SMART Recovery International and COVID-19: Expanding the reach of mutual support through online groups.

BACKGROUND: Mutual support groups play an extremely important role in providing opportunities for people to engage in alcohol and other drug (AOD) treatment and support. SMART Recovery groups employ cognitive, behavioural and motivational principles and strategies to offer support for a range of addictive behaviours. COVID-19 fundamentally changed the way that these groups could be delivered. METHODS: A series of online meetings were conducted by the lead author (PK) and the SMART Recovery International Executive Officer (KM), with representatives from the SMART Recovery National Offices in the Ireland (DO), United States (MR), Australia (RM), and Denmark (BSH, DA), and the United Kingdom (AK). The meetings focused on discussing the impacts of COVID-19 on SMART Recovery in each of the regions. RESULTS: As a result of restrictions to prevent the transmission of COVID-19, the vast majority of SMART Recovery face-to-face meetings were required to cease globally. To ensure people still had access to AOD mutual support, SMART Recovery rapidly scaled up the provision of online groups. This upscaling has increased the number of groups in countries that had previously provided a limited number of online meetings (i.e., United States, England, Australia), and has meant that online groups are available for the first time in Denmark, Ireland, Hong Kong, Spain, Malaysia and Brazil. DISCUSSION: Whilst the urgent and rapid expansion of online groups was required to support people during the pandemic, it has also created an opportunity for the ongoing availability of online mutual support post-pandemic. The challenge for the research community is to critically evaluate the online delivery of mutual support groups, to better understand the mechanisms through which they may work, and to help understand the experience of people accessing the groups.

Better Indigenous Risk stratification for Cardiac Health study (BIRCH) protocol: rationale and design of a cross-sectional and prospective cohort study to identify novel cardiovascular risk indicators in Aboriginal Australian and Torres Strait Islander adults.

BACKGROUND: Of the estimated 10-11 year life expectancy gap between Indigenous (Aboriginal and Torres Strait Islander people) and non-Indigenous Australians, approximately one quarter is attributable to cardiovascular disease (CVD). Risk prediction of CVD is imperfect, but particularly limited for Indigenous Australians. The BIRCH (Better Indigenous Risk stratification for Cardiac Health) project aims to identify and assess existing and novel markers of early disease and risk in Indigenous Australians to optimise health outcomes in this disadvantaged population. It further aims to determine whether these markers are relevant in non-Indigenous Australians. METHODS/DESIGN: BIRCH is a cross-sectional and prospective cohort study of Indigenous and non-Indigenous Australian adults (≥ 18 years) living in remote, regional and urban locations. Participants will be assessed for CVD risk factors, left ventricular mass and strain via echocardiography, sleep disordered breathing and quality via home-based polysomnography or actigraphy respectively, and plasma lipidomic profiles via mass spectrometry. Outcome data will comprise CVD events and death over a period of five years. DISCUSSION: Results of BIRCH may increase understanding regarding the factors underlying the increased burden of CVD in Indigenous Australians in this setting. Further, it may identify novel markers of early disease and risk to inform the development of more accurate prediction equations. Better identification of at-risk individuals will promote more effective primary and secondary preventive initiatives to reduce Indigenous Australian health disadvantage.

Randomised controlled trial of the efficacy of a blue-enriched light intervention to improve alertness and performance in night shift workers.

OBJECTIVES: Night workers often experience high levels of sleepiness due to misalignment of the sleep-wake cycle from the circadian pacemaker, in addition to acute and chronic sleep loss. Exposure to light, in particular short wavelength light, can improve alertness and neurobehavioural performance. This randomised controlled trial examined the efficacy of blue-enriched polychromatic light to improve alertness and neurobehavioural performance in night workers. DESIGN: Participants were 71 night shift workers (42 males; 32.8±10.5 years) who worked at least 6 hours between 22:00 and 08:00 hours. Sleep-wake logs and wrist actigraphy were collected for 1-3 weeks, followed by 48-hour urine collection to measure the circadian 6-sulphatoxymelatonin (aMT6s) rhythm. On the night following at least two consecutive night shifts, workers attended a simulated night shift in the laboratory which included subjective and objective assessments of sleepiness and performance. Workers were randomly assigned for exposure to one of two treatment conditions from 23:00 hours to 07:00 hours: blue-enriched white light (17 000 K, 89 lux; n=36) or standard white light (4000 K, 84 lux; n=35). RESULTS: Subjective and objective sleepiness increased during the night shift in both light conditions (p<0.05, ηp2=0.06-0.31), but no significant effects of light condition were observed. The 17 000 K light, however, did improve subjective sleepiness relative to the 4000 K condition when light exposure coincided with the time of the aMT6s peak (p<0.05, d=0.41-0.60). CONCLUSION: This study suggests that, while blue-enriched light has potential to improve subjective sleepiness in night shift workers, further research is needed in the selection of light properties to maximise the benefits. TRIAL REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry ACTRN12610000097044 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=320845&isReview=true).

