Possible explanations for the common clinical familial hypercholesterolemia phenotypes in the Faroe Islands.

BACKGROUND: The prevalence of clinical familial hypercholesterolemia (FH) is very high in the Faroe Islands, but the possible causes are unknown. OBJECTIVES: We aimed to describe potential genetic causes of FH in the Faroe Islands and to investigate whether levels of lipoprotein(a) and measures of dietary habits were associated with clinical FH in the Faroe Islands. METHODS: In this case-control study, we identified potential clinical FH cases aged 18-75 years registered within a nationwide clinical laboratory database in the Faroe Islands and invited them for diagnostic evaluation according to clinical FH scoring systems. Controls were identified in the background population. Lipoprotein(a) was measured in plasma, while the fatty acid composition was determined in adipose tissue. The habitual diet of the participants was assessed using a food frequency questionnaire. Genetic testing for FH and polygenic variants was performed in a selection of clinical FH cases. RESULTS: A total of 121 clinical FH cases and 123 age- and sex-matched controls were recruited. We found a very low frequency of monogenic FH (2.5%), but a high level of polygenic FH (63%) in those genetically tested (67%). High levels of plasma lipoprotein(a) were associated with high odds of clinical FH. Clinical FH cases had a lower intake of saturated fatty acids (SFAs) measured by a high fat-score and a lower content of SFAs in adipose tissue compared with controls. CONCLUSION: The high prevalence of FH in the Faroe Islands may be due to polygenic causes of hypercholesterolemia and to a lesser extent other genetic factors and elevated plasma lipoprotein(a) levels.

Meta-analysis of NAD(P)(H) quantification results exhibits variability across mammalian tissues.

Nicotinamide Adenine Dinucleotide (NAD+) plays an important role in energy metabolism and signaling pathways controlling crucial cellular functions. The increased interest in NAD+ metabolism and NAD+-boosting therapies has reinforced the necessity for accurate NAD+ quantification. To examine the published NAD(P)(H) measures across mammalian tissues, we performed a meta-analysis of the existing data. An Ovid MEDLINE database search identified articles with NAD(P)(H) quantification results obtained from mammalian tissues published between 1961 and 2021. We screened 4890 records and extracted quantitative data, as well as the quantification methods, pre-analytical conditions, and subject characteristics. The extracted physiological NAD(P)(H) concentrations in various tissues from mice, rats, and humans, revealed an important inter- and intra-method variability that extended to recent publications. This highlights the relatively poor potential for cross-experimental analyses for NAD(P)(H) quantitative data and the importance of standardization for NAD(P)(H) quantification methods and pre-analytical procedures for future preclinical and clinical studies.

Familial hypercholesterolaemia: a study protocol for identification and investigation of potential causes and markers of subclinical coronary artery disease in the Faroe Islands.

INTRODUCTION: Familial hypercholesterolaemia (FH) is the most common monogenic autosomal dominant genetic disorder and is associated with a high risk of premature atherosclerotic cardiovascular disease. The prevalence of FH has been reported to be particularly high in certain founder populations. The population of the Faroe Islands is a founder population, but the prevalence of FH has never been investigated here. We aim to assess the prevalence of FH and to describe the genetic and clinical characteristics and potential causes of FH in the Faroe Islands. Furthermore, we aim to investigate whether indicators of subclinical coronary artery disease are associated with FH. METHODS AND ANALYSIS: The prevalence of FH will be estimated based on an electronic nationwide laboratory database that includes all measurements of plasma lipid levels in the Faroe Islands since 2006. Subsequently, we will identify and invite subjects aged between 18 and 75 years registered with a plasma low-density lipoprotein cholesterol above 6.7 mmol/L for diagnostic evaluation. Eligible FH cases will be matched to controls on age and sex. We aim to include 120 FH cases and 120 controls.Detailed information will be collected using questionnaires and interviews, and a physical examination will be undertaken. An adipose tissue biopsy and blood samples for genetic testing, detailed lipid analyses and samples for storage in a biobank for future research will be collected. Furthermore, FH cases and controls will be invited to have a transthoracic echocardiography and a cardiac CT performed. ETHICS AND DISSEMINATION: The project has been approved by the Ethical Committee and the Data Protection Agency of the Faroe Islands. The project is expected to provide important information, which will be published in international peer-reviewed journals.

Subclinical atherosclerosis determined by coronary artery calcium deposition in patients with clinical familial hypercholesterolemia.

