bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term reduction in asthma morbidity following an asthma self-management programme
Authors: D'Souza WJ , Te Karu H , Fox C , Harper M , Gemmell T , Ngatuere M , Wickens K , Crane J , Pearce N , Beasley R
Published: November 2022

The adult "credit card" asthma self-management plan has been shown to be an effective and acceptable system for reducing asthma morbidity when introduced as part of a 6 month community-based asthma programme. The aim of the present study was to assess the effectiveness of the credit card plan 2 yrs after the end of the programme. Markers of asthma morbidity and use of medical services were compared during the 12 months before enrolment, and 2 yrs after completing the 6 month asthma programme. Of the 69 participants who originally enroled in the 6 month asthma programme, 58 were surveyed 2 yrs after completion of the programme. These participants showed a significant improvement in all but one of the asthma morbidity measures. The proportion waking most nights with asthma in the previous 12 months decreased from 29 to 9% (p=0.02), emergency visits to a general practitioner decreased from 43 to 16% (p=0.001), hospital emergency department visits with asthma decreased from 19 to 5% (p=0.02) and hospital admissions decreased from 17 to 5% (p=0.04). Only 24% of patients reported that they usually monitored their peak flow rate daily, but this increased to 73% during a "bad" attack of asthma. A long-term reduction in asthma morbidity and requirement for acute medical services can result following the introduction of the adult credit card asthma self-management plan. Adult patients with asthma are most likely to undertake peak flow monitoring preferentially during periods of unstable asthma, rather than routinely during periods of good control.
Effect of thromboxane A2 inhibitors on allergic pulmonary inflammation in mice
Authors: Shi H , Yokoyama A , Kohno N , Hirasawa Y , Kondo K , Sakai K , Hiwada K
Published: November 2022

Thromboxane (Tx)A2 synthase inhibitors and thromboxane prostanoid (TP) receptor antagonists have been developed as anti-asthma drugs. TxA2 may contribute to airflow limitation and bronchial hyperresponsiveness, and these compounds have been demonstrated to improve them. However, it is not known whether TxA2 is involved in bronchial inflammation. To address this question, we explored the influences of OKY-046 (a TxA2 synthase inhibitor) and S-1452 (a TP receptor antagonist) on eosinophilic inflammation of the airways using a murine model. BALB/c mice sensitized with ovalbumin and challenged by repeated exposure to ovalbumin yielded marked eosinophilia in bronchoalveolar lavage fluid (BALF). Treatment with either compound significantly reduced the number of total cells and eosinophils in BALF in a dose-dependent manner. The production of interleukin (IL)-5, IL-2 and interferon (IFN)-gamma by antigen-stimulated splenic mononuclear cells (SMNC) was significantly decreased in mice treated with either compound compared to that in untreated mice. Furthermore, both compounds inhibited proliferation and cytokine production of SMNC in vitro. These results suggest that both OKY-046 and S-1452 are capable of inhibiting production of cytokines, which in turn inhibits eosinophil infiltration into the murine airway. Thus, both thromboxane A2 synthesis inhibitors and thromboxane prostanoid antagonists may be effective as anti-inflammatory drugs in the treatment of asthma.
Local cytokine messenger ribonucleic acid expression and in vitro allergic late phase responses in Brown-Norway rats
Authors: Minshall EM , Dandurand RJ , Hamid Q , Eidelman DH
Published: November 2022

The events subsequent to antigen challenge in allergic asthmatics involve the synthesis of pro-inflammatory cytokines. However, little is known how cytokine gene activation prior to allergen challenge may influence this series of events, nor how cytokine gene expression is related to antigen-induced alterations in lung function. Using a novel in vitro explant technique, we hypothesized that the local expression of cytokines influenced the development of antigen-induced late-onset airway responses, and that alterations in cytokine messenger ribonucleic acid (mRNA) expression were associated with antigen-induced changes in airway luminal area. Explants were prepared from excised lungs of ovalbumin-sensitized Brown-Norway rats. Airways were challenged by direct application of ovalbumin or an irrelevant control antigen. Cryostat sections of explants were used for in situ hybridization and mRNA for interleukin (IL)-2, IL-4 and interferon (IFN)-gamma were detected using radiolabelled probes. We found that the presence of high numbers of cells expressing IFN-gamma and IL-2 mRNA within the airways attenuated the development of antigen-induced late airway responses in sensitized rat lung explants. Furthermore, we observed that cytokine mRNA for IL-4 was significantly increased following allergen exposure in sensitized lung explants exhibiting late airway responses. This study implicates the local expression of interferon-gamma and interleukin-2 messenger ribonucleic acid in the failure of sensitized rat lung explants to exhibit late airway responses, and provides evidence linking local interleukin-4 messenger ribonucleic acid expression to the sequelae of events occurring as a result of antigen exposure within the airways.
Lung diffusing capacity and exercise in subjects with previous high altitude pulmonary oedema
Authors: Steinacker JM , Tobias P , Menold E , Reissnecker S , Hohenhaus E , Liu Y , Lehmann M , Bartsch P , Swenson ER
Published: November 2022

