Prospective studies have also demonstrated an increased risk of ARDS among smokers

Posted on December 19, 2023 by hemp2022

In 2014, PM less than 10 mm in diameter and less than 2.5 mm in diameter accounted for at least 3 million deaths and 85 disability-adjusted life years, primarily because of impacts on chronic cardiovascular and pulmonary conditions.Recently, air pollution in the United States has begun increasing for the first time since 2016 .Ambient pollution is a risk factor not only for the development or worsening of chronic illnesses but also for acute illness. For example, a case control study of older adults in Canada found that long-term exposure to PM 2.5 and NO2 was independently associated with an increased risk of hospitalization for community-acquired pneumonia.Short-term exposure to increasing levels of PM 2.5 was also shown to increase the risk of hospital admission for cardiac and respiratory disease in the United States.Several recent studies have demonstrated that exposure to even low to moderate levels of ambient pollutants increases the risk of developing ARDS. In a prospectively enrolled cohort of patients with ARDS in the Southeastern United States, long-term ozone exposure was associated with the development of ARDS in a dose-dependent manner.This association was most pronounced among patients with trauma as their primary risk factor. Although the association between ozone exposure and the development of ARDS remained significant when controlling for potential confounders including smoking status, there was a statistically significant interaction between ozone exposure and smoking. When patients were stratified by smoking status, ozone exposure remained significantly associated with ARDS only among smokers. The investigators concluded that cigarette smoking likely potentiates the risk from ozone exposure.A subsequent study of patients from a prospectively enrolled cohort in Philadelphia further investigated the relationship between exposure to pollutants and ARDS development among patients with trauma.This study analyzed exposure to low to moderate levels of ozone, NO2, SO2, PM 2.5, and carbon monoxide . Long-term exposure to each of the pollutants was independently associated with an increased odds of developing ARDS. Furthermore,growing tables even 6 weeks of exposure to NO2, SO2, and PM 2.5 increased the odds of developing ARDS.

Differences between the findings of the 2 studies might be accounted for by regional variation in levels of pollutants and air quality monitoring and by the shared risk factor of the population in the second study. Together these studies suggest that exposure to ambient pollution even at low to moderate levels for time periods as short as 6 weeks increases the risk of ARDS. Large epidemiologic studies have also found associations between exposure to ambient pollution and an increased risk of developing ARDS. An observational study of more than 1 million hospitalizations between the years 2000 and 2012 among Medicare beneficiaries who developed ARDS used advanced modeling drawing on multiple data sources to predict average annual levels of ambient pollution across more than 30,000 zip codes.The investigators found that the rate of ARDS hospitalizations increased with increasing levels of both PM 2.5 and ozone. These findings were consistent even in regions where pollutant levels were within national air quality standards. The effect of PM 2.5 was most pronounced among patients whose primary risk factor was sepsis. Ozone exposure had the greatest effect among patients with pneumonia or trauma as their primary risk factor. Although fully accounting for confounding factors in observational studies can be difficult, results were similar in a propensity matched analysis that included variables such as demographic variations and percent of ever-smokers.The results of this large study demonstrate that the association between ambient pollution and ARDS is present outside of the trauma population in patients who are older with comorbid conditions. Another retrospective cohort study of more than 90,000 patients found that increases in average annual PM 2.5 and ozone concentrations independently increased the odds of death from ARDS, suggesting that ambient pollution impacts not only ARDS incidence but also its outcomes.High levels of ambient pollution have also been associated with incidence and adverse outcomes in the coronavirus disease 2019 pandemic, although further studies in this area are needed.

The preponderance of the literature examining the connection between ARDS and ambient pollution has revealed an association between long-term rather than short term exposure to pollutants and ARDS incidence and outcomes. For example, the investigators who found a link between long-term ozone exposure and ARDS did not find the same association for 3-day exposure to environmental pollutants.However, one study from Guangzhou, China, demonstrated an association between short-term PM exposure and incident ARDS.This association may be related to the exceptionally poor air quality of the region in contrast to the other studies, which focused on settings with low to moderate levels of pollutants. There is some evidence, however, that short-term exposure to low levels of ambient pollution is associated with adverse pulmonary outcomes in critically ill patients. A study from Antwerp, Belgium—an area with historically low levels of ambient pollution—found that short-term pollution exposure was associated with longer mechanical ventilation.This study included a broad range of critically ill patients, some of whom did not have ARDS, but does suggest that a deleterious effect from short-term pollution exposure is not limited to areas with exceptionally poor air quality. Various underlying biological mechanisms may explain the basis for the relationship between environmental pollution and ARDS. A meta-analysis of exposure studies in healthy volunteers found that ozone increases the number of bronchoalveolar lavage neutrophils,which are implicated in ARDS pathogenesis.Ozone exposure also increased total protein levels in this analysis,reflecting loss of alveolar epithelial/endothelial barrier integrity.Many components of air pollution exert deleterious effects on pulmonary surfactant.Urban air particles directly stimulate an inflammatory response by pulmonary macrophages in vitro.PM has also been shown to increase markers of apoptosis, oxidative stress, and inflammation and to directly cause lung injury in mouse models.In humans, increased PM 2.5 levels are associated with circulating markers of endothelial injury,which is one of the key pathophysiological mechanisms in the development of ARDS.Although environmental pollutants alone may not be sufficient to induce severe pulmonary injury in humans, they likely increase susceptibility to other causes of ARDS such as respiratory infection and prime the alveolus for damage in these settings.

