Systematic altering of semiflexible DNA-based polymer networks via tunable crosslinking.

In order to understand and predict the mechanical behaviours of complex, soft biomaterials such as cells or stimuli-responsive hydrogels, it is important to connect how the nanoscale properties of their constituent components impact those of the bulk material. Crosslinked networks of semiflexible polymers are particularly ubiquitous, being underlying mechanical components of biological systems such as cells or ECM, as well as many synthetic or biomimetic materials. Cell-derived components such as filamentous biopolymers or protein crosslinkers are readily available and well-studied model systems. However, as evolutionarily derived materials, they are constrained to a fixed set of structural parameters such as the rigidity and size of the filaments, or the valency and strength of binding of crosslinkers forming inter-filament connections. By implementing a synthetic model system based on the self-assembly of DNA oligonucleotides into nanometer-scale tubes and simple crosslinking constructs, we used the thermodynamic programmability of DNA hybridization to explore the impact of binding affinity on bulk mechanical response. Stepwise tuning the crosslinking affinity over a range from transient to thermodynamically stable shows an according change in viscoelastic behaviour from loosely entangled to elastic, consistent with models accounting for generalized inter-filament interactions. While characteristic signatures of concentration-dependent changes in network morphology found in some other natural and synthetic filament-crosslinker systems were not apparent, the presence of a distinct elasticity increase within a narrow range of conditions points towards potential subtle alterations of crosslink-filament architecture. Here, we demonstrate a new synthetic approach for gaining a deeper understanding of both biological as well as engineered hydrogel systems.

Pulmonary edema in a pediatric cancer patient after anesthetic induction.

Negative pressure pulmonary edema (NPPE) in the context of anesthesia is a rare condition, although pediatric patients are at higher risk. This case stands out for the severe respiratory clinic that quickly developed in a child with a cancer history whose radiological and clinical presentation suggested multiple differential diagnoses, including tumor recurrence with metastasis or pulmonary tuberculosis. NPPE is a well-described, but a probably underrecognized clinical syndrome, that occurs after intense inspiratory effort against an obstructed airway. In clinical practice, when unexplained pulmonary edema takes place, NPPE should be considered in the differential diagnosis. NPPE usually has a favorable prognosis but pediatricians, radiologists, and anesthesiologists should be aware of this complication.

Impact of indoor air pollution in nursery and primary schools on childhood asthma.

Poor indoor air quality in scholar environments have been frequently reported, but its impact on respiratory health in schoolchildren has not been sufficiently explored. Thus, this study aimed to evaluate the associations between children's exposure to indoor air pollution (IAP) in nursery and primary schools and childhood asthma. Multivariate models (independent and multipollutant) quantified the associations of children's exposure with asthma-related health outcomes: reported active wheezing, reported and diagnosed asthma, and lung function (reduced FEV1/FVC and reduced FEV1). A microenvironmental modelling approach estimated individual inhaled exposure to major indoor air pollutants (CO2, CO, formaldehyde, NO2, O3, TVOC, PM2.5 and PM10) in nursery and primary schools from both urban and rural sites in northern Portugal. Questionnaires and medical tests (spirometry pre- and post-bronchodilator) were used to obtain information on health outcomes and to diagnose asthma following the newest international clinical guidelines. After testing children for aeroallergen sensitisation, multinomial models estimated the effect of exposure to particulate matter on asthma in sensitised individuals. The study population were 1530 children attending nursery and primary schools, respectively 648 pre-schoolers (3-5 years old) and 882 primary school children (6-10 years old). This study found no evidence of a significant association between IAP in nursery and primary schools and the prevalence of childhood asthma. However, reported active wheezing was associated with higher NO2, and reduced FEV1 was associated with higher O3 and PM2.5, despite NO2 and O3 in schools were always below the 200 µg m-3 threshold from WHO and National legislation, respectively. Moreover, sensitised children to common aeroallergens were more likely to have asthma during childhood when exposed to particulate matter in schools. These findings support the urgent need for mitigation measures to reduce IAP in schools, reducing its burden to children's health.

COMPLICATED PNEUMONIA WITH EMPYEMA CAUSED BY STREPTOCOCCUS ANGINOSUS IN A CHILD.

