, some investigators have examined intentionally shunting the metabolism of azathioprine toward increasing 6-thioguanine nucleotide levels by using low doses of the xanthine oxidoreductase inhibitor allopurinol to improve efficacy and decrease toxicity of azathioprine in patients with inflammatory bowel disease. We performed a search of the MEDLINE and Embase databases for basic and clinical research reports of this modality. Pertinent articles were retrieved, reviewed, and assessed by the authors. Case series, cohort studies, and one randomized trial have investigated adding allopurinol to azathioprine therapy in patients with inflammatory bowel disease. Most reports primarily examined metabolite levels in these patients. In general, the literature suggests that this modality was successful at significantly increasing 6-thioguanine nucleotide levels while decreasing 6-methylmercaptopurine levels. Several small reports have suggested that patients with increased 6-thioguanine nucleotide levels had improved symptoms or symptom remission. Adverse effects and discontinuation rates remained similar or were improved in patients who were taking a thiopurine and started allopurinol. In conclusion, the addition of allopurinol may be an option for optimizing thiopurine metabolite production in select patients with low 6-thioguanine nucleotide levels. Appropriate care and monitoring of these patients are mandatory to prevent neutropenia or other adverse effects.

Recent Advances in Application of Pharmacogenomics for Biotherapeutics.

Biotherapeutics (BTs), one of the fastest growing classes of drug molecules, offer several advantages over the traditional small molecule pharmaceuticals because of their relatively high specificity, low off-target effects, and biocompatible metabolism, in addition to legal and logistic advantages. However, their clinical utility is limited, among other things, by their high immunogenic potential and/or variable therapeutic efficacy in different patient populations. Both of these issues, also commonly experienced with small molecule drugs, have been addressed effectively in a number of cases by the successful application of pharmacogenomic tools and approaches. In this introductory article of the special issue, we review the current state of application of pharmacogenomics to BTs and offer suggestions for further expansion of the field.

Clinical Trials of Poly(ADP-Ribose) Polymerase Inhibitors for Cancer Therapy: A Review.

Poly(ADP-Ribose) Polymerase (PARP) is a family of enzymes involved in DNA repair, genome stability, cellular energy metabolism and cell division. Inhibition of PARP-1, the well characterized member of this family, has been explored as a strategy for enhancing anti-cancer activity of existing drugs and for developing new drugs. Recently unique enzymatic properties and biological functions of PARP-2 and PARP-3 have been discovered, further expanding the utility of PARP as a target for cancer pharmacotherapy. We compare and contrast the structural and enzymatic properties of these three members of the PARP family. Interactions of these enzymes with proteins specific to different DNA repair pathways are summarized. Further, we evaluate progress on development of PARP inhibitors as anticancer agents. Results of Phase I and Phase II clinical trials of seven PARP inhibitors, used alone or in combination with known anticancer agents are reviewed highlighting common observations regarding the maximum tolerable dose, adverse reactions profile, PARP inhibition and anticancer effects. While further clinical studies are warranted, based on current data, Olaparib (Ola), Veliparib (Veli) and Rucaparib (Ruca) offer considerable potential. Prolonged exposure to Ola and Veli leads to resistant cancer cells, primarily through restoration of the HR pathway, overexpression of the P-glycoprotein efflux pump or modulation of PARP expression. Some resistant cancer cells continue to respond to platinum based drugs, encouraging further development of PARP inhibitors for cancer treatment. Future course of this research, specifically focusing on use of PARP inhibition as a strategy for personalized cancer therapy, is discussed.

Impact of mixtures of different fresh-cut fruits on respiration and ethylene production rates.

