Are there post-harvest processing techniques that enhance the final product?

Yes, there are several post-harvest processing techniques that can enhance the final quality of cannabis products. These techniques focus on refining the raw cannabis material to improve characteristics such as potency, flavor, and overall appeal. Here are some post-harvest processing techniques commonly used in the cannabis industry:

  1. Trimming and Bucking:
    • Properly trimming and bucking the harvested cannabis flowers involve removing excess leaves and stems. This not only improves the visual appeal of the buds but also enhances the efficiency of subsequent processing steps.
  2. Cannabis Extraction:
    • Cannabis extraction methods, such as solvent-based extraction (using ethanol, CO2, or hydrocarbons) or solventless extraction (such as rosin pressing), can be employed to isolate cannabinoids and terpenes from the plant material. This is commonly used to produce concentrates, oils, and tinctures with higher cannabinoid concentrations.
  3. Decarboxylation:
    • Decarboxylation is a process that involves heating cannabis to convert non-psychoactive cannabinoids (such as THCA and CBDA) into their active forms (THC and CBD). This step is crucial for making edibles, tinctures, and other products where the cannabinoids need to be in their activated state.
  4. Infusions:
    • Cannabis-infused products, such as edibles, beverages, and topicals, involve incorporating cannabis extracts or decarboxylated cannabis material into various mediums. This allows for precise dosing and diverse consumption methods.
  5. Terpene Preservation:
    • Some post-harvest processing techniques focus on preserving and enhancing the terpene profile of cannabis. For example, cold extraction methods, like live resin extraction, aim to capture and retain the full spectrum of terpenes found in fresh, uncured cannabis.
  6. Microbial and Contaminant Testing:
    • Rigorous testing for microbial contaminants, pesticides, heavy metals, and other impurities is a crucial post-harvest step to ensure the safety and quality of the final cannabis products.
  7. Quality Control and Testing:
    • Regular quality control measures involve testing for cannabinoid and terpene profiles, ensuring accurate labeling of products,dry cannabis and monitoring for any changes in quality over time.
  8. Packaging and Storage:
    • Proper packaging is essential to maintain the freshness, potency, and quality of cannabis products. Packaging should be airtight, light-resistant, and compliant with local regulations. Proper storage conditions, including temperature and humidity control, also contribute to preserving the quality of the final product.
  9. Product Formulation:
    • In the case of infused products, careful formulation can enhance the overall experience for the consumer. Balancing cannabinoids, terpenes, and other ingredients can create products with specific effects, flavors, and aromas.
  10. Product Innovation:
    • Continuous research and development lead to innovative post-harvest processing techniques and product formulations. This includes exploring new extraction methods, delivery systems, and product categories.

Each of these post-harvest processing techniques plays a role in creating a diverse range of cannabis products that cater to different consumer preferences and needs. The specific techniques employed depend on the intended end product and the goals of the cultivator or processor.

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Can you provide insights into the lifecycle of a cannabis plant in an indoor commercial cultivation facility, from seed to harvest?

Certainly! The lifecycle of a cannabis plant in an indoor commercial cultivation facility typically goes through several stages: germination, seedling, vegetative, flowering, and harvesting. Here’s an overview of each stage:

  1. Germination:
    • Duration: 1-7 days.
    • Conditions: Seeds are placed in a germination medium with warmth, moisture, and darkness. Once the seed cracks open, a young root (taproot) emerges.
    • Transfer: Once the taproot is a few centimeters long, the seedling is carefully transferred to the growing medium (soil, coco coir, or hydroponics) to continue growth.
  2. Seedling Stage:
    • Duration: 2-3 weeks.
    • Conditions: Seedlings need high humidity, moderate light, and a gentle breeze for strengthening stems.
    • Light Cycle: Typically, seedlings are kept under 18-24 hours of light per day.
    • Nutrients: A mild nutrient solution is introduced as the seedling develops.
  3. Vegetative Stage:
    • Duration: 4-8 weeks or longer (depending on desired plant size).
    • Conditions: Cannabis plants focus on leaf and stem growth. They require a balanced nutrient regimen, controlled temperature, and humidity.
    • Light Cycle: For vigorous growth, a light cycle of 18-24 hours of light per day is maintained.
    • Training: Some growers use techniques like topping, pruning,pipp grow racks or low-stress training to shape the plants.
  4. Pre-Flowering Transition:
    • Duration: 1-2 weeks.
    • Conditions: Light cycle is adjusted to 12 hours of light and 12 hours of darkness to induce flowering.
    • Sexing: Female and male plants become distinguishable. In commercial operations, male plants are typically removed to prevent pollination of female flowers.
  5. Flowering Stage:
    • Duration: 7-14 weeks (strain-dependent).
    • Conditions: Plants produce buds (flowers) in response to the change in light cycle. Temperature, humidity, and nutrient levels are carefully managed.
    • Light Cycle: Maintained at 12 hours of light and 12 hours of darkness.
    • Nutrient Changes: Adjustments are made to nutrient ratios to support bud development.
    • Pest and Disease Management: Vigilant monitoring for pests and diseases is crucial during the flowering stage.
  6. Ripening and Harvest:
    • Duration: Final weeks of flowering.
    • Conditions: As the buds ripen, some strains may show changes in color, and trichomes become more amber. The plant’s nutrient intake is usually reduced during the final weeks.
    • Harvest: Plants are harvested when the buds have reached their peak potency and maturity. Harvesting involves cutting the entire plant, after which it is trimmed, dried, and cured.
  7. Drying and Curing:
    • Duration: 1-3 weeks (drying), several weeks to months (curing).
    • Drying: Buds are hung in a controlled environment to dry slowly. Proper drying prevents mold and enhances flavor.
    • Curing: Buds are stored in airtight containers to cure. This process enhances the flavor, aroma, and smoothness of the final product.
  8. Post-Harvest Processing:
    • Trimming: Buds are trimmed to remove excess leaves and improve aesthetics.
    • Testing: Samples may be tested for potency, terpene profiles, and contaminants.
    • Packaging: Final products are weighed, packaged, and labeled for distribution.

Throughout the entire lifecycle, careful monitoring of environmental conditions, pest control, nutrient management, and adherence to regulations are critical for a successful and compliant commercial cannabis cultivation operation.

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What security measures are essential for safeguarding an indoor commercial cannabis cultivation operation?

Newton et al. found that positive reinforcement through pleasureseeking behaviors was the primary motivator for most METH+ individuals, however, pain avoidance was also an important, non-overlapping factor. Thus, people may engage in methamphetamine use and subsequent riskier sexual behaviors as coping methods to avoid the emotional pain associated with loneliness and/or rejection, particularly if they have poor inhibitory control. Torres and Gore-Felton proposed this type of paradigm, which they called the Loneliness and Sexual Risk Model , that posits that the relationship between loneliness and sexual risk behavior is mediated by substance use and impulsive behavior. In our sample, individuals who experienced potentially problematic levels of loneliness reported significantly higher impulsivity/disinhibition than those who reported loneliness within normal limits across both METH−/+ groups, providing initial support for the LSRM model. However, in separate multi-variable regression models with beliefs and intentions to practice safer sex as outcome variables, the interaction between potentially problematic loneliness and methamphetamine status was statistically significant while impulsivity/disinhibition was not, suggesting that an individual who is methamphetamine dependent and lonely has worse beliefs and intentions to practice safer sex than their lonely METH− counterparts, regardless of their impulsivity/disinhibition level. Polysubstance use is an important aspect in methamphetamine dependence that was also considered in our cohorts . Of the three nonmethamphetamine lifetime substance use disorders that were examined , there was a significant association between loneliness with lifetime opioid use disorder. This association was found in only the methamphetamine dependent group, but occurred in the opposite direction than what was to be expected. However, given the relatively low prevalence of positive lifetime opioid use disorder in the whole sample,grow glide rack as well as within the methamphetamine dependent group , these findings may have been driven by a skewed sample.

Even when DSM-IV substance use disorder criteria were not considered, the number of individuals reporting any lifetime opioid use was low , again suggesting a skewed, non-representative sample of opioid users. By contrast, alcohol and cannabis were the substances that had the most number of people reporting any lifetime use . Post-hoc analyses found that both cumulative densities of alcohol and cannabis were significantly higher in the METH+ than the METH− group, suggesting that methamphetamine dependent individuals consumed larger quantities of these substances over shorter periods of time relative to individuals who were not methamphetamine dependent. However, neither alcohol density or cannabis density predicted loneliness, beliefs about practicing safer sex, or intentions to practice safer sex. Rather, methamphetamine dependence consistently predicted these variables above and beyond alcohol use, cannabis use, and other covariates such as age and HIV status, indicating its robust effects on both loneliness and the potential of engaging in riskier sexual behaviors. Our study did not find a link between poorer norms and intentions to practice safer sex among people with HIV who had undetectable viral loads, suggesting that they are equally as concerned about taking part in unsafe sex compared to people with HIV who were detectable for the virus. However, people with HIV are more likely to engage in riskier sexual behaviors in the past 6 months and prior to the past 6 months than HIV− individuals. We did not find an association between loneliness and self-reported, past sexual risk behaviors in the whole sample. However, given the cross-sectional nature of our study, it may be inappropriate to link current feelings of loneliness with past risky sexual behaviors. Rather, it may be more informative to investigate the factors that have been shown to be significantly associated with future sexual risk behaviors in the literature such as attitudes, personal norms, and intentions of engaging in safer sex . Indeed, our data confirmed that beliefs and intentions of engaging in safer sex were significantly associated with lower current sexual risk. Findings from this study have potential, important public health implications related to identifying and treating individuals who may be at-risk for engaging in HIV-transmission risk behaviors. Prior work has shown that methamphetamine use is a predictor of riskier sexual intentions and riskier sexual practices . However, changing drug use behavior may not be a realistic goal, or sufficient target in sexual risk reduction interventions; rather, addressing maladaptive coping due to emotional distress may be more successful .

Thus, identification of lonely individuals who are dependent on methamphetamine, and whom we found were more likely to report poorer personal norms and intentions to engage in safer sex practices, allows us to capture an at-risk group and consider alternative approaches that could be integrated into substance use treatment programs to reduce riskier sexual behaviors. Increased opportunities for social contact , one-on-one or group interventions based on mutual aid, enhanced social support , improving social skills , and addressing maladaptive social cognitions may all be important target areas to reduce the prevalence of loneliness in this at-risk population. Though this study provides preliminary evidence for the importance of identifying those with high feelings of loneliness, and its implications on future attitudes and beliefs about engaging in potentially risky behaviors, it is not without limitations. First, our data are cross-sectional, so we cannot assume directionality or claim that loneliness influences riskier personal norms and intentions to practice safer sex. It is entirely possible that a bidirectional relationship may exist. Our selection criteria were developed such that they focused on studying methamphetamine effects while minimizing the potential confounding effects of other substances. By doing so, generalizability of findings to poly-substance users becomes more limited. Similarly, recruitment from HIV clinics may introduce some confounding factors that may not have been fully accounted for by controlling for HIV status, thus potentially limiting generalizability to non-HIV populations. Though results from our recruited sample suggest that the relationship between loneliness and riskier beliefs and intentions about practicing safer sex are theoretically relevant to many kinds of individuals , future work should specifically examine whether there are particularly risky periods of methamphetamine addiction in which loneliness more strongly influences riskier beliefs and intentions about safer sex practices, which could be investigated by evaluating the specific recruitment sources . Furthermore, given the discrepancy between average age of first methamphetamine use relative to the average age in the METH+ sample , a potential survival bias may exist, which may skew findings. Of note, the proportion of individuals with HIV in the METH− and METH+ groups were nearly identical , suggesting that if survival bias is present, it is more likely specific to methamphetamine-related characteristics rather than HIV-related selective survival bias. Our current design also did not query further into the dimensions of loneliness that an individual may be encountering . Additionally, although our sample was large enough to see robust effects, it was relatively small, especially considering the number of potentially important covariates.

