From risk communication about asymptomatic atherosclerosis to cognitive and emotional reactions and lifestyle modification.

BACKGROUND: Non-adherence in the general population to preventive guidelines on cardiovascular disease calls for an interdisciplinary approach acknowledging psychological factors of relevance for risk communication and lifestyle modification. Evidence is building up regarding the advantage of sharing arterial imaging evidence of subclinical atherosclerosis with asymptomatic individuals, but there is limited understanding of how this relates to mechanisms of importance for behavioural change. Longitudinal studies on associations between patients' reactions and lifestyle modification are missing. The population-based randomized controlled trial VIPVIZA investigates the impact of pictorial information about subclinical atherosclerosis, added to traditional risk factor-based communication. The intervention includes a personalized, colour-coded and age-related risk communication strategy and a motivational conversation, and has been shown to reduce cardiovascular disease risk. METHODS: In the present study we assessed cognitive and emotional reactions to the intervention, and how these reactions are associated to lifestyle modification. The participants' evaluation of the risk communication was assessed in the intervention group (n = 1749). Lifestyle modification was assessed with a lifestyle index based on physical activity, diet, smoking and alcohol consumption at baseline and after 3 years. Associations between cognitive and emotional response and lifestyle modification were tested with analyses of covariance in a subset of participants (n = 714-857). RESULTS: The intervention increased understanding of personal CVD risk, the possibility to influence the risk, and how to influence the risk. Severity of atherosclerosis was associated with emotional reactions, but emotions of strong negative valence were uncommon. Cognitive response and emotional arousal evoked by the intervention were positively associated with lifestyle modification, whereas negative emotions in isolation were not. High level of cognitive response in combination with high level of emotional arousal was found to be most beneficial for lifestyle modification. CONCLUSIONS: The results demonstrate the potential of communicating asymptomatic atherosclerosis with a pictorial, colour-coded and age-related strategy, also including a motivational conversation. Furthermore, the results show the importance of CVD risk communication evoking engagement, and that an interaction between cognitive and emotional reactions might be central for sustained lifestyle modification. Our results also indicate that, in an asymptomatic population, atherosclerosis screening may strengthen disease prevention and health promotion. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01849575. Registration date 08/05/2013.

Associations between emotional support and cardiovascular risk factors and subclinical atherosclerosis in middle-age.

OBJECTIVE: To test the hypothesis of low emotional support being associated with lifestyle and biomedical cardiovascular disease (CVD) risk factors, estimated risk of CVD morbidity and mortality, and subclinical atherosclerosis in middle-aged healthy adults. METHODS AND MEASURES: Cross-sectional data were obtained from participants aged 40-60 years who had one or more conventional CVD risk factor. They underwent assessment based on questionnaires, clinical examination, blood sampling, and carotid ultrasound of plaque formation and carotid intima-media wall thickness (cIMT). Based on the Interview Schedule for Social Interaction, the participants were categorised as either low in emotional support (n = 884) or as a referent (n = 2570). Logistic regression analyses were conducted to study the associations. RESULTS: Logistic regression analyses showed that low emotional support was significantly associated with smoking, alcohol consumption and physical inactivity (OR = 1.53 - 1.94), estimated risk of CVD morbidity and mortality (OR = 1.56 - 1.68), and plaque formation (OR = 1.39). No significant associations were found regarding biomedical CVD risk factors or cIMT. CONCLUSION: The findings suggest that low social support is associated with lifestyle CVD risk factors, estimated risk of CVD morbidity and mortality, and subclinical atherosclerosis in middle-aged healthy adults, encouraging causal evaluation with longitudinal data investigating an impact of emotional support on mechanisms underlying CVD.

Human resident liver myeloid cells protect against metabolic stress in obesity.

