bluuebunny/crossref_metadata_2025 huggingface dataset:
Community-Based HIV and STI Prevention in Women Working in Indoor Sex Markets
Authors: Bungay Vicky , Kolar Kat , Thindal Soni , Remple Valencia P. , Johnston Caitlin L. , Ogilvie Gina
Published: August 2012

Community research into women’s experiences in the indoor commercial sex industry illustrated an urgent need for sexually transmitted infection (STI) and HIV education, prevention, testing, and treatment and culturally appropriate services to support the sexual and reproductive health of commercial sex workers (CSWs). This work also revealed that a high number of immigrant—primarily Asian—women are involved in the indoor sex industry. In response, the authors developed a community–academic research partnership to design and implement a blended outreach research program to provide STI and HIV prevention interventions for indoor CSWs and their clients. This Community Health Worker Model HIV Prevention and Health Promotion Program incorporated health education, primary care referrals, STI testing using self-swab techniques, and a point-of-care HIV screening test. Here the authors report on program implementation, design, and the experiences of participants and team members and provide research and vaccination recommendations for future work in this area. This work work affirms that community-based service providers can be a key entry point for indoor CSWs to access health care and sexual health promotion and education and may be a solution to missed opportunities to provide culturally and contextually appropriate education and services to this population.
A Successful Rescue of Systematic Inflammatory Response Syndrome Resulting From Severe Wound Infection
Authors: Tian Ming , Wang Xiqiao , Xiao Yurui , Lu Shuliang , Jiang Yuzhi
Published: August 2012

This article reports a critical case of systematic inflammatory response syndrome (SIRS) due to wound infection. By intensive local wound treatment including debridement, topical negative pressure, and topical antibiotics, SIRS was effectively controlled, vital signs stabilized, and the wound healed in 45 days. This case reflects the close association between wound infection and SIRS while highlighting early diagnosis of local pathology and local treatment.
Three-Dimensional Reconstruction of Computed Tomography Scan Images for Estimating Skull Damage in Electrical Burned Patients
Authors: Chen Jian , Yan Hong , Peng Yizhi , Li Xiaolu , Hu Jianian , Wu Jun
Published: August 2012

Three cases of skull osteomyelitis due to electrical burn and delayed wound closure are presented. For better estimating skull damage before operation, 3-dimensional reconstruction of computed tomography scan images were used. Three-dimensional computed tomography could provide superior and visible stereoscopic images and help clinicians “see” the damage before operation and make more detailed therapeutic planning.
A Survey of Diabetic Foot Patients With Hospitalized Amputations Performed in a Medical Center Over 5 Years in China
Authors: Li Qiyin , Wang Xingang , Hu Xinlei , Han Chunmao
Published: August 2012

To perform a retrospective survey of the clinical features and clinical courses of diabetic foot patients with amputations hospitalized in the Second Affiliated Hospital of Zhejiang University from 2007 to 2011.According to the database from the medical records department in our hospital 36 cases of diabetic patients were selected out of 805 cases of amputees. The clinical information was recorded in detail. With the contact information provided in the medical record, telephone interviews were conducted for each patient and their family to complete the record for the current disease progression and the patient’s treatment process. Among all of the patients with hospitalized amputations, 36/805(4.47%) were diabetic foot patients with amputations, accounting for 36/273(13.19%) of non-traumatic amputations. The average age of the diabetic patients with first-time amputations was 62 years, the average BMI was greater than 24.5kg/m2, and the waist-to-hip ratio was greater than 0.92. Among the 22 patients who completed the follow-up interviews, 17 had only small amputations. Diabetic amputation has become a common clinical problem. The patients were mainly elderly, overweight or obese. Amputations at the toe level still accounted for a large proportion of the patients. Overall, the follow-up interviews indicated that the patients lacked good understanding of and concern for their own disease, with unclear control of blood sugar and no standardized control method. Helping the patients to understand the disease and paying attention to health education may play a role in the prevention and treatment of diabetes and diabetic foot disease.
Stem Cell Research, Repairing, and Regeneration Medicine
Authors: Chun Qing , Liang Lu Shu
Published: August 2012

Stem cell research has become one of the hot points in the medical field, including wound healing, repairing, or regeneration medicine, because stem cells have the characteristics of self-renewal and differentiating into multiple types of total specialized cells of the body. The researchers involved in stem cell research hope that they can use this skill to one day create tissues or even organs instead of treating damaged tissues or organs in severe injury or in terminal-stage diseases, thus prolonging the life of patients and improving their quality of the life. But it is still a long way ahead with many difficulties to overcome to realize this dream. In this article, the authors discuss some problems in this special field.
Lymphocutaneous Sporotrichosis in an Adolescent Girl Presenting as Mycetoma
Authors: Tilak Ragini , Kumari Varsha , Bansal Manish , Sharma Taniya , Pandey Shyam Sunder
Published: August 2012

