A cortico-amygdala neural substrate for endocannabinoid modulation of fear extinction.

Preclinical and clinical studies implicate endocannabinoids (eCBs) in fear extinction, but the underlying neural circuit basis of these actions is unclear. Here, we employed in vivo optogenetics, eCB biosensor imaging, ex vivo electrophysiology, and CRISPR-Cas9 gene editing in mice to examine whether basolateral amygdala (BLA)-projecting medial prefrontal cortex (mPFC) neurons represent a neural substrate for the effects of eCBs on extinction. We found that photoexcitation of mPFC axons in BLA during extinction mobilizes BLA eCBs. eCB biosensor imaging showed that eCBs exhibit a dynamic stimulus-specific pattern of activity at mPFC→BLA neurons that tracks extinction learning. Furthermore, using CRISPR-Cas9-mediated gene editing, we demonstrated that extinction memory formation involves eCB activity at cannabinoid CB1 receptors expressed at vmPFC→BLA synapses. Our findings reveal the temporal characteristics and a neural circuit basis of eCBs' effects on fear extinction and inform efforts to target the eCB system as a therapeutic approach in extinction-deficient neuropsychiatric disorders.

Food Security of Temporary Foreign Farm Workers under the Seasonal Agricultural Worker Program in Canada and the United States: A Scoping Review.

Temporary foreign farm workers (TFWs) are among the most vulnerable and exploitable groups. Recent research shows alarming rates of food insecurity among them. This review explores research focussing on food security of TFWs in Canada and the United States, summarizes findings, and identifies research gaps. Online databases, including MEDLINE, Web of Science, Scopus, Google Scholar, and government and nongovernment websites, and websites of migrant worker-supporting organizations were searched for peer-reviewed and non-peer-reviewed papers and reports published between 1966 and 2020 regarding food security of TFWs. Articles reviewed were analyzed to determine publication type, country, year, target population, and main findings. Content analysis was performed to identify major themes. Of 291 sources identified, 11 met the inclusion criteria. Most articles (n = 10) were based on studies conducted in the United States. The prevalence of food insecurity among TFWs ranged between 28% and 87%. From the content analysis, we formulated 9 themes, representing a diversity of perspectives, including access to resources, income, housing and related facilities, food access, dietary pattern and healthy food choices, and migrant's legal status. Instruments reported for the measurement of food security include USDA Household Food Security Survey Module (HFSSM; n = 8, 72.7%), the modified version of the USDA HFSSM (n = 1, 9%), hunger measure (n = 1, 9%), the modified CDC's NHANES (n = 1, 9%), and 24-h recall, diet history, and/or food-frequency questionnaire (n = 3, 27.3%). Factors impacting food security of TFWs working under the Seasonal Agricultural Worker Programs (SAWPs) in North America are understudied. There is a need to advance research looking particularly at policies and regulatory and administrative aspects of the SAWPs to improve the food security of this cohort. There is also a need for qualitative studies that explore lived experiences and perspectives of TFWs and key informants. Longitudinal studies may be useful to examine various factors, including policy-related, contributing to food insecurity of TFWs over time.

Chronic health disparities among refugee and immigrant children in Canada.

There are knowledge gaps in our understanding of the development of chronic disease risks in children, especially with regard to the risk differentials experienced by immigrants and refugees. The Healthy Immigrant Children study employed a mixed-methods cross-sectional study design to characterize the health and nutritional status of 300 immigrant and refugee children aged 3-13 years who had been in Canada for less than 5 years. Quantitative data regarding socioeconomic status, food security, physical activity, diet, and bone and body composition and anthropometric measurements were collected. Qualitative data regarding their experiences with accessing health care and their family lifestyle habits were gathered through in-depth interviews with the parents of newcomer children. Many newcomers spoke about their struggles to attain their desired standard of living. Regarding health outcomes, significantly more refugees (23%) had stunted growth when compared with immigrants (5%). Older children, those with better-educated parents, and those who consumed a poorer-quality diet were at a higher risk of being overweight or obese. Sixty percent of refugees and 42% of immigrants had high blood cholesterol. Significant health concerns for refugee children include stunting and high blood cholesterol levels, and emerging trends indicate that older immigrant children from privileged backgrounds in low-income countries may be more at risk of overweight and obesity. A variety of pathways related to their families' conceptualization of life in Canada and the social structures that limit progress to meeting their goals likely influence the development of health inequity among refugee and immigrant children. Public health initiatives should address these health inequities among newcomer families.

