Dairy beverages and energy balance

High dairy intakes have been associated with lower rates of obesity in observational studies, but mechanisms to explain the association are lacking. A high intake of dairy protein reduces spontaneous food intake and may be one important mechanism, but more specific effects of dairy calcium seem to exist.We have found that high versus low calcium intakes from dairy products had no effect on 24-h energy expenditure or substrate oxidation rates, but fecal fat excretion increased ∼ 2.5-fold on the high-calcium diets. In a meta-analysis of intervention studies we found that increasing dairy calcium intake by 1200 mg/day resulted in increased fecal fat excretion by 5.2 (1.6-8.8) g/day.Newer research shows that humans possess taste receptors for calcium in the gastrointestinal tract and that signaling may be linked to appetite regulation. A new line of evidence suggests that an inadequate calcium intake during an energy restricted weight loss program may trigger hunger and impair compliance to the diet.These mechanisms may be part of the explanation for the protective effects of dairy products with regard to obesity and metabolic syndrome.     

Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity

Plasmodium falciparum is the major cause of malaria globally and is transmitted by mosquitoes. During parasitic development, P. falciparum-infected erythrocytes (P. falciparum-IEs) express multiple polymorphic proteins known as variant surface antigens (VSAs), including the P. falciparum erythrocyte membrane protein 1 (PfEMP1). VSA-specific antibodies are associated with protection from symptomatic and severe malaria. However, the importance of the different VSA targets of immunity to malaria remains unclear, which has impeded an understanding of malaria immunity and vaccine development. In this study, we developed assays using transgenic P. falciparum with modified PfEMP1 expression to quantify serum antibodies to VSAs among individuals exposed to malaria. We found that the majority of the human antibody response to the IE targets PfEMP1. Furthermore, our longitudinal studies showed that individuals with PfEMP1-specific antibodies had a significantly reduced risk of developing symptomatic malaria, whereas antibodies to other surface antigens were not associated with protective immunity. Using assays that measure antibody-mediated phagocytosis of IEs, an important mechanism in parasite clearance, we identified PfEMP1 as the major target of these functional antibodies. Taken together, these data demonstrate that PfEMP1 is a key target of humoral immunity. These findings advance our understanding of the targets and mediators of human immunity to malaria and have major implications for malaria vaccine development.     

Human Parainfluenza Virus Infection after Hematopoietic Stem Cell Transplantation: Risk Factors,Management, Mortality,and Changes over Time

Human parainfluenza viruses (HPIVs) are uncommon, yet high-risk pathogens after hematopoietic stem cell transplant (HCT). We evaluated 5178 pediatric and adult patients undergoing HCT between 1974 and 2010 to determine the incidence, risk factors, response to treatment, and outcome of HPIV infection as well as any change in frequency or character of HPIV infection over time. HPIV was identified in 173 patients (3.3%); type 3 was most common (66%). HPIV involved upper respiratory tract infection (URTI; 57%), lower respiratory tract infection (LRTI; 9%), and both areas of the respiratory tract (34%), at a median of 62 days after transplantation. In more recent years, HPIV has occurred later after HCT, whereas the proportion with nosocomial infection and mortality decreased. Over the last decade, HPIV was more common in older patients and in those receiving reduced intensity conditioning (RIC). RIC was a significant risk factor for later (beyond day +30). HPIV infections, and this association was strongest in patients with URTI. HCT using a matched unrelated donor (MURD), mismatched related donor (MMRD), age 10 to 19 years, and graft-versus-host disease (GVHD) were all risk factors for HPIV infections. LRTI, early (<30 days), age 10 to 19 years, MMRD, steroid use, and coinfection with other pathogens were risk factors for mortality. The survival of patients with LRTI, especially very early infections, was poor regardless of ribavirin treatment. HPIV incidence remains low, but may have delayed onset associated with RIC regimens and improving survival. Effective prophylaxis and treatment for HPIV are needed.     

Exploring the DNA mixture deconvolution through simulation

ABSTRACT

If an unambiguous single-source DNA profile is obtained from a crime scene, then a potential person of interest can either match or not match the crime scene profile and the likelihood ratio for the single matching genotype can be easily computed. Mixed DNA profiles on the other hand are typically ambiguous and a vast number of different likelihood ratios can be obtained depending on the genotype of a potential person of interest that is compared with the mixture later. In the absence of a person of interest it can be unclear how suitable the profile is for discriminating between donors and non-donors. We introduce a simulation method to explore the range of likelihood ratios that is expected to be obtained when a non-donor or a true donor is compared with the mixed DNA profile. Sampling is conditional on the mixture deconvolution obtained using probabilistic genotyping. These simulations help to decide whether or not a (mixed) profile is suitable for comparison to a person of interest. Moreover, the methods can be used to determine whether a profile is suitable for upload to a database and whether or not potential rework could be advised.