bluuebunny/crossref_metadata_2025 huggingface dataset:
The Value of Netnography for Research in HRD
Authors: Discetti Roberta , Anderson Valerie
Published: November 2022

This paper argues for recognition of Netnography as a necessary methodological innovation for HRD research, enabling the field to address emerging research questions and contribute to theory building at the intersection of technology, work and social life. The paper defines ‘netnography’ and introduces its key methodological underpinnings; illustrates its application and procedures; and considers its benefit to HRD research. We identify three opportunities where Netnography can deliver important advances to HRD theory and practice: investigating hard-to-access online work contexts, such as gig work and other forms of precarious working; exploring marginalised, ‘hidden’, or under-researched voices in online spaces; and extending knowledge of learning in hybrid work environments where physical and digital dimensions are intertwined. We conclude with a call to action by HRD scholars to take forward, and further develop, the Netnographic methodology to contribute to new and inclusive theorizing as a basis for advancements in HRD scholarship and practice.
Bourdieu in the Women’s Prison Garden: Findings from Two Clinical Sociological Garden Interventions in the Carceral Field
Authors: Jauk-Ajamie Daniela , Everhardt Sharon , Caruana Christie L. , Gill Brenda
Published: November 2022

This paper presents preliminary findings from two prison horticulture intervention projects. Our project sites are located in a women’s community corrections facility in the U.S. Midwest and a women’s maximum-security prison in the Southeastern United States. These garden projects illustrate the importance of sociological theory and clinical sociological practice in the development of programs that will benefit incarcerated women who remain underserved and disenfranchised in U.S. society. We apply Bourdieu’s theories of capital to understand incarcerated women’s lived experiences. We find that clinical sociological prison gardens foster women’s rehabilitation and increase food security within incarcerated settings. They also are an important site of capital and skill-building for participants.
The spatial antecedents for drone governance in Afghanistan
Authors: Cheikhali Sarah
Published: November 2022

This paper problematizes the use of surveillance technologies such as drones for security governance in Afghanistan by foregrounding the spatial conditions of the possibility of such measures. How did the security architecture in Afghanistan become so fragmented to require technologies such as drones as extensions of the government security surveillance apparatus to govern ungoverned space? While much literature on drones considers how drones rewrite spaces in their theaters of operation, it is also true that space is rewritten to enact governance-by-drone in the first place. In Afghanistan, historical shifts in the global political economy resulted in spatially fragmented security architecture, thus laying the spatial pre-conditions for security governance-by-drone. This paper brings together debates on geopolitics and geoeconomics with those of roll-back, roll-out, and roll-over neoliberalism to construct a genealogy of spatial reconfiguration in Afghanistan. It begins by exploring earlier geopolitical forms of statecraft in Afghanistan, which focused on augmenting state power through large-scale development projects. It then moves on to show how these were replaced by geoeconomic forms of statecraft that emphasized the rolling back of government involvement, heavy privatization, and foreign investment, resulting in deeply fragmented security architecture. Finally, neoliberalism's roll-out and roll-over phases correlate with reviving geopolitical forms of statecraft aimed at territorial consolidation. The new geopolitical, however, is a form of statecraft that tends toward territorial power through compensatory technological means like drones as opposed to meaningful development. Rulership was leaning toward this new authoritarian, technocratic model well before the capture of these technologies by the Taliban after its transition to power following the 2021 US retreat.
Homogeneous ensemble models for predicting infection levels and mortality of COVID-19 patients: Evidence from China
Authors: Wang Jiafeng , Zhou Xianlong , Hou Zhitian , Xu Xiaoya , Zhao Yueyue , Chen Shanshan , Zhang Jun , Shao Lina , Yan Rong , Wang Mingshan , Ge Minghua , Hao Tianyong , Tu Yuexing , Huang Haijun
Published: November 2022

Background

Persistence of long-term COVID-19 pandemic is putting high pressure on healthcare services worldwide for several years. This article aims to establish models to predict infection levels and mortality of COVID-19 patients in China.

Methods

Machine learning models and deep learning models have been built based on the clinical features of COVID-19 patients. The best models are selected by area under the receiver operating characteristic curve (AUC) scores to construct two homogeneous ensemble models for predicting infection levels and mortality, respectively. The first-hand clinical data of 760 patients are collected from Zhongnan Hospital of Wuhan University between 3 January and 8 March 2020. We preprocess data with cleaning, imputation, and normalization.

Results

Our models obtain AUC = 0.7059 and Recall (Weighted avg) = 0.7248 in predicting infection level, while AUC=0.8436 and Recall (Weighted avg) = 0.8486 in predicting mortality ratio. This study also identifies two sets of essential clinical features. One is C-reactive protein (CRP) or high sensitivity C-reactive protein (hs-CRP) and the other is chest tightness, age, and pleural effusion.

Conclusions

Two homogeneous ensemble models are proposed to predict infection levels and mortality of COVID-19 patients in China. New findings of clinical features for benefiting the machine learning models are reported. The evaluation of an actual dataset collected from January 3 to March 8, 2020 demonstrates the effectiveness of the models by comparing them with state-of-the-art models in prediction.
The Incidence of Double Crush Syndrome in Surgically Treated Patients
Authors: Mills Emily S. , Mertz Kevin , Fresquez Zoe , Ton Andy , Buser Zorica , Alluri Ram K. , Hah Raymond J.
Published: November 2022

Study Design

Retrospective Cohort Study

Objectives

Cervical radiculopathy and peripheral entrapment neuropathies often have overlapping symptoms that are difficult to distinguish on physical examination. Small-scale studies have attempted to report the incidence of this phenomenon, often called double crush syndrome (DCS), with varying results. The present study aims to determine the incidence of concomitant cervical radiculopathy and peripheral nerve compression and to determine if the DCS hypothesis, which states that compression of a nerve at one site leaves it more susceptible to compression at another, is valid.

