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Human genetic studies have pointed to a prominent role for innate immunity and lipid pathways in immunological and neurodegenerative disorders. Our understanding of the composition and function of immunomodulatory lipid networks in innate immune cells, however, remains incomplete. Here, we show that phospholipase Cγ2 (PLCγ2 or PLCG2)--mutations in which are associated with autoinflammatory disorders and Alzheimer's disease--serves as a principal source of diacylglycerol (DAG) pools that are converted into a cascade of bioactive endocannabinoid and eicosanoid lipids by DAG lipase (DAGL) and monoacylglycerol lipase (MGLL) enzymes in innate immune cells. We show that this lipid network is tonically stimulated by disease-relevant human mutations in PLCγ2, as well as Fc receptor activation in primary human and mouse macrophages. Genetic disruption of PLCγ2 in mouse microglia suppressed DAGL/MGLL-mediated endocannabinoid-eicosanoid cross-talk and also caused widespread transcriptional and proteomic changes, including the reorganization of immune-relevant lipid pathways reflected in reductions in DAGLB and elevations in PLA2G4A. Despite these changes, Plcg2-/- mice showed generally normal proinflammatory cytokine and chemokine responses to lipopolysaccharide treatment, instead displaying a more restricted deficit in microglial activation that included impairments in prostaglandin production and CD68 expression. Our findings enhance the understanding of PLCγ2 function in innate immune cells, delineating a role in cross-talk with endocannabinoid/eicosanoid pathways and modulation of subsets of cellular responses to inflammatory stimuli. [ABSTRACT FROM AUTHOR]

The article focuses on the subjective-perception test's implications for same-sex harassment jurisprudence with the decision of the U.S. Court of Appeals of the Fifth Circuit in the case Equal Employment Opportunity Commission v. Boh Brothers Construction Company on same-sex harassment.

The article discusses legal issues regarding the decision taken by the U.S. Supreme Court in the court case Burwell v. Hobby Lobby Stores, Inc. on June 30, 2014. It mentions that the court opined that for-profit corporations are capable of exercising religion within the meaning of the Religious Freedom Restoration Act of 1993 and therefore be granted exemptions from generally applicable laws if compliance with those laws would substantially burden the corporations' religious freedom.

The article discusses a randomized controlled trial on the recommended use of direct oral anticoagulants (DOACs) instead of warfarin in the treatment of atrial fibrillation (AF). Topics include the effectiveness of DOACs in preventing systemic emboli and ischemic stroke, the lower bleeding rates of apixaban and dabigatran than warfarin and the health insurance cost of DOAC coverage.

This article provides the first comprehensive analysis of ENDA's shortcomings vis- ` a-vis Title VII of the Civil Rights Act of 1964. Whereas federal courts are increasingly likely to perceive LGBT-related employment discrimination as actionable sex discrimination under Title VII, the inclusion of gender identity protections in recent versions of ENDA has significantly diminished the bill's prospects for passage. This article contends that advocates should abandon their efforts to enact ENDA in favor of allowing Title VII's "sex" provision to continue on its LGBT-inclusive evolution. Title VII stands to provide LGBT persons with three distinct advantages relative to ENDA. First, Title VII allows plaintiffs to contest discrimination on either a disparate treatment or disparate impact theory. ENDA, in contrast, would permit only disparate treatment claims such that facially neutral employment practices having a disproportionately adverse effect on LGBT persons would not be actionable. Second, Title VII permits voluntary affirmative action plans whereas ENDA would prohibit preferential treatment on the basis of sexual orientation or gender identity even if LGBT persons were significantly underrepresented in a given workforce. Third, Title VII allows religious organizations to discriminate on the basis of religion but not race, color, ethnicity, or sex. ENDA, conversely, would allow religious organizations to discriminate on the basis of sexual orientation or gender identity without having to justify the discrimination on religious precepts. This article examines the feasibility of applying Title VII's protections to LGBT persons and concludes that, notwithstanding certain logistical difficulties in the short-run, LGBT individuals would benefit from the availability of disparate impact claims, voluntary affirmative action plans, and limited exemptions for religious organizations so that ENDA should be abandoned in favor of Title VII. [ABSTRACT FROM AUTHOR]

