Management of Mild-to-Moderate Hypertriglyceridemia

ObjectiveHypertriglyceridemia (HTG) is highly prevalent globally, and its prevalence is rising, with a worldwide increase in the incidence of obesity and diabetes. This review examines its current management and future therapies.MethodsFor this review, HTG is defined as mild-to-moderate elevation in the levels of triglyceride (TG): a fasting or nonfasting TG level of ≥150 mg/dL and <500 mg/dL. We reviewed scientific studies published over the last 30 years and current professional society recommendations regarding the evaluation and treatment of HTG.ResultsGenetics, lifestyle, and other environmental factors impact TG levels. In adults with mild-to-moderate HTG, clinicians should routinely assess and treat secondary treatable causes (diet, physical activity, obesity, metabolic syndrome, and reduction or cessation of medications that elevate TG levels). Because atherosclerotic cardiovascular disease risk is the primary clinical concern, statins are usually the first-line treatment. Patients with TG levels between ≥150 mg/dL and <500 mg/dL whose low-density lipoprotein cholesterol is treated adequately with statins (at “maximally tolerated“ doses, per some statements) and have either prior cardiovascular disease or diabetes mellitus along with at least 2 additional cardiovascular disease risk factors should be considered for added icosapent ethyl treatment to further reduce their cardiovascular disease risk. Fibrates, niacin, and other approved agents or agents under development are also reviewed in detail.ConclusionThe treatment paradigm for mild-to-moderate HTG is changing on the basis of data from recent clinical trials. Recent trials suggest that the addition of icosapent ethyl to background statin therapy may further reduce atherosclerotic cardiovascular disease risk in patients with moderate HTG, although a particular TG goal has not been identified.     

New Digital Health Technologies for Insulin Initiation and Optimization for People With Type 2 Diabetes

ObjectiveThe health and economic burden of type 2 diabetes is of global significance. Many people with type 2 diabetes eventually need insulin to help reduce their risk of serious associated complications. However, barriers to the initiation and/or optimization of insulin expose people with diabetes to sustained hyperglycemia. In this review, we investigated how new and future technologies may provide opportunities to help overcome these barriers to the initiation and/or optimization of insulin.MethodsA focused literature search of PubMed and key scientific congresses was conducted. Software tools and devices developed to support the initiation and/or optimization of insulin were identified by manually filtering >300 publications and conference abstracts.ResultsMost software tools have been developed for smartphone platforms. At present, published data suggest that the use of these technologies is associated with equivalent or improved glycemic outcomes compared with standard care, with additional benefits such as reduced time burden and improved knowledge of diabetes among health care providers. However, there remains paucity of good-quality evidence. Most new devices to support insulin therapy help track the dose and timing of insulin.ConclusionNew digital health tools may help to reduce barriers to optimal insulin therapy. An integrated solution that connects glucose monitoring, dose recording, and titration advice as well as records comorbidities and lifestyle factors has the potential to reduce the complexity and burden of treatment and may improve adherence to titration and treatment, resulting in better outcomes for people with diabetes.     

Genetic variability in Plantago species in relation to their ecology

Summary Twelve Plantago major plants, good representatives of their populations, appeared to be genetically different for several characters which are important for adaptation to the respective habitat conditions. These characters are: juvenile growth, leaf morphology, production of secondary rosettes, flowering time, seed production, seed size and adult leaf production. The adaptive value of some of these characters was investigated by transplantation experiments in the field and by intraspecific competition experiments. The roadside type of ssp. major was adapted to trampling by being erect and elastic. The lawn type of ssp. major was adapted to a short, frequently cut, vegetation by being prostrate and by producing leaves with short petioles throughout the growth season. In the natural situations in which ssp. pleiosperma occurs, growth rate and first-year seed production of this subspecies were considerably higher than that of ssp. major. In a number of experiments, F₁s and F₂s were included, derived from crosses between the original plants. The F₁s were generally rather well adapted to both parental habitats, whereas the F₂s appeared to be less fit. The various alternatives in spending resources relevant for fitness optimization in different habitats are discussed.Grassland Species Research Group Publication No. 93     

Evolutionary game theory meets social science: Is there a unifying rule for human cooperation?

Evolutionary game theory has shown that human cooperation thrives in different types of social interactions with a PD structure. Models treat the cooperative strategies within the different frameworks as discrete entities and sometimes even as contenders. Whereas strong reciprocity was acclaimed as superior to classic reciprocity for its ability to defeat defectors in public goods games, recent experiments and simulations show that costly punishment fails to promote cooperation in the IR and DR games, where classic reciprocity succeeds. My aim is to show that cooperative strategies across frameworks are capable of a unified treatment, for they are governed by a common underlying rule or norm. An analysis of the reputation and action rules that govern some representative cooperative strategies both in models and in economic experiments confirms that the different frameworks share a conditional action rule and several reputation rules. The common conditional rule contains an option between costly punishment and withholding benefits that provides alternative enforcement methods against defectors. Depending on the framework, individuals can switch to the appropriate strategy and method of enforcement. The stability of human cooperation looks more promising if one mechanism controls successful strategies across frameworks.     

