The effectiveness of social-support-based weight-loss interventions-a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis examined the effectiveness of social-support-based weight-loss interventions in adult populations with excess weight or obesity. METHODS: We performed a systematic review of randomized controlled trials that reported on the effectiveness of weight-loss interventions which incorporated a social connectedness component. To this end, we conducted a rigorous database search of MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, and PubMed for relevant articles. The quality of eligible trials was evaluated by the Cochrane Risk-of-Bias2 tool. Five meta-analyses on intervention effectiveness in terms of weight loss were executed at 2-4-month assessment, 6-month assessment, end of intervention, and 3- and 6-month follow-up. RESULTS: Twenty-four trials involving couples or peers targeting weight loss in 4 919 adults with BMI ≥ 25 met inclusion criteria. Meta-analyses detected no significant effect of social-support-based weight-loss interventions at either 2-4 month or 6-month assessment. There were, however, significant effects at end of intervention [95% CI 0.39, p = 0.04] and at 3-month [95% CI 0.63, p < 0.01] and 6-month [95% CI 0.34, p = 0.05] follow-up. CONCLUSIONS: There seem to be a significant effect at the end of intervention and 3- and 6-month follow-up. However, further high-quality studies are needed before drawing any clear conclusions. TRIAL REGISTRATION: PROSPERO 2020 CRD42020173696.

The metabolome of pink-footed goose: Heavy metals and lipid metabolism.

Wildlife is exposed to mixtures of environmental contaminants that affect health and population dynamics. Exposure to toxic heavy metals originating from anthropogenic sources may exert metabolic effects at even low exposure concentrations. Here we investigated the relationships between heavy metal exposure and metabolic changes in the migratory bird pink-footed goose (Anser brachyrhynchus). We used blood pellet and blood plasma samples from 27 free-ranging pink-footed geese to study heavy metal (Cd, Cr, Hg, and Pb) exposure in relation to the metabolome. The results relate blood concentrations of Cd (range: 0.218-1.09 ng/g), Cr (range: 0.299-5.60 ng/g), and Hg (range: 2.63-6.00 ng/g) to signal areas of fatty acids and other lipids, while no correlations were identified for Pb level (range: 21.0-64.2 ng/g) exposure. Lipid signal areas were negatively associated with concentrations of Cr and positively associated with Hg exposure (both p < 0.05). α-Linolenic acid and 9-oxononanoic acid were negatively correlated to Cr exposure (both p < 0.05) and were related in the α-linolenic acid metabolism pathway. Compared to known thresholds for aviary species, the heavy metal concentrations are below levels of toxicity, which may explain the low number of metabolites that significantly change. Nevertheless, the heavy metal exposure is still correlated to changes in the lipid metabolism that may reduce migrating birds' breeding success and increase mortality for an exposed part of the population.

Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force.

BACKGROUND: Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations. METHODS: The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials. RESULTS: We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking. CONCLUSIONS: Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.

Manual joint mobilisation techniques, supervised physical activity, psychological treatment, acupuncture and patient education in migraine treatment. A systematic review and meta-analysis.

BACKGROUND: Many people suffering from migraine combine pharmacological and non-pharmacological treatments. The purpose of this systematic review is to provide an updated guideline for some widely used non-pharmacological treatment options for migraine. METHODS: We conducted a systematic literature review of randomized studies of adults with migraine treated with manual joint mobilisation techniques, supervised physical activity, psychological treatment, acupuncture and patient education. The main outcomes measured were days with headache and quality of life. Recommendations were formulated based on the Grade of Recommendation, Assessment, Development and Evaluation (GRADE) approach including patient preferences based on expert opinion and questionnaire data. RESULTS: The overall level of certainty of the evidence was low to very low. Manual therapy techniques and psychological treatment did not change the studied outcomes. Supervised physical activity might have a positive impact on quality of life, acupuncture on headache frequency, intensity, quality of life and the use of attack-medicine. Patient education might improve self-rated health and quality of life and increase the number of well-informed patients. CONCLUSION: Based on observed effects, the lack of serious adverse events, and patients' preferences, we make weak recommendations for considering the investigated interventions as a supplement to standard treatment.Protocol registration: Prospero CRD42020220132.

The impact of hypoglycaemia in children and adolescents with type 1 diabetes on parental quality of life and related outcomes: A systematic review.

