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    In the current report, the committee presents a rigorous and thoughtful summary of the landscape of cannabis and health and puts forth recommendations to help advance the research field and better inform public health decisions.

    I wish to express my deepest gratitude to my fellow committee members who worked so hard and with good grace to accomplish this task. As with other National Academies of Sciences, Engineering, and Medicine reports, the work of the committee would have been far more difficult, if not impossible, without the support of a dedicated, knowledgeable and also very hardworking National Academies staff.

    An Evidence Review and Research Agenda xv. To date, 28 states and the District of Columbia have legalized cannabis for the treatment of medical conditions NCSL, These landmark changes in policy have markedly changed cannabis use patterns and perceived levels of risk. Based on a recent nationwide survey, Despite the extensive changes in policy at the state level and the rapid rise in the use of cannabis both for medical purposes and for recreational use, conclusive evidence regarding the short- and long-term health effects harms and benefits of cannabis use remains elusive.

    A lack of scientific research has resulted in a lack of information on the health implications of cannabis use, which is a significant public health concern for vulnerable populations such as adolescents and pregnant women. Unlike other substances, such as alcohol or tobacco, whose use may confer risk, no accepted standards exist to help guide individuals as they make choices regarding the issues of if, when, where, and how to use cannabis safely and, in regard to therapeutic uses, effectively.

    The resulting Committee on the Health Effects of Marijuana consisted of 16 experts in the areas of marijuana, addiction, oncology, cardiology, neurodevelopment, respiratory disease, pediatric and adolescent health, immunology, toxicology, preclinical research, epidemiology, systematic review, and public health.

    Of note, throughout the report the committee has attempted to highlight research conclusions that affect certain populations e. The committee s full statement of task is presented in Box S The committee will develop a consensus report with two primary sections: In addition, the report will outline and make recommendations regarding a research agenda identifying the most critical research questions regarding the association of marijuana use with health outcomes both risks and therapeutic that can be answered in the short term i.

    The committee should focus on questions and consequences with the potential for the greatest public health impact, while shedding light on the characteristics of marijuana use that impact both short- and long-term health. In conducting its work, the committee will conduct a comprehensive review of the evidence, using accepted approaches of literature search, evidence review, grading and synthesis.

    Studies reviewed regarding health risks should be as broad as possible, including but not limited to epidemiology and clinical studies, and toxicology and animal studies when determined appropriate by the committee. The committee will provide summary determinations regarding causality based on strength of evidence. Assessing the Science Base. Although these reports differed in scope, they were useful in providing a comprehensive body of evidence upon which the current committee could build.

    The committee conducted an extensive search of relevant databases, including Medline, Embase, the Cochrane Database of Systematic Reviews, and PsycINFO and initially retrieved more than 24, abstracts that could have potentially been relevant to this study. These abstracts were reduced by limiting articles to those published in English and removing case reports, editorials, studies by anonymous authors, conference abstracts, and commentaries.

    In the end, the committee considered more than 10, abstracts for their relevance to this report. Given the large scientific literature on cannabis, the breadth of the statement of task, and the time constraints of the study, the committee developed an approach that resulted in giving primacy to recently published systematic reviews since and high-quality primary research for eleven groups of health endpoints see Box S For each health endpoint, systematic reviews were identified and assessed for quality using published criteria; only fair- and goodquality reviews were considered by the committee.

    The committee s conclusions are based on the findings from the most recently published systematic review and all relevant fair- and goodquality primary research published after the systematic review.

    Where no systematic review existed, the committee reviewed all relevant primary research published between January 1, and August 1, Primary research was assessed using standard approaches e. Readers of this report should recognize two important points. First, the committee was not tasked to conduct multiple systematic reviews, which would have required a lengthy and robust series of processes.

    The committee did, however, adopt key features of that process: Second, there is a possibility that some literature was missed because of the practical steps taken to narrow a very large literature to one that was manageable within the timeframe available to the committee. Furthermore, very good research may not be reflected in this report because it did not directly address the health endpoint research questions that were prioritized by the committee.

    This report is organized into four parts and 16 chapters. Introduction and Background, Part II: Research Barriers and Recommendations. The evidence reviewed in Part III derives from epidemiological research that primarily reviews the effects of smoked cannabis. It is of note that several of the prioritized health endpoints discussed in Part III are also reviewed in Part II, albeit from the perspective of effects associated with using cannabis for primarily recreational, as opposed to therapeutic, purposes.

    Several health endpoints are discussed in multiple chapters of the report e. This is, in part, due to differences in the study design of the reviewed evidence, differences in characteristics of cannabis or cannabinoid exposure e. Informed by the reports of previous IOM committees, 3 the committee developed standard language to categorize the weight of evidence regarding whether cannabis or cannabinoids use for therapeutic purposes are an effective or ineffective treatment for the prioritized health endpoints of interest, or whether cannabis or cannabinoid use primarily for recreational purposes are statistically associated with the prioritized health endpoints of interest.

    Box S-3 below describes these categories and the general parameters for the types of evidence supporting each category. For a full listing of the committee s conclusions, please see the chapter s annex.

    There is strong evidence from randomized controlled trials to support the conclusion that cannabis or cannabinoids are an effective or ineffective treatment for the health endpoint of interest. For other health effects: There is strong evidence from randomized controlled trials to support or refute a statistical association between cannabis or cannabinoid use and the health endpoint of interest.

    For this level of evidence, there are many supportive findings from good-quality studies with no credible opposing findings. A firm conclusion can be made, and the limitations to the evidence, including chance, bias, and confounding factors, can be ruled out with reasonable confidence. There is strong evidence to support the conclusion that cannabis or cannabinoids are an effective or ineffective treatment for the health endpoint of interest. There is strong evidence to support or refute a statistical association between cannabis or cannabinoid use and the health endpoint of interest.

    For this level of evidence, there are several supportive findings from good-quality studies with very few 3 Adverse Effects of Vaccines IOM, ; Treatment of Posttraumatic Stress Disorder: A firm conclusion can be made, but minor limitations, including chance, bias, and confounding factors, cannot be ruled out with reasonable confidence. There is some evidence to support the conclusion that cannabis or cannabinoids are an effective or ineffective treatment for the health endpoint of interest.

    There is some evidence to support or refute a statistical association between cannabis or cannabinoid use and the health endpoint of interest. For this level of evidence, there are several supportive findings from good- to fair-quality studies with very few or no credible opposing findings.

    A general conclusion can be made, but limitations, including chance, bias, and confounding factors, cannot be ruled out with reasonable confidence. There is weak evidence to support the conclusion that cannabis or cannabinoids are an effective or ineffective treatment for the health endpoint of interest.

    There is weak evidence to support or refute a statistical association between cannabis or cannabinoid use and the health endpoint of interest. For this level of evidence, there are supportive findings from fair-quality studies or mixed findings with most favoring one conclusion.

    A conclusion can be made, but there is significant uncertainty due to chance, bias, and confounding factors. There is no or insufficient evidence to support the conclusion that cannabis or cannabinoids are an effective or ineffective treatment for the health endpoint of interest. There is no or insufficient evidence to support or refute a statistical association between cannabis or cannabinoid use and the health endpoint of interest.

