New echocardiographic techniques in the evaluation of left ventricular function in obesity

Objective:

Obesity has reached global epidemic proportions and is associated with numerous comorbidities, including major cardiovascular (CV) diseases.

Design and Methods:

It has many adverse effects on hemodynamics and CV structure and function: it increases total blood volume and cardiac output, and the cardiac workload is greater. Typically, obese patients have a higher cardiac output but a lower level of total peripheral resistance at any given level of arterial pressure. Most of the increase in cardiac output in obesity is caused by stroke volume, although heart rate typically mildly increases also due to enhanced sympathetic activation.

Results:

Over the last few years, experimental investigations have unraveled some important pathogenetic mechanisms that may underlie a specific form of “obesity cardiomyopathy.” Bariatric surgery represents an effective alternative to treat obesity when nonsurgical weight loss programs (diet + behavior modifications + regular exercise) have failed. A great numbers of questions are still open in the global comprehension of the pathophysiological interactions between obesity and heart.

Conclusion:

Conventional two‐dimensional Doppler echocardiography, integrated by relative new technological ultrasonic approaches, represents the reference technique to study and possibly clarify both the very complex hemodynamic changes induced by obesity and those relative to obesity treatment.     

Impact of participant and interventionist race concordance on weight loss outcomes

Objective:

We have previously shown that racial composition of behavioral intervention groups does not affect achieved weight loss. However, it is unclear if the race of the interventionist affects intervention outcomes. The objective of this analysis is to estimate the impact of race concordance between participant and interventionist on weight change in the initial weight loss phase (phase I) of the Weight Loss Maintenance trial (WLM).

Design and Methods:

A total of 1,685 overweight or obese adults (BMI 25‐45 kg/m²) who were taking medication for hypertension and/or dyslipidemia participated in phase I of the WLM trial. All participants received a 6‐month intensive behavioral intervention in groups of 15‐20 facilitated by a trained interventionist. The main outcome is change in weight at 6 months.

Results:

Participants were on average 55 years of age, 67% female and 44% African American (AA). Three of seventeen interventionists were AA, 14 were non‐AA. Seventy‐three percent of participants shared race concordance with the interventionist. There was a small but statistically significant difference in weight change of participants who were the same race as the interventionist (?5.84 kg, s.e. 0.17) as compared with those who were not race concordant (?5.04 kg, s.e. 0.33), a difference of 0.8 kg, (P = 0.04). The impact of concordance on weight change differed by race (i.e., interaction of race and concordance was significant, P = 0.02).

Conclusions:

In a post hoc analysis of a group‐based behavioral intervention, race concordance for non‐AA participants was associated with slightly greater weight loss. Race concordance was not associated with weight loss for AA participants.

     

Extracellular Sphingosine-1-Phosphate: A Novel Actor in Human Glioblastoma Stem Cell Survival

Glioblastomas are the most frequent and aggressive intracranial neoplasms in humans, and despite advances and the introduction of the alkylating agent temozolomide in therapy have improved patient survival, resistance mechanisms limit benefits. Recent studies support that glioblastoma stem-like cells (GSCs), a cell subpopulation within the tumour, are involved in the aberrant expansion and therapy resistance properties of glioblastomas, through still unclear mechanisms. Emerging evidence suggests that sphingosine-1-phosphate (S1P) a potent onco-promoter able to act as extracellular signal, favours malignant and chemoresistance properties in GSCs. Notwithstanding, the origin of S1P in the GSC environment remains unknown. We investigated S1P metabolism, release, and role in cell survival properties of GSCs isolated from either U87-MG cell line or a primary culture of human glioblastoma. We show that both GSC models, grown as neurospheres and expressing GSC markers, are resistant to temozolomide, despite not expressing the DNA repair protein MGMT, a major contributor to temozolomide-resistance. Pulse experiments with labelled sphingosine revealed that both GSC types are able to rapidly phosphorylate the long-chain base, and that the newly produced S1P is efficiently degraded. Of relevance, we found that S1P was present in GSC extracellular medium, its level being significantly higher than in U87-MG cells, and that the extracellular/intracellular ratio of S1P was about ten-fold higher in GSCs. The activity of sphingosine kinases was undetectable in GSC media, suggesting that mechanisms of S1P transport to the extracellular environment are constitutive in GSCs. In addition we found that an inhibitor of S1P biosynthesis made GSCs sensitive to temozolomide (TMZ), and that exogenous S1P reverted this effect, thus involving extracellular S1P as a GSC survival signal in TMZ resistance. Altogether our data implicate for the first time GSCs as a pivotal source of extracellular S1P, which might act as an autocrine/paracrine signal contributing to their malignant properties.     

