Detection of Bronchiolitis Obliterans Syndrome Following Pediatric Hematopoietic Stem Cell Transplantation. An Official American Thoracic Society Clinical Practice Guideline.

BACKGROUND: Many children undergo allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for the treatment of malignant and non-malignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common non-infectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent National Institutes of Health workshop highlighted the need for a standardized approach to post-HSCT monitoring. As such, this guideline provides an evidence-based approach to detection of post-HSCT BOS in children. METHODS: A multinational, multidisciplinary panel of experts identified six questions regarding surveillance for, and evaluation of post-HSCT BOS in children. Systematic review of the literature was undertaken to answer each question. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of recommendations. RESULTS: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations addressing the role of screening pulmonary function testing and diagnostic tests in children with suspected post-HSCT BOS were made. Following a Delphi process, new diagnostic criteria for pediatric post-HSCT BOS were also proposed. CONCLUSIONS: This document provides an evidence-based approach to detection of post-HSCT BOS in children, while also highlighting considerations for implementation of each recommendation. Further, the document describes important areas for future research.

Reactive astrocytes associated with prion disease impair the blood brain barrier.

BACKGROUND: Impairment of the blood-brain barrier (BBB) is considered to be a common feature among neurodegenerative diseases, including Alzheimer's, Parkinson's and prion diseases. In prion disease, increased BBB permeability was reported 40 years ago, yet the mechanisms behind the loss of BBB integrity have never been explored. Recently, we showed that reactive astrocytes associated with prion diseases are neurotoxic. The current work examines the potential link between astrocyte reactivity and BBB breakdown. RESULTS: In prion-infected mice, the loss of BBB integrity and aberrant localization of aquaporin 4 (AQP4), a sign of retraction of astrocytic endfeet from blood vessels, were noticeable prior to disease onset. Gaps in cell-to-cell junctions along blood vessels, together with downregulation of Occludin, Claudin-5 and VE-cadherin, which constitute tight and adherens junctions, suggested that loss of BBB integrity is linked with degeneration of vascular endothelial cells. In contrast to cells isolated from non-infected adult mice, endothelial cells originating from prion-infected mice displayed disease-associated changes, including lower levels of Occludin, Claudin-5 and VE-cadherin expression, impaired tight and adherens junctions, and reduced trans-endothelial electrical resistance (TEER). Endothelial cells isolated from non-infected mice, when co-cultured with reactive astrocytes isolated from prion-infected animals or treated with media conditioned by the reactive astrocytes, developed the disease-associated phenotype observed in the endothelial cells from prion-infected mice. Reactive astrocytes were found to produce high levels of secreted IL-6, and treatment of endothelial monolayers originating from non-infected animals with recombinant IL-6 alone reduced their TEER. Remarkably, treatment with extracellular vesicles produced by normal astrocytes partially reversed the disease phenotype of endothelial cells isolated from prion-infected animals. CONCLUSIONS: To our knowledge, the current work is the first to illustrate early BBB breakdown in prion disease and to document that reactive astrocytes associated with prion disease are detrimental to BBB integrity. Moreover, our findings suggest that the harmful effects are linked to proinflammatory factors secreted by reactive astrocytes.

A 5'-Flanking C/G Pair at the Core Region Enhances the Recognition and Binding of Kaiso to Methylated DNA.

Methyl CpG binding proteins (MBPs) are transcription factors that recognize the methylated CpG sites in DNA and mediate the DNA methylation signal into various downstream cellular processes. The C2H2 zinc finger (ZF) protein, Kaiso, also an MBP, preferentially binds to two symmetrically methylated CpG sites in DNA sequences via C-terminal C2H2 ZF domains and mediates the transcription regulation process. Investigation of the molecular mechanism of the recognition of methylated DNA (meDNA) by Kaiso is important to understand how this protein reads and translates this methylation signal into downstream transcription outcomes. Despite previous studies in Kaiso-meDNA interactions, detailed structural investigations on the sequence-specific interaction of Kaiso with the meDNA sequence are still lacking. In this work, we used molecular modeling and molecular dynamics (MD) simulation-based computational approaches to investigate the recognition of various methylated DNA sequences by Kaiso. Our MD simulation results show that the Kaiso-meDNA interaction is sequence specific. The recognition of meDNA by Kaiso is enhanced in the MeECad sequence compared to the MeCG2 sequence. Compared to the 5'-flanking T/A pair in MeCG2, both MeCG2_mutCG and MeECad sequences show that a C/G base pair allows GLU535 of Kaiso to preferably recognize and bind the core mCpG site. The core mCGmCG site is crucial for the recognition process and formation of a stable complex. Our results reveal that the 5'-flanking nucleotides are also important for the enhanced binding and recognition of methylated sites.

