Rapid, Selective, and Ultra-Sensitive Field Effect Transistor-Based Detection of Escherichia coli.

Escherichia coli (E. coli) was among the first organisms to have its complete genome published (Genome Sequence of E. coli 1997 Science). It is used as a model system in microbiology research. E. coli can cause life-threatening illnesses, particularly in children and the elderly. Possible contamination by the bacteria also results in product recalls, which, alongside the potential danger posed to individuals, can have significant financial consequences. We report the detection of live Escherichia coli (E. coli) in liquid samples using a biosensor based on a field-effect transistor (FET) biosensor with B/N co-coped reduced graphene oxide (rGO) gel (BN-rGO) as the transducer material. The FET was functionalized with antibodies to detect E. coli K12 O-antigens in phosphate-buffered saline (PBS). The biosensor detected the presence of planktonic E. coli bacterial cells within a mere 2 min. The biosensor exhibited a limit of detection (LOD) of 10 cells per sample, which can be extrapolated to a limit of detection at the level of a single cell per sample and a detection range of at least 10-108 CFU/mL. The selectivity of the biosensor for E. coli was demonstrated using Bacillus thuringiensis (B. thuringiensis) as a sample contaminant. We also present a comparison of our functionalized BN-rGO FET biosensor with established detection methods of E. coli k12 bacteria, as well as with state-of-the-art detection mechanisms.

Adaptive Effects of Endocrine Hormones on Metabolism of Macronutrients during Fasting and Starvation: A Scoping Review.

Food deprivation can occur for different reasons. Fasting (<24 h duration) occurs to meet religious or well-being goals. Starvation (>1-day duration) occurs when there is intentional (hunger strike or treatment of a medical condition) or unintentional (anorexia nervosa, drought, epidemic famine, war, or natural disaster) food deprivation. A scoping review was undertaken using the PubMed database to explore 1805 abstracts and review 88 eligible full-text articles to explore the adaptive relationships that emerge between cortisol, insulin, glucagon, and thyroid hormones on the metabolic pathways of macronutrients in humans during fasting and starvation. The collected data indicate that fasting and starvation prime the human body to increase cortisol levels and decrease the insulin/glucagon ratio and triiodothyronine (T3) levels. During fasting, increased levels of cortisol and a decreased insulin/glucagon ratio enhance glycogenolysis and reduce the peripheral uptake of glucose and glycogenesis, whereas decreased T3 levels potentially reduce glycogenolysis. During starvation, increased levels of cortisol and a decreased insulin/glucagon ratio enhance lipolysis, proteolysis, fatty acid and amino acid oxidation, ketogenesis, and ureagenesis, and decreased T3 levels reduce thermogenesis. We present a potential crosstalk between T3 and the above hormones, including between T3 and leptin, to extend their adaptive roles in the metabolism of endogenous macronutrients during food deprivation.

An Explanatory Model to Predict Pediatric Psychosis Spectrum Based on Parent Psychiatric Profile and Children and Adolescents Comorbid Disorders as a Mediator Construct.

Objective: Psychosis is one of the most vital disorders in children and youths. The definite pathophysiology of schizophrenia and other psychotic disorders in the growth period has remained ambiguous. Therefore, the purpose of the current study was to investigate the predictive value of parental psychiatric disorders and the mediator role of comorbid disorders of children and youths. Method : The sample, consisting of 29884 individuals aged between 6 to 18 years old from the Iranian population, were selected by multistage cluster sampling during September 22, 2016 to January 3, 2018. Parents were requested to complete a survey around their potential psychiatric disorders, based on their Millon's Clinical Multiaxial Inventory-III (MCMI-III). The Semi-Structured Interview (Kiddie-SADS-Present, Lifetime Form (K-SADS-PL)) was utilized to analyze psychiatric disorders concurring to the DSM. Results: The fit indices of the model show that the research model has a good fit and the psychiatric disorders of parents directly and indirectly through comorbid disorders are effective on the psychosis symptoms of children and adolescents (RMSEA=0.06, CFI=0.89, PGFI=0.75, PNFI=0.75).The incidence of Schizotypal Personality Disorder, Anxiety, Bipolar Spectrum Disorder, PTSD, Schizophrenia Spectrum and Delusional Disorder were statistically higher in parents of psychotic children and adolescents. However, Borderline Personality Disorder was more frequent among their mothers while Alcohol Dependency and Drug Dependency were significantly more prevalent among their fathers. Conclusion: The outcomes of our study showed that there were statistically significant differences between the mean scores of each scale assessed by Millon's inventory between parents of psychotic versus non-psychotic pediatric cases. In addition, psychiatric disorders were more common among children and youths with psychosis spectrum in comparison with the general population.