    For this level of evidence, there are mixed findings, a single poor study, or health endpoint has not been studied at all. No conclusion can be made because of substantial uncertainty due to chance, bias, and confounding factors. Shifting public sentiment, conflicting and impeded scientific research, and legislative battles have fueled the debate about what, if any, harms or benefits can be attributed to the use of cannabis or its derivatives.

    The committee has put forth a substantial number of research conclusions on the health effects of cannabis and cannabinoids. Based on their research conclusions, the committee members formulated four recommendations to address research gaps, improve research quality, improve surveillance capacity, and address research barriers. The report s full recommendations are described below. Address Research Gaps Recommendation 1: To develop a comprehensive evidence base on the short- and long-term health effects of cannabis use both beneficial and harmful effects , public agencies, 4 philanthropic and professional organizations, private companies, and clinical and public health research groups should provide funding and support for a national cannabis research agenda that addresses key gaps in the evidence base.

    Prioritized research streams and objectives should include, but need not be limited to: Clinical and Observational Research Examine the health effects of cannabis use in at-risk or under-researched populations, such as children and youth often described as less than 18 years of age and older populations generally over 50 years of age , pregnant and breastfeeding women, and heavy cannabis users.

    Investigate the pharmacokinetic and pharmacodynamic properties of cannabis, modes of delivery, different concentrations, in various populations, including the dose response relationships of cannabis and THC or other cannabinoids. Determine the benefits and harms associated with understudied cannabis products, such as edibles, concentrates, and topicals. Conduct well-controlled trials on the potential beneficial and harmful health effects of using different forms of cannabis, such as inhaled smoked or vaporized whole cannabis plant and oral cannabis.

    Characterize the health effects of cannabis on unstudied and understudied health endpoints, such as epilepsy in pediatric populations; symptoms of posttraumatic stress disorder; childhood and adult cancers; cannabis-related overdoses and poisonings; and other high-priority health endpoints. Health Policy and Health Economics Research Identify models, including existing state cannabis policy models, for sustainable funding of national, state, and local public health surveillance systems.

    Investigate the economic impact of recreational and medical cannabis use on national and state public health and health care systems, health insurance providers, and patients.

    Characterize public safety concerns related to recreational cannabis use and evaluate existing quality assurance, safety, and packaging standards for recreational cannabis products. Improve Research Quality Recommendation 2: To promote the development of conclusive evidence on the short- and long-term health effects of cannabis use both beneficial and harmful effects , agencies of the United States Department of Health and Human Services, including the National Institutes of Health and the Centers for Disease Control and Prevention should jointly fund a workshop to develop a set of research standards and benchmarks to guide and ensure the production of high-quality cannabis research.

    Workshop objectives should include, but need not be limited to: The development of a minimum dataset for observational and clinical studies, standards for research methods and design, and guidelines for data collection methods. Adaptation of existing research-reporting standards to the needs of cannabis research. The development of uniform terminology for clinical and epidemiological cannabis research. The development of standardized and evidence-based question banks for clinical research and public health surveillance tools.

    Improve Surveillance Capacity Recommendation 3: To ensure that sufficient data are available to inform research on the short- and long-term health effects of cannabis use both beneficial and harmful effects , the Centers for Disease Control and Prevention, the Substance Abuse and Mental Health Services Administration, the Association of State and Territorial Health Officials, National Association of County and City Health Officials, the Association of Public Health Laboratories, and state and local public health departments should fund and support improvements to federal public health surveillance systems and state-based public health surveillance efforts.

    Potential efforts should include, but need not be limited to: Determining the capacity to collect and reliably interpret data from diagnostic classification codes in administrative data e. The development of novel diagnostic technologies that allow for rapid, accurate, and non-invasive assessment of cannabis exposure and impairment.

    Strategies for surveillance of harmful effects of cannabis for therapeutic use. Address Research Barriers Recommendation 4: The Centers for Disease Control and Prevention, National Institutes of Health, Food and Drug Administration, industry groups, and nongovernmental organizations should fund the convening of a committee of experts tasked to produce an objective and evidence-based report that fully characterizes the impacts of regulatory barriers to cannabis research and that proposes strategies for supporting development of the resources and infrastructure necessary to conduct a comprehensive cannabis research agenda.

    Committee objectives should include, but need not be limited to: Proposing strategies for expanding access to research-grade marijuana, through the creation and approval of new facilities for growing and storing cannabis. Identifying nontraditional funding sources and mechanisms to support a comprehensive national cannabis research agenda.

    Investigating strategies for improving the quality, diversity, and external validity of research-grade cannabis products. An assessment of the evidence. IOM Adverse effects of vaccines: National Conference of State Legislatures State medical marijuana laws. For the treatment of chronic pain in adults cannabis As anti-emetics in the treatment of chemotherapy-induced nausea and vomiting oral cannabinoids For improving patient-reported multiple sclerosis spasticity symptoms oral cannabinoids a There is moderate evidence that cannabis or cannabinoids are effective for: Improving short-term sleep outcomes in individuals with sleep disturbance associated with obstructive sleep apnea syndrome, fibromyalgia, chronic pain, and multiple sclerosis cannabinoids, primarily nabiximols There is limited evidence that cannabis or cannabinoids are effective for: Improving symptoms associated with dementia cannabinoids Improving intraocular pressure associated with glaucoma cannabinoids Reducing depressive symptoms in individuals with chronic pain or multiple sclerosis nabiximols, dronabinol, and nabilone There is no or insufficient evidence to support or refute the conclusion that cannabis or cannabinoids are an effective treatment for: Cancers, including glioma cannabinoids Cancer-associated anorexia cachexia syndrome and anorexia nervosa cannabinoids Numbers in parentheses correspond to chapter conclusion numbers.

    Incidence of lung cancer cannabis smoking Incidence of head and neck cancers There is limited evidence of a statistical association between cannabis smoking and: Non-seminoma-type testicular germ cell tumors current, frequent, or chronic cannabis smoking There is no or insufficient evidence to support or refute a statistical association between cannabis use and: The triggering of acute myocardial infarction cannabis smoking a Ischemic stroke or subarachnoid hemorrhage Decreased risk of metabolic syndrome and diabetes a Increased risk of prediabetes b There is no evidence to support or refute a statistical association between chronic effects of cannabis use and: The increased risk of acute myocardial infarction b.

    Worse respiratory symptoms and more frequent chronic bronchitis episodes long-term cannabis smoking a There is moderate evidence of a statistical association between cannabis smoking and: Improved airway dynamics with acute use, but not with chronic use a Higher forced vital capacity FVC b There is moderate evidence of a statistical association between the cessation of cannabis smoking and: Improvements in respiratory symptoms b There is limited evidence of a statistical association between cannabis smoking and: An increased risk of developing chronic obstructive pulmonary disease COPD when controlled for tobacco use occasional cannabis smoking a There is no or insufficient evidence to support or refute a statistical association between cannabis smoking and: Hospital admissions for COPD b Asthma development or asthma exacerbation Chapter 8 Conclusions Immunity There is limited evidence of a statistical association between cannabis smoking and: A decrease in the production of several inflammatory cytokines in healthy individuals a There is limited evidence of no statistical association between cannabis use and: The progression of liver fibrosis or hepatic disease in individuals with viral Hepatitis C HCV daily cannabis use There is no or insufficient evidence to support or refute a statistical association between cannabis use and: Other adverse immune cell responses in healthy individuals cannabis smoking b Adverse effects on immune status in individuals with HIV cannabis or dronabinol use Increased incidence of oral human papilloma virus HPV regular cannabis use Increased risk of motor vehicle crashes There is moderate evidence of a statistical association between cannabis use and: Increased risk of overdose injuries, including respiratory distress, among pediatric populations in U.