Invasive Ventilatory Support in Patients With Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVE: To provide evidence for the Second Pediatric Acute Lung Injury Consensus Conference updated recommendations and consensus statements for clinical practice and future research on invasive mechanical ventilation support of patients with pediatric acute respiratory distress syndrome (PARDS). DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included clinical studies of critically ill patients undergoing invasive mechanical ventilation for PARDS, January 2013 to April 2022. In addition, meta-analyses and systematic reviews focused on the adult acute respiratory distress syndrome population were included to explore new relevant concepts (e.g., mechanical power, driving pressure, etc.) still underrepresented in the contemporary pediatric literature. DATA EXTRACTION: Title/abstract review, full text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize relevant evidence and develop recommendations, good practice statements and research statements. We identified 26 pediatric studies for inclusion and 36 meta-analyses or systematic reviews in adults. We generated 12 recommendations, two research statements, and five good practice statements related to modes of ventilation, tidal volume, ventilation pressures, lung-protective ventilation bundles, driving pressure, mechanical power, recruitment maneuvers, prone positioning, and high-frequency ventilation. Only one recommendation, related to use of positive end-expiratory pressure, is classified as strong, with moderate certainty of evidence. CONCLUSIONS: Limited pediatric data exist to make definitive recommendations for the management of invasive mechanical ventilation for patients with PARDS. Ongoing research is needed to better understand how to guide best practices and improve outcomes for patients with PARDS requiring invasive mechanical ventilation.

Alzheimer's disease-associated ß-amyloid does not protect against herpes simplex virus 1 infection in the mouse brain.

Alzheimer's disease (AD) is a devastating fatal neurodegenerative disease. An alternative to the amyloid cascade hypothesis is that a viral infection is key to the etiology of late-onset AD, with ß-amyloid (Aß) peptides playing a protective role. In the current study, young 5XFAD mice that overexpress mutant human amyloid precursor protein with the Swedish, Florida, and London familial AD mutations were infected with one of two strains of herpes simplex virus 1 (HSV-1), 17syn+ and McKrae, at three different doses. Contrary to previous work, 5XFAD genotype failed to protect mice against HSV-1 infection. The region- and cell-specific tropisms of HSV-1 were not affected by the 5XFAD genotype, indicating that host-pathogen interactions were not altered. Seven- to ten-month-old 5XFAD animals in which extracellular Aß aggregates were abundant showed slightly better survival rate relative to their wild-type (WT) littermates, although the difference was not statistically significant. In these 5XFAD mice, HSV-1 replication centers were partially excluded from the brain areas with high densities of Aß aggregates. Aß aggregates were free of HSV-1 viral particles, and the limited viral invasion to areas with a high density of Aß aggregates was attributed to phagocytic activity of reactive microglia. In the oldest mice (12-15 months old), the survival rate did not differ between 5XFAD and WT littermates. While the current study questions the antiviral role of Aß, it neither supports nor refutes the viral etiology hypothesis of late-onset AD.

Sequence Analysis of Novel Staphylococcus aureus Lineages from Wild and Captive Macaques.

Staphylococcus aureus is a widespread and common opportunistic bacterium that can colonise or infect humans as well as a wide range of animals. There are a few studies of both methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolated from monkeys, apes, and lemurs, indicating a presence of a number of poorly or unknown lineages of the pathogen. In order to obtain insight into staphylococcal diversity, we sequenced strains from wild and captive individuals of three macaque species (Macaca mulatta, M. assamensis, and M. sylvanus) using Nanopore and Illumina technologies. These strains were previously identified by microarray as poorly or unknown strains. Isolates of novel lineages ST4168, ST7687, ST7688, ST7689, ST7690, ST7691, ST7692, ST7693, ST7694, ST7695, ST7745, ST7746, ST7747, ST7748, ST7749, ST7750, ST7751, ST7752, ST7753, and ST7754 were sequenced and characterised for the first time. In addition, isolates belonging to ST2990, a lineage also observed in humans, and ST3268, a MRSA strain already known from macaques, were also included into the study. Mobile genetic elements, genomic islands, and carriage of prophages were analysed. There was no evidence for novel host-specific virulence factors. However, a conspicuously high rate of carriage of a pathogenicity island harbouring edinB and etD2/etE as well as a higher number of repeat units within the gene sasG (encoding an adhesion factor) than in human isolates were observed. None of the strains harboured the genes encoding Panton-Valentine leukocidin. In conclusion, wildlife including macaques may harbour an unappreciated diversity of S. aureus lineages that may be of clinical relevance for humans, livestock, or for wildlife conservation, given the declining state of many wildlife populations.

