CO2 concentration in day care centres is related to wheezing in attending children

Poor ventilation at day care centres (DCCs) was already reported, although its effects on attending children are not clear. This study aimed to evaluate the association between wheezing in children and indoor CO₂ (a ventilation surrogate marker) in DCC and to identify behaviours and building characteristics potentially related to CO₂. In phase I, 45 DCCs from Lisbon and Oporto (Portugal) were selected through a proportional stratified random sampling. In phase II, 3 months later, 19 DCCs were further reassessed after cluster analysis for the greatest difference comparison. In both phases, children’s respiratory health was assessed by ISAAC-derived questionnaires. Indoor CO₂ concentrations and building characteristics of the DCC were evaluated in both phases, using complementary methods. Mixed effect models were used to analyze the data. In phase I, which included 3,186 children (mean age 3.1?±?1.5 years), indoor CO₂ concentration in the DCC rooms was associated with reported wheezing in the past 12 months (27.5 %) (adjusted odds ratio (OR) for each increase of 200 ppm 1.04, 95 % CI 1:01 to 1:07). In phase II, the association in the subsample of 1,196 children seen in 19 out of the initial 45 DCCs was not significant (adjusted OR 1.02, 95 % CI 0.96 to 1.08). Indoor CO₂ concentration was inversely associated with the practices of opening windows and internal doors and with higher wind velocity. A positive trend was observed between CO₂ and prevalence of reported asthma (4.7 %). Conclusion: Improved ventilation is needed to achieve a healthier indoor environment in DCC.     

Load cycling enhances bioactivity at the resin–dentin interface

Objectives

The purpose of this study was to evaluate if mechanical loading promotes bioactivity at the resin interface after bonding with three different adhesive approaches.

Methods

Dentin surfaces were subjected to three different treatments: demineralisation by (1) 37% phosphoric acid (PA) followed by application of an etch-and-rinse dentin adhesive Single Bond (SB) (PA + SB), (2) by 0.5 M ethylenediaminetetraacetic acid (EDTA) followed by SB (EDTA + SB), (3) application of a self-etch dentin adhesive: Clearfil SE Bond (SEB). Bonded interfaces were stored in simulated body fluid during 24 h or 3 w. One half of each tooth was submitted to mechanical loading. Remineralisation of the bonded interfaces was assessed by AFM imaging/nano-indentation, Raman spectroscopy/cluster analysis, dye assisted confocal microscopy evaluation (CLSM) and Masson's trichrome staining.

Results

Loading cycling for 3 w promoted an increase of mechanical properties at the resin–dentin interface. Cluster analysis demonstrated an augmentation of the mineral–matrix ratio in SB-loaded specimens. CLSM showed an absent micropermeability and nanoleakage after loading EDTA + SB and SEB specimens. Trichrome staining reflected a narrow demineralised dentin matrix after loading, almost not observable in EDTA + SB and SEB.

Significance

In vitro mechanical loading promoted mineralization in the resin–dentin interfaces, at 24 h and 3 w of storage.     

Phospholipid‐induced silk fibroin hydrogels and their potential as cell carriers for tissue regeneration

Silk fibroin (SF) hydrogels can be obtained via self‐assembly, but this process takes several days or weeks, being unfeasible to produce cell carrier hydrogels. In this work, a phospholipid, namely, 1,2‐dimyristoyl‐sn‐glycero‐3‐phospho‐(1′‐rac‐glycerol) sodium salt (DMPG), was used to induce and accelerate the gelation process of SF solutions. Due to the amphipathic nature and negative charge of DMPG, electrostatic and hydrophobic interactions between the phospholipids and SF chains will occur, inducing the structural transition of SF chains to the beta sheet and consequently a rapid gel formation is observed (less than 50 min). Moreover, the gelation time can be controlled by varying the lipid concentration. To assess the potential of the hydrogels as cell carriers, several mammalian cell lines, including L929, NIH/3T3, SaOS‐2, and CaSki, were encapsulated into the hydrogel. The silk‐based hydrogels supported the normal growth of fibroblasts, corroborating their cytocompatibility. Interestingly, an inhibition in the growth of cancer‐derived cell lines was observed. Therefore, DMPG‐induced SF hydrogels can be successfully used as a 3D platform for in situ cell encapsulation, opening promising opportunities in biomedical applications, such as in cell therapies and tissue regeneration.     

