Comparison of CE and HPLC Methods for Determining Lovastatin and Its Oxidation Products after Exposure to an Oxidative Atmosphere

Lovastatin is a cholesterol-lowering agent, which competitively inhibits the enzyme HMG-CoA reductase. Several HPLC methods for its analysis have been developed but there is no report of its determination using capillary electrophoresis (CE). In this paper, we report the development of a simple CE method for lovastatin determination, which is selective with respect to its degradation products and useful for routine analyses. Since the molecule of lovastatin in its lactone form is uncharged and is only slightly soluble in water, base hydrolysis was used to open the lactone ring and transform the compound into a water-soluble acid form, which is negatively charged. Different solvents, different amounts of NaOH added, different hydrolysis times and different temperatures for sample preparation were tested. The CE and HPLC methods are compared in terms of susceptibility, precision, linearity and accuracy. HPLC method was found to be more susceptible and more precise

Elevated EBNA-1 IgG in MS is associated with genetic MS risk variants

Objective: To assess whether MS genetic risk polymorphisms (single nucleotide polymorphism [SNP]) contribute to the enhanced humoral immune response against Epstein-Barr virus (EBV) infection in patients with MS. Methods: Serum anti-EBV nuclear antigen 1 (EBNA-1) and early antigen D (EA-D) immunoglobulin γ (IgG) levels were quantitatively determined in 668 genotyped patients with MS and 147 healthy controls. Anti-varicella-zoster virus (VZV) IgG levels were used as a highly prevalent, non-MS-Associated control herpesvirus. Associations between virus-specific IgG levels and MS risk SNPs were analyzed. Results: IgG levels of EBNA-1, but not EA-D and VZV, were increased in patients with MS compared with healthy controls. Increased EBNA-1 IgG levels were significantly associated with risk alleles of SNP rs2744148 (SOX8), rs11154801 (MYB), rs1843938 (CARD11), and rs7200786 (CLEC16A/CIITA) in an interaction model and a trend toward significance for rs3135388 (HLA-DRB1-1501). In addition, risk alleles of rs694739 (PRDX5/BAD) and rs11581062 (VCAM1) were independently associated and interacted with normal EBNA-1 IgG levels. None of these interactions were associated with EA-D and VZV IgG titers. Conclusions: Several MS-Associated SNPs significantly correlated with differential IgG levels directed to a latent, but not a lytic EBV protein. The data suggest that the aforementioned immune-related genes orchestrate the aberrant EBNA-1 IgG levels

Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study

Objective: To evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization, and to test newly proposed cut-off values. Design: International, prospective, multicentre cohort study.SettingSix university or cantonal departments in Austria, Germany, and Switzerland, from 1 May 2016 to 31 January 2019.ParticipantsLow risk cohort of 829 participants aged 18-45 years with singleton pregnancies attending first trimester screening and consenting to have an early 75 g OGTT at 12-15 weeks of gestation. Participants and healthcare providers were blinded to the results. Main outcome measures: Fasting, one hour, and two hour plasma glucose concentrations after an early 75 g OGTT (12-15 weeks of gestation) and a late 75 g OGTT (24-28 weeks of gestation). Results: Of 636 participants, 74 (12%) developed gestational diabetes mellitus, according to World Health Organization 2013 criteria, at 24-28 weeks of gestation. Applying WHO 2013 criteria to the early OGTT with at least one abnormal value gave a low sensitivity of 0.35 (95% confidence interval 0.24 to 0.47), high specificity of 0.96 (0.95 to 0.98), positive predictive value of 0.57 (0.41 to 0.71), negative predictive value of 0.92 (0.89 to 0.94), positive likelihood ratio of 10.46 (6.21 to 17.63), negative likelihood ratio of 0.65 (0.55 to 0.78), and diagnostic odds ratio of 15.98 (8.38 to 30.47). Lowering the postload glucose values (75 g OGTT cut-off values of 5.1, 8.9, and 7.8 mmol/L) improved the detection rate (53%, 95% confidence interval 41% to 64%) and negative predictive value (0.94, 0.91 to 0.95), but decreased the specificity (0.91, 0.88 to 0.93) and positive predictive value (0.42, 0.32 to 0.53) at a false positive rate of 9% (positive likelihood ratio 5.59, 4.0 to 7.81; negative likelihood ratio 0.64, 0.52 to 0.77; and diagnostic odds ratio 10.07, 6.26 to 18.31). Conclusions: The results of this prospective low risk cohort study indicated that the 75 g OGTT as a screening tool in early pregnancy is not sensitive enough when applying WHO 2013 criteria. Postload glucose values were higher in early pregnancy complicated by diabetes in pregnancy. Lowering the postload cut-off values identified a high risk group for later development of gestational diabetes mellitus or those who might benefit from earlier treatment. Results from randomised controlled trials showing a beneficial effect of early intervention are unclear. Trial registrationClinicalTrials.govNCT02035059