Structural insights into the repair mechanism of AGT for methyl-induced DNA damage.

Methylation induced DNA base-pairing damage is one of the major causes of cancer. O6-alkylguanine-DNA alkyltransferase (AGT) is considered a demethylation agent of the methylated DNA. Structural investigations with thermodynamic properties of the AGT-DNA complex are still lacking. In this report, we modeled two catalytic states of AGT-DNA interactions and an AGT-DNA covalent complex and explored structural features using molecular dynamics (MD) simulations. We utilized the umbrella sampling method to investigate the changes in the free energy of the interactions in two different AGT-DNA catalytic states, one with methylated GUA in DNA and the other with methylated CYS145 in AGT. These non-covalent complexes represent the pre- and post-repair complexes. Therefore, our study encompasses the process of recognition, complex formation, and separation of the AGT and the damaged (methylated) DNA base. We believe that the use of parameters for the amino acid and nucleotide modifications and for the protein-DNA covalent bond will allow investigations of the DNA repair mechanism as well as the exploration of cancer therapeutics targeting the AGT-DNA complexes at various functional states as well as explorations via stabilization of the complex.

Global fading of the temperature-growth coupling at alpine and polar treelines.

Climate warming is expected to positively alter upward and poleward treelines which are controlled by low temperature and a short growing season. Despite the importance of treelines as a bioassay of climate change, a global field assessment and posterior forecasting of tree growth at annual scales is lacking. Using annually resolved tree-ring data located across Eurasia and the Americas, we quantified and modeled the relationship between temperature and radial growth at treeline during the 20th century. We then tested whether this temperature-growth association will remain stable during the 21st century using a forward model under two climate scenarios (RCP 4.5 and 8.5). During the 20th century, growth enhancements were common in most sites, and temperature and growth showed positive trends. Interestingly, the relationship between temperature and growth trends was contingent on tree age suggesting biogeographic patterns in treeline growth are contingent on local factors besides climate warming. Simulations forecast temperature-growth decoupling during the 21st century. The growing season at treeline is projected to lengthen and growth rates would increase and become less dependent on temperature rise. These forecasts illustrate how growth may decouple from climate warming in cold regions and near the margins of tree existence. Such projected temperature-growth decoupling could impact ecosystem processes in mountain and polar biomes, with feedbacks on climate warming.

Thresholds for oximetry alarms and target range in the NICU: an observational assessment based on likely oxygen tension and maturity.

BACKGROUND: Continuous monitoring of SpO2 in the neonatal ICU is the standard of care. Changes in SpO2 exposure have been shown to markedly impact outcome, but limiting extreme episodes is an arduous task. Much more complicated than setting alarm policy, it is fraught with balancing alarm fatigue and compliance. Information on optimum strategies is limited. METHODS: This is a retrospective observational study intended to describe the relative chance of normoxemia, and risks of hypoxemia and hyperoxemia at relevant SpO2 levels in the neonatal ICU. The data, paired SpO2-PaO2 and post-menstrual age, are from a single tertiary care unit. They reflect all infants receiving supplemental oxygen and mechanical ventilation during a 3-year period. The primary measures were the chance of normoxemia (PaO2 50-80 mmHg), risks of severe hypoxemia (PaO2 ≤ 40 mmHg), and of severe hyperoxemia (PaO2 ≥ 100 mmHg) at relevant SpO2 levels. RESULTS: Neonates were categorized by postmenstrual age: < 33 (n = 155), 33-36 (n = 192) and > 36 (n = 1031) weeks. From these infants, 26,162 SpO2-PaO2 pairs were evaluated. The post-menstrual weeks (median and IQR) of the three groups were: 26 (24-28) n = 2603; 34 (33-35) n = 2501; and 38 (37-39) n = 21,058. The chance of normoxemia (65, 95%-CI 64-67%) was similar across the SpO2 range of 88-95%, and independent of PMA. The increasing risk of severe hypoxemia became marked at a SpO2 of 85% (25, 95%-CI 21-29%), and was independent of PMA. The risk of severe hyperoxemia was dependent on PMA. For infants < 33 weeks it was marked at 98% SpO2 (25, 95%-CI 18-33%), for infants 33-36 weeks at 97% SpO2 (24, 95%-CI 14-25%) and for those > 36 weeks at 96% SpO2 (20, 95%-CI 17-22%). CONCLUSIONS: The risk of hyperoxemia and hypoxemia increases exponentially as SpO2 moves towards extremes. Postmenstrual age influences the threshold at which the risk of hyperoxemia became pronounced, but not the thresholds of hypoxemia or normoxemia. The thresholds at which a marked change in the risk of hyperoxemia and hypoxemia occur can be used to guide the setting of alarm thresholds. Optimal management of neonatal oxygen saturation must take into account concerns of alarm fatigue, staffing levels, and FiO2 titration practices.