This systematic review aims to summarize and critically evaluate the current evidence regarding the impact of hypoglycaemia in children and adolescents with type 1 diabetes on parental quality of life. MEDLINE, PsycINFO, CINAHL, and the Cochrane Library were searched. Inclusion criteria were: 1) quantitative design, 2) included parents of children or adolescents with type 1 diabetes, 3) assessment of hypoglycemia in children/adolescents with type 1 diabetes, 4) assessment of parent quality of life (or related domains of life), and 5) analysis of the relationship(s) between the child's hypoglycaemia and parents' quality of life. The data were summarised in accordance with Synthesis Without Meta-Analysis Guidelines. Twelve studies were included, reporting data from 1895 parents across six countries. Ten studies were cross-sectional; two included prospective data. Evidence suggested that greater frequency and severity of hypoglycemia was associated with greater parental fear of hypoglycemia, emotional distress and family burden. Children's hypoglycaemia has a negative impact on the well-being of parents, but there is an absence of evidence regarding the impact on their overall quality of life. Research into the hypoglycaemia-specific quality of life of parents is needed to explore the impact on various areas, such as social and physical dimensions.

Investigating the Dose-Response Relationship between Deep Breathing and Heart Rate Variability in Healthy Participants and Across-Days Reliability in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) are associated with autonomic dysfunction, potentially through reduced vagus nerve tone. Vagus nerve stimulation has been proposed as an anti-inflammatory treatment, and it can be performed through deep breathing (DB) exercises. In this study, the dose-response relationship between DB exercises and heart rate variability (HRV) was investigated in healthy participants and reliability across days in patients with RA and SLE. On three separate days, 41 healthy participants performed DB for: 5, 15, or 30 min. On two separate days, 52 RA or SLE patients performed DB with the dose associated with the highest HRV increase in healthy participants. The HRV was estimated from ECG-recordings recorded prior and post the DB exercises. Increases in dose led to larger HRV-responses. Thirty minutes led to the largest HRV-response. In the RA and SLE patients, this dose increased the HRV-parameters consistently across the two days, indicating reliability. DB increases HRV in healthy participants and RA or SLE patients, which indicates stimulation of the vagus nerve. Of the tested durations, 30 min of DB was the optimal period of stimulation. A potential anti-inflammatory effect of DB exercises should be investigated in future studies.

Modulating Heart Rate Variability through Deep Breathing Exercises and Transcutaneous Auricular Vagus Nerve Stimulation: A Study in Healthy Participants and in Patients with Rheumatoid Arthritis or Systemic Lupus Erythematosus.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with an impaired autonomic nervous system and vagus nerve function. Electrical or physiological (deep breathing-DB) vagus nerve stimulation (VNS) could be a potential treatment approach, but no direct comparison has been made. In this study, the effect of transcutaneous auricular VNS (taVNS) and DB on vagal tone was compared in healthy participants and RA or SLE patients. The vagal tone was estimated using time-domain heart-rate variability (HRV) parameters. Forty-two healthy participants and 52 patients performed 30 min of DB and 30 min of taVNS on separate days. HRV was recorded before and immediately after each intervention. For the healthy participants, all HRV parameters increased after DB (SDNN + RMSSD: 21-46%), while one HRV parameter increased after taVNS (SDNN: 16%). For the patients, all HRV parameters increased after both DB (17-31%) and taVNS (18-25%), with no differences between the two types of VNS. DB was associated with the largest elevation of the HRV parameters in healthy participants, while both types of VNS led to elevated HRV parameters in the patients. The findings support a potential use of VNS as a new treatment approach, but the clinical effects need to be investigated in future studies.

The impact of hypoglycaemia on the quality of life of family members of adults with type 1 or type 2 diabetes: A qualitative systematic review.