Subjects with a history of high-altitude pulmonary oedema (HAPE) have increased pulmonary artery pressure and more ventilation-perfusion (V'A/Q') inhomogeneity with hypoxia and exercise. We used noninvasive methods to determine whether there are differences in the pulmonary diffusing capacity for carbon monoxide (DL,CO) and cardiac output (Q') during exercise, indicative of a more restricted pulmonary vascular bed in subjects with a history of HAPE. Eight subjects with radiographically documented HAPE and five controls with good altitude tolerance had standard pulmonary function testing and were studied during exercise at 30 and 50% of normoxic maximal oxygen consumption (V'O2) at an inspiratory oxygen fraction of 0.14 and 0.21. DL,CO and Q' were measured by CO and acetylene rebreathing techniques. HAPE-resistant subjects had 35% greater functional residual capacity than HAPE-susceptible subjects. Vital capacity and total lung capacity were also 7-10% greater. There were no differences in airflow rates or resting diffusing capacity. However, DL,CO in HAPE-susceptible subjects was lower in hypoxia and with exercise, and showed less increase (32 versus 49%) with the combined stimulus of hypoxic exercise. HAPE-susceptible subjects had smaller increases in stroke volume, Q', and ventilation during exercise. The findings are consistent with lower pulmonary vasoconstriction, greater vascular capacitance and greater ventilatory responsiveness during exercise in subjects who are resistant to high-altitude pulmonary oedema. Their larger lung volumes suggest a constitutional difference in pulmonary parenchyma or vasculature, which may be a determinant of high-altitude pulmonary oedema resistance.
Asthma severity and susceptibility to air pollution
Authors: Hiltermann TJ , Stolk J , van der Zee SC , Brunekreef B , de Bruijne CR , Fischer PH , Ameling CB , Sterk PJ , Hiemstra PS , van Bree L
Published: November 2022

Exacerbations of asthma have been associated with exposure to ozone or particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10). We postulated in this study that the association of summertime air pollution (i.e. ozone and PM10) with acute respiratory symptoms, medication use and peak expiratory flow differs among patients grouped according to asthma severity. During the summer of 1995, effects of ambient air pollution on these parameters were studied in a panel of 60 nonsmoking patients with intermittent to severe persistent asthma. These patients were recruited from our Pulmonary Out-patient Clinic. Subgroup analysis was performed on the degree of hyperresponsiveness and lung steroid use before the start of the study, as indictors for the severity of asthma. Associations of the parameters studied with ozone, PM10, nitrogen dioxide (NO2), sulphur dioxide (SO2) and black smoke were evaluated using time series analysis. Several episodes with increased summertime air pollution occurred during the 96 day study period. Eight hour average ozone concentrations exceeded the World Health Organization (WHO) Air Quality Guidelines (120 microg x m(-3)) on 16 occasions. Daily mean levels of PM10 were moderately elevated (range 16-98 microg x m(-3)). Levels of the other measured pollutants were low. There was a consistent, positive association of the prevalence of shortness of breath (maximal relative risk (RRmax) 1.18) with ozone, PM10, black smoke and NO2. In addition, bronchodilator use was associated with both ozone and PM10 levels (RRmax 1.16). Stratification by airway hyperresponsiveness and steroid use did not affect the magnitude of the observed associations. No associations with peak expiratory flow measurements were found. We conclude that the severity of asthma is not an indicator for the sensitivity to air pollution.
Predictive value of response to treatment of T-lymphocyte subpopulations in idiopathic pulmonary fibrosis
Authors: Fireman E , Vardinon N , Burke M , Spizer S , Levin S , Endler A , Stav D , Topilsky M , Mann A , Schwarz Y , Kivity S , Greif J
Published: November 2022

T-cell types are important in maintaining immune homeostasis in the lung and their imbalance may be associated with several diseases. We examined the relationship between bronchoalveolar lavage (BAL) T-cell subset profiles and the clinical course of 46 patients with idiopathic pulmonary fibrosis (IPF). A flow cytometry cell sorter (FACS) was used to analyse the T-cell subsets. Pulmonary function tests (PFT) were performed at baseline and 6-12 months later. Patients were divided into two groups according to their CD4/CD8 ratio: CD4/CD8 >1 (group 1, n=21); and CD4/CD8 <1 (group 2, n=25). A lower percentage of lymphocytes, a higher percentage of CD8/S6F1 cells (cytotoxic T-lymphocytes) and a higher percentage of neutrophils were found in the BAL in group 2 compared to group 1 (11+/-7.5% versus 19+/-13.2%; p=0.024 and 29.8+/-17.6% versus 13.3+/-6.9%; p=0.068, respectively for lymphocytes and cytotoxic T-lymphocytes; and 8+/-11% versus 29+/-27%; p=0.003 for neutrophils). Inversely, in the peripheral blood, the distribution of CD8/S6F1 cells was lower in group 1 than in group 2 (8.3+/-6.9% versus 33.4+/-16.5%; p=0.0048). The patients were followed over a period of 1 yr in order to test whether those findings could determine efficacy of therapy. The baseline transfer factor of the lung for carbon monoxide (TL,CO) capacity in group 1 and group 2 was 59+/-22% and 51+/-21%, respectively (p=0.29), but only in group 1 was the TL,CO capacity improved significantly in response to steroids treatment after 6-12 months. IPF patients with a higher percentage of lymphocytes, a lower percentage of neutrophils, CD4/CD8 >1 and a low percentage of CD8/S6F1 may have a more benign course of disease. These parameters may identify an early stage of reversible disease responsive to therapy. We conclude that these measurements may be a useful tool in monitoring response to treatment in patients with idiopathic pulmonary fibrosis.
Accuracy of a pulse oximeter in the measurement of the oxyhaemoglobin saturation
Authors: Chiappini F , Fuso L , Pistelli R
Published: November 2022

