ABSTRACT
OBJECTIVE: To provide an overview of medication errors (MEs) in veterinary medicine, with a focus on the perianesthetic period; to compare MEs in veterinary medicine with human anesthesia practice, and to describe factors contributing to the risk of MEs and strategies for error reduction. DATABASES USED: PubMed and CAB abstracts; search terms: [("patient safety" or "medication error∗") AND veterin∗]. CONCLUSIONS: Human anesthesia is recognized as having a relatively high risk of MEs. In veterinary medicine, MEs were among the most commonly reported medical error. Predisposing factors for MEs in human and veterinary anesthesia include general (e.g. distraction, fatigue, workload, supervision) and specific factors (e.g. requirement for dose calculations when dosing for body mass, using several medications within a short time period and preparing syringes ahead of time). Data on MEs are most commonly collected in self-reporting systems, which very likely underestimate the true incidence, a problem acknowledged in human medicine. Case reports have described a variety of MEs in the perianesthetic period, including prescription, preparation and administration errors. Dogs and cats were the most frequently reported species, with MEs in cats more commonly associated with harmful outcomes compared with dogs. In addition to education and raising awareness, other strategies described for reducing the risk of MEs include behavioral, communication, identification, organizational, engineering and cognitive aids.
Subject(s)
Anesthesia , Medication Errors , Veterinary Medicine , Medication Errors/veterinary , Medication Errors/statistics & numerical data , Animals , Anesthesia/veterinary , Anesthesia/adverse effects , Humans , Dogs , Cats , Anesthetics/adverse effectsABSTRACT
OBJECTIVE: To provide evidence-based recommendations for the management of chronic pelvic pain in females. TARGET POPULATION: This guideline is specific to pelvic pain in adolescent and adult females and excluded literature that looked at pelvic pain in males. It also did not address genital pain. BENEFITS, HARMS, AND COSTS: The intent is to benefit patients with chronic pelvic pain by providing an evidence-based approach to management. Access to certain interventions such as physiotherapy and psychological treatments, and to interdisciplinary care overall, may be limited by costs and service availability. EVIDENCE: Medline and the Cochrane Database from 1990 to 2020 were searched for articles in English on subjects related to chronic pelvic pain, including diagnosis, overlapping pain conditions, central sensitization, management, medications, surgery, physiotherapy, psychological therapies, alternative and complementary therapies, and multidisciplinary and interdisciplinary care. The committee reviewed the literature and available data and used a consensus approach to develop recommendations. Only articles in English and pertaining to female subjects were included. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Family physicians, gynaecologists, urologists, pain specialists, physiotherapists, and mental health professionals. TWEETABLE ABSTRACT: Management of chronic pelvic pain should consider multifactorial contributors, including underlying central sensitization/nociplastic pain, and employ an interdisciplinary biopsychosocial approach that includes pain education, physiotherapy, and psychological & medical treatments. SUMMARY STATEMENTS: RECOMMENDATIONS.
Subject(s)
Chronic Pain , Adult , Female , Humans , Adolescent , Chronic Pain/diagnosis , Chronic Pain/therapy , Pelvic Pain/therapy , Pelvic Pain/surgeryABSTRACT
Phosphorus (P) and water are crucial for plant growth, but their availability is challenged by climate change, leading to reduced crop production and global food security. In many agricultural soils, crop productivity is confronted by both water and P limitations. The diminished soil moisture decreases available P due to reduced P diffusion, and inadequate P availability diminishes tissue water status through modifications in stomatal conductance and a decrease in root hydraulic conductance. P and water display contrasting distributions in the soil, with P being concentrated in the topsoil and water in the subsoil. Plants adapt to water- and P-limited environments by efficiently exploring localized resource hotspots of P and water through the adaptation of their root system. Thus, developing cultivars with improved root architecture is crucial for accessing and utilizing P and water from arid and P-deficient soils. To meet this goal, breeding towards multiple advantageous root traits can lead to better cultivars for water- and P-limited environments. This review discusses the interplay of P and water availability and highlights specific root traits that enhance the exploration and exploitation of optimal resource-rich soil strata while reducing metabolic costs. We propose root ideotype models, including 'topsoil foraging', 'subsoil foraging', and 'topsoil/subsoil foraging' for maize (monocot) and common bean (dicot). These models integrate beneficial root traits and guide the development of water- and P-efficient cultivars for challenging environments.