Although multiple populations of macrophages have been described in the human liver, their function and turnover in patients with obesity at high risk of developing non-alcoholic fatty liver disease (NAFLD) and cirrhosis are currently unknown. Herein, we identify a specific human population of resident liver myeloid cells that protects against the metabolic impairment associated with obesity. By studying the turnover of liver myeloid cells in individuals undergoing liver transplantation, we find that liver myeloid cell turnover differs between humans and mice. Using single-cell techniques and flow cytometry, we determine that the proportion of the protective resident liver myeloid cells, denoted liver myeloid cells 2 (LM2), decreases during obesity. Functional validation approaches using human 2D and 3D cultures reveal that the presence of LM2 ameliorates the oxidative stress associated with obese conditions. Our study indicates that resident myeloid cells could be a therapeutic target to decrease the oxidative stress associated with NAFLD.

Cognitive and emotional reactions to pictorial-based risk communication on subclinical atherosclerosis: a qualitative study within the VIPVIZA trial.

OBJECTIVES, SETTING AND SUBJECTS: Atherosclerosis screening with ultrasound is non-invasive and can be used as part of risk communication. The potential of personalised and pictorial-based risk communication is assessed in VIPVIZA, a population-based randomised controlled trial that aims at optimising cardiovascular disease (CVD) prevention by investigating the impact of visualisation of subclinical atherosclerosis. The present aim was to explore cognitive and emotional reactions evoked by the intervention as well as attitudes to any implemented life style changes in VIPVIZA participants in the intervention group with improved health status and furthermore to study possible interactions between these factors. Understanding mechanisms of action was central since non-adherence to preventive guidelines are often faced in clinical practice. DESIGN: In-depth interviews with 14 individuals were analysed with qualitative content analysis. RESULTS: Cognitive and emotional processes were highly interlinked and described by the main theme Cognitive and emotional reactions in strong interplay for orchestration of health oriented behavioural change. The informants' descriptions revealed two distinctly different psychological processes which constituted the two subthemes, Problem-focused coping and Encouragement-driven process. CONCLUSIONS: The results highlight that an interaction between emotional reactions and efficacy beliefs is important in facilitating behavioural change. Furthermore, the results underscore the importance of the risk message being perceived as clear, accurate, reliable and also emotionally engaging and thereby show why atherosclerosis screening and pictorial-based risk communication have the potential to contribute to effective CVD prevention strategies and shared decision making in primary care. Trial registration: ClinicalTrials.gov identifier: NCT01849575, registration 8 May 2013.Key pointsAtherosclerosis screening and pictorial-based risk communication have the potential to contribute to more effective CVD prevention strategies.Risk messages on atherosclerosis status were perceived as clear, accurate, reliable and emotionally engaging.An interplay between efficacy beliefs and emotional reactions facilitated behavioural change.Patients' understanding of CVD risk is important for shared decision-making and of relevance for non-adherence to preventive guidelines.

Exploring the Mental Health Challenges of Women Diagnosed with Breast Cancer in Vietnam: A Qualitative Study.

Breast cancer is the most frequently diagnosed cancer among Vietnamese women. This qualitative study describes and discusses the mental health challenges of women with breast cancer in Vietnam. Two-rounds of semi-structured in-depth interviews were conducted among thirteen women with breast cancer and four caregivers from northern and southern Vietnam. Participants were recruited using purposive sampling technique. Data was collaboratively analyzed by qualitative content analysis using the Open Code Software version 4.02 and discussed among a team of local and international researchers. Women in the study experienced significant mental health challenges associated with their breast cancer diagnosis. Both psychological and emotional health were adversely affected. Women with breast cancer had profound concerns about how the diagnosis impacted their families. They experienced challenges in spousal relationships as well as facing social stigma and discrimination. Appropriate public health interventions should be implemented to raise society's awareness and help improve the mental health of women with breast cancer.

Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death.

