Inconsequential role for chemerin-like receptor 1 in the manifestation of ozone-induced lung pathophysiology in male mice.

We executed this study to determine if chemerin-like receptor 1 (CMKLR1), a Gi/o protein-coupled receptor expressed by leukocytes and non-leukocytes, contributes to the development of phenotypic features of non-atopic asthma, including airway hyperresponsiveness (AHR) to acetyl-ß-methylcholine chloride, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Accordingly, we quantified sequelae of non-atopic asthma in wild-type mice and mice incapable of expressing CMKLR1 (CMKLR1-deficient mice) following cessation of acute inhalation exposure to either filtered room air (air) or ozone (O3), a criteria pollutant and non-atopic asthma stimulus. Following exposure to air, lung elastic recoil and airway responsiveness were greater while the quantity of adiponectin, a multi-functional adipocytokine, in bronchoalveolar lavage (BAL) fluid was lower in CMKLR1-deficient as compared to wild-type mice. Regardless of genotype, exposure to O3 caused AHR, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Nevertheless, except for minimal genotype-related effects on lung hyperpermeability and BAL adiponectin, we observed no other genotype-related differences following O3 exposure. In summary, we demonstrate that CMKLR1 limits the severity of innate airway responsiveness and lung elastic recoil but has a nominal effect on lung pathophysiology induced by acute exposure to O3.

How to move forward in shared decision-making in pediatric palliative care.

Pediatric palliative care has grown immensely in recent years in the world. However, shared decision-making remains a complex process, especially in pediatric palliative care. In particular, a number of issues are priorities to improve the shared decision-making process and ensure high-quality pediatric palliative care for every child. Working on these priorities will improve shared decision-making and thereby enhance high-quality pediatric palliative care around the globe.

Pediatric palliative care across continents: Communication and shared-decision-making.

Despite the significant growth and development of pediatric palliative care worldwide, significant challenges remain. One of those challenges is shared decision-making, by which parents, families and professionals all work together to develop a plan of care that reflects both the medical facts and the patient's family's values. Shared decision-making about palliative care and about death and dying may mean different things in different cultures and countries. It is therefore important to learn and compare practices around the world.

Impact of Cardiac and Cerebrovascular Complications During Hospitalization on Long-Term Prognosis in Patients With COVID-19.

The impact of cardiac and cerebrovascular events during COVID-19 hospitalization on long-term prognosis remains uncertain. We aimed to evaluate the effect of myocardial infarction (MI), cerebrovascular accident (CVA), and pulmonary embolism (PE) during hospitalization on the long-term prognosis in patients who survived COVID-19 hospitalization. A retrospective observational analysis was performed on a cohort of 2,389 patients who survived COVID-19 hospitalization in our institution between January and June 2020. The patients were divided into MI (n = 111) and non-MI (n = 2,278) groups according to the presence of MI during hospitalization. As a subanalysis, the patients were assigned to CVA (n = 97) and non-CVA (n = 2,292) and PE (n = 54) and non-PE (n = 2,335) groups. The primary outcome was long-term survival after discharge. During a median follow-up period of 2.4 years after discharge, 30 patients (27.0%) in the MI group and 140 patients (6.2%) in the non-MI group died (p <0.001). The Kaplan-Meier survival curve analysis demonstrated that the MI group was significantly associated with an increased incidence of all-cause death after discharge (log-rank p <0.001), as supported by the multivariate Cox proportional hazards model analysis (hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.61 to 3.74, p <0.001). However, the presence of CVA (HR 1.46, 95% CI 0.91 to 2.34, p = 0.113) or PE (HR 0.94, 95% CI 0.23 to 3.84, p = 0.937) were not associated with an increased incidence of all-cause death after discharge. In conclusion, among the cardiovascular and cerebrovascular complications associated with COVID-19 hospitalization, the presence of MI during hospitalization was proved to be a significant independent predictor of long-term mortality in patients who survived COVID-19 hospitalization.

Delayed Aortic Valve Perforation Caused by Blunt Trauma.