Urinary Sodium Excretion and Adherence to the Mediterranean Diet in Older Adults

Despite the well-known benefits of the Mediterranean Diet (MedDiet), data on the sodium intake is scarce. This study aimed to quantify the association between sodium excretion and the adherence to the MedDiet in the elderly. A representative sample of 1500 Portuguese adults (≥65 years) was assessed (1321 were eligible for the present analysis). A 24 h urine sample was collected and analysed for creatinine and sodium. Excessive sodium intake was defined as above 2000 mg/day. The adherence to the MedDiet was assessed by the PREDIMED. A binary logistic regression model was conducted to evaluate the association between urinary sodium excretion and the adherence to the MedDiet. Odds Ratios (OR) and respective 95% Confidence Intervals (95% CI) were calculated. Excessive sodium excretion was observed in 80.0% of men and 91.5% of women whereas a high adherence to the MedDiet was reported by 42.2% of women and 46.4% of men. After adjusting for confounders, excessive sodium excretion was associated with a high adherence to the MedDiet in men (OR = 1.94; 95% CI: 1.03–3.65) but not in women. These results show that the MedDiet can be an important source of sodium and highlight the need for implementing strategies to reduce sodium intake when following a MedDiet.     

The Use of a PEG/Ascorbate Booster Following Standard Bowel Preparation Improves Visualization for Capsule Endoscopy in a Randomized,Controlled Study

Background Background/Aims: The increasing use of capsule endoscopy (CE) to examine the gastrointestinal tract highlights the need to establish intestinal preparations that ensure optimal visualization while maximizing patient adherence. Thus, we assessed whether bowel preparation involving dietary restriction and a booster regimen produces adequate CE visualization in a real-world clinical setting.Methods We conducted a randomized, double-blind, prospective study of CE procedures at 2 tertiary-care centers. Patients were allocated to 3 groups: group 1 followed a clear liquid diet and fasting-based bowel preparation for the exploration (n = 55); group 2 followed the same procedure as group 1 and then ingested 1 L of a polyethylene glycol (PEG)/ascorbic acid booster solution when the capsule reached the small intestine (n = 55); and group 3 followed the same procedure but ingesting only 0.5 L of the booster solution (n = 56). The quality of visualization and the average gastric, orocecal and small-bowel transit times were evaluated.Results A total of 166 patients participated in the study. Significantly higher quality of visualization (Park score) was obtained in group 3 (2.28 ± 0.59) than in group 1 (1.84 ± 0.54, P < .001), while there were no significant differences in the average gastric (range: 36.58-48.32 min, P = .277), orocecal (range: 322.58-289.45 min, P = .072), and small-bowel transit time (range: 280.71-249.95 min, P = .286) between the 3 groups.Conclusions Following a clear liquid diet and fasting-based bowel preparation for CE exploration, administering a booster solution of PEG/ascorbic acid after the capsule had reached the small intestine improves mucosal visualization and cleansing without affecting capsule transit times.     

New carvacrol and thymol derivatives as potential insecticides: synthesis,biological activity,computational studies and nanoencapsulation

New compounds with potential insecticide activity were synthesized by structural modifications performed in the monoterpenoid phenolic moieties of carvacrol and thymol, resulting in a set of derivatives with the ether function containing the propyl, chloropropyl or hydroxypropyl chains, as well as a bicyclic ether with an unsaturated chain containing a carboxylic acid terminal. In addition, an analogue of carvacrol and thymol isomers bearing methoxyl, 1-hydroxyethyl and (3-chlorobenzoyl)oxy, instead of the three original methyl groups, was also synthesized. Several structural changes that resulted in diminished insecticide activity have been identified, but two significantly active molecules have been synthesized, one of them being less toxic to human cells than the naturally-derived starting materials. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these active molecules likely target the insect odorant binding proteins and/or acetylcholinesterase and are able to form stable complexes. For the most promising compounds, nanoencapsulation assays were carried out in liposomes of egg phosphatidylcholine/cholesterol (7 : 3) prepared by both thin film hydration and ethanolic injection methods. The compound-loaded liposomes were generally monodisperse and with sizes smaller than or around 200 nm. The thin film hydration method allowed high encapsulation efficiencies (above 85%) for both compounds and a delayed release, while for the systems prepared by ethanolic injection the encapsulation efficiency is lower than 50%, but the release is almost complete in two days.

