2-deoxyglucose inhibits induction of chemokine expression in 3T3-L1 adipocytes and adipose tissue explants

© 2016 The Obesity Society Objective: To determine the influence of glycolytic inhibition on the adipocyte inflammatory response. Methods: To determine the effect of 2-deoxyglucose (2-DOG) on the inflammatory response, mature 3T3-L1 adipocytes were co-treated with 2-DOG and LPS or TNF. To determine the effect of endoplasmic reticulum stress on TNF-induced induction of chemokines, adipocytes were pretreated with thapsigargin or salubrinal. Chemokine mRNA levels were determined using quantitative real-time PCR, and secretion of CCL2 was determined by Western blot. Results: 2-DOG treatment reduced the ability of LPS and TNF to induce CCL2 mRNA levels and reduced secreted CCL2 protein levels in a dose-dependent manner. A similar pattern of mRNA regulation was observed for other chemokines. The attenuation of TNF-induced CCL2 mRNA levels occurred regardless of whether glucose or pyruvate was present in the media, suggesting that mechanisms other than glycolysis might mediate the observed effects. Treatment with the endoplasmic reticulum stressor thapsigargin and the endoplasmic reticulum signaling activator salubrinal reduced chemokine mRNA levels similarly to 2-DOG. Conclusions: Collectively, our data indicate that 2-DOG suppresses inflammatory chemokine induction in adipocytes. The effects of 2-DOG do not seem to be linked to glycolysis but correlate with endoplasmic reticulum stress activation

Fat in flames: Influence of cytokines and pattern recognition receptors on adipocyte lipolysis

© 2015 the American Physiological Society. Adipose tissue has the largest capacity to store energy in the body and provides energy through the release of free fatty acids during times of energy need. Different types of immune cells are recruited to adipose tissue under various physiological conditions, indicating that these cells contribute to the regulation of adipose tissue. One major pathway influenced by a number of immune cells is the release of free fatty acids through lipolysis during both physiological (e.g., cold stress) and pathophysiological processes (e.g., obesity, type 2 diabetes). Adipose tissue expansion during obesity leads to immune cell infiltration and adipose tissue remodeling, a homeostatic process that promotes inflammation in adipose tissue. The release of proinflammatory cytokines stimulates lipolysis and causes insulin resistance, leading to adipose tissue dysfunction and systemic disruptions of metabolism. This review focuses on the interactions of cytokines and other inflammatory molecules that regulate adipose tissue lipolysis during physiological and pathophysiological states

The Lived Experiences of African-American Male Exoffenders in the Northeast United States

Discrimination, racism, and class bias affects the accessibility of resources available to African American males who are exoffenders. The purpose of this phenomenological study was to explore the lived experiences of African American, male exoffenders\u27 ability to access resources postincarceration. Guided by Bell and Freeman\u27s critical race theory, a purposeful sample of 6 African American, male exoffenders were recruited from 2 reentry programs in the Northeast United States. A semistructured interview approach was employed to examine the life history, details of experience, and reflection on the meaning of the lived experience from the participants. The modified Stevick, Colaizzi, and Keen method of analysis was used to analyze the interview data. Seven themes emerged that included the stigma of a criminal record, lack of resources, good family support, the importance of employment, accountability, responsibility, lack of education, and the environment that can impact the success or failure of an exoffender\u27s reentry. Policymakers in the criminal justice system can change the current policy that underestimates the extent to which the Violent Crime Control and Law Enforcement Act of 1994 has affected the resources that African American, male exoffenders need to reintegrate into society. The positive social change implication is that service providers can use the results of this study to better serve the needs of African American, male exoffenders as they transition from prison into society

The Gap in Human Resources to Deliver the Guaranteed Package of Prevention and Health Promotion Services at Urban and Rural Primary Care Facilities in Mexico

Background: The purpose of this study was to estimate the gap between the available and the ideal supply of human resources (physicians, nurses, and health promoters) to deliver the guaranteed package of prevention and health promotion services at urban and rural primary care facilities in Mexico. Methods: We conducted a cross-sectional observational study using a convenience sample. We selected 20 primary health facilities in urban and rural areas in 10 states of Mexico. We calculated the available and the ideal supply of human resources in these facilities using estimates of time available, used, and required to deliver health prevention and promotion services. We performed descriptive statistics and bivariate hypothesis testing using Wilcoxon and Friedman tests. Finally, we conducted a sensitivity analysis to test whether the non-normal distribution of our time variables biased estimation of available and ideal supply of human resources. Results: The comparison between available and ideal supply for urban and rural primary health care facilities reveals a low supply of physicians. On average, primary health care facilities are lacking five physicians when they were estimated with time used and nine if they were estimated with time required (P \u3c 0.05). No difference was observed between available and ideal supply of nurses in either urban or rural primary health care facilities. There is a shortage of health promoters in urban primary health facilities (P \u3c 0.05). Conclusion: The available supply of physicians and health promoters is lower than the ideal supply to deliver the guaranteed package of prevention and health promotion services. Policies must address the level and distribution of human resources in primary health facilities