Subject(s)
Phosphorus , Water , Phosphorus/metabolism , Water/metabolism , Plant Roots/metabolism , Plant Breeding , Phenotype , SoilABSTRACT
Nitrate (NO3 - ) and phosphate (Pi) deficiencies are the major constraints for chickpea productivity, significantly impacting global food security. However, excessive fertilization is expensive and can also lead to environmental pollution. Therefore, there is an urgent need to develop chickpea cultivars that are able to grow on soils deficient in both NO3 - and Pi. This study focused on the identification of key NO3 - and/or Pi starvation-responsive metabolic pathways in the leaves and roots of chickpea grown under single and double nutrient deficiencies of NO3 - and Pi, in comparison with nutrient-sufficient conditions. A global metabolite analysis revealed organ-specific differences in the metabolic adaptation to nutrient deficiencies. Moreover, we found stronger adaptive responses in the roots and leaves to any single than combined nutrient-deficient stresses. For example, chickpea enhanced the allocation of carbon among nitrogen-rich amino acids (AAs) and increased the production of organic acids in roots under NO3 - deficiency, whereas this adaptive response was not found under double nutrient deficiency. Nitrogen remobilization through the transport of AAs from leaves to roots was greater under NO3 - deficiency than double nutrient deficiency conditions. Glucose-6-phosphate and fructose-6-phosphate accumulated in the roots under single nutrient deficiencies, but not under double nutrient deficiency, and higher glycolytic pathway activities were observed in both roots and leaves under single nutrient deficiency than double nutrient deficiency. Hence, the simultaneous deficiency generated a unique profile of metabolic changes that could not be simply described as the result of the combined deficiencies of the two nutrients.
Subject(s)
Cicer , Amino Acids/metabolism , Carbon/metabolism , Cicer/metabolism , Glucose-6-Phosphate/metabolism , Nitrates/metabolism , Nitrogen/metabolism , Phosphates/metabolism , Plant Roots/metabolism , SoilABSTRACT
Following various immunotherapies, lack of proper anti-tumor immune responses is considered a significant problem in novel cancer therapeutic approaches. The expression of inhibitory checkpoint molecules on tumor-infiltrating T cells is one of the main reasons for the ineffectiveness of various immunotherapies. Therefore, we decided to inhibit two of the most important immune checkpoints expressed on tumor-associated T cells, PD-1 and A2aR. Ligation of PD-1 with PD-L1 and A2aR with adenosine significantly suppress T cell responses against tumor cells. Whitin tumors, specific inhibition of these molecules on T cells is of particular importance for successful immunotherapy as well as the elimination of treatment-associated side-effects. Thus, in this study, superparamagnetic iron oxide (SPION) nanoparticles (NPs) were covered by chitosan lactate (CL), functionalized with TAT peptide, and loaded with siRNA molecules against PD-1 and A2aR. Appropriate physicochemical properties of the prepared NPs resulted in efficient delivery of siRNA to tumor-derived T cells and suppressed the expression of A2aR and PD-1, ex vivo. T cell functions such as cytokine secretion and proliferation were considerably enhanced by the downregulation of these molecules which led to an increase in their survival time. Interestingly, treatment of CT26 and 4T1 mouse tumors with siRNA-loaded NPs not only inhibited tumor growth but also markedly increased anti-tumor immune responses and survival time. The results strongly support the efficacy of SPION-CL-TAT NPs loaded with anti-PD-1/A2aR siRNAs in cancer therapy and their further development for cancer patients in the near future.