This research would ideally be replicated in a larger sample of METH− and METH+ individuals. Further work should also investigate how loneliness may differentially influence attitudes about sex among individuals with different partner statuses , as well as among sexual and gender minorities,grow rack greenhouse especially given important considerations raised by Bryant et al. and Race et al. regarding the role of controlled drug use and safer sex in facilitating community, building identity, and responding to marginalization in such minority groups. Despite these limitations, our findings highlight the high prevalence of loneliness among individuals with methamphetamine use disorder, and explores the potential impact of loneliness among those who are typically at-risk of engaging in HIV-related risk behaviors by finding a unique association between loneliness and riskier beliefs and intentions regarding the practice safer sex. These results suggest potential areas of intervention, including promotion of adaptive beliefs and intentions to engage in safer behaviors. In addition, findings from this study are highly relevant during the current COVID-19 pandemic, as individuals have been required to engage in unprecedented social distancing and may be experiencing the effects of prolonged social isolation. Consequently, feelings of loneliness and mental health problems could be elevated , and may contribute to engagement in riskier behaviors such as practicing poorer safer sex in order to feel social connection, pleasure, and avoid emotional pain. In an era when antiretroviral therapy is recommended for all people living with HIV regardless of CD4+ T-cell count, best clinical practices and high-impact interventions emphasize retention in care and ART adherence. Achieving and maintaining viral suppression is crucial to optimizing health outcomes and substantially reducing the risk of onward HIV transmission. At the same time, consistent evidence indicates that economic disparity is a driving force of the HIV epidemic and undermines these efforts in regions throughout the world, including Africa, Asia, Europe and North America. Poverty is a major barrier to receiving care and achieving success at each step of the HIV care continuum for PLWH in countries across the spectrum of income and resource availability. Even in well-resourced settings, in which infrastructure exists to provide facilities, clinicians, laboratory, and supply chain management for various types of health care, a number of factors associated with poverty act as barriers to care. Recognition of such barriers has led to specific models for understanding health services use, including the Behavioral Model for Vulnerable Populations. This model posits that, in addition to factors limiting health services use in the general population, such as age, income and health insurance, there are factors uniquely common in vulnerable populations that act as additional barriers to care, including violence, incarceration, substance use and homelessness.

Homelessness can result from a variety of conditions and co-occurring predictors that are often associated with poverty, and it stands out as a strong predictor of poor HIV outcomes. In Canadian and U.S. cities, where resources exist to provide HIV care for low-income individuals, homelessness predicts a failure to use ART, housing eviction predicts unsuppressed viral load, and becoming housed predicts viral suppression. International guidelines for improving ART adherence recognize housing instability as a barrier to adherence and provide recommendations for homeless individuals that emphasize the need for retention in care as well as case management. The degree to which recent care and case management influence viral suppression among low-income and homeless persons is unclear. Their influences are particularly uncertain when considered alongside factors known to predict VL in low-income individuals, such as food insecurity, substance use and inconsistent health insurance. Similarly, their influences are uncertain among low-income women living with HIV , in whom substance use and violence are both disproportionately common and act synergistically to negatively influence health outcomes, particularly in the context of urban poverty. Issues of poverty and homelessness are important because homelessness is increasing around the world, including in resource-rich areas across Europe and North America. In fact, civil emergencies due to homelessness have been increasing in U.S. cities, and clinics caring for PLWH in resource-rich areas report that the degree of housing instability affects population-level rates of viral suppression. However, factors unique to the health of homeless and unstably housed persons are still routinely overlooked. In addition, while homeless women have different –often more severe –needs and patterns of morbidity and mortality compared to men, women are often under-sampled in homeless research, including HIV-specific homeless research. Moreover, while prior research points to any homelessness as a risk factor for negative health outcomes, data on exposure levels of various housing conditions, such as the number of nights spent sleeping in a given venue, and its impact on virologic outcomes among women, are lacking. We conducted one of the first longitudinal studies to determine independent associations between factors uniquely common in low-income women living in a well-resourced urban environment and unsuppressed viral load, with an emphasis on housing and SAVA syndemic factors. Prior research in this population suggests that different types of living conditions beyond “homeless,” including various types of homelessness and residence in low-income single room occupancy hotels, contribute to health status, but the impact of these factors on viral load has not previously been assessed. Informed by the Behavioral Model for Vulnerable Populations, we hypothesized that multiple types of living conditions would be associated with unsuppressed VL. Our goal was to inform programs and interventions aimed at decreasing detectable viremia in low-income WLWH. Participants provided written informed consent for all study activities, including medical record review. Reimbursement of $15 was given for each study interview and $5 per month was given to update contact information.

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Effortless Cannabis Cultivation: Explore the Best Indoor Grow Systems

Given this background, the aim of this paper is to outline briefly how ethnicity has been operationalized historically and continues to be conceptualized in mainstream epidemiological research on ethnicity and substance use. We will then critically assess this current state of affairs, using recent theorizing within sociology, anthropology, and health studies. In the final section of the paper, we hope to build upon our ”cultural critique” of the field by suggesting a more critical approach to examining ethnicity in relation to drug and alcohol consumption. According to Kertzer & Arel , the development of the nation states in the 19th century went hand in hand with the development of national statistics gathering which was used as a way of categorizing populations and setting boundaries across pre-existing shifting identities. Nation states became more and more interested in representing their population along identity criteria, and the census then arose as the most visible means by which states could depict and even invent collective identities . In this way, previous ambiguous and context-dependent identities were, by the use of the census technology, ‘frozen’ and given political significance. “The use of identity categories in censuses was to create a particular vision of social reality. All people were assigned to a single category and hence conceptualized as sharing a common collective identity” , yet certain groups were assigned a subordinate position. In France, for example, the primary distinction was between those who were part of the nation and those who were foreigners, whereas British, American, and Australian census designers have long been interested in the country of origin of their residents. In the US, the refusal to enfranchise Blacks or Native Americans led to the development of racial categories, and these categories were in the US census from the beginning. In some of the 50 federated states of the US, there were laws,grow rack including the “one drop of blood” rule that determined that to have any Black ancestors meant that one was de jure Black . Soon a growing number of categories supplemented the original distinction between white and black.

Native Americans appeared in 1820, Chinese in 1870, Japanese in 1890, Filipino, Hindu and Korean in 1920, Mexican in 1930, Hawaiian and Eskimo in 1960. In 1977, the Office of Management and Budget , which sets the standards for racial/ethnic classification in federal data collections including the US Census data, established a minimum set of categories for race/ethnicity data that included 4 race categories and two ethnicity categories . In 1997, OMB announced revisions allowing individuals to select one or more races, but not allowing a multiracial category. Since October 1997, the OMB has recognized 5 categories of race and 2 categories of ethnicity . In considering these classifications, the extent to which dominant race/ethnic characterizations are influenced both by bureaucratic procedures as well as by political decisions is striking. For example, the adoption of the term Asian-American grew out of attempts to replace the exoticizing and marginalizing connotations of the externally imposed pan-ethnic label it replaced, i.e. “Oriental”. Asian American pan-ethnic mobilization developed in part as a response to common discrimination faced by people of many different Asian ethnic groups and to externally imposed racialization of these groups. This pan-ethnic identity has its roots in many ways in a racist homogenizing that constructs Asians as a unitary group , and which delimits the parameters of “Asian American” cultural identity as an imposed racialized ethnic category . Today, the racial formation of Asian American is the result of a complex interplay between the federal state, diverse social movements, and lived experience. Such developments and characterizations then determine how statistical data is collected. In fact, the OMB itself admits to the arbitrary nature of the census classifications and concedes that its own race and ethnic categories are neither anthropologically nor scientifically based . Issues of ethnic classification continue to play an important role in health research. However, some researchers working in public health have become increasingly concerned about the usefulness or applicability of racial and ethnic classifications. For example, as early as 1992, a commentary piece in the Journal of the American Medical Association, challenged the journal editors to “do no harm” in publishing studies of racial differences .

Quoting the Hippocratic Oath, they urged authors to write about race in a way that did not perpetuate racism. However, while some researchers have argued against classifying people by race and ethnicity on the grounds that it reinforces racial and ethnic divisions; Kaplan & Bennett 2003; Fullilove, 1998; Bhopal, 2004, others have strongly argued for the importance of using these classifications for documenting health disparities . Because we know that substantial differences in physiological and health status between racial and ethnic groups do exist, relying on racial and ethnic classifications allows us to identify, monitor, and target health disparities . On the other hand, estimated disparities in health are entirely dependent upon who ends up in each racial/ethnic category, a process with arguably little objective basis beyond the slippery rule of social convention . If the categorization into racial groups is to be defended, we, as researchers, are obligated to employ a classification scheme that is practical, unambiguous, consistent, and reliable but also responds flexibly to evolving social conceptions . Hence, the dilemma at the core of this debate is that while researchers need to monitor the health of ethnic minority populations in order to eliminate racial/ethnic health disparities, they must also “avoid the reification of underlying racist assumptions that accompanies the use of ‘race’, ethnicity and/or culture as a descriptor of these groups. We cannot live with ‘race’, but we have not yet discovered how to live without it” .Reinarman and Levine have argued that investigations of ethnicity in alcohol and drugs research have typically taken the form, whether intentionally or not, of linking “a scapegoated substance to a troubling subordinate group – working-class immigrants, racial or ethnic minorities, or rebellious youth” . Different minority ethnic groups have often been framed at one time or another by their perceived use of alcohol and illicit drugs, regardless of their actual substance using behaviors and regardless of their relative use in comparison with drug and alcohol use among whites .In mainstream drug and alcohol research, traditional ethnic group categories continue to be assessed in ways which suggest little critical reflection in terms of the validity of the measurement itself.