A 13-year-old girl presented with multiple painless purulent ulcers with raised borders on the medial aspect of the sole of her right foot associated with inguinal lymphadenopathy for the past 4 years. There was history of local trauma at the site prior to the formation of ulcers. There were no other significant associated signs or symptoms. The patient was initially treated with multiple antibiotics with minimal improvement. Fungal cultures of biopsy specimens demonstrated the presence of colonies of Sporothrix schenckii thus confirming the diagnosis of sporotrichosis. Oral itraconazole at the dose of 100 mg twice daily was initiated with marked response at 4 weeks. This case demonstrated a rare morphological presentation of the lymphocutaneous sporotrichosis as mycetoma. The possible diagnosis of sporotrichosis should be kept in mind in such a clinical presentation not responding to antibiotics. Cutaneous sporotrichosis should be diagnosed and treated as early as possible because untreated cases may disseminate to cause visceral involvement with fatal outcome in immunocompromised patients.
The Effect of Information Analysis Automation Display Content on Human Judgment Performance in Noisy Environments
Authors: Bass Ellen J. , Baumgart Leigh A. , Shepley Kathryn Klein
Published: August 2012

Displaying both the strategy that information analysis automation employs to makes its judgments and variability in the task environment may improve human judgment performance, especially in cases where this variability impacts the judgment performance of the information analysis automation. This work investigated the contribution of providing either information analysis automation strategy information, task environment information, or both, on human judgment performance in a domain where noisy sensor data are used by both the human and the information analysis automation to make judgments. In a simplified air traffic conflict prediction experiment, 32 participants made probability of horizontal conflict judgments under different display content conditions. After being exposed to the information analysis automation, judgment achievement significantly improved for all participants as compared to judgments without any of the automation’s information. Participants provided with additional display content pertaining to cue variability in the task environment had significantly higher aided judgment achievement compared to those provided with only the automation’s judgment of a probability of conflict. When designing information analysis automation for environments where the automation’s judgment achievement is impacted by noisy environmental data, it may be beneficial to show additional task environment information to the human judge in order to improve judgment performance.
Addressing methodological challenges in implementing the nursing home pain management algorithm randomized controlled trial
Authors: Ersek Mary , Polissar Nayak , Pen Anna Du , Jablonski Anita , Herr Keela , Neradilek Moni B
Published: August 2012

Background

Unrelieved pain among nursing home (NH) residents is a well-documented problem. Attempts have been made to enhance pain management for older adults, including those in NHs. Several evidence-based clinical guidelines have been published to assist providers in assessing and managing acute and chronic pain in older adults. Despite the proliferation and dissemination of these practice guidelines, research has shown that intensive systems-level implementation strategies are necessary to change clinical practice and patient outcomes within a health-care setting. One promising approach is the embedding of guidelines into explicit protocols and algorithms to enhance decision making.

Purpose

The goal of the article is to describe several issues that arose in the design and conduct of a study that compared the effectiveness of pain management algorithms coupled with a comprehensive adoption program versus the effectiveness of education alone in improving evidence-based pain assessment and management practices, decreasing pain and depressive symptoms, and enhancing mobility among NH residents.

Methods

The study used a cluster-randomized controlled trial (RCT) design in which the individual NH was the unit of randomization. The Roger’s Diffusion of Innovations theory provided the framework for the intervention. Outcome measures were surrogate-reported usual pain, self-reported usual and worst pain, and self-reported pain-related interference with activities, depression, and mobility.

Results

The final sample consisted of 485 NH residents from 27 NHs. The investigators were able to use a staggered enrollment strategy to recruit and retain facilities. The adaptive randomization procedures were successful in balancing intervention and control sites on key NH characteristics. Several strategies were successfully implemented to enhance the adoption of the algorithm.