Subject(s)
Breast Neoplasms/therapy , Colorectal Neoplasms/therapy , Nanoparticles/administration & dosage , Programmed Cell Death 1 Receptor/antagonists & inhibitors , RNA, Small Interfering/genetics , Receptor, Adenosine A2A/chemistry , Vaccines/administration & dosage , Animals , Apoptosis , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Cell Proliferation , Chitosan/chemistry , Colorectal Neoplasms/genetics , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Combined Modality Therapy , Dendritic Cells/immunology , Dendritic Cells/transplantation , Female , Humans , Immunotherapy , Lactic Acid/chemistry , Mice , Mice, Inbred BALB C , Mice, Nude , Nanoparticles/chemistry , Programmed Cell Death 1 Receptor/immunology , Receptor, Adenosine A2A/genetics , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
INTRODUCTION: Current treatments for chronic pain (eg, opioids) can have adverse side effects and rarely result in resolution of pain. As such, there is a need for adjuvant analgesics that are non-addictive, have few adverse side effects and are effective for pain management across several chronic pain conditions. Oxytocin is a naturally occurring hormone that has gained attention for its potential analgesic properties. The objective of this trial is to evaluate the efficacy of intranasal oxytocin on pain and function among adults with chronic pain. METHODS AND ANALYSIS: This is a placebo-controlled, triple-blind, sequential, within-subject crossover trial. Adults with chronic neuropathic, pelvic and musculoskeletal pain will be recruited from three Canadian provinces (British Columbia, Alberta and Newfoundland and Labrador, respectively). Enrolled patients will provide one saliva sample pretreatment to evaluate basal oxytocin levels and polymorphisms of the oxytocin receptor gene before being randomised to one of two trial arms. Patients will self-administer three different oxytocin nasal sprays twice daily for a period of 2 weeks (ie, 24 IU, 48 IU and placebo). Patients will complete daily diaries, including standardised measures on day 1, day 7 and day 14. Primary outcomes include pain and pain-related interference. Secondary outcomes include emotional function, sleep disturbance and global impression of change. Intention-to-treat analyses will be performed to evaluate whether improvement in pain and physical function will be observed posttreatment. ETHICS AND DISSEMINATION: Trial protocols were approved by the Newfoundland and Labrador Health Research Ethics Board (HREB #20227), University of British Columbia Clinical Research Ethics Board (CREB #H20-00729), University of Calgary Conjoint Health Research Ethics Board (REB20 #0359) and Health Canada (Control # 252780). Results will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04903002; Pre-results.
Subject(s)
Chronic Pain , Oxytocin , Adult , Alberta , Chronic Pain/drug therapy , Cross-Over Studies , Double-Blind Method , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as TopicABSTRACT
In various pathological conditions, cellular immunity plays an important role in immune responses. Amongimmunecells, T lymphocytes pdomotecellular and humoralresponses as well as innate immunity. Therefore, careful investigation of these cells has a significant impact on accurate knowledge in COVID-19diseasepathogenesis. In current research, the frequency and function of various T lymphocytes involved in immune responses examined in SARS-CoV-2 patients with various disease severity compared to normal subjects. In order to make an accurate comparison among patients with various disease severity, this study was performed on asymptomatic recovered cases (n = 20), ICU hospitalized patients (n = 30), non-ICU hospitalized patients (n = 30), and normal subjects (n = 20). To precisely evaluate T cells activity following purification, their cytokine secretion activity was examined. Similarly, immediately after purification of Treg cells, their inhibitory activity on T cells was investigated. The results showed that COVID-19 patients with severe disease (ICU hospitalized patients) not only had a remarkable increase in Th1 and Th17 but also a considerable decrease in Th2 and Treg cells. More importantly, as the IL-17 and IFN-γ secretion was sharply increased in severe disease, the secretion of IL-10 and IL-4 was decreased. Furthermore, the inhibitory activity of Treg cells was reduced in severe disease patients in comparison to other groups. In severe COVID-19 disease, current findings indicate when the inflammatory arm of cellular immunity is significantly increased, a considerable reduction in anti-inflammatory and regulatory arm occurred.