Background and aims: Limited knowledge exists regarding the association between coronary artery calcium (CAC) deposition in patients with clinical familial hypercholesterolemia (FH) and FH subtypes such as polygenic causes. We studied CAC score in patients with clinical FH and subtypes including polygenic causes of FH compared to healthy controls. Methods: In a case-control study, we identified potential clinical FH cases registered with an LDL-C >6.7 mmol/l within a nationwide clinical laboratory database on the Faroe Islands and invited them for diagnostic evaluation according to clinical FH scoring systems. Controls were identified in the background population. All subjects were aged 18-75 years and without a history of cardiovascular disease. FH mutation testing and genotypes of twelve LDL-C associated single nucleotide polymorphisms were determined using conventional methods in selected individuals. CAC scores were assessed by cardiac CT. Odds ratios obtained using multivariate logistic regression were used as measures of association. Results: A total of 120 clinical FH patients and 117 age- and sex-matched controls were recruited. We found a very low frequency of monogenic FH (3%), but a high level of polygenic FH (60%) in those genetically tested (54%). There was a statistically significant association between the CAC score and a diagnosis of clinical FH with the highest observed odds ratio of 5.59 (95% CI 1.65; 18.94, p = 0.006) in those with a CAC score ≥300 compared to those with a CAC of zero. In supplemental analyses, there was a strong association between CAC scores and clinical FH of a polygenic cause. Conclusion: We found a statistically significant association between CAC levels and clinical FH with the highest observed risk estimates among clinical FH cases of a presumed polygenic cause.

Lipids, lipoproteins and prevalence of familial hypercholesterolemia in the Faroe Islands - Results from a nationwide laboratory database.

Background and aims: Familial hypercholesterolemia (FH) is one of the most common hereditary disorders. The population of the Faroe Islands was established by few founders, and genetic drift may have influenced lipid levels. The aim of this study was to describe the lipid distribution by providing age and sex-specific lipid values and to investigate the prevalence of FH in the Faroe Islands. Methods: We used an electronic nationwide laboratory database that included lipid measurements obtained in the Faroe Islands between January 2006 and September 2020. Percentiles of lipid levels were calculated using quantile regression. The prevalence of FH was estimated according to the Make Early Diagnosis Prevent Early Death (MEDPED) diagnostic criteria and according to the LDL-C cut-off levels included in the Dutch Lipid Clinic Network (DLCN) criteria using generalized linear models with robust variance. Results: According to the MEDPED age-specific cut-offs for LDL-C, a total of 216 subjects met the criteria for definite FH among 30,711 individuals corresponding to a prevalence of 0.70% (1:142). According to the LDL-C cut-offs included in the DLCN criteria, a total of 3,823 (1:8) subjects could be classified as having possible FH, and 10 (1:3,071) subjects could be classified as probable FH corresponding to a prevalence of 12.4% and 0.03%, respectively. Also, we found significant differences in lipid levels according to sex and age groups. Conclusion: The Faroe Islands might represent a founder population with a prevalence of possible FH as high as 1 in 8. Further investigation of genetic and clinical characteristics of FH in the Faroe Islands is needed.

Photodynamic Therapy of Ovarian Carcinoma Cells with Curcumin-Loaded Biodegradable Polymeric Nanoparticles.

Accumulation of photosensitisers in photodynamic therapy in healthy tissues is often the cause of unwanted side effects. Using nanoparticles, improved bioavailability and site-specific drug uptake can be achieved. In this study, curcumin, a natural product with anticancer properties, albeit with poor aqueous solubility, was encapsulated in biodegradable polymeric poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CUR-NP). Dynamic light scattering, laser Doppler anemometry and atomic force microscopy were used to characterise the formulations. Using haemolysis, serum stability and activated partial thromboplastin time tests, the biocompatibility of CUR-NP was assessed. Particle uptake and accumulation were determined by confocal laser scanning microscopy. Therapeutic efficacy of the formulation was tested in SK-OV-3 human ovarian adenocarcinoma cells post low level LED irradiation by determining the generation of reactive oxygen species and cytotoxicity. Pharmacologic inhibitors of cellular uptake pathways were used to identify the particle uptake mechanism. CUR-NP exhibited better physicochemical properties such as stability in the presence of light and improved serum stability compared to free curcumin. In addition, the novel nanoformulation facilitated the use of higher amounts of curcumin and showed strong apoptotic effects on tumour cells.