Traumatic aortic regurgitation (AR) is a rare complication of blunt chest trauma. We described the case of a 35-year-old male who presented to our hospital with shortness of breath 7 years after sustaining blunt chest trauma associated with a motorcycle accident. Transthoracic and transesophageal echocardiogram detected severe AR with two separate jets. The patient was diagnosed with congestive heart failure due to severe AR, and surgical aortic valve replacement was performed. A large perforation of the right coronary cusp likely sustained during the initial blunt chest trauma injury was confirmed surgically. As AR caused by blunt chest trauma can gradually worsen, it is necessary to confirm if there is a history of trauma in patients with severe AR of unknown origin.

Improvement and implementation of a national individual care plan in paediatric palliative care: a study protocol.

INTRODUCTION: Paediatric palliative care (PPC) is care for children with life-threatening or life-limiting conditions, and can involve complex high-tech care, which can last for months or years. In 2015, the National Individual Care Plan (ICP) for PPC was developed and has shown to be successful. The ICP can be seen as an instrument to facilitate coordination, quality and continuity of PPC. However, in practice, an ICP is often completed too late and for too few children. We aim to improve the coordination, quality and continuity of care for every child with a life-threatening or life-limiting condition and his/her family by further developing and implementing the ICP in the Netherlands. METHODS AND ANALYSIS: To evaluate the original ICP, ICP 1.0, interviews and questionnaires will be held among parents of children who have or have had an ICP 1.0 and healthcare professionals (HCPs) who used ICP 1.0. Based on the results, ICP 1.0 will be further developed. An implementation strategy will be written and the renewed ICP, ICP 2.0, will be nationally tested in an implementation period of approximately 7 months. During the implementation period, ICP 2.0 will be used for all children who are registered with Children's Palliative Care teams. After the implementation period, ICP 2.0 will be evaluated using interviews and questionnaires among parents of children who received ICP 2.0 and HPCs who worked with ICP 2.0. Based on these results, ICP 2.0 will be further optimised into the final version: ICP 3.0. ETHICS AND DISSEMINATION: This study received ethical approval. The ICP 3.0 will be disseminated through the Dutch Centre of Expertise in Children's Palliative Care, to ensure wide availability for the general public and HCPs within PPC. Additionally, we aim to publish study results in open-access, peer-reviewed journals and to present results at national and international scientific meetings.

Interleukin-11 receptor subunit α-1 is required for maximal airway responsiveness to methacholine after acute exposure to ozone.

Interleukin (IL)-11, a multifunctional cytokine, contributes to numerous biological processes, including adipogenesis, hematopoiesis, and inflammation. Asthma, a respiratory disease, is notably characterized by reversible airway obstruction, persistent lung inflammation, and airway hyperresponsiveness (AHR). Nasal insufflation of IL-11 causes AHR in wild-type mice while lung inflammation induced by antigen sensitization and challenge, which mimics features of atopic asthma in humans, is attenuated in mice genetically deficient in IL-11 receptor subunit α-1 (IL-11Rα1-deficient mice), a transmembrane receptor that is required conjointly with glycoprotein 130 to transduce IL-11 signaling. Nevertheless, the contribution of IL-11Rα1 to characteristics of nonatopic asthma is unknown. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11Rα1 attenuates lung inflammation and increases airway responsiveness after acute inhalation exposure to ozone (O3), a criteria pollutant and nonatopic asthma stimulus. Accordingly, 4 and/or 24 h after cessation of exposure to filtered room air or O3, we assessed lung inflammation and airway responsiveness in wild-type and IL-11Rα1-deficient mice. With the exception of bronchoalveolar lavage macrophages and adiponectin, which were significantly increased and decreased, respectively, in O3-exposed IL-11Rα1-deficient as compared with O3-exposed wild-type mice, no other genotype-related differences in lung inflammation indices that we quantified were observed in O3-exposed mice. However, airway responsiveness to acetyl-ß-methylcholine chloride (methacholine) was significantly diminished in IL-11Rα1-deficient as compared with wild-type mice after O3 exposure. In conclusion, these results demonstrate that IL-11Rα1 minimally contributes to lung inflammation but is required for maximal airway responsiveness to methacholine in a mouse model of nonatopic asthma.

Home care nurses more positive about the palliative care that is provided and their own competence than hospital nurses: a nationwide survey.