Wildfire smoke is an increasingly prevalent source of environmental pollution. Climate change has led to more frequent wildfires over a longer season.In the United States, PM air quality has improved over the past 3 decades except in areas that are prone to wildfires.Wildfires are associated with acute increases in ozone and PM as well as other pollutants such as volatile organic compounds.As noted earlier, previous studies of the relationship between ambient pollution and ARDS have generally focused on the average exposure in various regions over time, rather than on events that might be expected to acutely increase ambient pollution. In addition, smoke from wildfires may have chemical properties that make its risk profile different from that of PM or smoke from other sources.Although it is clear that wildfire-related pollution contributes to increased respiratory morbidity and health utilization overall,the specific relationship between ARDS and exposure to pollutants generated by wildfire smoke has not been studied . In vitro evidence demonstrates that wood smoke exposure diminishes alveolar barrier function and increases alveolar endothelial oxidative stress and apoptosis.In mice, PM collected during wildfires induced a more pro-inflammatory response and greater oxidative stress than ambient PM collected in the absence of wildfires.Wood fire smoke exposure has also been shown to induce a pulmonary and systemic inflammatory response in healthy volunteers.It is mechanistically plausible that the increased inflammation,grow tables 4×8 oxidative stress, and lung micro-vascular permeability in response to wood fire smoke demonstrated under experimental conditions would translate to an increased risk of ARDS. Future research should test whether ARDS incidence and outcomes change during or after wildfire events.The link between cigarette smoke and adverse health outcomes is well established, and reducing cigarette use has been a major focus of public health efforts over the past half century.Although rates of tobacco smoking have generally declined globally, they remain unacceptably high, and cigarette smoking is a leading cause of avoidable death. For example, the 2015 Global Burden of Disease Study found that approximately 11% of women and 14% of men in the United States report daily smoking and that smoking accounted for 6.4 million deaths globally.Alternative tobacco and nicotine delivery systems such as electronic cigarettes , or vapes, are increasingly popular, an especially concerning trend among children and adolescents.Although their long-term health consequences are not well established, e-cigarettes cause a specific lung injury syndrome, e-cigarette- or vaping-associated lung injury .E-cigarettes will be discussed in detail in a separate section. Although some retrospective studies have not found an association between cigarette smoking and ARDS,many studies demonstrate that both active smoking and passive cigarette smoke exposure are associated with ARDS, especially among certain clinical populations. Importantly, this association is independent of alcohol use, which is frequently associated with smoking and is a known risk factor for ARDS.A retrospective cohort study of patients in Northern California found that ARDS was more common among self-reported smokers in a dose-dependent manner. The investigators estimated that smoking carried an attributable risk in ARDS of 50%.A 2014 study of 381 patients with ARDS previously enrolled in randomized clinical trials examined the relationship between tobacco exposure and ARDS.Rather than relying on patient or surrogate reports, which lack sensitivity when compared with biomarkers for tobacco exposure,urine levels of NNAL -1–1-butanol were used to determine smoking history. The rate of active smoking among patients with ARDS in this study was significantly higher than the population average .

Smokers were younger and had fewer comorbidities than nonsmokers despite similar ARDS severity. Although unadjusted mortality among smokers was significantly lower than in nonsmokers, there was no significant difference after adjusting for comorbidities and severity of illness,suggesting that smokers develop ARDS when their illness is less severe than that of otherwise similar patients. Current cigarette smoking conferred increased odds for the development of transfusion-related acute lung injury in a two center prospective case-control study.Donor smoking history increased the odds of grade 3 primary graft dysfunction in a multi-center prospectively enrolled cohort of lung transplant recipients.A prospective study of the association between tobacco exposure and the development of ALI after blunt trauma used plasma levels of cotinine to differentiate between active and passive smoke exposure and to quantify exposure levels.Active smokers and passively exposed patients in this cohort from a single level 1 trauma center had similarly increased odds of developing ARDS independent of confounding factors, including alcohol use and trauma severity. Higher levels of plasma cotinine were associated with higher odds of developing ARDS.Another prospective study of patients with trauma enrolled between 2005 and 2015 confirmed that cigarette smoke exposure remains an important risk factor for ARDS and highlighted a particularly elevated risk among passive smokers in later years.In patients with trauma, impaired platelet aggregation likely mediates at least part of the effect of cigarette smoke exposure on ARDS risk.In addition, cigarette smoke alters the microbiota in patients with trauma such that their pulmonary microbiome is enriched for specific pathologic bacteria that are associated with ARDS development.In a prospectively enrolled cohort with diverse predisposing risk factors for ARDS, active cigarette smoking both by self-report and urine NNAL was associated with an increased odds of ARDS among patients with non-pulmonary sepsis as their primary predisposing risk factor.Patients with trauma and transfusion as their primary risk factor were not included in this study because of the previously established link between smoking and ARDS in these populations. Again, the mortality rate of active smokers was lower in an unadjusted analysis, but mortality was similar after adjusting for baseline severity of illness.This finding is consistent with the previous one that smokers are at increased risk of developing ARDS when their underlying illness is comparatively less severe. Similarly to ambient pollution, cigarette smoke exposure likely predisposes the lung to injury in the setting of a second insult such as trauma, multiple transfusions, or sepsis . This concept was elegantly demonstrated in an experimental model in healthy humans who were exposed to inhaled lipopolysaccharide .BAL and plasma biomarkers for alveolar epithelialcapillary permeability, inflammation, and alveolar endothelial dysfunction were compared between self-reported smokers and nonsmokers. Absolute measurements were consistent with more alveolar permeability to protein and inflammation in smokers, and statistical tests of interaction demonstrated that smoking potentiated these responses to LPS.In mice, cigarette smoke exposure itself does not cause frank lung injury, but mice exposed to cigarette smoke develop worse pulmonary edema, increased vascular permeability, worse histologic injury, and increased biomarker evidence of inflammation after exposure to LPS.

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Counts and rates were not reported when n < 16 to protect the identity of individuals in the dataset

Posted on December 18, 2023 by hemp2022

Specific to being a sexual minority, GBM who were not out about their gay identity were less likely to report having any other mental health condition at the univariable level than those who were open about being gay. We posit that this may be due to the fact that individuals who are public regarding their sexual orientation are easier targets for harassment or discrimination. This is supported by findings from D’Augelli and Grossman , where GBM who came out at an earlier age and GBM who spent more years out of the closet were more likely to experience victimization than individuals who came out later or who spent less time out of the closet. More generally speaking, Meyer argues that experiences of victimization in the forms of stigma, prejudice, and discrimination that GBM experience may be the cause for the higher prevalence of mental health conditions in GBM populations and refers to this as minority stress . Stigma may also help explain why HIV-positive GBM were more likely to report a substance use disorder in our study. HIV-related stigma has been linked to poorer mental health in a meta-analysis by Logie and Gadalla and a review by Smit and colleagues . Readers should be cautious when interpreting our results. Most notably our results rely on participants’ retrospective self-report of recent substance use and sexual behavior and compare these data with lifetime mental health diagnoses. As such, we are limited in determining causal direction, but instead position these findings as a more representative profile of GBM who had ever been diagnosed with a mental health condition given our use of respondent-driven sampling. We did not conduct diagnostic interviews to account for undiagnosed conditions,mobile racking for growing and thus underestimated the true burden of mental health issues. We attempted to address current symptomology through the inclusion of AUDIT and HADS scores.

However, given the paucity of validation studies for AUDIT, but particularly HADS within GBM populations, we caution the interpretation of these findings and call for new research validation studies with GBM populations. Regardless, our analyses demonstrate some measure of construct validity in that higher scores on both measures were linked to reporting mental health conditions in our study. Our measure of sexual orientation “outness” was only asked for gay-identified participants, and a general measure should be included in future studies. A nurse-administered structured interview was used to assess mental health diagnoses and current treatments to ensure these questions were more accurately understood and answered. Given the potential impact of social desirability and reporting bias , we used CASI to collect data regarding illicit substance use. However, we did not use drug testing to confirm or correct self-report data and likely underestimated the true prevalence of substances used . Despite these shortcomings, one of the strengths of our study is the use of RDS to overcome previous sampling shortfalls with GBM and produce a more accurate representation of the population parameters of these variables of interest for the GBM population of Metro Vancouver. Our study also adds new data regarding the detailed prevalence of substance use and mental health conditions among GBM populations in Canada filling a gap in currently available published literature. Finally, our work goes further to examine explicitly the relationship between substance use and mental health conditions among GBM identifying important relationships that have implications for counseling and public health services, interventions, and policy. The greater burden of mental health conditions and higher prevalence of substance use in GBM populations highlight the need for a more explicit focus on these issues in research and service provision. Mental health specialists should be aware of the relationships with sexuality and substance use when working with GBM clients, particularly issues regarding identity disclosure, number of sexual partners, and higher background community prevalence of substance use .

Future research should seek to validate current measures and to confirm the relationship between substance use and mental health conditions, which has been demonstrated to produce a syndemic including suicidal ideation among GBM and HIV acquisition . Our study was based in a major metropolitan area, which may limit generalizability to GBM in rural or remote regions, whom are a population with distinct needs and challenges that should be further examined. In order to evaluate generalizability, additional research is needed to explore these issues among GBM populations in other urban and non-urban centers across Canada, particularly if these studies employ RDS or other more representative sampling methods. Given the role of social factors in mental well-being, future research should directly examine experiences of homophobia or heterosexism as possible precursors to substance use and/or mental health issues, along with potential mediators and protective factors. Examining demographic factors independent of one another may not reflect the diversity of experiences that exists among GBM. Using an intersectional approach, which looks at how multiple identities such as race, sexual orientation, and class, interact with one another to shape experiences , may also explain the distribution and experiences of mental health and substance use within diverse communities of GBM. In spite of experiences of marginalization and discrimination, many GBM do not go on to develop mental health conditions or engage in harmful substance use. Shilo, Antebi, and Mor found that factors such as support of family and friends, meaningful connections with the LGBT community, and having a steady partner, protect against developing poorer mental health in lesbian, gay, bisexual, queer, and questioning adults. Thus, more focus on factors such as these that promote resiliency in GBM would be beneficial to include in future research on mental health and substance use in these populations. Compared with the Canadian population, GBM living in Metro Vancouver have increased levels of substance use and mental health conditions. The strong link between substance use and mental health among GBM has important implications for public health promotion programming and care service provision.

