Pharmacotherapeutic strategies for critical asthma syndrome: a look at the state of the art

ABSTRACT

Introduction

‘Critical Asthma Syndrome’ (CAS) is an umbrella term proposed to include several forms of asthma, responsible for acute and life-threatening exacerbations. CAS requires urgent and adequate supportive and pharmacological treatments to prevent serious outcomes.     

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

Food-grade titanium dioxide decreases hematocrit and hemoglobin and increases compulsive-like behavior in male mice

Food-grade titanium dioxide (E171) is widely used as a food additive, and it is known that after oral consumption, E171 is translocated into the bloodstream reaching the highest titanium level at 6 h. E171 is accumulated in some organs triggering toxicity, but the effects on the blood parameters after oral consumption have been less studied. Recently, evidence shows that oral exposure to E171 induces behavioral signs of anxiety and depression. The relation between blood alterations and psychiatric disorders has been previously demonstrated. However, the oral exposure to E171 effects on alterations in blood parameters and effects linked to alterations in animal behavior has not been explored. In this short communication, we aimed to investigate the effects of E171 on specific blood parameters (hematocrit, hemoglobin, number of erythrocytes, and leukocytes) and anxiety and compulsive-like behavior in males and females orally exposed to ~5 mg/kg for 4 weeks. The results showed that E171 decreased hematocrit and hemoglobin in male but not in female mice while leukocyte and erythrocyte count remained unaltered. Oral consumption of E171 decreased the levels of anxiety-like behavior in females but not in male mice, while compulsive-like behavior was increased in both male and female mice.     

Daily skin-to-skin contact in full-term infants and breastfeeding: Secondary outcomes from a randomized controlled trial

This randomized controlled trial evaluated the effect of a 5-week daily skin-to-skin contact (SSC) intervention between mothers and their full-term infants, compared with care-as-usual, on exclusive and continued breastfeeding duration during the first post-natal year. Healthy pregnant women (n = 116) from a community sample were enrolled and randomly allocated to the SSC or care-as-usual condition. SSC mothers were requested to provide one daily hour of SSC for the first five post-natal weeks. Twelve months post-partum, mothers indicated the number of exclusive and continued breastfeeding months. Multiple regression analyses were conducted using intention-to-treat, per-protocol and exploratory dose–response frameworks. In intention-to-treat analyses, exclusive and continued breastfeeding duration was not different between groups (exclusive: 3.61 ± 1.99 vs. 3.16 ± 1.77 months; adjusted mean difference 0.28, 95% confidence interval [CI] ?0.33 to 0.89; p = 0.36; continued: 7.98 ± 4.20 vs. 6.75 ± 4.06 months; adjusted mean difference 0.81, 95% CI ?0.46 to 2.08; p = 0.21). In per-protocol analyses, exclusive and continued breastfeeding duration was longer for SSC than care-as-usual dyads (exclusive: 4.89 ± 1.26 vs. 3.25 ± 1.80 months; adjusted mean difference 1.28, 95% CI 0.31–2.24; p = 0.01; continued: 10.81 ± 1.97 vs. 6.98 ± 4.08 months; adjusted mean difference 2.33, 95% CI 0.13–4.54; p = 0.04). Exploratory dose–response effects indicated that more SSC hours predicted longer exclusive and continued breastfeeding duration. This study demonstrates that for the total group, the 5-week daily SSC intervention did not extend exclusive and continued breastfeeding duration. However, for mothers performing a regular daily hour of SSC, this simple and accessible intervention may extend exclusive and continued breastfeeding duration by months. Future studies are required to confirm these promising findings. Trial registration: Netherlands Trial Register (NTR5697).