Vitamin C supplementation lowers advanced glycation end products (AGEs) and malondialdehyde (MDA) in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial.

This study evaluated how daily vitamin C administration impacts systemic oxidative stress and inflammation and its safety in T2D patients. This randomized, double-blinded, placebo-controlled, parallel-arm clinical trial included 70 patients with T2D. They were allocated to receive either 500 mg/day of vitamin C or a matching placebo for 8 weeks. Of the 70 subjects assigned to the trial, 57 were included in the statistical analysis (vitamin C: n = 32, placebo: n = 25). Inflammatory and oxidative markers, including advanced glycation end products (AGEs), malondialdehyde (MDA), advanced oxidation protein products (AOPP), oxidized low-density lipoprotein (ox-LDL), highly sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and ferric reducing ability of plasma (FRAP) were measured at baseline and the end of the trial. In addition, vitamin C tolerance was evaluated. A nutritionist visited all participants for a standard diabetic regimen. Following vitamin C supplementation, the serum levels of MDA (p-value < .001) and AGEs (p-value = .002) demonstrated a significant decrease after controlling for multiple confounders, including age, blood pressure, waist circumference, HbA1C, TG, and LDL-C, while no significant changes were observed for AOPP (p-value = .234) and ox-LDL (p-value = .480). The FRAP showed an increasing trend as an antioxidant marker but was not statistically significant (p-value = .312). The hs-CRP and TNF-α had no significant changes (p-value: .899 and .454, respectively). Also, no major adverse events were observed. Vitamin C supplementation may be beneficial in reducing AGEs and MDA in patients with T2D.

Mucins 3A and 3B Are Expressed in the Epithelium of Human Large Airway.

Aberrant mucus secretion is a hallmark of chronic obstructive pulmonary disease (COPD). Expression of the membrane-tethered mucins 3A and 3B (MUC3A, MUC3B) in human lung is largely unknown. In this observational cross-sectional study, we recruited subjects 45-65 years old from the general population of Stockholm, Sweden, during the years 2007-2011. Bronchial mucosal biopsies, bronchial brushings, and bronchoalveolar lavage fluid (BALF) were retrieved from COPD patients (n = 38), healthy never-smokers (n = 40), and smokers with normal lung function (n = 40). Protein expression of MUC3A and MUC3B in bronchial mucosal biopsies was assessed by immunohistochemical staining. In a subgroup of subjects (n = 28), MUC3A and MUC3B mRNAs were quantified in bronchial brushings using microarray. Non-parametric tests were used to perform correlation and group comparison analyses. A value of p < 0.05 was considered statistically significant. MUC3A and MUC3B immunohistochemical expression was localized to ciliated cells. MUC3B was also expressed in basal cells. MUC3A and MUC3B immunohistochemical expression was equal in all study groups but subjects with emphysema had higher MUC3A expression, compared to those without emphysema. Smokers had higher mRNA levels of MUC3A and MUC3B than non-smokers. MUC3A and MUC3B mRNA were higher in male subjects and correlated negatively with expiratory air flows. MUC3B mRNA correlated positively with total cell concentration and macrophage percentage, and negatively with CD4/CD8 T cell ratio in BALF. We concluded that MUC3A and MUC3B in large airways may be a marker of disease or may play a role in the pathophysiology of airway obstruction.

Control of release in active packaging/coating for food products; approaches, mechanisms, profiles, and modeling.