Methods

The PearlDiver database was queried from 2010 to 2020. The incidence of peripheral neuropathy in cervical radiculopathy was assessed. Propensity score matching was used to determine if patients with cervical radiculopathy were more likely to have peripheral nerve compression compared to controls, and vice versa, to test the DCS hypothesis.

Results

The database contains records of 90,772 632 patients. The incidence of carpal tunnel syndrome (CTS) or peripheral ulnar nerve compression (PUnC) in cervical radiculopathy was 9.98% and 3.15%, respectively. The incidence of both carpal tunnel syndrome and PUnC in cervical radiculopathy was 1.84%. Patients with cervical radiculopathy were more likely than matched controls to have both CTS ( P < .001) and PUnC ( P < .001). Patients with CTS ( P < .001) and with PUnC ( P < .001) were more likely to have cervical radiculopathy than the control cohort.

Conclusions

The incidence of DCS is reported. Patients with cervical radiculopathy are more likely than matched controls to have peripheral nerve compression, and vice versa, in support of the DCS hypothesis.
Anxiety levels among Palestinian university students during the COVID-19 pandemic: A cross-sectional study
Authors: Radwan Eqbal , Radwan Afnan , Alattar Etimad , Radwan Walaa , Alajez Mohammed
Published: November 2022

Background:

The widespread of COVID-19 causes serious distress on the mental health of the students during the lockdown period. The present study aimed to identify anxiety levels among students during the COVID-19 crisis.

Design and methods:

A cross-sectional web-based survey was carried out among university students aged 18–47 years. The 7-item Generalized Anxiety Disorder Scale (GAD-7) was used to assess anxiety symptoms.

Results:

Among the 1252 participants, the mean age was 28.82 (±7.28) years and 72.6% were female. Based on the results, 22.0% of the participants had no symptoms of anxiety, 25.2% had mild anxiety, 29.6% moderate anxiety, and 23.2% severe anxiety. Moreover, being a female (OR = 0.480, 95% CI = 0.257–0.704), younger age (OR = 0.359, 95% CI = 0.132–0.586), undergraduate level (OR = 0.493, 95% CI = 0.288–0.698), and stability of monthly income (OR = 0.516, 95% CI = 0.308–0.723) were found to be a protective factor against anxiety suffered by the participants. However, having a COVID-19-infected relative or acquaintance was a risk factor for anxiety (OR = 21.870, 95% CI = 21.870–21.870). The results revealed that the level of anxiety symptoms was positively associated with COVID-19 related stressors such as effects on daily living ( r = 0.163, p < 0.001), economic stressors ( r = 0.153, p < 0.001), and educational consequences ( r = 0.150, p < 0.001), however, social support ( r = 0.472, p < 0.001) was negatively associated with the anxiety.

Conclusion:

The psychological status of university students should be followed during times of health emergencies. It is essential to design a health program for influenced students to assist them to stay resilient throughout perilous situations.
Pain and Nausea Intensity, Social Function, and Psychological Well-Being among Women with Metastatic Breast Cancer
Authors: Senkpeil Ryan R. , Olson Julie S. , Fortune Erica E. , Zaleta Alexandra K.
Published: November 2022

Advances in diagnostics and therapeutics have improved prognosis for metastatic breast cancer (MBC). Yet, treatment and disease burden—including experiences of pain and nausea—present practical and emotional challenges. To better support patients and enhance quality of life, deeper understanding of the pathways linking physical and psychological health is needed. To this end, we examined associations of pain and nausea with depression and anxiety among women with MBC. In doing so, we highlighted social function as a potentially important mechanism in this relationship. This observational, cross-sectional study included 148 predominantly non-Hispanic White, highly educated women living with MBC. Multivariate regression models demonstrated that more intense pain and nausea were significantly associated with higher levels of depression and anxiety ( p < .001). Causal mediation analyses confirmed significant indirect effects whereby decreases in social function associated with pain and nausea contributed to depression and anxiety. Thus, our findings illustrate decreased social function as one pathway through which pain and nausea contribute to escalation of depression and anxiety. Our results, therefore, underscore the importance of supporting social function among women with MBC to potentially reduce psychological sequelae of pain and nausea.
AKT supports the metabolic fitness of multiple myeloma cells by restricting FOXO activity
Authors: Bloedjes Timon A. , de Wilde Guus , Khan Gerarda H. , Ashby Timothy C. , Shaughnessy John D. , Zhan Fenghuang , Houtkooper Riekelt H. , Bende Richard J. , van Noesel Carel J. M. , Spaargaren Marcel , Guikema Jeroen E. J.
Published: November 2022