Health trainers making a difference to mental health and wellbeing.

This short report explores the key findings from a review(1) of information on health trainers in 2013/2014 which had a particular focus on mental health and wellbeing. After summarising the key findings of the review, it focuses on mental health, briefly exploring the links between mental and physical health before discussing what differences engagement with a health trainer made to people's sense of self-efficacy and wellbeing. Health trainers are a non-clinical workforce introduced in 2004,(2) who receive training in competencies to enable them to support people in disadvantaged communities to improve their health.(3) The population groups or settings that health trainers focus on varies from service to service, but all work one-to-one, most spending at least an hour with a client at their first appointment, supporting and enabling them to decide what they want to do. The emphasis is on the client determining their own priorities and how to achieve them. Generally, health trainers see clients for a total of six sessions, where how to achieve goals and progress towards them is discussed. The Data Collection and Reporting System (DCRS) is used by approximately 60% of Health Trainer Services to record monitoring data. Around 90% of Health Trainer Services using DCRS record ethnographic data on health trainers and clients, plus the issues clients worked on and the progress they made. There is also a wide range of other data which can be recorded, including before and after mental health and wellbeing scores. We were given access to aggregate data in order to conduct an analysis. Descriptive statistics were generated to calculate percentage change pre- to post-intervention. A total of 1,377 (= 919 full time equivalents) health trainers were recorded in the DCRS system as working with 97,248 clients in England during 2013/2014. The health trainer model embodies the principle of lay support,(4) and services aim to recruit a high proportion of their staff from similar backgrounds to their clients. They have been reasonably successful with 32% of health trainers coming from the most deprived areas (Quintile 1),(i) with a further 20% from Quintile 2. In all, 40% percent of health trainers lived in the same areas as their clients.

Rewarding altruism: addressing the issue of payments for volunteers in public health initiatives.

Lay involvement in public health programmes occurs through formalised lay health worker (LHW) and other volunteer roles. Whether such participation should be supported, or indeed rewarded, by payment is a critical question. With reference to policy in England, UK, this paper argues how framing citizen involvement in health only as time freely given does not account for the complexities of practice, nor intrinsic motivations. The paper reports results on payment drawn from a study of approaches to support lay people in public health roles, conducted in England, 2007-9. The first phase of the study comprised a scoping review of 224 publications, three public hearings and a register of projects. Findings revealed the diversity of approaches to payment, but also the contested nature of the topic. The second phase investigated programme support matters in five case studies of public health projects, which were selected primarily to reflect role types. All five projects involved volunteers, with two utilising forms of payment to support engagement. Interviews were conducted with a sample of project staff, LHWs (paid and unpaid), external partners and service users. Drawing on both lay and professional perspectives, the paper explores how payment relates to social context as well as various motivations for giving, receiving or declining financial support. The findings show that personal costs are not always absorbed, and that there is a potential conflict between financial support, whether sessional payment or expenses, and welfare benefits. In identifying some of the advantages and disadvantages of payment, the paper highlights the complexity of an issue often addressed only superficially. It concludes that, in order to support citizen involvement, fairness and value should be considered alongside pragmatic matters of programme management; however policy conflicts need to be resolved to ensure that employment and welfare rights are maintained.

Nebulization of corticosteroids to asthmatic children: large variation in dose inhaled.