BLTR1 and CD36 Expressing Microvesicles in Atherosclerotic Patients and Healthy Individuals.

Aims: Monocytes/macrophages play a crucial role in the development, progression, and complication of atherosclerosis. In particular, foam cell formation driven by CD36 mediated internalization of oxLDL leads to activation of monocytes and subsequent release of microvesicles (MVs) derived from monocytes (MMVs). Further, pro-inflammatory leukotriene B4 (LTB4) derived from arachidonic acid promotes atherosclerosis through the high-affinity receptor BLTR1. Thus, we aimed to investigate the correlation between different MMV phenotypes (CD14+ MVs) on the one hand, and arachidonic acid and eicosapentaenoic acid contents in different compartments including atherosclerotic plaques, plasma, and granulocytes on the other. Methods and Results: Samples from patients with femoral atherosclerosis and healthy controls were analyzed on an Apogee A60 Micro-PLUS flow cytometer. Platelet-poor plasma was labeled with lactadherin-FITC, anti-CD14-APC, anti-CD36-PE, and anti-BLTR1-AF700. Eicosapentaenoic acid and arachidonic acid content in different compartments in patients were analyzed using gas chromatography. Compared to controls, patients had lower levels of BLTR1+ MVs (p = 0.007), CD14+BLTR1+ MVs (p = 0.007), and CD14+BLTR1+CD36+ MVs (p = 0.001). Further, in patients CD14+ MVs and CD14+CD36+ MVs correlated inversely with arachidonic acid in granulocytes (r = -0.302, p = 0.039 and r = -0.322, p = 0.028, respectively). Moreover, CD14+CD36+ MVs correlated inversely with arachidonic acid in plasma phospholipids in patients (r = -0.315, p = 0.029), and positively with triglyceride in both patients (r = 0.33, p = 0.019) and controls (r = 0.46, p = 0.022). Conclusion: This is the first study of its kind and thus the results are explorative and only indicative. BLTR1+ MVs and CD14+CD36+ MVs has potential as markers of atherosclerosis pathophysiology, but this needs further investigation.

Tanzanian midwives' perception of their professional role and implications for continuing professional development education.

This study explored Tanzanian midwives' perceptions of their professional role within their local context. Findings were to inform recommendations for continuing professional development education programs by Western midwifery educators. Using focus group interviews with sixteen Tanzanian midwives, the findings revealed that the midwives' overwhelming focus was on saving lives of women and newborns. The fundamental elements of saving lives involved prioritising care through receiving handover and undertaking physical assessment. Midwives were challenged by the poor working conditions, perceived lack of knowledge and associated low status within the local community. Based upon these findings, recommendations for continuing professional development education for Tanzanian midwives must ensure that saving lives is a major focus and that strategies taught must be relevant to the low-resource context of this developing country. In recognition of the high-risk women being cared for, there needs to be a focus on the prevention and management of maternity emergencies, in collaboration with medical practitioners.

Seeking empowerment to comfort patients in severe pain: a grounded theory study of the nurse's perspective.

BACKGROUND: Hospital patients experience significant pain, which can delay healing and increase the risk of developing chronic pain. Nurses are affected by patients' ongoing pain and may cope with consequent anxiety and helplessness by distancing themselves from such patients. Understanding nurses' responses to patients in severe pain will inform strategies to support their coping, their patients and, ultimately, their retention in the nursing workforce. OBJECTIVES: The aim of the study was to develop a substantive theory explaining the hospital nurse's perspective of caring for patients in severe pain. DESIGN: The study used grounded theory method. SETTINGS: Data were collected on four acute care wards in a 610 bed Australian hospital. PARTICIPANTS: The sample included 33 nurse participants and 11 patient participants. Selection criteria for nurse participants were those who worked in the four study wards, cared for patients who experienced severe pain, and consented to be included. Selection criteria for patient participants were those who self-reported pain at intensity of seven or more on a scale of 0-10, were aged 18 years or older, could speak and read English, and consented to be included. METHODS: Theoretical sampling directed the collection of data using semi-structured interviews with nurses and participant observation, including structured observations of nurses who cared for patients in pain. Data were analysed using constant comparison method. RESULTS: Nurse participants encountered a basic psychosocial problem of feelings of disempowerment when their patients experienced persisting severe pain. In response, they used a basic psychosocial process of seeking empowerment to provide comfort in order to resolve distress and exhaustion associated with disempowerment. This coping process comprised three stages: building connections; finding alternative ways to comfort; and quelling emotional turmoil. CONCLUSIONS: The substantive theory proposed a link between the stress of nurses' disempowerment and a coping response that provides direction to support nurses' practice. Strategies indicated include enhanced communication protocols, access to advanced practice nurses, use of nonpharmacological comfort measures, utilization of ward-based pain resource nurses, and unit-specific pain management education. Further research to verify and extend the substantive theory to other settings and nursing populations is warranted.