The aim of the present study was to evaluate the accuracy, in comparison with a reference method, of the Nellcor N-20P pulse oximeter in the assessment of oxyhaemoglobin saturation (Sa,O2). Sa,O2 was monitored at rest by the Nellcor N-20P pulse oximeter in 100 subjects (82 males, mean age 68+/-12 yrs) consecutively enroled. At the same time, an arterial blood sample was collected for the measurement of Sa,O2, carboxyhaemoglobin, and methaemoglobin by an IL-282 Co-oximeter. A significant difference was found between Sa,O2 values measured with the two methods (t=11.78, p<0.05), but the two series of measurements were significantly correlated (r=0.97). Both the level and the limits of agreement between the two methods were satisfactory when the more appropriate Bland and Altman method was applied. Nevertheless, a lack of accuracy of the pulse oximeter was found, but only for Sa,O2 values <82% and >94%, as demonstrated by the Youden index. In conclusion, these data show that Nellcor N-20P is sufficiently reliable for the assessment and monitoring of oxyhaemoglobin saturation. The lack of accuracy does not seem clinically relevant since it is appreciable only for values at the extremes of the oxyhaemoglobin saturation range.
Quantification of Clara cell protein in rat and mouse biological fluids using a sensitive immunoassay
Authors: Halatek T , Hermans C , Broeckaert F , Wattiez R , Wiedig M , Toubeau G , Falmagne P , Bernard A
Published: November 2022

Clara cell protein is a 16-17 kDa protein (CC16) secreted by Clara cells in the bronchiolar lining fluid of the lung. In order to investigate the potential of this protein as a pulmonary marker in animals, CC16 was isolated from rat bronchoalveolar lavage fluid (BALF) and a sensitive latex immunoassay applicable to both rat and mouse CC16 was developed. The pattern of CC16 concentrations in rat biological fluids determined by the immunoassay was consistent with the hypothesis of a passive diffusion of the protein across the bronchoalveolar/blood barriers showing a difference of more than 5,000 fold between the concentration in the epithelial lining fluid (mean, 140 mg x L(-1)) and that in serum (20 microg x L(-1)) or urine (3 microg x L(-1)). In BALF, the CC16 concentration averaged 5,500 microg x L(-1) and was of the same magnitude as that determined on lung and trachea homogenates. CC16 was also detectable in amniotic fluid with a mean value of 800 microg x L(-1) before delivery. Damage of Clara cells produced by methylcyclopentadienyl manganese tricarbonyl resulted in a significant decrease of CC16 in BALF but did not affect the serum levels of the protein. The nephrotoxicant sodium chromate by contrast had no influence on the CC16 content of BALF but markedly increased CC16 levels in both serum and urine as a result of impaired glomerular filtration and tubular reabsorption, respectively. In conclusion, mouse or rat Clara cell protein of 16-17 kDa can easily be quantified, not only in bronchoalveolar lavage fluid, but also in extrapulmonary fluids such as serum or urine. Thus, in rodents, Clara cell protein of 16-17 kDa follows the same metabolic pathway as in humans, diffusing from the respiratory tract into serum where it is eliminated by the kidneys. This serum Clara cell protein of 16-17 kDa may be useful as a peripheral marker of events taking place in the respiratory tract.
Reactive oxygen species in acute lung injury
Authors: Chabot F , Mitchell JA , Gutteridge JM , Evans TW
Published: November 2022

The acute respiratory distress syndrome (ARDS) in adults is associated with a wide variety of precipitating factors, often not directly involving the lung, and has an associated mortality of 50-80%. ARDS is almost invariably associated with sepsis, either as an initiating factor or as a secondary complication, which increases the expression of a number of cytokines impacting upon several cellular systems. Specifically, activation of neutrophils sequestered in the pulmonary circulation by this process, causes the release of free radicals and reactive oxygen species (ROS), increasingly regarded as key substances modulating the endothelial dysfunction and disruption responsible for the principal clinical manifestations of the syndrome. Here we discuss briefly the pathophysiology of ARDS and its impact upon pulmonary vascular control; the biological origins of free radicals and other ROS involved, the mechanisms of their damaging effects, their contribution to the modification of pulmonary vascular control mechanisms in lung injury and possible therapeutic perspectives.
Isolated pulmonary arteries involvement in a patient with Takayasu's arteritis
Authors: Brugiere O , Mal H , Sleiman C , Groussard O , Mellot F , Fournier M
Published: November 2022

Pulmonary arteries involvement is well described in Takayasu's arteritis (TA), a condition which is mainly associated with involvement of the systemic arteries. We report a case of TA with documented isolated pulmonary arteries involvement. Symptoms were quite similar to those encountered in chronic thromboembolic disease. A pulmonary angiogram showed bilateral stenosis and occlusion of pulmonary arteries. Diagnosis of TA was suspected, and as such a complete aortogram was made but proved to be normal. Massive haemoptysis suddenly occurred, which resulted in death. Autopsy disclosed characteristic pathological lesions of TA in pulmonary arteries and confirmed the lack of involvement of the aorta and its branches. The frequency of such a clinical form could be underestimated, given the difficulties of diagnosis and features similar to those of chronic thromboembolic disease.
Accelerated obstructive pulmonary disease in HIV infected patients with bronchiectasis
Authors: Bard M , Couderc LJ , Saimot AG , Scherrer A , Frachon I , Seigneur F , Caubarrere I
Published: November 2022