Antimicrobial or antioxidant active packaging (AP) is an emerging technology in which a bioactive antimicrobial or antioxidant agent is incorporated into the packaging material to protect the contained product during its shelf life from deterioration. The important issue in AP is making a balance between the deterioration rate of the food product and the controlled release of the bioactive agent. So, the AP fabrication should be designed in such a way that fulfills this goal. Modeling the controlled release is an effective way to avoid trial and error and time-consuming experimental runs and predict the release behavior of bioactive agents in different polymeric matrices and food/food simulants. To review the release of bioactive compounds from AP, in the first part of this review we present an introductory explanation regarding the release controlling approaches in AP. Then the release mechanisms are explained which are very important in defining the appropriate modeling approach and also the interpretation of the modeling results. Different release profiles that might be observed in different packaging systems are also introduced. Finally, different modeling approaches including empirical and mechanistic techniques are covered and the recent literature regarding the utilization of such approaches to help design new AP is thoroughly studied.

Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry.

Rationale: Postbronchodilator spirometry is used for the diagnosis of chronic obstructive pulmonary disease. However, prebronchodilator reference values are used for spirometry interpretation. Objectives: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or postbronchodilator reference values generated within SCAPIS (Swedish CArdioPulmonary bioImage Study) when interpreting postbronchodilator spirometry in a general population. Methods: SCAPIS reference values for postbronchodilator and prebronchodilator spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or postbronchodilator reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). Measurements and Main Results: Bronchodilation resulted in higher predicted medians and lower limits of normal (LLNs) for FEV1/FVC ratios. The prevalence of postbronchodilator FEV1/FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV1/FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV1/FVC ratio, and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%; P < 0.001), and self-reported physician-diagnosed chronic obstructive pulmonary disease (2.8% vs. 0.5%, P < 0.001) than subjects with a postbronchodilator FEV1/FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of postbronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using postbronchodilator reference values when interpreting postbronchodilator spirometry might enable the identification of individuals with mild disease and be clinically relevant.

Femtosecond laser irradiation as a novel method for nanosheet growth and defect generation in g-C3N4.

Among the many recently developed photo-catalytic materials, graphitic carbon nitride (g-C3N4) shows great promise as a catalytic material for water splitting, hydrogen generation, and related catalytic applications. Herein, synthesized bulk g-C3N4is simply irradiated under a 35 fs pulse at mixed photon energies (800 nm and its second harmonic). g-C3N4was synthesized from melamine following a facile thermal polymerization procedure. The prepared material was introduced, in an aqueous environment, to the femtosecond laser for various lengths of time. The treated material demonstrates a significant increase in surface area, relative to the untreated samples, indicating that irradiation is a successful method for exfoliation. The subsequent characterization reveals that the mixed irradiation process drives significant defect generation and sheet growth, which is not seen under 800 nm irradiation. Extended mixed irradiation results in 4 nm thick nanosheets with lateral dimensions 4× that of the bulk material. The treated material shows improved dye absorption/removal. This novel method of defect generation and nanosheet growth shows great potential as a g-C3N4pre-treatment method for co-catalytic applications. Herein it is shown that femtosecond laser irradiation drives exfoliation beyond 100 nm particle sizes, and sheet-like morphologies under extended irradiation, which must be taken into account when using this method to improve material performance.

Defect-Rich MoSe2 2H/1T Hybrid Nanoparticles Prepared from Femtosecond Laser Ablation in Liquid and Their Enhanced Photothermal Conversion Efficiencies.

MoSe2 2H/1T hybrid nanoparticles are prepared by femtosecond laser ablation of MoSe2 powder in isopropyl alcohol with different laser powers and ablation times, and their formation mechanisms and photothermal conversion efficiencies (PTCEs) are studied. Two types of spherical nanoparticles are observed. The first type is onion-structured nanoparticles that are formed by nucleation on the surfaces of melted droplets followed by inward growth of {002} planes of MoSe2 . The second type is polycrystalline nanoparticles, formed by coalescence of crystalline nanoclusters fragmented from the powder during the laser ablation. The nanoparticle size in all samples shows a bimodal distribution, corresponding to different fragmentation mechanisms. The 2H-to-1T phase transition in the nanoparticles is likely caused by electron doping from the laser-induced plasma. The PTCEs of the nanoparticles increase with laser power and ablation time; the highest PTCE is around 38%. After examining the bandgaps and the Urbach energies of the nanoparticles, it is found that the high PTCEs are primarily attributed to defects and structural disorder in the laser-synthesized nanoparticles, which allow absorption of photons with energies smaller than the bandgap energy and facilitate non-radiative recombination of photoexcited carriers.