Limitations/Lessons

The investigators encountered several methodological challenges that were inherent to both the design and implementation of the study. The most problematic issue concerned the measurement of outcomes in persons with moderate to severe cognitive impairment. It was difficult to identify valid, reliable, and sensitive outcome measures that could be applied to all NH residents regardless of the ability to self-report. Another challenge was the inability to incorporate advances in implementation science into the ongoing study

Conclusions

Methodological challenges are inevitable in the conduct of an RCT. The need to optimize internal validity by adhering to the study protocol is compromised by the emergent logistical issues that arise during the course of the study.
Stopping a trial early – and then what?
Authors: Wittes Janet
Published: August 2012

Background

This article addresses a problem arising when a trial shows such strong evidence of benefit of the tested intervention that it stops early with an observed effect size for the experimental treatment that is statistically significantly better than the control. Within the classical frequentist framework of group sequential trials, the observed estimated effect size, the associated naïve confidence interval, and the p-value are all biased estimates of the true values. The bias is in the direction of the overestimation of the treatment effect, creation of narrower confidence intervals than appropriate, and a p-value that is too small.

Purpose

To discuss methods for correcting the bias in observed effect sizes, confidence intervals, and p-values for trials stopped early and to show the extent to which such correction would have modified the conclusions of the Randomized Aldactone Evaluation Study (RALES).

Results

In RALES, the effect of not correcting for bias is negligible.

Limitations

This article does not show general results; it only explores a few examples that use conservative methods for early stopping. It does not consider sequential methods that allow a relatively high probability of stopping early.

Conclusions

This article points out that there is no unique solution to the correction of the p-value, but it recommends stagewise ordering, which states that earlier stopping of a trial is ipso facto stronger evidence of effect than later stopping so long as the stopping is governed by a monitoring boundary that preserves the Type I error rate. Associated with stagewise ordering is a method for calculating the estimated effect size and its confidence interval. In the RALES trial, which stopped at 50% information time, the corrections to the estimated values are small.
The issue of multiplicity in noninferiority studies
Authors: Ke Chunlei , Ding Beiying , Jiang Qi , Snapinn Steven M
Published: August 2012

Background

In a clinical study to evaluate noninferiority (NI) of an experimental drug relative to an established therapy, it is common to further test superiority of the experimental drug after NI is established. It has been shown that no multiplicity issue exists between NI and superiority tests of the primary endpoint. However, when there is an additional, or secondary, endpoint that will be tested for superiority in a hierarchical fashion to the NI testing of the primary endpoint, it is not clear whether the overall type I error rate is strictly controlled among all the tests.

Purpose

In this article, our goal is to evaluate if the family-wise type I error rate is strictly controlled in this setting. We also evaluate a multiplicity adjustment procedure based on the Hochberg procedure.

Methods

We use the closed testing principle to evaluate the family-wise type I error rate. Some simulations are performed to appreciate the magnitude of the potential inflation of the type I error rate.

Results

It is demonstrated that the family-wise type I error rate is not controlled and an appropriate multiplicity adjustment procedure must take into account the NI and superiority tests of the two endpoints. When the test statistic used for superiority testing of the primary endpoint is the same as that for the NI testing, a multiplicity adjustment method using the popular Hochberg procedure is shown to be potentially conservative.

Limitation

The assessment is based on a simplified set-up where there is only one secondary endpoint tested for superiority in addition to the primary endpoint.

Conclusion

It is necessary to evaluate the issue of multiplicity in non-inferiority studies to assure strict control of the family-wise type I error rate.
Implementing Pulse Oximetry in the School Health Office
Authors: DeSisto Marie C.
Published: August 2012

Pulse oximetry can be a useful tool for professional school nurses who daily assess students with a variety of health issues and injuries. Pulse oximeters are now smaller and more affordable and, therefore, an option for school districts to purchase. Before implementing this new tool into their practice, school nurses must have an understanding of how pulse oximeters work and how they measure the oxygen saturation of arterial hemoglobin. A review of the literature will guide a nurse in developing clinical guidelines for practice and facilitating competency in using a pulse oximeter with the ultimate goal of improving student health assessments.
In Vivo MRI Tracking of Polyethylenimine-Wrapped Superparamagnetic Iron Oxide Nanoparticle–Labeled BMSCs for Cartilage Repair
Authors: Chen Jiarong , Wang Fuyou , Zhang Yi , Jin Xuhong , Zhang Lin , Feng Yong , Yang Liu
Published: August 2012

Objective:

To evaluate the feasibility of tracking polyethylenimine (PEI)-wrapped superparamagnetic iron oxide (SPIO) nanoparticle–labeled, bone marrow–derived mesenchymal stem cells (BMSCs) by in vivo magnetic resonance imaging (MRI) in articular cartilage repair in a minipig model.