Human immunodeficiency virus (HIV) infection has been associated with a wide spectrum of pulmonary disease. We report three HIV-seropositive patients with rapidly worsening airway obstruction associated with bronchiectasis. All subjects (age range 33-39 yrs) were cigarette smokers. Two had previously used intravenous drugs. The CD4 lymphocyte count ranged 40-250 cells x mm(-3). All individuals had complained of increasing dyspnoea for 3-6 months. Within 1 yr, they all developed severe airway obstruction with a decrease in both forced expiratory volume in one second (FEV1) and ratio of FEV1 to forced vital capacity (FEV1/FVC) to less than 60% of predicted value, and a decrease in mean forced expiratory flow at 25-75% of the forced vital capacity (FEF25-75) to less than 35% of predicted value. Computed tomography of the chest disclosed bilateral dilated and thickened bronchi. No classical causes of genetic or acquired bronchiectasis were identified in our patients. Recurrent bacterial bronchitis occurred in the follow-up period of the three patients. In conclusion, unusually rapid airway obstruction associated with bronchiectasis should be added to the wide spectrum of respiratory complications of human immunodeficiency virus infection.
Pyothorax-associated lymphoma: relationship with Epstein-Barr virus, human herpes virus-8 and body cavity-based high grade lymphomas
Authors: Taniere P , Manai A , Charpentier R , Terdjman P , Boucheron S , Cordier JF , Berger F
Published: November 2022

Pyothorax-associated lymphoma (PAL) is a newly-described entity developing several decades after artificial pneumothorax treatment for pulmonary or pleural tuberculosis. It is known to be associated with Epstein-Barr virus (EBV) with constant expression of the two latent membrane proteins: latent membrane protein (LMP)-1 and EBV-associated nuclear antigen (EBNA)-2. We are reporting three new cases of PAL. All of the tumours were of B-cell lineage and classified as large-cell diffuse lymphomas according to the International Working Formulation for the Classification of Lymphomas. The EBV genome was detected in two of the cases with LMP-1 and EBNA-2 expression. No EBV could be detected in the third case suggesting that different mechanisms may be involved in the pathogenesis of the disease. Body cavity-based high grade lymphomas (BCBL) represent a new disease, developing mainly in human immunodeficiency virus (HIV) infected patients: the tumoural cells often contain both human herpes virus (HHV)-8 (or Kaposi's sarcoma herpes virus) and EBV genomes, suggesting that these viruses might co-operate in the pathogenesis of the disease. The pleural location and the association of EBV have led to speculation that PAL could also be related to HHV-8 infection. However, no HHV-8 genome could be detected in any of the 14 tested cases already reported in the literature nor in the two cases we studied (one EBV-positive and one EBV-negative), suggesting that PAL and BCBL are two different entities.
A nomogram for predicting cancer-specific survival for elderly patients with gallbladder cancer
Authors: Wen Chong , Tang Jie , Wang Tao , Luo Hao
Published: November 2022

Background

Gallbladder cancer (GBC) is a highly aggressive malignancy in elderly patients. Our goal is aimed to construct a novel nomogram to predict cancer-specific survival (CSS) in elderly GBC patients.

Method

We extracted clinicopathological data of elderly GBC patients from the SEER database. We used univariate and multivariate Cox proportional hazard regression analysis to select the independent risk factors of elderly GBC patients. These risk factors were subsequently integrated to construct a predictive nomogram model. C-index, calibration curve, and area under the receiver operating curve (AUC) were used to validate the accuracy and discrimination of the predictive nomogram model. A decision analysis curve (DCA) was used to evaluate the clinical value of the nomogram.

Result

A total of 4241 elderly GBC patients were enrolled. We randomly divided patients from 2004 to 2015 into training cohort (n = 2237) and validation cohort (n = 1000), and patients from 2016 to 2018 as external validation cohort (n = 1004). Univariate and multivariate Cox proportional hazard regression analysis found that age, tumor histological grade, TNM stage, surgical method, chemotherapy, and tumor size were independent risk factors for the prognosis of elderly GBC patients. All independent risk factors selected were integrated into the nomogram to predict cancer-specific survival at 1-, 3-, and 5- years. In the training cohort, internal validation cohort, and external validation cohort, the C-index of the nomogram was 0.763, 0.756, and 0.786, respectively. The calibration curves suggested that the predicted value of the nomogram is highly consistent with the actual observed value. AUC also showed the high authenticity of the prediction model. DCA manifested that the nomogram model had better prediction ability than the conventional TNM staging system.

Conclusion

We constructed a predictive nomogram model to predict CSS in elderly GBC patients by integrating independent risk factors. With relatively high accuracy and reliability, the nomogram can help clinicians predict the prognosis of patients and make more rational clinical decisions.
Examining socioeconomic status disparities in facility-based childbirth in Kenya: role of perceived need, accessibility, and quality of care
Authors: Kapula Ntemena , Shiboski Stephen , Dehlendorf Christine , Ouma Linet , Afulani Patience A.
Published: November 2022

Background

Giving birth in health facilities with skilled birth attendants (SBAs) is one of the key efforts promoted to reduce preventable maternal deaths in sub-Saharan Africa. However, research has revealed large socioeconomic status (SES) disparities in facility-based childbirth. We seek to extend the literature on the factors underlying these SES disparities. Drawing on the Disparities in Skilled Birth Attendance (DiSBA) framework, we examined the contribution of three proximal factors—perceived need, accessibility, and quality of care—that influence the use of SBAs.

