Prevention of internalizing difficulties in the middle years: Protocol for a noninferiority randomized trial of Mindfulness-Based Cognitive Therapy for Children and Cognitive Behavioural Therapy.

AIM: Mindfulness-based interventions have been tested as preventive programs for childhood internalizing difficulties, but most research has been at a 'universal' level with small to null effects. Mindfulness-Based Cognitive Therapy for Children (MBCT-C) has similar effects to Cognitive Behaviour Therapy (CBT) when used as a small-group, targeted preventive program. Knowledge gaps include the longer-term effectiveness of MBCT-C relative to CBT and the benefits of adding a parent module. This trial aims to compare MCBT-C to traditional CBT, including a parent module, to 15-months post-intervention and to test the feasibility and acceptability of adding a parent module. METHODS: Participants will be recruited from primary schools in areas of socio-economic disadvantage in South Australia (n = 194). Children (aged 9-12) years with signs of internalizing difficulties (e.g., shy, withdrawn, worried), and their parents, will be eligible for this two-armed randomized controlled non-inferiority trial (RCT). Children will participate in 10 group sessions of MBCT-C or CBT, facilitated by psychologists, and parents from both conditions will participate in two parent-only group sessions. Child self-report measures include depression and anxiety, as well as attention, mindfulness and self-compassion. Parent measures include symptoms of depression and anxiety, mindfulness, and parent-child relationship strength. The primary outcome will be child anxiety and depression (Revised Child Anxiety and Depression Scale-25). Measures will be collected pre and post intervention, and at 3, 6, 12 and 15-month follow up. RESULTS: Schools will be recruited from October 2022. Nomination of children will commence from February 2023. Program implementation will begin May 2023. CONCLUSIONS: This trial will have implications for the feasibility of involving parents in preventative programs, as well as whether mindfulness-based interventions prevent internalizing difficulties over time.

Mitochondria as Target for Tumor Management of Hemangioendothelioma.

Aims: Hemangioendothelioma (HE) may be benign or malignant. Mouse hemangioendothelioma endothelial (EOMA) cells are validated to study mechanisms in HE. This work demonstrates that EOMA cells heavily rely on mitochondria to thrive. Thus, a combination therapy, including weak X-ray therapy (XRT, 0.5 Gy) and a standardized natural berry extract (NBE) was tested. This NBE is known to be effective in managing experimental HE and has been awarded with the Food and Drug Administration Investigational New Drug (FDA-IND) number 140318 for clinical studies on infantile hemangioma. Results: NBE treatment alone selectively attenuated basal oxygen consumption rate of EOMA cells. NBE specifically sensitized EOMA, but not murine aortic endothelial cells to XRT-dependent attenuation of mitochondrial respiration and adenosine triphosphate (ATP) production. Combination treatment, selectively and potently, influenced mitochondrial dynamics in EOMA cells such that fission was augmented. This was achieved by lowering of mitochondrial sirtuin 3 (SIRT3) causing increased phosphorylation of AMP-activated protein kinase (AMPK). A key role of SIRT3 in loss of EOMA cell viability caused by the combination therapy was evident when pyrroloquinoline quinone, an inducer of SIRT3, pretreatment rescued these cells. Innovation and Conclusion: Mitochondria-targeting NBE significantly extended survival of HE-affected mice. The beneficial effect of NBE in combination with weak X-ray therapy was, however, far more potent with threefold increase in murine survival. The observation that safe natural products may target tumor cell mitochondria and sharply lower radiation dosage required for tumor management warrants clinical testing.

Early life exposures associated with risk of small intestinal neuroendocrine tumors.

Small intestinal neuroendocrine tumors (SINT) are rare with incidence increasing over the past 40 years. The purpose of this work is to examine the role of environmental exposures in the rise of SINT incidence using the Utah Population Database, a resource of linked records including life events, cancer diagnoses and residential histories. SINT cases born in Utah were identified through the Utah Cancer Registry with: diagnosis years of 1948 to 2014 and age at diagnosis of 23 to 88 years. Controls were matched to cases 10:1 based on sex, birth year and residence time in Utah. Cases and controls were geocoded to their birth locale. An isotonic spatial scan statistic was used to test for the occurrence and location(s) of SINT clusters. Potential environmental exposures and economic conditions in the birth locales at the time of the birth (1883-1982) were generated using historical references. Conditional logistic regression was used to estimate odd ratios. We report a spatial cluster central to historic coal mining communities, associated with a 2.86 relative risk (p = 0.016) of SINT. Aspatial analyses of industry and mining exposures further suggest elevated risk for early life exposure near areas involved in the construction industry (OR 1.98 p = 0.024). Other exposures approached significance including coal, uranium and hard rock mining during the earliest period (1883-1929) when safety from exposures was not considered. We do observe a lower risk (OR 0.58 p = 0.033) associated with individuals born in rural areas in the most recent period (1945-1982). Environmental exposures early in life, especially those from industries such as mining, may confer an elevated risk of SINT.