The Mechanism of Flexible Controlling as an Innovative Method in Management of Corporate Structures

У статті представлений принцип дії механізму гнучкого контролінгу як інноваційного методу управління корпоративними структурами. Розглянуто принципи застосування даного методу як інструменту ефективного управління корпоративними структурами, що дозволяють забезпечити різноманітність і гнучкість процесів управління для досягнення поставлених цілей. Розглянуто особливості контролінгу в управлінні корпоративними структурами в умовах нестабільного економічного середовища. Подано концепцію механізму контролінгу в управлінні корпоративними структурами, яка дозволяє забезпечити необхідну різноманітність процесів управління для досягнення динамічного комплексу цілей. Розглянуто особливості функціонування корпоративних структур у нестабільному ринковому оточенні. На прикладі механізму гнучкого контролінгу як способу адаптації до реалій сформованої нестабільності в економіці України представлена його здатність оперативно і тонко спрямовувати управління корпоративними структурами для прийняття правильних рішень та погодження роботи всіх підсистем підприємства.В статье представлен принцип действия механизма гибкого контроллинга как инновационного метода управления корпоративными структурами. Рассмотрены принципы применения данного метода как инструмента эффективного управления корпоративными структурами, позволяющие обеспечить разнообразие и гибкость процессов управления для достижения поставленных целей. Рассмотрены особенности контроллинга в управлении корпоративными структурами в условиях нестабильной экономической среды. Представлена концепция механизма контроллинга в управлении корпоративными структурами, которая позволяет обеспечить необходимое разнообразие процессов управления для достижения динамического комплекса целей. Рассмотрены особенности функционирования корпоративных структур в нестабильном рыночном окружении. На примере механизма гибкого контроллинга как способа адаптации к реалиям сложившейся нестабильности в экономике Украины представлена его способность оперативно и тонко направлять управление корпоративными структурами для принятия правильных решений и согласования работы всех подсистем предприятия.This article presents the principle of the mechanism controlling the flexible as an innovative method of managing corporate structures. The principles of this method as a tool for the effective management of corporate structures, allowing for variety and flexibility of management processes to achieve their goals. Features of controlling in management of corporate structures in the conditions of the unstable economic environment are considered. The concept of the mechanism of controlling in management of corporate structures which allows to provide a necessary variety of management processes for achievement of a dynamic complex of the purposes is presented. Features of functioning of corporate structures in an unstable market environment are considered. On the example of controlling a flexible mechanism as a way of adapting to the realities of the current instability in the economy of Ukraine, represented by its ability to quickly and subtly direct the management of the corporate structure to make the right decisions and coordination of all sub-systems of the enterprise