Methods

We used data from a survey conducted in Migori County, Kenya in 2016, among women aged 15–49 years who gave birth nine weeks before the survey (N = 1020). The primary outcome is facility-based childbirth. The primary predictors are wealth, measured in quintiles calculated from a wealth index based on principal component analysis of household assets, and highest education level attained. Proposed mediating variables include maternal perceptions of need, accessibility (physical and financial), and quality of care (antenatal services received and experience of care). Logistic regression with mediation analysis was used to investigate the mediating effects.

Results

Overall, 85% of women in the sample gave birth in a health facility. Women in the highest wealth quintile were more likely to give birth in a facility than women in the lowest quintile, controlling for demographic factors (adjusted odds ratio [aOR]: 2.97, 95% CI: 1.69–5.22). College-educated women were five times more likely than women with no formal education or primary education to give birth in a health facility (aOR: 4.96; 95% CI: 1.43–17.3). Women who gave birth in health facilities had higher perceived accessibility and quality of care than those who gave birth at home. The five mediators were estimated to account for between 15% and 48% of the differences in facility births between women in the lowest and higher wealth quintiles.

Conclusion

Our results confirm SES disparities in facility-based childbirth, with the proximal factors accounting for some of these differences. These proximal factors – particularly perceived accessibility and quality of care – warrant attention due to their relationship with facility-birth overall, and their impact on inequities in this care.
Comprehensive analysis of the expression and prognosis for IQ motif-containing GTPase-activating proteins in hepatocellular carcinoma
Authors: Dai Qingqing , Song Fei , Li Xincheng , Huang Fan , Zhao Hongchuan
Published: November 2022

Background

IQ motif-containing GTPase-activating proteins (IQGAPs) are a group of scaffold proteins which have been identified to be involved in tumor initiation and progression in diverse types of cancer. Clinical studies and experimental evidence suggest that IQGAPs play an essential role in hepatocellular carcinoma (HCC) progression and alterations in their expression are closely related to patient prognosis. However, the different expression patterns and prognostic values of all three IQGAP isoforms in HCC have not yet been analyzed simultaneously.

Methods

We analyzed the transcriptional and survival data of IQGAPs in HCC patients using Oncomine, UALCAN, Kaplan–Meier Plotter, cBioPortal, and GeneMANIA. We further examined tumor and adjacent normal tissues from 250 HCC patients using immunohistochemistry to assess the relationship between IQGAPs expression and clinicopathological features and validate the prognostic value of IQGAPs. In addition, we analyzed transcriptional changes of IQGAPs with regards to survival data in HCC patients from the TCGA-LIHC (liver hepatocellular carcinoma) cohort to validate our results.

Results

We found that the expression levels of IQGAP1 and 3 were significantly elevated in HCC tissues than in normal liver tissues, whereas the expression level of IQGAP2 was decreased in the former than in the latter. The clinical data showed that positive IQGAP1 expression was associated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, poor relapse-free survival (RFS), and overall survival (OS), and positive IQGAP3 expression was associated with poorer tumor differentiation, RFS, and OS. Conversely, positive IQGAP2 expression predicted less tumor numbers and microvascular invasion, as well as higher RFS and OS in these patients.

Conclusions

IQGAPs may serve as new prognostic biomarkers and potential targets for precision therapy in HCC.
Paradoxes of breast cancer incidence and mortality in two corners of Europe
Authors: Roginski Mikaela , Sifaki-Pistolla Dimitra , Stomby Andreas , Velivasaki Georgia , Faresjö Tomas , Lionis Christos , Faresjö Åshild
Published: November 2022

Background

Breast cancer incidence is rising globally, while mortality rates show a geographical heterogenous pattern. Early detection and treatment have been proven to have a profound impact on breast cancer prognosis. The aim of his study was to compare breast cancer incidence, mortality, and survival rates in two contrasting corners of Europe, Sweden and Crete, to better understand cancer determinants with focus on disease burden and sociocultural factors.

Methods

Breast cancer data from Sweden and Crete was derived from registries. Incidence and mortality were expressed as Age-Standardized Incidence Rates (ASIR), Age-Standardized Mortality Rates (ASMR).

Findings

Breast cancer incidence has for decades risen in Sweden and on Crete. In 2019, ASIR was 217.5 in Sweden and 58.9 on Crete, (p < 0.001). Mortality rates showed opposite trends. ASMR in Sweden was reduced from 25.5 to 16.8 (2005-2019) while on Crete, ASMR increased from 22.1 to 25.3. A successive rise in survival rate in Sweden with a 5-year survival rate of 92% since 2015, but a converse development on Crete with 85% 5-year survival rate the same year.

Interpretation

The incidence of breast cancer is slowly rising in both studied regions, but mortality increases on Crete in contrast to Sweden with sinking mortality rates. The interpretation of these findings is that differences in health care systems and health policies including differences in early detection like screening programs and early treatment, as well as sociocultural factors in the two countries might play an important role on the differences found in breast cancer burden.
Obesity paradox among patients undergoing total knee arthroplasty: a retrospective cohort study
Authors: Ma Lulu , Yu Xuerong , Weng Xisheng , Lin Jin , Qian Wenwei , Huang Yuguang
Published: November 2022

Background

Obesity has been recognized as the risk factor for postoperative complication for surgical patients. However, recent studies have showed protective effect of obesity in surgical and non-surgical patients. Our study is to examine the association of body mass index(BMI) with early postoperative complications in patients undergoing total knee arthroplasty.