Jaakko Seikkula (2008) has pointed towards the importance of practitioners working in the present moment in dialogical therapy. Extrapolating from Seikkula's work, this article considers the significance of the qualities of therapist attentiveness, generosity and negative capability in dialogical family meetings for psychosis. It is proposed that these qualities are of particular importance when family meetings occur in crisis situations, as when under pressure practitioners can easily be drawn into prematurely interventionist stances that may unintentionally promote chronicity for the person experiencing psychosis. The value of co-working arrangements in enabling practitioners to maintain attentiveness and negative capability in this work is also considered. [ABSTRACT FROM AUTHOR]

Meeting a service user with his or her family in acute care settings to discuss their thoughts, hopes and concerns provides important therapeutic benefits. It can help counter some of the potentially negative consequences of hospital admission for the service user and family. Because people usually enter hospital during a period of crisis, approaches that are flexible and responsive to the specific needs of each client and family are required. To practise in this way, staff require access to training and continuing supervision that also needs to be delivered flexibly and responsively. [ABSTRACT FROM AUTHOR]

Meeting a service user with his or her family in acute care settings to discuss their thoughts, hopes and concerns provides important therapeutic benefits. It can help counter some of the potentially negative consequences of hospital admission for the service user and family. Because people usually enter hospital during a period of crisis, approaches that are flexible and responsive to the specific needs of each client and family are required. To practise in this way, staff require access to training and continuing supervision that also needs to be delivered flexibly and responsively. INSETS: Case study one;Case study two. [ABSTRACT FROM AUTHOR]

Presenting dialogical approaches to therapy calls for training approaches that are themselves participatory and dialogical. The use of chance operations is one way of enhancing an interactive and co-constructive learning process. [ABSTRACT FROM AUTHOR]

This article describes a single session aimed at helping participants on a family therapy foundation course to move from a position of anxiety and discomfort about completing a written assignment to a position of safe uncertainty. Evaluation from the perspectives of course participants, course facilitators and assignment markers has shown participants engaging more enthusiastically with the writing of the assignment and expressing less anxiety about the process. [ABSTRACT FROM AUTHOR]

In this article the authors reflect on the impact of differences in accent, dialect, and vocabulary in a family meeting that occurred in a family therapy training clinic. Some ways in which these linguistic factors may provoke social distancing between participants and impede the development of meaning between therapist, family, and reflecting team are examined. Because language is constructive of our personal and social worlds, dilemmas associated with these aspects of communication are framed as ethical in nature. Some tentative implications for a relationally responsive ethical practice are discussed. [ABSTRACT FROM AUTHOR]

Examines the work of R.D. Scott regarding crisis intervention in psychiatry in London, England. Career background of Scott; Issues increasing public anxiety about mental illness; Relevance of research of Scott to mental health nurses and psychiatric professionals.

A recent study evaluated the effectiveness of 3 direct oral anticoagulants and warfarin in patients with atrial fibrillation. So which agents came out on top? [ABSTRACT FROM AUTHOR]

Objective: A diagnosis of Parkinson's often leads to uncertainty about the future and loss of perceived control. Peer support may offer a means to address these concerns and promote self-management. Design: A programme evaluation of the feasibility and potential effects of 'First Steps', utilising a pragmatic step wedge approach. Comparing First Steps (intervention) to (control) conditions. Setting: In the community at four sites in southern England. Participants: Newly diagnosed (≤ 12months) people with Parkinson's. Intervention: First Steps was a 2-day peer-conceived, developed and led intervention to support self-management. Main measures: At 0, 12 and 24 weeks anxiety and depression (Hospital, Anxiety and Depression Scale, HADS), daily functioning (World Health Organisation Disability Assessment Schedule, WHODAS), physical activity, quality of life (EQ5D), carer strain and service utilisation were assessed. Results: Between February 2018 and July 2019, 36 participants were enrolled into intervention and 21 to control conditions, all were included in statistical analysis. Lost to follow up was n = 1 (intervention) and n = 1 adverse event was reported (control, unrelated). Of the 36 allocated to the intervention n = 22 participants completed both days of First Steps during the study period. Completion of outcome measures was >95% at 24 weeks. Small effects favouring the intervention were found for HADS (odds ratio (OR) = 2.06, 95% confidence interval (CI) 0.24:17.84), Carer Strain Index (OR = 2.22, 95% CI 0.5:9.76) and vigorous (d = 0.42, 95% CI −0.12:0.97) and total physical activity (d = 0.41, 95% CI −0.13:0.95). EQ5D, WHOSDAS and service utilisation, was similar between groups. Conclusions: First Steps was feasible and safe and we found potential to benefit physical activity, mental health and carer strain. Further research with longer-term follow up is warranted. [ABSTRACT FROM AUTHOR]