Metabolic alterations are important cancer-associated features that allow cancer cell transformation and survival under stress conditions. Multiple myeloma (MM) plasma cells show increased glycolysis and oxidative phosphorylation (OXPHOS), which are characteristics associated with recurrent genetic aberrations that drive the proliferation and survival of MM cells. The protein kinase B/AKT acts as a central node in cellular metabolism and is constitutively active in MM cells. Despite the known role of AKT in modulating cellular metabolism, little is known about the downstream factors of AKT that control the metabolic adaptability of MM cells. Here, we demonstrate that negative regulation of the forkhead box O (FOXO) transcription factors (TFs) by AKT is crucial to prevent the metabolic shutdown in MM cells, thus contributing to their metabolic adaptability. Our results demonstrate that the expression of several key metabolic genes involved in glycolysis, the tricarboxylic acid (TCA) cycle, and OXPHOS are repressed by FOXO TFs. Moreover, the FOXO-dependent repression of glycolysis- and TCA-associated genes correlates with a favorable prognosis in a large cohort of patients with MM. Our data suggest that repression of FOXO by AKT is essential to sustain glycolysis and the TCA cycle activity in MM cells and, as such, predicts patient survival.
Chronic GvHD NIH Consensus Project Biology Task Force: evolving path to personalized treatment of chronic GvHD
Authors: Buxbaum Nataliya P. , Socié Gerard , Hill Geoffrey R. , MacDonald Kelli P. A. , Tkachev Victor , Teshima Takanori , Lee Stephanie J. , Ritz Jerome , Sarantopoulos Stefanie , Luznik Leo , Zeng Defu , Paczesny Sophie , Martin Paul J. , Pavletic Steven Z. , Schultz Kirk R. , Blazar Bruce R.
Published: November 2022

Chronic graft-versus-host disease (cGvHD) remains a prominent barrier to allogeneic hematopoietic stem cell transplantion as the leading cause of nonrelapse mortality and significant morbidity. Tremendous progress has been achieved in both the understanding of pathophysiology and the development of new therapies for cGvHD. Although our field has historically approached treatment from an empiric position, research performed at the bedside and bench has elucidated some of the complex pathophysiology of cGvHD. From the clinical perspective, there is significant variability of disease manifestations between individual patients, pointing to diverse biological underpinnings. Capitalizing on progress made to date, the field is now focused on establishing personalized approaches to treatment. The intent of this article is to concisely review recent knowledge gained and formulate a path toward patient-specific cGvHD therapy.
miR-148a-3p and DDX6 functional link promotes survival of myeloid leukemia cells
Authors: Ghashghaei Maryam , Le Cong Truc , Shaalan Haya , Escano Leo , Yue Marty , Arsalan Aaremish , Rouhi Arefeh , Nguyen Tuan Anh , Vu Ly P.
Published: November 2022

Regulation of gene expression at the RNA level is an important regulatory mechanism in cancer. However, posttranscriptional molecular pathways underlying tumorigenesis remain largely unexplored. In this study, we uncovered a functional axis consisting of microRNA (miR)-148a-3p, RNA helicase DDX6, and its downstream target thioredoxin-interacting protein (TXNIP) in acute myeloid leukemia (AML). Using a DROSHA-knockout cell system to evaluate miR-mediated gene expression control, we comprehensively profiled putative transcripts regulated by miR-148a-3p and identified DDX6 as a direct target of miR-148a-3p in AML cells. DDX6 depletion induced cell cycle arrest, apoptosis, and differentiation, although delaying leukemia development in vivo. Genome-wide assessment of DDX6-binding transcripts and gene expression profiling of DDX6-depleted cells revealed TXNIP, a tumor suppressor, as the functional downstream target of DDX6. Overall, our study identified DDX6 as a posttranscriptional regulator that is required for AML survival. We proposed the regulatory link between miR-148a-3p and DDX6 as a potential therapeutic target in leukemia.
Factor VIII mutated with Lys1813Ala within the factor IXa-binding region enhances intrinsic coagulation potential
Authors: Nakajima Yuto , Takeyama Masahiro , Oda Akihisa , Shimonishi Naruto , Nogami Keiji
Published: November 2022

Factor VIII (FVIII) functions as a cofactor of FIXa for FX activation in the intrinsic tenase complex. The 1811-1818 region in the FVIII A3 domain was observed to contribute to FIXa binding, and the K1813A/K1818A mutant increased the binding affinity for FIXa. The current study aims to identify mutated FVIII protein(s) that increase FVIIIa cofactor activity in the 1811-1818 region. FVIII mutants with K1813A, K1818A, and K1813A/K1818A were expressed in baby hamster kidney cells and were followed by assessments using purified and global coagulation assays for mouse models with hemophilia A (HA). A surface plasmon resonance–based assay revealed that the Kd value of FVIII-K1813A for FIXa interaction was lower than that of the wild-type (WT) (3.9±0.7/6.3±0.3 nM). However, the Km value of FVIII-K1813A for FIXa on tenase activity was comparable with that of the WT, whereas the kcat of this mutant was significantly greater than that of the WT. Thrombin-catalyzed FVIII-K1813A activation was ∼1.3-fold more enhanced than that of the WT, and the spontaneous decay of activated FVIII-K1813A was ∼2.5-fold slower than that of WT. The heat stability assay revealed that the decay rate of FVIII-K1813A was ∼2.5-fold slower than that of WT. Thrombin generation assay and rotational thromboelastometry using blood samples from patients with HA demonstrated that the addition of FVIII-K1813A (0.5 nM) exhibited a coagulation potential compatible with that of WT (1 nM). In the tail clip assay of HA mice, FVIII-K1813A showed a two- to fourfold higher hemostatic potential than that of the WT. FVIII-K1813A, with higher a FIXa binding affinity, enhances the global coagulation potential because of the stability of FVIII/FVIIIa molecules.
Hydrogen peroxide in exhaled air is increased in stable asthmatic children
Authors: Jobsis Q , Raatgeep HC , Hermans PW , de Jongste JC
Published: November 2022