BACKGROUND: People often prefer to stay at home until the end of life, but hospital admissions are quite common. In previous research bereaved relatives were found to be less positive about palliative care in hospital. However, it was not known how the content and quality of palliative care differ between home care and hospitals from the perspectives of hospital nurses and home care nurses and how palliative care in these settings could be improved. METHODS: A survey was held among hospital and home care nurses, recruited from a nationwide Nursing Staff Panel and through open calls on social media and in an online newsletter. The pre-structured online survey included questions on the palliative care provided, the quality of this care and the respondent's perceived competence in providing palliative care. The questionnaire was completed by 229 home care nurses and 106 hospital nurses. RESULTS: Most nurses provided palliative care in the physical and psychological domains, fewer provided care in the social and spiritual domains. A higher percentage of home care nurses stated that they provided care in these domains than hospital nurses. Overall, 70% of the nurses rated the quality of palliative care as very good to excellent. This percentage was higher among home care nurses (76.4%) than hospital nurses (59.4%). Moreover, a higher percentage of home care nurses (94.4%) stated they felt competent to a great extent to provide palliative care compared to hospital nurses (84.7%). Competencies regarding the physical domain were perceived as better compared to the competencies concerning the other domains. The nurses recommended paying more attention to inter-professional collaboration and communication, timely identification of the palliative phase and advance care planning, and more time available for palliative care patients. CONCLUSION: Although the quality of palliative care was rated as very good to excellent by nurses, improvements can still be made, particularly regarding palliative care in hospitals. Although patients often prefer to die at home rather than in hospital, still a considerable number of people do die in hospital; therefore hospital nurses must also be trained and be able to provide high-quality palliative care.

Prevalence and Functional Implication of Silent Coronary Artery Disease in Marathon Runners Over 40 Years of Age: The MATCH-40 Study.

BACKGROUND: Marathon participation is becoming increasingly popular among individuals ≥40 years of age. Little is known about the prevalence of subclinical coronary artery disease (CAD) and corresponding ischemia in this patient population. The study objectives are: (1) to characterize the prevalence of silent CAD in marathoners ≥ 40 years old using cardiac computed tomography angiography (CCT); and (2) if subclinical CAD was detected, to determine the functional significance of occult lesions by stress echocardiography (SE). METHODS: Marathoners aged ≥ 40 years who completed a full marathon between 2018 and 2019 were recruited to undergo a prospective CCT. Coronary artery stenosis was graded as zero, mild (1%-49%), moderate (50%-69%), or severe (> 70%). All study participants diagnosed with mild-to-severe atherosclerotic CAD on CCT further underwent functional imaging with exercise treadmill SE. RESULTS: A total of 65 individuals (53 ± 7 years, 65% males, 24 ± 3 kg/m2) underwent a prospective CCT within 12 months of marathon completion. Of the total study population, 13 participants (20%) were diagnosed with CAD, of whom 10 (77%) had mild disease, 1 (8%) had moderate disease, and 2 (15%) had severe disease by CCT. Despite the identification of subclinical CAD on CCT, none of the 13 patients had any evidence of inducible ischemia on SE. CONCLUSIONS: This is the first study to incorporate both CCT and SE in the evaluation of subclinical CAD in marathoners ≥40 years old. Although the overall prevalence of anatomic CAD was 20%, there was no evidence of functional ischemia in this highly competitive cohort.