    All-cause mortality self-reported cannabis use Occupational accidents or injuries general, non-medical cannabis use Death due to cannabis overdose a Chapter 10 Conclusions Prenatal, Perinatal, and Neonatal Exposure There is substantial evidence of a statistical association between maternal cannabis smoking and: Lower birth weight of the offspring There is limited evidence of a statistical association between maternal cannabis smoking and: Pregnancy complications for the mother Admission of the infant to the neonatal intensive care unit NICU There is insufficient evidence to support or refute a statistical association between maternal cannabis smoking and: Later outcomes in the offspring e.

    The impairment in the cognitive domains of learning, memory, and attention acute cannabis use a There is limited evidence of a statistical association between cannabis use and: Impairments in the cognitive domains of learning, memory, and attention b.

    The development of schizophrenia or other psychoses, with the highest risk among the most frequent users There is moderate evidence of a statistical association between cannabis use and: Better cognitive performance among individuals with psychotic disorders and a history of cannabis use a Increased symptoms of mania and hypomania in individuals diagnosed with bipolar disorders regular cannabis use A small increased risk for the development of depressive disorders Increased incidence of suicidal ideation and suicide attempts with a higher incidence among heavier users a Increased incidence of suicide completion b Increased incidence of social anxiety disorder regular cannabis use b There is moderate evidence of no statistical association between cannabis use and: Worsening of negative symptoms of schizophrenia e.

    An increase in positive symptoms of schizophrenia e. Changes in the course or symptoms of depressive disorders The development of posttraumatic stress disorder Stimulant treatment of attention deficit hyperactivity disorder ADHD during adolescence is not a risk factor for the development of problem cannabis use e Being male and smoking cigarettes are risk factors for the progression of cannabis use to problem cannabis use i Initiating cannabis use at an earlier age is a risk factor for the development of problem cannabis use j There is substantial evidence of a statistical association between: Increases in cannabis use frequency and the progression to developing problem cannabis use Being male and the severity of problem cannabis use, but the recurrence of problem cannabis use does not differ between males and females b There is moderate evidence that: Anxiety, personality disorders, and bipolar disorders are not risk factors for the development of problem cannabis use b Major depressive disorder is a risk factor for the development of problem cannabis use c Adolescent ADHD is not a risk factor for the development of problem cannabis use d Being male is a risk factor for the development of problem cannabis use f Exposure to the combined use of abused drugs is a risk factor for the development of problem cannabis use g Neither alcohol nor nicotine dependence alone are risk factors for the progression from cannabis use to problem cannabis use h During adolescence the frequency of cannabis use, oppositional behaviors, a younger age of first alcohol use, nicotine use, parental substance use, poor school performance, antisocial behaviors, and childhood sexual abuse are risk factors for the development of problem cannabis use k There is moderate evidence of a statistical association between: A persistence of problem cannabis use and a history of psychiatric treatment a Problem cannabis use and increased severity of posttraumatic stress disorder symptoms c There is limited evidence that: Childhood anxiety and childhood depression are risk factors for the development of problem cannabis use a.

    The initiation of tobacco use Changes in the rates and use patterns of other licit and illicit substances Chapter 15 Conclusions Challenges and Barriers in Conducting Cannabis and Cannabinoid Research There are several challenges and barriers in conducting cannabis and cannabinoid research, including: There are specific regulatory barriers, including the classification of cannabis as a Schedule I substance, that impede the advancement of cannabis and cannabinoid research It is often difficult for researchers to gain access to the quantity, quality, and type of cannabis product necessary to address specific research questions on the health effects of cannabis use A diverse network of funders is needed to support cannabis and cannabinoid research that explores the beneficial and harmful health effects of cannabis use To develop conclusive evidence for the effects of cannabis use on short- and long-term health outcomes, improvements and standardization in research methodology including those used in controlled trials and observational studies are needed Over the past 20 years there have been substantial changes to the cannabis policy landscape.

    Despite this reported rapid rise in the use of cannabis, both for medical purposes and for recreational use, conclusive evidence regarding the short- and long-term health effects of cannabis use remains elusive. While a myriad of studies have examined cannabis use in all its various forms Calabria et al.

    Unlike other substances whose use may confer risk, such as alcohol or tobacco, no accepted standards for the safe use or appropriate doses are available to help guide individuals as they make choices regarding the issues of if, when, where, and how to use cannabis safely and, in regard to therapeutic uses, effectively Freeman et al.

    Moreover, studying the potential health impacts of cannabis presents its own set of unique challenges. Current challenges include the existence of certain regulations and policies that restrict access to cannabis products suited for research purposes e. Additionally, researchers are often unable to obtain the necessary quantity, quality, or type of cannabis product to address cutting-edge public health research questions.

    STUDY CHARGE Shifting public sentiment, conflicting and impeded scientific research, and legislative battles have fueled the debate about what, if any, harms or benefits can be attributed to the use of cannabis or its derivatives.

    In addition, the committee was asked to make recommendations for a research agenda that will identify the most critical research questions regarding the association of cannabis use with health outcomes both harms and benefits that can be answered in the short term i. Of note, throughout this report the committee has attempted to highlight research conclusions that affect certain populations e.

    The committee s full statement of task is presented in Box The resulting Committee on the Health Effects of Marijuana included experts in the areas of marijuana, addiction, oncology, cardiology, neurodevelopment, pulmonary, pediatric and adolescent health, immunology, toxicology, preclinical research, epidemiology, systematic review, and public health.

    See Appendix E for the biographical sketches of committee members. In conducting its work, the committee met six times from March through December In conjunction with two of those meetings, the committee held half-day public information-gathering sessions which allowed the committee to hear from study sponsors, experts, and other stakeholders. These discussions helped to inform the committee s deliberations.

    Sponsors of this report include federal, state, philanthropic and nongovernmental organizations. The committee should focus on questions and consequences with the. The study s committee was appointed to 1 analyze the potential hazards of marijuana use on user safety and health, 2 analyze data concerning the therapeutic value of marijuana, 3 assess the federal research programs, 4 identify new research directions, and 5 draw conclusions that would assist future policy decision making.

    The authoring committee concluded that there was evidence indicating that marijuana has a broad range of psychological and biological effects, some of which under certain conditions are harmful to human health, but there was a substantial lack of definitive evidence to characterize the seriousness of harm. The committee s major conclusion was that what little we know for certain about the effects of marijuana on human health and all that we have reason to suspect justifies serious national concern IOM, , p.

    The committee s major recommendation called for an intensification and more comprehensive research effort into the effects of marijuana on the health of the American people. In the White House Office of National Drug Control Policy contracted with the Institute of Medicine to conduct a scientific review of available literature to determine the potential health benefits and risks of marijuana and its constituent cannabinoids.

    The resulting report, Marijuana and Medicine IOM, , offered several conclusions and recommendations see Box on the effects of isolated cannabinoids, the efficacy of cannabinoid drugs, the influence of psychological effects on therapeutic effects, physiological risks, marijuana dependence and withdrawal, marijuana as a gateway drug, and the use of smoked marijuana.