Exhaled air condensate provides a noninvasive means of obtaining samples from the lower respiratory tract. Hydrogen peroxide (H2O2) in exhaled air has been proposed as a marker of airway inflammation. We hypothesized that in stable asthmatic children the H2O2 concentration in exhaled air condensate may be elevated as a result of airway inflammation. In a cross-sectional study, 66 allergic asthmatic children (of whom, 41 were treated with inhaled steroids) and 21 healthy controls exhaled through a cold trap. The resulting condensate was examined fluorimetrically for the presence of H2O2. All subjects were clinically stable, nonsmokers, without infection. The median H2O2 level in the exhaled air condensate of the asthmatic patients was significantly higher than in healthy controls (0.60 and 0.15 micromol, respectively; p<0.05), largely because of high values in the stable asthmatic children who did not use anti-inflammatory treatment (0.8 micromol; p<0.01 compared to controls). We conclude that hydrogen peroxide is elevated in exhaled air condensate of children with stable asthma, and may reflect airway inflammation.
Inspiratory muscle training in chronic airflow limitation: effect on exercise performance
Authors: Lisboa C , Villafranca C , Leiva A , Cruz E , Pertuze J , Borzone G
Published: November 2022

The effect of inspiratory muscle training (IMT) on exercise capacity in patients with chronic airflow limitation (CAL) has been debated. The present study was planned to further investigate the effects of IMT on exercise performance. Twenty patients (aged 62+/-1 yrs; forced expiratory volume in one second/forced vital capacity (FEV1/FVC) 36+/-2%) were trained 30 min daily for 6 days a week during 10 weeks, with either 30% (Group 1) or 10% (Group 2) of peak maximal inspiratory pressure (PI,max) as a training load. Exercise performance was evaluated by the distance walked in 6 min (6MWD) and by changes in oxygen consumption (V'O2) and minute ventilation (V'E) during a progressive exercise test. Changes in PI,max and dyspnoea were also measured. Results showed a significant increment in peak PI,max in both groups, whereas dyspnoea and 6MWD improved only in Group 1 (p<0.05 and p<0.01, respectively). No increment in maximal workload or in peak V'O2 was observed in either group. Patients in Group 1, however, showed a reduction in V'E and V'O2 for the same exercise. A correlation between changes in V'E and V'O2 during a workload of 75 kpm x min(-1) was observed in Group 1 (r=0.92; p<0.001). We conclude that inspiratory muscle training using a load of 30% peak maximal inspiratory pressure, improves dyspnoea, increases walking capacity and reduces the metabolic cost of exercise.
Comparison of ResMed AutoSet (version 3.03) with polysomnography in the diagnosis of the sleep apnoea/hypopnoea syndrome
Authors: Gugger M
Published: November 2022

In patients with the sleep apnoea/hypopnoea syndrome (SAHS), accurate and timely diagnostic evaluation and initiation of effective treatment is important. Therefore, an increasing number of limited sleep studies are now performed nowadays diagnosing the SAHS in typical patients. It was the aim of the present study to evaluate the diagnostic accuracy of one such system, the updated ResMed Sullivan AutoSet, against polysomnography. Sixty seven patients underwent full overnight polysomnography and simultaneous data acquisition with the AutoSet. Up to now, the AutoSet was designed for apnoea detection only. The new AutoSet, with software version 3.03, detects apnoeas if ventilation drops to <25%, and apnoeas+hypopnoeas if ventilation drops to <50%, compared with the recent average (100 s), using two independent detectors. A two page report with graphically displayed information on oximetry, snoring and breathing parameters, and an apnoea+hypopnoea index (AHI) and an apnoea index (AI) are provided at the end of each study night. There was a correlation between the AHI assessed by the AutoSet (AHI-AutoSet) and by polysomnography (AHI-PSG; r=0.95). The mean difference between the AHI-AutoSet minus the AHI-PSG was 4.2 (SD 7.2) respiratory events x h(-1) (p<0.001). The AutoSet identified patients with an AHI-PSG >20 events x h(-1) (a level of respiratory disturbance that would warrant consideration for treatment in most centres for sleep disorders), with a sensitivity of 97% and a specificity of 77%. The AutoSet was superior to oximetry alone. As event counting was similar between the two methods, the AHI-AutoSet may provide a reasonable indicator of the respiratory disturbance at night, especially when taking the patients graphic study report into consideration. In conjunction with full clinical information on the patients under investigation, the AutoSet might become a useful device in diagnosing the sleep apnoea/hypopnoea syndrome.
Dendritic cells with a potent accessory activity are present in human exudative malignant pleural effusions
Authors: Gjomarkaj M , Pace E , Melis M , Spatafora M , D'Amico D , Toews GB
Published: November 2022