Materials and methods

All patients who had primary total knee arthroplasty between January 2014 and December 2019 were included. Medical records were retrospectively reviewed and BMI was categorized as underweight(BMI < 18.5), normal weight(18.5 < BMI < 24.9), overweight I(25 < BMI < 27.4), overweight II(27.5 < BMI < 29.9), obese I(30 < BMI < 34.9) and obese II(BMI ≥ 35). The association between BMI and occurrence of early postoperative complications was examined and logistic regression was used to calculate relationship between BMI and early postoperative complications.

Results

A total of 2969 patients were included in our analysis. The overall complication rate in patients undergoing total knee arthroplasty was 14.8%, with the highest complication being 22.2% in the underweight group, the second highest in the normal weight group(17.5%), the lowest in the overweight I(13.8%) and obese I(12.0%) group and then higher again in obese II group(16.7%). In multivariable analyses, overweight I (OR 0.737, 95% CI 0.559–0.972,P = 0.031) and obese I (OR 0.631, 95% CI 0.449–0.885,P = 0.008) were associated with lower risk of early postoperative complications after total knee arthroplasty.

Conclusion

In this retrospective study, overweight and obese patients had a lower risk of early postoperative complications after total knee arthroplasty. Further studies are necessary to confirm and investigate the mechanism of obesity paradox in this surgical population.

Trial registration

This study had been registrated inwww.chictr.org.cnon 25/10/2021 and the registration ID was ChiCTR2100052408.
Hospital ethical climate survey - selected psychometric properties of the scale and results among polish nurses and midwives
Authors: Dziurka Magdalena , Ozdoba Patrycja , Olson Linda , Jedynak Anna , Ozga Dorota , Jurek Krzysztof , Dobrowolska Beata
Published: November 2022

Background:

The hospital ethical climate affects the quality of nursing care. A positive ethical climate is likely to reduce the proportion of those who consider leaving the profession, so it is necessary to develop tools which will enable assessment and analysis of the hospital ethical climate. The aim of this study was to examine selected psychometric properties of the Polish version of the Hospital Ethical Climate Survey, assess the hospital ethical climate perceived by nurses and midwives from Polish hospitals, and to determine its correlations with job-related variables.

Methods:

A cross-sectional study among 558 nurses and midwives working in hospitals in Poland.

Results:

The 21-item model showed acceptable model fitness between the hypothetical model of ethical climate and the data in the study. Five items with low factor loadings were removed from the study. The internal consistency was satisfactory (0.93). The mean score for the overall hospital ethical climate was 3.62. The highest mean score of hospital ethical climate in the present study was found in the ”peers” subscale and the lowest in the ”physicians” subscale. A positive correlation was found between overall hospital ethical climate and respondents’ satisfaction with work, salary, and working time. The hospital ethical climate was associated with problems found in nurses and midwives’ work, such as: limited time for direct face-to-face care, the lack of equipment and resources to provide high-quality health care, strained relations with hospital managers and other health care professionals, limitations to one’s own competences or those of other medical professionals, moral dilemmas related to patient care, the low prestige of nurses’/midwives‘ work, physical and mental burden, and the risk of making a mistake.

Conclusion:

The Polish 21-item version of the Hospital Ethical Climate Survey is a reliable tool. Correlations revealed that relationships with managers and physicians, and working conditions should be improved in order for the hospital ethical climate to improve.
Sclerosing encapsulating peritonitis in a dog with pancreatic ductal adenocarcinoma
Authors: Tsukada Yusuke , Park Young Tae , Mitsui Ikki , Murakami Masahiro , Tsukamoto Atsushi
Published: November 2022

Background

Sclerosing encapsulating peritonitis (SEP) is a rare clinical syndrome characterised by fibrosis and thickening of the peritoneum with massive adhesions of the abdominal organs. In humans, abdominal tumours, such as pancreatic adenocarcinoma, can be underlying diseases of SEP. This report describes a case of SEP in a dog with pancreatic ductal adenocarcinoma.

Case presentation

An 11-year-old male neutered French Bulldog presented with chronic vomiting. Ultrasonography revealed a mass in the centre of the abdomen. A small amount of ascites, interpreted as modified transudate, was present in the abdominal cavity. Computed tomography (CT) revealed peritoneal effusion with a thickened peritonium. Laparoscopy revealed a large nodular lesion occupying the central portion of the abdomen, continuous with the falciform ligament. Histological examination of the biopsy specimens of the mass, abdominal wall, and gastric peritoneum revealed marked fibroplasia with mild lymphoplasmacytic infiltrates. Based on these results, a tentative diagnosis of early stage sclerosing encapsulating peritonitis (SEP) was made. Prednisolone and tamoxifen were administered with the expectation of ameliorating SEP, however, the dog died 61 days post diagnosis. At autopsy, the intestinal loop and mesentery were encased in the fibrous membrane, which is a typical finding in SEP. Histopathology and immunohistochemistry of the samples obtained at autopsy supported the diagnosis of pancreatic ductal adenocarcinoma with peritoneal dissemination and distant metastasis with desmoplasia. The unexpectedly hardened skin, where previously laparoscopic ports were inserted, histologically contained the same carcinoma cells with desmoplasia.