    At this point, our knowledge about the biology of marijuana and cannabinoids allows us to make some general conclusions: Animal research demonstrates the potential for dependence, but this potential is observed under a narrower range of conditions than with benzodiazepines, opiates, cocaine, or nicotine. Withdrawal symptoms can be observed in animals but appear to be mild compared to opiates or benzodiazepines, such as diazepam Valium.

    The different cannabinoid receptor types found in the body appear to play different roles in normal human physiology. In addition, some effects of cannabinoids appear to be independent of those receptors.

    The variety of mechanisms through which cannabinoids can influence human physiology underlies the variety of potential therapeutic uses for drugs that might act selectively on different cannabinoid systems. Scientific data indicate the potential therapeutic value of cannabinoid drugs, primarily tetrahydrocannabinol THC , for pain relief, control of nausea and vomiting, and appetite stimulation; smoked marijuana, however, is a crude THC delivery system that also delivers harmful substances.

    The psychological effects of cannabinoids, such as anxiety reduction, sedation, and euphoria can influence their potential therapeutic value. Those effects are potentially undesirable for certain patients and situations and beneficial for others.

    In addition, psychological effects can complicate the interpretation of other aspects of the drug s effect. Numerous studies suggest that marijuana smoke is an important risk factor in the development of respiratory disease.

    A distinctive marijuana withdrawal syndrome has been identified, but it is mild and short lived. The syndrome includes restlessness, irritability, mild agitation, insomnia, sleep disturbance, nausea, and cramping. Present data on drug use progression neither support nor refute the suggestion that medical availability would increase drug abuse. However, this question is beyond the issues normally considered for medical uses of drugs and should not be a factor in evaluating the therapeutic potential of marijuana or cannabinoids.

    Research should continue into the physiological effects of synthetic and plant-derived cannabinoids and the natural function of cannabinoids found in the body. Because different cannabinoids appear to have different effects, cannabinoid research should include, but not be restricted to, effects attributable to THC alone. Clinical trials of cannabinoid drugs for symptom management should be conducted with the goal of developing rapid-onset, reliable, and safe delivery systems.

    Psychological effects of cannabinoids such as anxiety reduction and sedation, which can influence medical benefits, should be evaluated in clinical trials. Studies to define the individual health risks of smoking marijuana should be conducted, particularly among populations in which marijuana use is prevalent. Short-term use of smoked marijuana less than six months for patients with debilitating symptoms such as intractable pain or vomiting must meet the following conditions: IOM, The scientific literature on cannabis use has grown substantially since the publication of Marijuana and Medicine in The current committee conducted an extensive search of relevant databases, including Medline, Embase, the Cochrane Database of Systematic Reviews, and PsycINFO and initially retrieved more than 24, abstracts for articles published since the report that could potentially be relevant to this study.

    See Appendix B for details. The methodological approach taken by the committee to conduct this comprehensive literature review and meet the objectives outlined in the Statement of Task is detailed in Appendix B and briefly described here. Given the large scientific literature on cannabis, the breadth of the statement of task, and the time constraints of the study, the committee developed an approach that resulted in giving primacy to recently published systematic reviews since and high-quality primary research that studied one or more of eleven groups of health endpoints see Figure and Box For each health endpoint, systematic reviews were identified and assessed for quality using methods adapted from published criteria Whiting et al.

    The committee s conclusions are based on the findings from the most recently published systematic review and all relevant primary literature that was determined to be fair- and good-quality that was published after the most recent systematic review. Where no systematic review existed, the committee reviewed all relevant primary research from January 1, through August 1, Primary research was evaluated using global assessments of the quality of available studies guided by standard approaches and methodologies Cochrane Quality Assessment [Higgins et al.

    Any deviations from this approach are noted in the relevant chapters. For a comprehensive description of the committees approach to evaluating the available literature, please refer to Appendix B.

    Box below describes these categories and the general parameters for the types of evidence supporting each category. The committee used these weight-of-evidence categories in their conclusions. For this level of evidence, there are several supportive findings from good-quality studies with very few or no credible opposing findings. For this level of evidence, there are several supportive findings from good- to fair-quality studies with 3 Adverse Effects of Vaccines IOM, ; Treatment of Posttraumatic Stress Disorder: The search strategies and processes described above were developed and adopted by the committee in order to adequately address a broad statement of task in a limited timeframe, while adhering to the National Academies high standards for the quality and rigor of committee reports.

    First, the committee was not tasked with conducting multiple systematic reviews, which would have implied a lengthy and robust series of processes. The committee, however, adopted key features of that process: Furthermore, some very good research may not have been reviewed in this report because it did not directly address the specific health endpoint questions formulated by the committee.

    This policy was in part dictated by the time constraints available for crafting this report. Also, while basic research is in the end critical for understanding health outcome mechanisms and suggesting new and innovative interventions, it often can t explain the large number of null findings, the frequent variation among human study outcomes, the adverse clinical effects seen in some studies, nor the diversity in host susceptibility to cannabis exposure.

    Given the methodologic variation in the studies reviewed, as well as potential deficiencies in study design and execution, the committee focused its attention and energy on identifying high quality studies with the best information and lowest risk of bias as the way to ensure that report findings and conclusions were as informative and relevant as possible.

    In those instances where cannabis-disease associations seemed relatively secure and evidence-based, the committee believed that the findings would have clinical and public health importance even in the absence of supporting basic studies. Similarly, for those experimental studies where causation could be more explicitly determined, mostly in the area of therapeutics, these findings, if sufficiently robust and replicable, were deemed to stand on their own whether or not bolstered with mechanistic or biologically plausible underpinnings.

    Considerations of Observational Studies The vast majority of the systematic reviews, meta-analyses, and primary literature reviewed in Part II: Other Health Effects consists of observational studies.

    This is in contrast to the literature base in other fields such as therapeutics discussed in Part I: As such, it was not possible to restrict the literature reviews to those that synthesized evidence from randomized clinical trials RCTs. The methodology used for systematic reviews and metaanalysis originates in the synthesis of data from RCTs, where methodology is highly standardized and structured. The synthesis of observational studies presents some challenges that have not been fully met, arising, in part, out of the greater variety in study design.

    Exposure measurement is always an additional concern when evaluating comprehensive reviews of observational studies. Assessment of cannabis exposure is particularly challenging because of its illegal status in most settings and the reliance on self-report. Inherent difficulties in accurately assessing the exposure in terms of dose, specific type of cannabis product used, mode of intake, duration, frequency, and other variables result in the variability in definitions used to operationalize cannabis exposure.

    Additionally, observational studies often have to contend with confounders related to polysubstance use, which obscures the ability to answer. Moreover, in some cases, samples included different populations adolescents versus adults , cannabis use history i. Additional limitations include a lack of longitudinal assessments and small study cohorts. There is also a concern about the broad reporting standards across cannabis research fields.

    For example, several systematic reviews on cognition discussed in the report s Psychosocial chapter did not consistently describe the methods for scoring the evidence for each endpoint. That is, the reviews include scores of the strength and consistency of the evidence for each outcome, but provided less information about issues such as study design and statistical analyses. As a result, the committee found that the reviews did not include the conventional data generally found within quantitatively-based systematic examinations of a topic, or such as would be found in meta-analytic reviews.