Educational innovation for infection control in Tanzania: bridging the policy to practice gap.

The incidence of hospital acquired infection in developing countries is between two to 20 times higher than in developed countries and is attributable to multiple causes. Evidence-based international policies and guidelines developed to improve infection prevention and control are often not used in practice in these countries. To combat this challenge, this article presents an innovative educational framework used to bridge the gap between policy written by global health agencies and the realities of practice in Tanzania.

The effect of low-dose marine n-3 fatty acids on plasma levels of sCD36 in overweight subjects: a randomized, double-blind, placebo-controlled trial.

CD36 is a scavenger receptor involved in lipid uptake and inflammation. Recently, non-cell-bound CD36 (sCD36) was identified in plasma and suggested to be a marker of lipid accumulation in the vessel wall. Marine n-3 polyunsaturated fatty acids (PUFA) may have cardioprotective effects. This study evaluated the effect of marine n-3 PUFA on sCD36 levels in overweight subjects. Fifty overweight subjects were randomized to 1.1 g of n-3 PUFA or 2 g of olive oil daily for six weeks. Neutrophils were isolated at baseline and after six weeks of treatment while an adipose tissue biopsy was obtained at baseline. The content of n-3 PUFA in adipose tissue and neutrophils was analyzed by gas chromatography, while plasma levels of sCD36 were determined using an enzyme-linked immunosorbent assay (ELISA). After six weeks of supplement plasma sCD36 did not differ between supplements (P = 0.18). There was no significant correlation between plasma sCD36 levels and n-3 PUFA in neutrophils at baseline (r = -0.02, P = 0.88), after six weeks supplement (r = -0.03, P = 0.85) or in adipose tissue (r = 0.14, P = 0.34). This study therefore does not provide evidence for a cardioprotective effect of n-3 PUFA acting through a CD36-dependent mechanism.

Attributes for effective nurse management within the health services of Western Australia, Singapore and Tanzania.

OBJECTIVE: To identify the perceptions of nurse managers in Western Australia, Singapore and Tanzania regarding desirable attributes for effective management of their health services, and to identify and discuss the implications for health-management education provided by Australian universities. METHODS: Nurse managers completed a questionnaire covering four key dimensions: personality characteristics, knowledge and learning, skills, and beliefs and values. Each of 75 items were rated as to their effect on management effectiveness, according to a 5-point Likert scale. RESULTS: Skills were considered the most important for management effectiveness by each group. Tanzanian respondents rated knowledge and learning almost as highly, and significantly higher than Western Australian respondents. They also rated personality characteristics and beliefs and values significantly higher than Western Australian respondents. No significant differences were found between Singapore and Western Australia. CONCLUSIONS: Participants desired a different relative mix of attributes in their nurse managers, with Western Australian respondents most likely to indicate that transformational leadership contributed most to managerial effectiveness. Tanzanian nurse managers were most likely to advocate transactional leadership, whereas Singaporean nurse managers' views were located somewhere between. Given that these perceptions are valid, the content and curricula of management-development courses need to be cognisant of the cultural backgrounds of participants. WHAT IS KNOWN ABOUT THE TOPIC? Views differ as to the extent to which the criteria for management effectiveness are broadly universal or contingent on culture. This applies to the area of nurse management as it does to healthcare management in general. WHAT DOES THIS PAPER ADD? It is demonstrated that each of the three quite different countries or states considered identified a distinctive combination of attributes as desirable, with the nurse managers of Western Australia most likely to favour a transformational style of leadership, those from Tanzania a transactional leadership style and those from Singapore somewhere in between. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Given the country- or state-specific desire for a different relative mix of attributes in their nurse managers, management educators in Australia need to ensure that the content and curricula of their courses are cognisant of the cultural backgrounds of their students. There are also important lessons to be taken on board regarding recruitment of nurses into management positions in terms of each of the four dimensions considered, particularly in terms of desirable personality characteristics and beliefs and values.