A number of social determinants increase the likelihood of mental health diagnosis among GBM, including disclosure of sexuality, low income, and race/ethnicity. GBM living with HIV were significantly more likely to have a lifetime doctor-substance use disorder compared with HIVnegative GBM. Greater attention to these issues is needed across all health and social services given their disproportionate effect on GBM populations. Health promotion and interventions should address issues of substance use, mental health, and sexuality in unison and future research can help direct these efforts by examining possible precursors of these issues, which may be the result of discrimination, prejudice, and stigma.Tobacco use in the general population has declined substantially in the past three decades, but rates remain high in certain populations. The prevalence of tobacco use in the homeless population is 3 to 4 times that of the general population.Among homeless adults, tobacco-related chronic diseases including heart disease, cancer and chronic obstructive pulmonary disease are common and contribute significantly to the increased morbidity and mortality in this population.Among a clinic-based sample of homeless adults aged 50 and older, tobacco-attributable deaths accounted for 26% of the overall mortality and 54% of substance-related mortality.The health consequences of smoking occur disproportionately among older individuals because of the cumulative effects of long term smoking.Among older adults,modular cannabis grow racks tobacco-related chronic diseases, particularly chronic obstructive pulmonary disease and coronary heart disease, are among the most common reasons for emergency health care services and preventable hospitalizations.Current tobacco use contributes significantly to all-cause mortality among older adults, suggesting that tobacco cessation at any age is likely to significantly reduce tobacco-related morbidity and mortality.In a nationally representative sample, older adults were less likely to quit smoking than younger adults because of reduced interest in quitting smoking, higher nicotine dependence, and lower support for smoke-free norms.This highlights the need for tobacco cessation interventions that address tobacco-related beliefs and practices among older adults. Over the past 2 decades, the median age of homeless adults increased from 37 years in 1990 to almost 50 years in 2010.Despite increased tobacco-related morbidity and mortality among older homeless adults, little is known about tobacco use and cessation behaviors in this population. Prior research on tobacco use in the homeless population has focused on younger adults, where the average age of study participants in previous studies was less than 44 years.The high prevalence of tobacco use and the increased burden of tobacco-related chronic diseases with aging underscore a need for studies that characterize tobacco use and cessation behaviors among older homeless adults in order to develop tobacco control interventions that address the unique needs of this population. We conducted a study of a cohort of homeless individuals aged 50 and older sampled from the community to examine rates of and factors associated with tobacco cessation.

We hypothesized a priori that current smoking would be associated with symptoms of depression, substance use disorders, history of incarceration, and history of staying in shelters.We also hypothesized that persons who reported smoking heavily or having symptoms of depression at enrollment would be less likely to make a quit attempt at follow-up.We used previously validated questions on tobacco use at the enrollment and 6-month follow-up interviews. We asked participants whether they had ever smoked 100 cigarettes in their lifetime, and classified those who did as ever-smokers. We classified ever-smokers who reported smoking “every day or some days” as current smokers, and those who reported “not smoking at all” as former smokers. We asked current daily smokers to report the number of cigarettes smoked daily. For current non-daily smokers, we estimated average daily cigarette consumption based on self-reported numbers of cigarettes smoked on smoking days in the past 30 days. Participants reported how soon they had smoked their first cigarette after waking, which we dichotomized as greater or less than 30 minutes. We asked current smokers about their intentions to quit smoking . We asked current smokers to report whether they had stopped smoking for 1 day or longer in the past 6 months because they were trying to quit smoking. We asked participants who responded affirmatively to making a quit attempt to report the length of their last quit attempt. We defined reporting a quit attempt in the past 6-months at the follow-up visit as the primary outcome variable. We determined the proportion of participants who were abstinent for 30 days and 90 days at the 6-month study visit using self-reported information on the length of the last quit attempt. At the 6-month follow-up visit, we obtained additional information from participants on their quitting behaviors.If participants reported having made a quit attempt during the past 6 months, we asked them to report the medications, strategies, and support system they had used during their last quit attempt. Participants reported whether they had used nicotine replacement therapy and/ or any of the US Food and Drug Administration -approved medications for smoking cessation during their last quit attempt. Participants reported whether they had used other strategies to quit smoking including gradually cutting back on cigarettes, switching to smokeless tobacco, other combustible tobacco , or electronic cigarettes, or giving up cigarettes all at once. Participants self-reported their use of a telephone quit line, group or one-on-one smoking cessation counseling, hypnosis or acupuncture, and other internet or family-based support for smoking cessation. Participants also reported whether they had received advice to quit cigarette smoking from their health care provider in the past 6 months, and whether they had acted on the advice to quit smoking.Participants self-reported age, gender and race/ethnicity at the enrollment visit. At the enrollment and follow-up interviews, participants reported whether they had spent any time in jail or prison in the past 6 months. At both visits, we gathered residential history of every place that the individual had stayed, by using a 6-month follow-back residential calendar.We categorized participants as having stayed in shelters if they reported staying in a homeless shelter for single adults or families during the past 6 months.We used questions derived from the World Health Organization’s Alcohol, Smoking, and Substance Involvement Screening Test  to assess use of cannabis, cocaine, amphetamines, and opioids. We dichotomized the severity of substance use as low versus moderate to high risk .We administered the WHO’s Alcohol Use Disorders Identification Test with a shortened time frame of the previous 6 months to assess risk and severity of alcohol use disorders. We categorized AUDIT scores of 8 or more as indicative of hazardous and harmful alcohol use or an alcohol disorder.