UNLABELLED: Packaging and storage of fresh-cut fruits and vegetables are a challenging task, since fresh produce continue to respire and senesce after harvest and processing accelerates the physiological processes. The response on respiration and ethylene production rates of fresh produce to changes in O2 and CO2 concentrations and temperature has been extensively studied for whole fruits but literature is limited on processed and mixed fresh-cut fruits. This study aimed to investigate the effects of mixing various proportions of fresh-cut fruits (melon chunks, apple slices, and pineapples cubes) on respiration and ethylene production rates and to develop predictive models for modified atmosphere packaging. The experiment was designed according to a simplex lattice method and respiration and ethylene production rates were measured at 10 °C. Results showed that single component pineapple cubes, apple slices, and melon chunks, in this order, had significant constant coefficients (P = 0.05) and the greatest impact on respiration rate while the interactive binary and tertiary coefficients were insignificant. For ethylene production rates, single component apple slices, melon chunks, and pineapple cubes, and their 3-component mixtures, in this order, had significant constant coefficients (P = 0.05) while binary coefficients were insignificant. Mathematical models were developed and validated; the cubical model was the best to describe the influence of proportion of fruit on respiration and ethylene production rates, however, considering simplicity the linear part of the model is recommended to quantify respiration and ethylene production rates of mixed fresh-cut fruits. PRACTICAL APPLICATION: This research helps to quantify the ethylene production and respiration rates of multicomponent mixed fresh-cut fruit, which then can be used for packaging design of fresh-cut produce.

Modified Atmosphere Packaging Technology of Fresh and Fresh-cut Produce and the Microbial Consequences-A Review.

Modified atmosphere packaging (MAP) technology offers the possibility to retard the respiration rate and extend the shelf life of fresh produce, and is increasingly used globally as value adding in the fresh and fresh-cut food industry. However, the outbreaks of foodborne diseases and emergence of resistant foodborne pathogens in MAP have heightened public interest on the effects of MAP technology on the survival and growth of pathogenic organisms. This paper critically reviews the effects of MAP on the microbiological safety of fresh or fresh-cut produce, including the role of innovative tools such as the use of pressurised inert/noble gases, predictive microbiology and intelligent packaging in the advancement of MAP safety. The integration of Hazard Analysis and Critical Control Points-based programs to ensure fresh food quality and microbial safety in packaging technology is highlighted.

Clinical applications of pharmacogenomics guided warfarin dosing.

AIM OF THE REVIEW: To assess the state of the literature concerning pharmacogenomic testing in patients requiring vitamin K antagonists, specifically warfarin. METHOD: We conducted a literature search of MEDLINE and International Pharmaceutical Abstracts using the following words: warfarin, pharmacogenetic, and pharmacogenomic. The search results were reviewed by the authors and papers concerning pharmacogenomic testing in warfarin dosing were procured and reviewed. Additionally bibliographies of papers procured were also examined for other studies. The authors focused on clinical trials concerning the use of pharmacogenomic testing in warfarin dosing. RESULTS: Although numerous studies have demonstrated that a significant portion of warfarin dosing variability can be explained by genetic polymorphisms, few prospective studies have been conducted that examine the integration of this information in practical dosing situations. Those that have, have shown that using pharmacogenomic information improves initial dosing estimates and decreases the need for frequent clinic visits and laboratory testing. Data showing a reduction in serious bleeding events is sparse. Cost-effectiveness analyses have generally shown a small but positive effect with pharmacogenomic testing in patients receiving warfarin. CONCLUSION: Several studies have shown that pharmacogenomic testing for warfarin dosing is more accurate that other dosing schemes. Pharmacogenomic testing improves time to a therapeutic international normalized ratio while requiring fewer dosing adjustments. Patients who require higher or lower than usual doses seem to benefit the most. The cost-effectiveness of pharmacogenomic testing as well as preventing of outcomes such as bleeding or thrombosis are not yet elucidated. Pharmacists, especially those in a community setting can play a role in this new technology by educating prescribers and patients concerning pharmacogenomic testing, and by developing and using dosing protocols that incorporate its use.

Determinants of immunogenic response to protein therapeutics.

Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation.

Modeling the effect of time and temperature on respiration rate of pomegranate arils (cv. "Acco" and "Herskawitz").