Hepatocyte transplantation is a promising treatment for liver failure and inborn metabolic liver diseases, but progress has been hampered by a scarcity of available organs. Here, hepatocytes isolated from livers procured for a neonatal hepatocyte donation program within a research setting were assessed for metabolic function and suitability for transplantation. Organ donation was considered for infants who died in neonatal intensive care in the Stockholm region during 2015-2021. Inclusion was assessed when a decision to discontinue life-sustaining treatment had been made and hepatectomy performed after declaration of death. Hepatocyte isolation was performed by three-step collagenase perfusion. Hepatocyte viability, yield, and function were assessed using fresh and cryopreserved cells. Engraftment and maturation of cryopreserved neonatal hepatocytes were assessed by transplantation into an immunodeficient mouse model and analysis of the gene expression of phase I, phase II, and liver-specific enzymes and proteins. Twelve livers were procured. Median warm ischemia time (WIT) was 190 [interquartile range (IQR): 80-210] minutes. Median viability was 86% (IQR: 71%-91%). Median yield was 6.9 (IQR: 3.4-12.8) x106 viable hepatocytes/g. Transplantation into immunodeficient mice resulted in good engraftment and maturation of hepatocyte-specific proteins and enzymes. A neonatal organ donation program including preterm born infants was found to be feasible. Hepatocytes isolated from neonatal donors had good viability, function, and engraftment despite prolonged WIT. Therefore, neonatal livers should be considered as a donor source for clinical hepatocyte transplantation, even in cases with extended WIT.

Mucosal-associated invariant T-cell tumor infiltration predicts long-term survival in cholangiocarcinoma.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is a malignancy arising from biliary epithelial cells of intra- and extrahepatic bile ducts with dismal prognosis and few nonsurgical treatments available. Despite recent success in the immunotherapy-based treatment of many tumor types, this has not been successfully translated to CCA. Mucosal-associated invariant T (MAIT) cells are cytotoxic innate-like T cells highly enriched in the human liver, where they are located in close proximity to the biliary epithelium. Here, we aimed to comprehensively characterize MAIT cells in intrahepatic (iCCA) and perihilar CCA (pCCA). APPROACH AND RESULTS: Liver tissue from patients with CCA was used to study immune cells, including MAIT cells, in tumor-affected and surrounding tissue by immunohistochemistry, RNA-sequencing, and multicolor flow cytometry. The iCCA and pCCA tumor microenvironment was characterized by the presence of both cytotoxic T cells and high numbers of regulatory T cells. In contrast, MAIT cells were heterogenously lost from tumors compared to the surrounding liver tissue. This loss possibly occurred in response to increased bacterial burden within tumors. The residual intratumoral MAIT cell population exhibited phenotypic and transcriptomic alterations, but a preserved receptor repertoire for interaction with tumor cells. Finally, the high presence of MAIT cells in livers of iCCA patients predicted long-term survival in two independent cohorts and was associated with a favorable antitumor immune signature. CONCLUSIONS: MAIT cell tumor infiltration associates with favorable immunological fitness and predicts survival in CCA.

Pride and Uncertainty: A Qualitative Study of Danish Nursing Staff in Temporary COVID-19 Wards.

There is limited knowledge about the psychosocial stress among the nursing staff working on the COVID-19 wards. This article reports on the experiences of frontline health care workers as it was described to supervisors counseling the nursing staff engaged in the response to the outbreak of COVID-19. Frontline health care workers, nurses, and nurses' aides experienced major work changes. Some were transferred to the newly formed COVID-19 wards in a large Danish hospital, were given new tasks, and had to collaborate with new colleagues, while treating a new deadly and contagious disease. This study aimed to describe the reflections and experiences of the nursing staff attending supervision sessions. The palliative unit offered supervision from April 2020. A total of 9 supervision sessions were held as part of this study, and 57 nursing staff members participated in the sessions. The supervision was available to employees until the first COVID wave subsided in June 2020. During each session, supervisors took field notes and wrote field memos. The topics raised by the nursing staff during the supervision sessions ranged between pride and uncertainty. Nursing staff in COVID-19 wards were at risk of feeling an increasing burden, and there was a need for ongoing managerial attention as well as continuous visible presence and support.

Blood Group Antigen Expression in Isolated Human Liver Cells in Preparation for Implementing Clinical ABO-Incompatible Hepatocyte Transplantation.

