Analytical considerations for accurately capturing the relevant species contributing to vitamin D status in liquid chromatography-tandem mass spectrometry assays

This tutorial review focuses on analytical challenges encountered with the liquid chromatography-tandem mass spectrometry determination of 25-hydroxyvitamin D, which is currently still considered the metabolite that is most representative of vitamin D status. It describes how multiple binding states of circulating 25-hydroxyvitamin D (phase II metabolites, epimers, free/bioavailable/protein-bound species) can influence the accuracy of the analytical determination. It also summarizes important chemical species that can inadvertently contribute to vitamin D status and thus cause systematic errors. These interfering endogenous and exogenous compounds might be isomers of vitamin D, constitutional isomers or isobars and the article outlines techniques to eliminate or minimize these interferences, including chromatographic separations, ion mobility spectrometry, and high-resolution mass spectrometry.Peer Reviewe

Noninvasive monitoring of liver fat during treatment with GLP‐1 analogues and SGLT‐2 inhibitors in a real‐world setting

Introduction: Patients with NAFLD have a two‐fold increased risk of diabetes, and conversely, NAFLD affects up to 80% of patients with type 2 diabetes. Due to the co‐occurrence of both diseases and the lack of approved pharmacotherapy for NAFLD, the anti‐steatogenic potential of diabetes‐related drugs is being explored. In this study, we aim to monitor liver fat noninvasively during treatment with SGLT‐2 inhibitors or GLP‐1 analogues in a real‐world setting. Methods: Overall, 39 patients (49% women, age 57.7 ± 10.9 years) with type 2 diabetes and hepatic steatosis (defined by controlled attenuation parameter [CAP] values ≥ 215 dB/m) were observed for 6 months and routinely monitored with respect to hepatic fat contents and liver stiffness (VCTE); body composition (BIA); and blood biochemistry, including liver function tests (LFTs), serum lipids and glucose metabolism markers. Results: Median liver fat contents were significantly (P = .026) reduced by 9% in patients taking either SGLT‐2 (n = 22) or GLP‐1 (n = 17) for 6 months (absolute median CAP decrease: −32 dB/m [−58 to 32 dB/m]). In parallel, serum ALT and γ‐GT activities decreased significantly (P = .002 and P = .049, respectively). These improvements were accompanied by significant (P < .0001) changes to body weight and BMI (−2.5 ± 3.3 kg and −0.9 ± 1.2 kg/m2, respectively) and glucose homeostasis, with significant reductions in HbA1c and fasting plasma glucose (FDG) (both P < .0001). Of note, significant reductions of intrahepatic lipid contents occured in patients receiving SGLT‐2 inhibitors only. Conclusions: In this real‐world observational evaluation of fatty liver monitored noninvasively in patients with type 2 diabetes treated with either SGLT2 or GLP‐1, improvements in measures of hepatic steatosis, glucose and weight parameters were observed after 6 months, with significant reductions of intrahepatic lipid contents seen specifically in the SGLT2 subgroup

The Effect of the Paleolithic Diet vs. Healthy Diets on Glucose and Insulin Homeostasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Recently, the Paleolithic diet became popular due to its possible health benefits. Several, albeit not all, studies suggested that the consumption of the Paleolithic diet might improve glucose tolerance, decrease insulin secretion, and increase insulin sensitivity. Therefore, the aim of this meta-analysis was to compare the effect of the Paleolithic diet with other types of diets on glucose and insulin homeostasis in subjects with altered glucose metabolism. Four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) were searched to select studies in which the effects of the Paleolithic diet on fasting glucose and insulin levels, glycated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), and area under the curve (AUC 0–120) for glucose and insulin during the oral glucose tolerance test were assessed. In total, four studies with 98 subjects which compared the effect of the Paleolithic diet with other types of diets (the Mediterranean diet, diabetes diet, and a diet recommended by the Dutch Health Council) were included in this meta-analysis. The Paleolithic diet did not differ from other types of diets with regard to its effect on fasting glucose (standardized mean difference (SMD): −0.343, 95% confidence interval (CI): −0.867, 0.181, p = 0.200) and insulin (SMD: −0.141; 95% CI: −0.599, 0.318; p = 0.548) levels. In addition, there were no differences between the Paleolithic diet and other types of diets in HOMA-IR (SMD: −0.151; 95% CI: −0.610, 0.309; p = 0.521), HbA1c (SMD: −0.380; 95% CI: −0.870, 0.110; p = 0.129), AUC 0–120 glucose (SMD: −0.558; 95% CI: −1.380, 0.264; p = 0.183), and AUC 0–120 insulin (SMD: −0.068; 95% CI: −0.526, 0.390; p = 0.772). In conclusion, the Paleolithic diet did not differ from other types of diets commonly perceived as healthy with regard to effects on glucose and insulin homeostasis in subjects with altered glucose metabolism

