Incidence of complications in bronchoscopy. Multicentre prospective study of 20,986 bronchoscopies.

Aim. To evaluate the frequency of complications in bronchoscopy from data compiled between 1/2/2002 to 1/2/2003. Materials and methods. Nineteen Italian centres of thoracic endoscopy participated in the study, for a total of 20,986 bronchoscopies (FBS), including 10,658 explorative bronchoscopies (EB) (50.79%), 5,520 bronchial biopsies (BB) (26.30%), 1,660 transbronchial biopsies (TBB) (7.91%), 1,127 broncho-alveolar lavages (BAL) (5.37%), 930 transbronchial needle-aspirates (TBNA) (4.43%), 1.091 therapeutic bronchoscopies (TB), comprising NDYAG Laser, argon-plasma, electrocautery knife, stent insertion (5.20%). 82.4% of the procedures involved the use of a flexible bronchoscope, 16.3% were carried out using a rigid bronchoscope and 1.3% using the mixed technique. Results. The total number of complications recorded was 227 (1.08% of the cases examined), including 20 (0.09%) during local anesthesia and pre-medication, 195 (0.92%) during the endoscopic procedures and 12 (0.05%) in the two hours following FBS. The total number of deaths was 4 (0.02%), due to cardiac arrest, pulmonary edema, delayed respiratory failure and shock in pre-medication, respectively. 68.28% of the complications were treated medically, 25.99% by means of endoscopy and 5.72% with surgery. The healing percentage was 98.2%. Conclusions. This study has shown that bronchoscopy is a safe method with low incidence of mortality and complications. The preparation, experience and continuous training of the operators of the medical and nursing team seem to play a fundamental role in reducing the incidence of complications at least in certain procedures such as BB and TBB

In vivo magnetic resonance spectroscopy in the brain of Cdkl5 null mice reveals a metabolic profile indicative of mitochondrial dysfunctions

Mutations in the X‐linked CDKL5 gene cause CDKL5 deficiency disorder (CDD), a severe neurodevelopmental condition mainly characterized by infantile epileptic encephalopathy, intellectual disability, and autistic features. The molecular mechanisms underlying the clinical symptoms remain largely unknown and the identification of reliable biomarkers in animal models will certainly contribute to increase our comprehension of CDD as well as to assess the efficacy of therapeutic strategies. Here, we used different Magnetic Resonance (MR) methods to disclose structural, functional, or metabolic signatures of Cdkl5 deficiency in the brain of adult mice. We found that loss of Cdkl5 does not cause cerebral atrophy but affects distinct brain areas, particularly the hippocampus. By in vivo proton‐MR spectroscopy (MRS), we revealed in the Cdkl5 null brain a metabolic dysregulation indicative of mitochondrial dysfunctions. Accordingly, we unveiled a significant reduction in ATP levels and a decrease in the expression of complex IV of mitochondrial electron transport chain. Conversely, the number of mitochondria appeared preserved. Importantly, we reported a significant defect in the activation of one of the major regulators of cellular energy balance, the adenosine monophosphate‐activated protein kinase (AMPK), that might contribute to the observed metabolic impairment and become an interesting therapeutic target for future preclinical trials. In conclusion, MRS revealed in the Cdkl5 null brain the presence of a metabolic dysregulation suggestive of a mitochondrial dysfunction that permitted to foster our comprehension of Cdkl5 deficiency and brought our interest towards targeting mitochondria as therapeutic strategy for CDD

Training and practice in bronchoscopy: A national survey in Italy

Training and practice in bronchoscopy. A national survey in Italy. N. Facciolongo, R. Piro, F. Menzella, M. Lusuardi, M. Salio, L. Lazzari Agli, M. Patelli. Background and Aim. Bronchoscopy is performed in a variety of different settings in Italy. The surveys conducted so far have highlighted the heterogeneity of the procedures and the frequent inability to adhere to the guidelines. The aim of this survey was to analyse procedures, training, and opinions of Italian respiratory physicians performing interventional bronchology in the clinical practice. Methods. The study was conducted retrospectively on 300 pulmonologists. From January to June 2008, these were invited to participate in an email survey to be sent out monthly to each participant for four consecutive months. Results. Two hundred and one respiratory physicians took part in the study, most of whom (83.5%) work in either Pulmonology or Interventional Pulmonology Units. The year before the survey, 21.2% of the participants had performed fewer than 100 examinations, 42.3% 100 to 300, and 36.6% more than 300 bronchoscopies; 53.9% were familiar with the international guidelines on the topic. Among the responders, 34.1% had received less than 6 months training, 55.3% considered further training in rigid bronchoscopy, laser procedures and thoracoscopy, invaluable for their professional activity. Adequate training for transbronchial needle aspirates, was reported by 49.6% of respondents. Conclusions. Our data show that interventional bronchoscopy procedures are regularly performed according to current recommendations by over half of the Italian Pulmonologists participating in our survey. The need for more comprehensive basic education and training was put forward by the majority of physicians