Whole-Plant Manual and Image-Based Phenotyping in Controlled Environments.

Phenotypic measurements and images of crops grown under controlled-environment conditions can be analyzed to compare plant growth and other phenotypes from diverse varieties. Those demonstrating the most favorable phenotypic traits can then be used for crop improvement strategies. This article details a protocol for image-based root and shoot phenotyping of plants grown in the greenhouse to compare traits among different varieties. Diverse maize lines were grown in the greenhouse in large 8-gallon treepots in a clay granule substrate. Replicates of each line were harvested at 4 weeks, 6 weeks, and 8 weeks after planting to capture developmental information. Whole-plant phenotypes include biomass accumulation, ontogeny, architecture, and photosynthetic efficiency of leaves. Image analysis was used to measure leaf surface area and tassel size and to extract shape variance information from complex 3D root architectures. Notably, this framework is extensible to any number of above- or below-ground phenotypes, both morphological and physiological. © 2017 by John Wiley & Sons, Inc.

Transforming growth factor-ß directly induces p53-up-regulated modulator of apoptosis (PUMA) during the rapid induction of apoptosis in myc-driven B-cell lymphomas.

c-Myc transformed human Burkitt's lymphoma (BL) cells are highly sensitive to TGF-ß-induced apoptosis. Previously we demonstrated that TGF-ß-mediated cell death in BL cells is regulated via the mitochondrial intrinsic apoptosis pathway, which is dependent on the activation of BAX and/or BAK. TGF-ß directly induces transcription of the BH3-only protein BIK and represses expression of the pro-survival factor BCL-X(L) but has no effect on the direct BAX/BAK "activators" BIM or BID (tBID). Here we show that TGF-ß induces the BH3-only activator PUMA to aid induction of the intrinsic cell death pathway. TGF-ß also induced PUMA in normal germinal center CD77-positive centroblasts isolated from human tonsil tissue. PUMA was a direct TGF-ß target gene in B-cells, and we identify a putative Smad-binding region within the human PUMA promoter that recruits Smad3 and Smad4 in cells in response to TGF-ß signaling. Constitutive activity of the isolated Smad-binding region in luciferase reporter assays was dependent on Smad consensus sequences and was partially dependent on endogenous TGF-ß signaling and Smad4. Knockdown of PUMA in BL cells using lentiviral shRNA resulted in slower kinetics of the TGF-ß-mediated apoptotic response. Analysis of Eµ-Myc cell lines demonstrated that c-myc-driven murine lymphomas are also sensitive to TGF-ß-mediated apoptosis. Moreover, Puma(-/-) Eµ-Myc lines demonstrated significantly delayed kinetics of the apoptotic response when compared with wild type lymphomas. TGF-ß therefore induces a polygenic response in Myc-driven lymphomas involving transcription of PUMA, which is necessary for the rapid induction of cell death.

Epigenetic downregulation of human disabled homolog 2 switches TGF-beta from a tumor suppressor to a tumor promoter.