Current practice in the rehabilitation of complex regional pain syndrome: a survey of practitioners.

INTRODUCTION: International clinical guidelines for Complex Regional Pain Syndrome recommend a wide range and variation of rehabilitation therapies as the core treatment. It is likely that most therapists employ a range of approaches when managing people with Complex Regional Pain Syndrome but a recent Cochrane review identified little evidence relating to the effectiveness of multi-modal rehabilitation. There is need for up to date trials of rehabilitation for Complex Regional Pain Syndrome, but in order to develop a clear model of best practice that can be rigorously evaluated we need to understand current practice. METHOD: An electronic survey was disseminated internationally to clinicians involved in the rehabilitation of individuals with Complex Regional Pain Syndrome. The survey aimed to establish which criteria are used for diagnosis and which modalities clinicians use to treat Complex Regional Pain Syndrome and which they consider ineffective or harmful. RESULTS: 132 valid responses were received. A third of participants did not use any established criteria to diagnose Complex Regional Pain Syndrome. Current practice commonly included patient education, encouragement of self-management, and physical exercises. Cortically directed treatments such as graded motor imagery and psychological approaches were often incorporated into treatment whereas pain provocative therapies, splinting, contrast bathing, and cold and heat therapy were rarely used in the acute or chronic phase of Complex Regional Pain Syndrome. CONCLUSION: A broad range of modalities are currently used in Complex Regional Pain Syndrome rehabilitation. Practice appears to be characterized by educational and exercise based interventions delivered in a pain-contingent manner which largely echoes recommendations in international clinical guidelines. Implications for Rehabilitation: Patients with Complex Regional Pain Syndrome suffer from a painful and disabling condition for which we still do not know the best treatment options. From our survey sample most clinicians use treatments recommended in the international guidelines. A large proportion of clinicians from our survey sample are not using internationally recognized diagnostic criteria and we therefore recommend that clinicians become familiar with these criteria and use them for all suspected Complex Regional Pain Syndrome cases.

A randomized trial assessing the effects of health claims on choice of foods in the presence of front-of-pack labels.

Background: As a public health intervention, front-of-pack labels (FoPLs) have the potential to reach large numbers of consumers and promote healthier food choices. Of the different FoPLs, those that summarize a product's overall nutritional profile tend to be most effective in guiding healthier choices. However, information is lacking as to whether FoPLs are as effective when nutrient or health claims also appear on-pack. Objective: The aim of this study was to examine how the choice of foods of varying levels of healthfulness (less healthy, moderately healthy, and healthier) is affected by the appearance of various FoPLs (Daily Intake Guide, Multiple Traffic Lights, Health Star Rating) when shown in combination with different claim conditions (no claim, nutrient claim, general-level health claim, and higher-level health claim). Design: Adults and children (n = 2069) completed a discrete-choice experiment online. Respondents were shown 8 choice sets, each containing 4 alternatives of the same food type (cookies, cornflakes, pizza, or yogurt) of varying levels of healthfulness and were asked which product they would likely purchase (or they could select none). Respondents were randomly assigned to view 1 of the 3 FoPLs across all choice sets. Claim type and healthfulness varied within choice sets in accordance with a D-efficient design. Results: The probability of choosing a healthy product and avoiding an unhealthy product was greatest when only an FoPL (especially the Health Star Rating) appeared on-pack. The addition of a nutrient or health claim did not affect the likelihood of picking healthier products but did increase the likelihood of selecting less healthy foods across all FoPL conditions. Conclusions: FoPLs are most effective in helping consumers make better food choices when nutrient and health claims are not present. Policies are required to control how nutrient and health claims are applied to less healthy foods. This trial was registered as ACTRN12617000015347 (www.anzctr.org.au/Trial/Resgistration/TrialReview.aspx?id=372055&isReview=true).