Subject(s)
COVID-19/blood , COVID-19/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/virology , Adult , Aged , Cytokines/immunology , Cytokines/metabolism , Female , Healthy Volunteers , Humans , Immunity, Cellular , Inflammation/metabolism , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-17/metabolism , Interleukin-4/metabolism , Leukocytes/immunology , Leukocytes/metabolism , Male , Middle Aged , Severity of Illness Index , T-Lymphocyte Subsets/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Th1 Cells/immunology , Th1 Cells/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism , Young AdultABSTRACT
In nature, plants may suffer rapid dehydration (RD), which causes significant loss of the annual global chickpea production. Thus, ascertaining more knowledge concerning the RD-tolerance mechanisms in chickpea is crucial for developing high drought-tolerant varieties to assure sustainable chickpea production under sudden water deficit. Here, we focused on genotype-driven variation in leaf relative water content (RWC) and associated differences in RD-responsive physiological and biochemical attributes in roots and leaves of two chickpea varieties, FLIP00-21C and FLIP02-89C, subjected to well-watered and RD conditions. FLIP00-21C showed higher RD-tolerance than FLIP02-89C, evident by its higher leaf RWC during RD. Consistently, FLIP00-21C exhibited lower membrane injury due to lower hydrogen peroxide (H2 O2 ) accumulation than FLIP02-89C during RD, indicating reduced RD-induced oxidative damage. Under RD conditions, total phenolics in roots and flavonoids in roots and leaves increased more in FLIP02-89C compared to FLIP00-21C; however, the increased activities of superoxide dismutase and H2 O2 -scavenging enzymes were more properly coordinated in FLIP00-21C than in FLIP02-89C, which might contribute to more efficient antioxidant defense in FLIP00-21C than in FLIP02-89C. The higher leaf RWC of FLIP00-21C versus FLIP02-89C under RD might be associated with greater increases in the levels of the osmo-regulators proline and total free amino acids (TFAAs) in FLIP00-21C than in FLIP02-89C. Collectively, the higher RD-tolerance of FLIP00-21C is mainly associated with the maintenance of higher RWC, stronger antioxidant defense, and greater accumulation of proline and TFAAs. These traits could be useful for evaluating the drought-tolerance of chickpea varieties and further marker-assisted breeding approaches for improvement of chickpea productivity.
Subject(s)
Cicer , Cicer/genetics , Dehydration , Droughts , Genotype , Plant LeavesABSTRACT
The negative effects of phosphate (Pi) and/or nitrate (NO3- ) fertilizers on the environment have raised an urgent need to develop crop varieties with higher Pi and/or nitrogen use efficiencies for cultivation in low-fertility soils. Achieving this goal depends upon research that focuses on the identification of genes involved in plant responses to Pi and/or NO3- starvation. Although plant responses to individual deficiency in either Pi (-Pi/+NO3- ) or NO3- (+Pi/-NO3- ) have been separately studied, our understanding of plant responses to combined Pi and NO3- deficiency (-Pi/-NO3- ) is still very limited. Using RNA-sequencing approach, transcriptome changes in the roots and leaves of chickpea cultivated under -Pi/+NO3- , +Pi/-NO3- or -Pi/-NO3- conditions were investigated in a comparative manner. -Pi/-NO3- treatment displayed lesser effect on expression changes of genes related to Pi or NO3- transport, signalling networks, lipid remodelling, nitrogen and Pi scavenging/remobilization/recycling, carbon metabolism and hormone metabolism than -Pi/+NO3- or +Pi/-NO3- treatments. Therefore, the plant response to -Pi/-NO3- is not simply an additive result of plant responses to -Pi/+NO3- and +Pi/-NO3- treatments. Our results indicate that nutrient imbalance is a stronger stimulus for molecular reprogramming than an overall deficiency.
Subject(s)
Cicer/genetics , Nitrates/metabolism , Phosphates/metabolism , Transcriptome , Cicer/metabolism , Plant Leaves/genetics , Plant Leaves/metabolism , Plant Roots/genetics , Plant Roots/metabolismABSTRACT
OBJECTIVE: To investigate the effect of intranasal oxytocin on chronic pelvic pain in a randomized, double-blind, within-subject crossover trial. Aims included: (1) determine intranasal oxytocin's effect on pain intensity and pain interference relative to placebo; (2) assess feasibility and acceptability. METHODS: Women with chronic pelvic pain were recruited from chronic pain and gynecology clinics between September 2017 and December 2018. Pain was recorded at pre-trial screening, and while administering intranasal oxytocin and placebo. Pain and pain-related interference were measured using the Brief Pain Inventory - Short Form. Feasibility and acceptability were measured using validated measures and interviews. RESULTS: Twenty-one women were randomized with sufficient data available from 12 to permit analyses. Relative to placebo, a 2-week course of oxytocin administration resulted in improvement in pain severity with no effect on pain-related interference. This effect was driven by four women who demonstrated a minimal clinically significant improvement in pain following intranasal oxytocin (no women met this threshold for placebo). Adherence to dosing was excellent and occurrence of adverse effects did not differ between oxytocin and placebo. CONCLUSION: Intranasal oxytocin may represent an adjuvant analgesic that could result in a minimal clinically significant improvement in pain among one in three women with chronic pelvic pain. Registration: ClinicalTrials.gov (Registration# NCT02888574).