Final Report:Thematic Review of No Wrong Door – Redcar and Cleveland

Executive SummaryThe No Wrong Door (NWD) model is a residential and outreach service for young people who are on the edge of care or in care.Pressures on funding and resources on local authorities and the care system can lead young people to feel as though they are being ‘bounced between services and residential or foster placements.’ The NWD model offers a hub at the heart of the model, within the local authority, opposed to moving young people out of area.The NWD service, developed by North Yorkshire Council, and adopted by Redcar and Cleveland, offers a new approach for local provisions for young people, including those within the local authority of Redcar and Cleveland. The service offers a multidisciplinary team of professionals who work collaboratively. To carry out an immersive evaluation of the Redcar and Cleveland NWD provision a mixed method approach was undertaken by the current research team, with the following five objectives:1.Conduct a quantitative analysis of existing data collected by the service linked to three key areas; speech and language, policing and health.2.Conduct a thematic review of case studies.3.Work and spend time within the hub to get to know staff and how the service operates (researcher in residence).4.Design longer term process and outcome evaluation for years two and three.5.Conduct a focus group with staff who deliver NWD services within, and alongside the hub.A focus group was conducted with six members of the NWD professional team working at the Redcar and Cleveland NWD hub. Furthermore, four case studies were analysed, written by four NWD professionals, with differing specialisms. Additionally, quantitative data obtained from the NWD Redcar and Cleveland Model were analysed. Eight themes were identified within the thematic review of the qualitative data obtained, in both the focus group and case study findings. •Inter-Professional Collaboration•Education•Family•Finance•No Wrong Door Interventions•Outreach•Residential Care•Vulnerable GroupsThe NWD staff discussed the specific strengths of the current NWD model on offer in Redcar and Cleveland. Staff spoke of the importance of collaborative working and trust between NWD specialists, young people and their families. For instance, staff placed an emphasis on building personable and meaningful working relationships with young people. There was a perception that NWD staff work in a collaborative manner, to assist young people with their multiple needs – for instance- educational needs, communication needs, psychological welfare needs and familial relationships.This report accounts for the period from October 2020 to mid-2023 within the evaluation. Within such a time,103 participants engaged with the NWD service in Redcar &amp; Cleveland. Within the period evaluated, police engagement, outreach and residential elements of the NWD model compiled several considerations within the report. Data indicates that engagement with NWD may have an impact on engagement with the criminal justice system. Prior to engagement with NWD, 21 young people who would go on to be supported by NWD were arrested, and seven were charged. In contrast after the establishment of NWD, 29 young people who were actively engaged with NWD were arrested, with 14 being charged. However, when looking at the period after engagement with NWD, 14 former young people were arrested, with 5 being charged. Whilst it may be viewed as a negative that numbers of NWD actively engaged young people were arrested and charged this would be an incorrect view. Due to the embedded nature of the Police post (the Police Intelligence Analyst) there are opportunities for greater information gathering and identification of issues and concerns with the young people and more scope to develop trust with the families of the engaged young people. Therefore, the likelihood of any issues of concern being identified may increase identification of issues which are subsequently reported to the police amongst this population in the short to medium term.We noted a similar trend when looking at missing person incidents. When looking at all participants prior to engagement there were 55 young people who had a missing incident, totalling 280 missing incident (5.1 incidents per young person), with a median missing time period of 4 hours 17 minutes. This cost approximately £562,928. When looking at young people whilst engaged with NWD there were 49 young people who had a missing incident, totalling 422 missing incident (8.6 incidents per young person), with a median missing time period of 6 hours 59 minutes. This cost approximately £971,232. However, when looking at data once young people had been discharged from NWD 14 young people had a missing incident, totalling 75 missing incidents (5.4 incidents per young person), with a median missing time of 4 hours 56 minutes. This cost approximately £157,040. To contextualise such quantitative data is imperative, as the NWD specialists work with young people with very complex socio-economic positionings. Thus, there is an anticipated level of missing episodes which will have an impact on costs. The NWD team work to reduce police time by responding to the missing episodes professionally, and actively search for all their young people who go missing (see section 3.1.1). Of the 103 outreach young people who engaged with NWD during the lifetime of the evaluation, 86 completed the SALT screening tool, 43 of whom also completed a SALT assessment and screening tool, with 37 of them going on to complete a communication plan. The communication support worker delivered an average of 17 working instances with young people per month across the evaluation period. Total savings associated with having an embedded communication support worker within this service are estimated at £87,078. Similarly, the life coach embedded within the service delivered an average of 14.7 working instances with young people per month. Total savings associated with having an embedded life coach within the hub are estimated at £115,279 across the evaluation period of 22 months.In total, using data provided by the hub it is estimated that engagement with the NWD has resulted in a total cost avoidance of £459,379 for the three young people who were residential to the Hub and is the cumulative cost of partners.Following the completion of the evaluation the following recommendations were made:1.The inter-professional collaboration and multi-agency approach in Redcar and Cleveland NWD was a particular strength of the service. It is recommended that the nurturing and growth of in-house specialists continues in the NWD project, including the roles of the Speech and Language Therapist, police liaison officer, Police Intelligence Analyst and clinical psychologist. This recommendation is related to the data provided by NWD staff who state this element is quintessential within the NWD model; assisting young people in avoiding large waiting lists and avoiding the perception of a non-personal clinical approach. In terms of financial savings in the short, medium and long term this approach has already shown itself to be effective in reducing costs by the disengagement of young people from Criminal Peer Group (CPG). Financial savings in the medium and long term will occur through the in-house identification of young people with previously unidentified SALT needs to enable their support needs which will reduce future costs.2.The use of non-terminology driven and accessible language within written documents about and addressed to young people was perceived to be employed in a successful manner; - an aspect that would benefit from being included as standard protocol for all internal and external staff documenting information about (and addressed to) the child. Partners may wish to reflect on this in their own organisations. 3.The practice of the NWD model to support young people until the age of 25 was identified as a strength of the NWD service and has been identified as supporting financial savings in the short, medium and long term.4.The SALT assessment procures should remain in-house within NWD as they represent an immediate cost saving and being conducted ‘'in-house' reduces the delay of transmission of information between professionals. In-house working also allows for the rapid development of supporting strategies to assist in working with the young person on a) communication issues b) issues appropriate to life coach intervention.5.Future evaluations would benefit from the inclusion of a robust cost-benefit analysis to more accurately predict the cost savings of the NWD in Redcar and Cleveland.6.Future evaluations should include the views of young people who have been involved with NWD both on an outreach, and a residential basis.<br/