Conclusions

To the best of our knowledge, this is the first report of canine SEP with pancreatic ductal adenocarcinoma that also caused metastasis to port insertion sites as well as distant organs.
Extracellular vesicles isolated from hyperuricemia patients might aggravate airway inflammation of COPD via senescence-associated pathway
Authors: Liu Xuanqi , Li Zheng , Zheng Yang , Wang Wenhao , He Peiqing , Guan Kangwei , Wu Tao , Wang Xiaojun , Zhang Xuelin
Published: November 2022

Backgrounds

Chronic obstructive pulmonary disease (COPD) is a major health issue resulting in significant mortality worldwide. Due to the high heterogeneity and unclear pathogenesis, the management and therapy of COPD are still challenging until now. Elevated serum uric acid(SUA) levels seem to be associated with the inflammatory level in patients with COPD. However, the underlying mechanism is not yet clearly established. In the current research, we aim to elucidate the effect of high SUA levels on airway inflammation among COPD patients.

Methods

Through bioinformatic analysis, the common potential key genes were determined in both COPD and hyperuricemia (HUA) patients. A total of 68 COPD patients aged 50—75-year were included in the study, and their clinical parameters, including baseline characteristics, lung function test, as well as blood chemistry test were recorded. These parameters were then compared between the COPD patients with and without HUA. Hematoxylin & Eosin (HE), immunofluorescence (IF), and Masson trichrome staining were performed to demonstrate the pathological changes in the lung tissues. Furthermore, we isolated extracellular vesicles (EVs) from plasma, sputum, and bronchoalveolar lavage fluid (BALF) samples and detected the expression of inflammatory factor (Interleukin-6 (IL-6), IL-8 and COPD related proteases (antitrypsin and elastase) between two groups. Additionally, we treated the human bronchial epithelial (HBE) cells with cigarette smoke extract (CSE), and EVs were derived from the plasma in vitro experiments. The critical pathway involving the relationship between COPD and HUA was eventually validated based on the results of RNA sequencing (RNA-seq) and western blot (WB).

Results

In the study, the COPD patients co-existing with HUA were found to have more loss of pulmonary function compared with those COPD patients without HUA. The lung tissue samples of patients who had co-existing COPD and HUA indicated greater inflammatory cell infiltration, more severe airway destruction and even fibrosis. Furthermore, the high SUA level could exacerbate the progress of airway inflammation in COPD through the transfer of EVs. In vitro experiments, we determined that EVs isolated from plasma, sputum, and BALF played pivotal roles in the CSE-induced inflammation of HBE. The EVs in HUA patients might exacerbate both systemic inflammation and airway inflammatory response via the senescence-related pathway.

Conclusion

The pulmonary function and clinical indicators of COPD patients with HUA were worse than those without HUA, which may be caused by the increased airway inflammatory response through the EVs in the patient's peripheral blood. Moreover, it might mediate the EVs via senescence-related pathways in COPD patients with HUA.
Retrospective observation of subacute thyroiditis before and during the COVID-19 vaccination campaign in a single secondary endocrine centre in the Savona district, Liguria, Italy
Authors: Giusti Massimo , Sidoti Marilena
Published: November 2022

Background

Clinicians should be aware that subacute thyroiditis (SAT) might be an under-reported adverse effect of COVID-19 vaccines.

Aim

In records from endocrinological examinations, we reviewed the incidence of diagnoses of SAT from 2000 to 2020 and during the 2021 COVID-19 vaccination campaign.

Methods

Review of electronic records from June to December in each year from 2000 to 2021.

Results

From 2000 to 2020, 51 patients in our centre had SAT (0.6%). From June to December 2021, 7 females were diagnosed with SAT after vaccination. The percentage of SAT in 2021 medical files was 1.5%. SAT diagnoses significantly (P = 0.03) increased in 2021 in comparison with the 2000–2020 period. The median age of SAT patients in 2021 (51 years; IQR 35–66 years) was higher than in the 2000–2020 period (45 years, IQR 38–52 years; P = 0.05).

Conclusion

To date, few cases of SAT after COVID-19 vaccinations have been described in the literature, with sub-clinical, normal or increased thyroid function during 1-3-month follow-up. Our findings indicate that SAT after COVID-19 vaccination occurs more frequently than in other virus-related cases and at a greater age. Our observation of a local increase in SAT during the 2021 COVID-19 vaccination campaign indicates that physicians should be aware of this infrequent side effect, which must be considered and monitored after COVID-19 vaccination.
Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer
Authors: Borneman Rebecca M. , Gavin Elaine , Musiyenko Alla , Richter Wito , Lee Kevin J. , Crossman David K. , Andrews Joel F. , Wilhite Annelise M. , McClellan Steven , Aragon Ileana , Ward Antonio B. , Chen Xi , Keeton Adam B. , Berry Kristy , Piazza Gary A. , Scalici Jennifer M. , da Silva Luciana Madeira
Published: November 2022