Design and validation of a German version of the GSRS-IBS - an analysis of its psychometric quality and factorial structure

Background: Currently, a suitable questionnaire in German language is not available to monitor the progression and evaluate the severity of irritable bowel syndrome (IBS). Therefore, this study aimed to translate the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) into German and to evaluate its psychometric qualities and factorial structure. Methods: This study is based on a total sample of 372 participants [62.6% female, mean age = 41 years (SD = 17 years)]. 17.5% of the participants had a diagnosis of IBS, 19.9% were receiving treatment for chronic inflammatory bowel disease, 12.1% of the participants were recruited from a psychosomatic clinic, and 50.5% belonged to a control group. All participants completed the German version of GSRS-IBS (called Reizdarm-Fragebogen, RDF), as well as the Gießen Subjective Complaints List (GBB-24) and the Hospital Anxiety and Depression Scale - German version (HADS-D). Results: The internal consistency of the RDF total scale was at least satisfactory in all subsamples (Cronbach’s Alpha between .77 and .92), and for all subscales (Cronbach’s Alpha between .79 and .91). The item difficulties (between .25 and .73) and the item-total correlations (between .48 and .83) were equally satisfactory. Principal axis analysis revealed a four-factorial structure of the RDF items, which mainly resembled the structure of the English original. Convergent validity was established based on substantial and significant correlations with the stomach-complaint scale of the GBB-24 (r = .71; p &lt; .01) and the anxiety (r = .42; p &lt; .01) and depression scales (r = .43; p &lt; .01) of the HADS-D. Conclusion: The German version of the GSRS-IBS RDF proves to be an effective, reliable, and valid questionnaire for the assessment of symptom severity in IBS, which can be used in clinical practice as well as in clinical studies

Hepatic steatosis in patients with acromegaly

Objective Comorbid NAFLD is increasingly being diagnosed in patients with diabetes and nondiabetic endocrinopathies. The aim of this study was to assess hepatic steatosis noninvasively by transient elastography in patients with acromegaly. Design A cross‐sectional study including 22 patients with acromegaly. Methods Hepatic steatosis was quantified using controlled attenuation parameter (CAP) during elastography. Anthropometric measurements were obtained, serum liver function tests and lipid and hormone profiles were measured, and prosteatogenic gene variants were genotyped using standard assays. Results In total, 41% of patients were women (mean age 60 ± 14.7 years, mean BMI 31.2 ± 4.6 kg/m2). Hepatic steatosis, as defined by CAP > 248 dB/m, was present in 66% of patients. Five (45%) of the patients with hepatic steatosis also had fibrosis, and one presented with cirrhosis. Nine patients were carriers of the PNPLA3 p.I148M prosteatogenic [M] risk allele, eight of whom were heterozygotes. CAP values were significantly (P = .045) higher in these patients and corresponded to advanced steatosis, as compared to patients with the wild‐type genotype, who demonstrated CAP values consistent with mild steatosis (311 ± 33 dB/m. vs 254 ± 62 dB/m). CAP values did not differ significantly in carriers of distinct TM6SF2 and MBOAT7 genotypes; however, carriers of the risk alleles displayed higher CAP as compared to wild‐type patients. Conclusions This study shows that in patients with acromegaly, carriers of the PNPLA3 susceptibility allele are at risk of developing hepatic steatosis, as assessed by CAP. Comorbid NAFLD might compound prognosis in such patients; thus, further research into the pathomechanisms and treatment of NAFLD in acromegaly is warranted

Making Sense of a New Transport System: An Ethnographic Study of the Cambridgeshire Guided Busway