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection.

The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/ß) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue. We infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNA-sequencing and functional assays. The dominant transcriptional pathway induced by HRV infection is a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activate IFN-stimulated genes. However, this endogenous response does not restrict HRV replication because replication-competent HRV antagonizes the type III IFN response at pre- and posttranscriptional levels. In contrast, exogenous IFN treatment restricts HRV replication, with type I IFN being more potent than type III IFN, suggesting that extraepithelial sources of type I IFN may be the critical IFN for limiting enteric virus replication in the human intestine.

Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline.

BACKGROUND: This Guideline, a collaborative effort from the American Thoracic Society, Society of Thoracic Surgeons, and Society of Thoracic Radiology, aims to provide evidence-based recommendations to guide contemporary management of patients with a malignant pleural effusion (MPE). METHODS: A multidisciplinary panel developed seven questions using the PICO (Population, Intervention, Comparator, and Outcomes) format. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the Evidence to Decision framework was applied to each question. Recommendations were formulated, discussed, and approved by the entire panel. RESULTS: The panel made weak recommendations in favor of: 1) using ultrasound to guide pleural interventions; 2) not performing pleural interventions in asymptomatic patients with MPE; 3) using either an indwelling pleural catheter (IPC) or chemical pleurodesis in symptomatic patients with MPE and suspected expandable lung; 4) performing large-volume thoracentesis to assess symptomatic response and lung expansion; 5) using either talc poudrage or talc slurry for chemical pleurodesis; 6) using IPC instead of chemical pleurodesis in patients with nonexpandable lung or failed pleurodesis; and 7) treating IPC-associated infections with antibiotics and not removing the catheter. CONCLUSIONS: These recommendations, based on the best available evidence, can guide management of patients with MPE and improve patient outcomes.

The complete genomic sequence of Streptomyces spectabilis NRRL-2792 and identification of secondary metabolite biosynthetic gene clusters.

This is the first report of a fully annotated genomic sequence of Streptomyces spectabilis NRRL-2792, isolated and identified by The Upjohn Company in 1961. The genome was assembled into a single scaffold for annotation and analysis. The chromosome is linear, 9.5 Mb in size which is one of the largest Streptomyces genomes yet described, has a G+C content of 72%, and encodes for approximately 7943 genes. Antibiotic Secondary Metabolite Analysis Shell (antiSMASH) and Basic Local Alignment Search Tool (BLAST) bioinformatics analyses identified six complete secondary metabolite biosynthetic gene clusters for ectoine, melanin, albaflavenone, spectinomycin, 2-methylisoborneol and coelichelin. Additionally, biosynthetic clusters were identified that shared ≥ 90% gene content with complestatin, hopene, neoaureothin, or undecylprodigiosin. Thirty-one other likely secondary metabolite gene clusters were identified by antiSMASH. BLAST identified two subsets of undecylprodigiosin biosynthetic genes at polar opposites of the chromosome; their duplication was subsequently confirmed by primer walking.

Non-Linear Dynamical Analysis of Resting Tremor for Demand-Driven Deep Brain Stimulation.

Parkinson's Disease (PD) is currently the second most common neurodegenerative disease. One of the most characteristic symptoms of PD is resting tremor. Local Field Potentials (LFPs) have been widely studied to investigate deviations from the typical patterns of healthy brain activity. However, the inherent dynamics of the Sub-Thalamic Nucleus (STN) LFPs and their spatiotemporal dynamics have not been well characterized. In this work, we study the non-linear dynamical behaviour of STN-LFPs of Parkinsonian patients using ε -recurrence networks. RNs are a non-linear analysis tool that encodes the geometric information of the underlying system, which can be characterised (for example, using graph theoretical measures) to extract information on the geometric properties of the attractor. Results show that the activity of the STN becomes more non-linear during the tremor episodes and that ε -recurrence network analysis is a suitable method to distinguish the transitions between movement conditions, anticipating the onset of the tremor, with the potential for application in a demand-driven deep brain stimulation system.

Smallholder farmers' willingness to pay for scale-appropriate farm mechanization: Evidence from the mid-hills of Nepal.