Electromagnetic navigation bronchoscopy in the European cohort of the prospective, multicenter NAVIGATE study

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Differential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization

Inhibition in spinal nociceptive pathways is weaker and more labile in lamina I —where thermal input is primarily processed— than in lamina II that encodes predominantly high threshold mechanical input. This explains why noxious thermal input makes spinal circuits prone to catastrophic sensitization

Heterogeneous disease-propagating stem cells in juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is a poor-prognosis childhood leukemia usually caused by RAS-pathway mutations. The cellular hierarchy in JMML is poorly characterized, including the identity of leukemia stem cells (LSCs). FACS and single-cell RNA sequencing reveal marked heterogeneity of JMML hematopoietic stem/progenitor cells (HSPCs), including an aberrant Lin-CD34+CD38-CD90+CD45RA+ population. Single-cell HSPC index-sorting and clonogenic assays show that (1) all somatic mutations can be backtracked to the phenotypic HSC compartment, with RAS-pathway mutations as a "first hit,"(2) mutations are acquired with both linear and branching patterns of clonal evolution, and (3) mutant HSPCs are present after allogeneic HSC transplant before molecular/clinical evidence of relapse. Stem cell assays reveal interpatient heterogeneity of JMML LSCs, which are present in, but not confined to, the phenotypic HSC compartment. RNA sequencing of JMML LSC reveals upregulation of stem cell and fetal genes (HLF, MEIS1, CNN3, VNN2, and HMGA2) and candidate therapeutic targets/biomarkers (MTOR, SLC2A1, and CD96), paving the way for LSC-directed disease monitoring and therapy in this disease

Role of natural killer T cells in the pathogenesis of dengue infections

Objectives: The dengue virus exploits cellular lipid metabolism pathways and natural killer T cells (iNKT), which recognize glycolipids have been suggested to play a role in mouse models of acute dengue. Therefore, we set out to determine if iNKT cells play a role in acute dengue infectionMethods: The frequency of iNKT cells (CD3+, Vα24+) was determined in 49 acute dengue and 22 healthy individuals. The functionality and phenotype of iNKT cell subsets were defined only in 19 patients and 10 controls by flow cytometry. Clinical disease severity was determined by the WHO 2011 guidelinesResults: The proportion of iNKTs in patients with acute dengue were significantly higher (P=0.03) compared to healthy individuals. We found that the CD4+ iNKTs, which produce inflammatory cytokines and are less cytotoxic, were significantly expanded (p=0.01) in acute dengue. iNKTs of patients were also significantly (p=0.02) more activated (both CD38+ and HLA-DR+), that iNKT cell activation significantly and positively correlated with dengue-specific IgG antibody titres (Spearmans’ r=0.5018, P=0.03). iNKT of patients were also predominantly of the immature phenotype, as the expression of CD161 was significantly more than in healthy individuals (p=0.01).Conclusions: As the iNKT cell population, especially of the CD4+ T cell subset appears to be highly activated and expanded in acute dengue, iNKT cells could be contributing to the pathogenesis of dengue infection

Linking Inflammation to Natural Killer T Cell Activation

Immune activation is often associated with inflammation, but inflammation's role in the expansion of antigen-specific immune responses remains unclear. This primer focuses on recent findings that show how specific natural killer T cells are activated by inflammatory messengers, thus illuminating the cellular and molecular links between immunity and inflammation

Observations of Prolific Transient Luminous Event Production Above a Mesoscale Convective System in Argentina During the Sprite2006 Campaign in Brazil