An increase in public transport use has the potential to contribute to improving population health, and there is growing interest in innovative public transport systems. Yet how new public transport infrastructure is experienced and integrated (or not) into daily practice is little understood. We investigated how the Cambridgeshire Guided Busway, UK, was used and experienced in the weeks following its opening, using the method of participant observation (travelling on the busway and observing and talking to passengers) and drawing on Normalization Process Theory to interpret our data. Using excerpts of field notes to support our interpretations, we describe how the ease with which the new transport system could be integrated into existing daily routines was important in determining whether individuals would continue to use it. It emerged that there were two groups of passengers with different experiences and attitudes. Passengers who had previously travelled frequently on regular bus services did not perceive the new system to be an improvement; consequently, they were frustrated that it was differentiated from and not coherent with the regular system. In contrast, passengers who had previously travelled almost exclusively by car appraised the busway positively and perceived it to be a novel and superior form of travel. Our rich qualitative account highlights the varied and creative ways in which people learn to use new public transport and integrate it into their everyday lives. This has consequences for the introduction and promotion of future transport innovations. It is important to emphasise the novelty of new public transport, but also the ways in which its use can become ordinary and routine. Addressing these issues could help to promote uptake of other public transport interventions, which may contribute to increasing physical activity and improving population health. © 2013 Jones et al

Managing talent across advanced and emerging economies: HR issues and challenges in a Sino-German strategic collaboration

The human resource (HR) practices involved in global talent management continue to advance and evolve. A majority of talent management commentary is from multinational corporation (MNC) perspectives. However, the less commented small-to-medium-sized enterprise (SME) also confronts challenges grounded in economic (i.e. resources, finance), organisational (i.e. size, scope and structure) and consequent behavioural rationales (i.e. mindsets and stances). This paper establishes and examines a number of propositions which consider how these factors impact on an advanced economy SME’s talent management in emerging economy collaborations. An interpretive qualitative methodology is employed using interviews conducted within two cases – SME and an MNC comparator case. The SME case is used as the driving force of the paper and its theoretical focus and findings. The MNC is used to develop issues as a comparator case. The findings show SME economic and organisational drivers producing behavioural dynamics in relation to mimesis of planned actions yet informal serendipitous responses in reality; a predilection for the proximate and familiar; design configurations of short-term expatriate visits and inpatriates; cumulating in ongoing inpatriate acculturisation and re-acculturation oscillation. Consequently, the implication is that the SME needs a HR practices encompassing resignation to the situation, flexibility and resilience in order to survive and progress

Liver phenotypes in PCOS : Analysis of exogenous and inherited risk factors for liver injury in two European cohorts

Background & Aims Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. Methods Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. Results A total of 42 German (age range 18–53 years) and 143 Polish (age range 18–40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). Conclusions FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS

Stakeholder engagement in the city branding process

This paper explores perceptions of stakeholder engagement in the city branding process from the perspective of two post-industrial cities: Sheffield, UK and Essen, Germany. This qualitative research utilises a multi case study approach, which allowed for semi-structure interviews and semiotics to be used. Preliminary findings highlight that there are four stakeholder ‘levels’. Each of these stakeholder groupings is involved in the city branding process to some extend. Findings suggest that the degree of involvement strongly depends on the primary stakeholders, who are seen as key decision-makers in the branding process. These primary stakeholders select other stakeholders that ‘can’ be involved in the branding process. Although this may be beneficial it is vital to provide more opportunities and incorporate stakeholders that are willing to participate in the branding process. Alienating stakeholders may also lead to losing parts of an identity that is based on heritage. The focus is on two cities with a highly industrialised background, thus findings may not be applicable to cities without this heritage. The paper looks at both stakeholder engagement and city branding, thereby proposing four layers of stakeholder involvement in the city branding process

Interventions to increase engagement with rehabilitation in adults with acquired brain injury: A systematic review

Rehabilitation in adults with acquired brain injury is often hampered by a lack of client engagement with the rehabilitation process, leading to frustration, withdrawal of services and poorer recovery. Motivation, apathy and awareness are potential mechanisms underlying engagement, but few studies have suggested potential intervention techniques. A systematic review of the literature was carried out to identify and evaluate interventions designed to increase rehabilitation engagement in adults with acquired brain injury. Database searches used the following terms: rehabilitation, brain injury, and compliance/engagement/adherence in PsychInfo, Medline, Cinahl, Embase, AMED, Web of Knowledge, PsycBite, Cochrane clinical trials, and clinicaltrials.org. Hand searches were conducted of reference lists and relevant journals. Fifteen studies were included in the review. Intervention techniques fell into two broad categories: behavioural modification techniques and cognitive/meta-cognitive skills. Contingent reward techniques were most effective at increasing adherence and compliance, while interventions enabling clients' active participation in rehabilitation appeared to increase engagement and motivation. The review highlighted methodological and measurement inconsistencies in the field and suggested that interventions should be tailored to clients' abilities and circumstances