Cytokine Profiling in Immigrants with Clinical Malaria after Extended Periods of Interrupted Exposure to Plasmodium falciparum

Immunity to malaria is believed to wane with time in the absence of exposure to Plasmodium falciparum infection, but immunoepidemiological data on longevity of immunity remain controversial. We quantified serum cytokines and chemokines by suspension array technology as potential biomarkers for durability of immunity in immigrants with clinical malaria after years without parasite exposure. These were compared to serum/plasma profiles in naïve adults (travelers) and semi-immune adults under continuous exposure, with malaria, along with immigrant and traveler patients without malaria. Immigrants had higher levels of IL-2, IL-5 and IL-8 compared to semi-immune adults with malaria (P≤0.0200). Time since immigration correlated with increased IL-2 (rho=0.2738P=0.0495) and IFN-γ (rho=0.3044P=0.0282). However, immigrants did not show as high IFN-γ concentrations as travelers during a first malaria episode (P<0.0001). Immigrants and travelers with malaria had higher levels of IFN-γ, IL-6, and IL-10 (P<0.0100) than patients with other diseases, and IL-8 and IL-1β were elevated in immigrants with malaria (P<0.0500). Therefore, malaria patients had a characteristic strong pro-inflammatory/Th1 signature. Upon loss of exposure, control of pro-inflammatory responses and tolerance to P. falciparum appeared to be reduced. Understanding the mechanisms to maintain non-pathogenic effector responses is important to develop new malaria control strategies.     

Morphological study for understanding the sexual pattern in ghost shrimp Callichirus major (Crustacea: Axiidea)

Callichirus major is a species of ghost shrimp that has burrowing habits, building underground galleries in the intertidal region of beaches. This study aimed to analyse some morphological parameters to verify its type of sexual pattern. A sample of 79 individuals, collected at the beach of Corujão, Espírito Santo, Brazil, was used. Data on the external morphology, presence of gonopores, carapace length (CL) and cheliped lengths (Lch) were obtained. In addition, the gonads were processed for histological analysis. The animals were divided into three categories: A, individuals with male characteristics; B, those presenting exclusively female characteristics; C, animals with characteristics of intersex, which presented supernumerary gonopores. Positive allometries were found for Lch versus CL only for category A, characterizing the group's marked heterochely. Histologically, it was possible to observe the presence of oocytes in category A and one case of male tissue in an intersex individual (category C). However, no genital ducts of both sexes were found in that individual. Callichirus major presents controversial sexual characters, which makes it difficult to understand the reproductive parameters and sexual pattern. However, maybe that species can develop a sexual system of hermaphroditism.     

Anatomy and histology of the gastrointestinal tract of the neo-tropical opossum (Didelphis marsupialis insularis,Allen 1902)

The morphology of the gastrointestinal tract (GI) is a strong indicator of the dietary habits of a species. The goal of this study was to describe the gross and microanatomy of the digestive tract of the neo-tropical opossum (Didelphis marsupialis insularis) and relate them to the animals’ food habits. GI tracts from 12 adult animals were used for this study. Results found the small intestine made up 65.9% of the GI tract, and the stomach was simple with a prominent caecum. Histologically, the oesophageal mucosa was non-keratinized and glands were found throughout the oesophagus. The large intestine showed a great number of goblet cells, the jejunum possessed well-developed villi, and Peyer's patches were absent in the ileum. The absence of keratinization of the epithelial lining of the oesophagus and stomach and a high lymphocytic infiltration throughout the small and large intestine reflected a more carnivorous diet, whereas the presence of a well-developed caecum in the large intestine indicated the ability to digest plant matter. Overall, the morphology of GI tract of D. m. insularis displayed both carnivorous and herbivorous features, allowing us to conclude that it is an omnivorous animal.