This is surprising given that social scientists since the early 1990s have critiqued the propensity of researchers to essentialize identity as something ’fixed’ or ’discrete’ and to neglect to consider how social structure shapes identity formation. Recent social science literature on identity suggests that people are moving away from root edidentities based on place and towards a more fluid, strategic, positional, and context-reliant nature of identity . This does not mean, however,growing racks that there is an unfettered ability to freely choose labels or identities, as if off of a menu . An individual’s ability to choose an identity is constrained by social structure, context, and power relations. Structural constraints on identity formation cannot be ignored, as people do not exist as free floating entities but instead are influenced and constrained in various ways by their socioeconomic and geographical environment . As such, an identity is not just claimed by an individual but is also recognized and validated by an audience, resulting in a dialectical relationship between an individual and the surrounding social structures . Similarly, a ‘new’ perspective on ethnic identity specifically has emphasized the fluidity and contextually-dependent nature of ethnicity, minimizing notions about ethnicity as a cultural possession or birthright and instead emphasizing ethnicity as a socially, historically, and politically located struggle over meaning and identity . Ethnicity or ethnic identity is not some immutable sense of one’s identity but rather something produced through the performance of socially and culturally determined boundaries . Hence, individuals are not passive recipients of acquired cultures but instead active agents who constantly construct and negotiate their ethnic identities within given social structural conditions .In spite of these sociological contributions, which have enriched our understanding of identity generally and ethnicity specifically, the alcohol and drugs fields have not adequately integrated these perspectives, thwarting our ability to understand the relationships between ethnicity and substance use. As such, the field is ripe with correlations between ethnic group categories and substance use problems, resulting in solutions to problems that focus on reifying questionable social group categorizations and revealing little about how drugs are connected to identities and shaped by broader social and cultural structures. It is important to note that we do not intend to argue that existing categories of ethnicity be disregarded in the alcohol and drugs fields. As Krieger and colleagues have noted in another context , surveillance data documenting health disparities, in our case in substance use, are exceedingly important in terms of identifying potential inequities in health. However, without understanding the complexity of ethnic identity and its relationship to substance use, these surveillance data may perpetuate stereotypes and the victimization of specific socially-delineated ethnic groupings, obfuscate the root causes of substance use and elated problems, and reify politicized categories of ethnicity which may have little meaning for the people populating those categories. While acknowledging that socially-deliented ethnic categories are important for documenting social injustices, we must also be vigilant about questioning the appropriateness of those categories .

Conceptually this type of critical approach is important for considering how substance use is related to negotiations of ethnicity over time and place and bounded by structure. Maintaining a static and homogenous approach towards ethnic categorizations in the alcohol and drugs fields presents at least two problems. First, it risks overlooking how drugs and alcohol play into a person’s negotiation of identity, particularly ethnic identity, thus revealing little about the pathways that lead to substance use. Cultural researchers have long emphasized the importance of commodity consumption in the construction of identities and lifestyles , particularly within youth cultures , and how it can be an important factor in demarcating and constituting social group boundaries . A limited body of research in the alcohol and drugs field has emphasized the role of substance use in constructing and performing identities , particularly ethnic identities , uncovering how subgroups within traditionally-defined ethnic minority categories use drugs and alcohol to distinguish themselves from ethnically similar others. For example, in a qualitative study of Asian American youth in the San Francisco Bay area in the US, narratives illustrated how youths’ drug use and drug using practices were a way of constructing an identity which differentiated them from “other Asian” youth groups, specifically allowing them to construct an alternative ethnic identity that set them apart from the “model minority” stereotype . Thus taste cultures and consumption-oriented distinctions highlight the continuing salience of and interconnections not just between substance use and changing notions of ethnicity but also between substance use, class and ethnicity. Ethnic identity gets translated into social captial which in turn has ramifications for one’s economic and social standing . Second, failing to critically appraise our use of fixed and homogenous ethnicity categories in the alcohol and drugs fields jeopardizes our ability to identify the broader social and structural determinants of alcohol and drug use and related problems—like poverty, social exclusion, and discrimination—which are crucial issues for addressing social injustices. So often studies revealing correlations between ethnic categories and substance use related problems result in discussions about the importance of developing culturally-appropriate prevention and treatment interventions, overlooking the structural conditions that adversely affect socially-defined ethnic groupings and may result in some form of engagement with alcohol and/or drugs. For example, research on street cultures, where ethnic identifications and drugs play a central part, illustrates how some ethnic minority youth use and/or sell drugs to actively construct counter-images or ethnically-infused street cultures of resistance within their neighborhoods, which some researchers have called “neighborhood nationalism” , as a way of resisting or transcending “inferior images” ascribed to them by the wider society . These street cultures provide alternative definitions of self-identity, especially for young men, who live in communities marked by poverty and marginalization and who have little access to masculine status in the formal economy .

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From Seed to Harvest: Mastering the Art of Cannabis Farming

Human use of these devices for ingestion of cannabis extracts or cannabidiol is becoming so popular that terming these devices e-cigarettes or ENDS is becoming a misnomer; Electronic Drug Delivery Systems is more accurate. The primary goal of this study was to establish methods for delivering physiologically and behaviorally significant amounts of heroin to rats via vapor inhalation. To this end we adapted an e-cigarette based vaporization system we have previously shown is effective for the delivery of nicotine , THC , cannabidiol , methamphetamine , 3,4-methylenedioxypyrovalerone and oxycodone to rats. Other work has demonstrated antinociceptive effects of inhaled oxycodone in male rats and a preliminary work demonstrates antinociceptive efficacy of inhaled heroin and methadone in male and female rats, and reinforcing effects of inhaled heroin in female rats. Nearly identical systems have been shown to deliver nicotine , THC from cannabis extracts and the potent synthetic opioids sufentanil and fentanyl , to laboratory rodents. To validate the delivery of heroin by vapor inhalation, we used a warm water tail-withdrawal assay for assessing effects on nociception, and a radiotelemetry system capable of reporting body temperature and activity responses. The telemetry measures were selected based on prior evidence that parenteral injection of opioids causes hyperthermia and increased locomotor activity in both rats and mice. For example, intravenous morphine increased the rectal temperature of anesthetized rats , as did intrathecal morphine in freely moving male Wistar rats measured with telemetry . Both morphine and oxycodone produce hyperthermia when injected subcutaneously in rats . Solis and colleagues showed that intravenous fentanyl initially decreased body temperature of rats in the first hour after administration, did not, but each drug induced hyperthermia in the interval approximately 60–120 minutes after injection .

Heroin has also been shown to increase the locomotor activity of rats when injected subcutaneously or intraperitoneally in doses of ~0.25–1.0 mg/kg, although in some early studies a contrast of this described effect with vehicle injection was not made clear . Nevertheless,vertical growing racks system in other studies it was shown that heroin injection ~0.25–0.5 mg/kg, s.c., significantly increases the locomotor activity of rats in comparison with a vehicle injection. A secondary goal of this study was to determine the parameters necessary for dose control / manipulation within an effective range. As we’ve shown in prior studies , this can be effected with changes in drug concentration in the vapor vehicle and the duration of exposure, thus these parameters were under investigation. The final goal was to determine if there are any substantive sex differences in the response to heroin inhalation, see Craft for review, consistent with current suggestions for the inclusion of both male and female subjects in research where possible . While male and female rats acquire intravenous oxycodone self-administration at similar rates with 1-h access sessions , our recent study with 8-h access found that female rats self-administered more oxycodone in acquisition, but did not reach higher breakpoints in a PR dose-substitution . A prior study reported no sex difference in the anti-nociceptive effect of heroin or oxycodone injected subcutaneously in Sprague-Dawley rats , thus no sex difference was predicted for this study. The rats were implanted with sterile radiotelemetry transmitters in the abdominal cavity as previously described on Post-Natal Day 31. For studies, animals were evaluated in clean standard plastic homecages in a dark testing room, separate from the vivarium, during the dark cycle. Radiotelemetry transmissions were collected via telemetry receiver plates placed under the cages as described in prior investigations . Test sessions for exposure studies started with a 15-minute interval to ensure data collection, then a 15-minute interval for baseline temperature and activity values. The rats were then moved to a separate room for the vapor exposure sessions and then returned to the recording chambers for up to 300 minutes after the start of vapor exposure.

These experiments were conducted over the adult age interval of PND. The subjects had participated in similar telemetry recording experiments following vapor and injected exposure to doses of nicotine and THC from PND 50 to PND 190 with active dosing conducted no more frequently than two times per week, in studies not previously reported. The telemeterized body temperature and activity rate were collected on a 5-minute schedule in telemetry studies but are expressed as the average of six sequential measurements for primary analysis. The time courses for data collection are expressed relative to the initiation of vapor exposure and times in the figures refer to the end of the interval . Any missing temperature values were interpolated from the values before and after the lost time point. Activity rate values were not interpolated because 5-minute to 5-minute values can change dramatically, thus there is no justification for interpolating. Data for the first time-point after the start was inadvertently missing for two female rats in the 30-minute PG condition. The values for the second time point were used in place of the missing values. These ended up being very similar to the respective values recorded for this time point for the 15-minute PG condition. The telemetry data were generally analyzed with two-way Analysis of Variance including repeated measures factors for the Vapor condition and the Time after vapor initiation. A mixed-effects model was used instead of ANOVA wherever there were missing data points. The nociception data were analyzed by three-way ANOVA including repeated-measures factors for Duration of exposure and Vapor condition and a between-groups factor of Sex. Any significant main effects were followed with posthoc analysis using Tukey or Sidak procedures. All analysis used Prism 8 for Windows . This study confirms that this method of inhalation of heroin, based on vapor created by an Electronic Drug Delivery System device, produces significant effects in vivo in both male and female rats. The effects are dose-dependent, as they vary with both inhalation duration and with drug concentration in the e-cigarette vehicle .

We have previously shown that heroin vapor exposure produces moderate anti-nociceptive effects in male and female Wistar rats and that is extended to Sprague-Dawley rats, and to a wider range of inhalation conditions, in the present study. As we’ve previously shown, differences between common laboratory rat strains can result in quantitative or even qualitative differences in response to vapor inhalation of drugs, effects which may vary depending on the outcome measure . The present results obtained near-maximal antinociceptive effects in more animals in the 100 mg/mL condition, compared with that prior study, however there were equipment differences between the two studies which may have resulted in more effective drug delivery. For example that prior study reported no antinociceptive effect of oxycodone vapor inhalation using first generation Protank 3 canisters, whereas a study using the second-generation Herakles Sub Ohm canisters, more similar to the present second-generation SMOK canisters,vertical marijuana grow did report anti-nociception subsequent to 100 mg/mL oxycodone vapor inhalation . Although vapor cloud density and chamber fill can be roughly equated by eye, it may be the case that different devices generate different droplet sizes or drug concentrations per droplet that produce complex interactions of a given drug with a given device to effect in vivo drug delivery. In that prior study a 1 mg/kg, s.c., heroin injection produced antinociception comparable to the effects of 30 minutes of 50–100 mg/mL exposure in this study. The data also show that the threshold for statistically reliable effects is 15-minutes of exposure to the 50 mg/mL condition. These exposure parameters led to significant antinociception and produced significant effects on body temperature in the female rats. This study therefore establishes 50–100 mg/mL as an effective concentration range, and 1 mg/mL as an ineffective concentration, for 15–30 minutes of non-contingent inhalation exposure to heroin in rats. This is a nontrivial advance from the prior demonstrations that rats and mice, respectively, will self-administer the potent opioids sufentanil and fentanyl . First, the doses needed to produce robust changes in nociception, thermoregulation and locomotor behavior are often far in excess of the doses that rodents will self-administer. Second, we found previously that cocaine and some amphetamine or cathinone class psychomotor stimulants which exhibit both low potency and lower solubility in PG may not readily be delivered in active doses with this approach . Thus, it was critical to show that a less potent opioid such as heroin can be delivered with this method. There were biphasic dose-dependent effects of inhaled heroin on body temperature which was expressed as lower exposure conditions producing reliable increases in temperature, and higher doses / exposures initially reducing body temperature, at least in the female rats. A prior study found similar biphasic effects after intravenous fentanyl, which initially decreased body temperature of male Long-Evans rats in the first hour after administration, but induced hyperthermia thereafter . This may reflect potency, or brain penetration speed, as potential differences between the two opioids that permitted this initial hypothermia to be observed.