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Edaravone is an antioxidant and ROS scavenger marketed as a neurovascular protective agent

Posted on December 15, 2023 by hemp2022

While the consensus on a healthy diet has generally been interpreted to mean limiting intake of sodium, red meat and saturated fat intake, several other dietary factors have been reported to reduce stroke risk, such as diets rich in magnesium, flavonoids, lycopenes, fruits and vegetables, and chocolate. Further, the Mediterranean diet was found to reduce cardiovascular risk in a randomized trial.Intensive exercise has been also reported to have a benefit in secondary stroke prevention.Thus, it is incumbent upon healthcare providers to emphasize lifestyle changes for stroke risk reduction. Pharmacological approaches to reduce stroke risk often include agents which prevent or reduce thrombus formation. Anti-platelet agents are used for secondary prevention in most non-cardiogenic IS patients to prevent worsening of atherosclerotic disease. The main mechanism of IS reduction are through blockade of platelet aggregation and activation through the suppression of thromboxane A2 via cyclooxygenase-1 blockade and upregulation of cAMP via phosphodiesterase 3 or P2Y12 receptor blockade. Aspirin, clopidgrel, dipyridamole, and cilostazol have all demonstrated efficacy for secondary prevention of IS through this anti-platelet effect. Prasugrel is newer antiplatelet agent, but has not been shown to be superior to conventional anti-platelet agents in recent study.Ticagrelor, a recently approved anti-platelet inhibitor of the P2Y12 ADP receptor in coronary disease, was shown to also have efficacy in primary and secondary IS prevention.Dual antiplatelet treatment typically consists of aspirin plus clopidogrel has met with conflicting results. Early studies suggested that such combination therapy led to unacceptably high risks of major cerebral and gastrointestinal bleeding and a recent metaanalysis indicated that such hemorrhage due to DAPT negated any antithrombotic benefit. It should be pointed out that these early studies used long term DAPT for months or even years. More recent studies of short term DAPT have now shown that this approach can further reduce stroke risk while not increasing the risk of significant hemorrhage .As such,grow racks indoor it is now common practice to prescribe DAPT for periods of 21 or 90 days after non-cardiogenic IS.

It should also be noted that DAPT may increase HTf when used with t-PA in experimental stroke models,In contrast, a recent study showed that combination therapy of aspirin or clopidogrel with cilostazol has been reported not to increase the incidence of HTf and to reduce relative risk of recurrent IS by 51% compared to single anti-platelet therapy.Cilostazol is also thought to have pleiotropic effects such as an improvement of endothelial function by inhibition of smooth muscle cell proliferation and reduction of inflammation.In a recent experimental study, cilostazol was also shown to have a neuroprotective effect via reduction of inflammatory molecules, stabilization of the blood-brain barrier, and prevented apoptosis.Significant extracranial carotid artery stenosis is detected about 15% of IS patients. Revascularization, either via endarterectomy or endovascular approaches, of symptomatic stenotic carotids has been shown to significantly reduce stroke risk, especially if carried out within two weeks of the index transient ischemic attack or stroke.While endarterectomy has long been the mainstay of revascularizing stenotic carotids, endovascular approaches include carotid artery angioplasty followed by stenting , which has the advantage of being less invasive and similarly efficacious.Less clear is the role of carotid revascularization on asymptomatic carotids.In patients with a cardiogenic cause of stroke, anti-thrombotic therapy to prevent thrombus formation has been shown in several studies to substantially reduce recurrent stroke, particularly for atrial fibrillation.The vitamin K antagonist warfarin has been the most widely studied and used, but recently, orally available direct thrombin and factor X inhibitors have been shown to be as effective and easier to manage than warfarin. Several clinical studies have shown that DOACs are noninferior to warfarin in the prevention of IS with a lower incidence of significant HTf. Further, the presence of cerebral microbleeds , which may be an indication of underlying cerebral amyloid angiopathy, increases the risk for cerebral hemorrhage in association with anti-thrombotic therapy. The incidence of intracranial hemorrhage in the presence of CMBs during DOAC treatment has been reported to be less than anti-platelet and warfarin therapy. This is thought to be due to the ability of DOACs to avoid inhibiting factor VII, although hemorrhage risk is still higher compared to that amongst patients without CMBs.

Thus, it is still not recommended to initiate DOAC or other anticoagulant treatment in this patient population.ESUS are now increasingly thought to be due to occult atrial fibrillation , in part, due to the availability of long term cardiac monitoring technology ; however, it is unclear whether these patients should be empirically anticoagulated.DOACs were considered for secondary prevention of ESUS; however, a few studies have failed to show that this approach is effective.Other embolic sources such as aortic plaque, patent foramen ovale, and neoplasm have been identified as the etiology of ESUS where anticoagulation is not always the indicated treatment. Hence, documentation of occult AF will be important prior to initiating anticoagulant therapy. Other beneficial effects of DOACs have been suggested in experimental studies. Dabigatran, a direct thrombin inhibitor, has been shown to inhibit microglial and astrocyte activation.Edoxaban, a factor X inhibitor, has also been shown to have anti-inflammatory effects via suppression of PAI-1, MCP-1, and TNF-α. Some ‘natural’ approaches have been studied in stroke prevention as well, but have not been routinely implemented at the clinical level. Polyphenol supplementation has been proposed as a preventive agent for IS. In a previous study, polyphenol intake was thought to act as an antioxidant, leading to reduction in atherosclerosis.It is also thought to have other beneficial properties such as regulating neurotrophin levels, especially nerve growth factor and brain-derived neurotrophic factor . Epigallocatechin gallate , which is a polyphenol found in green tea, has gained interest for its putative antioxidant and neuroprotective effects via prevention of NF-κB activation, inhibition on PI3K/Akt signaling, and improvement of mitochondrial dysfunction.EGCG also seems to the downregulate MMP-2 and MMP-9 and upregulate the endogenous t-PA inhibitor plasminogen activator inhibitor-1 . These latter observations suggest that EGCG may have a role as an adjunctive agent to t-PA by extending the therapeutic time-window for thrombolytic treatment while reducing other undesirable side effects of t-PA treatment such as severe HTf, brain edema and BBB disruption. Other polyphenols have demonstrated antioxidant effects, which have the potential to reduce stroke risk. Resveratol, a component of red wine, has been shown to inhibit phosphodiesterase and regulate cAMP, AMPK, and SIRT1 pathways during ischemic injury. Salvianolic acid has been shown to have neuroprotective effects dependent on mitochondrial connexin43 via PI3K/Akt pathway.