Understanding the effect of time and temperature on the respiration rate (RR) of fresh-cut produce, towards the design of a suitable modified atmosphere packaging (MAP) system, requires an adequate mathematical model for prediction of RR as a function of both time and temperature. This study investigated the effect of temperature (5, 10, and 15 °C) and storage time (1 to 5 d) on the RR (R(O2) and R(CO2)) of 2 pomegranate cultivars (cv. "Acco" and "Herskawitz") fresh arils. R(O2) and R(CO2) were 3 to 4 folds significantly higher with increased temperature from 5 to 15 °C and were within the range of 2.51 to 7.59 mL/kg h and 2.72 to 9.01 mL/kg h, respectively, for both cultivars. At 15 °C R(CO2) increased significantly from 8.4 to 25.96 mL/kg h from day 1 to 5, respectively, while at 5 °C R(CO2) changed from 2.9 to 2.05 mL/kg h from day 1 to 5. Temperature had the greatest influence on RR and the interaction of time and temperature also significantly affected R(O2) and R(CO2). The respiratory quotient (RQ) estimated by linear regression was 0.98 at 95% significant level. The dependence of RR on temperature and time was accurately described with a combination of an Arrhenius-type and power equation model for and of fresh pomegranate arils.

Clinical applications of pharmacogenomics guided warfarin dosing.

AIM OF THE REVIEW: To assess the state of the literature concerning pharmacogenomic testing in patients requiring vitamin K antagonists, specifically warfarin. METHOD: We conducted a literature search of MEDLINE and International Pharmaceutical Abstracts using the following words: warfarin, pharmacogenetic, and pharmacogenomic. The search results were reviewed by the authors and papers concerning pharmacogenomic testing in warfarin dosing were procured and reviewed. Additionally bibliographies of papers procured were also examined for other studies. The authors focused on clinical trials concerning the use of pharmacogenomic testing in warfarin dosing. RESULTS: Although numerous studies have demonstrated that a significant portion of warfarin dosing variability can be explained by genetic polymorphisms, few prospective studies have been conducted that examine the integration of this information in practical dosing situations. Those that have, have shown that using pharmacogenomic information improves initial dosing estimates and decreases the need for frequent clinic visits and laboratory testing. Data showing a reduction in serious bleeding events is sparse. Cost-effectiveness analyses have generally shown a small but positive effect with pharmacogenomic testing in patients receiving warfarin. CONCLUSION: Several studies have shown that pharmacogenomic testing for warfarin dosing is more accurate that other dosing schemes. Pharmacogenomic testing improves time to a therapeutic international normalized ratio while requiring fewer dosing adjustments. Patients who require higher or lower than usual doses seem to benefit the most. The cost-effectiveness of pharmacogenomic testing as well as preventing of outcomes such as bleeding or thrombosis are not yet elucidated. Pharmacists, especially those in a community setting can play a role in this new technology by educating prescribers and patients concerning pharmacogenomic testing, and by developing and using dosing protocols that incorporate its use.

Recombinant expression of maize nucleotide excision repair protein Rad23 in Escherichia coli.

Nucleotide excision is a highly conserved DNA repair pathway for correcting DNA lesions that cause distortion of the double helical structure. The protein heterodimer XPC-Rad23 is involved in recognition of and binding to such lesions. We have isolated full-length cDNAs encoding two different members of the maize Rad23 family. The deduced amino acid sequences of both maize orthologues show a high degree of homology to plant and animal Rad23 proteins. The cDNA encoding maize Rad23A was cloned as an in-frame C-terminal fusion of glutathione S-transferase. This chimera was expressed in Escherichia coli as a soluble protein and purified to homogeneity using glutathione-agarose followed by MonoQ column chromatography. Purified recombinant maize Rad23 protein was used to generate polyclonal antibodies that cross-react with a approximately 48-kDa protein in extracts from plant as well as mammalian cells. The purified recombinant protein and antibodies would be useful reagents to study the biochemistry of nucleotide excision repair in plants.