It could similarly be the case in the present study that the inhaled route of administration speeds the brain entry of heroin versus the more common s.c. or i.p. or even i.v. routes of administration. The observation that injected heroin did not have immediate effects on female rats’ body temperature , and induced less complete suppression of activity compared with inhaled heroin , supports this interpretation. If so, this may be a key area in which the development of this inhalation model allows the investigation of effects of heroin which are unique to this route of administration. It may also be the case that effects of inhalation are more similar to the effects of the intravenous route, in this case the method offers several practical advantages over implanting and maintaining intravenous catheters in rodents. Such advantages include overall cost, surgical expertise and avoiding subject loss due to occluded catheters or health complications related to the catheter. The apparent sex difference is most likely a difference in effective dose when heroin is inhaled, since pilot work with a group of male Sprague-Dawley rats illustrated a consistent hypothermia associated with a high exposure condition and hyperthermia with a lower exposure condition . Also, female rats in this study were affected in terms of body temperature and anti-nociception after 15-minute inhalation of Heroin 50 mg/mL, whereas male rats were only affected on the anti-nociception assay and only to an extent that failed to reach statistical significance. Overall, these patterns are more consistent with a dosing difference across sex rather than a sex difference per se; additional work with more expanded dosing conditions might further explicate this interpretation. Interestingly, when mg/kg equivalent doses were injected the males’ body temperature was consistently elevated whereas the females’ temperature was not. A previous study found no difference in the ED50 for heroin in a warm water tail-withdrawal test between male and female Sprague-Dawley rats and where sex differences were found the males were more sensitive. Nevertheless, female mice develop greater hypothermia than do males after a mg/kg equivalent injection of morphine . The initial suppression of activity, followed by a rebound of increased activity, is similar to that reported for injected morphine but differs somewhat from prior results for injected heroin, which appeared to show a monotonic effect of time where activity is highest at the first time-points observed after dosing and then declined steadily with time. The pattern of initial suppression followed by a rebound was observed in the 1.0 mg/kg, s.c. injection study, as well as in the 30-minute inhalation experiments, suggesting the difference is not due to route of administration. One possible difference is that some of those studies were conducted with rats in the light part of the cycle , however others reporting similar monotonic time courses were on a reverse cycle and were tested in the dark . A more consistent difference is that many studies of the effects of injected heroin used a non-housing, specialized photo cell cage with mesh or rod floors, unlike the plastic floored normal housing cages with a thin layer of bedding used here. It may be the case that the more familiar, housing-type environment facilitated expression of a more naturalistic response. There are a few necessary caveats; given the selected repeated measures experimental design it is always possible that a degree of plasticity, either sensitization or tolerance, may have developed. The counterbalanced testing order, however, minimizes the concern that this would have a systematic effect on any specific dosing conditions. Likewise, the animals had participated in prior studies involving exposure to THC, which might potentially produce cross tolerance, and because of that the animals were in the middle adult age range. It is entirely possible that responses in younger adults might differ.

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The Science Behind the Strain: A Deep Dive into Cannabis Cultivation

Notably missing from the HIV literature is an examination of differential associations by sex or race/ethnicity and APOE’s association with cognition and brain integrity. In a meta analysis of aging research studies, APOE e4 women were found to be at greater risk of AD compared to APOE e4 men but only between the ages of 65 and 75 . Additionally, there are known differential effects of APOE status on AD risk by race. The effect of APOE status on AD risk is significantly attenuated in African Americans/Black people compared to non-Hispanic white people . Therefore, future examination of the relationship between sex, race/ethnicity, APOE status, and other genetic markers of AD risk within PWH is certainly warranted. In summary, considering the HIV literature, the middle-aging literature, and the finding that episodic memory was associated with prefrontal structures rather than medial temporal lobe structures, episodic memory in middle-aged PWH is more likely related to frontally mediated etiologies. This could indicate that memory in middle-aged PWH is associated with HIV disease. Notably, this association was seen in PWH on ART without a detectable viral load, showing that this association is seen even in PWH who are virally suppressed. However, it is of course difficult to differentiate between the effect of HIV itself versus the effect of comorbid conditions, many of which may be increased in PWH due to the downstream effects of HIV and ART, or a combination of the two. The medial temporal lobe was not associated with episodic memory, which overall may indicate that at this age range, preclinical AD is not likely a contributor to memory functioning. However, the middle-aging literature does not provide a good estimate of when, on average, to expect to start detecting differences, even small,vertical grow factory in memory and medial temporal structures in those that are on an AD trajectory; therefore, it is possible that this group is too young to even start detecting any preclinical AD effect.

This is further complicated because the middle-aging literature is demographically different from the CHARTER sample, thus highlighting the need for more diverse aging studies. Additionally, this study did not specifically examine differences in the associations between memory and brain structures by AD risk ; thus, future research should examine memory associations by AD risk, particularly given that APOE status was associated with delayed recall. Relatedly, these findings show that on average this group is not showing associations with memory and the medial temporal lobe and early signs of preclinical AD, but this does not mean that no participants are on an AD trajectory. In fact, given base rates, some of this group will eventually develop AD. First, the multi-level models examining the cross-level interactions between time and medial temporal structures with dichotomous recognition as the outcome did not converge. This analysis would have examined if baseline medial temporal lobe structures are associated with greater likelihood of impaired recognition over time. Given that the models did not converge, this indicates the models were over parameterized and that the model was not supported by the data. This was possibly affected by the modest sample size, with a particularly small group of participants with impaired recognition at baseline. Examining the variability in recognition over time within this study is still meaningful. For example, of the 12 participants that were impaired at baseline, only two remained impaired. Moreover, in those that were not impaired at baseline but were impaired at some point in time, most reverted back to unimpaired at subsequent visits. Only four participants remained impaired in recognition over time, although with limited follow-up. There is not data on why these participants do not have additional follow-up , and thus it is hard to make any definitive conclusion as to if consistently impaired recognition is a risk factor for negative outcomes. However, it would certainly be warranted to examine if consistent recognition impairment is associated with negative outcomes in a larger group of middle-aged and older PWH. For example, this small group of participants that were consistently impaired in recognition memory could represent those that are progressively declining and are on more of an AD trajectory. Moreover, a better understanding of how those that are consistently impaired differ from those that revert to unimpaired recognition would be beneficial.

There are multiple reasons that may explain why recognition impairment status was variable over time. First, HIV-associated neurocognitive impairments are known to fluctuate over time. For example, in the CHARTER study, 17% of the sample improved over time . Therefore, this could simply reflect the heterogeneous and fluctuating course of HAND over time. Second, recognition is sometimes used as an embedded performance validity measure. While all participants were administered a standalone performance validity test at the beginning of the neuropsychological evaluation to verify credible test performance, effort can fluctuate throughout testing. That said, none of the participants at baseline were below the proposed cut-off of ≤5 for HVLT-R recognition , making this explanation less likely. Lastly, this variability over time may be in part due to the psychometric properties of the HVLT-R and the BVMT-R. Recognition for both the BVMT-R and the HVLT-R are skewed with known ceiling effects, meaning that there is limited variability in this variable . Therefore, a one- or two-point difference can result in large differences in the normative score. Moreover, there are known modest interform differences on the HVLT-R recognition . Additionally, while the HVLT-R and BVMT-R test-retest reliability of recognition show adequate test-retest stability coefficients, the test-retest reliability of recognition is less reliable than other test measures such as total learning or delayed recall . Next, longitudinal delayed recall was examined. Most notably, there was little decline in delayed recall over time; the delayed recall T-score decreased by 0.041 per year. Additionally, there was little variability in this slope given that the standard deviation of the slope was 0.678. None of the cross-level interactions between medial temporal lobe structures and years since baseline were significant indicating that medial temporal lobe structures at baseline were not associated with a change in delayed recall. However, given that there was little variability in delayed recall over time, this was not surprising.

As discussed in the introduction, worse baseline medial temporal lobe structures, particularly the hippocampus and entorhinal cortex, have been associated with an increased risk of future AD, MCI, and decline in cognition in older adults without HIV . This relationship is less understood in middle age. One study by Gorbach et al. found that hippocampal atrophy was associated with a decline in episodic memory in adults over the age of 65 but not in middle-aged adults between the ages of 55 to 60. As highlighted above, it is possible that the cohort from the current study is too young to expect to see associations between medial temporal lobe structures and longitudinal memory. Importantly, the current study only examined cross-sectional structural MRI; therefore, we cannot assume that smaller or thinner medial temporal lobe structures are indicative of atrophy. Additionally, this study does not have an HIV-negative comparison group and did not use normatively-adjusted morphometric values , so it is unclear if participants in this cohort deviate from average, although accelerated brain atrophy has been demonstrated in PWH previously . Therefore, research examining changes in the medial temporal lobe and how that change relates to episodic memory, particularly recognition memory,vertical grow indoor in persons with and without HIV over the age of 65 is needed. This research may help to better understand if medial temporal lobe structures are associated with the risk of an AD trajectory and if these associations differ by HIV-serostatus. While there may be some individuals in this group that are experiencing objective decline, on average, in this group of middle-aged PWH we did not observe a decline in delayed recall T-scores over time. These T-scores are age-corrected, so the raw scores on the tests may be declining but they are not declining at a rate greater than what would be expected for age. Additionally, these T-scores also account for practice effects, which if unaccounted for can mask decline, although the best method of practice-effect correction is still debated . Similar results showing stable cognition over time were found in a study by Saloner et al. in a larger sample of CHARTER participants aged 50 and over. This study employed growth mixture modeling, and none of the three latent classes demonstrated a decline in global T-score over time. However, other studies of PWH over the age of 50 have observed a greater than expected effect of aging on episodic memory and a recent systematic review found accelerated neurocognitive aging in 75% of longitudinal studies in PWH . Some researchers have questioned if accelerated aging could be due to a neurodegenerative cause such as AD given the high prevalence of risk factors for AD in PWH such as chronic inflammation, increased cardiometabolic comorbidities, and lower brain reserve . While emerging studies have demonstrated some possible ways to disentangle HAND and aMCI , it remains unclear if PWH are at increased risk of AD or if a neurodegenerative etiology could, at least in part, account for someof the observed accelerated aging.