AIM: To summarize and critically appraise the recent qualitative evidence regarding the impact of hypoglycaemia on the quality of life of family members of adults with type 1 or type 2 diabetes. METHODS: Four databases were searched systematically (MEDLINE, PsycINFO, CINAHL and Cochrane Library), and results were screened for eligibility. Article quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. Data were extracted, coded and analysed using thematic analysis. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Enhancing transparency in reporting of qualitative research (ENTREQ) guidelines. RESULTS: Eight qualitative studies were included in the final review. The majority of participants were partners or spouses of adults with type 1 diabetes. Thematic synthesis resulted in six analytical themes: 'Hypoglycaemia alters everyday life, reducing freedoms and increasing disruptions', 'Hypoglycaemia has an adverse impact on sleep', 'Hypoglycaemia negatively changes the relationship with the person with diabetes', 'Hypoglycaemia negatively impacts emotional well-being', 'The detection, prevention, and treatment of hypoglycaemia consumes time and energy' and 'Family members have unmet needs for informational and emotional support regarding hypoglycaemia'. Across the six analytical themes, family members described how hypoglycaemia has a severe negative impact on different aspects of their lives, including daily living, personal relationships and emotional well-being. CONCLUSIONS: Family members experience the impact of hypoglycaemia as a major recurrent challenge in their lives. The unmet needs of family members need further attention in research and clinical practice.

The exogenous progesterone-free luteal phase: two pilot randomized controlled trials in IVF patients.

RESEARCH QUESTION: Is the reproductive outcome similar after gonadotrophin-releasing hormone agonist (GnRHa) trigger followed by luteal human chorionic gonadotrophin (HCG) boluses compared with HCG trigger and a standard luteal phase support (LPS)? DESIGN: Two open-label pilot randomized controlled trials (RCT) with 250 patients from 2014 to 2019, with a primary outcome of ongoing pregnancy per embryo transfer. Patients with ≤13 follicles on the trigger day were randomized (RCT 1) to: Group A (n = 65): GnRHa trigger followed by a bolus of 1500 IU HCG s.c. on the oocyte retrieval day (ORD) and 1000 IU HCG s.c. 4 days later, and no vaginal LPS; or Group B (n = 65): 6500 IU HCG trigger, followed by a standard vaginal progesterone LPS. Patients with 14-25 follicles on the trigger day were randomized (RCT 2) to Group C (n = 60): GnRHa trigger followed by 1000 IU HCG s.c. on ORD and 500 IU HCG s.c. 4 days later, and no vaginal LPS; or Group D (n = 60): 6500 IU HCG trigger and a standard vaginal LPS. RESULTS: In RCT 1, the ongoing pregnancy rate was 44% (22/50) in the GnRHa group versus 46% (25/54) in the HCG trigger group (RR 0.95, 95% CI 0.62-1.45). No ovarian hyperstimulation syndrome (OHSS) was seen in Groups A or B. In RCT 2, the ongoing pregnancy rate was 51% (25/49) in the GnRHa group versus 60% (31/52) in the HCG trigger group (RR 0.86, 95% CI 0.60-1.22). The OHSS rates were 3.3% and 6.7%, respectively. CONCLUSIONS: Although a larger-scale study is needed before standard clinical implementation, the present study supports that the exogenous progesterone-free LPS is efficacious, simple and patient-friendly.

Early clinical predictors of functional recovery following traumatic spinal cord injury: a population-based study of 143 patients.

BACKGROUND: Traumatic spinal cord injuries (TSCI) are associated with uncertainty regarding the prognosis of functional recovery. The aim of the present study was to evaluate the potential of early clinical variables to predict the degree of functional independence assessed by Spinal Cord Independence Measure III (SCIM-III) up to 1 year after injury. METHODS: Prospectively collected data from 143 SCI patients treated in Western Denmark during 2012-2019 were retrospectively analysed. Data analysis involved univariate methods and multivariable linear regression modelling total SCIM-III scores against age, gender, body mass index (BMI), comorbidity, American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades A-B and C-D, ASIA Motor Score (AMS), timing of surgical treatment and occurrence of medical complications. Statistical significance was set at p < .05. RESULTS: Univariate analyses indicated that variables significantly associated with decreased functional independence included increased age (p = .023), increased BMI (p = .012), pre-existing comorbidity (p = .001), AIS grades A-B (p < .001), decreased AMS (p < .001) and occurrence of medical complications (p < .001). However, in the multivariable regression model were pre-existing comorbidity (p = .010), AIS grades A-B (p < .001), low AMS (p < .001) and late surgical treatment (p = .018) significant predictors of decreased functional independence 1 year after injury. CONCLUSION: TSCI patients with greatest potential for functional recovery up to 1 year after injury seem to be patients that immediately after trauma present with few or no comorbidities, who sustain motor-incomplete injuries and undergo early decompressive surgery.

Deep Breathing Increases Heart Rate Variability in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus.