BACKGROUND: ABO blood group antigens in the liver are expressed mainly on endothelial cells or biliary epithelial cells but not on hepatocytes. This suggests that ABO-incompatible hepatocyte transplantation (ABOi-HTx) is theoretically feasible. However, the effects of stress on ABO blood group antigen expression caused by isolation and intraportal infusion require thorough investigation before ABOi-HTx can be implemented in clinical settings. METHODS: Human hepatocytes were isolated from liver tissue obtained from liver resection or deceased donor livers. The expression of blood group antigens on cryopreserved human liver tissues and isolated hepatocyte smear specimens were examined by immunofluorescent staining. The effect of proinflammatory cytokines on blood group antigen expression of hepatocytes was evaluated by flow cytometry. Instant blood-mediated inflammatory reaction after hepatocyte incubation with ABO-incompatible whole blood was examined using the tubing loop model. RESULTS: Blood group antigens were mainly expressed on vessels in the portal area. In hepatocyte smear specimens, isolated hepatocytes did not express blood group antigens. In contrast, a subset of cells in the smear specimens of nonparenchymal liver cells stained positive. In the flow cytometry analysis, isolated hepatocytes were negative for blood group antigens, even after 4-h incubation with cytokines. Platelet counts and complement activation were not significantly different in ABO-identical versus ABO-incompatible settings in the tubing loop model. CONCLUSION: Our study showed that blood group antigens were not expressed on hepatocytes, even after isolation procedures or subsequent incubation with cytokines. This finding is an important step toward removing the restriction of ABO matching in hepatocyte transplantation. Our results suggest that ABOi-HTx is a feasible therapeutic option, especially in patients who require urgent treatment with freshly isolated hepatocytes, such as those with acute liver failure.

Chenodeoxycholic Acid Modulates Bile Acid Synthesis Independent of Fibroblast Growth Factor 19 in Primary Human Hepatocytes.

Bile acids (BAs) are detergents essential for intestinal absorption of lipids. Disruption of BA homeostasis can lead to severe liver damage. BA metabolism is therefore under strict regulation by sophisticated feedback mechanisms. The hormone-like protein Fibroblast growth factor 19 (FGF19) is essential for maintaining BA homeostasis by down regulating BA synthesis. Here, the impact of both FGF19 and chenodeoxycholic acid (CDCA) on primary human hepatocytes was investigated and a possible autocrine/paracrine function of FGF19 in regulation of BA synthesis evaluated. Primary human hepatocytes were treated with CDCA, recombinant FGF19 or conditioned medium containing endogenously produced FGF19. RNA sequencing revealed that treatment with CDCA causes deregulation of transcripts involved in BA metabolism, whereas treatment with FGF19 had minor effects. CDCA increased FGF19 mRNA expression within 1 h. We detected secretion of the resulting FGF19 protein into medium, mimicking in vivo observations. Furthermore, medium enriched with endogenously produced FGF19 reduced BA synthesis by down regulating CYP7A1 gene expression. However, following knockdown of FGF19, CDCA still independently decreased BA synthesis, presumably through the regulatory protein small heterodimer partner (SHP). In summary, we show that in primary human hepatocytes CDCA regulates BA synthesis in an FGF19-independent manner.

Diiodothyronines regulate metabolic homeostasis in primary human hepatocytes by modulating mTORC1 and mTORC2 activity.

Until three decades, ago 3,5-diiodothyronine (3,5-T2) and 3,3'-diiodothyronine (3,3'-T2) were considered products of thyroid hormone catabolism without biological activity. Some metabolic effects have been described in rodents, but the physiological relevance in humans and the mechanisms of action are unknown. Aim of this work was to investigate the role and the mechanisms of action of 3,5-T2 and 3,3'-T2 in the regulation of metabolic homeostasis in human liver. We used primary human hepatocytes freshly isolated from donors and grown on Matrigel as the golden standard in vitro model to study human hepatic metabolism. Results show that diiodothyronines in the range of plasma physiological concentrations reduced hepatic lipid accumulation, by modulating the activity of the mTORC1/Raptor complex through an AMPK-mediated mechanism, and stimulated the mTORC2/Rictor complex-activated pathway, leading to the down regulation of the expression of key gluconeogenic genes. Hence, we propose that diiodothyronines act as key regulators of hepatic metabolic homeostasis in humans.