For example, Milanini et al. showed a low frequency of amyloid positivity, measured via PET imaging, among virally suppressed PWH over the age of 60, and the rates of amyloid positivity were similar to published rates among an age-matched seronegative sample. However, a recent study among Medicare enrollees did find a higher prevalence of AD and related disorders among PWH . In summary, this aim showed that recognition was variable over time. While amnestic decline could not specifically be tested given that recognition models did not converge, these analyses indicated that within this group, medial temporal lobe integrity was not associated with a decline in delayed recall over time. Additionally, delayed recall only marginally declined over time , thus adding to the mixed literature examining episodic memory in middle-aged and older PWH. Overall, this study did not detect clear signs of preclinical AD in this group, as delayed recall did not change over time and baseline measures of medial temporal lobe integrity were not associated with memory over time as seen in HIV-negative older adults. However, it is not clear if these associations would be expected in a middle-aged cohort of PWH due to a lack of literature on this topic in middle-aged adults. Therefore, it would be beneficial to re-examine this analysis in an older cohort of PWH.The last aim of this study was to examine if the medial temporal lobe mediates a relationship between peripheral inflammation and memory. It was hypothesized that medial temporal lobe structures would mediate a relationship between peripheral inflammation and episodic memory. Five peripheral biomarkers of inflammation were examined , and these biomarkers were chosen given that they have been associated with cognition in AD and HIV. In this mediation model, the association between peripheral biomarkers of inflammation and medial temporal lobe structures was also explored and the relationship between medial temporal lobe structures and memory was also reported, although this second relationship was already explored in aim 1. First, the mediation models examining recognition indicated poor model fit. Therefore, the relationship between the five plasma biomarkers of inflammation and recognition was examined instead. Greater levels of plasma CRP were associated with lower odds of having impaired recognition. None of the other plasma biomarkers of inflammation were associated with recognition impairment. These findings are generally not in line with the HAND , middle-aging , or older adult literature . Aging and HIV studies have found that a greater concentration of these plasma biomarkers of inflammation are associated with greater risk of HAND, worse memory, and an increased risk of future development of MCI or AD. However, many of these studies only find weak associations, and these studies do not examine recognition memory. The current study had a very small sample of PWH with impaired recognition; thus, it is possible that the CRP finding is spurious, and this finding should not be over-interpreted. Therefore, analyses should be reexamined in a larger, more generalizable sample. Next, a single-mediator model was used to examine if medial temporal lobe structures mediate the relationship between plasma biomarkers of inflammation and delayed recall.

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Vertical Harvest: Revolutionizing Cannabis Farming for Increased Efficiency

This drop is significant as it does not appear in BEA_beta, showing that sites with the same DoC can have drastically different contributions to capacitance. The source of this low-CCpC region becomes clear when examining representative configurations of the most highly confined anions of BEA and BEA_beta in Figure 5.8. In BEA, the anion islocated in a cylindrical, nanotube-like structure, with a coordination shell of electrode atoms encircling the anion on all sides, while the anion in BEA_beta is only confined on two out of four sides by the electrode. The cylindrical pore of BEA is too small to fit another anion or even solvent molecule, but too large to snugly fit BF4 – , causing it to be stuck in the middle of the pore where it is not close enough to induce a strong compensating charge on any of the atoms within its coordination shell. As a result, the coordination shell atoms in BEA have a total charge of 0.026 e, while the coordination shell in BEA_beta has a total charge of 0.223 e. This effect has also been observed in the literature; for example, Kondrat et al. showed a local minimum in capacitance when the pore-to-ion-diameter ratio L/d was around 1.5, and increased capacitance when L/d was near 1 and 2.The charge storage efficiency also depends on the ion size in relation to the pore size: In the electrolyte studied here the cation is larger than the anion and its charge is distributed on three sites. As such, when a cation is at the center of the nanotube-like pore, the partial charges of its coarse-grained sites are able to approach more closely to the electrode surface, making the equivalent pore in the cathode more efficient at storing charge. This explains why there is no drop in h CCpCi DoC in the BEA cathode . These observations highlight one important role of pore geometry in determining charge storage efficiency, by influencing local ion density and electrolyte coordination environment. We show in Figure 5.11 the structures of the materials with highest and lowest Csim − Cf it,vertical garden grow system indicating the average charge of each crystallographically unique electrode carbon atom during the equilibrated constant potential run, along with the probability density isosurfaces of counterion locations within the electrodes.

Isosurfaces for adsorption sites with more than 0.1 e total charge compensation are shown in purple, while sites with less than 0.1 e charge compensation are shown in green. This allows us to visually associate geometry with average contribution to capacitance for an individual pore. We observe that the adsorption site iso surfaces which have more than 0.1 e coordination shell charge compensation are close to the surface of the frameworks, while the isosurfaces associated with less than 0.1 e charge compensation tend to be in the middle of the pores. Inspecting the average atomic charges, we observe that BEC and h91 have more individual carbon atoms with high charge, corresponding to high CCpC. As seen in Figure 5.9, BEC and h91 are also the two materials with the highest enhancement in capacitance compared to materials of similar A/h dsepi . In contrast, h18, h49, and ISV, which have A/h dsepi similar or greater than that of BEC, but lower capacitance, have fewer highly charged atoms. Figure 5.11f provides further quantitative evidence of the correlation between the probability of highly-charged atoms and Csim −Cf it: structures with a higher probability density of average atomic charge greater than 0.1 e tend to have a higher Csim − Cf it. In order to rationalize the differences in charge storage between these materials, we focus on the local radius of curvature of the materials, as this roughly determines the distribution of ion-electrode distances at a particular adsorption site. In BEC, which has square-shaped windows with right-angle “corners,” we see electrode atoms with large average partial charges at two locations for each adsorption isosurface, corresponding the positions at which an adsorbed ion can be in close proximity with two “walls” of the framework simultaneously. In h91, cynlindrical pores adjoining with rounded beams create small-radius of curvature sites where ions can again approach the electrode surface closely at multiple sites, leading to more electrode atoms with large partial charges. In contrast, adsorption sites which are near large radius of curvature sites, such as in h18, h49, and ISV, , tend to be associated with materials with lower capacitances relative to their respective A/h dsepi . In adsorption sites with a large radius of curvature, an ion is not able to induce as many favorable Coulombic interactions with the electrode surface, leading to lower charge compensation for ions within those materials.

ISV merits particular mention, as it does contain some adsorption sites with low radius of curvature and high charge compensation , but because it also has high radius of curvature/low charge compensation sites , ISV still has a relatively low capacitance considering its high A/h dsepi . Overall, our results demonstrate that pore geometries which are capacitance-enhancing tend to faciliate the close approach of counterions to multiple carbons within the electrode via low radius of curvature adsorption sites, so that the compensating charge from the electrodes can be localized and large in magnitude to most efficiently screen counter charges and allow for higher counterion loading in the pores. Conversely, capacitance-diminishing properties include pores with high radius of curvature and cylindrical and ill-fitting pores, as these types of sites have inefficient charge storage and therefore decrease the overall capacitance of the material.For a preliminary assessment of the ability of the different models, method and protocols to describe the adsorption of THC in microporous materials and MOFs, we investigated the well-studied Mg-MOF-74. This MOF was chosen because of its large channel diameter, which can host the bulky THC molecule, and because of the presence of strongly charged Mg open metal sites, which have a partial charge of 1.59 e as computed with the DDEC protocol.190 This allows us to asses the contribution of Coulombic interactions in the adsorption of THC, a weakly charged molecule within frameworks having strongly charged binding sites. The THC-head model was used for a preliminary simulations. Since the alkyl tail is charge-neutral, the THC-head portion of the molecule is also neutral and therefore it can be used to assess the contribution of Coulombic interactions. We ran NVT Monte Carlo simulations at 309 K, the human body temperature, and at infinite dilution, i.e., with one THC-head particle per simulation box, for a total of 2 · 106 Monte Carlo steps . To equilibrate the system before the production, 10 000 cycles were added, i.e., one tenth of the total number of steps. Each move was chosen from translation, rotation, and random insertion with equal probability. From the output of these calculations we observed that, while the acceptance ratios of translation and rotation moves are close to the 50%, the regrow acceptance ratio is only 4.8%. This means that it is particularly difficult for the THC molecule to find a new position in the pore volume that is not overlapping with the framework.

Nonetheless, we determined that this move is reasonably explored in our 2 · 106 steps of simulation. The average adsorption energy of THC in Mg-MOF-74 from the NVT simulation is kJ mol1 , where the contribution from the Coulombic interaction is less than 0.5%, while most of the adsorption energy comes from dispersion interactions. Indeed, a new calculation with the charges turned off resulted in an adsorption energy of kJ mol1 , and very similar acceptance ratios for the MC moves. It was therefore reasonable to neglect in the protocol Coulombic interactions even when strongly charged open metals site are present, as in the test case. This assumption has the twofold benefit of speeding up the MC simulations and avoiding the need to compute partial charges for the frameworks. We next compared the rigid THC-head rigid model with the flexible THC-full model that includes four coarse-grained sites to represent the alkyl tail. For this models we added the “reinsertion in place” step, where the algorithm attempts to regrow the alkyl tail from while keeping the aromatic head of the THC molecule fixed,vertical greenhouse growing occurring with the same probability as the other MC steps. The NVT calculation, with Coulomb interactions turned off, gave a resulting adsorption energy of kJ mol1 , i.e., ca. 26 kJ mol1 more favourable than using the THC-head model. This difference is due to the additional dispersion interactions of the four beads of the tail with the framework. However, we can not assume a priori that the same difference would be found for all the frameworks. Indeed, even in MOFs with similar chemistries, where we might assume that the dispersion interactions are similar, there is the possibility that in some frameworks, the THC-head model is confined in a small pore in such a way that there would be no room to grow the tail. The advantage, however, of using the rigid THC-head particle is a speedup of ca. 2X times for the non-charged model. Moreover, one has to consider that the reinsertion moves are accepted more rarely using the full model: the acceptance ratios lower to 1.8% for reinsertion and 2.2% for reinsertion in place. Finally, we compared the results from NVT simulations with Widom insertions: both methods are supposed to converge to the same adsorption energy, albeit faster in the first case, but the Widom insertion allows us to compute the Henry coefficient as well. This value quantifies the adsorption free energy at infinite dilution, including the entropy of adsorption which is expected to be largely influenced by the topology of the framework. As before, we tested the THC-head and THC-full particles in the charged MOF-74, for 2 and 20 million Widom insertions. Results are summarized in Table B.1. The electrode charging exhibits multiple timescales which are not captured by the single exponential charging of an ideal RC circuit. Modeling the system with additional RC elements, as in a transmission line model, would better capture charging dynamics, especially since we observe that the electrodes charge progressively, starting from the electrode-bulk interface and moving inward . This spatially progressive charging is a key characteristic of the transmission line model, and is more marked in the materials with smaller pores since slower ion diffusion creates a bigger difference between charging times for the outer and inner regions of the electrode. We observe that in many of the structures, particularly in the outer slice, the total ion occupancy exhibits a maximum value during charging which is higher than the equilibrated value, suggesting that the electrolyte molecules may encounter kinetic trapping as counter-ions enter the pores .