BACKGROUND AND OBJECTIVE: Despite problems associated with assessing the clinical effect and side effects of nebulized corticosteroids, little is known of the amount of drug that is inhaled by children with asthma or how this is affected by different drug formulations. The aim of this study was to test the hypothesis that children with asthma inhale the same proportion of the prescribed dose of nebulized fluticasone, beclomethasone dipropionate (BDP) and flunisolide. METHODS: The amount of nebulized drug that would have been inhaled by asthmatic children was captured on filters between the patient and nebulizer, and the amount contained in particles likely to reach the lung (i.e. <5 µm) is determined. RESULTS: The children studied would have inhaled 13% of the prescribed dose of fluticasone propionate, 21% of BDP and 25% of flunisolide. However, the percentage of the dose inhaled that was contained in particles <5 µm, and therefore more likely to reach the lungs, was only 5% of the prescribed dose of fluticasone propionate, 8% for BDP and 16% for flunisolide. The inter-subject variation coefficient of the dose inhaled was much greater for suspensions of fluticasone propionate (34%) and BDP (45%) than for suspensions of flunisolide solution (9%). CONCLUSIONS: Our results demonstrate that the prescribed dose may bear little resemblance to the dose delivered from a nebulizer and that the dose inhaled is significantly affected by the drug formulation prescribed.

Addressing inequalities in health--what is the contribution of health trainers?

AIMS: The role that members of the public (non-professional lay people) can play in improving health is being increasingly recognised in research and policy. This paper explores what contribution lay people employed as health trainers are making to addressing health inequalities in England. METHODS: Data from eight local evaluations of health trainer services were synthesised using a data-extraction framework to find out about client populations, any lifestyle changes made, health trainers' background and community engagement activities. These data were compared with national data to assess how findings relating to addressing inequalities compared with the national picture. RESULTS: Local data largely matched national data and showed that health trainers are reaching people living with disadvantage and enabling them to make lifestyle changes. The data suggest that they do this by engaging with communities and taking a person-centred approach. Being non-clinical peers is also important. However, no evidence was found that health trainers were impacting on health inequalities at a population level. CONCLUSION: Health trainers are contributing to addressing health inequalities but the services evaluated were small and had been operating for a limited time, so to expect reductions in inequalities at a population level within districts would be unrealistic. The findings of this synthesis present a challenge to primary care and public health to employ health trainers in order to engage marginalised communities as one element of plans to address health inequalities.

Improving health and well-being through community health champions: a thematic evaluation of a programme in Yorkshire and Humber.

AIMS: The contribution that lay people can make to the public health agenda is being increasingly recognised in research and policy literature. This paper examines the role of lay workers (referred to as 'community health champions') involved in community projects delivered by Altogether Better across Yorkshire and Humber. The aim of the paper is to describe key features of the community health champion approach and to examine the evidence that this type of intervention can have an impact on health. METHODS: A qualitative approach was taken to the evaluation, with two strands to gathering evidence: interviews conducted with different stakeholder groups including project leads, key partners from community and statutory sectors and community workers, plus two participatory workshops to gather the views of community health champions. Seven projects (from a possible 12) were identified to be involved in the evaluation. Those projects that allowed the evaluation team to explore fully the champion role (training, infrastructure, etc.) and how that works in practice as a mechanism for empowerment were selected. In total, 29 semi-structured interviews were conducted with project staff and partners, and 30 champions, varying in terms of age, gender, ethnicity and disability, took part in the workshops. RESULTS: Becoming a community health champion has health benefits such as increased self-esteem and confidence and improved well-being. For some champions, this was the start of a journey to other opportunities such as education or paid employment. There were many examples of the influence of champions extending to the wider community of family, friends and neighbours, including helping to support people to take part in community life. Champions recognised the value of connecting people through social networks, group activities, and linking people into services and the impact that that had on health and well-being. Project staff and partners also recognised that champions were promoting social cohesiveness and helping to integrate people into their community. CONCLUSIONS: The recent public health White Paper suggested that the Altogether Better programme is improving individual and community health as well as increasing social capital, voluntary activity and wider civic participation. This evaluation supports this statement and suggests that the community health champion role can be a catalyst for change for both individuals and communities.