    Reasons for this may include variations in study methodologies, instrumentation, populations, or research designs. Despite these special considerations regarding the use of systematic reviews, metaanalyses, and primary literature of observational studies, the committee determined that using recent good- or fair-quality systematic reviews was the most appropriate approach to adequately address the committee s broad statement of task and comprehensive, prioritized research questions while maintaining a high standard for quality and rigor.

    For additional information on these considerations, please see Box in Chapter Psychosocial and Box in Chapter Comparing Harms and Benefits of Cannabis Use Several health endpoints are discussed in multiple chapters of the report e. As such, it is important that the reader is aware that this report was not designed to reconcile the proposed harms and benefits of cannabis or cannabinoid use across the report s chapters. Key Definitions The terms marijuana and cannabis are often used interchangeably, particularly within the United States; however, these are two separate entities.

    Cannabis is a broad term that can be used to describe organic products e. These products exist in various forms and are used for a number of different purposes e. Given its broad potential, the allencompassing word cannabis has been adopted as the standard terminology within scientific and scholarly communities.

    The committee uses the term cannabis rather than marijuana throughout this report. The committee notes the existence of cannabimimetic agents often referred to as K2 or spice which are made up of dried plant matter sprayed with synthetic chemicals that mimic the effect of THC by interacting with cannabinoid receptors in the brain King, At the request of the study sponsors, non-therapeutic synthetic cannabinoids are not considered in this study.

    Introduction and Background Chapters 1 3 provides an overview of the origin, purpose, and organization of the report, as well as essential information on cannabis and cannabis-derived medications and products, and the history and current state of federal and state cannabis policy.

    In addition to this Introduction Chapter 1 , Chapter 2 Cannabis reviews the biology of cannabis and its constituent compounds, exploring the biochemistry of the marijuana plant, its derivatives, and the different routes of administration.

    Additionally this chapter provides an overview of synthetic versions of cannabis, including Food and Drug Administration approved medicinal synthetics and manufactured cannabis street drugs such as K2, spice.

    Prevalence of Use, Regulation, and Current Policy Landscape provides an overview of cannabis use in the United States and reviews policy related to cannabis legislation. Therapeutic Effects of Cannabis and Cannabinoids Chapter 4 discusses the health effects of cannabis and cannabinoids used for therapeutic purposes, in relation to the most commonly reported conditions for medical cannabis use in states where usage is legal , as well as the current qualifying ailments recognized by state medical marijuana programs.

    The vast majority of these studies examined the potential therapeutic effect of cannabinoids e. Most of the evidence reviewed in Part III derives from epidemiological research primarily focusing on smoked cannabis. It is of note that several of the prioritized health conditions discussed in Part III are also reviewed in Part II, albeit from the perspective of effects associated with using cannabis for primarily recreational, as opposed to therapeutic, purposes.

    Chapter 6 addresses cardiometabolic risks of cannabis use, including effects on acute myocardial infarction, stroke, and metabolic effects metabolic dysregulation, metabolic syndrome, prediabetes, and diabetes mellitus. Flavones are abundant in parsley and celery and possess unique anti-inflammatory properties in vitro and in animal models. However, their bioavailability and bioactivity depend in part on the conjugation of sugars and other functional groups to the flavone core.

    The effects of juice extraction, acidification, thermal processing, and endogenous enzymes on flavone glycoside profile and concentration in both parsley and celery were investigated.

    Flavones in steamed parsley and celery were predominantly malonyl apiosylglucoside conjugates, whereas those in fresh samples were primarily apiosylglucoside conjugates; this was apparently the result of endogenous malonyl esterases.

    Acidification and thermal processing of celery converted flavone apiosylglucosides to flavone glucosides, which may affect the intestinal absorption and metabolism of these compounds.

    Endogenous enzymes, heat, and pH affect flavone profiles in parsley Petroselinum crispum var. Isolation, purification, and characterization of AgUCGalT1, a galactosyltransferase involved in anthocyanin galactosylation in purple celery Apium graveolens L. This study showed that a galactosyltransferase, AgUCGalT1, is involved in anthocyanin galactosylation in purple celery.

    Celery is a well-known vegetable because of its rich nutrients, low calories, and medicinal values. Its petioles and leaf blades are the main organs acting as nutrient sources. This process enhances the stability and water solubility of anthocyanins. In the present study, LC-MS data indicated that abundant cyanidin-based anthocyanins accumulated in the petioles of purple celery 'Nanxuan liuhe purple celery '.

    A gene encoding UDP-galactose: The expression levels of AgUCGalT1 were positively correlated with the total anthocyanin contents in purple and non-purple celery varieties. Crude enzymes extracted from purple celery exhibited glycosylation ability, whereas crude enzymes obtained from non-purple celery did not have this ability.

    This work provided evidence as a basis for investigations on the function of AgUCGalT1 in anthocyanin glycosylation in purple celery. Apium graveolens extract influences mood and cognition in healthy mice. Apium graveolens is a food flavoring which possesses various health promoting effects. This study investigates the effect of a sub-acute administration of A. Cognition and depression was assessed by various models of behavior. The results indicated that the effect of the intake of A.

    Moreover, there was a decrease in immobility time in both the forced swimming and tail suspension tests. In addition, the A. Thus, our data have shown that the consumption of A. This result indicated an important role for A. Biological characterization and complete genomic sequence of Apium virus Y infecting celery.

    Apium virus Y ApVY isolated from celery plants Ce with ring spot and line pattern symptoms from a commercial field in California was characterized in this study. The experimental host range of the virus included 13 plant species in the families Apiaceae, Chenopodiaceae and Solanaceae, and almost First report of Tomato spotted wilt virus on celery in China.

    Celery Apium graveolens L. In June , irregular chlorotic blotches, necrotic flecks, concentric ring spots, and shrinking symptoms were observed on leaves of celery plants in fields of Tonghai County, Yunnan P Chemical composition, antioxidant activity and larvicidal effects of essential oil from leaves of Apium graveolens. The leaves of Apium graveolens were extracted and the essential oil composition, immunotoxicity effects, and antioxidant activity were studied.

    The analyses were conducted by gas chromatography and mass spectroscopy GC-MS , which revealed the essential oils of A. Twenty-eight components, representing The major components are 4-chloro-4,4-dimethyl 1-imidazolyl -valerophenone The leaf oil had significant toxic effects against the larvae of A. The essential oil from the A. The above data indicate that the major compounds may play an important role in the toxicity of essential oils and also as natural antioxidant.

    Keeping in view the adverse effects of chemical insecticides-based intervention measures, the eco-friendly and bio-degradable essential oil extracted from the seeds of celery , Apium graveolens were investigated for its efficacy against Ae. Larvicidal bioassay carried out with the seed oil against early fourth instars of Ae.

    The cidal effect of the celery seed oil augmented by 1. Interestingly, the seed oil did not cause immediate larval mortality, suggesting a delayed toxicity against the larval stage. The qualitative phytochemical analysis of the seed oil showed the presence of flavonoids, lactones, and terpenoids as the major constituents suggesting their probable role in the toxicity.

    Our results confirmed that celery seed essential oil can be used as an efficient larvicide and repellent against Ae. The identification of the bioactive components, their mode of action, and studying effects on non-target organisms and the.

    Subcellular localization of celery mannitol dehydrogenase. A cytosolic metabolic enzyme in nuclei. Mannitol is an important photoassimilate, as well as providing plants with resistance to salt and osmotic stress. Previous work has shown that expression of the celery Mtd gene is regulated by many factors, such as hexose sugars, salt and osmotic stress, and salicylic acid.