BACKGROUND/OBJECTIVE: Autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have been associated with an impaired function of the autonomic nervous system and reduced vagus nerve (VN) tone measured through lower heart rate variability (HRV). Targeting the VN through electrical stimulation has been proposed as a treatment strategy with promising results in patients with RA. Moreover, it has been suggested that the VN can be stimulated physiologically through deep breathing. In this study, the aim was to investigate if the VN can be stimulated through deep breathing in patients with RA and SLE, as measured by HRV. METHODS: Fifty-seven patients with RA and SLE performed deep breathing exercises for 30 minutes in this explorative study. Before the breathing exercise, 2 electrocardiogram recordings were obtained to determine the patient's baseline HRV during rest. After the 30-minute breathing exercise, 5 minutes of electrocardiogram recordings were obtained to determine postintervention HRV and used as a measure of vagal activity. RESULTS: No change was observed in the HRV between the 2 recordings prior the exercise, but the heart rate and HRV significantly decreased and increased, respectively, after the deep breathing exercise. CONCLUSIONS: HRV can be modulated in patients with RA and SLE; this may have implications for future treatment with medications in conjunction with deep breathing. However, the biological and clinical effect of deep breathing must be investigated in future studies.

Manual joint mobilisation techniques, supervised physical activity, psychological treatment, acupuncture and patient education for patients with tension-type headache. A systematic review and meta-analysis.

BACKGROUND: Tension-type headache (TTH) has been ranked the second most prevalent health condition worldwide. Non-pharmacological treatments for TTH are widely used as a supplement or an alternative to medical treatment. However, the evidence for their effects are limited. Therefore, the aim of this study was to review the evidence for manual joint mobilisation techniques, supervised physical activity, psychological treatment, acupuncture and patient education as treatments for TTH on the effect of headache frequency and quality of life. METHODS: A systematic literature search was conducted from February to July 2020 for clinical guidelines, systematic reviews, and individual randomised controlled trials (RCT). The primary outcomes measured were days with headache and quality of life at the end of treatment along with a number of secondary outcomes. Meta-analyses were performed on eligible RCTs and pooled estimates of effects were calculated using the random-effect model. The overall certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach (GRADE). In addition, patient preferences were included in the evaluation. RESULTS: In all, 13 RCTs were included. Acupuncture might have positive effects on both primary outcomes. Supervised physical activity might have a positive effect on pain intensity at the end of treatment and headache frequency at follow-up. Manual joint mobilisation techniques might have a positive effect on headache frequency and quality of life at follow-up. Psychological treatment might have a positive effect on stress symptoms at the end of treatment. No relevant RCTs were identified for patient education. The overall certainty of evidence was downgraded to low and very low. No serious adverse events were reported. A consensus recommendation was made for patient education and weak recommendations for the other interventions. CONCLUSION: Based on identified benefits, certainty of evidence, and patient preferences, manual joint mobilisation techniques, supervised physical activity, psychological treatment, acupuncture, and patient education can be considered as non-pharmacological treatment approaches for TTH. Some positive effects were shown on headache frequency, quality of life, pain intensity and stress symptoms. Few studies and low sample sizes posed a challenge in drawing solid conclusions. Therefore, high-quality RCTs are warranted.

A large national outbreak of COVID-19 linked to air travel, Ireland, summer 2020.

An outbreak of 59 cases of coronavirus disease (COVID-19) originated with 13 cases linked by a 7 h, 17% occupancy flight into Ireland, summer 2020. The flight-associated attack rate was 9.8-17.8%. Spread to 46 non-flight cases occurred country-wide. Asymptomatic/pre-symptomatic transmission in-flight from a point source is implicated by 99% homology across the virus genome in five cases travelling from three different continents. Restriction of movement on arrival and robust contact tracing can limit propagation post-flight.

First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria.