Hydrogen can be a critical part of the energy transition and salt caverns have been considered for underground hydrogen storage. Although there have been some successful experiences of hydrogen storage in salt caverns in Europe and the United States, it is essential to exercise caution when selecting caverns for storage to ensure safe operations. This study investigates the relationship between rock heterogeneity and helium diffusion by testing salt-rock cores from the Lotsberg Formation, Alberta, Canada. We characterized salt rock heterogeneity by analyzing the results of X-ray diffraction (XRD) analysis, thin-section microscopy, scanning electron microscopy/energy dispersive X-ray spectrometry (SEM/EDS), and high-resolution CT scans. Then, diffusion tests were conducted using a custom-designed HPHT visualization cell on core samples with different compositions and crystal sizes. The samples in this study were categorized as Lotsberg Salt and Lotsberg Marlstone. Lotsberg Salt mainly consisted of halite with trace amounts of carbonate impurities, while Lotsberg Marlstone comprised halite with a carbonate matrix containing carbonates, clays, quartz, and muscovite. Helium diffusion through pure and intact halite crystals was negligible, and the micro-scale halite crystal boundaries are non-open or poorly unconnected for helium diffusion. Halite samples with macro-scale grain boundaries and carbonate impurities exhibited more interconnected pore networks, resulting in increased rates of helium diffusion. However, the formation of secondary halite veins between grain boundaries can lead to tightly sealed boundaries that have poor connectivity, limiting helium diffusion within the sample. Salt-rock cores with intergranular fractures and unsealed grain boundaries showed accelerated pressure declines, attributed to the preferential diffusion of helium through these fracture and crack pathways. • Gas transport into salt rocks depends on mineralogy, crystal shape and size. • Gas diffusion through intact halite crystals with no discontinuities is negligible. • Salt crystal boundaries and fractures within grains can be the preferential flow paths for Gas diffusion. [ABSTRACT FROM AUTHOR]

To explore, in a European cohort of people living with Parkinson's (PD), issues affecting employment and economic consequences, considering age at diagnosis. A cross-sectional survey (European convenience sample). Inclusion criteria were ≥18 years, a PD diagnosis and in work when diagnosed. Data were collected online on demographics, employment status, occupation, and perceived health. For those no longer in paid work, time from diagnosis until loss of employment, reasons for leaving and enablers to stay in work were ascertained. Between April and November 2019, n = 692 enrolled and n = 560 were eligible. Those who had lost paid work (n = 190, 34%) reported worse fatigue, sleep, and general health than those still in work (p < 0.05). Average annual income reduced from €26973.48 ± 12013.22 (year-1) to €14843.85 ± 16969.84 (year-10). Post-diagnosis lost employment potential was 20.1 (95% confidence interval (CI): 16.6–23.6) years at career establishment, 9.8 (95%CI: 8.9–10.7) years at mid working and 1.2 (95%CI: 0.6–1.6) years for those nearing retirement age. A greater proportion of individuals at career establishment age reported dexterity, eating, sleep, fatigue, and anxiety as factors for leaving work (p < 0.05). This study confirms lost productivity after a PD diagnosis, especially in those with many years of potential employment ahead. The study also identified potential targets for interventions. Clinical trial registration: Clincaltrials.gov (NCT03905954). People with Parkinson's diagnosed at career establishment or at mid working age risk losing many years of potential employment. Most people with Parkinson's do not receive early intervention to support self-management of problems identified with leaving work early, such as fatigue. Adaptations to the work environment and more flexible working patterns were identified factors that may help people remain in work. [ABSTRACT FROM AUTHOR]

An introduction to the journal focusing on international research studies of undergraduate is presented.

Background In the United States, vaccines have eliminated wild poliovirus (WPV) infection, though resettling refugees may lack immunity and importation of WPV remains a concern. Methods A cross-sectional survey was performed to determine the prevalence of poliovirus immunity in adult refugees resettling in Boise, Idaho, U.S.A.; immunity was evaluated using two definitions: serotypes 1, 2 and 3 positive, or serotypes 1 and 3 positive. Results This survey evaluated 795 adult refugees between August 2010 and November 2012. Poliovirus immunity in adults >18 years was 55.3% for serotypes 1, 2 and 3 combined, and 60% for serotypes 1 and 3 only. Conclusion This study demonstrated a WPV immunity rate of <60% in a recently resettled adult refugee population in the United States, reinforcing the need to ensure poliovirus immunity in all newly arrived adult refugees, either by expanding pre-departure immunization or by screening for immunity at resettlement and vaccinating when indicated. [ABSTRACT FROM AUTHOR]