CONTEXTE: Les marathons ont gagné en popularité auprès des individus âgés de 40 ans ou plus. On en sait toutefois peu sur la prévalence de la coronaropathie subclinique et de l'ischémie qui lui est associée dans cette population de patients. L'étude visait à 1) caractériser la prévalence de la coronaropathie silencieuse chez les marathoniens âgés de 40 ans ou plus à l'aide d'une angiographie cardiaque par tomodensitométrie (ACTDM) si une coronaropathie subclinique était détectée, à déterminer l'importance fonctionnelle des lésions occultes par une échocardiographie d'effort (EE). MÉTHODOLOGIE: Des marathoniens âgés de 40 ans ou plus ayant réalisé un marathon entre 2018 et 2019 ont été recrutés et soumis à une ACTDM prospective. Les sténoses des artères coronaires étaient classées selon une échelle allant de zéro, légère (1 à 49 %), modérée (50 à 69 %) à sévère (> 70 %). Tous les participants à l'étude ayant reçu un diagnostic de coronaropathie athéroscléreuse légère à sévère à la suite de l'ACTDM ont été soumis à une imagerie fonctionnelle avec EE sur tapis roulant. RÉSULTATS: Au total, 65 sujets (53 ± 7 ans, 65 % d'hommes, 24 ± 3 kg/m2) ont été soumis à une ACTDM prospective dans un délai de 12 mois à la suite de leur dernier marathon. Dans l'ensemble de la population à l'étude, 13 participants (20 %) ont reçu un diagnostic de coronaropathie; 10 (77 %) présentaient une maladie bénigne, 1 (8 %) présentait une maladie modérée et 2 (15 %) présentaient une maladie sévère selon l'ACTDM. Même si une coronaropathie subclinique a été diagnostiquée lors de l'ACTDM, aucun des 13 patients ne présentait de signe d'ischémie inductible à l'EE. CONCLUSIONS: Il s'agit de la première étude à utiliser l'ACTDM et l'EE pour évaluer la présence d'une coronaropathie chez des marathoniens âgés de 40 ou plus. Même si la prévalence globale de la coronaropathie anatomique était de 20 %, il n'y avait aucun signe d'ischémie fonctionnelle au sein de cette cohorte hautement compétitive.

The Cardioprotective Role of Flaxseed in the Prevention of Doxorubicin- and Trastuzumab-Mediated Cardiotoxicity in C57BL/6 Mice.

BACKGROUND: Although the combination of doxorubicin (DOX) and trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anticancer drugs are associated with significant cardiotoxic side effects. OBJECTIVE: We investigated whether prophylactic administration of flaxseed (FLX) and its bioactive components, α-linolenic acid (ALA) and secoisolariciresinol diglucoside (SDG), would be cardioprotective against DOX + TRZ-mediated cardiotoxicity in a chronic in vivo female murine model. METHODS: Wild-type C57BL/6 female mice (10-12 wk old) received daily prophylactic treatment with one of the following diets: 1) regular control (RC) semi-purified diet; 2) 10% FLX diet; 3) 4.4% ALA diet; or 4) 0.44% SDG diet for a total of 6 wks. Within each arm, mice received 3 weekly injections of 0.9% saline or a combination of DOX [8 mg/(kg.wk)] and TRZ [3 mg/(kg.wk)] starting at the end of week 3. The main outcome was to evaluate the effects of FLX, ALA, and SDG on cardiovascular remodeling and markers of apoptosis, inflammation, and mitochondrial dysfunction. Significance between measurements was determined using a 4 (diet) × 2 (chemotherapy) × 2 (time) mixed factorial design with repeated measures. RESULTS: In the RC + DOX + TRZ-treated mice at week 6 of the study, the left ventricular ejection fraction (LVEF) decreased by 50% compared with the baseline LVEF (P < 0.05). However, the prophylactic administration of the FLX, ALA, or SDG diet was partially cardioprotective, with mice in these treatment groups showing an ∼68% increase in LVEF compared with the RC + DOX + TRZ-treated group at week 6 (P < 0.05). Although markers of inflammation (nuclear transcription factor κB), apoptosis [poly (ADP-ribose) polymerase-1 and the ratio of BCL2-associated X protein to B-cell lymphoma-extra large], and mitochondrial dysfunction (BCL2-interacting protein 3) were significantly elevated by approximately 2-fold following treatment with RC + DOX + TRZ compared with treatment with RC + saline at week 6, prophylactic administration of FLX, ALA, or SDG partially downregulated these signaling pathways. CONCLUSION: In a chronic in vivo female C57BL/6 mouse model of DOX + TRZ-mediated cardiotoxicity, FLX, ALA, and SDG were partially cardioprotective.

Scleraxis as a prognostic marker of myocardial fibrosis in hypertrophic cardiomyopathy (SPARC) study.