The increase of counter-ions in the pores allows for faster-than exponential charging upon initial application of a potential difference, but then the local density increase makes it more difficult for co-ions to diffuse out of the electrode, slowing further charging. This phenomenon is similar to the “overfilling” observed by Kondrat et al., in which the total number of ions inside the pore during the course of charging reaches values higher than the steady-state value.If the initial charging period after the constant potential is characterized by kinetic trapping, then we should see that the charging profile in this initial period differs between independent charging cycles of the same EDLC. When fit to an exponential, independent runs may have different τ as this is determined by dynamic processes during charging, but they should have similar Qinf . In order to test this we generated independent configurations of the 19 ZTCs from zero-charge runs, and repeated constant-potential simulations to compare the charging curves of the independent runs. These results, shown in Figure C.10, demonstrate that there is indeed more reproducibility in the maximum charge than in the charging rate between independent runs. While all but four of the maximum charges are within 10% of each other in independent runs, two-thirds of the materials have time constants that are more than 10% different from each other. Cancer is the leading cause of overall dog deaths with up to 27% of dog deaths attributed to this disease.This risk is highest for large breed dogs and those over 10 years of age.Cancer and its treatments cause disruptions in nutritional status, such as loss of appetite and cachexia in many species.In humans undergoing or surviving beyond treatment, evidence for the effectiveness of dietary strategies is inconsistent, which might reflect the complexity of the relationships among various nutritional factors, cancer biology, and both general and cancer-specific outcomes.

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Homegrown Bliss: Mastering the Art of Cannabis Cultivation

With cigarette users as the referent category, the analysis suggests that exclusive e-cigarette users are less likely to have their respiratory symptoms worsen, along with consistent findings , than they are more likely to have their symptoms improve. In sum, with respect to short-term changes in functionally-important respiratory symptoms, the results suggest risk for exclusive e-cigarette users are intermediate–increased harm compared to never tobacco users, but reduced harm compared to cigarette users. Cigar smokers had consistently lower risk for functionally-important respiratory symptoms compared to exclusive cigarette smokers, as was previously reported for some of the single respiratory symptom items in another PATH Study report.Cigar smoking has been associated with higher mortality from respiratory disease and lung cancer,increased risk for diagnosis of lung cancer and COPD,decreased lung function and airflow obstruction,and respiratory symptoms. In all studies including cigarette smokers, risks associated with cigars were lower than for cigarettes; former cigarette smokers switching to cigars had higher risk vs. those who had smoked only cigars.Respiratory symptom risk among hookah smokers has not been studied extensively but was intermediate between never smokers and cigarette smokers in one study.Lower symptom risk with exclusive cigar use may be explained by reduced smoke inhalation.In contrast to cigarettes, cigar tobacco is fermented, and many cigars are smoked with lower frequency. Cigar smokers also tend to inhale less deeply because of smoke alkalinity which also enhances oral nicotine absorption. Only 15% of exclusive cigar smokers report actively inhaling the smoke, compared to two-thirds for users of both cigars and cigarettes .Marijuana was associated with functionally-important respiratory symptoms, consistent with 8 of 10 previous studies.The findings are backed by research involving dual users of marijuana and cigarettes showing higher puff volumes, deeper inhalation,movable vertical grow rack system and greater tar retention from marijuana vs. cigarettes,animal research documenting pulmonary cell changes with chronic marijuana smoking, and prospective research showing changes in lung function among marijuana smokers.

Marijuana use was also a confounder of the e-cigarette—respiratory symptoms association. One study showing an association between e-cigarette use and cough among young never cigarette smokers, failed to adjust for marijuana use in the multi-variable model . Another study of adult PATH Study W4 data found vaping with marijuana to be associated with wheezing , consistent with our findings.Two other studies of youth, one using PATH Study data, have shown that the e-cigarette—respiratory outcome is confounded by marijuana use and marijuana vaping.Clinicians need to be aware of the association between marijuana use and respiratory symptoms as use increases.The study strengths include a nationally representative sample, a validated respiratory outcome related to functional impairment, and adjustment for multiple confounding influences. Limitations include small numbers in some product groups, increasing the probability of a chance finding. Because switching from cigarette smoking to exclusive e-cigarette use is an uncommon event, randomized e-cigarette switching trials may be required to better assess how e-cigarette substitution affects wheezing symptoms among adult cigarette smokers. Risk of marijuana smoking on respiratory symptoms may be underestimated because marijuana use may have included non-combustible products. Relying on self-report of COPD may have resulted in some who were unaware of their diagnosis being retained in the study. The findings relate only to short-term changes in wheezing and nighttime cough, not other bothersome symptoms , longer-term symptom effects, relation to respiratory disease onset, or vaping-related acute lung injury—medical issues that underline concern about any inhaled product use. The analysis included many comparisons and nevertheless employed a p-value of 0.05; the associations reported should be confirmed in other samples. Finally, future analyses with the latest available data from the PATH Study may provide a more refined look at the questions addressed in the present study. In summary, this study of a nationally representative sample of US adults without severe respiratory disease found an association between cigarette smoking and functionally-important respiratory symptoms – and substantially less evidence of associations between respiratory symptoms and exclusive non-cigarette tobacco product use. Microporous materials, which are defined by a pore size of less than 2 nm, are used in both research and industrial applications in chemical separations, catalysis, and energy storage.

They comprise a diverse group of materials, including zeolites, metal-organic frameworks, covalent organic frameworks, and porous carbons. These classes of materials are distinct in their synthesis methods and compositions, but are united by their small pore sizes, which are on the scale of many chemically and industrially important molecules, as well as their potential for large accessible surface areas. Zeolites are naturally occuring aluminosilicate materials that were discovered in 1756.Today, they are produced on an industrial scale, and are ubiquitous in catalysis and other industrial applications due to their chemical and thermal stability.234 distinct zeolite framework types have been classified as of 2019,and the potential for chemical modifications such as ion exchange further increases the design space of such materials. Metal-organic frameworks are a newer class of materials, first synthesized a few decades ago, and comprise a three-dimensional network of metal centers connected to organic linkers by coordination bonds. They are synthesized using reticular chemistry, in which molecular building blocks are assembled to form extended crystalline structures. Like other microporous materials, MOFs also have very high surface areas, with record Brunauer-Emmett-Teller surface areas of about 7000 m g2 reported to date and hypothetical maximum surface areas predicted to be up to two times larger.The design and synthesis of new MOFs has been a flourishing research area in the past few decades, and the development of more chemically stable MOFs has led to their increasingly widespread use in organic catalysis, gas separations, imaging, sensing, and proton, electron, and ion conduction.Zeolites and MOFs are both crystalline materials, which is a desirable characteristic as it means that composition and pore geometry are well-defined on a large scale. Other microporous materials which have short-range order but can be disordered on longer scales include covalent organic frameworks ,which are also synthesized using reticular chemistry but are composed of organic nodes and linkers and are therefore fully covalently bonded, as well as zeolite-templated carbons .

Reticular synthesis is modular in nature, yielding a virtually limitless design space for MOFs as different combinations of nodes and linkers can be used, which assemble in different topological nets. Ca. 70 000 MOFs have been synthesized to date, as reported on the Cambridge Crystallographic Structure Database ,and thousands of new structures are reported each year. To add to this abundance of experimental structures, there exist libraries of hypothetical MOFs which bring the total number of experimentally synthesized and hypothetical structures into the hundreds of thousands. In order to make this design space tractable, computational chemistry, and in particular molecular simulations, can be used to predict the properties of structures even before synthesis and identify promising structures for a particular application.In this way, computation and experiment can work in tandem, with simulations “discovering” hypothetical materials in silico to inform and inspire experimental synthesis, and experimental results demonstrating new structures and unexpected properties to direct computational study. Achieving correspondence between experimental and theoretical results is not always straightforward, but has led to breakthroughs in material design and elucidation of mechanisms toward better understanding of material properties. Microporous materials have great potential in technologies to decrease the energy needed for existing industrial processes, to mitigate the effects of increased anthropogenic emissions to the atmosphere through carbon capture and sequestration , and to provide more sustainable energy storage solutions. For example, the amine-appended MOF N,N’-dimethylethylenediamine-Mg2 , was shown to exhibit a step-shaped CO2 adsorption isotherm, which indicates potential for high deliverable capacity in a temperature- or pressure-swing adsorption process,movable vertical growing solutions with lower energy requirements than the currently used amine scrubbing technologies for CCS.This step-shaped adsorption isotherm was shown to be due to a phase-change adsorption mechanism involving the amine functional groups.Another study synthesized a library of COFs in silico and screened them for methane storage applications, finding that one of the materials had better predicted methane deliverable capacity than any other reported structures.Similarly, a screening study of the materials in the Nanoporous Materials Genome identified promising materials for hydrogen storage.Microporous materials are also used extensively in electrochemical energy storage applications as the electrode material for batteries and super capacitors.The field is dominated by carbon-based materials due to their affordability and conductivity,though recently asuper capacitor with electrodes made from a neat MOF was demonstrated.Though the equations that describe force fields are simple, when combined they represent a powerful tool that allows for simulation of large systems with relatively high accuracy. Several features of force fields lend themselves to computational efficiency: the first is that non-bonded interactions are pairwise, meaning that the non-bonded potential of a configuration of atoms can be computed by summing interactions between pairs of atoms. In addition, while the electronic density of atoms is spread over a nonzero volume, in classical force fields the electron density is usually treated as a point charge. These features lead to several computational algorithms that allow for short range cutoffs coupled with long-range corrections . As mentioned throughout this overview of force fields, there are myriad ways to increase the complexity of classical force fields, for example by describing bonding implicitly using “reactive” force field methods that calculate bond order on the fly, or by using functional forms that involve more parameters to fit to a class of systems. With the increase of computational power in the last few decades, it is also possible to compute the potential energy of increasingly large configurations of atoms using electronic structure methods. However, due to the computational efficiency of classical simulations, it is likely that they will always enable simulations of larger and more complex systems compared to quantum mechanical methods, and thus classical force fields will remain relevant for a long time.

The 10.0% enhancement in linear conversion of Ni-MOF-74 relative to FAU is in good agreement with the 11.1% enhancement observed experimentally by Mlinar et al., suggesting that our model and theoretical framework capture quantitatively the influence of the adsorbent material on product distribution. Interestingly, the absolute predicted linear conversions are 13.0% lower than their respective experimental values. This means the experimental materials are consistently more selective towards linear isomers than their simulated counterparts. This could be due to diffusive barriers not accounted for by our simulations, which would favor the less-bulky linear isomers. We also want to emphasize that these calculations rely on equilibrium thermodynamics, and thus presume that Brønsted-Evans-Polanyi conditions are met. From this comparison with the experimental results of Mlinar et al., we can conclude that the contribution of the pores to the free energy of formation is indeed a useful indicator of how the product distribution varies with the catalyst material. It is therefore interesting to explore how this distribution can be further changed by using a different zeolite MOF structure. Expanding the database of structures allows us to better understand how molecular descriptors correlate with product distribution, and further elucidate design principles of materials for propene dimerization.Cannabis has in recent years seen increasing decriminalization for both recreational and medical use under some local and state jurisdictions. Since 2012, 10 U.S. states have legalized recreational use of cannabis and 33 states medical use of the drug, coinciding with a shift in societal attitudes regarding cannabis use.Immoderate cannabis use has been shown to have public health and safety implications, for example a moderate increase in risk of injury or fatality while driving under intoxication.As a result, increasing use of cannabis requires improved methods, similar to alcohol, for portable detection of cannabis intoxication in order to promote more consistent cannabis regulation and safer cannabis use. The pharmacological effects of cannabis result from a variety of chemical compounds, including several hundred types of cannabinoid which can be found in the plant. The principal psychoactive component of cannabis is ∆9 -tetrahydrocannabinol , which affects motor and cognitive function and has been linked to increased risk of motor vehicle crashes.For roadside testing applications, breath-based testing of THC has the greatest potential as it is less invasive than testing of urine or blood. Breath detection has other advantages as well. The window of detection of THC in breath coincides with the period of peak impairment.THC and its metabolites can also be detected in blood and urine, but as cannabinoid compounds persist for several times longer in these bodily fluids they are not a reliable indicator of intoxication.Though the full window of driving impairment may extend longer than 2 h, the short detection window in breath may be able to be extended using methods that have increased sensitivity.