Dendritic cells are human leucocyte antigen (HLA)-DR positive accessory cells, that play a critical role in the development of cell-mediated immune reactions. Since the pleural space is frequently involved in cell-mediated immune reactions, we sought to isolate dendritic cells from pleural fluid. Pleural effusion mononuclear cells (PEMCs) were obtained by Ficoll centrifugation of exudative pleural effusions recovered from 19 patients with malignant pleurisy. After double-step adherence, firmly-adherent mononuclear cells (FAMs) and loosely-adherent mononuclear cells (LAMs) were recovered. The latter cells were centrifuged on a bovine plasma albumin gradient to obtain a loosely-adherent low density fraction. Nonadherent cells were rosetted with sheep red blood cells (SRBC) to obtain a nonadherent nonrosetting (NANR) cell fraction. Mitomycin C-treated PEMCs, NANRs, FAMs, and LAMs served as stimulatory cells in mixed leucocyte reaction experiments. 3H-thymidine incorporation by purified normal allogeneic blood T-lymphocytes was assessed as an index of accessory cell function. The phenotype of NANR, FAM and LAM cells was characterized using single and double stainings with a panel of monoclonal antibodies (MoAbs). Accessory cell (AC) activity (counts per minute (cpm) x 10(3)(+/-SE); 2.5 x 10(4) AC x well(-1) of LAM (148+/-24) and NANR (108.4+/-11.2) was greater than that observed for FAM (59.3+/-9.4) and for unfractioned PEMC (13.8+/-4.9). The FAM fraction was virtually entirely composed of CD68+ HLA-DR+ mononuclear phagocytes. NANR and LAM contained 51+/-12% and 65+/-6% HLA-DR+ cells, respectively, and most HLA-DR positive cells were negative for CD3, CD19, and CD68, markers for T-, B-lymphocytes and mononuclear phagocytes. Moreover, both NANR and LAM fractions contained significant numbers of cells bearing the RFD1 surface marker, expressed on dendritic cells. These results suggest that dendritic cells are present in exudative pleural effusions, and that they may be involved in the development of cell-mediated immune reactions in the pleural space.
Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: a Bayesian analysis
Authors: Pastor A , Menendez R , Cremades MJ , Pastor V , Llopis R , Aznar J
Published: November 2022

The aim of this study was to evaluate the diagnostic value of three tumour markers, squamous cell carcinoma (SCC) antigen, carcinoembryonic antigen (CEA) and CYFRA 21.1, in lung cancer using a Bayesian analysis to obtain the predictive values for different pretest probabilities or prevalences. A cross-sectional study included 94 patients with lung cancer, 40 with benign lung disease, and 40 healthy controls. SCC antigen and CEA were measured in blood samples by microparticle enzyme immunoassay (MEIA), and CYFRA by enzyme-linked immunosorbent assay (ELISA). The results of tumour marker determinations were expressed as percentiles, and showed significantly higher levels in the cancer group than in the two control groups. Taking the 95th percentile of benign lung diseases as the cut-off point (specificity 95%), the following sensitivities were found: SCC 41%, CEA 31% and CYFRA 79%. After a Bayesian analysis, the best results for the three tumour markers were found in prevalences of 30-40%. The highest incremental gain was obtained by CYFRA (at prevalence of 36%, positive and negative predictive value approximately 90%). The three tumour markers were included in a stepwise regression analysis to predict lung cancer, and CYFRA was the only selected variable. We conclude that CYFRA 21.1 may be a useful marker in lung cancer when there is an intermediate pretest probability of disease.
Neonatal BCG vaccination in Ireland: evidence of its efficacy in the prevention of childhood tuberculosis
Authors: Kelly P , McKeown D , Clancy L
Published: November 2022

Data from the 1986 and 1991 National Tuberculosis Survey were used, together with the Census of Population for those years, to try and determine whether bacille Calmette-Guerin (BCG) vaccination policy had any influence on the reported incidence of tuberculosis in the Republic of Ireland. The age-specific incidence of tuberculosis for the country as a whole and for local areas, was determined with respect to neonatal BCG vaccination. Based on these data, the reported incidence of tuberculosis in people aged 15 yrs or younger in areas without a policy of neonatal BCG was shown to be significantly higher compared to areas that use neonatal BCG vaccination (p = 1.5x10(-5) in 1986; and p = 1.0x10(-7) for 1991). It was estimated that some 646 vaccinations needed to be given to prevent one case of tuberculosis in 1986, and that the figure for 1991 was 551 vaccinations. This evidence supports a policy of continued neonatal bacille Calmette-Guerin vaccination in the population of the Republic of Ireland at present.
Measurement characteristics of two asthma symptom diary scales for use in clinical trials
Authors: Santanello NC , Barber BL , Reiss TF , Friedman BS , Juniper EF , Zhang J
Published: November 2022

The measurement characteristics of two asthma symptom diary scales developed for use as health outcome measures in clinical trials of asthma therapy were investigated. A daytime diary scale was designed to capture the frequency and inconvenience of daytime asthma symptoms and their effects on activities, and a nocturnal asthma symptom diary scale was designed to capture awakenings with asthma symptoms. The internal consistency, reliability, validity and responsiveness of both asthma diary scales were assessed in 346 adult asthma patients in two placebo-controlled clinical trials of an investigational asthma therapy, a leukotriene biosynthesis inhibitor. The daytime symptom scale showed sufficient internal consistency (0.90-0.92), and the daytime and nocturnal symptom scales showed sufficient test retest reliability (0.69-0.87). Construct validity was demonstrated by generally moderate-to-strong correlations for changes in the diary scales with changes in other measures of asthma status, such as forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and puffs of beta-agonist inhaler. Both scales demonstrated significant responsiveness to change in asthma due to therapy in one of the clinical trials. Based on these results, the daytime and nocturnal asthma symptom diary scales show measurement characteristics appropriate for use as asthma outcome measures in clinical trials of asthma therapy.
Accuracy of asthma treatment in schoolchildren in NSW, Australia
Authors: Paterson NA , Peat JK , Mellis CM , Xuan W , Woolcock AJ
Published: November 2022