    Furthermore, MTD is present in cells of sink organs, phloem cells, and mannitol-grown suspension cultures. Immunogold localization and biochemical analyses presented here demonstrate that celery MTD is localized in the cytosol and nuclei.

    Although the cellular density of MTD varies among different cell types, densities of nuclear and cytosolic MTD in a given cell are approximately equal. Biochemical analyses of nuclear extracts from mannitol-grown cultured cells confirmed that the nuclear-localized MTD is enzymatically active. The function s of nuclear-localized MTD is unknown.

    Clinical reactivity of celery cultivars in allergic patients: Role of Api g 1. Celery stalks and celeriac roots are often ingredients in convenient food products like spice blends and soups. In this study, we examined the allergenicity of distinct celeriac cultivars.

    Sixteen celery -allergic patients were identified using a double-blind, placebo-controlled food challenge. Ten different celeriac cultivars were used for skin prick testing in the patients. Two cultivars were further applied for oral food challenges; their protein composition was analysed by immunoblotting, and contents of major allergen Api g 1 were quantified. From the 10 investigated celeriac cultivars, two cultivars elicited significantly different skin reactivity "Anita": The effect of excess macronutrients in the root environment on mannitol and sucrose metabolism was investigated in celery Apium graveolens L.

    Plant growth was inhibited progressively as macronutrient concentration in the media, as measured by electrical conductivity E. Plants grown for 35 d at higher E. Macronutrient concentrations of leaves, roots, and petioles were not affected by the imposed stress, indicating that the macronutrient stress resulted in a water-deficit stress response rather than a salt-specific response.

    Mannitol accumulated in sink tissues and was accompanied by a drastic decrease in activity of mannitoloxidoreductase. Sucrose concentration and activities of sucrose-metabolizing enzymes in sink tissues were not affected by the macronutrient stress. Mature leaves exhibited increased concentrations of both mannitol and sucrose, together with increased activity of mannosephosphate reductase and sucrose phosphate synthase, in response to macronutrient stress.

    Thus, mannitol accumulation in osmotically stressed celery is regulated by diminished catabolism in sink tissues and increased capacity for mannitol biosynthesis in source leaves.

    Allergenic relevance of nonspecific lipid transfer proteins 2: Identification and characterization of Api g 6 from celery tuber as representative of a novel IgE-binding protein family. Apium graveolens represents a relevant food allergen source linked with severe systemic reactions. A low molecular weight protein exclusively present in celery tuber was purified and designated Api g 6.

    Api g 6 is monomeric in solution with a molecular mass of Da. Endolysosomal degradation demonstrated low susceptibility and the presence of a dominant peptide cluster at the C-terminus. Thirty-eight percent of A. No correlation in IgE binding and limited cross-reactivity was observed with Api g 2 and Art v 3, nsLTP1 from celery stalks and mugwort pollen.

    Api g 6, a novel nsLTP2 from celery tuber represents the first well-characterized allergen in this protein family. Despite similar structural and physicochemical features as nsLTP1, immunological properties of Api g 6 are distinct which warrants its inclusion in molecule-based diagnosis of A.

    This transporter was successfully expressed in two different heterologous expression systems: When expressed in tobacco, AgMaT2 decreased the sensitivity to the mannitol-secreting pathogenic fungi Alternaria longipes, suggesting a role for polyol transporters in defense mechanisms.

    In celery , in situ hybridization showed that AgMaT2 was expressed in the phloem of leaflets, petioles from young and mature leaves, floral stems, and roots. In the phloem of petioles and leaflets, AgMaT2, as localized with specific antibodies, was present in the plasma membrane of three ontologically related cell types: These new data are discussed in relation to the physiological role of AgMaT2 in regulating mannitol fluxes in celery petioles.

    Little information exists concerning the biochemical route of mannitol catabolism in higher plant cells. In this study, the role of a recently discovered mannitol 1-oxidoreductase MDH in mannitol catabolism was investigated.

    Suspension cultures of celery Apium graveolens L. Cell cultures grown on any of the three carbon sources did not differ in relative growth rate, as measured by packed cell volume, but differed drastically in internal carbohydrate concentration. Mannitol-grown cells contained high concentrations of mannitol and extremely low concentrations of sucrose, fructose, glucose, and mannose.

    Sucrose-grown cells had high concentrations of sucrose early in the growth cycle and contained a substantial hexose pool. Mannose-grown cells had a high mannose concentration early in the cycle, which decreased during the growth cycle, whereas their internal sucrose concentrations remained relatively constant during the entire growth cycle.

    Throughout the growth cycle, MDH activity was 2- to 4-fold higher in mannitol-grown cells compared with sucrose- or mannose-grown cells, which did not contain detectable levels of mannitol, indicating that MDH functions pre-dominantly in an oxidative capacity in situ.

    The MDH activity observed in celery cells was 3-fold higher than the minimum amount required to account for the observed rate of mannitol utilization from the media. Cultures transferred from mannitol to mannose underwent a decrease in MDH activity over a period of days, and transfer from mannose to mannitol resulted in an increase in MDH activity.

    These data provide strong evidence that MDH plays an important role in mannitol utilization in celery suspension cultures. This study aims to identify the essential antioxidant compounds present in parsley Petroselinum sativum and celery Apium graveolens leaves belonging to the Umbelliferae Apiaceae family, and in stinging nettle Urtica dioica belonging to Urticaceae family, to measure the total antioxidant capacity TAC of these compounds with CUPRAC cupric ion reducing antioxidant capacity and ABTS spectrophotometric methods, and to correlate the TAC with high performance liquid chromatography HPLC findings.

    The individual antioxidant constituents of plant extracts were identified and quantified by HPLC on a C18 column using a modified mobile phase of gradient elution comprised of MeOH Celery -based topical repellents as a potential natural alternative for personal protection against mosquitoes. Celery -based products were investigated for chemical composition, skin irritation, and mosquito repellency in comparison to commercial repellents and the standard chemical, N,N-diethylmethylbenzamide DEET , with a goal to develop a natural alternative to synthetic repellents for protection against mosquitoes.

    Chemical identification by gas chromatography coupled with mass spectrometry discovered that the major constituents of Apium graveolens hexane extract AHE were 3-n-butyl-tetrahydrophthalide Laboratory investigated repellent against female Aedes aegypti mosquitoes demonstrated that G10 formula, the best AHE-developed product, provided remarkable repellency with a median protection time of 4.

    According to significantly promising results, including highly effective repellency and no potential skin irritation or other side effects, the G10 formula is a worthwhile product that has the promise of being developed for commercialized registration. This developed AHE product could be an acceptable and affordable alternative to conventional synthetic chemicals in preventing mosquito bites, and in turn, helping to interrupt mosquito-borne disease transmission.

    Sensitization prevalence, antibody cross-reactivity and immunogenic peptide profile of Api g 2, the non-specific lipid transfer protein 1 of celery.

    Celery Apium graveolens represents a relevant allergen source that can elicit severe reactions in the adult population. To investigate the sensitization prevalence and cross-reactivity of Api g 2 from celery stalks in a Mediterranean population and in a mouse model.