Flavonol rich diets has been reported for a 14% relative risk reduction of IS. Flavonoids is main sources of apple polyphenol, which has been reported to reverse oxidative stress via P38 mitogen-activated protein kinase signaling pathway.harmacological recanalization with t-PA has been the mainstay for acute IS treatment for several decades. t-PA therapy has been shown to improve neurological outcome provided it is initiated within 4.5 h from symptom onset. In addition to rt-PA therapy, recent randomized controlled trials have demonstrated the efficacy of mechanical thrombectomy in large vessel stroke.98) In several of these trials, pre-treatment with t-PA before MT intervention was superior to t-PA alone. A few studies also showed that MT could be extended to even 24h after stroke onset, provided imaging studies showed a large mismatch. The DAWN ,DEFUSE3 , and EXTEND studies all evaluated endovascular methods of thrombectomy to acutely revascularize occluded large cerebral vessels that cause stroke. These studies have not only shown that acute revascularization can improve stroke outcome from longer time windows,grow shelf rack but can also lengthen the therapeutic time windows for t-PA. These studies utilized imaging based criteria to identify appropriate candidates. In particular, those studies which showed longer time windows for thrombectomy used imaging to demonstrate a large, and thus salvageable ischemic penumbra in relation to the ischemic core . Further, imaging criteria have allowed for the use of t-PA therapy in so-called “wake-up stroke”, where the time of stroke onset is unclear because the patient reports waking up with a neurological deficit after being neurologically intact at the time of sleep. Such cases may be pre-selected by mismatch from diffusion weighted and FLAIR MRI.While the expansion of therapeutic time windows and improved outcomes have been shown in acute revascularization approaches, reperfusion injury has the potential to worsen outcome, compared to no revascularization. While this phenomenon is well established in experimental stroke models, its existence in clinical stroke has been debated. Nevertheless, some have reported a hyperintense acute reperfusion marker on MRI which is thought to predict HTf and clinical worsening in some IS patients, and this has been suggested R/I in humans.In experimental studies, R/I has been attributed to the introduction and generation of ROS when a previously occluded vessel is opened. This flood of ROS leads to inflammation. Inflammation then results in the generation of various damaging immune mediators, effector molecules and more ROS. ROS can also lead to apoptosis/necrosis via DNA/RNA damage, lipid peroxidation, and the reduction of ATP production. Further, t-PA treatment can promote extracellular matrix damage to lead to HTf. Hence, targeted R/I treatments in conjunction with t-PA and/or MT has the potential to further improve neurological outcomes.A few potential adjunctive agents have been explored at the clinical level.At the clinical level, edaravone contributes to improving neurological function and reducing adverse events. In the PROTECT 4.5 trial, the efficacy and safety of combination therapy with edaravone and t-PA in stroke patients suggested that combination therapy might increase the numbers of patients with better outcomes, accelerated recanalization and reduced HTf.

The YAMATO study showed that the timing of edaravone infusion did not affect the rate of early recanalization, symptomatic HTf, or favorable outcomes after t-PA therapy. However, early edaravone infusion in parallel with endovascular revascularization led to better functional outcomes at discharge, lower mortality, and lower incidence of HTf in a recent clinical trial. Edaravone has been already approved for the treatment of IS patients who present within 24 h of the onset of symptoms in Japan and other countries, but not the United States. Thus, the prospects of adding edaravone to t-PA and MT seem favorable. Therapeutic hypothermia has already been shown to improve neurological outcomes in comatose survivors of cardiac arrest and neonatal hypoxic encephalopathy. While it has yet to be shown whether it has any role in patients with IS, major mechanisms for its neuroprotective effect seems to be related to its effects on multiple cell death pathways including inflammation, apoptosis, excitotoxicity and preservation of metabolic stores.HT has also been shown to reduce BBB disruption and HTf in relation to t-PA use in experimental models.Combination therapy with HT and t-PA also reduced HTf and endogeneous tPA expression, and has the potential to extend the time window for other acute therapies. Few clinical studies have been carried out in IS. The ReCCLAIM and ICTuS studies assessed the combination therapy with rt-PA and HT in IS patients with large pretreatment infarcts, and both trials showed that this approach was safe and may even reduce reperfusion injury, as outcomes were improved compared to stroke patients who did not receive HT. The ICTuS2 study showed the safety and feasibility of both HT and HT with t-PA, although cooling increased the incidence of pneumonia. HT has been also combined with MT with selective brain cooling elicited by intra-arterial chilled saline infusion and was shown to be both safe and feasible.The RECCLAIM-Ⅱ also examined MT with HT; however, this trial was stopped early for lack of funding.A recent laboratory study also showed that the neuroprotective effect of HT differentially affects cells of neurovascular unit depending on the depth, duration and even timing of cooling.Yet, clinical studies used a single target temperature with fixed duration . Thus, it may be important to design future clinical trials with adjusted temperature and cooling duration depending on targeted cell type for neuroprotection versus vasculoprotection. Recent years have seen an advent in population-based studies that examine the prevalence, etiology, and developmental trajectories of diverse sub-clinical psychopathological symptoms that pose a risk for the later development of severe mental illnesses. It is increasingly recognized that most categorically defined psychiatric disorders occur on a spectrum or continuum that is not necessarily normally distributed , show high heterogeneity and symptom overlap, and share genetic and environmental risk factors . Therefore, population-based studies of psychopathology in youth assess a broad spectrum of symptoms as well as genetic risk, cognitive and general functioning, socioeconomic, and environmental factors to yield a more complete understanding of symptom etiology and development.