Insufficient use of anti-inflammatory drugs, such as inhaled corticosteroids and cromoglycate, may contribute to the disease burden associated with asthma. Conversely, aggressive treatment of mild disease may result in avoidable costs and/or adverse drug effects. The aim of this study was to determine the relationship between asthma severity and inhaled corticosteroid/cromoglycate use in a large (n=4,909) random sample of children, aged 8-11 yrs, in NSW, Australia. Asthma and its treatment were assessed by questionnaire responses. Asthma, defined as diagnosis plus current wheeze, was present in 901 children (18% of the sample), of whom 225 (5%) had moderate asthma, defined as asthma plus additional symptoms (sleep disturbance), utilization (hospital, casualty), or disability (reduced activity, school absence). Use of inhaled corticosteroid/cromoglycate was reported by 636 children (13% of the sample). Determinants of use included: asthma diagnosis, current wheeze, and troublesome dry nocturnal cough. There was also a strong relationship between anti-inflammatory treatment and a multicomponent asthma severity score constructed for each child. Inhaled corticosteroids and/or cromoglycate were used by 56% of the children with asthma (24% daily) and by 76% of children with moderate asthma (42% daily). Undertreatment, defined as less than daily inhaled corticosteroids/cromoglycate in moderate asthma, was identified in 130 children (14% of those with asthma or 3% of the sample). Conversely, apparently aggressive treatment, defined as inhaled corticosteroid/cromoglycate use in children with persistent minimal symptoms (asthma severity score of less than 3) was identified in 101 children (2% of the sample). Although there were significant differences between regions in the choice of anti-inflammatory drugs and in the prevalence both of undertreatment and apparently aggressive treatment, there was no clear relationship to regional utilization of emergency and hospital services for asthma. Nevertheless, the frequency of undertreatment suggests an opportunity to reduce asthma morbidity by more consistent application of current therapeutic guidelines.
Allergic and nonallergic interactions between house dust mite allergens and airway mucosa
Authors: Roche N , Chinet TC , Huchon GJ
Published: November 2022

Asthma and allergy are extremely frequent diseases, affecting 5-10% and 30% of the population, respectively. The prevalence of asthma has increased in many developed countries, which may be due to several factors, including increased exposure to house dust mite (HDM) allergens. HDM to which humans are most frequently sensitized are Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Euroglyphus maynei. These mites multiply in carpets, bedding and upholstered furniture in a hot and humid atmosphere. The allergens are digestive enzymes of the mites. Several epidemiological studies have shown that an increase in exposure to HDMs is associated with an increase in the prevalence of sensitization and asthma, whereas mite avoidance leads to a decrease in respiratory symptoms of sensitized asthmatic subjects. Sensitized subjects have specific immunoglobulin G and E (IgG and IgE) humoral responses, as well as proliferative T-cell responses to HDM allergens. Experimental exposure to HDM allergens induces bronchoalveolar inflammatory responses, that are characterized by the recruitment and activation of eosinophils, mastocytes, neutrophils, monocytes and lymphocytes. The cysteine protease activity of Der p 1 (a major allergen of D. pteronyssinus) has been shown to increase airway mucosal permeability, and may thereby contribute to the pathogenesis of airway inflammation and hyperresponsiveness by nonimmunological mechanisms. These epidemiological and experimental data support the recommendations for mite avoidance, especially in persons at high risk of developing asthma.
Diffuse microvascular pulmonary thrombosis associated with primary antiphospholipid antibody syndrome
Authors: Maggiorini M , Knoblauch A , Schneider J , Russi EW
Published: November 2022

Thromboembolism is a well-known complication of the hypercoagulable state associated with antiphospholipid (aPL) antibodies. Acute respiratory failure (ARF) with diffuse pulmonary infiltrates has been reported in only a few patients with aPL antibodies. We describe a 49 year old patient with spiking fever, livedo reticularis, mild haemoptysis and ARF. Chest radiography revealed diffuse bilateral pulmonary infiltrates, and high resolution computed tomography (CT) revealed patchy distribution of areas of ground-glass attenuations. Pulmonary emboli were excluded with angiography. Lung biopsy revealed diffuse microvascular thrombosis, without capillaritis. High serum levels of anticardiolipin (aCL) antibodies were found. The patient's condition improved dramatically after intravenous infection of 1 g methylprednisolone on three consecutive days, followed by 50 mg prednisone orally. The rapid improvement following the administration of glucocorticosteroids suggests that anticardiolipin associated microvascular thrombosis, without inflammatory lesions, may depend on an interference with beta2-glycoprotein I (beta2=GPI) by anticardiolipin.
High prevalence of mollusc shell hypersensitivity pneumonitis in nacre factory workers
Authors: Orriols R , Aliaga JL , Anto JM , Ferrer A , Hernandez A , Rodrigo MJ , Morell F
Published: November 2022