Health literacy is independently and inversely associated with carotid artery plaques and cardiovascular risk.

AIMS: Health literacy, the degree to which individuals understand and act upon health information, may have a pivotal role in the prevention of cardiovascular disease (CVD), with low health literacy potentially explaining poorer adherence to prevention guidelines. We investigated the associations between health literacy, ultrasound-detected carotid atherosclerosis and cardiovascular risk factors. METHODS: Baseline data (cross-sectional analysis) from a randomized controlled trial, integrated within the Västerbotten Intervention Program, Northern Sweden, was used. We included 3459 individuals, aged 40 or 50 years with ≥1 conventional risk factor or aged 60 years old. The participants underwent clinical examination, blood sampling, carotid ultrasound assessment of intima-media wall thickness (CIMT) and plaque formation, and answered a questionnaire on health literacy - the Brief Health Literacy Screen. The European Systematic Coronary Risk Evaluation and Framingham Risk Score were calculated. RESULTS: About 20% of the participants had low health literacy. Low health literacy was independently associated with the presence of ultrasound-detected carotid artery plaques after adjustment for age and education, odds ratio (95% confidence interval) 1.54 (1.28-1.85), demonstrating a similar level of risk as for smoking. Health literacy was associated with CIMT in men. Low health literacy was associated with higher CVD risk scores. Sensitivity analyses with low health literacy set to 9% or 30% of the study sample, respectively, yielded essentially the same results. CONCLUSIONS: Low health literacy was independently associated with carotid artery plaques and a high level of CVD risk scores. Presenting health information in a fashion that is understood by all patients may improve preventive efforts.

Lipidomic analysis of human primary hepatocytes following LXR activation with GW3965 identifies AGXT2L1 as a main target associated to changes in phosphatidylethanolamine.

Liver X receptor (LXR) agonists have the potential to alleviate obesity related diseases, particularly atherosclerosis. However, LXRs are transcriptional regulators that induce de novo lipogenesis and lipid accumulation in hepatocytes which represents a serious adverse effect. In this work, we sought to characterize the LXR agonist GW3965 effects on fatty acid (FA) and phospholipid (PL) remodelling and the correlation with gene expression in order to better understand the underlying effects leading to hepatic pathology upon LXR activation. Human primary hepatocytes treated for 48 h with GW3965 were analysed for changes in lipid metabolism gene expression by qPCR, variations in the FA profile was evaluated by GC-FID and in PL profiles using thin layer chromatography, ESI-MS and MS/MS analysis. Changes in cell membrane biochemical properties were studied using bilayer models generated with CHARMM-GUI. ELOLV6 and SCD1 mRNA increase was consistent with higher C16:1 and C18:1n9 at the expense of C16:0 and C18:0. The reduction of C18:2n6 and increase in C20:2n6 was in agreement with ELOVL5 upregulation. Phosphatydilethanolamine (PE) levels tended to decrease and phosphatidylinositol to increase; although differences did not reach significance, they correlated with changes in AGXT2L1, CDS1 and LPIN1 mRNA levels that were increased. The overall effect of GW3965 on PEs molecular profiles was an increase of long-chain polyunsaturated FA chains and a decrease of C16/C18 saturated and monounsaturated FAs chains. Additionally, PC (32:1) and PC (34:2) were decreased, and PC (36:1) and PC (34:1) were increased. AGXT2L1 is an enzyme with strict substrate specificity for phosphoethanolamine, which is converted into ammonia in GW3965-treated hepatocytes and could explain the PE reduction. In summary, LXR activation by GW3965 targets PE biosynthesis and FA elongation/desaturation, which tends to decrease PE in relation to total PL levels, and remodelling of PC and PE molecular species. We identified the human AGXT2L1 gene as induced by LXR activation by both synthetic and endogenous agonist treatment. The increase in acetaldehyde-induced oxidative stress, and in the lipid species identified have the potential to enhance the inflammatory process and impair membrane function. Future studies should focus on inhibition of AGXT2L1 activity with the aim of reverting the steatosis induced by LXR activation.