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The second research question involved longitudinal analyses of youth tobacco use initiation

The wave 2 questionnaire introduced the term “electronic nicotine products,” of which “ecigarettes ” was a subset. In this analysis, we considered the most inclusive electronic nicotine product wording at each wave as e-cigarette use. The first research question was used to assess parent or guardian knowledge or suspicion of their child’s tobacco use. Each wave, parents or guardians were asked, “Asfar as you know, has [child’s first name] ever smoked a cigarette or used other tobacco products, such as e-cigarettes, cigars, a pipe, a hookah, smokeless tobacco, dissolvable tobacco, bidis, or kreteks?” Parents were categorized as knowing or suspecting tobacco use if endorsing “you know that she/he has” or “you strongly suspect she/he has.” The responses “you don’t think she/he has” and “you are confident that she/ he has not” were categorized as not aware or suspicious. “Don’t know” responses were uncommon and were coded as not aware or suspicious. Parents or guardians and youth were independently asked to consider “rules about using tobacco inside your home” as applied to “everyone who might be in your home, including children, adults, visitors, guests, or workers.” Separate items referred to “tobacco products that are burned, such as cigarettes, cigars, pipes, or hookah” and “tobacco products that are not burned, like smokeless tobacco, dissolvable tobacco, and e-cigarettes.” Endorsing that product use “is not allowed anywhere or at any time inside my home” was classified as strict household rules, whereas endorsing “in some places or at some times,” “anywhere and at any time,” or “don’t know” was considered more permissive. Additionally, youth were asked, “In the past 12 months, have your parents or guardians talked with you, even once,vertical grow racking system about not using any type of tobacco product?” which we categorized as “yes” versus “no” or “don’t know.” For both research questions, covariables included in multivariable models were parent or guardian educational attainment ; the child’s age , sex, and race and/or ethnicity; whether anyone who now lives with the child uses tobacco ; and whether the child lives somewhere else with another parent .

Models of parental knowledge or suspicion additionally included whether the parent or guardian was the child’s biological mother. Models of tobacco initiation additionally included child ever use of alcohol and cannabis, whether the child has a curfew , and the sensation seeking score.For the pseudo time-series analysis, parental knowledge or suspicion of their child’s tobacco use was modeled as the dependent variable by using logistic regression with wave-specific, cross-sectional, balanced repeated replicate weights, allowing each wave to be nationally representative despite participant overlap. Youth tobacco use category was the main predictor variable, with tobacco use 3 survey wave interaction terms added to assess wave-specific differences in parental knowledge or suspicion according to youth tobacco use status. For longitudinal analyses, youth tobacco initiation at waves 2, 3, and 4 were the dependent variables in separate logistic regression models with longitudinal weights. Wave 1 household tobacco rules and talking about not using tobacco were the main predictor variables. Household rules was specified as a 5-level categorical variable: both parent or guardian and child endorse more permissive rules on both product types, both endorse strict rules on burned tobacco , both endorse strict rules on not burned tobacco , parent and youth discordant on both product types, and both endorse strict rules on both products types. As exploratory analyses, we examined several alternative model specifications. We hypothesized that changes in social environments as youth age could reduce any impact of household rules on tobacco initiation over time. Therefore, we explored interactions of household rules with baseline age. Additionally, we explored whether household rules may differentially impact initiation of different types of tobacco by specifying multinomial logistic regression models for a 4-level dependent variable: no initiation, initiation of combustible tobacco only, initiation of noncombustible tobacco only, initiation of both product types. Finally, given that exposures and covariables are potentially time varying, we specified a repeated measures model using generalized estimating equations for 1-year initiation outcomes, taking any observation of a youth tobacco never user in waves 1, 2, and 3. For all models, missing covariable values were multiply imputed .

Although missingness was uncommon for any one tobacco use variable , missing tobacco responses were also imputed when examining parental knowledge or suspicion because missingness compounded when deriving categories: 7.7% of participant observations were missing $1 tobacco variable. Analyses were conducted by using Stata 16.0 . Results were considered statistically significant at P , .05.Tobacco poly use was the most common behavior among current youth tobacco users in waves 1 to 3; in wave 4, e-cigarette only use was most common . Among poly tobacco users, 77% to 80% reported smoking cigarettes, depending on the survey wave. Social and demographic variables were similar in distribution over time . In all waves, parents or guardians were substantially less likely to report knowledge or suspicion that their children had used tobacco if their children reported use of only e-cigarettes, non-cigarette combustible products, or smokeless tobacco compared with use of cigarettes or multiple tobacco products . In covariable adjusted models, other factors associated with greater parent knowledge or suspicion included lower parent educational attainment; the child being older, being male, identifying as non-Hispanic white, living with a tobacco user, or residing in another home; and the parent respondent being the child’s mother .Among wave 1 youth who reported never using tobacco, most parent child pairs mutually endorsed having strict household rules that prohibited use of any burned tobacco and not-burned tobacco . Half of youth reported that a parent or guardian had talked with them about not using tobacco within the past 12 months. There was high percentage agreement between parent and youth responses regarding household rules , although inter rater reliability was constrained under a high marginal prevalence of strict rules . Household rules and talking about tobacco were uncorrelated . Strict household tobacco rules were associated with less tobacco initiation . Among wave 1 tobacco never users, 15% initiated use of $1 tobacco product by wave 2, 24% by wave 3, and 33% by wave 4. At all time points, children in households with the strictest rules prohibiting tobacco use had 20% to 26% lower odds of tobacco initiation compared with children in the most permissive households .

Households with strict rules only for burned or not burned tobacco were also numerically associated with less initiation compared with the most permissive households, albeit not statistically significantly in these groups of smaller sample size. In contrast, youth who reported that their parent or guardian had talked with them about not using tobacco did not demonstrate lower odds of tobacco initiation; in fact, tobacco initiation was higher at waves 3 and 4 . Other factors positively associated with tobacco initiation in all waves were the child being older, the child living with another tobacco user, the child residing at least part-time in another home, the child having used alcohol or cannabis, and greater sensation seeking . In exploratory analyses, although interaction by child age was not statistically significant overall, numerically, strict household rules were associated with lower odds of tobacco initiation among children who were younger at wave 1 . In multinomial models, strict household rules were associated with lower odds of noncombustible tobacco initiation at all 3 time points but not necessarily with lower odds of combustible tobacco initiation . However, initiation of only combustible tobacco was uncommon , which yielded imprecise estimates. In the repeated measures analysis, strict household rules remained associated with lower odds of tobacco initiation within a year .In this assessment,vertical growing cannabis we identified substantial lapses in parents’ awareness of their children’s tobacco use. Most parents or guardians registered suspicion when their children smoked cigarettes or reported poly tobacco use . Only approximately half as many knew or suspected when their children used only e-cigarettes or non-cigarette combustible products. Of parental strategies to prevent future tobacco use by their children, setting strict household rules that prohibit all forms of tobacco use by anyone within the home was associated with less youth tobacco initiation, whereas talking with children about tobacco was not. The percentage of parents aware or suspecting their children’s cigarette smoking was higher than in previous findings suggesting poor parental awareness of youth smoking. Greater awareness may be due to increasing social concern around youth smoking or survey measurement differences. However, low parental awareness of e-cigarette use belies rising public and media attention surrounding youth vaping.

Constantly changing e-cigarette device designs and terminology pose an increasing challenge for parents to recognize, whereas lack of smoke and odor enhance concealability.Notably, PATH Study data were collected before a 2019 outbreak of vaping-associated lung injury,which could heighten parental awareness going forward. Cigarette smoking youth smoke more frequently than e-cigarette users use e-cigarettes, potentially increasing parental awareness opportunities. Lower awareness for cigars and hookah, which do produce smoke and odors, suggests a wider need for parents to monitor for all tobacco products, including those they may perceive as less common or concerning. Findings related to tobacco-free households align with previous research revealing that home anti-smoking attitudes and rules contribute significantly to youth smoking prevention.The present work suggests that this benefit extends beyond cigarettes to include initiation of any tobacco product use. Creating home tobacco-free environments offers the additional advantage of protecting children from harmful secondhand smoke exposure and may also benefit household adults by aiding smoking cessation.Our results align with longitudinal findings revealing a benefit of household smoking bans, whether or not youth lived with smokers.Our finding that the benefits of strict household rules appear greatest at younger ages suggests a need for additional focused prevention when adolescents transition to young adulthood and potentially enter new social environments. Unexpectedly, strict household tobacco rules were more strongly associated with prevention of noncombustible tobacco use than combustible tobacco use. This result must be interpreted cautiously because many youth initiate use of both product types, and strong concordance between burned and not-burned household tobacco rules makes it difficult to isolate independent effects. Nonetheless, setting household tobacco use rules may be a promising tool against the rise in youth e-cigarette use. Contrary to rules governing tobacco use in the home, youth who reported that that their parent or guardian had talked with them about not using tobacco were at higher odds of initiating tobacco use after 2 or 3 years. An implication of this result is that telling children not to use tobacco does not benefit youth compared with setting norms and examples via tobacco-free rules that apply to everyone. Alternatively, it is possible that parents were more inclined to talk about tobacco with youth already at elevated risk of tobacco use on the basis of personality aspects not captured by study variables.In the current study, we did not measure the quality or frequency of parents’ anti-tobacco communication: likely key elements of effectiveness.Therefore, although strong household rules appears to be a much more promising approach, it should not necessarily be concluded that all parental communication is unhelpful in youth tobacco use prevention. Advantageously, the current study features a large, prospective, nationally representative sample. To our knowledge, this analysis is the first to assess prospective outcomes of home tobacco use policies on youth initiation of cigarette and noncigarette tobacco use and the first national study to assess parental awareness of their children’s use of multiple noncigarette tobacco products. Numeric findings were robust to the length of follow-up and adjusted for an extensive suite of established youth tobacco use risk factors. Among methodologic considerations and limitations, the main outcome measure in this study, initiation of any tobacco use, is a critical milestone, particularly among youth for whom daily smoking may develop over several years.However, long-term established tobacco use deserves attention in future research. Speculatively, youth might report tobacco use differently with in-home questionnaire administration versus in-school questionnaire administration, with unclear impact on the present results. In our 2- and 3-year models, we did not account for the timing of tobacco initiation or time-varying exposures or covariables. However, in an 11-year longitudinal study in Italy, the authors reported that living with smoking family members in adolescence and absence of a household smoking ban in young adulthood were both associated with established smoking among young adults.