    Clinical data of 32 selected patients with reactivity to LTP under investigation were evaluated. Simulated endolysosomal digestion was performed using microsomes obtained from human DCs. IgE testing showed a sensitization prevalence of Considerable IgE cross-reactivity was observed between Api g 2, Art v 3, and Pru p 3 with varying inhibition degrees of individual patients' sera. Simulating LTP mono-sensitization in a mouse model showed development of more congruent antibody specificities between Api g 2 and Art v 3.

    Notably, biologically relevant murine IgE cross-reactivity was restricted to the latter and diverse from Pru p 3 epitopes. Endolysosomal processing of LTP showed generation of similar clusters, which presumably represent T-cell peptides. Api g 2 represents a relevant celery stalk allergen in the LTP-sensitized population.

    The molecule displays common B cell epitopes and endolysosomal peptides that encompass T cell epitopes with pollen and plant-food derived LTP. Background Celery Apium graveolens represents a relevant allergen source that can elicit severe reactions in the adult population.

    Results IgE testing showed a sensitization prevalence of Conclusions Api g 2 represents a relevant celery stalk allergen in the LTP-sensitized population. Bloomin' Color Celery Prints. Describes a second and third grade art activity in which students used celery cores to create pictures in the style of Georgia O'Keefe.

    Explains that the students learned about O'Keefe's artwork and describes how the students created their prints. Spice allergy in celery -sensitive patients. Positive SCT to aniseed, fennel, coriander and cumin--all from the same botanical family Apiaceae as celery --were observed in more than 24 patients.

    Spices from unrelated families red pepper, white pepper, ginger, nutmeg, cinnamon elicited positive immediate skin test reactions only in three of 11 patients. Specific serum IgE to spices determined in 41 patients with positive RAST to celery up to class 3 were seen especially in patients with celery -mugwort or celery -birch-mugwort association, and concerned various botanical families. Celery -birch association pattern was linked to positive reactions RAST classes to spices from the Apiaceae family only.

    Capsicum Capsicum frutescens L. Caraway Carum carvi L. Caraway, black black cumin Celery seed Apium graveolens L. Paprika Capsicum annuum L. Parsley Petroselinum crispum Mill. Perfluoroalkyl acid distribution in various plant compartments of edible crops grown in biosolids-amended soils. Crop uptake of perfluoroalkyl acids PFAAs from biosolids-amended soil has been identified as a potential pathway for PFAA entry into the terrestrial food chain. The effect of mechanical perturbation and the involvement of ethylene in petiole pithiness in celery.

    Mechanical perturbation MP applied to celery Appium graveolens L. Florida leaf petioles or ethephon application to the plant did not induce thigmomorphogenesis inhibition of elongation and increase in thickness of the petiole.

    However, the two treatments did cause the parenchyma breakdown which leads to pithiness or increased natural pithiness, mainly at the base of the petiole. Nevertheless, MP but not ethephon decreased the severity of drought-stress or GA3-induced pithiness. Although MP stimulates ethylene production, mainly at the middle part of the petiole, it seems that the protection by MP of the petiole may not be directly mediated by ethylene production.

    The exposure of the plant to drought stress brought about an increase in ethylene evolution. Upon reirrigating the plants, the first steps of pithiness were accompanied by a sharp decline in ethylene production.

    This decrease might be due to membrane disruption. The increase in ethylene production during drought stress may be one of the events which stimulate pithiness of the celery leaf petiole. Parasaccharibacter apium , gen. Apidae Resistance to Nosema. The honey bee, Apis mellifera L. The bacterial community that occupies the adult worker gut contains a core group of approximately seven taxa, while the hive environment contains its own distribution of bacteria that is in many ways distinct from the gut.

    Parasaccharibacter apium increases larval survival under laboratory conditions. To determine if this benefit is extended to colonies in the field, we tested if P.

    Parasaccharibacter apium survived in supplemental diet and was readily consumed by bees. It was distributed throughout the hive under field conditions, moving from the pollen patty to hive larvae. Our data suggest that P. AgFNS overexpression increase apigenin and decrease anthocyanins in petioles of transgenic celery. Apigenin and anthocyanin biosyntheses share common precursors in plants. Flavone synthase FNS converts naringenin into apigenin in higher plants.

    Celery is an important edible and medical vegetable crop that contains apigenin in its tissues. However, the effect of high AgFNS gene expression on the apigenin and anthocyanins contents of purple celery remains to be elucidated.

    In this study, the AgFNS gene was cloned from purple celery 'Nanxuan liuhe purple celery ' and overexpressed in this purple celery to determine its influence on anthocyanins and apigenin contents. Results showed that the AgFNS gene was bp, which encodes amino acid residues. In AgFNS transgenic celery , the anthocyanins content in petioles was lower than that wild-type celery plants.

    Apigenin content increased in the petioles of AgFNS transgenic celery. This work provides basic knowledge about the function of the AgFNS gene in the anthocyanin and apigenin biosyntheses of celery. Elasticity of carrot, celery , and plasticware. This article presents several simple cantilever-based experiments using common household items celery , carrot, and a plastic spoon that are appropriate for introductory undergraduate laboratories or independent student projects.

    By applying Hooke's law and Euler beam theory, students are able to determine Young's modulus, fracture stress, yield stress, strain energy, and sound speed of these apparently disparate materials. In addition, a cellular foam elastic model is introduced—applicable to biologic materials as well as an essential component in the development of advanced engineering composites—that provides a mechanism to determine Young's modulus of the cell wall material found in celery and carrot.

    These experiments are designed to promote exploration of the similarities and differences between common inorganic and organic materials, fill a void in the typical undergraduate curriculum, and provide a foundation for more advanced material science pursuits within biology, botany, and food science as well as physics and engineering.

    Draft genome sequences of four parasaccharibacter apium strains isolated from honey bees. Parasaccharibacter apium is a newly described bacterium of honey bees that exhibits multiple ecological strategies in their host, from beneficial to pathogenic. Using niche-specific 16S rRNA gene sequences and bacterial genomes, we describe the ecology of this bacterium and its relationship to other Y-tube olfactometer and net cages experiments were used to investigate the repellent effects of different celery varieties in biotype Q of sweetpotato whitefly, Bemisia tabaci Gennadius Hemiptera: Aleyrodidae , on cucumber, Cucumis sativus L.

    Y-tube olfactometer tests showed that whiteflies have strong repellent behavior to different celery varieties. Intercropping different celery varieties with cucumbers had significant repellent effects and oviposition deterrent effects in whiteflies. Results obtained demonstrated that the Western Europe celery varieties, Juventus and Ventura, and the Chinese celery variety, Jinnan, had good repellent efficacy against the whitefly.

    In Western Europe celery varieties, D-limonene was the main volatile component for the repellent effects in B. For Permissions, please email: Ruta graveolens Extracts and Metabolites against Spodoptera frugiperda.

    The biological activity of Ruta graveolens leaf tissue extracts obtained with different solvents ethyl acetate, ethanol, and water and metabolites psoralen, 2- undecanone and rutin against Spodoptera frugiperda was evaluated.

    Additionally, psoralen metabolite showed a high mortality as cypermethrin. Metabolite quantification in extracts shows the presence of 2-undecanone We suggest that these concentrations of 2-undecanone and psoralen in R.

    Effects of Anethum graveolens L. The effects of Anethum graveolens seed extract on fertility of male rats were investigated. Male Wistar rats were divided into five groups according to the treatment they received during 42 days: Sperm count and motility and testosterone concentration were measured. Sections of the testes, epididymis, and seminal vesicles were stained with peroxidase-conjugated lectins of Ulex europaeus agglutinin, peanut agglutinin, Dolichos biflorus agglutinin, soy bean agglutinin and concanavalin A.