Raising positive expectations helps patients with minor ailments: A cross-sectional study

Background: Consultations for minor ailments constitute a large part of the workload of general practitioners (GPs). As medical interventions are not always available, specific communication strategies, such as active listening and positive communication, might help GPs to handle these problems adequately. This study examines to what extent GPs display both strategies during consultations for minor ailments and investigates how each of these relate to the patients' perceived health, consultation frequency and medication adherence. Methods: 524 videotaped consultations between Dutch GPs and patients aged 18 years or older were selected. All patients presented a minor ailment, and none of them suffered from a diagnosed chronic illness. The observation protocol included the validated Active Listening Observation Scale (ALOS-global), as well as three domains of positive communication, i.e. providing reassurance, a clear explanation, and a favourable prognosis. Patients completed several questionnaires before, immediately after, and two weeks after the consultation. These included measures for state anxiety (STAI), functional health status (COOP/ WONCA charts) and medication adherence (MAQ). Consultation frequency was available from an ongoing patient registration. Data were analysed using multivariate regression analyses. Results: Reassurance was related to patients' better overall health. Providing a favourable prognosis was linked to patients feeling better, but only when accompanied by a clear explanation of the complaints. A clear explanation was also related to patients feeling better and less anxious, except when patients reported a low mood pre-visit. Active listening alone was positively associated with patients feeling worse. Among patients in a good mood state, active listening was associated with less adherence. Conclusion: To some extent, it seems helpful when GPs are at the same time clear and optimistic about the nature and course of minor ailments. Yet, it does not seem helpful always and in all cases, e.g. when patients feel low upon entering the consulting room. Although communication strategies might to some extent contribute to the management of minor ailments, the results of this observational study also indicate that it is important for a physician to pay attention to the mood of the patient who enters the consulting room. (aut. ref.

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Sport and Politics in the Twenty-First Century

In this article, we address the aporia(s) of the Olympic discourse produced by the troubled split between sport and politics. To start our argument, we will show that sporting governing bodies continuously insist that they are still on the other side of any kind of politics. Guided by Aristotle, who presented the reciprocity of ethics and politics, we will unveil the fallacy of this discourse. In a short genealogy of the relationship between sport, ethics, and politics, we will highlight the Munich Olympics 1936 and Mexico Olympics 1968, where political engagement of sport was exposed clearly. At the same time, the supposed political neutrality of sport manifested an aristocratic preference for radical right regimes. After that, we will analyse the contemporary relation between sport, ethics, and politics in the light of recent developments, including sport’s ambiguous reaction on the Ukraine war. Further argument will be that sport’s in- and external politics, supported by sport ethics and the inherited mantra of the split between sport and politics, is more than just a hypocrisy. At the start, modern sport claims autonomy of governance to keep away from state domination, yet this very autonomy also freezes sport’s ethical core, forbidding athletes, coaches and others active in sport, to express any political engagement, other than passive acceptance of the regulation by governing sport bodies, as the only politics to be respected without deliberation. In the final part an alternative understanding of the dynamics between politics, the political and sport’s ethical core, will be presented to be included in the philosophy of sport and fully developed in following articles

Pediatric medical stress and trauma

Events related to various illnesses, injuries and chronic conditions, as well as related treatment and medical interventions, represent the most common potential traumatic experiences in childhood. In the article, the author inquires about the occurrence of traumatic stress and medical trauma in children and their families. A theoretical model of long-term somatic threat designed to distinguish between medical trauma and trauma not caused by medical events can be used to identify medical trauma. Various studies report that up to 80% of children and their families experience some traumatic stress in dealing with life-threatening illnesses, injuries or painful medical procedures. About 20-30% of parents and 15-25% of children and their relatives even experience lasting traumatic stress that impedes daily functioning and affects the very course of treatment and recovery. The development and course of pediatric medical trauma is exemplified by the model of pediatric medical traumatic stress, which also outlines the goals of interventions for each stage of the course. In addition to the psychologist, health care staff also play an important role in preventing the trauma that can occur when treating children, adolescents and their parents. All professionals and healthcare professionals should strive to address and care for children, including awareness of and informing about trauma, and thus prevent or reduce the negative effects of trauma that can occur in the medical environment