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1.
Paediatr Anaesth ; 34(6): 568-574, 2024 06.
Article in English | MEDLINE | ID: mdl-38379426

ABSTRACT

BACKGROUND: The need for dental rehabilitation under general anesthesia is increasing, with varying needs between patients. Mortality has been found to be a rare event in these patients; however other perioperative events can and do occur. Previous studies have established increased incidence of perioperative events with younger, sicker children, and longer anesthetics, however, no studies to date have evaluated if the incidence of perioperative events is more closely associated with one long anesthetic or multiple anesthetics per patient. AIMS: To evaluate the association of perioperative events related to single anesthetic duration or number of anesthetics per patient for dental rehabilitation. METHODS: After Children's Wisconsin Human Research Protection Program determined this quality activity did not meet the definition of human subjects research, we performed an epidemiologic observational evaluation by extracting all dental related cases (dental alone or with oral surgeon vs. dental with other specialties) with an associated general anesthesia encounter from Children's Wisconsin electronic data warehouse from June 1, 2015 to December 31, 2021. These cases occurred at a free-standing children's hospital or associated pediatric-only ambulatory surgery center. The risk of perioperative safety events was analyzed for previously identified risk groups such as American Society of Anesthesiologists Physical Status (ASA-PS), patient age, anesthesia case time with the addition of number of dental cases per patient. RESULTS: In this study, 8468 procedures were performed on 8082 patients. Of this cohort, 7765 patients underwent one procedure for dental care while 317 patients underwent a total of 703 dental-related procedures, ranging from two to five procedures per patient. Multivariable logistic regression identified increased risk of perioperative events in patients with ASA-PS 3 (n = 1459, rate 1.78%, p value .001, OR 5.7, CI 2.1-15.5) and ASA-PS 4 (n = 86, rate 5.8%, p < .001, OR 17.2, CI 4.4-67.3), anesthesia duration (p < .001, OR 1.46, CI 1.21-1.76), but no increased risk with number of anesthetics per patient (p value .54, OR 0.81, CI 0.4-1.61). CONCLUSIONS: Limiting dental care under general anesthesia to multiple short cases may decrease the risk of perioperative events when compared to completing all treatment in one long operative session.


Subject(s)
Anesthesia, General , Humans , Child , Female , Male , Child, Preschool , Anesthesia, General/methods , Anesthesia, General/adverse effects , Adolescent , Patient Safety , Wisconsin/epidemiology , Infant , Time Factors
2.
Public Health ; 217: 89-94, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36867987

ABSTRACT

OBJECTIVES: This national survey aimed to explore how existing pandemic preparedness plans (PPP) accounted for the demands placed on infection prevention and control (IPC) services in acute and community settings in England during the first wave of the COVID-19 pandemic. STUDY DESIGN: This was a cross-sectional survey of IPC leaders working within National Health Service Trusts or clinical commissioning groups/integrated care systems in England. METHODS: The survey questions related to organisational COVID-19 preparedness pre-pandemic and the response provided during the first wave of the pandemic (January to July 2020). The survey ran from September to November 2021, and participation was voluntary. RESULTS: In total, 50 organisations responded. Seventy-one percent (n = 34/48) reported having a current PPP in December 2019, with 81% (n = 21/26) indicating their plan was updated within the previous 3 years. Around half of IPC teams were involved in previous testing of these plans via internal and multi-agency tabletop exercises. Successful aspects of pandemic planning were identified as command structures, clear channels of communication, COVID-19 testing, and patient pathways. Key deficiencies were lack of personal protective equipment, difficulties with fit testing, keeping up to date with guidance, and insufficient staffing. CONCLUSIONS: Pandemic plans need to consider the capability and capacity of IPC services to ensure they can contribute their critical knowledge and expertise to the pandemic response. This survey provides a detailed evaluation of how IPC services were impacted during the first wave of the pandemic and identifies key areas, which need to be included in future PPP to better manage the impact on IPC services.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Pandemics/prevention & control , COVID-19 Testing , Cross-Sectional Studies , State Medicine , Infection Control
3.
Phys Rev Lett ; 128(8): 083001, 2022 Feb 25.
Article in English | MEDLINE | ID: mdl-35275674

ABSTRACT

Photoelectron interferometry with femtosecond and attosecond light pulses is a powerful probe of the fast electron wave-packet dynamics, albeit it has practical limitations on the energy resolution. We show that one can simultaneously obtain both high temporal and spectral resolution by stimulating Raman interferences with one light pulse and monitoring the modification of the electron yield in a separate step. Applying this spectroscopic approach to the autoionizing states of argon, we experimentally resolved its electronic composition and time evolution in exquisite detail. Theoretical calculations show remarkable agreement with the observations and shed light on the light-matter interaction parameters. Using appropriate Raman probing and delayed detection steps, this technique enables highly sensitive probing and control of electron dynamics in complex systems.

4.
Br J Surg ; 108(9): 1090-1096, 2021 09 27.
Article in English | MEDLINE | ID: mdl-33975337

ABSTRACT

BACKGROUND: Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with health-related quality of life. METHODS: This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models. RESULTS: Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms. CONCLUSION: A long-term symptom burden is common after oesophageal cancer surgery.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/methods , Patient Reported Outcome Measures , Postoperative Complications/epidemiology , Aged , Cross-Sectional Studies , Europe/epidemiology , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Quality of Life , Retrospective Studies , Time Factors , Treatment Outcome
5.
Ann Oncol ; 31(9): 1240-1250, 2020 09.
Article in English | MEDLINE | ID: mdl-32473302

ABSTRACT

BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. RESULTS: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. CONCLUSION: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.


Subject(s)
Cystadenocarcinoma, Serous , Ovarian Neoplasms , Cystadenocarcinoma, Serous/genetics , Female , Humans , Ovarian Neoplasms/genetics , Prognosis , Proportional Hazards Models , Survival Analysis , Transcriptome
6.
Mol Psychiatry ; 23(11): 2156-2166, 2018 11.
Article in English | MEDLINE | ID: mdl-28993710

ABSTRACT

Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible 'knockdown' mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3-4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin-5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder.


Subject(s)
Claudin-5/genetics , Claudin-5/physiology , Schizophrenia/metabolism , 22q11 Deletion Syndrome/genetics , 22q11 Deletion Syndrome/psychology , Animals , Blood-Brain Barrier/metabolism , Brain/metabolism , Disease Models, Animal , Endothelial Cells/metabolism , Female , Gene Expression Profiling/methods , HEK293 Cells , Humans , Male , Mice , Mice, Inbred C57BL , Schizophrenia/physiopathology , Tight Junctions
7.
Eur J Clin Microbiol Infect Dis ; 36(1): 33-42, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27638007

ABSTRACT

Patients with end-stage renal failure undergo regular haemodialysis (HD) and often develop episodes of Staphylococcus aureus bloodstream infection (BSI), which can re-occur. However, clinically, patients on HD, with S. aureus BSI, respond well to treatment, rarely developing overt signs of sepsis. We investigated the contributions of bacterial virulence and cytokine responses to the clinical course of S. aureus BSI in HD and non-HD patients. Seventy patients were recruited, including 27 (38.6 %) patients on HD. Isolates were spa-typed and virulence and antimicrobial resistance gene carriage was investigated using DNA microarray analysis. Four inflammatory cytokines, IL-6, RANTES, GROγ and leptin, were measured in patient plasma on the day of diagnosis and after 7 days. There was no significant difference in the prevalence of genotypes or antimicrobial resistance genes in S. aureus isolates from HD compared to non-HD patients. The enterotoxin gene cluster (containing staphylococcal enterotoxins seg, sei, sem, sen, seo and seu) was significantly less prevalent among BSI isolates from HD patients compared to non-HD patients. Comparing inflammatory cytokine response to S. aureus BSI in HD patients to non-HD patients, IL-6 and GROγ were significantly lower (p = 0.021 and p = 0.001, respectively) in HD patients compared to other patients on the day of diagnosis and RANTES levels were significantly lower (p = 0.025) in HD patients on day 7 following diagnosis. Lowered cytokine responses in HD patients and a reduced potential for super-antigen production by infecting isolates may partly explain the favourable clinical responses to episodes of S. aureus BSI in HD patients that we noted clinically.


Subject(s)
Bacteremia/pathology , Cytokines/blood , Enterotoxins/genetics , Renal Dialysis/adverse effects , Staphylococcal Infections/pathology , Staphylococcus aureus/genetics , Aged , Aged, 80 and over , Bacteremia/microbiology , Female , Humans , Kidney Failure, Chronic/therapy , Male , Microarray Analysis , Microbial Sensitivity Tests , Molecular Typing , Oligonucleotide Array Sequence Analysis , Plasma/chemistry , Prospective Studies , Staphylococcal Infections/microbiology , Staphylococcal Protein A/genetics , Staphylococcus aureus/isolation & purification , Virulence Factors/genetics
8.
Lett Appl Microbiol ; 63(4): 233-9, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27479925

ABSTRACT

UNLABELLED: The human opportunistic pathogen, Acinetobacter baumannii, has the propensity to form biofilms and frequently cause medical device-related infections in hospitals. However, the physio-chemical properties of medical surfaces, in addition to bacterial surface properties, will affect colonization and biofilm development. The objective of this study was to compare the ability of A. baumannii to form biofilms on six different materials common to the hospital environment: glass, porcelain, stainless steel, rubber, polycarbonate plastic and polypropylene plastic. Biofilms were developed on material coupons in a CDC biofilm reactor. Biofilms were visualized and quantified using fluorescent staining and imaged using confocal laser scanning microscopy (CLSM) and by direct viable cell counts. Image analysis of CLSM stacks indicated that the mean biomass values for biofilms grown on glass, rubber, porcelain, polypropylene, stainless steel and polycarbonate were 0·04, 0·26, 0·62, 1·00, 2·08 and 2·70 µm(3) /µm(2) respectively. Polycarbonate developed statistically more biofilm mass than glass, rubber, porcelain and polypropylene. Viable cell counts data were in agreement with the CLSM-derived data. In conclusion, polycarbonate was the most accommodating surface for A. baumannii ATCC 17978 to form biofilms while glass was least favourable. Alternatives to polycarbonate for use in medical and dental devices may need to be considered. SIGNIFICANCE AND IMPACT OF THE STUDY: In the hospital environment, Acinetobacter baumannii is one of the most persistent and difficult to control opportunistic pathogens. The persistence of A. baumannii is due, in part, to its ability to colonize surfaces and form biofilms. This study demonstrates that A. baumannii can form biofilms on a variety of different surfaces and develops substantial biofilms on polycarbonate - a thermoplastic material that is often used in the construction of medical devices. The findings highlight the need to further study the in vitro compatibility of medical materials that could be colonized by A. baumannii and allow it to persist in hospital settings.


Subject(s)
Acinetobacter Infections/microbiology , Acinetobacter baumannii/growth & development , Acinetobacter baumannii/metabolism , Biofilms/growth & development , Equipment and Supplies/microbiology , Opportunistic Infections/microbiology , Ceramics , Colony Count, Microbial , Glass , Hospitals , Humans , Microscopy, Confocal , Polymers , Polypropylenes , Rubber , Stainless Steel , Surface Properties
9.
J Oral Rehabil ; 40(7): 546-61, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23691977

ABSTRACT

The defining characteristic of a profession - and especially a health-care profession - is that the behaviour of its members is proscribed by a formal code of ethics. The main purpose of such codes is to guide practitioners' interactions with patients, assuring that patient interests are protected. In other words, the ethical code requires practitioners to place their patients' needs for proper diagnosis and appropriate treatment ahead of their own needs for income and advancement. The dental profession has a code of ethics that was developed by the American Dental Association many years ago; in most clinical situations, determination of proper behaviour is self-evident. However, the field of temporoman-dibular disorders (TMDs) has been the subject of considerable controversy for over half a century, and many people have argued that this makes it impossible to evaluate various approaches to treatment of TMDs within an ethical framework. In this article, the authors argue that the large volume of scientific evidence in the contemporary TMD literature provides an ethical framework for the diagnosis and treatment of patients with TMDs within a biopsychosocial medical model. They present a summary of the research with contemporary scientific integrity, which has produced that information over a period of many years. Based on that research, they conclude that dentists may provide conservative and reversible treatments that will be successful for most TMDs and in doing so will comply with the profession's code of ethics. Conversely, the authors claim that those dentists who continue to follow the older mechanistic models of TMD aetiology and treatment are not only out of step scientifically, but are placing their patients' welfare at risk by providing unnecessary irreversible bite-changing and jaw-repositioning interventions. Therefore, debate of these issues should not be solely focused on scientific merit, but also upon the compelling ethical obligations that dentists have as a result of the contemporary scientific literature regarding TMDs.


Subject(s)
Ethical Analysis , Ethics, Dental , Evidence-Based Medicine , Temporomandibular Joint Disorders , Codes of Ethics , Humans , Temporomandibular Joint Disorders/diagnosis , Temporomandibular Joint Disorders/therapy
10.
Ir J Psychol Med ; 40(2): 152-165, 2023 06.
Article in English | MEDLINE | ID: mdl-31973774

ABSTRACT

OBJECTIVE: This study examines the association between attention-deficit/hyperactivity disorder (ADHD) and overweight/obesity in a large-scale longitudinal study of children, while controlling for a range of psychosocial factors. METHOD: Data were obtained from Growing Up in Ireland, a nationally representative and longitudinal study of approximately 6500 children who were assessed at 9 and 13 years of age. Body mass index (BMI) was determined using measured height and weight, ADHD status was determined by parent reports of professional diagnoses and ADHD symptoms were measured using the Strengths and Difficulties Questionnaire (SDQ). RESULTS: The associations between ADHD status, ADHD symptoms (SDQ) and BMI category at age 9 and 13 years were evaluated using logistic regression. Adjustments were made for child factors (sex, developmental coordination disorder, emotional symptoms, conduct problems, birth weight and exercise) and parental factors (socio-economic status, parental BMI, parental depression, and maternal smoking and alcohol use during pregnancy). Logistic regression indicated that ADHD status was not associated with BMI category at 9 or at 13 years of age, but children with ADHD at 9 years were significantly more likely to be overweight/obese at 13 years than those without ADHD. However, when other child and parental factors were adjusted for, ADHD status was no longer significantly associated with weight status. Female sex, low levels of exercise, overweight/obese parents and prenatal smoking during pregnancy consistently increased the odds of childhood overweight/obesity. CONCLUSIONS: While ADHD and overweight/obesity co-occur in general populations, this relationship is largely explained by a variety of psychosocial factors.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Overweight , Pregnancy , Child , Humans , Female , Adolescent , Overweight/epidemiology , Overweight/complications , Overweight/diagnosis , Attention Deficit Disorder with Hyperactivity/diagnosis , Longitudinal Studies , Obesity/complications , Obesity/psychology , Body Mass Index
11.
Mol Genet Metab ; 105(2): 249-54, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22137130

ABSTRACT

Most newborn screening (NBS) laboratories use second-tier molecular tests for cystic fibrosis (CF) using dried blood spots (DBS). The Centers for Disease Control and Prevention's NBS Quality Assurance Program offers proficiency testing (PT) in DBS for CF transmembrane conductance regulator (CFTR) gene mutation detection. Extensive molecular characterization on 76 CF patients, family members or screen positive newborns was performed for quality assurance. The coding, regulatory regions and portions of all introns were sequenced and large insertions/deletions were characterized as well as two intronic di-nucleotide microsatellites. For CF patient samples, at least two mutations were identified/verified and four specimens contained three likely CF-associated mutations. Thirty-four sequence variations in 152 chromosomes were identified, five of which were not previously reported. Twenty-seven of these variants were used to predict haplotypes from the major haplotype block defined by HapMap data that spans the promoter through intron 19. Chromosomes containing the F508del (p.Phe508del), G542X (p.Gly542X) and N1303K (p.Asn1303Lys) mutations shared a common haplotype subgroup, consistent with a common ancient European founder. Understanding the haplotype background of CF-associated mutations in the U.S. population provides a framework for future phenotype/genotype studies and will assist in determining a likely cis/trans phase of the mutations without need for parent studies.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/genetics , DNA Mutational Analysis , Haplotypes/genetics , Adolescent , Adult , Cystic Fibrosis/diagnosis , Dried Blood Spot Testing , Female , Genetic Testing , Humans , Linkage Disequilibrium , Male , Microsatellite Repeats , Population , Reference Standards , United States
12.
Cytokine ; 59(2): 195-202, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22579700

ABSTRACT

Toll-like receptors induce a complex inflammatory response that can function to alert the body to infection, neutralize pathogens and repair damaged tissues. Toll-like receptors are expressed on kupffer, endothelial, dendritic, biliary epithelial, hepatic stellate cells, and hepatocytes in the liver. The endoplasmic reticulum (ER) is a central organelle of eukaryotic cells that exists as a place of lipid synthesis, protein folding and protein maturation. The ER is a major signal transduction organelle that senses and responds to changes in homeostasis. Conditions interfering with the function of the ER are collectively known as ER stress and can be induced by accumulation of unfolded protein aggregates or by excessive protein traffic as can occur during viral infection. The ability of ER stress to induce an inflammatory response is considered to play a role in disease pathogenesis. Importantly, ER stress is viewed as a contributor to the pathogenesis of liver diseases with evidence linking components of ER homeostasis as requirements for optimal Toll-like receptor function. In this context this review discusses the association of Toll-like receptors with ER stress. This is an emerging paradigm in the understanding of Toll-like receptor signalling which may have an underlying role in the pathogenesis of liver disease.


Subject(s)
Endoplasmic Reticulum Stress/immunology , Liver Diseases/immunology , Signal Transduction/immunology , Toll-Like Receptors/metabolism , Animals , Humans , Models, Biological , Protein Transport
13.
Thorax ; 66(2): 140-3, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21160087

ABSTRACT

BACKGROUND: Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated. METHODS: This was a cross-sectional case-control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes. RESULTS: The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng/ml vs 4.3 (4.0) ng/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng/ml vs 1.4 (0.9) ng/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status. CONCLUSIONS: Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.


Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Cystic Fibrosis/metabolism , Interleukin-8/analysis , Pepsin A/analysis , Adolescent , Biomarkers/analysis , Case-Control Studies , Child , Child, Preschool , Cystic Fibrosis/complications , Female , Humans , Infant , Male , Respiratory Aspiration/diagnosis , Respiratory Aspiration/etiology
15.
Eur Respir J ; 35(5): 1155-63, 2010 May.
Article in English | MEDLINE | ID: mdl-19840955

ABSTRACT

alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of alpha(1)-AT is produced by the liver, it is also produced by bronchial epithelial cells, amongst others, in the lung. Herein, we investigate the effects of mutant Z alpha(1)-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved. Control, M variant alpha(1)-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-kappaB activation and induced expression of a selection of pro- and anti-apoptotic genes. Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by 57% compared with control cells (p = 0.05) and was a more potent inhibitor than MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated NF-kappaB-dependent gene expression above control or MAAT-expressing cells. In 16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an upstream regulator of NF-kappaB. cIAP1 expression was increased in ZAAT versus MAAT bronchial biopsies. The data suggest a novel mechanism by which ZAAT may promote human bronchial epithelial cell survival.


Subject(s)
Apoptosis/drug effects , Emphysema/metabolism , Epithelial Cells/metabolism , Respiratory Mucosa/metabolism , alpha 1-Antitrypsin/pharmacology , Adult , Biopsy , Blotting, Western , Caspase 3/metabolism , Cell Line , Cell Proliferation , Emphysema/genetics , Female , Gene Expression , Humans , Immunoenzyme Techniques , In Situ Nick-End Labeling , Inhibitor of Apoptosis Proteins/genetics , Male , NF-kappa B/metabolism , Phosphorylation , Reverse Transcriptase Polymerase Chain Reaction , Up-Regulation , alpha 1-Antitrypsin Deficiency/metabolism , bcl-Associated Death Protein/metabolism
16.
J Vet Intern Med ; 24(1): 192-7, 2010.
Article in English | MEDLINE | ID: mdl-19925574

ABSTRACT

BACKGROUND: Nonregenerative cytopenias such as nonregenerative anemia, neutropenia, and thrombocytopenia in cats with feline leukemia virus (FeLV) antigen are assumed to be caused by the underlying FeLV infection. In addition, cats with negative FeLV antigen-test results that have cytopenias of unknown etiology often are suspected to suffer from latent FeLV infection that is responsible for the nonregenerative cytopenias. OBJECTIVE: The purpose of this study was to assess the role of latent FeLV infection by polymerase chain reaction (PCR) in bone marrow of cats with nonregenerative cytopenias that had negative FeLV antigen test results in blood. ANIMALS: Thirty-seven cats were included in the patient group. Inclusion criteria were (1) nonregenerative cytopenia of unknown origin and (2) negative FeLV antigen test result. Antigenemia was determined by detection of free FeLV p27 antigen by ELISA in serum. Furthermore, 7 cats with positive antigen test results with nonregenerative cytopenia were included as control group I, and 30 cats with negative antigen test results without nonregenerative cytopenia were included as control group II. METHODS: Whole blood and bone marrow samples were tested by 2 different PCR assays detecting sequences of the envelope or long terminal repeat genes. FeLV immunohistochemistry was performed in bone marrow samples. RESULTS: Two of the 37 cats (5.4%) in the patient group were positive on the bone marrow PCR results and thus were latently infected with FeLV. CONCLUSIONS AND CLINICAL IMPORTANCE: The findings of this study suggest that FeLV latency is rare in cats with nonregenerative cytopenias.


Subject(s)
Cat Diseases/etiology , Hematologic Diseases/veterinary , Leukemia Virus, Feline , Retroviridae Infections/veterinary , Tumor Virus Infections/veterinary , Animals , Cats , Female , Hematologic Diseases/complications , Hematologic Diseases/virology , Immunohistochemistry/veterinary , Male , Polymerase Chain Reaction/veterinary , Retroviridae Infections/complications , Tumor Virus Infections/complications , Virus Latency
17.
J Vet Intern Med ; 24(2): 372-8, 2010.
Article in English | MEDLINE | ID: mdl-20102497

ABSTRACT

BACKGROUND: Vector-transmitted microorganisms in the genera Ehrlichia, Anaplasma, Rickettsia, Bartonella, and Borrelia are commonly suspected in dogs with meningoencephalomyelitis (MEM), but the prevalence of these pathogens in brain tissue and cerebrospinal fluid (CSF) of dogs with MEM is unknown. HYPOTHESIS/OBJECTIVES: To determine if DNA from these genera is present in brain tissue and CSF of dogs with MEM, including those with meningoencephalitis of unknown etiology (MUE) and histopathologically confirmed cases of granulomatous (GME) and necrotizing meningoencephalomyelitis (NME). ANIMALS: Hundred and nine dogs examined for neurological signs at 3 university referral hospitals. METHODS: Brain tissue and CSF were collected prospectively from dogs with neurological disease and evaluated by broadly reactive polymerase chain reaction (PCR) for Ehrlichia, Anaplasma, Spotted Fever Group Rickettsia, Bartonella, and Borrelia species. Medical records were evaluated retrospectively to identify MEM and control cases. RESULTS: Seventy-five cases of MUE, GME, or NME, including brain tissue from 31 and CSF from 44 cases, were evaluated. Brain tissue from 4 cases and inflammatory CSF from 30 cases with infectious, neoplastic, compressive, vascular, or malformative disease were evaluated as controls. Pathogen nucleic acids were detected in 1 of 109 cases evaluated. Specifically, Bartonella vinsonii subsp. berkhoffii DNA was amplified from 1/6 dogs with histopathologically confirmed GME. CONCLUSION AND CLINICAL IMPORTANCE: The results of this investigation suggest that microorganisms in the genera Ehrlichia, Anaplasma, Rickettsia, and Borrelia are unlikely to be directly associated with canine MEM in the geographic regions evaluated. The role of Bartonella in the pathogenesis of GME warrants further investigation.


Subject(s)
Brain/microbiology , Dog Diseases/microbiology , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/veterinary , Meningoencephalitis/veterinary , Polymerase Chain Reaction/veterinary , Animals , DNA, Bacterial/classification , DNA, Bacterial/isolation & purification , Dog Diseases/cerebrospinal fluid , Dogs , Female , Gram-Negative Bacterial Infections/cerebrospinal fluid , Gram-Negative Bacterial Infections/microbiology , Male , Meningoencephalitis/microbiology
18.
Sci Rep ; 10(1): 1141, 2020 01 24.
Article in English | MEDLINE | ID: mdl-31980676

ABSTRACT

A gender gap exists in cystic fibrosis (CF). Here we investigate whether plasma microRNA expression profiles differ between the sexes in CF children. MicroRNA expression was quantified in paediatric CF plasma (n = 12; six females; Age range:1-6; Median Age: 3; 9 p.Phe508del homo- or heterozygotes) using TaqMan OpenArray Human miRNA Panels. Principal component analysis indicated differences in male versus female miRNA profiles. The miRNA array analysis revealed two miRNAs which were significantly increased in the female samples (miR-885-5p; fold change (FC):5.07, adjusted p value: 0.026 and miR-193a-5p; FC:2.6, adjusted p value: 0.031), although only miR-885-5p was validated as increased in females using specific qPCR assay (p < 0.0001). Gene ontology analysis of miR-885-5p validated targets identified cell migration, motility and fibrosis as processes potentially affected, with RAC1-mediated signalling featuring significantly. There is a significant increase in miR-885-5p in plasma of females versus males with CF under six years of age.


Subject(s)
Cystic Fibrosis/blood , MicroRNAs/blood , Sex Characteristics , Child , Child, Preschool , Cystic Fibrosis/genetics , Female , Gene Ontology , Humans , Infant , Male , Prognosis , Reverse Transcriptase Polymerase Chain Reaction
19.
Science ; 206(4418): 580-2, 1979 Nov 02.
Article in English | MEDLINE | ID: mdl-17759428

ABSTRACT

Enzymes of the glyoxylate cycle, isocitrate lyase and malate synthase, are active during the germination of spores of the fern Dryopteris filix-mas. Increases in activity of both enzymes are correlated with the breakdown of lipid reserves. The occurrence of these enzymes suggests that the microbodies previously described in these spores are glyoxysomes.

20.
Science ; 241(4863): 359-61, 1988 Jul 15.
Article in English | MEDLINE | ID: mdl-17734865

ABSTRACT

High-density demersal layers of krill have been detected in the submarine canyons off Georges Bank by means of a high-frequency, dual-beam bioacoustical technique. Krill densities in these demersal layers were observed to be two to three orders of magnitude greater than the highest densities observed in water-column scattering layers. Such abundances may help explain the unusually high squid and demersal fish production estimates attributed to the Georges Bank ecosystem.

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