Interstitial fibrosis is a histopathological hallmark of hypertrophic cardiomyopathy (HCM). Although extracellular matrix (ECM) biomarkers, including matrix metalloproteinases, are overexpressed in HCM patients, they do not correlate with sudden cardiac death (SCD) risk. The objective of this study was to determine whether scleraxis, a transcription factor that regulates collagen gene expression, is detectable in HCM patients and correlates with disease burden. Between 2017 and 2018, a total of 46 HCM patients were enrolled (58 ± 14 years (31 males, 15 females)) with a mean 5 year SCD risk of 2.3% ± 1.3%. Cardiac MRI confirmed HCM in all patients with a mean interventricular septal thickness of 20 ± 2 mm. Late gadolinium enhancement (LGE) was present in 32 (70%) study participants occupying 18% ± 7% of the left ventricular (LV) myocardium. Serum scleraxis levels were significantly higher in the HCM patients by approximately twofold as compared to controls (0.76 ± 0.06 versus 0.32 ± 0.02 ng/mL, p < 0.05). No correlation was demonstrated between serum scleraxis levels and markers of disease severity in HCM patients, including maximum LV wall thickness, %LGE, and SCD risk factors. Serum scleraxis is elevated in the HCM population. Future studies are warranted to evaluate the prognostic value of scleraxis in identifying high-risk HCM patients who require aggressive management for prevention of SCD.

In-Hospital Cardiac Arrest in the Cardiac Catheterization Laboratory: Effective Transition from an ICU- to CCU-Led Resuscitation Team.

OBJECTIVES: (1) To examine the incidence and outcomes of in-hospital cardiac arrests (IHCAs) in a large unselected patient population who underwent coronary angiography at a single tertiary academic center and (2) to evaluate a transitional change in which the cardiologist is positioned as the cardiopulmonary resuscitation (CPR) leader in the cardiac catheterization laboratory (CCL) at our local tertiary care institution. BACKGROUND: IHCA is a major public health concern with increased patient morbidity and mortality. A proportion of all IHCAs occurs in the CCL. Although in-hospital resuscitation teams are often led by an Intensive Care Unit- (ICU-) trained physician and house staff, little is known on the role of a cardiologist in this setting. METHODS: Between 2012 and 2016, a single-center retrospective cohort study was performed examining 63 adult patients (70 ± 10 years, 60% males) who suffered from a cardiac arrest in the CCL. The ICU-led IHCAs included 19 patients, and the Coronary Care Unit- (CCU-) led IHCAs included 44 patients. RESULTS: Acute coronary syndrome accounted for more than 50% of cardiac arrests in the CCL. Pulseless electrical activity was the most common rhythm requiring chest compression, and cardiogenic shock most frequently initiated a code blue response. No significant differences were observed between the ICU-led and CCU-led cardiac arrests in terms of hospital length of stay and 1-year survival rate. CONCLUSION: In the evolving field of Critical Care Cardiology, the transition from an ICU-led to a CCU-lead code blue team in the CCL setting may lead to similar short-term and long-term outcomes.

The Role of Cardiac Magnetic Resonance Imaging in Severe Anorexia Nervosa.

Objective Anorexia nervosa (AN) patients are at an increased risk of developing cardiac complications including bradyarrhythmias, systolic dysfunction, pericardial effusions, and sudden cardiac death. Although previous echocardiographic studies in AN patients have demonstrated a reduction in overall left ventricular (LV) mass, systolic dysfunction, and silent pericardial effusions, little is known about the role of cardiac magnetic resonance imaging (CMR) in assessing this patient population. The objective of this study was to assess cardiac indices and the presence of myocardial fibrosis in AN patients. Methods Between 2014 and 2015, a cross-sectional pilot study of 16 female patients who met the Diagnostic and Statistics Manual of Mental Disorders, fifth edition (DSM-5) criteria for AN was conducted at a single tertiary care center. Baseline characteristics including age, weight, food restriction behavior, over-exercise, self-induced vomiting, and laxative abuse were collected in the study population. Electrocardiography, transthoracic echocardiography (TTE), and CMR were performed. Results The mean age was 17 years (range: 13-22 years). There were no conduction abnormalities as the average PR interval was 152 ms (range: 130-190 ms) and QTc was 413 ms (range: 360-450 ms). Using TTE, the left ventricular ejection fraction (LVEF) was 54 ± 4% with a lower LV mass/body surface area (BSA) of 56 ± 7g/m2 in AN patients as compared to controls. Using CMR, both the mean LVEF of 52 ± 9% and LV mass/BSA of 45 ± 4g/m2 were lower in AN patients as compared to controls. Using CMR, both right ventricular ejection fraction (RVEF) of 50 ± 10% and a right ventricular (RV) mass/BSA of 18 ± 3g/m2 were smaller in AN patients as compared to controls. There was no evidence of late gadolinium enhancement (LGE) in the study population. Conclusions Young patients with AN have lower cardiac mass and volumes with no evidence of myocardial fibrosis.