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D9 -THC is the only natural cannabinoid presently used in the clinic

In the age ranges and samples in which we found that ERO was significant for the onset of alcohol use or alcohol dependence, it was the lower values which characterize the risk factor, which is consistent with the results in adolescents and young adults in the studies by Rangaswamy et al. , Kamarajan et al. , and Gilmore et al. . In those investigations high risk groups had lower ERO values than the low risk groups. That no effects of regular alcohol use on ERO values were found is consistent with similar results obtained by Perlman et al. .It is important to note that the objectives of the twin studies considered here and of this study are quite different. The twin studies investigate the presence of a ‘‘disease’’ condition, although exactly which condition varies considerably among studies. The objective of this study, as a survival analysis, is to analyze the factors contributing to an event, the onset of a condition. Once the condition has come to pass, it is not of further interest in survival analysis. The genetic effects which produce the condition are only significant at the onset of the condition, and their effects persist only if the subsequent onset of the condition in other subjects is attributable to them. In the twin studies post-onset presence of the condition is part of the outcome analyzed. That is, in the longitudinal studies using multistage models, the affected subjects are retained throughout the study subsequent to their becoming affected, while in the survival analysis method used in this study, the affected subjects are removed from consideration in the study once they have become affected, and no longer influence the results. Therefore, although the use of a longitudinal multi-stage model in van Beek et al. and Baker et al. enables genetic influences to have age-specific characteristics,vertical growing garden these effects are modeled as persisting through time as a result of an effect at a single age range. If early onset alcohol use is associated with the more genetically determined form of alcoholism then it would be expected that genetic factors leading to early drinking and dependence would be manifest. Our results are consistent with this hypothesis.

The pattern of genetic results obtained here, albeit from a single gene, is weighted towards the strongest effects manifesting themselves in the youngest age range. However, most twin studies find low genetic influences at younger ages and increases in genetic influences with age , although not all twin studies have this conclusion . These results can be understood after examination of the populations from which the twin samples are drawn and the outcomes which are modeled. The samples in the twin studies are drawn from the general population, not from the densely affected families which form the bulk of the sample used here. Thus genetic effects will be more difficult to find in the twin studies, particularly for the rarer, more genetically affected conditions. In a number of studies outcome definitions are broad, and are not subject to as strong genetic effect as more restricted outcomes such as alcohol dependence or externalizing disorders.The discovery of the cannabinoid receptors and endocannabinoid ligands has generated a great deal of interest in identifying opportunities for the development of novel cannabinergic therapeutic drugs. Such an effort was first undertaken three decades ago by a number of pharmaceutical industries, but was rewarded with only modest success. However, the newly acquired knowledge on the physiological roles of the endocannabinoid system has significantly enhanced these prospects. At the June 27, 2004 workshop ‘‘Future Directions in Cannabinoid Therapeutics II: From the Bench to the Clinic’’, sponsored by the University of California Center for Medicinal Cannabis Research, we on the Scientific Planning Committee were asked to identify the areas of research with the most immediate promise for the development of novel therapeutic agents.

The Committee identified four broad areas involving modulation of the endocannabinoid system as particularly promising in this regard: agonists for central CB1 cannabinoid receptors and peripheral CB2 receptors, antagonists of CB1 receptors, inhibitors of endocannabinoid deactivation, and endocannabinoid-like compounds that act through mechanisms distinct from CB1 and CB2 receptors activation. Below, we summarize the data presented at the Workshop and the consensus of its participants on the most exciting opportunities for drug discovery.Two endogenous agonists of cannabinoid receptors have been well characterized and are now widely used in research: anandamide , and 2-arachidonoylglycerol . Both molecules derive chemically from the polyunsaturated fatty acid, arachidonic acid, which is used in nature as the starting material for other important signaling compounds, such as the eicosanoids. Additional endocannabinoid-related compounds present in the body include virodhamine, which may act as an endogenous antagonist of CB1 receptors, and arachidonoylserine, which may engage an as-yet-uncharacterized cannabinoid-like receptor expressed in the vasculature. As is well-known, the Cannabis plant contains more than 60 cannabinoids, which include -D9 -tetrahydrocannabinol , cannabigerol, cannabidiol, cannabinol, cannabichromene and cannabicyclol. Attention has been mostly focused on D9 -THC, because of its multiple biological properties. Nevertheless, less studied compounds such as cannabidiol may also be important, although we do not yet know at which receptors they may act to achieve their effects. In addition to these plant-derived cannabinoids, an extensive set of synthetic cannabinergic agonists has been developed over the last 30 years. Products of these efforts include CP-55940 , created by opening one of the rings of the tricyclic D9 -THC structure and introducing other small changes in its structure; HU-210 , a very potent cannabinoid agonist resembling some D9 -THC metabolites; and WIN55212-2 , which belongs to an altogether different class of chemicals, the aminoalkylindoles.

Additionally, the metabolically stable synthetic analog of anandamideR-methanandamide is routinely used as a pharmacological probe to circumvent the short half life of the natural substance. Two important new additions to this armamentarium under discussion at the workshop include a peripherally acting cannabinoid agonist in preclinical development by Novartis for the treatment of neuropathic and inflammatory pain , andBAY-387271 , a centrally acting cannabinoid agonist in Phase II clinical studies for the treatment of stroke. The interest of the pharmaceutical industry in the application of cannabinoid agonists to the treatment of pain conditions is not recent. Indeed, most of the compounds now in experimental use derive from such an interest. Historically however cannabinoid agonist development has not proved clinically fruitful, largely because of the profound psychotropic side effects of centrally active cannabinoid agonists, hence the attention given to peripherally acting cannabinoids, which exhibit significant analgesic efficacy and low central activity in animal models. Neuroprotection is a relatively new area for cannabinoid agonists, but one that appears to be already well advanced. Preclinical studies have made a convincing case for the efficacy of cannabinoid agents not only in experimental brain ischemia, but also in models of Parkinson’s disease and other forms of degenerative brain disorders. The results of a Phase II clinical trial with BAY-387271 are awaited with great excitement. Also highlighted during the conference were various derivatives of cannabidiol. Particularly interesting in this regard was the compound -7-hydroxy-4#- dimethylheptyl-cannabidiol a hydroxylated, dimethylheptylated cannabidiol,vertical growing greenhouse structurally related to HU-210. Like D9 -THC, 7-OH-DMH-CBD is a potent inhibitor of electrically evoked contractions in the mouse vas deferens. However, 7-OH-DMH-CBD does not significantly bind to either CB1 or CB2 receptors and its inhibitory effects on muscle contractility are not blocked by CB1 or CB2 receptor antagonists, suggesting that the compound may target an as-yet-uncharacterized cannabinoid-like receptor. This hypothesis is reinforced by pharmacological experiments, which suggest that 7-OH-DMH-CBD displays anti-inflammatory and intestinal-relaxing properties, but does not exert overt psychoactive effects in mice. However, the nature of this hypothetical receptor and its relationship to other cannabinoid-like sites in the vasculature and in the brain hippocampus remains to be determined.Another way to reduce central side effects is to target peripheral CB2 receptors, which are expressed in the brain only during inflammatory states and even then are limited to microglia. Selective CB2 receptor agonists include the compounds AM1241 and HU-308 . Compounds of this type offer a great deal of promise in the treatment of pain and inflammation. Studies conducted on multiple animal models of pain have shown that the CB2-selective agonist AM1241 has robust analgesic effects and is very potent in neuropathic pain models.

These effects are maintained in CB1-deficient, but not in CB2-deficient mice.Cannabinoid analogs are currently in development or being tested by Astra, Bayer, Endo, GSK, GW Pharmaceuticals, Indevus, Kadmus Pharmaceuticals, MAK Scientific, and Pharmos. Some of the obvious issues in drug development are efficacy, side effects, and regulatory scheduling. With regard to efficacy, the primary clinical targets are pain, stroke, nausea, appetite, and cough. Potential side effects in addition to the well-known central psychotropic actions include cardiovascular and immune perturbations, as well as fertility problems. Finally, a major question from the perspective of drug industry is one of regulatory scheduling: that is, whether any drug acting either directly or indirectly through the endocannabinoid system will be subject to the restrictive scheduling of D9 -THC, or whether scheduling will be determined by side effects, as is the case with most drugs. A large number of pharmaceutical companies have started active CB1 antagonist programs, mostly as a result of the clinical success of SR141716A , the first CB1 antagonist to be developed. This molecule has successfully completed Phase III studies and is anticipated to become available within a year for the treatment of obesity and tobacco addiction. Rimonabant is an inverse CB1 agonist with a Ki of 11 nM at the CB1 receptors and 1640 nM at CB2. Additional agents currently in development include SLV-326 and LY320135 . However, all of these compounds are inverse agonists. A series of neutral antagonists has been generated, but remains not as well characterized in the literature. Examples of this class are the compounds O-2654 and AM5171 . As noted above, therapeutic areas for cannabinoid antagonists include obesity, drug addiction and perhaps CNS disorders.The mechanism by which cannabinoid antagonists exert their anti-obesity effects is still not fully understood. Data on rimonabant presented at the workshop identified two possibilities. First, there is a loss of appetite. Mutant mice that are deficient in CB1 receptors eat less than wild-type controls. Second, there is an increase in metabolic rate and a loss of fat mass. These effects may be linked, on the one hand, to the ability of rimonabant to affect corticotropin-releasing hormone , as suggested by the fact that CB1 receptors colocalize with CRH receptors in the hypothalamus. This may be significant for explaining the drug’s effects on appetite drive, as it is known that CRH is anorexigenic. On the other hand, mice that lack CB1 receptors display a hyperactivity of the hypothalamicpituitary-adrenal axis, with increases in both ACTH and corticosterone. This phenotype may be important in regard to overall metabolic rate. Another possible mediator of the long-lasting effect on body weight reduction unrelated to altered food intake is the adipocyte, because CB1 receptor activation causes lipogenesis, which is blocked by rimonabant.CB1 cannabinoid receptors are present on the cell surface of neurons within the brain reward circuitry. Furthermore, endocannabinoids may be released from dopamine neurons in the ventral tegmental area , and from medium spiny neurons in the nucleus accumbens of the brain reward circuit. Additionally, endocannabinoids and D9 -THC activate CB1 receptors and by doing so regulate reward strength and drug craving. Though we do not know how this occurs, it is likely that these mechanisms extend to all drugs of abuse, because collectively these drugs show the propensity to increase VTA dopamine neuron activity, which might be coupled to augmented endocannabinoid production from the dopamine neurons themselves. Finally, cannabinoid receptor antagonists block the effects of endocannabinoids in these reward circuits. Preclinical work shows that priming injections of cannabinoid agonists reinstate heroin-seeking behavior after a prolonged period of abstinence in rats trained to self-administer heroin. The cannabinoid antagonist rimonabant fully prevents heroin-induced reinstatement of heroin-seeking behavior. Additionally, rimonabant significantly attenuates cannabinoid-induced reinstatement of heroinseeking behavior. All these findings clearly support the hypothesis of a functional interaction between opioid and cannabinoid systems in the neurobiological mechanisms of relapse and might suggest a potential clinical use of cannabinoid antagonists for preventing relapse to heroin abuse.

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