Final Report:Thematic Review of No Wrong Door – Redcar and Cleveland

Executive SummaryThe No Wrong Door (NWD) model is a residential and outreach service for young people who are on the edge of care or in care.Pressures on funding and resources on local authorities and the care system can lead young people to feel as though they are being ‘bounced between services and residential or foster placements.’ The NWD model offers a hub at the heart of the model, within the local authority, opposed to moving young people out of area.The NWD service, developed by North Yorkshire Council, and adopted by Redcar and Cleveland, offers a new approach for local provisions for young people, including those within the local authority of Redcar and Cleveland. The service offers a multidisciplinary team of professionals who work collaboratively. To carry out an immersive evaluation of the Redcar and Cleveland NWD provision a mixed method approach was undertaken by the current research team, with the following five objectives:1.Conduct a quantitative analysis of existing data collected by the service linked to three key areas; speech and language, policing and health.2.Conduct a thematic review of case studies.3.Work and spend time within the hub to get to know staff and how the service operates (researcher in residence).4.Design longer term process and outcome evaluation for years two and three.5.Conduct a focus group with staff who deliver NWD services within, and alongside the hub.A focus group was conducted with six members of the NWD professional team working at the Redcar and Cleveland NWD hub. Furthermore, four case studies were analysed, written by four NWD professionals, with differing specialisms. Additionally, quantitative data obtained from the NWD Redcar and Cleveland Model were analysed. Eight themes were identified within the thematic review of the qualitative data obtained, in both the focus group and case study findings. •Inter-Professional Collaboration•Education•Family•Finance•No Wrong Door Interventions•Outreach•Residential Care•Vulnerable GroupsThe NWD staff discussed the specific strengths of the current NWD model on offer in Redcar and Cleveland. Staff spoke of the importance of collaborative working and trust between NWD specialists, young people and their families. For instance, staff placed an emphasis on building personable and meaningful working relationships with young people. There was a perception that NWD staff work in a collaborative manner, to assist young people with their multiple needs – for instance- educational needs, communication needs, psychological welfare needs and familial relationships.This report accounts for the period from October 2020 to mid-2023 within the evaluation. Within such a time,103 participants engaged with the NWD service in Redcar &amp; Cleveland. Within the period evaluated, police engagement, outreach and residential elements of the NWD model compiled several considerations within the report. Data indicates that engagement with NWD may have an impact on engagement with the criminal justice system. Prior to engagement with NWD, 21 young people who would go on to be supported by NWD were arrested, and seven were charged. In contrast after the establishment of NWD, 29 young people who were actively engaged with NWD were arrested, with 14 being charged. However, when looking at the period after engagement with NWD, 14 former young people were arrested, with 5 being charged. Whilst it may be viewed as a negative that numbers of NWD actively engaged young people were arrested and charged this would be an incorrect view. Due to the embedded nature of the Police post (the Police Intelligence Analyst) there are opportunities for greater information gathering and identification of issues and concerns with the young people and more scope to develop trust with the families of the engaged young people. Therefore, the likelihood of any issues of concern being identified may increase identification of issues which are subsequently reported to the police amongst this population in the short to medium term.We noted a similar trend when looking at missing person incidents. When looking at all participants prior to engagement there were 55 young people who had a missing incident, totalling 280 missing incident (5.1 incidents per young person), with a median missing time period of 4 hours 17 minutes. This cost approximately £562,928. When looking at young people whilst engaged with NWD there were 49 young people who had a missing incident, totalling 422 missing incident (8.6 incidents per young person), with a median missing time period of 6 hours 59 minutes. This cost approximately £971,232. However, when looking at data once young people had been discharged from NWD 14 young people had a missing incident, totalling 75 missing incidents (5.4 incidents per young person), with a median missing time of 4 hours 56 minutes. This cost approximately £157,040. To contextualise such quantitative data is imperative, as the NWD specialists work with young people with very complex socio-economic positionings. Thus, there is an anticipated level of missing episodes which will have an impact on costs. The NWD team work to reduce police time by responding to the missing episodes professionally, and actively search for all their young people who go missing (see section 3.1.1). Of the 103 outreach young people who engaged with NWD during the lifetime of the evaluation, 86 completed the SALT screening tool, 43 of whom also completed a SALT assessment and screening tool, with 37 of them going on to complete a communication plan. The communication support worker delivered an average of 17 working instances with young people per month across the evaluation period. Total savings associated with having an embedded communication support worker within this service are estimated at £87,078. Similarly, the life coach embedded within the service delivered an average of 14.7 working instances with young people per month. Total savings associated with having an embedded life coach within the hub are estimated at £115,279 across the evaluation period of 22 months.In total, using data provided by the hub it is estimated that engagement with the NWD has resulted in a total cost avoidance of £459,379 for the three young people who were residential to the Hub and is the cumulative cost of partners.Following the completion of the evaluation the following recommendations were made:1.The inter-professional collaboration and multi-agency approach in Redcar and Cleveland NWD was a particular strength of the service. It is recommended that the nurturing and growth of in-house specialists continues in the NWD project, including the roles of the Speech and Language Therapist, police liaison officer, Police Intelligence Analyst and clinical psychologist. This recommendation is related to the data provided by NWD staff who state this element is quintessential within the NWD model; assisting young people in avoiding large waiting lists and avoiding the perception of a non-personal clinical approach. In terms of financial savings in the short, medium and long term this approach has already shown itself to be effective in reducing costs by the disengagement of young people from Criminal Peer Group (CPG). Financial savings in the medium and long term will occur through the in-house identification of young people with previously unidentified SALT needs to enable their support needs which will reduce future costs.2.The use of non-terminology driven and accessible language within written documents about and addressed to young people was perceived to be employed in a successful manner; - an aspect that would benefit from being included as standard protocol for all internal and external staff documenting information about (and addressed to) the child. Partners may wish to reflect on this in their own organisations. 3.The practice of the NWD model to support young people until the age of 25 was identified as a strength of the NWD service and has been identified as supporting financial savings in the short, medium and long term.4.The SALT assessment procures should remain in-house within NWD as they represent an immediate cost saving and being conducted ‘'in-house' reduces the delay of transmission of information between professionals. In-house working also allows for the rapid development of supporting strategies to assist in working with the young person on a) communication issues b) issues appropriate to life coach intervention.5.Future evaluations would benefit from the inclusion of a robust cost-benefit analysis to more accurately predict the cost savings of the NWD in Redcar and Cleveland.6.Future evaluations should include the views of young people who have been involved with NWD both on an outreach, and a residential basis.<br/