This paper analyzes smallholder farmers' willingness to pay (WTP) for the purchase of scale-appropriate farm mechanization in the hill ecologies of Nepal using the case of mini-tiller technology: a small, 5-7 horsepower two-wheel tractor primarily used for agricultural land preparation. Using primary survey data from 628 randomly-selected households, we find that farm size, local wage rates, out-migration, access to credit services, and associations with agricultural cooperatives positively influence the WTP for mini-tillers while the number of draft animals owned negatively influence the WTP for mini-tillers. On average, farmers were willing to pay 31% less than the actual price of a mini-tiller. Results also exhibited a heterogeneous demand in which the lowest quartile farm size households, typically the poorest farm households, were willing to pay 26% less for the mini-tiller than the top quartile of farms. In the context of labor scarcity and rising rural wages, agricultural policy on farm mechanization in Nepal should aim to prioritize small farms through robust service provision models in order to increase the level of farm mechanization in the country.

Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology.

UNLABELLED: Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE: Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of gastrointestinal infections such as HRV infection. HRVs remain a major worldwide cause of diarrhea-associated morbidity and mortality in children ≤5 years of age. Current in vitro models of rotavirus infection rely primarily on the use of animal rotaviruses because HRV growth is limited in most transformed cell lines and animal models. We demonstrate that HIEs are novel, cellularly diverse, and physiologically relevant epithelial cell cultures that recapitulate in vivo properties of HRV infection. HIEs will allow the study of HRV biology, including human host-pathogen and live, attenuated vaccine interactions; host and cell type restriction; virus-induced fluid secretion; cell-cell communication within the epithelium; and the epithelial response to infection in cultures from genetically diverse individuals. Finally, drug therapies to prevent/treat diarrheal disease can be tested in these physiologically active cultures.

Colloidal Vesicular System of Inositol Hexaphosphate to Counteract DMBA Induced Dysregulation of Markers Pertaining to Cellular Proliferation/Differentiation and Inflammation of Epidermal Layer in Mouse Model.

Cancer is a global health problem and chemoprevention is a promising approach for reducing cancer burden. Inositol hexaphosphate (IP6), a natural bioactive constituent of cereals, legumes, etc., has momentous potential as an antiangiogenic agent, that specifically affects malignant cells. The shortcoming is its quick absorption on oral/topical administration. Niosomes are flexible carriers for topical drug delivery. The central venture of current research was to optimize and characterize niosomal delivery system of IP6 for treatment of skin cancer. Thin film hydration method was utilized to prepare IP6 niosomes, and these were dispersed as a suspension in a suitable base. Developed formulations were analyzed for various physicochemical and pharmacological parameters such as particle size, encapsulation efficiency, morphology, drug release, texture analysis, irritability, cell line studies, Western blotting, RT-PCR, and histopathology. IP6 niosomal suspension and IP6 in acetone displayed IC50 value at the concentration of 0.96 mM (0.63 mg/mL) and 1.39 mM (0.92 mg/mL), respectively. IP6 niosomal suspension showed significantly higher (p < 0.05) activity and showed cytotoxic effect in SK-MEL-2 cancer cell line. Crucial events of cellular proliferation and differentiation, like expression of ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), cycloxygenase-2 (COX-2) and Cyclin D1 were initiated from the fourth hour through application of 7,12-dimethylbenzanthracene (DMBA) on albino mice. The DMBA altered expression of aforesaid enzymes was significantly (P < 0.001) prevented by concomitant application of niosomal formulations. Results of cell line study, Western blotting, RT-PCR, and histopathology suggested that IP6 niosomal suspension could constitute a promising approach for prevention of cellular proliferation as well as DMBA induced dysregulation of cellular proliferation/differentiation and inflammation.

Neural breathing pattern in newborn infants pre- and postextubation.

AIM: To describe the neural breathing pattern before and after extubation in newborn infants. METHODS: Prospective, observational study. In infants deemed ready for extubation, the diaphragm electrical activity (EAdi) was continuously recorded from 30 minute before to two hours after extubation. RESULTS: Total of 25 neonates underwent 29 extubations; 10 extubations resulted in re-intubation within 72 hours. Postextubation, there was an increase in peak EAdi (EAdi-max) and EAdi-delta (peak minus minimum EAdi) in both groups. The pre- to postextubation change in EAdi-max (8.9-11.1 µv) and EAdi-delta (6-8 µv) was less in the failure group in comparison with the change in EAdi-max (10.2-13.4 µv) and EAdi-delta (6.3-10.6 µv) in the success group, (p = 0.02 and 0.01, respectively). CONCLUSION: In our neonatal cohort, extubation failure was associated with a smaller increase in peak and delta EAdi after extubation. If confirmed, these findings indicate an important cause of extubation failure in preterm infants.