Analysis of the role of the PAC1 receptor in neutrophil recruitment, acute-phase response, and nitric oxide production in septic shock

Infections caused by Gram-negative bacteria constitute one of the major causes of septic shock, which results from the inability of the immune system to limit bacterial spread during the ongoing infection. In the last decade, it has been demonstrated that vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two endogenous immunopeptides, which together with three G protein-coupled receptors (VPAC1, VPAC2, and PAC1) exert a significant, therapeutic effect attenuating the deleterious consequences of septic shock by balancing pro- and anti-inflammatory factors. We have recently shown PAC1 receptor involvement in vivo as an anti-inflammatory receptor, at least in part, by attenuating lipopolysaccharide-induced production of proinflammatory interleukin-6. The present study deepens in the protective role of PAC1 receptor in septic shock, elucidating its involvement in the modulation of neutrophil recruitment and in the expression of different molecular sensors such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, fibrinogen, serum amyloid A, and nitric oxide as important, systemic players of the development of septic shock. Our results, using a mice deficient in PAC1 and a PAC1 antagonist, show that VIP and PACAP as well as the PAC1 receptor are involved in neutrophil recruitment in different target organs, in adhesion molecules expression, and in coagulation-related molecule fibrinogen synthesis. Thus, this study provides some important insights with respect to the involvement of PAC1 into the complexities of sepsis and represents an advantage for the design of more specific drugs complementing standard intensive care therapy in severe sepsis, confirming VIP and PACAP as candidates for multitarget therapy of septic shock.     

Description of Maritrema formicae sp. nov. (Digenea, Microphallidae) parasitic in the kelp gull, Larus dominicanus, from the Patagonian coast, Argentina

Maritrema formicae sp. nov. is described from the Patagonian coast, Argentina, based on adults obtained from the kelp gull, Larus dominicanus. The new species fits with the "eroliae complex" and can be distinguished from other related species mainly in shape and size of body, shape, size, and pattern of distribution of cirrus spines, uterus extension, number and size of eggs, vitellarium in a complete ring in all specimens, and its Neotropical distribution. The new species is sympatric with another species of the genus, Maritrema madrynense, which was recorded in the same host and locality.     

The impact of infection with human metapneumovirus and other respiratory viruses in young infants and children at high risk for severe pulmonary disease

We conducted a prospective, observational study to characterize the clinical manifestations of respiratory infections caused by human metapneumovirus (hMPV) and other viruses in 194 premature infants and young children with chronic lung disease or congenital heart disease in Buenos Aires. Children had 567 episodes of respiratory illness and were monitored until they were 2 years old or until the completion of the study. hMPV elicited 12 infections (2%) year-round; 30% were of moderate or greater severity. Human parainfluenza virus type 3 caused 24 infections (4%), and 5 (25%) of 20 lung infections led to hospitalization. Respiratory syncytial virus (RSV) caused 33 episodes--17% of infections and 32% of hospitalizations during the respiratory season. None of the 10 children infected with influenza virus had severe disease. The present study of at-risk children suggests that hMPV and influenza virus are infrequent agents of severe disease and highlights the need for preventive interventions against RSV in developing countries.     

A longitudinal twin study on IQ, executive functioning, and attention problems during childhood and early adolescence

Variation in human behavior may be caused by differences in genotype and by non-genetic differences ("environment") between individuals. The relative contributions of genotype (G) and environment (E) to phenotypic variation can be assessed with the classical twin design. We illustrate this approach with longitudinal data collected in 5 and 12-year-old Dutch twins. At age 5 data on cognitive abilities as assessed with a standard intelligence test (IQ), working memory, selective and sustained attention, and attention problems were collected in 237 twin pairs. Seven years later, 172 twin pairs participated again when they were 12 years old and underwent a similar protocol. Results showed that variation in all phenotypes was influenced by genetic factors. For IQ the heritability estimates increased from 30% at age 5, to 80% at age 12. For executive functioning performance genetic factors accounted for around 50% of the variance at both ages. Attention problems showed high heritabilities (above 60%) at both ages, for maternal and teacher ratings. Longitudinal analyses revealed that executive functioning during childhood was weakly correlated with IQ scores at age 12. Attention problems during childhood, as rated by the mother and the teacher were stronger predictors (r = -0.28 and -0.36, respectively). This association could be attributed to a partly overlapping set of genes influencing attention problems at age 5 and IQ at age 12. IQ performance at age 5 was the best predictor of IQ at age 12. IQ at both ages was influenced by the same genes, whose influence was amplified during development.     

The Effects of 12-Week Beta-Hydroxy-Beta-Methylbutyrate Supplementation in Patients with Liver Cirrhosis: Results from a Randomized Controlled Single-Blind Pilot Study

Background and Aim: Sarcopenia is considered an important risk factor for morbidity and mortality in liver cirrhosis. Beta-hydroxy-beta-methylbutyrate (HMB) has the potential to increase muscle mass and performance by stimulating protein synthesis and reducing muscle catabolism. The present study aimed at evaluating the effect of HMB supplementation on muscle mass and function in patients with liver cirrhosis. Changes in frailty during the study were also estimated, and the safety of HMB supplementation was verified. Methods: This is a randomized, single-blind, placebo-controlled pilot trial. Twenty-four patients (14 HMB and 10 placebo) affected by liver cirrhosis were enrolled in the study. Each patient received dedicated counseling, which included nutrition and physical activity recommendations for chronic liver disease patients. Patients were randomized to receive 3 g/day of HMB or placebo (sorbitol powder) for 12 consecutive weeks. A diet interview, anthropometry, electrical bioimpedance analysis (BIA), quadriceps ultrasound, physical performance battery, Liver Frailty Index (LFI), and cognitive tests were completed at enrolment (T0), at 12 weeks (T1), and 24 weeks after enrolment (T2). Results: At baseline, the two groups were similar in demography, severity of liver disease, muscle mass, muscle function, and cognitive tests. LFI at baseline was higher in patients in the HMB group vs. those in the placebo group (4.1 ± 0.4 vs. 3.4 ± 0.6, p < 0.01). After treatment, a statistically significant increase in muscle function was seen in the HMB group (chair stand test: 14.2 ± 5 s vs. 11.7 ± 2.6 s, p < 0.05; six-minute walk test: 361.8 ± 68 m vs. 409.4 ± 58 m, p < 0.05). Quadriceps muscle mass measured by ultrasound also increased (4.9 ± 1.8 vs. 5.4 ± 1.8 mm, p < 0.05) after HMB, while LFI decreased (4.1 ± 0.4 vs. 3.7 ± 0.4, p < 0.05). HMB was well tolerated by patients, and no adverse events were documented. Conclusions: Our study suggests the efficacy of 12-week beta-hydroxy-beta-methylbutyrate supplementation in promoting improvements in muscle performance in compensated cirrhotic patients. LFI was also ameliorated. Further studies with a greater number of patients are required to reinforce this hypothesis.