Thymol and carvacrol derivatives were synthesised. Two of them proved to be mildly active against Sf9 insect cell line and one has presented selectivity by proving to be less toxic to human cells than the naturally derived starting materials.     

Characterization of a Parkinson’s disease rat model using an upgraded paraquat exposure paradigm

Animal models of human diseases are crucial experimental tools to investigate the mechanisms involved in disease pathogenesis and to develop new therapies. In spite of the numerous animal models currently available that reproduce several neuropathological features of Parkinson disease (PD), it is challenging to have one that consistently recapitulates human PD conditions in both motor behaviors and biochemical pathological outcomes. Given that, we have implemented a new paradigm to expose rats to a chronic low dose of paraquat (PQ), using osmotic minipumps and characterized the developed pathologic features over time. The PQ exposure paradigm used lead to a rodent model of PD depicting progressive nigrostriatal dopaminergic neurodegeneration, characterized by a 41% significant loss of dopaminergic neuron in the substantia nigra pars compacta (SNpc), a significant decrease of 18% and 40% of dopamine levels in striatum at week 5 and 8, respectively, and a significant 1.5‐fold decrease in motor performance. We observed a significant increase of microglia activation state, sustained levels of α‐synucleinopathy and increased oxidative stress markers in the SNpc. In summary, this is an explorative study that allowed to characterize an improved PQ‐based rat model that recapitulates cardinal features of PD and may represent an attractive tool to investigate several mechanisms underlying the various aspects of PD pathogenesis as well as for the validation of the efficacy of new therapeutic approaches that targets different mechanisms involved in PD neurodegeneration.     

Right single coronary artery as an incidental finding in Takotsubo syndrome and acute heart failure: Case report and review of the literature

Introduction

Single coronary artery (SCA) with no associated congenital heart disease is a rare congenital anomaly. Most cases are asymptomatic and incidental findings, but SCA can cause ischemia, congestive heart failure, and sudden cardiac death (SCD).

Outbreak of Acute Respiratory Infection among Infants in Lisbon,Portugal, Caused by Human Adenovirus Serotype 3 and a New 7/3 Recombinant Strain