The cytokine TGF-beta acts as a tumor suppressor in normal epithelial cells and during the early stages of tumorigenesis. During malignant progression, cancer cells can switch their response to TGF-beta and use this cytokine as a potent oncogenic factor; however, the mechanistic basis for this is poorly understood. Here we demonstrate that downregulation of disabled homolog 2 (DAB2) gene expression via promoter methylation frequently occurs in human squamous cell carcinomas (SCCs) and acts as an independent predictor of metastasis and poor prognosis. Retrospective microarray analysis in an independent data set indicated that low levels of DAB2 and high levels of TGFB2 expression correlate with poor prognosis. Immunohistochemistry, reexpression, genetic knockout, and RNAi silencing studies demonstrated that downregulation of DAB2 expression modulated the TGF-beta/Smad pathway. Simultaneously, DAB2 downregulation abrogated TGF-beta tumor suppressor function, while enabling TGF-beta tumor-promoting activities. Downregulation of DAB2 blocked TGF-beta-mediated inhibition of cell proliferation and migration and enabled TGF-beta to promote cell motility, anchorage-independent growth, and tumor growth in vivo. Our data indicate that DAB2 acts as a tumor suppressor by dictating tumor cell TGF-beta responses, identify a biomarker for SCC progression, and suggest a means to stratify patients with advanced SCC who may benefit clinically from anti-TGF-beta therapies.

Targeting the Fas/Fas ligand pathway in cancer.

Fas is a transmembrane receptor that can induce apoptosis after cross-linking with either agonistic antibodies or with Fas ligand (FasL). Although originally described as an important regulator of peripheral immune homeostasis, accumulating evidence suggests that the Fas/FasL system plays an important role in tumour development. In addition to its proapoptotic functions, accumulating evidence demonstrates that Fas can activate numerous nonapoptotic signalling pathways, and that activation of these pathways can result in increased tumourigenicity and metastasis. This review summarises the current understanding of the Fas/FasL system in tumorigenesis and discusses attempts to utilise the Fas/FasL system in the treatment of cancer.

The role of substance P in inflammatory disease.

The diffuse neuroendocrine system consists of specialised endocrine cells and peptidergic nerves and is present in all organs of the body. Substance P (SP) is secreted by nerves and inflammatory cells such as macrophages, eosinophils, lymphocytes, and dendritic cells and acts by binding to the neurokinin-1 receptor (NK-1R). SP has proinflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems. Many substances induce neuropeptide release from sensory nerves in the lung, including allergen, histamine, prostaglandins, and leukotrienes. Patients with asthma are hyperresponsive to SP and NK-1R expression is increased in their bronchi. Neurogenic inflammation also participates in virus-associated respiratory infection, non-productive cough, allergic rhinitis, and sarcoidosis. SP regulates smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function in the gastrointestinal tract. Elevated levels of SP and upregulated NK-1R expression have been reported in the rectum and colon of patients with inflammatory bowel disease (IBD), and correlate with disease activity. Increased levels of SP are found in the synovial fluid and serum of patients with rheumatoid arthritis (RA) and NK-1R mRNA is upregulated in RA synoviocytes. Glucocorticoids may attenuate neurogenic inflammation by decreasing NK-1R expression in epithelial and inflammatory cells and increasing production of neutral endopeptidase (NEP), an enzyme that degrades SP. Preventing the proinflammatory effects of SP using tachykinin receptor antagonists may have therapeutic potential in inflammatory diseases such as asthma, sarcoidosis, chronic bronchitis, IBD, and RA. In this paper, we review the role that SP plays in inflammatory disease.

Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.

Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory nerves and inflammatory cells. Increased levels of SP are found in sarcoid bronchoalveolar lavage fluid. SP acts by binding to the neurokinin-1 receptor and increases secretion of tumor necrosis factor-alpha in many cell types. We sought to determine neurokinin-1 receptor expression in patients with sarcoidosis compared with normal controls. Neurokinin-1 receptor messenger RNA and protein expression were below the limits of detection by reverse transcriptase-polymerase chain reaction and immunohistochemistry in peripheral blood mononuclear cells of healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n = 10), but were detected in 1/9 bronchoalveolar lavage cells of controls compared with 8/10 patients with sarcoidosis (p = 0.012) and 2/9 biopsies of controls compared with 9/10 patients with sarcoidosis (p = 0.013). Immunohistochemistry localized upregulated neurokinin-1 receptor expression to bronchial and alveolar epithelial cells, macrophages, lymphocytes, and sarcoid granulomas. The patient in whom neurokinin-1 receptor was not detected was taking corticosteroids. Incubation of the type II alveolar and bronchial epithelial cell lines A549 and SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression. Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis.

Activation of the p38 MAPK and ERK1/2 pathways is required for Fas-induced IL-8 production in colonic epithelial cells.

This paper aims to examine the contribution of all three of the MAP kinase signaling pathways to Fas-induced IL-8 up-regulation in HT29 colon epithelial cells.