Subject(s)
Oxytocin/administration & dosage , Pelvic Pain/drug therapy , Administration, Intranasal , Adult , Double-Blind Method , Feasibility Studies , Female , Humans , Pain Measurement , Surveys and Questionnaires , Treatment OutcomeABSTRACT
INTRODUCTION: Botulinum toxin has proven therapeutic effects in alleviating pain in several myofascial disorders, with an expanding potential in chronic pelvic pain. The objective of this systematic review is to evaluate the efficacy and safety of botulinum toxin injection as an off-label treatment for female chronic pelvic pain. MATERIAL AND METHODS: Using PRISMA guidelines, MEDLINE, EBM Reviews, PubMed, CINAHL, TRIP Database, EMBASE, Web of Science and gray literature were searched. Studies assessing the efficacy of botulinum toxin for chronic pelvic pain in adult females, with 10 or more women, published in English up to 13 January 2020, were included. All eligible studies were reviewed and data were extracted by two independent reviewers using a standardized form. Quality of evidence was graded using the Cochrane Risk of Bias 2 tool for randomized controlled trials and the Ottawa-Newcastle scale for observational studies. RESULTS: In all, 491 records were screened. Seventeen articles were included in the final review: 5 randomized controlled trials and 12 observational studies. The quality of evidence ranged from low to high. There was a large degree of heterogeneity in study designs, and thus a meta-analysis was not feasible. All observational studies concluded that botulinum toxin was an effective treatment for chronic pelvic pain, with the greatest change in visual analog scale from 8.69 at baseline to 3.07 at 24 months post-injection. However, only one of the five randomized controlled trials found statistical significant differences favoring botulinum toxin in the reporting of the EQ-5D (botulinum 0.78 [0.69-1.00], control 0.69 [0.25-0.81], P = .03) and frequency of intercourse (botulinum 1 [1-1.75], placebo 1 [0-1], P = .025). The most common adverse effect was transient localized pain at injection site (6%-88%). No serious adverse events were reported. CONCLUSIONS: Although observational studies were encouraging, there is insufficient high quality evidence to recommend botulinum toxin injection for chronic pelvic pain. However, it appears to be safe to use. Future studies of higher quality in its treatment efficacy are indicated.
Subject(s)
Botulinum Toxins/pharmacology , Pelvic Pain , Chronic Pain , Female , Humans , Neuromuscular Agents/pharmacology , Pain Measurement , Pelvic Pain/diagnosis , Pelvic Pain/drug therapyABSTRACT
BACKGROUND: The purpose of the present study was to produce a pcDNA3.1(+)-ureA recombinant vector and evaluate the capacity of this vector to stimulate the immune response against H. pylori infection in infused BALB/c mice. MATERIALS AND METHODS: The pcDNA3.1(+)-ureA construct was prepared and transformed into E. coli, successfully. The animals we used in the study were allotted into three groups for infusion of 1) recombinant plasmid, 2) pcDNA3.1(+)-ureA + nanoparticles, and 3) pcDNA3.1(+). Blood and tissue specimens from each group of mice were collected at days 15, 30, and 45 after the last infusion and the expression levels of cytokines such as TGF-ß1, IL-4, and IFNγ genes comparing to GAPDH as well as the expression of ureA in the mice's thigh muscle were evaluated. RESULTS: The genes expression analysis showed that the IL4 expression significantly decreased (p<0.001) but IFNγ and TGF-ß1 expression increased in the blood of infused mice (p<0.001). Also, the urea expression level in pcDNA3.1(+)-urea and pcDNA3.1(+)-ureA+ nanoparticle 15, 30, and 45 days after the last infusion was significantly different (p<0.001) and its expressions at days 15 and 30 were significantly different (p<0.001), but 45 days after the last infusion it was not significantly different (p>0.05). CONCLUSION: The pcDNA3.1(+)-ureA recombinant vector with or without chitosan nanoparticles can stimulate the immune response in animal models against H. pylori infection. Also, after combining the recombinant vector with nanoparticles we observed a better immune response was observed. In future studies this recombinant construct can be used as a biomarker and therapeutic approaches in eukaryotic systems.