Methods:

Eighteen Guizhou minipigs were randomly divided into three groups (groups A, B, and C). In group A, PEI-wrapped SPIO nanoparticle (PEI/SPIO) and green fluorescent protein (GFP) colabeled, autologous BMSCs seeded in type II collagen gel were transplanted into the articular cartilage defects of the minipig model. In group B, GFP-labeled, autologous BMSCs seeded in type II collagen gel were transplanted. In group C, no treatment was applied for cartilage defects. All minipigs underwent clinical 3.0-T MR imaging at 4, 8, 12, and 24 weeks postsurgery. The findings were compared histologically.

Results:

Prussian staining and transmission electron microscope showed that BMSCs were efficiently labeled by PEI/SPIO. Cell viability, proliferation, and differentiation were comparable between labeled and unlabeled cells. MRI SET2WI sequence revealed that marked hypointense signal void areas representing the transplanted labeled BMSCs could be observed for at least 24 weeks. Histochemical staining confirmed the presence of Prussian blue–positive cells and GFP-positive cells at the hypointense signal void areas. At 24 weeks postsurgery, both MR signals and histologic staining of minipigs in groups A and B at the cartilage defect were close to the normal cartilage.

Conclusions:

3.0-T MRI in vivo tracking of PEI/SPIO-labeled BMSCs seeded in type II collagen gel on cartilage repair following transplantation is feasible in minipigs.
Intra-abdominal Umbilical Vein Varix Thrombus
Authors: McFadzen Michael , Harper Deann
Published: August 2012

Fetal intra-abdominal umbilical vein varix (FIUVV) is an uncommon finding with poorly understood clinical significance. Numerous fetal complications are associated with this anomaly. This case report demonstrates FIUVV in which thrombus develops leading to early induction of labor for successful delivery. The literature regarding FIUVV is reviewed and discussed with implications for sonographic follow-up during pregnancy and patient management.
Methemoglobinemia and ascorbate deficiency in hemoglobin E β thalassemia: metabolic and clinical implications
Authors: Allen Angela , Fisher Christopher , Premawardhena Anuja , Bandara Dayananda , Perera Ashok , Allen Stephen , St Pierre Timothy , Olivieri Nancy , Weatherall David
Published: August 2012

During investigations of the phenotypic diversity of hemoglobin (Hb) E β thalassemia, a patient was encountered with persistently high levels of methemoglobin associated with a left-shift in the oxygen dissociation curve, profound ascorbate deficiency, and clinical features of scurvy; these abnormalities were corrected by treatment with vitamin C. Studies of erythropoietin production before and after treatment suggested that, as in an ascorbate-deficient murine model, the human hypoxia induction factor pathway is not totally dependent on ascorbate levels. A follow-up study of 45 patients with HbE β thalassemia showed that methemoglobin levels were significantly increased and that there was also a significant reduction in plasma ascorbate levels. Haptoglobin levels were significantly reduced, and the high frequency of the 2.2 haptoglobin genotype may place an additional pressure on ascorbate as a free-radical scavenger in this population. There was, in addition, a highly significant correlation between methemoglobin levels, splenectomy, and factors that modify the degree of globin-chain imbalance. Because methemoglobin levels are modified by several mechanisms and may play a role in both adaptation to anemia and vascular damage, there is a strong case for its further study in other forms of thalassemia and sickle-cell anemia, particularly when splenic function is defective.
Prevention of hyperoxia-mediated pulmonary inflammation in neonatal rats by caffeine
Authors: Weichelt Ulrike , Cay Ruhuye , Schmitz Thomas , Strauss Evelyn , Sifringer Marco , Bührer Christoph , Endesfelder Stefanie
Published: August 2012

In preterm human infants, briefly elevated concentrations of oxygen are associated with a prolonged increase in blood chemokine concentrations and the development of bronchopulmonary dysplasia (BPD). Caffeine given to preterm infants for the prevention or treatment of apnoea has been shown to reduce the rate of BPD.

We tested the hypotheses that infant rats exposed to a combination of caffeine and hyperoxia would be less susceptible to lung injury than those exposed to hyperoxia alone and that caffeine decreases the pulmonary tissue expression of chemokines and leukocyte influx following hyperoxia.

Using 6-day-old rat pups, we demonstrated that 24 h of 80% oxygen exposure caused pulmonary recruitment of neutrophils and macrophages. High levels of oxygen upregulated the expression of: the CXC chemokines, cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2; the CC-chemokine monocyte chemoattractant protein-1; the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6, as measured by realtime PCR after the administration of caffeine (10 mg·kg−1body weight); and attenuated chemokine and cytokine upregulation, as well as the influx of CD11b+, ED-1+and myeloperoxidase+leukocytes.

