Absence of Malaria-Associated Coagulopathy in Asymptomatic Plasmodium falciparum Infection: Results From a Cross-sectional Study in the Ashanti Region, Ghana.

Background: Coagulopathy is common in acute symptomatic Plasmodium falciparum malaria, and the degree of coagulation abnormality correlates with parasitemia and disease severity. Chronic asymptomatic malaria has been associated with increased morbidity. However, the role of coagulation activation in asymptomatic, semi-immune individuals remains unclear. This study investigates the potential effect of asymptomatic P falciparum infection on coagulation activation in semi-immune Ghanaian adults. Methods: Blood from asymptomatic Ghanaian adults with P falciparum blood stage infection detectable by polymerase chain reaction (PCR) or by both PCR and rapid diagnostic test and from noninfected individuals, was investigated. Markers of coagulation activation including global coagulation tests, D-dimer, antithrombin III, fibrinogen, and von Willebrand factor antigen were tested. Furthermore, blood count, inflammation markers, and liver and kidney function tests were assessed. Results: Acquired coagulopathy was not found in asymptomatic P falciparum infection. Asymptomatic malaria was associated with significantly lower platelet counts. Systemic inflammation markers and liver and kidney function tests were not altered compared to noninfected controls. Conclusions: There is no laboratory evidence for acquired coagulopathy in adults with asymptomatic P falciparum malaria in highly endemic regions. Lack of laboratory evidence for systemic inflammation and liver and kidney dysfunction indicates that asymptomatic malaria may not be associated with significant morbidity.

Insulin sensitivity in mesolimbic pathways predicts and improves with weight loss in older dieters.

Central insulin is critically involved in the regulation of hedonic feeding. Insulin resistance in overweight has recently been shown to reduce the inhibitory function of insulin in the human brain. How this relates to effective weight management is unclear, especially in older people, who are highly vulnerable to hyperinsulinemia and in whom neural target systems of insulin action undergo age-related changes. Here, 50 overweight, non-diabetic older adults participated in a double-blind, placebo-controlled, pharmacological functional magnetic resonance imaging study before and after randomization to a 3-month caloric restriction or active waiting group. Our data show that treatment outcome in dieters can be predicted by baseline measures of individual intranasal insulin (INI) inhibition of value signals in the ventral tegmental area related to sweet food liking as well as, independently, by peripheral insulin sensitivity. At follow-up, both INI inhibition of hedonic value signals in the nucleus accumbens and peripheral insulin sensitivity improved with weight loss. These data highlight the critical role of central insulin function in mesolimbic systems for weight management in humans and directly demonstrate that neural insulin function can be improved by weight loss even in older age, which may be essential for preventing metabolic disorders in later life.

Evaluation of the AFIAS-1 thyroid-stimulating hormone point of care test and comparison with laboratory-based devices.

OBJECTIVES: Thyroid-stimulating hormone (TSH) is the routine primary screening test to assess thyroid function and rapid measurement of TSH levels is highly desirable especially in emergency situations. In the present study, we compared the analytical performance of a commercially available point-of-care test (AFIAS-1) and five laboratory-based systems. METHODS: Left over material of 60 patient plasma samples was collected from patient care and used in the respective assay. For statistical analysis of the produced data Bland-Altman and Passing-Bablok regression analysis were applied. RESULTS: Good correlation (r=0.982 or higher) was found between all devices. Slopes from regression analysis ranged from 0.972 (95% CI: 0.927-1.013) to 1.276 (95% CI: 1.210-1.315). Among the compared devices, imprecision was high in terms of coefficient of variation (CV=10.3%) for low TSH concentrations and lower (CV=7.3%) for high TSH concentrations. Independent of the method used, we demonstrated a poor standardization of TSH assays, which might impact clinical diagnosis e.g. of hyperthyreosis. CONCLUSIONS: This study shows that the point-of-care (POC) test AFIAS-1 can serve as an alternative to laboratory-based assays. In addition the data imply that better standardization of TSH measurements is needed.

Mesolimbic white matter connectivity mediates the preference for sweet food.

Dopaminergic brain structures like the nucleus accumbens (NAc) are thought to encode the incentive salience of palatable foods motivating appetitive behaviour. Animal studies have identified neural networks mediating the regulation of hedonic feeding that comprise connections of the NAc with the ventral tegmental area (VTA) and the lateral hypothalamus (LH). Here, we investigated how structural connectivity of these pathways relates to individual variability in decisions on sweet food consumption in humans. We therefore combined probabilistic tractography on diffusion imaging data from 45 overnight fasted lean to overweight participants with real decisions about high and low sugar food consumption. Across all individuals, sugar preference and connectivity strength were not directly related, however, multiple regression analysis revealed interaction of mesolimbic structure and sugar preference to depend on individuals' BMI score. In overweight individuals (BMI: ≥25 kg/m², N = 22) higher sugar preference was thereby specifically related to stronger connectivity within the VTA-NAc pathway while the opposite pattern emerged in participants with normal BMI (BMI: <25 kg/m², N = 23). Our structural results complement previous functional findings on the critical role of the human mesolimbic system for regulating hedonic eating in overweight individuals.

Central insulin modulates food valuation via mesolimbic pathways.

Central insulin is thought to act at the neural interface between metabolic and hedonic drives to eat. Here, using pharmacological fMRI, we show that intranasal insulin (INI) changes the value of food cues through modulation of mesolimbic pathways. Overnight fasted participants rated the palatability of food pictures and attractiveness of non-food items (control) after receiving INI or placebo. We report that INI reduces ratings of food palatability and value signals in mesolimbic regions in individuals with normal insulin sensitivity. Connectivity analyses reveal insulinergic inhibition of forward projections from the ventral tegmentum to the nucleus accumbens. Importantly, the strength of this modulation predicts decrease of palatability ratings, directly linking neural findings to behaviour. In insulin-resistant participants however, we observe reduced food values and aberrant central insulin action. These data demonstrate how central insulin modulates the cross-talk between homeostatic and non-homeostatic feeding systems, suggesting that dysfunctions of these neural interactions may promote metabolic disorders.