OBJECTIVE: To highlight the pathogenicity of Streptococcus anginosus, which is rare in pediatric patients, but can cause severe infections that are known to have a better outcome when treated early with interventional procedures and prolonged antibiotic therapy. CASE: description: The patient is a 6-year-old boy with global developmental delay, examined in the emergency room due to fever and respiratory distress. The physical examination and diagnostic workout revealed complicated pneumonia with empyema of the left hemithorax; he started antibiotic therapy and underwent thoracic drainage. Pleural fluid cultures grew Streptococcus anginosus. On day 11, the child had a clinical deterioration with recurrence of fever, hypoxia, and respiratory distress. At this point, considering the causative agent, he was submitted to video-assisted thoracoscopic decortication, with good progress thereafter. COMMENTS: Streptococcus anginosus is a commensal bacterium of the human oral cavity capable of causing severe systemic infections. Although reports of complicated thoracic infections with this agent are rare in the pediatric population, they have been increasing in adults. Streptococcus anginosus has a high capacity to form abscess and empyema, requiring different therapeutic approaches when compared to complicated pneumonia caused by other agents.

Complicated pneumonia with empyema caused by streptococcus anginosus in a child / Complicated pneumonia with empyema caused by streptococcus anginosus in a child

ABSTRACT Objective: To highlight the pathogenicity of Streptococcus anginosus, which is rare in pediatric patients, but can cause severe infections that are known to have a better outcome when treated early with interventional procedures and prolonged antibiotic therapy. Case description: The patient is a 6-year-old boy with global developmental delay, examined in the emergency room due to fever and respiratory distress. The physical examination and diagnostic workout revealed complicated pneumonia with empyema of the left hemithorax; he started antibiotic therapy and underwent thoracic drainage. Pleural fluid cultures grew Streptococcus anginosus. On day 11, the child had a clinical deterioration with recurrence of fever, hypoxia, and respiratory distress. At this point, considering the causative agent, he was submitted to video-assisted thoracoscopic decortication, with good progress thereafter. Comments: Streptococcus anginosus is a commensal bacterium of the human oral cavity capable of causing severe systemic infections. Although reports of complicated thoracic infections with this agent are rare in the pediatric population, they have been increasing in adults. Streptococcus anginosus has a high capacity to form abscess and empyema, requiring different therapeutic approaches when compared to complicated pneumonia caused by other agents.

RESUMO Objetivo: Alertar para a patogenicidade do Streptococcus anginosus que, apesar de raro em pediatria, pode causar infeções graves que necessitam de tratamento invasivo e antibioterapia de longo curso para obter um melhor prognóstico. Descrição do caso: Criança de seis anos, com atraso do desenvolvimento psicomotor, avaliado no serviço de urgência por febre e dificuldade respiratória. O exame físico, juntamente com os exames complementares, revelou uma pneumonia complicada com empiema no hemitórax esquerdo, tendo iniciado antibioterapia e sido submetido à drenagem do líquido pleural. Foi identificado Streptococcus anginosus nesse líquido. No 11º dia de doença, a criança agravou o seu estado clínico, com recidiva da febre, hipoxemia e dificuldade respiratória. Considerando-se o microrganismo identificado, o paciente foi submetido à decorticação pulmonar por videotoracoscopia, com boa evolução clínica posterior. Comentários: Streptococcus anginosus é uma bactéria comensal da cavidade oral humana, que pode causar infecções sistêmicas graves. Apesar de serem raros os casos descritos em pediatria, têm sido cada vez mais descritas infecções torácicas complicadas em adultos. Esse microrganismo também tem a capacidade de formar abcessos e empiemas, que precisam de intervenções terapêuticas diferentes, quando comparados a pneumonias complicadas causadas por outros agentes.

Nocardia lung abscess in an immunocompetent adolescent.

The authors report a case of a lung abscess caused by Nocardia sp. in a previously healthy adolescent. A 17-year-old young man presented with tonsillitis that did not respond to ß-lactamic antibiotic, dyspnoea and thoracic pain. The X-ray revealed a cavitation in the right pulmonary upper lobe. He was admitted and completed a 14-day empirical antimicrobial therapy for a pulmonar abscess, although no clinical recovery was observed. He then underwent pulmonary biopsy of the lesion and PCR analysis of the collected pulmonary tissue, which revealed the presence of Nocardia This case emphasises the importance of considering nocardiosis in the differential diagnosis of a lung abscess, particularly if no response to empirical therapy is obtained.