Subject(s)
Bacterial Proteins/genetics , Cytokines/drug effects , Helicobacter pylori/genetics , Immunity/drug effects , Urease/genetics , Vaccines, DNA/pharmacology , Animals , Chitosan , Cytokines/genetics , Female , Helicobacter Infections , Interferon-gamma/drug effects , Interferon-gamma/genetics , Interleukin-4/genetics , Mice , Mice, Inbred BALB C , Nanoparticles , Reverse Transcriptase Polymerase Chain Reaction , Transforming Growth Factor beta1/drug effects , Transforming Growth Factor beta1/geneticsABSTRACT
Phosphate (Pi) deficiency is known to be a major limitation for symbiotic nitrogen fixation (SNF), and hence legume crop productivity globally. However, very little information is available on the adaptive mechanisms, particularly in the important legume crop chickpea (Cicer arietinum L.), which enable nodules to respond to low-Pi availability. Thus, to elucidate these mechanisms in chickpea nodules at molecular level, we used an RNA sequencing approach to investigate transcriptomes of the nodules in Mesorhizobium mediterraneum SWRI9-(MmSWRI9)-chickpea and M. ciceri CP-31-(McCP-31)-chickpea associations under Pi-sufficient and Pi-deficient conditions, of which the McCP-31-chickpea association has a better SNF capacity than the MmSWRI9-chickpea association during Pi starvation. Our investigation revealed that more genes showed altered expression patterns in MmSWRI9-induced nodules than in McCP-31-induced nodules (540 vs. 225) under Pi deficiency, suggesting that the Pi-starvation-more-sensitive MmSWRI9-induced nodules required expression change in a larger number of genes to cope with low-Pi stress than the Pi-starvation-less-sensitive McCP-31-induced nodules. The functional classification of differentially expressed genes (DEGs) was examined to gain an understanding of how chickpea nodules respond to Pi starvation, caused by soil Pi deficiency. As a result, more DEGs involved in nodulation, detoxification, nutrient/ion transport, transcriptional factors, key metabolic pathways, Pi remobilization and signalling were found in Pi-starved MmSWRI9-induced nodules than in Pi-starved McCP-31-induced nodules. Our findings have enabled the identification of molecular processes that play important roles in the acclimation of nodules to Pi deficiency, ultimately leading to the development of Pi-efficient chickpea symbiotic associations suitable for Pi-deficient soils.
Subject(s)
Cicer/genetics , Mesorhizobium/genetics , Phosphates/deficiency , Transcriptome , Cicer/microbiology , Gene Expression Profiling , Mesorhizobium/physiology , Nitrogen Fixation , Plant Roots/genetics , Plant Roots/microbiology , Soil , SymbiosisABSTRACT
INTRODUCTION: This protocol presents the rationale and design for a trial evaluating the efficacy of intranasal oxytocin in improving pain and function among women with chronic pelvic musculoskeletal pain. Oxytocin is a neuropeptide traditionally recognised for involvement in labour, delivery and lactation. Novel evidence suggests that oxytocin decreases pain sensitivity in humans. While oxytocin administration has been reported to lower pain sensitivity among patients experiencing chronic back pain, headache, constipation and colon pain, no research has evaluated the association between intranasal oxytocin and chronic pelvic musculoskeletal pain. The association between oxytocin and pain may differ in women with chronic pelvic musculoskeletal pain relative to other chronic pain conditions because of the abundance of oxytocin receptors in the uterus. METHODS AND ANALYSIS: This is a prospective, randomised, placebo-controlled, double-blind, within-participants crossover trial. 50 women with chronic pelvic musculoskeletal pain will be recruited through a local chronic pain centre and gynaecology clinics. Women will complete baseline measures and be randomised to an experimental or control condition that involve 2â weeks of self-administering twice-daily doses of 24â IU intranasal oxytocin or placebo, respectively. Women will then undergo a 2-week washout period before crossing over to receive the condition that they had not yet received. The primary outcome will be pain and function measured using the Brief Pain Inventory-Short Form. Secondary outcomes include emotional function, sleep disturbance and global impression of change. This trial will provide data on the 14-day safety and side-effect profile of intranasal oxytocin self-administered as an adjuvant treatment for chronic pelvic musculoskeletal pain. ETHICS AND DISSEMINATION: This trial was granted approval from Health Canada and the University of Calgary Conjoint Health Research Ethics Board, and is registered online at ClinicalTrials.gov (#NCT02888574). Results will be disseminated to healthcare professionals through peer-reviewed publications and to the general public through press releases. TRIAL REGISTRATION NUMBER: NCT02888574; Pre-results.