Interaction between ß-glucans and gut microbiota: a comprehensive review.

Gut microbiota (GMB) in humans plays a crucial role in health and diseases. Diet can regulate the composition and function of GMB which are associated with different human diseases. Dietary fibers can induce different health benefits through stimulation of beneficial GMB. ß-glucans (BGs) as dietary fibers have gained much interest due to their various functional properties. They can have therapeutic roles on gut health based on modulation of GMB, intestinal fermentation, production of different metabolites, and so on. There is an increasing interest in food industries in commercial application of BG as a bioactive substance into food formulations. The aim of this review is considering the metabolizing of BGs by GMB, effects of BGs on the variation of GMB population, influence of BGs on the gut infections, prebiotic effects of BGs in the gut, in vivo and in vitro fermentation of BGs and effects of processing on BG fermentability.

Rumen-protected glucose hastens uterine involution and increases numbers of ovarian follicles in early post-partum dairy cows.

The primary objectives were to investigate the effects of feeding a new rumen-protected glucose (RPG) on uterine involution and ovarian follicular dynamics in recently calved dairy cattle. From 4 to 30 days after calving, 16 Holsteins (first to third lactation, mean parity 1.75) were randomly assigned to be fed either a basal diet top-dressed with either 600 g RPG (RPG group) or 600 g of the coating material and glucose (CONT group). Based on transrectal ultrasonography, conducted every 3 days starting 20 days after calving, the interval from calving to complete uterine involution was shorter in RPG versus CONT (27.1 vs. 30.4 days, p < .01). Furthermore, based on transrectal ultrasonography conducted every 2 days, cattle fed RPG had smaller (3.0-4.9 mm) ovarian follicles (2.96 vs. 0.9, p < .001) and more total follicles (5.26 vs. 2.85, p < .01). Feeding RPG had increased serum insulin concentrations (4.59 ± 0.54 vs. 3.13 ± 0.57, p < .05), but had no significant effects on serum glucose concentrations, dry matter intake or milk yield. In conclusion, we inferred that cattle fed RPG had increased glucose turnover that was responsible for higher insulin concentrations, faster uterine involution, and more ovarian follicles.

Assessment of Spine Patient Preferences for the Location of Surgery Between a Hospital and an Ambulatory Surgical Center in the Time of COVID-19: An Analysis of Patient Surveys.

Introduction There has been a recent increase in the number of spinal procedures that can be performed in ambulatory surgical centers (ASCs). Studies have found that patients who undergo procedures at ASCs tend to have lower complication rates following procedures, including lower infection rates. Furthermore, ASCs offer significantly lower costs of procedures to patients and health insurance companies as compared to the costs of procedures performed in a hospital. Despite precautions and screening in place by ASCs, patients may be hesitant to undergo procedures outside of the hospital. Conversely, the ongoing COVID-19 pandemic has created hesitancy for many to go to the hospital for care due to the presence of COVID patients.  Objective To assess patient preferences in the location of elective spine procedures between ASCs and hospitals, the authors conducted a survey of spine surgery candidates in a single practice. Methods A survey measuring patient age, vaccination status, fear of contracting COVID-19, and preference of surgery location was given to spinal surgery candidates at a single practice between fall 2021 and winter 2022. Statistical differences between the means of response groups were measured by a two-sample Z-score test. Results A total of 58 surveys were completed by patients. No difference in preference was observed by age. A difference was observed between genders, with 66% of females preferring ASCs to 40% of males (α=0.03). Patients with a fear of contracting COVID-19 preferred to have their procedure performed in an ASC. No difference was observed in location due to vaccination status, but unvaccinated patients had a significantly lower fear of contracting COVID-19 (α=0.02). Conclusion The differences in patient preferences have no clear cause, highlighting the need for better patient education in regard to the risks and benefits of each location of surgery. The fear of contracting COVID-19 on the day of surgery appears to be more ideological than rational for unvaccinated patients, who had less fear of contracting COVID-19 than vaccinated patients, despite being more likely to contract COVID-19 than vaccinated patients.