Pulmonary involvement in neonatal lupus: a challenging diagnosis - case report and literature review.

INTRODUCTION: Pulmonary involvement is relatively frequent in adult and juvenile patients with Systemic Lupus Erythematosus (SLE), but its occurrence in newborns with Neonatal Lupus Erythematosus (NLE) is exceedingly rare. CASE REPORT: A mother with SLE and positive anti-SSA/Ro and anti-SSB/La delivered a preterm newborn with third-degree heart block and positive anti-SSA/Ro confirmed postnatally. A temporary pacemaker was placed at D3 and a definitive pacemaker only at D15 due to sepsis with concurrent mild respiratory failure. Despite adequate antibiotic therapy, negative cultures and decreasing inflammatory parameters, at D17 severe respiratory failure ensued, requiring mechanical ventilation. Chest x-ray showed symmetrical interstitial infiltrates. Acute Lupus Pneumonitis (ALP) and Pulmonary Embolism were suspected and the chest angio-CT revealed diffuse ground glass opacities. After 3 methylprednisolone pulses he improved rapidly. DISCUSSION: The diagnosis of ALP in NLE, mostly one of exclusion, is a challenge. A high degree of suspicion and a multidisciplinary approach to these patients are fundamental in order not to delay establishing a diagnosis. Although few reports in the literature, early aggressive treatments are probably crucial for a favorable outcome without long-term sequelae.

Pneumococcal pneumonia vaccine breakthroughs and failures after 13-valent pneumococcal conjugated vaccine.

The rate of invasive pneumococcal disease has markedly declined after the introduction of pneumococcal conjugated vaccines. In spite of the high effectiveness of this vaccine, there are some reports of vaccine failure and vaccine breakthroughs. Data on children with pneumococcal pneumonia in a European tertiary Hospital, from 2012 to 2014, were retrospectively collected before the implementation of pneumococcal conjugated vaccines in our country. We found four cases of pneumococcal serotype 3 vaccine failure and three cases of vaccine breakthroughs (two with serotype 3 and one with serotype 19A). All of these children were previously healthy.

Spontaneous Pneumothorax With Subcutaneous Emphysema: A Rare Complication of Respiratory Syncytial Virus Infection.

Viral bronchiolitis is the most common lower respiratory tract infection in infants and children under the age of 2. Respiratory syncytial virus (RSV) is the infecting agent in more than 50% of the cases. Usually the clinical course is uneventful and complications are uncommon. Secondary air leaks are a recognized rare complication of bronchiolitis, although the real incidence remains unknown. We report a case of a 21-month-old female that developed a spontaneous pneumothorax (PNO) with subcutaneous emphysema (SE) late in the course of RSV acute bronchiolitis. Additional investigation ruled out any underlying disease predisposing to spontaneous PNO. Physicians, especially those who work with small children, must be aware of this uncommon complication of bronchiolitis that may appear late in the course of the disease despite an initial clinical improvement.

Severe IgG4-Related Disease in a Young Child: A Diagnosis Challenge.

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome that can appear with multiple organ involvement, typically with tumor-like swelling, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and elevated serum IgG4 concentrations. We report the case of a 22-month-old female child with failure to thrive and recurrent respiratory tract infections since 8 months of age. Physical examination was normal except for pulmonary auscultation with bilateral crackles and wheezes. Laboratory tests revealed elevated erythrocyte sedimentation rate, and elevated serum IgG and IgG4 with polyclonal hypergammaglobulinemia. Thoracic CT and MRI showed multiple mediastinal lymphadenopathies and a nodular posterior mediastinal mass in right paratracheal location with bronchial compression. Initial fine needle aspiration biopsy was compatible with reactive lymphadenopathy but after clinical worsening a thoracoscopic partial resection of the mass was performed and tissue biopsy revealed lymphoplasmacytic infiltrate and increased number of IgG4-positive plasma cells and a ratio of IgG4/IgG positive cells above 40%. Glucocorticoids therapy was started with symptomatic improvement, reduction in the size of the mass, and decrease of serum IgG4 levels after 6 weeks. There are very few reports of IgG4-RD in children. Long-term follow-up is necessary to monitor relapses and additional organ involvement.