Background: Practice-based research networks (PBRNs) promote the conduct of research in real-world settings by engaging primary care clinicians as champion research collaborators. Card studies are brief surveys administered to patients or clinicians at the point of care. The objective of this paper is to describe the design and evaluation of a card study methodology that the WWAMI Region Practice and Research Network (WPRN) used to develop research partnerships across multiple member sites. Methods: We used a collaborative model to develop, implement and disseminate the results of a network-wide card study to assess patient preferences for weight loss in primary care. After the card study data collection was completed, we conducted individual and focus group interviews and a brief survey of participating practice champions. Results: Increased research engagement and personal and professional developments were the primary motivators for participating in the development of the card study. Increasing research activity at practices and learning information about patients were motivators for implementing the study. Their participation resulted in champions reporting increased confidence in collaborating on research projects as well as the development of new clinical services for patients. Discussion: This collaborative model positively influenced research capacity in the WPRN and may be a useful strategy for helping PBRNs conducted translational research. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) act as cellular signal transducers through repression of protein translation. Elucidating targets using bioinformatics and traditional quantitation methods is often insufficient to uncover global miRNA function. Herein, alteration of protein function caused by miRNA-185 (miR-185), an immunometabolic miRNA, was determined using activity-based protein profiling, transcriptomics, and lipidomics. Fluorophosphonate-based activity-based protein profiling of miR-185-induced changes to human liver cells revealed that exclusively metabolic serine hydrolase enzymes were regulated in activity, some with roles in lipid and endocannabinoid metabolism. Lipidomic analysis linked enzymatic changes to levels of cellular lipid species, such as components of very-low-density lipoprotein particles. Additionally, inhibition of one miR-185 target, monoglyceride lipase, led to decreased hepatitis C virus levels in an infectious model. Overall, the approaches used here were able to identify key functional changes in serine hydrolases caused by miR-185 that are targetable pharmacologically, such that a small molecule inhibitor can recapitulate the miRNA phenotype. • Identified serine hydrolases that are regulated by the immunometabolic microRNA-185 • microRNA-regulated enzymes are involved in lipid and endocannabinoid metabolism • Showed that inhibition of microRNA-targeted enzymes is antiviral • Activity-based protein profiling identifies pharmacological targets of a microRNA Filip et al. show that microRNA signaling for miR-185 leads to changes in individual enzyme activity. Altered enzymatic functions include lipid and endocannabinoid metabolism. Inhibition of one of these enzymes, MGLL, leads to an antiviral state in liver cells. Inhibition of MGLL recapitulates the function of miR-185 as an antiviral microRNA. [ABSTRACT FROM AUTHOR]

Aim: The dual aim of this research was to consider the impact of providing the First Steps program on the stories of people with Parkinson's Disease (PD) and to investigate the psychosocial and emotional mechanisms which may explain this impact. Methods: A qualitative study using a subtle realist paradigm and hermeneutic phenomenological methodology was undertaken. A single semi-structured interview was used to consider the impact and experiences of people with PD who completed either the intervention (2-day peer-led behavior intervention using storytelling 6–8 weeks apart) or received telephone support calls as part of the active control group. Descriptive statistics and a narrative analysis were undertaken on the results. Results: Forty-two participants were invited to participate, forty of whom completed the interview. This included 18 from the intervention group and 22 from the active control group. The intervention group identified the value of the program as worth-while, demonstrating improved exercise behavior and coping mechanisms following the intervention. Three major stories (the affirmed, the validated and the transformed story) identified the impact of the intervention. Three internal mechanisms (perceived control, hope and action, and the individual's mind set) alongside three social mechanisms (social comparison, social control and the first opportunity to share with peers) appeared to explain this impact. Conclusion: This study provides exciting and novel evidence of the impact of a peer-led psycho-educational intervention for people newly diagnosed with PD. Further research is needed to consider the impact of stories-based approaches on participants and consider a critical evaluation of the mechanisms which may explain changes in stories and self-reported behaviour. [ABSTRACT FROM AUTHOR]

No. Exercise doesn't decrease the frequency or severity of vasomotor menopausal symptoms in perimenopausal and postmenopausal women (strength of recommendation: A, systematic review of randomized controlled trials [RCTs] and consistent RCT). [ABSTRACT FROM AUTHOR]

An answer to a question on the effectiveness of exercise in decreasing the frequency or severity of vasomotor menopausal symptoms in women is presented.