Role of renin-angiotensin system antagonists in the prevention of bevacizumab- and sunitinib-mediated cardiac dysfunction.

Although anticancer systemic therapy agents clearly lead to improved survival in patients with cancer, these can come at the cost of serious complications including cardiotoxicity. Two types of targeted systemic therapies currently in use for colorectal cancer (CRC) and renal cell cancer (RCC), respectively, include the vascular endothelial growth factor inhibitor bevacizumab (BVZ) and the tyrosine kinase inhibitor sunitinib (SNT). Despite the beneficial effects of BVZ and SNT in improving clinical outcomes in the settings of CRC and RCC, there is an increased risk of cardiac dysfunction. The aim of the present study was to determine whether prophylactic administration of renin-angiotensin system (RAS) inhibitors would attenuate the cardiotoxic side effects of BVZ or SNT in a chronic in vivo murine model. A total of 194 wild-type C57Bl/6 male mice received: 1) 0.9% saline, 2) BVZ (10 mg·kg-1·wk-1), or 3) SNT (40 mg·kg-1·day-1) for 4 wk. Within each arm, mice received daily prophylactic treatment with hydralazine (0.05 mg/ml), aliskiren (50 mg/kg), perindopril (4 mg/kg), or valsartan (2 mg/kg). Although hydralazine effectively lowered blood pressure in BVZ- or SNT-treated mice, it did not prevent left ventricular systolic dysfunction. Prophylactic administration of aliskiren, perindopril, or valsartan prevented adverse cardiovascular remodeling in mice treated with either BVZ or SNT. The addition of RAS antagonists also downregulated expression of phosphorylated p38 and Bcl-2-like 19-kDa interacting protein 3 in SNT-treated mice. In our chronic in vivo murine model, RAS antagonists partially attenuated the development of BVZ- or SNT-mediated cardiac dysfunction. Future clinical studies are warranted to investigate the cardioprotective effects of prophylactic treatment with RAS inhibitors in the settings of CRC and RCC. NEW & NOTEWORTHY In the evolving field of cardio-oncology, bevacizumab and sunitinib improve clinical outcomes in the settings of metastatic colorectal cancer and renal cell cancer, respectively. These anticancer drugs, however, are associated with an increased risk of cardiotoxicity. The prophylactic administration of renin-angiotensin system antagonists is partially cardioprotective against bevacizumab- and sunitinib-mediated cardiac dysfunction.

Airway Autoimmune Inflammatory Response (AAIR) Syndrome: An Asthma-Autoimmune Overlap Disorder?

Asthma encompasses numerous phenotypes that may require alternate approaches to diagnosis and therapy, particularly for patients whose symptoms remain poorly controlled despite escalating treatment. We describe 3 patients with apparent asthma who demonstrated unusual findings on cryobiopsy by flexible bronchoscopy and responded to therapy directed against autoimmune disease.

Cryotherapy to treat and prevent airway stenosis in a patient with granulomatosis with polyangiitis.

We report our use of cryotherapy delivered via flexible bronchoscopy in a 15-year old girl with granulomatosis with polyangiitis to both treat established airway stenosis and prevent multi-level progression of disease.

Chemokine (C-C Motif) Receptor-Like 2 is not essential for lung injury, lung inflammation, or airway hyperresponsiveness induced by acute exposure to ozone.