Health-Care Administrator Perspectives on Prevention Guidelines and Healthy Lifestyle Counseling in a Primary Care Setting in New York State.

INTRODUCTION: The incidence of chronic disease and treatment costs have been steadily increasing in the United States over the past few decades. Primary prevention and healthy lifestyle counseling have been identified as important strategies for reducing health-care costs and chronic disease prevalence. This article seeks to examine decision-makers' experiences and self-perceived roles in guideline and lifestyle counseling implementation in a primary care setting in the United States. METHODS: Qualitative interviews were conducted with administrators at a health-care network in Upstate New York and with state-level administrators, such as insurers. Decision-makers were asked to discuss prevention guidelines and healthy lifestyle counseling, as well as how they support implementation of these initiatives. Interviews were analyzed using a thematic analysis framework and relevant sections of text were sorted using a priori codes. RESULTS: Interviews identified numerous barriers to guideline implementation. These included the complexity and profusion of guidelines, the highly politicized nature of health-care provision, and resistance from providers who sometimes prefer to make decisions autonomously. Barriers to supporting prevention counseling included relatively time-limited patient encounters, the lack of reimbursement mechanisms for counseling, lack of patient resources, and regulatory complexities. CONCLUSIONS: Our research indicates that administrators and administrative structures face barriers to supporting prevention activities such as guideline implementation and healthy lifestyle counseling in primary care settings. They also identified several solutions for addressing existing primary prevention barriers, such as relying on nurses to provide healthy lifestyle support to patients. This article provides an important assessment of institutional readiness to support primary prevention efforts.

Imbalance of Genes Encoding Natural Killer Immunoglobulin-Like Receptors and Human Leukocyte Antigen in Patients With Biliary Cancer.

BACKGROUND & AIMS: Bile duct tumors are rare and have poor prognoses. Natural killer (NK) cells are frequent in human liver and infiltrate these tumors but do not control their progression. Responses of NK cells are regulated by NK immunoglobulin-like receptors (KIRs), which interact with HLA class I ligands. We aimed to characterize the features of the KIR gene loci and their ligands in patients with bile duct cancer (BDC). METHODS: We performed combined multidimensional characterization of genes that encode KIRs and their ligands in blood samples from patients with BDC from Sweden, followed for up to 8 years after diagnosis (n = 148), in 2 geographically matched cohorts of healthy individuals from Northern Europe (n = 204 and n = 900), and in healthy individuals from 6 geographically unrelated populations (n = 2917). We used real-time polymerase chain reaction, RNA sequencing, immunohistochemistry, and flow cytometry to evaluate NK-cell presence, as well as KIR and KIR-ligand expression in bile duct tumors and control tissues. RESULTS: Patients with bile duct tumors had multiple alterations at the KIR gene loci. KIR loci are grouped into genotypes that encode more inhibitory (group A) and more activating (group B) receptors, which can be subdivided into centromeric and telomeric fragments. Patients with BDC had a lower prevalence of KIR2DL3, which was linked to disequilibrium in centromeric A/B and B/B genotypes, compared with control individuals. The associations between KIRs and KIR ligands differed between patients with BDC and control individuals; patients had an altered balance between activating and inhibitory KIRs. KIR-positive NK cells infiltrated biliary tumors that expressed matched KIR ligands. CONCLUSIONS: In a multidimensional analysis of DNA from blood samples of patients with BDC in Europe, we found patients to have multiple alterations at the KIR and HLA gene loci compared with control individuals. These alterations might affect NK-cell tumor surveillance. NK cells from bile duct tumors expressed KIRs and were found in tumors that expressed cognate ligands. This should be considered in development of immune-based therapies for BDC.