BACKGROUND: Malaria in pregnancy has major impacts on mother and child health. To complement existing interventions, such as intermittent preventive treatment and use of impregnated bed nets, we developed a malaria vaccine candidate with the aim of reducing sequestration of asexual "blood-stage" parasites in the placenta, the major virulence mechanism. METHODS: The vaccine candidate PAMVAC is based on a recombinant fragment of VAR2CSA, the Plasmodium falciparum protein responsible for binding to the placenta via chondroitin sulfate A (CSA). Healthy, adult malaria-naive volunteers were immunized with 3 intramuscular injections of 20 µg (n = 9) or 50 µg (n = 27) PAMVAC, adjuvanted with Alhydrogel or glucopyranosyl lipid adjuvant in stable emulsion (GLA-SE) or in a liposomal formulation with QS21 (GLA-LSQ). Allocation was random and double blind. The vaccine was given every 4 weeks. Volunteers were observed for 6 months following last immunization. RESULTS: All PAMVAC formulations were safe and well tolerated. A total of 262 adverse events (AEs) occurred, 94 (10 grade 2 and 2 grade 3) at least possibly related to the vaccine. No serious AEs occurred. Distribution and severity of AEs were similar in all arms. PAMVAC was immunogenic in all participants. PAMVAC-specific antibody levels were highest with PAMVAC-GLA-SE. The antibodies inhibited binding of VAR2CSA expressing P. falciparum-infected erythrocytes to CSA in a standardized functional assay. CONCLUSIONS: PAMVAC formulated with Alhydrogel or GLA-based adjuvants was safe, well tolerated, and induced functionally active antibodies. Next, PAMVAC will be assessed in women before first pregnancies in an endemic area. CLINICAL TRIALS REGISTRATION: EudraCT 2015-001827-21; ClinicalTrials.gov NCT02647489.

Apoptotic properties of the type 1 interferon induced family of human mitochondrial membrane ISG12 proteins.

BACKGROUND INFORMATION: Interferons are a family of cytokines with growth inhibitory and antiviral functions, which exert their biological actions through the expression of interferon-stimulated genes (ISGs). The human ISG12 family of proteins comprises ISG12A, ISG12B, ISG12C and ISG6-16. Due to differential splicing and a gene variation, the human ISG12A protein exists as a full-length ISG12A form and three ISG12A variants. ISG12 genes have been found transcriptionally dysregulated in many disorders. High levels of ISG12A mRNA have been found in breast and ovarian cancers. Loss of heterozygosity at the position of the ISG12 genes often occurs in ovarian carcinomas and lymphoblastic leukemias. Both ISG12A and ISG6-16 are up-regulated in psoriasis. RESULTS: We demonstrate here that expression of the human full-length ISG12A protein sensitises cells for TNFα and the BH3 mimetic gossypol induced apoptosis, and the other ISG12A variants as well as ISG12B and ISG12C can induce apoptosis directly in HEK293 cells. Also ISG6-16 sensitises HEK293 cells for gossypol-induced apoptosis. In the ISG12 motif, two putative Bcl-2 homology (BH)3 like motifs were found, which may be decisive for the apoptotic properties of the ISG12 proteins. A series of BH3 mutants was made in ISG12AΔ-S, the smallest apoptosis-inducing ISG12A variant and our results indicate that ISG12AΔ-S indeed possesses features resembling those of BH3-only proteins. Supporting this notion are our findings that the full-length ISG12A co-immunoprecipitates with the Bcl-2 protein, and the apoptotic properties of the ISG12A variants are reduced in Bcl-2 expressing HEK293 cells. In addition, full-length ISG12A is able to form homodimers, which suggests a possible involvement in pore formation during apoptosis. The full-length ISG12A, the three ISG12A variants and the ISG12B proteins were found to be localised in the mitochondria. CONCLUSIONS: Our results suggest that the ISG12 family of proteins has an important role for the apoptotic properties induced by type 1 interferon. SIGNIFICANCE: The ISG12 family constitute small hydrophic proteins involved in apoptosis. This is the first comparison of the apoptotic potentials of the full-length ISG12A protein and the three ISG12A variants. The differential apoptotic potentials of these proteins might have an impact on the strategies to monitor and interpret their dysregulation associated with many disorders.

Metabolomics applied to islet nutrient sensing mechanisms.

After multiple decades of investigation, the precise mechanisms involved in fuel-stimulated insulin secretion are still being revealed. One avenue for gaining deeper knowledge is to apply emergent tools of "metabolomics," involving mass spectrometry and nuclear magnetic resonance-based profiling of islet cells in their fuel-stimulated compared with basal states. The current article summarizes recent insights gained from application of metabolomics tools to the specific process of glucose-stimulated insulin secretion, revealing 2 new mechanisms that may provide targets for improving insulin secretion in diabetes.