Posaconazole as rescue therapy in African histoplasmosis

Posaconazole Histoplasmosis Salvage therapy African histoplasmosis is a granulomatous mycosis caused by Histoplasma capsulatum var. duboisii. Treatment is usually extrapolated from guidelines for classical histoplasmosis, and includes 2-4 weeks of amphotericin B followed by a step-down maintenance therapy with itraconazole. Pediatric usage of posaconazole, an oral second-generation azole, remains off-label, but recent surveys show that it is safe and well tolerated in children. We report a case of disseminated African histoplasmosis in a 12-year-old boy from Guinea-Bissau. Therapy with amphotericin B and itraconazole led to a progressive clinical deterioration. A dramatic and lasting improvement was observed using posaconazole. He completed 12 months of therapy. No relapse was noted during or 3 months after treatment. We report that posaconazole may be a safe and efficacious drug in the salvage management of disseminated AH, either in patients with disease refractory to conventional anti-fungal therapy, or in patients whose serious adverse effects of first-line drugs preclude its use.

Posaconazole as rescue therapy in African histoplasmosis.

African histoplasmosis is a granulomatous mycosis caused by Histoplasma capsulatum var. duboisii. Treatment is usually extrapolated from guidelines for classical histoplasmosis, and includes 2-4 weeks of amphotericin B followed by a step-down maintenance therapy with itraconazole. Pediatric usage of posaconazole, an oral second-generation azole, remains off-label, but recent surveys show that it is safe and well tolerated in children. We report a case of disseminated African histoplasmosis in a 12-year-old boy from Guinea-Bissau. Therapy with amphotericin B and itraconazole led to a progressive clinical deterioration. A dramatic and lasting improvement was observed using posaconazole. He completed 12 months of therapy. No relapse was noted during or 3 months after treatment. We report that posaconazole may be a safe and efficacious drug in the salvage management of disseminated AH, either in patients with disease refractory to conventional anti-fungal therapy, or in patients whose serious adverse effects of first-line drugs preclude its use.

Indoor air pollution on nurseries and primary schools: impact on childhood asthma--study protocol.

BACKGROUND: Several studies have demonstrated an association between the exposure to indoor air pollution (IAP) and childhood asthma. Evidence is suggesting that several air pollutants may contribute to both exacerbation and development of asthma, but some uncertainty remains concerning the specific causative role of IAP. This paper reports an epidemiologic study aiming to reduce the existing lacks on the association between long-term exposure to pollution mixtures and the development and exacerbation of childhood asthma. METHODS/DESIGN: Based on the implementation of the study in 8 nurseries and 8 primary schools, from which, 2 nurseries and 2 primary schools in sites influenced by traffic and other 2 nurseries and 2 primary schools in background sites at urban and rural areas, the study will analyse the exposure to both urban and rural pollution as well as to traffic emissions (some homes of the children will be included in the study). Furthermore, based on the answers to validated questionnaires (as those used in the International Study of Asthma and Allergies in Childhood - ISAAC) filled in by the parents and on medical exams, the study will assess the prevalence, incidence and exacerbation of asthma, thus considering both short and long-term effects. The approximate number of children in the study will never be less than 600, guaranteeing 80% of study power (significant at a 5% level). DISCUSSION: This study intends to contribute for the understanding of the role of environmental factors, namely indoor air pollution, on asthma considering a risk group of different ages, and for the development of preventive measures, which are considered priority issues by the European Commission, according to the European Environmental Agency and the World Health Organization.

Carbamazepine-induced interstitial pneumonitis associated with pan-hypogammaglobulinemia.

Carbamazepine remains a first-line drug for treatment of epilepsy in children. A wide variety of side effects have been attributed to its use, including a mild involvement of the immune system, usually a transient decline in IgA. Pulmonary complications, including interstitial pneumonitis, were mainly described in adults, and are considered rare side effects. In this report we describe the first pediatric patient who developed a severe interstitial pneumonitis and a pan-hypogammaglobulinemia 2 months after starting carbamazepine. A gradual resolution of symptoms and complete immune recovery was observed after the drug withdrawal, but 6 months later our patient still has a marked reduction in lung volumes and decreased exercise tolerance. We suggest that immunoglobulins should be carefully examined after carbamazepine initiation, particularly if the patient develops any sign of immunosuppression.