Care providers' perceptions towards challenges and opportunities for service improvement at diabetes management clinics in public primary health care in Muscat, Oman: a qualitative study.

BACKGROUND: The literature has described several challenges related to the quality of diabetes management clinics in public primary health care centres in Oman. These clinics continue to face challenges due to the continuous growth of individuals diagnosed with type 2 diabetes. We sought to explore the challenges faced in these clinics and discuss opportunities for improvement in Oman. METHODS: This qualitative study was designed to include non-participant observations of diabetic patients and care providers during service provision at diabetes management clinics, as well as semi-structured interviews with care providers, at five purposively selected public primary health care centres. Care providers included physicians, nurses, dieticians, health educators, pharmacists, an assistant pharmacist, a psychologist, and a medical orderly. The data were analysed using qualitative content analysis. RESULTS: The study disclosed three different models of service delivery at diabetes management clinics, which, to varying degrees, face challenges related to health centre infrastructure, technical and pharmaceutical support, and care providers' interests, knowledge, and skills. Challenges related to the community were also found in terms of cultural beliefs, traditions, health awareness, and public transportation. CONCLUSION: The challenges encountered in diabetes management clinics fall within two contexts: health care centres and community. Although many challenges exist, opportunities for improvement are available. However, improvements in the quality of diabetic clinics in primary health care centres might take time and require extensive involvement, shared responsibilities, and implications from the government, health care centres, and community.

Are the resources adoptive for conducting team-based diabetes management clinics? An explorative study at primary health care centers in Muscat, Oman.

AimThe aim of this study is to explore the perceptions among primary health center staff concerning competencies, values, skills and resources related to team-based diabetes management and to describe the availability of needed resources for team-based approaches. BACKGROUND: The diabetes epidemic challenges services available at primary health care centers in the Middle East. Therefore, there is a demand for evaluation of the available resources and team-based diabetes management in relation to the National Diabetes Management Guidelines. METHOD: A cross-sectional study was conducted with 26 public primary health care centers in Muscat, the capital of Oman. Data were collected from manual and electronic resources as well as a questionnaire that was distributed to the physician-in-charge and diabetes management team members.FindingsThe study revealed significant differences between professional groups regarding how they perceived their own competencies, values and skills as well as available resources related to team-based diabetes management. The perceived competencies were high among all professions. The perceived team-related values and skills were also generally high but with overall lower recordings among the nurses. This pattern, along with the fact that very few nurses have specialized qualifications, is a barrier to providing team-based diabetes management. Participants indicated that there were sufficient laboratory resources; however, reported that pharmacological, technical and human resources were lacking. Further work should be done at public primary diabetes management clinics in order to fully implement team-based diabetes management.

Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA): a pragmatic, open-label, randomised controlled trial.