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What Can You Grow With Vertical Farming

Posted on December 14, 2023 by hemp2022

Frequent testing for HIV infection can identify new infections early, and it is essential in ending the HIV epidemic. HIV self-testing is an alternative HIV screening method that is commercially available, approved by the Food and Drug Administration, and can reach individuals who have never tested before. It can reach populations at risk, such as Black and Latinx individuals, identify new cases of HIV infection, and lead individuals to seek additional HIV prevention options, such as testing for sexually transmitted infections or pre-exposure prophylaxis. Prevention studies and public health programs have been adopting HIV self-tests and combining them with new technologies, such as smartphone apps or smart devices, to reach populations with high incidence of HIV infection, such as Black and Latinx MSM. Despite multiple efforts, the uptake of HIV testing remains inadequate, especially among individuals at high risk for HIV infection. Thus, optimizing the promotion of HIV testing is important. Due to their extensive popularity, social media sites and dating apps have been used to promote and recruit participants for HIV prevention research studies with high rates of success. According to a recent Centers for Disease Control and Prevention report reviewing HIV self-testing programs, 27 health departments and community organizations used multiple platforms for promotion, mainly social media followed by “traditional” printed media and dating apps . Compared to in-person recruitment, web-based platforms have the capacity to reach a high number of difficult-to-reach populations and individuals at risk , overcoming stigma or other logistic obstacles in a cost-efficient manner. Indeed, the New York Department of Public Health used advertisements on social media, dating apps,plant grow rack and websites to reach 28,921 users, identifying 17,383 eligible MSM, transgender, and gender nonconforming individuals during its HIV self-testing campaign. Most of the participants were under the age of 35 years and identified as Black or Latinx. In addition, the first wave of this campaign reached 3359 users in only 23 days, distributing 2497 home test kit voucher codes to eligible users.

Social media and dating apps have been widely adopted as means of promoting HIV home testing. Although different from dating apps and social media sites, information search sites are commonly used for seeking information on HIV testing and PrEP and could represent a promising outreach avenue. Their use for enrollment and HIV testing promotion has not been evaluated. However, little is known about the relative effectiveness of these different web-based platforms in promoting HIV self-testing. Parker et al conducted a secondary analysis in a study enrolling substance-using sexual and gender minority adolescents and young adults to evaluate the efficacy of their enrollment strategy. The study used multiple methods to enroll participants, including social media platforms , dating apps , internet-based health boards, and venue-based enrollment. They recorded 17,328 visits to the eligibility screener on the landing page, with a 36.2% screener survey completion ratio. Researchers identified 580 participants among those who consented and were eligible to participate , indicating a high recruitment proportion. The majority of their participants were enrolled from Facebook, Instagram, and Grindr. Studies and programs use these platforms based on the experience of previous studies and expert recommendations. Data on the effectiveness of public health promotion through different platforms leading to testing or PrEP are missing. We can only infer the effectiveness of promotion indirectly, as head-to-head comparisons of the effectiveness of the different platforms and sites to reach individuals for public health promotion are missing. This would allow researchers and prevention programs to optimize their budget and strategy. The primary objective of this study was to compare ordering of HIV self-testing kits among users recruited through 3 different types of web-based platforms, including social media, dating apps, and information search sites. Test kit ordering was used as a proxy for analyzing the effectiveness of promoting HIV self-testing on different sites. The secondary goal was to evaluate the association of key moderating variables—substance use, psychological readiness to test, and perceptions and attitudes related to HIV testing—with the ordering of HIV self-testing kits.

In this longitudinal observational cohort study, advertisements promoting free HIV self-testing were placed on three platform types: social media , dating apps , and information search sites . The advertisements were organized in 2 “waves,” with each wave consisting of 1 social media website, 1 dating app, and 1 information search site. The Wave 1 recruitment stopped early, as Grindr unexpectedly stopped running all self-service platform advertisements due to a change in corporate ownership. We continued with Wave 2 as planned and a relaunched Wave 1 once Grindr access was restored. Before launching each wave, we allocated the same amount of funds for each of the 3 sites and optimized them to run for at least 30 calendar days by dividing the available funds in the prespecified promotional period. However, due to slow enrollment during the COVID-19 pandemic, we extended the second phase of Wave 1 up to 63 days. The advertisement used on social media and dating apps was an image that included a person and text , whereas promotional keywords related to HIV testing and PrEP were selected for information search sites . The same image and keywords were used in all waves. The advertisements were launched in the District of Columbia and 8 states , which were selected based on their high incidence of HIV infection. More information regarding the promotional campaign can be found in the published protocol. Upon clicking on the study advertisement, website users landed on the study information page, where they received general information about the study, underwent eligibility screening, and reviewed study procedures. Following electronic informed consent, participants completed the baseline assessment and were emailed a unique electronic code to order their HIV home self-test kit through Orasure.com . Participants also received an electronic coupon for a free telemedicine PrEP visit. Participants were followed up at 14 and 60 days after enrollment. At follow-up, participants were asked about their HIV self-test use and self-test results; depending on their self-test result, they were asked if they visited a PrEP provider and started PrEP, as well as their opinions on PrEP. If they tested positive for HIV antibodies with the home self-test kit, they were asked if they had visited a clinic for confirmatory testing and HIV treatment. In addition, we tracked test kit orders through automated reports, collected anonymous advertisement metrics through the web applications of the platforms, and recorded the costs for each promotion site and wave.