Microencapsulation of Bacillus velezensis Using Alginate-Gum Polymers Enriched with TiO2 and SiO2 Nanoparticles.

Bacillus bacteria are a group of plant growth stimulants that increase plant growth and resistance to plant pathogens by producing various metabolites. With their large surface area and small size, nanoparticles can be used in controlled-release formulations and increase the efficiency of the desired product. Encapsulation of biological agents in combination with nanoparticles can be an essential step in increasing the performance of these agents in adverse environmental conditions. In this study, which is the result of a collaboration between scientists from Italy and Iran, Bacillus velezensis was encapsulated in alginate combined with whey protein and zedo, mastic, and tragacanth gums in the presence of silica and titania nanoparticles to obtain two-layer and multilayer assemblies acting as novel, smart micro-encapsulation systems. The results of laboratory studies showed that the B. velezensis could produce protease, lipase, siderophore, auxin, and a dissolution of mineral phosphate. Scanning electron microscopy images (SEM) showed that the studied microcapsules were almost spherical. Moisture affinity, swelling, and efficiency of each microcapsule were examined. The results showed that the highest encapsulation efficiency (94.3%) was related to the multilayer formulation of alginate-whey protein-zedo. XRD and FTIR spectroscopy showed that the alginate, whey protein, and zedo were mixed properly and no incompatible composition occurred in the reaction. This study aimed to provide a suitable formulation of biofertilizers based on biodegradable compounds as an alternative to chemical fertilizers, which is low cost and very effective without harming humans and the environment.

Exploring the impact of the United States-based accreditation council for pharmacy education certification on pharmacy education outside the United States.

Introduction: The Accreditation Council for Pharmacy Education (ACPE) offers certification for interested pharmacy programs outside the United States. This study aimed to explore the reported impact of this certification on the quality of pharmacy education among ACPE-certified pharmacy programs outside the US. Methods: This cross-sectional study was based on highly structured, standardized interviews. A predetermined questionnaire was designed to include both quantitative and qualitative items, which assessed participants' thoughts on the impact of ACPE certification on the quality of pharmacy education as well as programmatic and student learning outcomes. A total of 15 pharmacy colleges and schools outside the US have received the ACPE certification as of July 2020. After IRB approval, these programs were invited to participate in online live interviews, which were scheduled from May to July 2020 via Zoom®, and lasted approximately 45 min each. Results: Administrators from 13 programs participated in this study (87% respondent rate). The majority of these international pharmacy programs reported that the ACPE certification had promoted the quality of pharmacy education at their institutions. However, there were different views on how the ACPE certification has affected the operation of these international pharmacy programs. There was little or no impact of the certification on financial resources, such as salaries and development funds. Conclusion: Despite being confined to little or no change in certain areas of their programs, all the interviewees believed the ACPE certification had an overall positive impact on the quality of their programs, particularly in the area of assessment, preceptor quality and development, improving teaching and learning methods in both didactic and experiential curricula, and developing an inclusive feedback system to receive input from various stakeholders.

Hydrodynamic interactions significantly alter the dynamics of actin networks and result in a length scale dependent loss modulus.

Actin, the primary component of the cytoskeleton, is the most studied semiflexible filament. Yet, the dynamics of actin filamentous network is still a subject of debate. Here we show that hydrodynamic interactions may significantly alter the time scale of actin network deformation. The alteration may be easily in the range of 2-20 fold depending on the structural conformations and scales of interest. We show that for a single fiber, hydrodynamic interactions between the cytoskeletal mesh-sized segments can change the net force by up to 7 folds. We also demonstrate that cytoskeletal relaxation times are underestimated if hydrodynamic interaction effects are ignored, but bending mode shapes are not appreciably influenced. Ignoring hydrodynamic interactions can result in up to 20-fold overestimation of shear loss modulus in the 2 µm range we investigated. Moreover, in agreement with experimental studies, our models explain a highly length scale dependent loss modulus. Taken together, our data suggest that including hydrodynamic interactions is key to proper modeling and analysis of actin dynamics at any scales and dimensions, and therefore must not be neglected in future models and experimental analyses of cytoskeletal dynamics.