Subject(s)
Chronic Pain/drug therapy , Musculoskeletal Pain/drug therapy , Oxytocin/administration & dosage , Pelvic Pain/drug therapy , Administration, Intranasal , Adult , Canada , Cross-Over Studies , Double-Blind Method , Female , Humans , Oxytocin/adverse effects , Pain Threshold/drug effects , Prospective Studies , Research Design , Self ReportABSTRACT
Low inorganic phosphate (Pi) availability is a major constraint for efficient nitrogen fixation in legumes, including chickpea. To elucidate the mechanisms involved in nodule acclimation to low Pi availability, two Mesorhizobium-chickpea associations exhibiting differential symbiotic performances, Mesorhizobium ciceri CP-31 (McCP-31)-chickpea and Mesorhizobium mediterranum SWRI9 (MmSWRI9)-chickpea, were comprehensively studied under both control and low Pi conditions. MmSWRI9-chickpea showed a lower symbiotic efficiency under low Pi availability than McCP-31-chickpea as evidenced by reduced growth parameters and down-regulation of nifD and nifK These differences can be attributed to decline in Pi level in MmSWRI9-induced nodules under low Pi stress, which coincided with up-regulation of several key Pi starvation-responsive genes, and accumulation of asparagine in nodules and the levels of identified amino acids in Pi-deficient leaves of MmSWRI9-inoculated plants exceeding the shoot nitrogen requirement during Pi starvation, indicative of nitrogen feedback inhibition. Conversely, Pi levels increased in nodules of Pi-stressed McCP-31-inoculated plants, because these plants evolved various metabolic and biochemical strategies to maintain nodular Pi homeostasis under Pi deficiency. These adaptations involve the activation of alternative pathways of carbon metabolism, enhanced production and exudation of organic acids from roots into the rhizosphere, and the ability to protect nodule metabolism against Pi deficiency-induced oxidative stress. Collectively, the adaptation of symbiotic efficiency under Pi deficiency resulted from highly coordinated processes with an extensive reprogramming of whole-plant metabolism. The findings of this study will enable us to design effective breeding and genetic engineering strategies to enhance symbiotic efficiency in legume crops.
Subject(s)
Fabaceae/microbiology , Mesorhizobium/physiology , Phosphates/metabolism , Symbiosis , Adaptation, Physiological , Fabaceae/metabolism , Phosphates/deficiencyABSTRACT
Drought causes detrimental effect to growth and productivity of many plants, including crops. NAC transcription factors have been reported to play important role in drought tolerance. In this study, we assessed the expression profiles of 19 dehydration-responsive CaNAC genes in roots and leaves of two contrasting drought-responsive chickpea varieties treated with water (control) and dehydration to examine the correlation between the differential expression levels of the CaNAC genes and the differential drought tolerability of these two cultivars. Results of real-time quantitative PCR indicated a positive relationship between the number of dehydration-inducible and -repressible CaNAC genes and drought tolerability. The higher drought-tolerant capacity of ILC482 cultivar vs. Hashem cultivar might be, at least partly, attributed to the higher number of dehydration-inducible and lower number of dehydration-repressible CaNAC genes identified in both root and leaf tissues of ILC482 than in those of Hashem. In addition, our comparative expression analysis of the selected CaNAC genes in roots and leaves of ILC482 and Hashem cultivars revealed different dehydration-responsive expression patterns, indicating that CaNAC gene expression is tissue- and genotype-specific. Furthermore, the analysis suggested that the enhanced drought tolerance of ILC482 vs. Hashem might be associated with five genes, namely CaNAC02, 04, 05, 16, and 24. CaNAC16 could be a potential candidate gene, contributing to the better drought tolerance of ILC482 vs. Hashem as a positive regulator. Conversely, CaNAC02 could be a potential negative regulator, contributing to the differential drought tolerability of these two cultivars. Thus, our results have also provided a solid foundation for selection of promising tissue-specific and/or dehydration-responsive CaNAC candidates for detailed in planta functional analyses, leading to development of transgenic chickpea varieties with improved productivity under drought.