Reducing saturated fat intake lowers LDL-C but increases Lp(a) levels in African Americans: the GET-READI feeding trial

Reducing dietary saturated fatty acids (SFA) intake results in a clinically significant lowering of low-density lipoprotein cholesterol (LDL-C) across ethnicities. In contrast, dietary SFA’s role in modulating emerging cardiovascular risk factors in different ethnicities remains poorly understood. Elevated levels of lipoprotein(a) [Lp(a)], an independent cardiovascular risk factor, disproportionally affect individuals of African descent. Here, we assessed the responses in Lp(a) levels to dietary SFA reduction in 166 African Americans enrolled in GET-READI (The Gene-Environment Trial on Response in African Americans to Dietary Intervention), a randomized controlled feeding trial. Participants were fed two diets in random order for 5 weeks each: 1) an average American diet (AAD) (37% total fat: 16% SFA), and 2) a diet similar to the Dietary Approaches to Stop Hypertension (DASH) diet (25% total fat: 6% SFA). The participants’ mean age was 35 years, 70% were women, the mean BMI was 28 kg/m², and the mean LDL-C was 116 mg/dl. Compared to the AAD diet, LDL-C was reduced by the DASH-type diet (mean change: −12 mg/dl) as were total cholesterol (−16 mg/dl), HDL-C (−5 mg/dl), apoA-1 (−9 mg/dl) and apoB-100 (−5 mg/dl) (all P < 0.0001). In contrast, Lp(a) levels increased following the DASH-type diet compared with AAD (median: 58 vs. 44 mg/dl, P < 0.0001). In conclusion, in a large cohort of African Americans, reductions in SFA intake significantly increased Lp(a) levels while reducing LDL-C. Future studies are warranted to elucidate the mechanism(s) underlying the SFA reduction-induced increase in Lp(a) levels and its role in cardiovascular risk across populations.     

Evolution of mixed maturation strategies in semelparous life histories: the crucial role of dimensionality of feedback environment

We study the evolution of age at maturity in a semelparous life history with two age classes. An individual may either breed in the first year of its life and die, or delay breeding to the second year. In this setting a mixed strategy means that a fraction of the individual''s offspring breed in the first possible breeding event, while the remaining fraction delay breeding. Current theory seems to imply that mixed strategies are not evolutionarily stable strategies (ESSs) under a steady-state population dynamical regime. We show that a two-dimensional feedback environment may allow the evolution of mixed age at maturity. Furthermore, different phenotypes need to perceive the environment differently. The biological reasoning behind these conditions is different resource usage or predation pressure between two age classes. Thus, the conventional explanations for the occurrence of mixed strategies in natural populations, environmental stochasticity or complex dynamics, are not needed. <br>     

Aggressive interventions and matrilineal dominance relations in semifree-ranging barbary macaques (Macaca sylvanus)

Female Barbary macaques (Macaca sylvanus) form matrilineal hierarchies, i.e. they come to rank below their mother in relation to non-kin females in the course of maturation. The stability of such hierarchies and the acquisition of the matrilineal rank are achieved through dyadic aggressions and third party interventions in conflicts. This study examines the dynamics of interventions in non-kin conflicts in a semifree-ranging group of 109 Barbary macaques at “La Montagne des Singes,” Kintzheim, France. Focal sampling on 13 females aged 3 and 4 years not yet dominant over all older females from lower ranking kin groups (lower born females) was carried out during 16 months in 1987 and 1988. Results on the direction of support in non-kin female conflicts (all samples pooled) show that interventions were generally provided on behalf of the female from the higher ranking kin group (higher born female). Rates of interventions (derived from focal samples) given and received were correlated with the hierarchy; higher born females received more support and intervened more often than lower born females. A subset of interventions (based on the age of the females involved) was analyzed according to the rank distance between the opponents and the type of support provided (spontaneous or solicited). On the basis of their representation, intermediate-ranking supporters (i.e. females ranking between the opponents) intervened more often than above-ranking supporters (i.e. females dominant to both opponents), and they intervened more often spontaneously than following a solicitation. The results on interventions are discussed in the perspective of benefits to supporters. Twenty-one instances of outranking of older females (matrilineal rank acquisition) were observed. By the end of the study, the number of older lower born females not yet outranked by the focal females was negatively correlated to the rank distance between the two sets of females. However no such correlation was found between these two groups when compared according to their age difference in years.     

Hierarchical analysis of the relationship between spatial distribution and abundance of epiphytic lichens (Mt. Olympos-Greece)

The relationship between distribution and abundance of epiphytic lichens on five different substrates (Fagus sylvatica, Pinus nigra, Quercus coccifera, Pinus heldreichii and Quercus pubescens) has been studied. For the first three substrates the above relationship has been studied hierarchically. It was concluded that this relationship is partly represented by the core-satellite distribution. This abundance-distribution pattern could probably be explained by more than one hypothesis and it is probably related with the life strategies of lichen species.     

Selective depletion of basophils ameliorates immunoglobulin E-mediated anaphylaxis

Basophils, which are the rarest granulocytes, play crucial roles in protective immunity against parasites and development of allergic disorders. Although immunoglobulin (Ig)E-dependent responses via receptor for IgE (FcεRI) in basophils have been extensively studied, little is known about cell surface molecules that are selectively expressed on this cell subset to utilize the elimination in vivo through treatment with monoclonal antibody (mAb). Since CD200 receptor 3 (CD200R3) was exclusively expressed on basophils and mast cells (MCs) using a microarray screening, we have generated anti-CD200R3 mAb recognizing CD200R3A. In this study we examined the expression pattern of CD200R3A on leukocytes, and the influence of the elimination of basophils by anti-CD200R3A mAb on allergic responses. Flow cytometric analysis showed that CD200R3A was primarily expressed on basophils and MCs, but not on other leukocytes. Administration with anti-CD200R3A mAb led to the prominent specific depletion of tissue-resident and circulating basophils, but not MCs. Furthermore, in vivo depletion of basophils ameliorated IgE-mediated systemic and local anaphylaxis. Taken together, these findings suggest that CD200R3A is reliable cell surface marker for basophils in vivo, and targeting this unique molecule with mAb for the elimination of basophils may serve as a novel therapeutic strategy in ameliorating the allergic diseases.