The Impact of Fasting on Major Metabolic Pathways of Macronutrients and Pharmacokinetics Steps of Drugs.

In this review, we have investigated how fasting promotes an adaptive cross-talk between different hormones and metabolic pathways to supply and meet the body's daily energy demands. We highlight in biochemical terms and mechanisms how fasting impacts four metabolic pathways-glycogenolysis, gluconeogenesis, amino acid oxidation, and fatty acid ß-oxidation-that are actively engaged in the metabolism of carbohydrates, proteins, and lipids. Fasting results in reduced insulin secretion and increased glucagon and epinephrine release to prevent or stimulate metabolic reaction(s). Fasting stimulates glycogenolysis, amino acid and glucose oxidation, aminotransferase reactions in skeletal muscle, and promotes gluconeogenesis and urea production in the liver. In addition, fasting promotes gene expression of lipid metabolism in skeletal muscle, the synthesis of ketone bodies in the liver, and intracellular hormone-sensitive lipase activity in adipose tissue. Furthermore, the impact of fasting on reducing cellular damage by mitochondrial reactive oxygen species is discussed. Lastly, we briefly describe the impact of fasting on the four steps of pharmacokinetics-the absorption, distribution, metabolism, and excretion of a few select drugs-with an emphasis on the elimination of drugs related to the cytochrome-P450 family of enzymes.

Evaluation of the risk factors associated with emergency department boarding: A retrospective cross-sectional study.

PURPOSE: Boarding is a common problem in the emergency department (ED) and is associated with poor health care and outcome. Imam Khomeini Hospital is the main healthcare center in Urmia, a metropolis in the northwest of Iran. Due to the overcrowding and high patient load, we aim to characterize the rate, cause and consequence of boarding in the ED of this center. METHODS: All medical records of patients who presented to the ED of Imam Khomeini Hospital from August 1, 2017 to August 1, 2018 were retrospectively analyzed. Patients with uncompleted records were excluded. Boarding was defined as the inability to transfer the admitted ED patients to a downstream ward in ≥2 h after the admission order. Demographic data, boarding rate, mortality and triage levels (1-5) assessed by emergency severity index were collected and analyzed. The first present time of patients was classified into 4 ranges as 0:00-5:59, 6:00-11:59, 12:00-17:59 and 18:00-23:59. Descriptive, parametric and non-parametric statistical tests were performed and the risk of boarding was determined by Pearson Chi-square test. RESULTS: Demographic data analysis showed that 941 (58.5%) male and 667 (41.5%) female, altogether 1608 patients were included in this study. Five patients (0.3%) died. The distribution of patients with the triage levels 1-5 was respectively 79 (4.9%), 1150 (71.5%), 374 (23.3%), 4 (0.2%) and 0 (0%). Most patients were of level 2. Only 75 (4.7%) patients required intensive care. The majority of patients (84.2%) were presented at weekdays. The maximum patient load was observed between 12:00-17:59. Of the 1608 patients, 340 (21.1%) experienced boarding within a mean admission time of 13.70 h. Among the 340-boarded patients, 20.1% belonged to surgery, 12.1% to orthopedics, 10.9% to neurosurgery and 10.3% to neurology. The boarding rate was higher in females, patients requiring intensive care and those with low triage levels. Compared with the non-boarded, the boarded patients had a higher mean age. CONCLUSION: The boarding rate is higher in the older and female patients. Moreover, boarding is dependent on the downstream ward sections: patients requiring surgical management experience the maximum boarding rate.

Smoking-associated increase in mucins 1 and 4 in human airways.

