ABSTRACT
Infection with Influenza A virus (IAV) causes the well-known symptoms of the flu, including fever, loss of appetite, and excessive sleepiness. These responses, mediated by the brain, will normally disappear once the virus is cleared from the system, but a severe respiratory virus infection may cause long-lasting neurological disturbances. These include encephalitis lethargica and narcolepsy. The mechanisms behind such long lasting changes are unknown. The hypothalamus is a central regulator of the homeostatic response during a viral challenge. To gain insight into the neuronal and non-neuronal molecular changes during an IAV infection, we intranasally infected mice with an H1N1 virus and extracted the brain at different time points. Using single-nucleus RNA sequencing (snRNA-seq) of the hypothalamus, we identify transcriptional effects in all identified cell populations. The snRNA-seq data showed the most pronounced transcriptional response at 3 days past infection, with a strong downregulation of genes across all cell types. General immune processes were mainly impacted in microglia, the brain resident immune cells, where we found increased numbers of cells expressing pro-inflammatory gene networks. In addition, we found that most neuronal cell populations downregulated genes contributing to the energy homeostasis in mitochondria and protein translation in the cytosol, indicating potential reduced cellular and neuronal activity. This might be a preventive mechanism in neuronal cells to avoid intracellular viral replication and attack by phagocytosing cells. The change of microglia gene activity suggest that this is complemented by a shift in microglia activity to provide increased surveillance of their surroundings.
When you are ill, your behaviour changes. You sleep more, eat less and are less likely to go out and be active. This behavioural change is called the 'sickness response' and is believed to help the immune system fight infection. An area of the brain called the hypothalamus helps to regulate sleep and appetite. Previous research has shown that when humans are ill, the immune system sends signals to the hypothalamus, likely initiating the sickness response. However, it was not clear which brain cells in the hypothalamus are involved in the response and how long after infection the brain returns to its normal state. To better understand the sickness response, Lemcke et al. infected mice with influenza then extracted and analysed brain tissue at different timepoints. The experiments showed that the major changes to gene expression in the hypothalamus early during an influenza infection are not happening in neurons the cells in the brain that transmit electrical signals and usually control behaviour. Instead, it is cells called glia which provide support and immune protection to the neurons that change during infection. The findings suggest that these cells prepare to protect the neurons from influenza should the virus enter the brain. Lemcke et al. also found that the brain takes a long time to go back to normal after an influenza infection. In infected mice, molecular changes in brain cells could be detected even after the influenza infection had been cleared from the respiratory system. In the future, these findings may help to explain why some people take longer than others to fully recover from viral infections such as influenza and aid development of medications that speed up recovery.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Animals , Mice , Humans , Hypothalamus , Solitary Nucleus , AppetiteABSTRACT
BACKGROUND: Airway management with supraglottic airway devices (SGA) in life-threatening emergencies involving children is becoming increasingly more important. The laryngeal mask (LM) and the laryngeal tube (LT) are devices commonly used for this purpose. This article presents a literature review and consensus statement by various societies on the use of SGA in pediatric emergency medicine. MATERIAL AND METHODS: Literature search in the database PubMed and classification of studies according to the criteria of the Oxford Centre for Evidence-based Medicine levels of evidence. RESULTS: The evidence for successful application of the various types of LM is significantly higher than for LT application. Reports of smaller series of successful applications of LT are currently limited to selected research groups and centers. Insufficient evidence currently exists for the successful application of the LT especially for children below 10 kg body weight and, therefore, its routine use cannot currently be recommended. SGAs used for emergencies should have a possibility for gastric drainage. DISCUSSION: Considering the scientific data and the large clinical experience with the LM in medical routine and emergency situations in children, currently only the LM can be recommended for alternative (i.e. non-intubation) airway management in children. If alternative airway management is part of a local emergency strategy, the LM should be provided in all pediatric sizes (1, 1.5, 2, 2.5, 3, 4 and 5) for prehospital and in-hospital emergency use and all users should be regularly trained in its application.
Subject(s)
Airway Management/instrumentation , Airway Management/standards , Emergency Medical Services/standards , Emergency Medicine/instrumentation , Emergency Medicine/standards , Laryngeal Masks/trends , Pediatrics/instrumentation , Adolescent , Child , Child, Preschool , Consensus , Evidence-Based Medicine , Humans , Infant , Infant, Newborn , Intubation, IntratrachealSubject(s)
Evidence-Based Medicine , Homeopathy , History of Medicine , Homeopathy/standards , Humans , Meta-Analysis as TopicABSTRACT
Diagnostic flexible endoscopy for pediatric respiratory diseases is performed in many centers. Technical advances have resulted in performance of interventional bronchoscopies, and new diagnostic indications are being explored. Indications with documented clinical benefit include congenital or acquired progressive or unexplained airway obstruction. Pulmonary infections in immunodeficient children who do not respond to empirical antibiotic treatment may be diagnosed by bronchoscopy and bronchoalveolar lavage (BAL). The potential usefulness of bronchoscopy and BAL for managing chronic cough, wheeze, or selected cases with asthma or cystic fibrosis requires further study. The use of transbronchial biopsies (TBB) is established in pediatric lung transplantation. The role of TBB in the diagnosis of chronic interstitial lung disease in children remains to be determined. For a number of interventional applications, rigid endoscopy is required, and pediatric bronchoscopists should be trained in its use. Complications in pediatric bronchoscopy are rare, but severe nosocomial infection or overdosing with local anesthetics has occurred. The issues of quality control, video documentation, interobserver variability of findings, and educational standards will have to be addressed in the future as bronchoscopy use becomes less restricted to only large pediatric pulmonary units.
Subject(s)
Bronchoscopy/methods , Respiratory Tract Diseases/diagnosis , Airway Obstruction/therapy , Anesthesia, Local , Asthma/diagnosis , Bronchoalveolar Lavage/methods , Child , Child, Preschool , Chronic Disease , Conscious Sedation , Cough/etiology , Humans , Infant , Infant, Newborn , Intensive Care Units , Lung Transplantation , Respiratory Sounds/etiologyABSTRACT
A number of sharp fractions from low methoxyl citrus pectin have been studied using dynamic and static light scattering and size exclusion chromatography. The efficiency of the dynamic light scattering technique for the characterization of aqueous pectin solutions is demonstrated even when aggregages are present. The measured molar mass dependence of the Stokes radius confirms the semi-rigid structure of pectin. The effect of a number of sample manipulations on the aggregate content has been investigated and a simple but effective purification method is presented.