Validation of a liquid chromatography-tandem mass spectrometry method for analyzing cannabinoids in oral fluid.

A liquid chromatography tandem mass spectrometry method was developed for quantifying ten cannabinoids in oral fluid (OF). This method utilizes OF collected by the Quantisal™ device and concurrently quantifies cannabinol (CBN), cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), 11-hydroxy-Δ9-THC (11-OH-THC), 11-nor-9-carboxy-Δ9-THC (THC-COOH), 11-nor-9-carboxy-Δ9-THC glucuronide (THC-COOH-gluc), Δ9-THC glucuronide (THC-gluc), cannabigerol (CBG), tetrahydrocannabiverin (THCV), and Δ9-tetrahydrocannabinolic acid A (THCA-A). Solid phase extraction was optimized using Oasis Prime HLB 30 mg 96-well plates. Cannabinoids were separated by liquid chromatography over a BEH C18 column and detected by a Waters TQ-S micro tandem mass spectrometer. The lower limits of quantification (LLOQ) were 0.4 ng/mL for CBN, CBD, THC, 11-OH-THC, THC-gluc, and THCV; and 1.0 ng/mL for THC-COOH, THC-COOH-gluc, CBG and THCA-A. Linear ranges extended to 2000 ng/mL for THC and 200 ng/mL for all other analytes. Inter-day analytical bias and imprecision at three levels of quality control (QC) was within ±15%. Mean extraction efficiencies ranged from 26.0-98.8%. Applicability of this method was tested using samples collected from individuals randomly assigned to smoke either a joint containing &lt;0.1%, 5.9%, or 13.4% THC content. This method was able to identify and calculate the concentration of 6 of 10 cannabinoids validated in this method