RATIONALE: Smoking-related chronic obstructive pulmonary disease (COPD) is associated with dysregulated production of mucus. Mucins (MUC) are important both for mucus secretion and epithelial defense. We have examined the distribution of MUC1 and MUC4 in the airway epithelial cells of never-smokers and smokers with and without COPD. METHODS: Mucosal biopsies and bronchial wash samples were obtained by bronchoscopy from age- and sex-matched COPD-patients (n = 38; GOLD I-II/A-B), healthy never-smokers (n = 40) and current smokers with normal lung function (n = 40) from the Karolinska COSMIC cohort (NCT02627872). Cell-specific expressions of MUC1, MUC4 and regulating factors, i.e., epithelial growth factor receptor (EGFR) 1 and 2, were analyzed by immunohistochemistry. Soluble MUC1 was measured by quantitative immunodetection on slot blot. RESULTS: The levels of cell-bound MUC1 expression in basal cells and in soluble MUC1 in bronchial wash were increased in smokers, regardless of airway obstruction. Patients with chronic bronchitis had higher MUC1 expression. The expression of MUC4 in cells with goblet cell phenotype was increased in smokers. The expression of EGFR2, but not that of EGFR1, was higher in never-smokers than in smokers. CONCLUSIONS: Smoking history and the presence of chronic bronchitis, regardless of airway obstruction, affect both cellular and soluble MUC1 in human airways. Therefore, MUC1 may be a novel marker for smoking- associated airway disease.

Association between number and type of different ACPA fine specificities with lung abnormalities in early, untreated rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA)-associated anticitrullinated protein/peptide antibodies (ACPA) might originate at mucosal sites such as the lungs. We aimed to examine the relationship between the ACPA repertoire and lung abnormalities on high-resolution CT (HRCT) in patients with earlyuntreated RA. METHODS: 106 patients with newly diagnosed untreated RA were examined with HRCT of the lungs. Blood samples were analysed for presence of rheumatoid factor (RF) and ACPA using either a CCP2 detection kit or an immunochip containing 10 different citrullinated peptides. Association between HRCT findings and the antibody repertoire was assessed by logistic regression analysis. RESULTS: The number (%) of patients with HRCT abnormalities was 58 (54.7%) for parenchymal abnormalities and 68 (64.2%) for airway abnormalities. CCP2 IgG, RF IgA and antibodies against citrullinated fibrinogen were associated with the presence of parenchymal lung abnormalities. Interestingly, a high number of ACPA fine specificities gave a high risk of having parenchymal lung abnormalities at the time of RA diagnosis. No significant signals were identified between ACPA specificities and risk for airway abnormalities. CONCLUSIONS: The presence of RF and ACPAs (especially against citrullinated fibrinogen peptides) as well as high number of ACPAs fine specificities are associated with parenchymal lung abnormalities in patients with early, untreated RA. This provides further support for an important pathogenic link between the lung and systemic autoimmunity, contributing to RA development.

Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis.

OBJECTIVE: A 'mucosal connection' in RA presently attracts increasing attention. We recently described the occurrence of secretory antibodies to citrullinated protein (SC-ACPA) in sera from patients with recent-onset RA. The current study was performed to evaluate possible associations between serum levels of secretory ACPA and signs of lung involvement in patients with early, untreated RA. METHODS: One hundred and forty-two RA patients were included as part of the 'LUng Investigation in newly diagnosed RA' study. One hundred and six patients were examined with high-resolution CT (HRCT) and 20 patients underwent bronchoscopy, where bronchial biopsies and bronchoalveolar lavage fluid (BALF) samples were obtained. SC-ACPA in serum and BALF were detected by an enzyme-linked immunoassay. Antibody levels were related to smoking history, pulmonary function, HRCT, BALF cell counts and findings in bronchial biopsies. RESULTS: SC-ACPA occurred in 16% of the serum samples and in 35% of the BALF samples. SC-ACPA levels in serum correlated with SC-ACPA levels in BALF (σ = 0.50, P = 0.027) and were higher among patients with HRCT parenchymal lung abnormalities (P = 0.022) or bronchiectasis (P = 0.042). Also, ever smoking was more frequent among serum SC-ACPA-positive patients (91% vs 67%, P = 0.023), and the SC-ACPA levels correlated with the number of pack-years (σ=0.20, P = 0.020). CONCLUSION: In early, untreated RA, serum levels of SC-ACPA reflect lung involvement in terms of local ACPA levels, smoking and lung abnormalities on HRCT. These findings strengthen the link between mucosal ACPA responses and the lungs in RA.