Acceleration of the meckel syndrome by near-infrared light therapy.

BACKGROUND/AIMS: Phototherapy using a narrow-band, near-infrared (NIR) light (using a light-emitting diode, LED) is being used to treat certain medical conditions. This narrow-band red light has been shown to stimulate cytochrome c oxidase (CCO) in mitochondria that would stimulate ATP production and has the ability to stimulate wound healing. LED treatment also decreases chemical-induced oxidative stress in tested systems. As renal cystic diseases are known to have evidence of oxidative stress with reduced antioxidant protection, we hypothesized that NIR light therapy might ameliorate the renal pathology in renal cystic disease. METHODS: Wistar-Wpk/Wpk rats with Meckel syndrome (MKS) were treated with light therapy on days 10-18 at which time disease severity was evaluated. Wpk rats were either treated daily for 80 s with narrow-band red light (640-690 nm wavelength) or sham treated. At termination, renal and cerebral pathology was evaluated, and renal expression and activity of enzymes were assessed to evaluate oxidative stress. Blood was collected for blood urea nitrogen (BUN) determination, the left kidney frozen for biochemical evaluation, and the right kidney and head fixed for morphological evaluation. RESULTS: There were no significant effects of LED treatment on body weight (BW) or total kidney weight in non-cystic rats. Total kidney weight was increased and anephric BW was decreased in cystic versus non-cystic controls. LED reduced BW and total kidney weight in cystic rats compared to non-light-treated cystic (control) rats. BUN was already increased almost 6-fold in cystic rats compared to control rats. BUN was further increased almost 2-fold with NIR treatment in both non-cystic and cystic rats compared to cystic and control rats. The hydrocephalus associated with Wpk/Wpk (ventricular volume expressed as total volume and as percent of anephric BW) was also more severe in NIR-treated cystic rats compared to the normal control rats. Renal glutathione peroxidase and catalase (CAT) were reduced in the cystic kidney while superoxide dismutase and CCO were increased. NIR increased CAT and CCO, marginally decreased glutathione S-transferase and slightly decreased glutathione reductase in cystic rats compared to the normal control rats. The detrimental effects of NIR may be related to reduced renal blood flow associated with progression of cystic pathology. Compression by cysts may not allow sufficient oxygen or nutrient supply necessary to support the increased oxidative phosphorylation-associated cellular activity, and the increased demand induced by NIR-increased CCO may have created further oxidative stress. CONCLUSION: LED phototherapy initiated after the onset of symptoms was detrimental to MKS-induced pathology. NIR stimulates CCO thereby increasing the kidney's need for oxygen. We hypothesize that cystic compression of the vasculature impairs oxygen availability and the enhanced CCO activity produces more radicals, which are not sufficiently detoxified by the increased CAT activity.

An integrated brief intervention to address smoking in pregnancy.

OBJECTIVE: Evaluate the impact of an integrated brief intervention to assist antenatal staff in addressing smoking with pregnant women. DESIGN: Three studies were conducted: (a) antenatal staff surveys pre- and post-training to deliver the brief intervention; (b) retrospective audit of pregnancy records; (c) post-intervention follow-up interviews with a cohort of pregnant women who smoked at baseline. SETTING: South Australia. SAMPLE: (a) Antenatal health professionals at two major birthing hospitals (n = 117 pre-survey and n = 62 post-survey); (b) 1,024 pregnancy records; (c) follow-up interviews with women at one month (n = 58), 6 months (n = 40) and 12 months (n = 31) post-intervention. METHODS: (a) Staff surveys about current practice prior to training (via written questionnaire) and 12 months post-training (by telephone); (b) pregnancy record audit for presence and use of the Smoke-Free Assessment & Intervention Form (SFA&IF) conducted at 12 months; (c) telephone surveys assessing smoking behavior. MAIN OUTCOME MEASURES: Staff practice change and compliance with the intervention. Cessation rates among pregnant women. RESULTS: At 12 months, 89% of staff reported that the intervention integrated well into their work; The SFA&IF was physically present in 80% of pregnancy records and 89% had been completed. Over 65% of current smokers were offered advice about the benefits of quitting; quit rates were highest at 6 months (18, 13% conservative estimate), but women tended to relapse after the birth of their baby. CONCLUSIONS: The intervention was well-received and staff compliance was high. Quit rates exceeded spontaneous quit rates in the community. This project has been expanded nationally.