Human adenoviruses (AdVs) typically cause mild illnesses in otherwise healthy hosts. We investigated a pediatric outbreak of acute respiratory infection with fatal outcomes that occurred in Lisbon, Portugal, in 2004. Biological specimens were collected from 83 children attending two nurseries, a kinesiotherapy clinic, and the household of a nanny. Adenovirus infection was confirmed in 48 children by PCR and virus isolation. Most (96%) isolates were classified as being of subspecies B1. Phylogenetic analysis of fiber and hexon gene sequences revealed that most infants were infected with AdV serotype 3 (AdV3) strains. Infants attending one nursery harbored a new recombinant strain containing an AdV serotype 7 hexon and serotype 3 fiber (AdV7/3). Both the AdV3 and the AdV7/3 strains caused fatal infections. Two different serotype 3 strains were circulating in Lisbon in 2004, and the new AdV7/3 recombinant type originated from only one of those strains. These results demonstrate that recombination leads to the emergence of new adenovirus strains with epidemic and lethal potential.Human adenoviruses (HAdVs) have been associated with a wide spectrum of clinical diseases with respiratory and gastrointestinal symptoms (23, 32). Severe illness can occur in newborns, elderly individuals, and patients with underlying medical conditions. In otherwise healthy adults, infections caused by human adenoviruses do not represent a life-threatening clinical condition. Adenoviruses are characterized by a linear double-stranded DNA genome of 2 to 45 kbp that encodes 30 to 40 proteins (6). HAdV comprises 51 serotypes (HAdV-1 to HAdV-51), on the basis of type-specific antiserum-mediated neutralization of infectivity (10). The serotypes can be divided into seven species, named HAdV-A to HAdV-G, on the basis of hemagglutination inhibition and biochemical criteria (13). HAdV-B is further classified into subspecies B1 and B2, which use different cellular receptors for viral entry (29). These variants can be segregated by different geographic areas, time periods, and clinical conditions.Serotype identification is critical for epidemiological surveillance, the detection of new strains, assessment of treatment efficacy, and understanding the pathogenesis of HAdV. For example, acute respiratory disease is primarily caused by HAdV-B1 serotypes 3, 7, 16, and 21; HAdV-B2 serotypes 11 and 14; and HAdV-E serotype 4 (8, 23, 25, 28, 35, 38, 41). Respiratory infections caused by HAdV-B1 serotypes 3 and 7 (16) and HAdV-B2 serotype 14 (17) are potentially fatal. Neutralization tests are the classical reference method used for the typing of adenovirus and require virus isolation from infected organs or tissues (20). The main type-specific neutralizing epitope, the ɛ determinant, consists of loop 1 (L1) and loop 2 (L2) on the hexon protein, the major capsid protein and the most abundant structural protein (26). Cases of the failure of neutralization with the available antisera require extensive cross-neutralization studies to define a new HAdV type. To circumvent the practical problems associated with traditional serum neutralization studies, molecular methods for the typing of adenovirus have been established. Examples are restriction fragment length polymorphism (RFLP) analysis of adenoviral DNA (16), PCR-based assays (1, 36), and microarray-based methods (36). However, these methods cannot discriminate between all serotypes and do not allow detailed studies of molecular epidemiology and viral evolution to be performed.More recently, analysis of the nucleotide and amino acid sequences from different genes has shown that adenovirus species form three distinct phylogenetic clusters: HAdV-C belongs to cluster 1; HAdV-A and HAdV-F belong to cluster 2; and HAdV-B, HAdV-D, and HAdV-E belong to cluster 3 (6, 22). In addition, phylogenetic analysis of selected gene fragments has increasingly been used to classify human adenoviruses at the serotype and species levels (7, 19, 40), to detect cases of coinfection with multiple adenoviral species (36, 38), and to identify new recombinant strains formed between similar species (18, 37, 41) or different species (19). Finally, phylogenetic analysis has become an important tool in the epidemiological investigation of many disease outbreaks caused by adenovirus (11, 17, 27, 40, 41). In the present study, we have used epidemiological, virological, and molecular phylogenetic methods to investigate the causes and origin of a recent outbreak of acute respiratory infection in Lisbon, Portugal, that resulted in the deaths of two children.     

Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus

Cortical and medullary thymic epithelial cells (cTECs and mTECs, respectively) provide inductive microenvironments for T‐cell development and selection. The differentiation pathway of cTEC/mTEC lineages downstream of common bipotent progenitors at discrete stages of development remains unresolved. Using IL‐7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show that the stepwise acquisition of chemokine (C–C motif) receptor‐like 1 (CCRL1) is a late determinant of cTEC differentiation. Although cTECs expressing high CCRL1 levels (CCRL1^hi) develop normally in immunocompetent and Rag2^?/?thymi, their differentiation is partially blocked in Rag2^?/?Il2rg^?/? counterparts. These results unravel a novel checkpoint in cTEC maturation that is regulated by the cross‐talk between TECs and immature thymocytes. Additionally, we identify new Ulex europaeus agglutinin 1 (UEA)⁺ mTEC subtypes expressing intermediate CCRL1 levels (CCRL1^int) that conspicuously emerge in the postnatal thymus and differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in Rag2^?/? thymi, CCRL1^int mTECs are restored in Rag2^?/?Marilyn TCR‐Tg mice, indicating that the appearance of postnatal‐restricted mTECs is closely linked with T‐cell selection. Our findings suggest that alternative temporally restricted routes of new mTEC differentiation contribute to the establishment of the medullary niche in the postnatal thymus.