Consumer behaviour towards price-reduced suboptimal foods in the supermarket and the relation to food waste in households.

To combat food waste, supermarkets offer food items at a reduced price in-store when they are close to the expiration date or perceived as suboptimal. It is yet unknown, however, which considerations consumers engage in when deciding about the offer, and whether focusing particularly on the price during food purchase might be related to greater food waste at home. Knowledge about both the consumers' food purchase process for these price-reduced foods and the potential wastage of price-focused consumers can contribute to the assessment of whether or not offering suboptimal food at reduced prices in-store actually reduces food waste across the supply chain. We explore these questions in a mixed-method study including 16 qualitative accompanied shopping interviews and a quantitative online experimental survey with 848 consumers in Denmark. The interviews reveal that the consumers interviewed assess their ability to consume the price-reduced suboptimal food at home already while in the store. Consumers consider the relation between product-related factors of package unit, expiration date, and product quality, in interaction with household-related factors of freezing/storing, household size/demand, and possible meal/cooking. The survey shows that consumers who are more price-focused report lower food waste levels and lower tendency to choose the optimal food item first at home, than those who are not emphasizing the price-quality relation or do not search for price offers to the same extent. Higher age and high education also played a role, and the price-focus is lower in high-income groups and among single households. The findings allow deriving recommendations for retailers and policy makers to support both the marketability and the subsequent actual consumption of price-reduced suboptimal food, but they also raise questions for further research of this underexplored area.

Nkx6.1 regulates islet ß-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.

Loss of functional ß-cell mass is a hallmark of type 1 and type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor NK6 homeobox 1 (Nkx6.1) in rat pancreatic islets induces ß-cell proliferation and enhances glucose-stimulated insulin secretion, but the pathway by which Nkx6.1 activates ß-cell expansion has not been defined. Here, we demonstrate that Nkx6.1 induces expression of the nuclear receptor subfamily 4, group A, members 1 and 3 (Nr4a1 and Nr4a3) orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated ß-cell proliferation. Consistent with this finding, global knockout of Nr4a1 results in a decrease in ß-cell area in neonatal and young mice. Overexpression of Nkx6.1 and the Nr4a receptors results in increased expression of key cell cycle inducers E2F transcription factor 1 and cyclin E1. Furthermore, Nkx6.1 and Nr4a receptors induce components of the anaphase-promoting complex, including ubiquitin-conjugating enzyme E2C, resulting in degradation of the cell cycle inhibitor p21. These studies identify a unique bipartite pathway for activation of ß-cell proliferation, suggesting several unique targets for expansion of functional ß-cell mass.

Out-of-hospital cardiac arrests in the older population in Ireland.

INTRODUCTION: Age influences survival from an out-of-hospital cardiac arrest (OHCA) but it is unclear to what extent. Improved understanding of the impact of increasing age may be helpful in improving decision making on who should receive attempted resuscitation to optimise outcomes and minimise inappropriate end-of-life management. Our aim is to describe the demographics, characteristics and outcomes following resuscitation attempts in OHCA patients aged 70 years and older in Ireland. METHODS: Data were extracted from the national OHCA Register. Patient and event characteristics were compared across three age categories (70-79; 80-89; ≥90 years). Multivariable logistic regression was used to determine the predictors of the primary outcome (survival to hospital discharge). RESULTS: A total of 2281 patients aged 70 years and older were attended by emergency medical services and had resuscitation attempted between 2012 and 2014. Overall survival to hospital discharge was 2.9%. For those aged 70-79 years, 80-89 years, 90 years and older survival to hospital discharge in each age group was 4.0%, 1.8% and 1.4%, respectively. Older age (adjusted OR (AOR) 0.95 95% CI 0.90 to 0.99) and having an arrest in the subjects own home (AOR 0.14 95% CI 0.07 to 0.28) were independent predictor associated with reduced odds of survival to hospital discharge. An initial shockable rhythm (AOR 17.9. 95% CI 8.19 to 39.2) and having a bystander witnessed OHCA (AOR 3.98. 95% CI 1.38 to 11.50) were independent predictors associated with increased odds of survival to hospital discharge. CONCLUSION: In those aged 70 years and older, the rate of survival to hospital discharge declined with increasing age group. Younger age, an initial shockable rhythm and witnessed arrest were independent predictors of survival to hospital discharge.