Circulating anandamide and blood pressure in patients with obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea chronically increases blood pressure through sympathetic nervous system activation. In animals, hypertension and sympathetic activity are restrained by cannabinoid receptor activation. Therefore, we hypothesized that increased blood pressure in patients with obstructive sleep apnea is associated with increased circulating endocannabinoid concentrations. METHODS: Arterial oxygen saturation and apnea/hypopnea episodes were recorded in 29 patients with normal glucose tolerance, 26 patients with type 2 diabetes mellitus, and 21 patients obese subjects without sleep apnea. We determined seated blood pressure, insulin, glucose, and high-sensitive C-reactive protein in the morning, and insulin sensitivity by euglycemic-hyperinsulinemic clamp the next day. Anandamide, the sum of 1-arachidonoylglycerol and 2-arachidonoylglycerol, and oleoylethanolamide were measured in plasma by liquid chromatography-tandem mass spectrometry. RESULTS: Endocannabinoid concentrations in sleep apnea patients were increased compared to obese individuals without disordered nocturnal breathing. Correction for variables of obesity and insulin resistance almost completely abrogated this difference in endocannabinoids. Anandamide strongly correlated with blood pressure in sleep apnea patients (r = 0.60 for SBP and r = 0.58 for DBP, P < 0.001). In multivariate regression analysis, anandamide was a stronger determinant of blood pressure than sleep apnea severity, obesity, insulin resistance, and inflammation. CONCLUSION: Obstructive sleep apnea patients show positive correlations between blood pressure and venous anandamide concentrations independent of confounding factors. Our data suggest a previously not recognized role of the endocannabinoid system for blood pressure regulation in patients with high risk for hypertension and cardiovascular disease.

What's the future for health promotion in England? The views of practitioners.

Specialized health promotion is an internationally recognized occupation and field of activity which has had a chequered history in England. After flourishing briefly in some areas in the early years of the New Labour government it has been in decline in most parts of the country. The last survey of practice conducted in 2005 found that the specialized health promotion workforce was unevenly distributed and much in need of advocacy and development. Since then there has been another major reorganization of primary care trusts (PCTs) and a split between commissioning and provider functions. Practitioners' views on the impact of this on health promotion were gathered in a survey in 2008-2009. Participants comprised 36 people attending a Shaping the Future workshop in the North of England and 40 practitioners studying a masters course in health promotion. The findings reveal that organizational structure has a major impact on the nature of health promotion activity: the split between commissioning and provider functions of PCTs has presented huge challenges to practitioners irrespective of the arm in which they are placed, as one of the strengths of health promotion has always been its ability to straddle both strategic and operational levels and offer a joined-up approach to tackling the causes of ill health. For the specialized health promotion workforce, there has been a loss of identity and critical mass as the discipline is increasingly reduced and fragmented, a trend that looks set to worsen following further reorganization and reductions in public sector spending introduced by the new coalition government.

Seeking asylum and motherhood: health and wellbeing needs.

Pregnant asylum-seeking women and those with young babies living in initial accommodation centres are a highly vulnerable group. The care that these women receive during pregnancy, childbirth and in the postnatal period can have a lifelong impact on them and their babies. This study, conducted in June 2008, investigates the health and wellbeing needs of this group of women through holding in-depth consultations with professionals from the main organisations involved in their care and accommodation. Analysis of consultations identified areas of concern--health needs, women in transition, access to services, access to resources and information, and working environment. Several recommendations are made, which constitute small changes in practice that could make large differences to the quality of life of women in this group.

Nebulisation of corticosteroid suspensions and solutions with a beta(2) agonist.