A leading theory for ovarian carcinogenesis proposes that inflammation associated with incessant ovulation is a driver of oncogenesis. Consistent with this theory, nonsteroidal anti-inflammatory drugs (NSAIDs) exert promising chemopreventive activity for ovarian cancer. Unfortunately, toxicity is associated with long-term use of NSAIDs due to their cyclooxygenase (COX) inhibitory activity. Previous studies suggest the antineoplastic activity of NSAIDs is COX independent, and rather may be exerted through phosphodiesterase (PDE) inhibition. PDEs represent a unique chemopreventive target for ovarian cancer given that ovulation is regulated by cyclic nucleotide signaling. Here we evaluate PDE10A as a novel therapeutic target for ovarian cancer. Analysis of The Cancer Genome Atlas (TCGA) ovarian tumors revealed PDE10A overexpression was associated with significantly worse overall survival for patients. PDE10A expression also positively correlated with the upregulation of oncogenic and inflammatory signaling pathways. Using small molecule inhibitors, Pf-2545920 and a novel NSAID-derived PDE10A inhibitor, MCI-030, we show that PDE10A inhibition leads to decreased ovarian cancer cell growth and induces cell cycle arrest and apoptosis. We demonstrate these pro-apoptotic properties occur through PKA and PKG signaling by using specific inhibitors to block their activity. PDE10A genetic knockout in ovarian cancer cells through CRISP/Cas9 editing lead to decreased cell proliferation, colony formation, migration and invasion, andin vivotumor growth. We also demonstrate that PDE10A inhibition leads to decreased Wnt-induced β-catenin nuclear translocation, as well as decreased EGF-mediated activation of RAS/MAPK and AKT pathways in ovarian cancer cells. These findings implicate PDE10A as novel target for ovarian cancer chemoprevention and treatment.
Flecainide-induced pneumonitis: a case report
Authors: Moureau Gauthier , Zarrouk Elies , Hoton Delphine , Saint-Marcoux Franck , Boland Lidvine , Haufroid Vincent , Hantson Philippe
Published: November 2022

Background

We report a case of acute respiratory distress associated with a histological pattern of acute fibrinous and organizing pneumonia, and discuss the possible responsibility of flecainide therapy.

Case presentation

A 61-year-old African woman developed a rapidly progressive dyspnea and required admission in the intensive care unit for orotracheal intubation and mechanical ventilation. Chest X-ray examination revealed bilateral infiltrates predominating in the basal part of both lungs. Lung computed tomography disclosed bilateral ground-glass opacities and septal thickening. After exclusion of the most common causes of infectious or immune pneumonia, a toxic origin was investigated and flecainide toxicity was considered. Lung biopsy was consistent with the unusual pattern of acute fibrinous and organizing pneumonia. Clinical and radiological improvement was noted after corticosteroid therapy, but the patient died from septic complications.

Conclusion

Flecainide-induced lung injury has rarely been reported in the literature and remains a diagnosis of exclusion. The histological pattern of acute fibrinous and organizing pneumonia has been previously observed with amiodarone. There are no firm guidelines for the treatment of acute fibrinous and organizing pneumonia, but some patients may positively respond to corticosteroids.
Mechanical stretching boosts expansion and regeneration of intestinal organoids through fueling stem cell self-renewal
Authors: Meng Fanlu , Shen Congcong , Yang Li , Ni Chao , Huang Jianyong , Lin Kaijun , Cao Zanxia , Xu Shicai , Cui Wanling , Wang Xiaoxin , Zhou Bailing , Xiong Chunyang , Wang Jihua , Zhao Bing
Published: November 2022

Intestinal organoids, derived from intestinal stem cell self-organization, recapitulate the tissue structures and behaviors of the intestinal epithelium, which hold great potential for the study of developmental biology, disease modeling, and regenerative medicine. The intestinal epithelium is exposed to dynamic mechanical forces which exert profound effects on gut development. However, the conventional intestinal organoid culture system neglects the key role of mechanical microenvironments but relies solely on biological factors. Here, we show that adding cyclic stretch to intestinal organoid cultures remarkably up-regulates the signature gene expression and proliferation of intestinal stem cells. Furthermore, mechanical stretching stimulates the expansion of SOX9+ progenitors by activating the Wnt/β-Catenin signaling. These data demonstrate that the incorporation of mechanical stretch boosts the stemness of intestinal stem cells, thus benefiting organoid growth. Our findings have provided a way to optimize an organoid generation system through understanding cross-talk between biological and mechanical factors, paving the way for the application of mechanical forces in organoid-based models.
What makes Chinese rural migrants self-employed: a qualitative perspective
Authors: Xia Shuting
Published: November 2022

This study scrutinizes the causes, configuration, and consequences of rural migrants’ motivations for becoming self-employed. It aims to solve two main problems in the current literature. The first is that previous studies primarily explain migrants’ self-employment through economic variables when other factors (e.g., autonomy, meaningfulness, and work environment) might be more important. Second, no study has been conducted to qualitatively understand migrants’ self-employment outcomes. By drawing on in-depth qualitative interviews with rural-to-urban migrant workers conducted in four regions of China, this article provides insights into the pecuniary and nonpecuniary motivations of rural migrants’ employment decisions. Notably, it finds that most rural migrant workers in wage employment sectors are not in a position to exercise free choice regarding their working arrangements. In contrast, the prospect of achieving a higher level of income, greater autonomy, and more flexibility and freedom is important and attractive aspects of self-employment, with apparent gender differences. Nevertheless, migrants’ self-employment often involves self-sacrifice and economic and social marginalization. Therefore, it is unlikely that migrants select self-employment as an effective means for status acquisition.