    The treated male rats were mated with females and the crown-rump lengths and weights of their newborn pups were measured. No significant differences in sperm count, sperm motility or testosterone concentration were observed in the experimental groups. However, female rats did not become pregnant after mating with rats given the high dose of the ethanol extract. The distribution of terminal sugars on the epithelial surface of the reproductive structures decreased in the experimental groups.

    Anethum graveolens extract decreased fertility rate by modifying some terminal sugars on the cell surface of male reproductive organs involved in sperm maturation, capacitation and oocyte recognition. Antioxidant activities of celery and parsley juices in rats treated with doxorubicin. We have examined the influence of diluted pure celery and parsley leaf and root juices and their combinations with doxorubicin on the antioxidant status [as measured by the content of reduced glutathione GSH and ferric reducing antioxidant power FRAP ] in liver homogenate and hemolysate and on the contents of cytochrome P in liver homogenate.

    It was found that doxorubicin significantly decreased the content of reduced glutathione and the total antioxidative status FRAP in liver homogenate and hemolysate, while celery and parsley juices alone and in combination with doxorubicin had different actions. Doxorubicin and celery juice had no effect on content of cytochrome P However, in combination with doxorubicin, parsley root juice significant increased, and parsley leaves juice decreased the cytochrome P content compared to doxorubicin treated animals.

    Only parsley root juice significantly increased the content of cytochrome P Effects of food formulation and thermal processing on flavones in celery and chamomile. Flavones isolated from celery varied in their stability and susceptibility to deglycosylation during thermal processing at pH 3, 5, or 7. Apigenin, luteolin, and chrysoeriol were most stable at pH 3 but progressively degraded at pH 5 or 7.

    Chamomile and celery were used to test the effects of glycosidase-rich foods and thermal processing on the stability of flavone glycosides. Apigenin 7-O-glucoside in chamomile extract was readily converted to apigenin aglycone after combination with almond, flax seed, or chickpea flour.

    Thus, combinations of acid hydrolysis and glycosidase enzymes in almond and flax seed were most effective for developing a flavone-rich, high aglycone food ingredient from celery. Races of the celery pathogen Fusarium oxysporum f. Fusarium oxysporum species complex FOSC isolates were obtained from celery with symptoms of Fusarium yellows between and primarily in California.

    Virulence tests and a two-gene dataset from isolates indicated that virulent isolates collected before were a highly clonal populatio Hospital-acquired listeriosis outbreak caused by contaminated diced celery --Texas, Listeria monocytogenes causes often-fatal infections affecting mainly immunocompromised persons.

    Sources of hospital-acquired listeriosis outbreaks can be difficult to identify. We investigated a listeriosis outbreak spanning 7 months and involving 5 hospitals. Outbreak-related cases were identified by pulsed-field gel electrophoresis PFGE and confirmed by multiple-locus variable-number tandem-repeat analysis MLVA. We conducted patient interviews, medical records reviews, and hospital food source evaluations. Food and environmental specimens were collected at a hospital hospital A where 6 patients had been admitted before listeriosis onset; these specimens were tested by culture, polymerase chain reaction PCR , and PFGE.

    We collected and tested food and environmental samples at the implicated processing facility. All patients had been admitted to or visited an acute-care hospital during their possible incubation periods.

    The outbreak strain of L. PCR testing detected Listeria in only 3 of 10 environmental and food samples from which it was isolated by culturing. The facility was closed, products were recalled, and the outbreak ended. Contaminated diced celery caused a baffling, lengthy outbreak of hospital-acquired listeriosis.

    PCR testing often failed to detect the pathogen, suggesting its reliability should be further evaluated. Listeriosis risk should be considered in fresh produce selections for immunocompromised patients. The chemical composition and in vitro antimicrobial activities of Dittrichia graveolens L.

    Greuter essential oil was studied. The major components were borneol Multivariate analysis showed that the compounds borneol and bornyl acetate exerted the greatest influence on the spatial differences in the composition of the reported oils.

    The antimicrobial activity against five bacterial and one fungal strain was determined using a disk-diffusion assay. The studied essential oil was active only against Gram-positive bacteria. Races of the Celery Pathogen Fusarium oxysporum f. Virulence tests and a two-gene dataset from isolates indicated that virulent isolates collected before were a highly clonal population of F.

    In , new highly virulent clonal isolates, designated race 4, were discovered in production fields in Camarillo, California. Long-read Illumina data were used to analyze 16 isolates: Analyses of a gene dataset comprising 38 kb indicated that F.

    Next generation sequences were used to develop PCR primers that allow rapid diagnosis of races 2 and 4 in planta. Federal Register , , , , Based on the findings of three pest risk analyses, which we made In the celery -mugwort-birch-spice syndrome, a significant proportion of IgE is directed against high molecular weight HMW glycoproteins, including the celery allergen Api g 5.

    BIP3, a monoclonal antibody originally raised against birch pollen, recognizes HMW allergens in birch and mugwort pollens, celery , and Apiaceae spices. Our aim was to generate mimotopes using BIP3 for immunization against the HMW allergens relevant in the celery -mugwort-birch-spice cross reactivity syndrome. Mimotopes were selected from a random-peptide display library by BIP3 and applied in IgE inhibition assays.

    Mouse immune sera were tested for IgG binding to blotted birch pollen extract and used for inhibiting patients' IgE binding. The mimotopes characterized in this study mimic the epitope of BIP3 relevant for Api g 5, one of the cross-reactive HMW allergens relevant in the celery -mugwort-birch-spice syndrome. BIP3 mimotopes may be used in the future for hyposensitization in this clinical syndrome by virtue of good and specific immunogenicity.

    Antifungal mechanism of the combination of Cinnamomum verum and Pelargonium graveolens essential oils with fluconazole against pathogenic Candida strains.

    The present study aimed to investigate the anti-Candida activity of ten essential oils EOs and to evaluate their potential synergism with conventional drugs. The effect on secreted aspartic protease SAP activity and the mechanism of action were also explored. The antifungal properties of essential oils were investigated using standard micro-broth dilution assay. Only Cinnamomum verum, Thymus capitatus, Syzygium aromaticum, and Pelargonium graveolens exhibited a broad spectrum of activity against a variety of pathogenic Candida strains.

    Chemical composition of active essential oils was performed by gas chromatography-mass spectrometry GC-MS. Synergistic effect was observed with the combinations C.

    Investigation of the mechanism of action revealed that C. A total inhibition was observed for the combination C. An increase of MIC values of P.

    Furthermore, the combination with fluconazole may affect ergosterol biosynthesis and disturb fatty acid homeostasis in C. The combination of P. To our knowledge, this is the first report underlying the mechanism of action and the inhibitory effect of SAP activity of essential oils in synergy with fluconazole. Naturally occurring phytochemicals C.

    Pratylenchus penetrans was obtained from Premier strawberry in Norfolk County and the Niagara Peninsula and from celery in the latter area. Host affected the dimensions of P. The presence of three lip annules was consistent in the seven populations studied, although in some specimens one of the annules did not entirely encompass the head. Crenations around the tail tip of females of P. Not all of the morphological characters were proportional in size to length of the females of P.

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