Following the discovery of hypersensitivity pneumonitis caused by the inhalation of mollusc shell dust in two workers from a nacre-button factory, the health status of 26 workers employed in sawing mollusc shells was investigated. The evaluation included the administration of two questionnaires and radiological, functional and immunological assessments of all workers at the outset and 1 year later, when hygienic and therapeutic measures had been taken. Six workers, in whom specific inhalation challenge test was positive, were diagnosed with mollusc shell hypersensitivity pneumonitis, thus yielding a prevalence of 23%. Evidence of diffuse lung disease and systemic symptoms was found in these patients. Nonspecific bronchial hyperreactivity was also found more frequently in patients with mollusc shell hypersensitivity pneumonitis. Specific immunoglobulin G (IgG) level and specific skin testing failed to differentiate patients with mollusc shell hypersensitivity pneumonitis from other exposed workers; whereas, nonspecific skin testing, which was impaired in the patients, did differentiate. Bronchoalveolar lavage and transbronchial biopsy performed in patients with mollusc shell hypersensitivity pneumonitis were consistent with the disease. Removal from an environment containing mollusc shell dust was followed by regression of clinical, radiological and functional changes. The clinical picture of the 20 workers who did not present mollusc shell hypersensitivity pneumonitis remained unchanged, but functional decline was observed despite improvement in the environmental conditions of the factory. This report describes the first series of patients with mollusc shell hypersensitivity pneumonitis studied, and underlines the importance of careful follow-up of workers occupationally-exposed to mollusc shell dust.
Dissociation of neutrophil emigration and metabolic activity in lobar pneumonia and bronchiectasis
Authors: Jones HA , Sriskandan S , Peters AM , Pride NB , Krausz T , Boobis AR , Haslett C
Published: November 2022

In animal models of pulmonary inflammation, neutrophils exhibit a dramatic influx of glucose in periods of high metabolic activity. This information was utilized to develop a technique, involving positron emission tomography (PET) of 2-[18F]-fluoro-2-deoxy-D-glucose (18FDG), which measures neutrophil activity in situ. This technique was applied in a comparative study of neutrophil function in patients with acute lobar pneumonia or bronchiectasis. Neutrophil emigration was measured by gamma-scintigraphy of intravenously injected 111In-labelled granulocytes and neutrophil activity determined by PET of 18FDG. Neutrophil emigration was evident in 4 out of 5 bronchiectasis patients, whilst no emigration was apparent in the two pneumonia patients studied, consistent with animal studies showing maximum emigration soon after challenge. In contrast, 18FDG uptake was markedly increased in 4 out of 5 pneumonia patients but not in the patients with bronchiectasis. Localization of radioactivity to neutrophils was confirmed by microautoradiography of lavage fluid in a patient with pneumonia. These results suggest that the elevated uptake of glucose by neutrophils during the inflammatory response is a postmigratory event, most likely reflecting the respiratory burst, and that high levels of neutrophil emigration are not necessarily associated with significantly increased metabolic activity of these cells.
Transtracheal oxygen therapy: an effective and safe alternative to nasal oxygen administration
Authors: Kampelmacher MJ , Deenstra M , van Kesteren RG , Melissant CF , Douze JM , Lammers JW
Published: November 2022

Transtracheal oxygen therapy (TTOT) improves the efficiency of oxygen delivery and overcomes the discomfort associated with nasal oxygen delivery in patients on long-term oxygen therapy (LTOT). In addition, TTOT improves compliance and quality of life, and may reduce morbidity. Experience with TTOT in Europe is, however, scarce and the safety of TTOT has not yet been completely determined. These were reasons for testing the acceptance, efficacy and safety of TTOT. Patients were selected on the basis of the accepted indications and contraindications for TTOT. In 75 patients (48 males and 27 females) the mean follow-up time was 16 (range 0.5-51.5) months. Compared to nasal cannulae, TTOT caused a reduction in the oxygen flow rate of 47 (33-60)% at rest and a significant increase in the number of hours that oxygen was used. All patients on TTOT used oxygen for at least 20 h x day(-1). Most patients saw the procedure as a minor intervention. It was usually performed on an out-patient basis. In 34 patients, 51 mainly minor complications were seen, and most of these occurred in the first 10 patients. After precautions had been taken, complications occurred less frequently. No patient needed to be hospitalized because of a complication. TTOT had to be stopped in two patients; nevertheless, all patients preferred TTOT to the nasal cannulae. We conclude that transtracheal oxygen therapy is an effective and safe alternative to nasal oxygen administration, provided that it is restricted to a well-defined group of patients and applied by a motivated and experienced group of physicians.
Effect of corticosteroids on release of RANTES and sICAM-1 from cultured human bronchial epithelial cells, induced by TNF-alpha
Authors: Wang JH , Devalia JL , Sapsford RJ , Davies RJ
Published: November 2022