Participants who were enrolled from Google and Facebook while Grindr was inactive were excluded from analyses. This ensured that we included data when all 3 sites were active and thus had an equal chance to enroll participants. Participants who did not order a test kit within 60 days of the test code being emailed to them were classified as “not ordered a self-test kit.” The 2 advertisement periods of Wave 1 were combined before analysis. Prior to statistical modeling, the number of HIV home self-test kits ordered from each platform, specific platform types , and number days of recruitment in each wave were summarized. In addition, the observed daily self-test kit order rates for each site and platform type were calculated . Per our primary research question, we intended to determine the statistical difference in the self-test kit ordering rates by platform type using a Poisson regression model; however, due to significant platform-by-wave interactions and widely differing order rates between sites within the same platform, it was not appropriate to combine or pool sites across the same platform for statistical evaluation of the platform difference. Therefore, we compared the specific platform differences in terms of the order rates within the same wave. We conducted pairwise comparison for all 6 sites from the 2 waves with multiple testing adjustments using the Hochberg method. Demographic and baseline characteristics were presented using summary statistics. Continuous variables were summarized using percentiles , and means with their SDs. Categorical variables were summarized with frequencies and percentages. To assess differences in the measures between participants who ordered a test kit and those who did not order a test kit, we used the Student t test for continuous variables, Fisher exact test for categorical variables,sliding grow racks and Wilcoxon rank sum test for Likert responses. Data analysis was carried out using Statistical Analysis Software . In this study of MSM at risk for HIV infection, we investigated the effectiveness of promoting free home HIV self-test kits on various internet platforms. More than half of the participants ordered a self-test kit, although only a small proportion of HIV-negative individuals reported seeking PrEP services. Our results showed that dating apps were the most efficient platform to distribute HIV self-test kits to men at high risk for HIV infection. Risk behavior, attitudes toward HIV testing and treatment, perception of HIV-related stigma, and medical mistrust were not associated with ordering a self-test kit. Finally, we recorded high prevalence of alcohol and cannabis use among participants. Overall, information search sites performed poorly in recruiting and enrolling individuals. The site advertisement metrics showed a better click-through rate than social media and a similar number of users screened, but ultimately only a small number of individuals enrolled in the study. Search engines have a broad audience as they are available to everyone with access to the internet, and they do not require an account. In comparison, dating apps had the highest click-through rate, screening numbers, and enrollment. Users of dating apps are more likely to be MSM and engage in high-risk behaviors, which could explain the higher engagement with the promoted study advertisements. Consequently, dating apps may be more cost-efficient in enrolling select individuals compared to other platforms. Using search engines for promotion may reach higher numbers of individuals, but dating apps achieved higher interaction with the promotion message in this study. Another important difference between platforms that may have affected individual site performance is the type of advertisement message.

Social media and dating apps use blast advertisements with images and text, whereas search engines use text-only promotional content. Researchers attempting to identify the best type of advertisement to reach MSM through the internet for free at-home HIV testing showed that the click-through rate for a text-only advertisement on Google was 0.38%, whereas that for advertisements with images, such as the ones used in social media and dating apps, was higher, between 0.77% and 2%. There is a lack of published data regarding the performance of promotional campaigns to enroll participants or promote HIV prevention messages. This limits our capacity to make comparisons with similar campaigns. Our data showed that the cost of enrolling individuals from dating apps is lower compared to that for social media and information search sites. This is mainly due to the higher engagement and higher number of participants enrolled through dating apps. Future studies should collect and report advertisement campaign metrics as well as the costs of enrollment per participant screened and enrolled, which can allow for a better evaluation of the cost-effectiveness of different platforms.Our study demonstrated that HIV self-testing can reach individuals at high risk. We enrolled Latino and Black MSM at a high risk for HIV infection in 10 areas with a high incidence of HIV infection. The study population included individuals with inconsistent and infrequent condom use, and nearly 25% of them reported that they had never tested for HIV. We also identified individuals who reported a preliminary positive result, which demonstrates the capacity of HIV home testing to reach hard-to-reach populations, overcome obstacles, and increase testing. Our findings underline the importance of identifying the best possible promotional platform that will allow public health programs to reach an even larger number of individuals at risk. Our findings did not identify any major differences between participants who ordered a kit compared to those who did not order a test kit. However, our data showed a small statistical difference in terms of the questionnaires on self-perceived stigma, as well as the participant perceptions about the risks of HIV infection. Public health stakeholders should continue their efforts to educate individuals about HIV and support vulnerable individuals against stigma. Substance use was common among study participants, especially alcohol and cannabis use. Similarly, Westmoreland et al also reported a high incidence of cannabis use and alcohol use among a sample of MSM, transgender men, and transgender women. Heavy alcohol use is associated with an increase in sexual behaviors that might put persons at risk for HIV acquisition and transmission.

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

Posted on December 13, 2023 by hemp2022

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?

Posted on December 12, 2023 by hemp2022

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?

Posted on December 11, 2023 by hemp2022

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

Posted on December 8, 2023 by hemp2022

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

Posted on December 7, 2023 by hemp2022

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

Posted on December 6, 2023 by hemp2022

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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