The aim of this study was to determine the output of salbutamol nebulised in combination with either flunisolide or beclometasone dipropionate (BDP) from two different nebulisers under simulated breathing conditions. The BimboNeb and Nebula nebulisers were used to nebulise 3.0 mL of the two drug mixtures (salbutamol, 5000 microg plus either flunisolide, 600 microg, or BDP, 800 microg). Particle size was determined by inertial impaction. Total outputs of all drugs from both nebulisers were measured using a sinus flow pump under simulated paediatric and adult breathing patterns. The mass median aerodynamic diameter (MMAD) of BDP particles from the mixture was 6.34 mum using the BimboNeb and 5.34 mum using the Nebula. Values for salbutamol in this mixture were 3.93 and 3.32 microm, respectively. The MMAD of flunisolide particles from the BimboNeb and Nebula were 3.74 and 3.65 microm, respectively, while for salbutamol were 3.79 and 3.74 microm, respectively. With the simulated adult breathing pattern, all drug outputs from both mixtures were greater from the BimboNeb than from the Nebula after 5 and 10 min' nebulisation. Drug delivery from the BimboNeb, but not the Nebula, was affected by the simulated breathing pattern. Outputs with the BimboNeb were lower with the paediatric breathing pattern than with the adult pattern. In the majority of cases, nebulising for 10 min produced significantly greater drug output than after 5 min. For the Nebula, outputs were generally similar at 5 and 10 min, irrespective of the breathing pattern. These results highlight the need to assess the amount of aerosolised drug available when drugs are combined, when different nebulisers are used and when they are used with patients of different ages.

The effects of Heliox on the output and particle-size distribution of salbutamol using jet and vibrating mesh nebulizers.

There are theoretical benefits of delivering drug aerosols to patients with asthma and chronic obstructive pulmonary disease (COPD) using Heliox as a carrier gas. The objective of this study was to develop systems to allow bronchodilators nebulized by a breath enhanced jet nebulizer and a vibrating mesh nebulizer to be delivered to patients in Heliox. This was achieved by attaching a reservoir to the nebulizers to ensure inhaled Heliox was not diluted by entrained air. For the vibrating mesh nebulizer, the total output was significantly higher after 5 min of nebulization when Heliox rather than air was used as the delivery gas (p < 0.001). The proportion of drug in particles <5 microm was 58.1% for Heliox and 50.1% when air was entrained. When the breath enhanced nebulizer was used a much higher driving flow of Heliox, compared to air, was required to deliver a similar dose of drug (p < 0.05). The total amount of drug likely to be inhaled was significantly higher when the vibrating mesh nebulizer (Aerogen) was used compared to the breath enhanced jet nebulizer (Pari LC plus) (p < 0.001). The amount of drug likely to be inhaled was also significantly greater for the adult as opposed to pediatric breathing pattern for all nebulizers and flows tested with the exception of the Aeroneb and Heliox entrainment. In this case, total amounts were similar for both patterns but for the pediatric pattern, the time taken to reach this output was longer. Such information is required to allow appropriate interpretation of clinical trials of drug delivery using Heliox.

Enhanced delivery of nebulised salbutamol during non-invasive ventilation.

Non-invasive ventilation (NIV) is used to treat acute respiratory failure. Nebulised drugs can be delivered concurrently with NIV or during breaks from ventilatory support. We hypothesised that the amount of nebulised salbutamol inhaled when delivered via bi-level ventilation would be no different to the amount available directly from the same nebuliser. A standard bi-level ventilation circuit was attached to a lung model simulating adult respiration. Drug delivery was compared when salbutamol (5 mg) was nebulised at different positions in the circuit and separately, with no ventilator. The amount of salbutamol contained in various particle size fractions was also determined. Nebuliser position within the NIV circuit was critically important for drug delivery. Optimal delivery of salbutamol occurred with the expiration port between the facemask and nebuliser (647+/-67 micro g). This was significantly better than nebulisation without the ventilator (424+/-61 micro g; P < 0.01). Delivery when the nebuliser was positioned between the facemask and expiration port was 544+/-85 micro g. The amount of salbutamol contained in particles < 5 micro m was significantly increased when the nebuliser was used in conjunction with bi-level ventilation (576+/-60 micro g vs 300+/-43 micro g, P < 0.001). We conclude that nebulised bronchodilator therapy, using a Cirrus jet nebuliser, during bi-level ventilation increases respirable particles likely to be inhaled when the nebuliser is optimally positioned within the circuit.

Activation of the peripheral endocannabinoid system in human obesity.

Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P < 0.05). Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). A strong negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity.

Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolase.