We have recently demonstrated that human bronchial epithelial cells can synthesise and release several inflammatory mediators, including the factor regulated on activation, normal T-cell expressed and secreted (RANTES) and soluble intercellular adhesion molecule-1 (sICAM-1), which influence the activity of eosinophils, and may, therefore play a role in the aetiology of asthma. In this study we investigated whether corticosteroids could influence the release of these proinflammatory mediators from human bronchial epithelial cells. Human bronchial epithelial cells were cultured to confluence as explant cultures, and incubated in the presence of 50 ng x mL(-1) tumour necrosis factor-alpha (TNF-alpha) +/- 0-10(-4) M of either fluticasone propionate (FP), beclomethasone dipropionate (BDP), or hydrocortisone (HC) for 24 h. The culture medium was collected and analyzed for RANTES and sICAM-1, by enzyme-linked immunosorbent assay (ELISA), and the cells were analysed for total protein. The TNF-alpha significantly increased the release both of RANTES and sICAM-1 (63.0 fg RANTES x microg(-1) protein; p<0.05; 8.8 pg sICAM-1 x microg(-1) protein; p<0.02), when compared with untreated cells (10.3 fg RANTES x microg(-1) protein; 2.6 pg sICAM-1 x microg(-1) cellular protein). The TNF-alpha-induced release both of RANTES and sICAM-1 occurred in a time-dependent manner, and was maximal by 24 h incubation. FP 10(-6)-10(-4) M significantly attenuated the TNF-alpha-induced release both of RANTES and sICAM-1. In contrast, 10(-4) M BDP or HC significantly attenuated the release of only sICAM-1. These results suggest that corticosteroids may prevent airway inflammation by downregulating the synthesis and/or release of proinflammatory mediators from bronchial epithelial cells. Furthermore, fluticasone propionate may be more efficacious than beclomethasone dipropionate or hydrocortisone in this respect.
The effect of inhaled sodium cromoglycate on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in asthmatics
Authors: Hoshino M , Nakamura Y
Published: November 2022

There is no direct evidence of the anti-inflammatory effect of inhaled sodium cromoglycate (SCG). To investigate whether inhaled SCG has any effect on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in patients with asthma, biopsies of the bronchial mucosa were taken from nine patients with atopic bronchial asthma before and after treatment with inhaled SCG (8 mg x day(-1)) from a metered-dose inhaler (MDI). Eosinophils were stained with anti-EG2, neutrophils with anti-NP57, mast cells with anti-AA1, T-lymphocytes with anti-CD4, CD8 and CD3, and macrophages with anti-CD68. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and P-selectin were stained at the same time as adhesion molecules expressed in vascular endothelium. The intensity of ICAM-1 expression in the bronchial epithelium was also evaluated. The numbers of eosinophils, mast cells, T-lymphocytes and macrophages were significantly reduced as a result of SCG administration, and the expression of ICAM-1, VCAM-1 and ELAM-1 was also significantly inhibited. A significant correlation was found between ICAM-1 expression and T-lymphocytes and between VCAM-1 expression and eosinophils. It was concluded that sodium cromoglycate does have an effect on the infiltration of the bronchial mucosa by inflammatory cells and also on the expression of adhesion molecules.
Activity of inhaled lysine acetylsalicylate (L-ASA) on bradykinin-induced bronchoconstriction in asthmatics: evidence of contribution of prostaglandins
Authors: Polosa R , Milazzo VL , Magri S , Pagano C , Paolino G , Santonocito G , Prosperini G , Crimi N
Published: November 2022

When administered by inhalation, bradykinin provokes dose-related bronchoconstriction in asthmatic subjects by a mechanism believed to involve activation of sensory nerve endings. However, little is known of the change in airway responsiveness to bradykinin after cyclo-oxygenase blockade. The aim of the present study was to investigate the effect of the potent cyclo-oxygenase inhibitor, lysine acetylsalicylate (L-ASA), administered by inhalation, on bradykinin-induced bronchoconstriction in a group of 12 asthmatic subjects. The subjects attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg x mL(-1)) or matched placebo (glycine, solution of 30 mg x mL(-1)) 15 min prior to bronchoprovocation tests with bradykinin and methacholine in a randomized, double-blind order with at least a 5 day interval. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1), and responsiveness to agonists was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). Administration both of L-ASA and glycine solution caused a small but significant acute fall in FEV1 from baseline, with gradual recovery within 20 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to bradykinin in 11 of the 12 subjects studied, the geometric mean (range) values for PC20 bradykinin increasing significantly (p<0.001) by 1.7 doubling dose from 0.55 (0.11-5.05) to 1.72 (0.26-6.05) mg x mL(-1) after placebo and L-ASA, respectively. No significant change in airway responsiveness to methacholine was recorded after L-ASA. It is concluded that administration of lysine acetylsalicylate by inhalation protects the asthmatic airways against bradykinin-induced bronchoconstriction, thus suggesting that endogenous prostaglandins may play a contributory role in the bronchoconstriction to kinins in human asthma.
Home intravenous therapy in cystic fibrosis: a prospective randomized trial examining clinical, quality of life and cost aspects
Authors: Wolter JM , Bowler SD , Nolan PJ , McCormack JG
Published: November 2022

In this study, we set out to determine if home intravenous (i.v.) antibiotic therapy in adult patients with cystic fibrosis (CF) is a feasible, effective and less costly alternative to hospitalization, and to assess the impact of home therapy on quality of life. The study was a prospective, randomized, two-factor mixed design involving adults presenting with respiratory exacerbations of CF. Patients were randomized such that they were discharged home after 2-4 days, or remained in hospital. Seventeen patients had 31 admissions (13 home and 18 hospital). Following 10 days of therapy, there were no significant differences between home or hospital arms with respect to body weight, 12 minute walking distance, sputum weight, pulse oximetry, or improvement in lung function (forced expiratory volume in one second (FEV1), or forced vital capacity (FVC)). Patients who remained in hospital were less fatigued and noted a greater degree of mastery. Patients discharged early noted less disruption to their family life, personal life and sleeping pattern. The total cost for the home therapy arm was approximately half that of the hospital therapy arm. Home intravenous antibiotic therapy in patients with cystic fibrosis was a feasible, cost-effective alternative to receiving therapy in hospital. Although there was no clinical compromise associated with home therapy, there were advantages and disadvantages in terms of quality of life.