BACKGROUND: Primary prevention of cardiovascular disease often fails because of poor adherence among practitioners and individuals to prevention guidelines. We aimed to investigate whether ultrasound-based pictorial information about subclinical carotid atherosclerosis, targeting both primary care physicians and individuals, improves prevention. METHODS: Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) is a pragmatic, open-label, randomised controlled trial that was integrated within the Västerbotten Intervention Programme, an ongoing population-based cardiovascular disease prevention programme in northern Sweden. Individuals aged 40, 50, or 60 years with one or more conventional risk factors were eligible to participate. Participants underwent clinical examination, blood sampling, and ultrasound assessment of carotid intima media wall thickness and plaque formation. Participants were randomly assigned 1:1 with a computer-generated randomisation list to an intervention group (pictorial representation of carotid ultrasound plus a nurse phone call to confirm understanding) or a control group (not informed). The primary outcomes, Framingham risk score (FRS) and European systematic coronary risk evaluation (SCORE), were assessed after 1 year among participants who were followed up. This study is registered with ClinicalTrials.gov, number NCT01849575. FINDINGS: 3532 individuals were enrolled between April 29, 2013, and June 7, 2016, of which 1783 were randomly assigned to the control group and 1749 were assigned to the intervention group. 3175 participants completed the 1-year follow-up. At the 1-year follow-up, FRS and SCORE differed significantly between groups (FRS 1·07 [95% CI 0·11 to 2·03, p=0·0017] and SCORE 0·16 [0·02 to 0·30, p=0·0010]). FRS decreased from baseline to the 1-year follow-up in the intervention group and increased in the control group (-0·58 [95% CI -0·86 to -0·30] vs 0·35 [0·08 to 0·63]). SCORE increased in both groups (0·13 [95% CI 0·09 to 0·18] vs 0·27 [0·23 to 0·30]). INTERPRETATION: This study provides evidence of the contributory role of pictorial presentation of silent atherosclerosis for prevention of cardiovascular disease. It supports further development of methods to reduce the major problem of low adherence to medication and lifestyle modification. FUNDING: Västerbotten County Council, the Swedish Research Council, the Heart and Lung Foundation, the Swedish Society of Medicine, and Carl Bennet Ltd, Sweden.

Circulating Fibroblast Growth Factor 19 in Portal and Systemic Blood.

BACKGROUND: Bile acid homeostasis is essential and imbalance may lead to liver damage and liver failure. The bile acid induced intestinal factor fibroblast growth factor 19 (FGF19) has been identified as a key protein for mediating negative feedback inhibition of bile acid synthesis. The aim of the study was to define FGF19 and bile acid concentrations in portal and systemic blood in the fasted and postprandial state. We also addressed the question if physiological portal levels of FGF19 can be extrapolated from the concentration in systemic blood. METHODS: Portal and systemic blood was collected from 75 fasted patients undergoing liver surgery and from three organ donors before and after enteral nutrition. Serum concentration of FGF19 was determined with ELISA and bile acid concentration with gas chromatography-mass spectrometry. RESULTS: Concentration of bile acids was twice as high in portal compared to systemic blood in the fasted group and 3-5 times higher in the postprandial group. FGF19 increased after enteral nutrition but did not differ between portal and systemic blood, in either group. In addition, a strong, positive correlation between bile acids and FGF19 was found. CONCLUSION: Our results confirm that bile acids drive the postprandial increase of circulating FGF19 but a hepatic clearance of FGF19 is unlikely. We conclude that systemic concentrations of FGF19 reflect portal concentrations of FGF19.

Serial Assessment of Growth Factors Associated with Liver Regeneration in Patients Operated with Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy.

BACKGROUND: There is limited knowledge about the mechanisms behind the unparalleled growth of the future liver remnant (FLR) linked to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). In this study, liver regenerative markers were examined in patients subjected to ALPPS. METHODS: Ten patients with colorectal liver metastases treated with neoadjuvant chemotherapy and ALPPS were included. Plasma was sampled at 6 time points and biopsies from both liver lobes were collected at both stages of ALPPS. The levels of interleukin (IL)-6, hepatocyte growth factor (HGF), tumor necrosis factor-α, epidermal growth factor, and vascular endothelial growth factor in plasma were measured at each time point. Expression of mRNA for markers of proliferation and apoptosis was studied in the biopsies from both liver lobes taken at both stages. RESULTS: ALPPS resulted in a peak of IL-6 after stage 1 (p = 0.004), which decreased rapidly and did not increase again after stage 2. HGF also increased after stage 1 (p = 0.048), and the HGF levels correlated significantly with the degree of growth of the FLR before stage 2 (p = 0.02, r2 = 0.47). There was a correlation between peak levels of IL-6 and HGF (p = 0.03, r2 = 0.84). CONCLUSIONS: IL-6 and HGF seem to be early mediators of hypertrophy after stage 1 in the ALPPS procedure. The peak HGF plasma level correlates with the degree of FLR growth in patients subjected to ALPPS.