On the night of 22–23 February 2006, 444 transient luminous events (TLEs), 86% sprites, were observed above a prolific mesoscale convective system (MCS) over Argentina, as part of the third sprite campaign in Brazil. GOES infrared (IR) cloud top temperatures (Tc) and Tropical Rainfall Measuring Mission (TRMM) radar (PR) and microwave (TMI) data were used to investigate the MCS convective characteristics and their relationship with World Wide Location Network (WWLLN) detected cloud‐to‐ground (CG) lightning and TLE activity. The MCS had a minimum lifetime of 20 hours, 8.5 as a MCS, a maximum extent of ∼430,000 km2, and gusty winds of ∼39–50 km/h. It had several distinctive characteristics: exceptionally high TLE rate, multicellular structure with 19 distinguishable convective regions, and cloud tops temperatures (Tc) ∼10–20 °C higher than regular TLEproducing MCSs over the central USA and South America. Most TLEs occurred above “individual stratiform regions”, where Tc varied from −45 °C to −53 °C from the beginning to the end of the night, surrounding the areas of strong convections, with convective cores at Tc −59 °C to −74 °C, which did not extend up to or overshoot the tropopause, estimated at −75 °C (∼17.1 km) as normally observed for TLE‐producing MCS in these regions. The moderated convection is contrary to the expectation that large charge production is accompanied by vigorous updrafts within deep convection that give rise to cold cloud overshooting tops, thus prompting a detailed study of this prolific TLE‐producing thunderstorm. On the basis of a charge moment change threshold of 350 Ckm and estimated 5 km charge removal altitude, a lower threshold of ∼4,300 C/h was estimated for the hourly charge transfer rate necessary for the observed sprite production (383 events), which is twice the rate for an average TLE‐producingMCS (70 events), also estimated.TMI/TRMM data for the storm at early development showed a low brightness temperature of 84 K, indicative of significant ice content, which is important for cloud electrification processes. We suggest that the unusually high incidence of TLEs in this moderately convective MCS may be related to other local geophysical phenomena such as a large tropospheric aerosol concentration due to smoke from forest fires. Satellite fire count data showed that there were ∼200 fires between 20 and 22 February immediately north of the MCS initiation region and a transport simulation with the Coupled Aerosol‐Tracer Transport model from the Brazilian developments on Regional Atmospheric Modeling System (CATT/BRAMS) model showed a large PM2.5 aerosol concentration, 10,000 mg/m2 (column integrated), at the region where the MCS developed. The aerosols present in the smoke may have been a source of ice nuclei affecting the production of ice particles that get positively charged, accounting for the charge transfer rate necessary to originate the observed TLE production

HSV-2 Infection of Dendritic Cells Amplifies a Highly Susceptible HIV-1 Cell Target

Herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection and, although several reports describe the interaction between these two viruses, the exact mechanism for this increased susceptibility remains unclear. Dendritic cells (DCs) at the site of entry of HSV-2 and HIV-1 contribute to viral spread in the mucosa. Specialized DCs present in the gut-associated lymphoid tissues produce retinoic acid (RA), an important immunomodulator, able to influence HIV-1 replication and a key mediator of integrin α4β7 on lymphocytes. α4β7 can be engaged by HIV-1 on the cell-surface and CD4+ T cells expressing high levels of this integrin (α4β7high) are particularly susceptible to HIV-1 infection. Herein we provide in-vivo data in macaques showing an increased percentage of α4β7high CD4+ T cells in rectal mucosa, iliac lymph nodes and blood within 6 days of rectal exposure to live (n = 11), but not UV-treated (n = 8), HSV-2. We found that CD11c+ DCs are a major target of HSV-2 infection in in-vitro exposed PBMCs. We determined that immature monocyte-derived DCs (moDCs) express aldehyde dehydrogenase ALDH1A1, an enzyme essential for RA production, which increases upon HSV-2 infection. Moreover, HSV-2-infected moDCs significantly increase α4β7 expression on CD4+ T lymphocytes and HIV-1 infection in DC-T cell mixtures in a RA-dependent manner. Thus, we propose that HSV-2 modulates its microenviroment, influencing DC function, increasing RA production capability and amplifying a α4β7highCD4+ T cells. These factors may play a role in increasing the susceptibility to HIV-1