The endocannabinoid anandamide exerts neurobehavioral, cardiovascular, and immune-regulatory effects through cannabinoid receptors (CB). Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the in vivo degradation of anandamide. Recent experimental studies have suggested that targeting the endocannabinergic system by FAAH inhibitors is a promising novel approach for the treatment of anxiety, inflammation, and hypertension. In this study, we compared the cardiac performance of FAAH knockout (FAAH-/-) mice and their wild-type (FAAH+/+) littermates and analyzed the hemodynamic effects of anandamide using the Millar pressure-volume conductance catheter system. Baseline cardiovascular parameters, systolic and diastolic function at different preloads, and baroreflex sensitivity were similar in FAAH-/- and FAAH+/+ mice. FAAH-/- mice displayed increased sensitivity to anandamide-induced, CB1-mediated hypotension and decreased cardiac contractility compared with FAAH(+/+) littermates. In contrast, the hypotensive potency of synthetic CB1 agonist HU-210 and the level of expression of myocardial CB1 were similar in the two strains. The myocardial levels of anandamide and oleoylethanolamide, but not 2-arachidonylglycerol, were increased in FAAH-/- mice compared with FAAH+/+ mice. These results indicate that mice lacking FAAH have a normal hemodynamic profile, and their increased responsiveness to anandamide-induced hypotension and cardiodepression is due to the decreased degradation of anandamide rather than an increase in target organ sensitivity to CB1 agonists.

Expression of the unconventional myosin Myo1c alters sodium transport in M1 collecting duct cells.

Epithelial cells rely on proper targeting of cellular components to perform their physiological function. This dynamic process utilizes the cytoskeleton and involves movement of vesicles to and from the plasma membrane, thus traversing the actin cortical cytoskeleton. Studies support both direct interaction of actin with channels and an indirect mechanism whereby actin may serve as a track in the final delivery of the channel to the plasma membrane. Actin-dependent processes are often mediated via a member of the myosin family of proteins. Myosin I family members have been implicated in multiple cellular events occurring at the plasma membrane. In these studies, we investigated the function of the unconventional myosin I Myo1c in the M1 mouse collecting duct cell line. Myo1c was observed to be concentrated at or near the plasma membrane, often in discrete membrane domains. To address the possible role of Myo1c in channel regulation, we expressed a truncated Myo1c, lacking ATP and actin domains, in M1 cells and compared electrophysiological responses to control M1 cells, M1 cells expressing the empty vector, and M1 cells expressing the full-length Myo1c construct. Interestingly, cells expressing the Myo1c constructs had modulated antidiuretic hormone (ADH)-stimulated short-circuit current and showed little inhibition of short-circuit current with amiloride addition. Evaluation of enhanced green fluorescent protein-Myo1c constructs supports the importance of the IQ region in targeting the Myo1c to its respective cellular domain. These data are consistent with Myo1c participating in the regulation of the Na+ channel after ADH stimulation.

The 2001 Kentucky Childrens Oral Health Survey: findings for children ages 24 to 59 months and their caregivers.

PURPOSE: This study was performed to provide a 2001 benchmark of oral health status of children in Kentucky with a comparison to the most recent state (1987) and national surveys. METHODS: Using Basic Screening Survey protocols for visual screenings, a sample of 572 children ages 24 to 59 months was screened in health department clinics and physicians' and pediatric dentists' offices across Kentucky after caregivers completed a questionnaire. Screeners were provided modified Association of State and Territorial Dental Directors training materials. Analyses on the sample and population estimates were done with SAS and SUDAAN software. This weighted population estimate analysis is based on the assumption that sampled children at participating sites are representative of other children at that site, as well as children at refusing sites. RESULTS: Sample data and adjusted population estimates closely approximated each other. Population estimates indicated that 43% had untreated caries, 47% had caries experience (early childhood caries), and 31% had severe early childhood caries. Thirty-seven percent of the children needed early care, 9% needed urgent care, 39% had never been to the dentist, 44% had a history of "bad bottle behaviors," and 35% of the parents had not been to the dentist within the last year. CONCLUSIONS: Dental caries is a major health and early childhood development problem in high-risk preschool children in Kentucky.