Inhalation of ozone (O3), a gaseous air pollutant, causes lung injury, lung inflammation, and airway hyperresponsiveness. Macrophages, mast cells, and neutrophils contribute to one or more of these sequelae induced by O3 Furthermore, each of these aforementioned cells express chemokine (C-C motif) receptor-like 2 (Ccrl2), an atypical chemokine receptor that facilitates leukocyte chemotaxis. Given that Ccrl2 is expressed by cells essential to the development of O3-induced lung pathology and that chemerin, a Ccrl2 ligand, is increased in bronchoalveolar lavage fluid (BALF) by O3, we hypothesized that Ccrl2 contributes to the development of lung injury, lung inflammation, and airway hyperresponsiveness induced by O3 To that end, we measured indices of lung injury (BALF protein, BALF epithelial cells, and bronchiolar epithelial injury), lung inflammation (BALF cytokines and BALF leukocytes), and airway responsiveness to acetyl-ß-methylcholine chloride (respiratory system resistance) in wild-type and mice genetically deficient in Ccrl2 (Ccrl2-deficient mice) 4 and/or 24 hours following cessation of acute exposure to either filtered room air (air) or O3 In air-exposed mice, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice. O3 increased BALF chemerin in mice of both genotypes, yet following O3 exposure, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice. O3 increased indices of lung injury, lung inflammation, and airway responsiveness. Nevertheless, no indices were different between genotypes following O3 exposure. In conclusion, we demonstrate that Ccrl2 modulates chemerin levels in the epithelial lining fluid of the lungs but does not contribute to the development of O3-induced lung pathology.

Plasminogen activator inhibitor-1 does not contribute to the pulmonary pathology induced by acute exposure to ozone.

Expression of plasminogen activator inhibitor (PAI)-1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O3), a gaseous air pollutant. PAI-1 regulates expression of interleukin (IL)-6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O3 Given these observations, we hypothesized that PAI-1 contributes to the severity of the aforementioned sequelae by regulating expression of IL-6, KC, and MIP-2 following acute exposure to O3 To test our hypothesis, wild-type mice and mice genetically deficient in PAI-1 (PAI-1-deficient mice) were acutely exposed to either filtered room air or O3 (2 ppm) for 3 h. Four and/or twenty-four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL-6, KC, MIP-2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl-ß-methylcholine chloride (respiratory system resistance) were measured in wild-type and PAI-1-deficient mice. O3 significantly increased indices of lung injury, pulmonary inflammation, and airway responsiveness in wild-type and PAI-1-deficient mice. With the exception of MIP-2, which was significantly lower in PAI-1-deficient as compared to wild-type mice 24 h following cessation of exposure to O3, no other genotype-related differences occurred subsequent to O3 exposure. Thus, following acute exposure to O3, PAI-1 neither regulates pulmonary expression of IL-6 and KC nor functionally contributes to any of the pulmonary pathological sequelae that arise from the noxious effects of inhaled O3.

Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure.

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1ß)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1ß, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-ß-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.

Health & Demographic Surveillance System Profile: The Taabo Health and Demographic Surveillance System, Côte d'Ivoire.

The Taabo Health and Demographic Surveillance System (HDSS) is located in south-central Côte d'Ivoire, approximately 150 km north-west of Abidjan. The Taabo HDSS started surveillance activities in early 2009 and the man-made Lake Taabo is a key eco-epidemiological feature. Since inception, there has been a strong interest in research and integrated control of water-associated diseases such as schistosomiasis and malaria. The Taabo HDSS has generated setting-specific evidence on the impact of targeted interventions against malaria, schistosomiasis and other neglected tropical diseases. The Taabo HDSS consists of a small town, 13 villages and over 100 hamlets. At the end of 2013, a total population of 42 480 inhabitants drawn from 6707 households was under surveillance. Verbal autopsies have been conducted to determine causes of death. Repeated cross-sectional epidemiological surveys on approximately 5-7% of the population and specific, layered-on haematological, parasitological and questionnaire surveys have been conducted. The Taabo HDSS provides a database for surveys, facilitates interdisciplinary research, as well as surveillance, and provides a platform for the evaluation of health interventions. Requests to collaborate and to access data are welcome and should be addressed to the secretariat of the Centre Suisse de Recherches Scientifiques en Côte d'Ivoire: [secretariat@csrs.ci].