Exosomes and immune response in cancer: Friends or foes?

Exosomes are a type of extracellular vesicle whose study has grown exponentially in recent years. This led to the understanding that these structures, far from being inert waste by-products of cellular functioning, are active players in intercellular communication mechanisms, including in the interactions between cancer cells and the immune system. The deep comprehension of the crosstalk between tumors and the immune systems of their hosts has gained more and more importance, as immunotherapeutic techniques have emerged as viable options for several types of cancer. In this review, we present a comprehensive, updated, and elucidative review of the current knowledge on the functions played by the exosomes in this crosstalk. The roles of these vesicles in tumor antigen presentation, immune activation, and immunosuppression are approached as the relevant interactions between exosomes and the complement system. The last section of this review is reserved for the exploration of the results from the first phase I to II clinical trials of exosomes-based cell-free cancer vaccines.The laboratory is supported by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by FCT— Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Inovacao in the framework of the projects “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274), (PTDC/BIM-ONC/2754/2014), and (PTDC/BIM-MEC/2834/2014); and by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), in the framework of the project NORTE- 01-0145-FEDER-000029. SM is supported by FCT (IF/00543/2013)

Maternal Diabetes Mellitus as a Risk Factor for High Blood Pressure in Late Childhood

Intrauterine fetal conditions can have lifelong cardiovascular effects. The impact of maternal diabetes mellitus on children’s cardiovascular profile is not well established. The goal of this study was to explore the association between maternal diabetes mellitus and offspring’s blood pressure (BP) ≤10 years of age. Generation XXI is a prospective birth cohort, which enrolled 8301 mother-offspring pairs, including 586 (7.1%) children of diabetic mothers. The associations between maternal diabetes mellitus and BP at 4, 7, and 10 years of age was modeled using linear regression. A mixed-effects model was built to assess differences in BP variation over time. Path analysis was used to quantify effects of potential mediators. Maternal diabetes mellitus was associated with higher BP in offspring at the age of 10 (systolic: β, 1.48; 95% CI, 0.36–2.59; and diastolic: β, 0.86; 95% CI, 0.05–1.71). This association was independent of maternal perinatal characteristics, and it was mediated by child’s body mass index and, to a lesser extent, by gestational age, type of birth, and birth weight (indirect effect proportion, 73%). No significant differences in BP were found at 4 and 7 years of age. Longitudinal analysis showed an accelerated systolic BP increase on maternal diabetes mellitus group (β, 1.16; 95% CI, 0.03–2.28). These finding were especially relevant in males, suggesting sex differences in the mechanisms of BP prenatal programing. Our results provide further evidence that maternal diabetes mellitus is associated with high BP late in childhood, demonstrating a significant role of child’s body mass in the pathway of this association.This work was supported by Programa Operacional de Saúde–Saúde XXI, Quadro Comunitário de Apoio III, and Administração Regional de Saúde Norte (Regional Department of Ministry of Health); FEDER (European Regional Development Fund) through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology–FCT (Portuguese Ministry of Science, Technology and Higher Education) through Unidade de Investigação em Epidemiologia–Instituto de Saúde Pública da Universidade do Porto (EPI Unit; POCI-01-0145-FEDER-006862; Ref UID/DTP/04750/2013); Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund-DOCnet (NORTE-01-0145-FEDER-000003); and from the Calouste Gulbenkian Foundation

Physicochemical and microbiological characteristics of Italian salami made of lamb and enriched with pequi (Caryocar brasiliense, Cambess)

The purpose of this study was to evaluate and compare the inclusion of different levels of pequi (Caryocar Brasiliense, Cambess) pulp in the processing of Italian salami made of lamb for the evaluation of their physicochemical and microbiological characteristics. Six formulations of Italian salamis were processed: no pequi pulp (control - treatment 1); 4% pequi pulp (treatment 2); 8% pequi pulp (treatment 3), 12% pequi pulp (Treatment 4), 16% pequi pulp (treatment 5) and 20% pequi pulp (treatment 6). During the maturation period, all Italian salamis made of lamb enriched with pequi presented similar behaviors; and acidity (pH) and water activity (aw) results showed stable end values. For protein, the Italian salami made of lamb without pequi pump presented a higher content. For one of the lowest contents of fat, treatment 3 showed the highest content of humidity. The contents of fat and ashes did not present any significant difference when comparing the Italian salami formulations. A color tending to dark, yellowish and reddish shades was observed in the Italian salamis made of lamb and enriched with pequi. All Italian salamis were microbiologically satisfactory, showing ideal sanitary conditions for consumption. Pequi is a typical fruit from the Brazilian cerrado region, with characteristic color, odor and flavor, and it is an option for inclusion in Italian salamis, but additional studies should be conducted to inspect the sensory acceptability of these products.Keywords: Cerrado fruit, fermented stuffed meat sausages, physicochemical parameters, microbiological parameters

Hydrocephalus in children less than 1 year of age in northern Mozambique

Background:In developed countries, the incidence of neonatal hydrocephalus ranges from 3 to 5 cases per 1000 live births, but little is known about the frequency of hydrocephalus in Africa. In Mozambique, there is no primary information related to this disorder, but using the above data, the expected incidence of neonatal hydrocephalus would range from 2900 to 4800 cases per year. Methods:This study is based on 122 children younger than 1 year with neonatal hydrocephalus, followed up between January 2010 and December 2012, their origin and treatment, and aims to evaluate difficulties with diagnosis, treatment, and follow-up in northern Mozambique. Results:Identified cases were mainly less than 6 months old (77%), with severe macrocephaly and the classic stigmata of this condition. A high rate of follow-up loss (44.3%) was detected, particularly among children from more distant locations. Our findings contrast with the expected 1000-1700 cases that would occur in the area during the study period, being considerably lower. Conclusions:Hydrocephalus is a serious problem in sub-Saharan Africa, whose effects can be minimized by a better organization of the health system in hydrocephalus prevention, referral, and follow-up. New management alternatives to provide treatment to more children with this disorder and reduction of the follow-up difficulties caused due to geographical reasons for the children undergoing treatment are essential

Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children

Background: We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (H2O2) play a role in the putative association. Methods: Cross-sectional evaluation of 305 children aged 8–9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and H2O2 by a microplate fluorometric assay. Results: U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary H2O2 decreased with P-AGT. Conclusions: A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin–angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary H2O2 and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.This project was supported by funds from Fundo Europeu de Desenvolvimento Regional (FEDER) from Programa Operacional Factores de Competitividade – COMPETE (FCOMP-01-0124-FEDER-028751), by national funds from the Portuguese Foundation for Science and Technology (FCT) (PTDC/DTP-PIC/0239/2012) and by Calouste Gulbenkian Foundation, that granted the study design and data collection and analysis. Liane Correia-Costa was supported by FCT (grant SFRH/SINTD/95898/2013), Teresa Sousa was supported by FCT and POPH/FSE (EC) (Ciência 2008 and SFRH/BPD/112005) and Franz Schaefer was supported by the ERA-EDTA Research Programme and the KfH Foundation for Preventive Medicine. The Epidemiology Research Unit (EPIUnit) is funded by FCT (UID/DTP/04750/2013)

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P < 0.001), age, bisphosphonate use, and rodding (P < 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie