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1.
Surgeon ; 22(2): e100-e108, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38081758

ABSTRACT

BACKGROUND: Hepatectomy is an established treatment for colorectal liver metastasis (CLM) or neuroendocrine liver metastasis. However, its role in non-colorectal non-neuroendocrine liver metastasis (NCNNLM) is controversial. This study aims to compare long-term survival outcomes after hepatectomy between NCNNLM and CLM in a population-based cohort. METHODS: From 2009 to 2018, curative hepatectomy were performed in 964 patients with NCNNLM (n â€‹= â€‹133) or CLM (n â€‹= â€‹831). Propensity score (PS) matching was performed. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. RESULTS: There were 133 patients in the NCNNLM group and 266 patients in the CLM group. The mortality (1.5 â€‹% vs 1.5 â€‹%) and morbidity (19.5 â€‹% vs 20.3 â€‹%) rates were comparable between the two groups. There was no statistically significant difference in 5-year overall (48.9 â€‹% vs 39.8 â€‹%) and recurrence-free (25.1 â€‹% vs 23.4 â€‹%) survival rates between NCNNLM and CLM groups. A high pre-operative serum bilirubin level, severe postoperative complications and multiple tumors were independent prognostic factors for poor survival. CONCLUSION: Hepatectomy for selected patients with NCNNLM can achieve similar long-term oncological outcomes as those with CLM. High serum bilirubin, severe postoperative complication and multiple tumors are poor prognostic factors for survival.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Hepatectomy , Propensity Score , Colorectal Neoplasms/pathology , Retrospective Studies , Liver Neoplasms/surgery , Postoperative Complications/surgery , Survival Rate , Bilirubin , Treatment Outcome
2.
Psychol Trauma ; 16(1): 39-48, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37561436

ABSTRACT

OBJECTIVE: Religious coping has implications for the development of psychopathology in the aftermath of traumatic events. This study explored the relationship between religious coping (positive and negative) and posttraumatic stress disorder (PTSD) symptomology among survivors of a large industrial explosion that devastated parts of Beirut in August of 2020. METHOD: Three months after the disaster, 996 residents of Beirut and Lebanon completed validated measures of religious coping (RCOPE) and PTSD symptomatology (Impact of Events Scale-Revised) in either English or Arabic. The majority of participants were young adults aged between 18 and 25 years. RESULTS: Results indicated that higher levels of negative religious coping were a significant predictor of higher levels of PTSD symptomatology and were associated with a two-fold risk of meeting the criteria for probable PTSD. Other significant predictors included female gender, being a resident of Beirut at the time of the explosion, having personally sustained an injury, or knowing a person injured in the explosion. Effects sizes ranged from .34 to .68. CONCLUSIONS: Higher scores on measures of negative religious coping were associated with higher levels of PTSD symptomatology. However, negative religious coping may be better construed as a set of religious-based appraisals of event causality and may represent a form of peritraumatic appraisal in the wake of traumatic events. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Disasters , Stress Disorders, Post-Traumatic , Young Adult , Humans , Female , Adolescent , Adult , Explosions , Adaptation, Psychological , Coping Skills
3.
Biotechniques ; 75(4): 157-167, 2023 10.
Article in English | MEDLINE | ID: mdl-37815826

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) is an important tool for understanding disease pathophysiology, including airway diseases. Currently, the majority of scRNA-seq studies in airway diseases have used invasive methods (airway biopsy, surgical resection), which carry inherent risks and thus present a major limitation to scRNA-seq investigation of airway pathobiology. Bronchial brushing, where the airway mucosa is sampled using a cytological brush, is a viable, less invasive method of obtaining airway cells for scRNA-seq. Here we describe the development of a rapid and minimal handling protocol for preparing single-cell suspensions from bronchial brush specimens for scRNA-seq. Our optimized protocol maximizes cell recovery and cell quality and facilitates large-scale profiling of the airway transcriptome at single-cell resolution.


Subject(s)
Gene Expression Profiling , Software , Gene Expression Profiling/methods , Bronchoscopy , Single-Cell Analysis/methods , Sequence Analysis, RNA/methods
4.
J Appl Physiol (1985) ; 135(5): 1001-1011, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37767558

ABSTRACT

Emphysema is one of the pathological hallmarks of chronic obstructive pulmonary disease. We have recently reported that radiofrequency therapy improves lung function in rodent models of emphysema. However, preclinical data using large animals is necessary for clinical translation. Here, we describe the work performed to establish a unilateral porcine emphysema model. Different doses of porcine pancreatic elastase (PPE) were instilled into the left lung of 10 Yucatan pigs. Three additional pigs were used as controls. Six weeks after instillation, lungs were harvested. Lung compliance was measured by a water displacement method and plethysmography. Systematic uniform random sampling of the left and right lungs was performed independently to measure alveolar surface area using micro-computed tomography (micro-CT) and histology. In pigs instilled with 725-750 U/kg of PPE (PPE group, n = 6), the compliance of the left lung was significantly higher by 37.6% than that of the right lung (P = 0.03) using the water displacement method. With plethysmography, the volume of the left lung was significantly larger than that of the right lung at 3, 5, and 10 cmH2O. Measurements from either micro-CT or histology images showed a significant decrease in alveolar surface area by 14.2% or 14.5% (P = 0.031) in the left lung compared with the right lung of the PPE group. A unilateral model for mild emphysema in Yucatan pigs has been established, which can now be used for evaluating novel therapeutics and interventional strategies.NEW & NOTEWORTHY For clinical translation, preclinical data using large animal models is necessary. However, papers describing an emphysema model in pigs, which are anatomically and physiologically similar to humans, are lacking. Here, we report success in creating a unilateral mild-emphysema model in pigs with only one single dose of porcine pancreatic elastase. This model will be useful in bringing novel technologies and therapies from small animals to humans with emphysema.


Subject(s)
Emphysema , Pulmonary Emphysema , Humans , Swine , Animals , Pancreatic Elastase/adverse effects , X-Ray Microtomography , Lung , Emphysema/pathology , Water , Disease Models, Animal
5.
Bioact Mater ; 27: 303-326, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37122902

ABSTRACT

Microneedle, as a novel drug delivery system, has attracted widespread attention due to its non-invasiveness, painless and simple administration, controllable drug delivery, and diverse cargo loading capacity. Although microneedles are initially designed to penetrate stratum corneum of skin for transdermal drug delivery, they, recently, have been used to promote wound healing and regeneration of diverse tissues and organs and the results are promising. Despite there are reviews about microneedles, few of them focus on wound healing and tissue regeneration. Here, we review the recent advances of microneedles in this field. We first give an overview of microneedle system in terms of its potential cargos (e.g., small molecules, macromolecules, nucleic acids, nanoparticles, extracellular vesicle, cells), structural designs (e.g., multidrug structures, adhesive structures), material selection, and drug release mechanisms. Then we briefly summarize different microneedle fabrication methods, including their advantages and limitations. We finally summarize the recent progress of microneedle-assisted wound healing and tissue regeneration (e.g., skin, cardiac, bone, tendon, ocular, vascular, oral, hair, spinal cord, and uterine tissues). We expect that our article would serve as a guideline for readers to design their microneedle systems according to different applications, including material selection, drug selection, and structure design, for achieving better healing and regeneration efficacy.

6.
Cells ; 11(19)2022 09 27.
Article in English | MEDLINE | ID: mdl-36230980

ABSTRACT

Genome-wide association studies (GWAS) have shown that variants of patched homolog 1 (PTCH1) are associated with lung function abnormalities in the general population. It has also been shown that sonic hedgehog (SHH), an important ligand for PTCH1, is upregulated in the airway epithelium of patients with asthma and is suggested to be involved in airway remodeling. The contribution of hedgehog signaling to airway remodeling and inflammation in asthma is poorly described. To determine the biological role of hedgehog signaling-associated genes in asthma, gene silencing, over-expression, and pharmacologic inhibition studies were conducted after stimulating human airway epithelial cells or not with transforming growth factor ß1 (TGFß1), an important fibrotic mediator in asthmatic airway remodeling that also interacts with SHH pathway. TGFß1 increased hedgehog-signaling-related gene expression including SHH, GLI1 and GLI2. Knockdown of PTCH1 or SMO with siRNA, or use of hedgehog signaling inhibitors, consistently attenuated COL1A1 expression induced by TGFß1 stimulation. In contrast, Ptch1 over-expression augmented TGFß1-induced an increase in COL1A1 and MMP2 gene expression. We also showed an increase in hedgehog-signaling-related gene expression in primary airway epithelial cells from controls and asthmatics at different stages of cellular differentiation. GANT61, an inhibitor of GLI1/2, attenuated TGFß1-induced increase in COL1A1 protein expression in primary airway epithelial cells differentiated in air-liquid interface. Finally, to model airway tissue remodeling in vivo, C57BL/6 wildtype (WT) and Ptch1+/- mice were intranasally challenged with house dust mite (HDM) or phosphate-buffered saline (PBS) control. Ptch1+/- mice showed reduced sub-epithelial collagen expression and serum inflammatory proteins compared to WT mice in response to HDM challenge. In conclusion, TGFß1-induced airway remodeling is partially mediated through the hedgehog signaling pathway via the PTCH1-SMO-GLI axis. The Hedgehog signaling pathway is a promising new potential therapeutic target to alleviate airway tissue remodeling in patients with allergic airways disease.


Subject(s)
Airway Remodeling , Asthma , Animals , Dermatophagoides pteronyssinus , Genome-Wide Association Study , Hedgehog Proteins/metabolism , Humans , Inflammation , Ligands , Matrix Metalloproteinase 2/genetics , Mice , Mice, Inbred C57BL , Patched-1 Receptor/genetics , Patched-1 Receptor/metabolism , Phosphates , Pyroglyphidae , RNA, Small Interfering , Transforming Growth Factor beta1/metabolism , Zinc Finger Protein GLI1/metabolism
7.
Vaccines (Basel) ; 10(9)2022 Sep 05.
Article in English | MEDLINE | ID: mdl-36146550

ABSTRACT

Inactivated vaccines are the main influenza vaccines used today; these are usually presented as split (detergent-disrupted) or subunit vaccines, while whole-virus-inactivated influenza vaccines are rare. The single radial immune diffusion (SRD) assay has been used as the gold standard potency assay for inactivated influenza vaccines for decades; however, more recently, various alternative potency assays have been proposed. A new potency test should be able to measure the amount of functional antigen in the vaccine, which in the case of influenza vaccines is the haemagglutinin (HA) protein. Potency tests should also be able to detect the loss of potency caused by changes to the structural and functional integrity of HA. To detect such changes, most alternative potency tests proposed to date use antibodies that react with native HA. Due to the frequent changes in influenza vaccine composition, antibodies may need to be updated in line with changes in vaccine viruses. We have developed two ELISA-based potency assays for group 1 influenza A viruses using cross-reactive nanobodies. The nanobodies detect influenza viruses of subtype H1N1 spanning more than three decades, as well as H5N1 viruses, in ELISA. We found that the new ELISA potency assays are sensitive to the nature of the reference antigen (standard) used to quantify vaccine antigens; using standards matched in their presentation to the vaccine type improved correspondence between the ELISA and SRD assays.

8.
Biomedicines ; 10(6)2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35740433

ABSTRACT

The associations between airway eosinophilia, measured in sputum or peripheral blood, and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are inconsistent. We therefore aimed to determine the association between eosinophilia in bronchoalveolar lavage (BAL) fluid and AECOPD in a clinical cohort. We analyzed differential cell counts from baseline BAL fluid in participants in the DISARM clinical trial (Clinicaltrials.gov #NCT02833480) and classified participants by the presence or absence of BAL eosinophilia (>1% of total leukocytes). We determined the association between BAL eosinophilia and AECOPD over 1 year of follow-up using negative binomial regression and Cox proportional hazards test. N = 63 participants were randomized, and N = 57 had BAL differential cell counts available. Participants with BAL eosinophilia (N = 21) had a significantly increased rate of acute exacerbations (unadjusted incidence rate ratio (IRR) 2.0, p = 0.048; adjusted IRR 2.24, p = 0.04) and a trend toward greater probability of acute exacerbation (unadjusted hazard ratio (HR) 1.74, p = 0.13; adjusted HR 2.3, p = 0.1) in the year of follow-up compared to participants without BAL eosinophilia (N = 36). These associations were not observed for BAL neutrophilia (N = 41 participants), BAL lymphocytosis (N = 27 participants) or peripheral blood eosinophilia at various threshold definitions (2%, N = 37; 3%, N = 27; 4%, N = 16). BAL may therefore be a sensitive marker of eosinophilic inflammation in the distal lung and may be of benefit for risk stratification or biomarker-guided therapy in COPD.

9.
Epidemiol Infect ; 150: e101, 2022 04 27.
Article in English | MEDLINE | ID: mdl-35606895

ABSTRACT

Influenza virus infections can lead to a number of secondary complications, including sepsis. We applied linear regression models to mortality and hospital admission data coded for septicaemia from 1998 to 2019 in Hong Kong, and estimated that septicaemia was associated with an annual average excess mortality rate of 0.23 (95% CI 0.04-0.40) per 100 000 persons per year and an excess septicaemia hospitalisation rate of 1.73 (95% CI 0.94-2.50) per 100 000 persons per year. The highest excess morbidity and mortality was found in older adults and young children, and during influenza A(H3N2) epidemics.


Subject(s)
Influenza, Human , Sepsis , Aged , Child , Child, Preschool , Hong Kong/epidemiology , Hospitalization , Humans , Influenza A Virus, H3N2 Subtype , Sepsis/epidemiology
10.
Sci Rep ; 11(1): 20056, 2021 10 08.
Article in English | MEDLINE | ID: mdl-34625605

ABSTRACT

Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in "volume reduction" and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema. Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100 g body weight). RF treatment (0.5 W/ g body weight) was administered extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score. There were 3 experimental groups: controls (instilled with saline, n = 12), emphysema (instilled with porcine pancreatic elastase, PPE, n = 11) and emphysema + treatment (instilled with PPE and given RF, n = 9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p = 0.01). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p = 0.03). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p < 0.01). No severe adverse events from RF were observed. RF treatment improved the exercise capacity of mice with emphysema. These data highlight the therapeutic potential of RF treatment in improving the functional status of patients with COPD.


Subject(s)
Exercise Tolerance , Physical Conditioning, Animal , Pulmonary Emphysema/radiotherapy , Pulmonary Fibrosis/prevention & control , Radiofrequency Therapy/methods , Animals , Lung Compliance , Male , Mice , Mice, Inbred C57BL , Pancreatic Elastase/administration & dosage , Pulmonary Emphysema/etiology , Pulmonary Emphysema/metabolism , Swine
11.
J Ment Health ; 30(6): 743-750, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34264784

ABSTRACT

BACKGROUND: Posttraumatic stress disorder (PTSD) as a result of a bombing has been studied in the literature. Limited studies have focused attention on PTSD following a suicide car bombing. However, more research is needed to explore the risk factors for this psychological response. AIMS: To examine a hypothesised model that death anxiety would be associated with PTSD and psychiatric comorbidity following a suicide car bombing, and that attachment styles and religious coping would influence the impact of this anxiety on distress outcomes. METHODS: 185 Iraqi civilians exposed to the first suicide car bombing completed questionnaires measuring PTSD, psychiatric comorbidity, death anxiety, religious coping, and attachment experiences. RESULTS: 82% met diagnostic criteria for PTSD, the remainder did not. Path analysis showed that death anxiety was significantly correlated with psychiatric comorbidity; it was also correlated with attachment, which was correlated with psychiatric comorbidity. Death anxiety was also significantly correlated with religious coping, which was correlated with both distress outcomes. CONCLUSIONS: Although Iraqi civilians reported increased death anxiety following a suicide car bombing, those who used religion to cope with the traumatic experience and had functional attachment experiences in the past reported low levels of psychological distress.


Subject(s)
Stress Disorders, Post-Traumatic , Suicide , Adaptation, Psychological , Anxiety/epidemiology , Automobiles , Humans , Stress Disorders, Post-Traumatic/epidemiology
12.
Sci Rep ; 11(1): 8282, 2021 04 15.
Article in English | MEDLINE | ID: mdl-33859282

ABSTRACT

The classical M1/M2 polarity of macrophages may not be applicable to inflammatory lung diseases including chronic obstructive pulmonary disease (COPD) due to the complex microenvironment in lungs and the plasticity of macrophages. We examined macrophage sub-phenotypes in bronchoalveolar lavage (BAL) fluid in 25 participants with CD40 (a M1 marker) and CD163 (a M2 marker). Of these, we performed RNA-sequencing on each subtype in 10 patients using the Illumina NextSeq 500. Approximately 25% of the macrophages did not harbor classical M1 or M2 surface markers (double negative, DN), and these cells were significantly enriched in COPD patients compared with non-COPD patients (46.7% vs. 14.5%, p < 0.001). 1886 genes were differentially expressed in the DN subtype compared with  all other subtypes at a 10% false discovery rate. The 602 up-regulated genes included 15 mitochondrial genes and were enriched in 86 gene ontology (GO) biological processes including inflammatory responses. Modules associated with cellular functions including oxidative phosphorylation were significantly down-regulated in the DN subtype. Macrophages in the human BAL fluid, which were negative for both M1/M2 surface markers, harbored a gene signature that was pro-inflammatory and suggested dysfunction in cellular homeostasis. These macrophages may contribute to the pathogenesis and manifestations of inflammatory lung diseases such as COPD.


Subject(s)
Antigens, CD , Antigens, Differentiation, Myelomonocytic , Antigens, Surface , Bronchoalveolar Lavage Fluid/cytology , CD40 Antigens , Macrophages , Pulmonary Disease, Chronic Obstructive/etiology , Receptors, Cell Surface , Homeostasis/immunology , Humans , Inflammation/genetics , Inflammation/immunology , Macrophages/immunology , Oxidative Phosphorylation
13.
EClinicalMedicine ; 33: 100789, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33758801

ABSTRACT

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are highly susceptible from respiratory exacerbations from viral respiratory tract infections. However, it is unclear whether they are at increased risk of COVID-19 pneumonia or COVID-19-related mortality. We aimed to determine whether COPD is a risk factor for adverse COVID-19 outcomes including hospitalization, severe COVID-19, or death. METHODS: Following the PRISMA guidelines, we performed a systematic review of COVID-19 clinical studies published between November 1st, 2019 and January 28th, 2021 (PROSPERO ID: CRD42020191491). We included studies that quantified the number of COPD patients, and reported at least one of the following outcomes stratified by COPD status: hospitalization; severe COVID-19; ICU admission; mechanical ventilation; acute respiratory distress syndrome; or mortality. We meta-analyzed the results of individual studies to determine the odds ratio (OR) of these outcomes in patients with COPD compared to those without COPD. FINDINGS: Fifty-nine studies met the inclusion criteria, and underwent data extraction. Most studies were retrospective cohort studies/case series of hospitalized patients. Only four studies examined the effects of COPD on COVID-19 outcomes as their primary endpoint. In aggregate, COPD was associated with increased odds of hospitalization (OR 4.23, 95% confidence interval [CI] 3.65-4.90), ICU admission (OR 1.35, 95% CI 1.02-1.78), and mortality (OR 2.47, 95% CI 2.18-2.79). INTERPRETATION: Having a clinical diagnosis of COPD significantly increases the odds of poor clinical outcomes in patients with COVID-19. COPD patients should thus be considered a high-risk group, and targeted for preventative measures and aggressive treatment for COVID-19 including vaccination.

14.
Respir Res ; 22(1): 75, 2021 Mar 02.
Article in English | MEDLINE | ID: mdl-33653328

ABSTRACT

BACKGROUND: Asthma was identified as the most common comorbidity in hospitalized patients during the 2009 H1N1 influenza pandemic. We determined using a murine model of allergic asthma whether these mice experienced increased morbidity from pandemic H1N1 (pH1N1) viral infection and whether blockade of interleukin-4 receptor α (IL-4Rα), a critical mediator of Th2 signalling, improved their outcomes. METHODS: Male BALB/c mice were intranasally sensitized with house dust mite antigen (Der p 1) for 2 weeks; the mice were then inoculated intranasally with a single dose of pandemic H1N1 (pH1N1). The mice were administered intraperitoneally anti-IL-4Rα through either a prophylactic or a therapeutic treatment strategy. RESULTS: Infection with pH1N1 of mice sensitized to house dust mite (HDM) led to a 24% loss in weight by day 7 of infection (versus 14% in non-sensitized mice; p < .05). This was accompanied by increased viral load in the airways and a dampened anti-viral host responses to the infection. Treatment of HDM sensitized mice with a monoclonal antibody against IL-4Rα prior to or following pH1N1 infection prevented the excess weight loss, reduced the viral load in the lungs and ameliorated airway eosinophilia and systemic inflammation related to the pH1N1 infection. CONCLUSION: Together, these data implicate allergic asthma as a significant risk factor for H1N1-related morbidity and reveal a potential therapeutic role for IL-4Rα signalling blockade in reducing the severity of influenza infection in those with allergic airway disease.


Subject(s)
Asthma/metabolism , Hypersensitivity/metabolism , Influenza, Human/metabolism , Pyroglyphidae/metabolism , Receptors, Cell Surface/antagonists & inhibitors , Receptors, Cell Surface/metabolism , Animals , Antibodies, Monoclonal/administration & dosage , Asthma/chemically induced , Asthma/drug therapy , Disease Models, Animal , Humans , Hypersensitivity/drug therapy , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H1N1 Subtype/physiology , Influenza, Human/drug therapy , Male , Mice , Mice, Inbred BALB C
15.
Tob Prev Cessat ; 7: 5, 2021.
Article in English | MEDLINE | ID: mdl-33511319

ABSTRACT

INTRODUCTION: There is a lack of information regarding factors associated with successful smoking cessation on a population and European Union (EU)-wide level. Our study seeks to explore individual and country-level factors associated with abstinence after a recent smoking cessation attempt across the EU. METHODS: We obtained data from the March 2017 Special Eurobarometer 87.1 (n=27901). Regression analysis was performed on a subset of 1472 individuals who made quit attempts in the past 12 months. Sociodemographic, policy and country-level factors were assessed using logistic regression among smokers and ex-smokers who attempted to quit approximately 12 months before the survey date. We defined and examined the Cessation Ratio (ratio of number of recent quitters to those who did not succeed) across 28 EU Member States. RESULTS: In all, 14.9% (n=1018) of current smokers and 8.80% (n=454) of ex-smokers attempted to quit in approximately the last 12 months (n=1472). Cessation Ratios ranged from 0.182 (95% CI: 0.045-0.319) in Estonia to 1.060 (95% CI: 0.262-1.860) in Sweden. There is a quadratic, U-shaped relationship between odds of quitting and smoking prevalence. The lowest odds of cessation were observed at a prevalence of 26.3%, with higher odds of cessation observed above and below this point. Respondents who reported financial difficulties were less likely to quit (AOR=0.66; 95% CI: 0.52-0.83). There was no association of likelihood of success with other sociodemographic factors or the Tobacco Control Scale treatment score. CONCLUSIONS: These findings highlight a need for exploring reasons behind the variation in likelihood of abstinence following a recent quit attempt, in order to design policies targeted at population groups or countries that need greater support.

17.
Antibodies (Basel) ; 8(1)2019 Feb 10.
Article in English | MEDLINE | ID: mdl-31544820

ABSTRACT

Influenza B virus (IBV) circulates in the human population and causes considerable disease burden worldwide, each year. Current IBV vaccines can struggle to mount an effective cross-reactive immune response, as strains become mismatched, due to constant antigenic changes. Additional strategies which use monoclonal antibodies, with broad reactivity, are of considerable interest, both, as diagnostics and as immunotherapeutics. Alternatives to conventional monoclonal antibodies, such as single domain antibodies (NanobodiesTM) with well-documented advantages for applications in infectious disease, have been emerging. In this study we have isolated single domain antibodies (sdAbs), specific to IBV, using alpacas immunised with recombinant hemagglutinin (HA) from two representative viruses, B/Florida/04/2006 (B/Yamagata lineage) and B/Brisbane/60/2008 (B/Victoria lineage). Using phage display, we have isolated a panel of single domain antibodies (sdAbs), with both cross-reactive and lineage-specific binding. Several sdAbs recognise whole virus antigens, corresponding to influenza B strains included in vaccines spanning over 20 years, and were capable of neutralising IBV pseudotypes corresponding to prototype strains from both lineages. Lineage-specific sdAbs recognised the head domain, whereas, sdAbs identified as cross-reactive could be classified as either head binding or stem binding. Using yeast display, we were able to correlate lineage specificity with naturally occurring sequence divergence, at residue 122 in the highly variable 120 loop of the HA1 domain. The single domain antibodies described, might have applications in IBV diagnostics, vaccine potency testing and as immunotherapeutics.

18.
Biofabrication ; 11(3): 032003, 2019 06 06.
Article in English | MEDLINE | ID: mdl-30965297

ABSTRACT

The central nervous system (CNS) has a highly complex biophysical and biochemical environment. Despite decades of intensive research, it is still an enormous challenge to restore its functions and regenerate lost or damaged CNS tissues. Current treatment strategies remain sub-optimal because of (1) the hostile microenvironment created post CNS injury, and (2) insufficient understanding of the pathophysiology of acute and chronic CNS diseases. Two-dimensional (2D) in vitro models have provided tremendous insights into a wide range of cellular interactions. However, they fail to recapitulate the complex cellular, topographical, biochemical, and mechanical stimuli found within the natural three-dimensional (3D) CNS. Also, the growing ethical needs to use fewer animals for research further necessitates 3D in vitro models to mimic all or part of the CNS. In this review, we critically appraise the status quo and design considerations of 3D in vitro neural disease and injury models that resemble in vivo conditions. This review mainly focuses on the most recent advances in tissue engineering techniques such as microfluidics, organs-on-a-chip and stem cell technology. Furthermore, we review recent models aiming to elucidate the underlying pathophysiology of CNS diseases. If armed with deeper understanding, it will be possible to develop high-throughput drug screening platforms and new treatments for CNS diseases and injuries.


Subject(s)
Cellular Microenvironment , Central Nervous System Diseases/pathology , Models, Biological , Tissue Engineering/methods , Animals , Humans , Microfluidics , Tissue Scaffolds/chemistry
19.
J Healthc Qual ; 41(1): e1-e6, 2019.
Article in English | MEDLINE | ID: mdl-29634594

ABSTRACT

BACKGROUND: Efficient clinical pathways are needed to meet the growing pressures in dermatology due to the significant rise in the number of suspected skin cancer referrals. Our hospital serves a wide geographical area and receives a large number of 2-week-wait (2WW) suspected skin cancer referrals. In the United Kingdom, approximately 10-12% of 2WW referrals are diagnosed as skin cancers fulfilling the 2WW criteria. PURPOSE: We sought to assess the role of teledermatology in reducing hospital consultations for patients referred via the dermatology 2WW pathway. METHODS: We piloted a teledermatology service and detailed the clinical outcomes of patients with solitary skin lesions of uncertain diagnosis triaged through this pathway. Seventy-six primary care referrals were reviewed by consultant dermatologists and analyzed against the British Association of Dermatologists' teledermatology audit standards. RESULTS: In 52/76 (68%) of patients, confident benign diagnoses were made, avoiding the need for a face-to-face (FTF) consultation. CONCLUSIONS: Our results showed that with adequate image quality, teledermatology can be used to accurately diagnose skin lesions. IMPLICATIONS: Teledermatology can significantly reduce the number of urgent referrals necessitating FTF appointments, therefore providing a new solution to streamline care delivery.


Subject(s)
Dermatology/methods , Early Detection of Cancer/methods , Skin Neoplasms/diagnosis , Telemedicine/methods , Adult , Female , Humans , London , Male , Middle Aged , Pilot Projects , United Kingdom
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