ABSTRACT
Water deficit is one of the major constraints for soybean production in Vietnam. The soybean breeding research efforts conducted at the Agriculture Genetics Institute (AGI) of Vietnam resulted in the development of promising soybean genotypes, suitable for the drought-stressed areas in Vietnam and other countries. Such a variety, namely, DT2008, was recommended by AGI and widely used throughout the country. The aim of this work was to assess the growth of shoots, roots, and nodules of DT2008 versus Williams 82 (W82) in response to drought and subsequent rehydration in symbiotic association as a means to provide genetic resources for genomic research. Better shoot, root, and nodule growth and development were observed in the cultivar DT2008 under sufficient, water deficit, and recovery conditions. Our results represent a good foundation for further comparison of DT2008 and W82 at molecular levels using high throughput omic technologies, which will provide huge amounts of data, enabling us to understand the genetic network involved in regulation of soybean responses to water deficit and increasing the chances of developing drought-tolerant cultivars.
Subject(s)
Glycine max/growth & development , Nitrogen Fixation/physiology , Plant Roots/metabolism , Plant Shoots/metabolism , Stress, Physiological , Symbiosis/physiology , Droughts , Plant Roots/genetics , Plant Shoots/genetics , Glycine max/genetics , VietnamABSTRACT
Drought negatively impacts symbiotic nitrogen fixation (SNF) in Cicer arietinum L. (chickpea), thereby limiting yield potential. Understanding how drought affects chickpea nodulation will enable the development of strategies to biotechnologically engineer chickpea varieties with enhanced SNF under drought conditions. By analyzing carbon and nitrogen metabolism, we studied the mechanisms of physiological adjustment of nitrogen fixation in chickpea plants nodulated with Mesorhizobium ciceri during both drought stress and subsequent recovery. The nitrogenase activity, levels of several key carbon (in nodules) and nitrogen (in both nodules and leaves) metabolites and antioxidant compounds, as well as the activity of related nodule enzymes were examined in M. ciceri-inoculated chickpea plants under early drought stress and subsequent recovery. Results indicated that drought reduced nitrogenase activity, and that this was associated with a reduced expression of the nifK gene. Furthermore, drought stress promoted an accumulation of amino acids, mainly asparagine in nodules (but not in leaves), and caused a cell redox imbalance in nodules. An accumulation of organic acids, especially malate, in nodules, which coincided with the decline of nodulated root respiration, was also observed under drought stress. Taken together, our findings indicate that reduced nitrogenase activity occurring at early stages of drought stress involves, at least, the inhibition of respiration, nitrogen accumulation and an imbalance in cell redox status in nodules. The results of this study demonstrate the potential that the genetic engineering-based improvement of SNF efficiency could be applied to reduce the impact of drought on the productivity of chickpea, and perhaps other legume crops.
Subject(s)
Carbon/metabolism , Cicer/physiology , Gene Expression Regulation, Plant , Mesorhizobium/physiology , Nitrogen/metabolism , Water/physiology , Cell Respiration , Cicer/genetics , Cicer/microbiology , Droughts , Malates/metabolism , Models, Biological , Nitrogen Fixation , Nitrogenase/genetics , Nitrogenase/metabolism , Oxidation-Reduction , Oxidative Stress , Plant Leaves/genetics , Plant Leaves/physiology , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Roots/genetics , Plant Roots/physiology , Root Nodules, Plant/genetics , Root Nodules, Plant/physiology , SymbiosisABSTRACT
OBJECTIVE: We sought to assess the concurrent validity and interrater reliability of the cotton-tipped applicator (CTA) test as a screening tool for diagnosis of cutaneous allodynia in patients with viscerally related chronic pelvic pain (CPP). STUDY DESIGN: We performed a prospective cohort comparative observational study of referred patients to a gynecology clinic with CPP. A total of 22 females with CPP were compared to 23 pain-free controls and 12 cyclic pain patients. Participants were evaluated by 2 clinicians. The CTA test was performed to detect the appearance of pain in dermatomes of T10-L1. RESULTS: Interrater reliability resulted in 98% agreement for the 3 study groups. CTA test showed 73% sensitivity and 100% specificity for differentiating patients with CPP from pain-free patients. CONCLUSION: The CTA test had excellent interrater reliability and concurrent validity for diagnosis of cutaneous allodynia in CPP patients with visceral diseases versus controls.