These experiments suggest that protective effects of caffeine in the neonatal lung are mediated, at least in part, by reduction of pulmonary inflammation.
The impact of depressive symptoms on recovery and outcome of hospitalised COPD exacerbations
Authors: Papaioannou Andriana I. , Bartziokas Konstantinos , Tsikrika Stamatoula , Karakontaki Foteini , Kastanakis Emmanouil , Banya Winston , Haniotou Aikaterini , Papiris Spyros , Loukides Stelios , Polychronopoulos Vlassis , Kostikas Konstantinos
Published: August 2012

The impact of depressive symptoms on outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has not been thoroughly evaluated in prospective studies.

We prospectively enrolled 230 consecutive patients hospitalised for AECOPD, without previous diagnosis of depression. Depressive symptoms were evaluated with Beck's depression inventory. Pulmonary function tests, arterial blood gases, COPD assessment test (CAT) and Borg dyspnoea scale were recorded on admission and on days 3, 10 and 40. Patients were evaluated monthly for 1 year.

Patients with depressive symptoms required longer hospitalisation (mean±sd11.6±3.7versus5.6±4.1 days, p<0.001). Clinical variables improved during the course of AECOPD, but depressive symptoms on admission had a significant impact on dyspnoea (p<0.001) and CAT score (p=0.012) improvement. Patients with depressive symptoms presented more AECOPD (p<0.001) and more hospitalisations for AECOPD (p<0.001) in 1 year. In multivariate analysis, depressive symptoms were an independent predictor of mortality (hazard ratio 3.568, 95% CI 1.302–9.780) and risk for AECOPD (incidence rate ratio (IRR) 2.221, 95% CI 1.573–3.135) and AECOPD hospitalisations (IRR 3.589, 95% CI 2.319–5.556) in 1 year.

The presence of depressive symptoms in patients admitted for AECOPD has a significant impact on recovery and is related to worse survival and increased risk for subsequent COPD exacerbations and hospitalisations in 1 year.
Short-form Sun-style t’ai chi as an exercise training modality in people with COPD
Authors: Leung Regina Wai Man , McKeough Zoe J. , Peters Matthew J. , Alison Jennifer A.
Published: August 2012

The aims of the study were to determine the effect of short-form Sun-style t’ai chi (SSTC) (part A) and investigate exercise intensity of SSTC (part B) in people with chronic obstructive pulmonary disease (COPD).

Part A: after confirmation of eligibility, participants were randomly allocated to either the t’ai chi group or control group (usual medical care). Participants in the t’ai chi group trained twice weekly for 12 weeks. Part B: participants who had completed training in the t’ai chi group performed a peak exercise test (incremental shuttle walk test) and SSTC while oxygen consumption (VO2) was measured. Exercise intensity of SSTC was determined by the per cent ofVO2reserve.

Of 42 participants (mean±sdforced expiratory volume in 1 s 59±16% predicted), 38 completed part A and 15 completed part B. Compared to control, SSTC significantly increased endurance shuttle walk time (mean difference 384 s, 95% CI 186–510); reduced medial-lateral body sway in semi-tandem stand (mean difference -12.4 mm, 95% CI -21– -3); and increased total score on the chronic respiratory disease questionnaire (mean difference 11 points, 95% CI 4–18). The exercise intensity of SSTC was 53±18% ofVO2reserve.

SSTC was an effective training modality in people with COPD achieving a moderate exercise intensity which meets the training recommendations.
Regional lung function and heterogeneity of specific gas volume in healthy and emphysematous subjects
Authors: Aliverti Andrea , Pennati Francesca , Salito Caterina , Woods Jason C.
Published: August 2012

The aim of our study was to study regional lung function by standard computed tomography (CT) and characterise regional variations of density and specific gas volume (SVg) between different lung volumes.

We studied 10 healthy and 10 severely emphysematous subjects. Corresponding CT images taken at high and low lung volumes were registered by optical flow to obtain two-dimensional maps of pixel-by-pixel differences of density (ΔHU) and SVg (ΔSVg) at slice levels near the aortic arch, carina and top diaphragm.

In healthy subjects, ΔHU was higher at all levels (p<0.001) with higher variability expressed as interquartile range (p<0.001), largely due to its differences between dorsal and ventral regions. In patients, median ΔSVg values were 3.2 times lower than healthy volunteers (p<0.001), while heterogeneity of ΔSVg maps, expressed as quartile coefficient of variation, was 5.4 times higher (p<0.001). In all patients, there were areas with negative values of ΔSVg.

In conclusion, ΔSVg is uniform in healthy lungs and minimally influenced by gravity. The significant ΔSVg heterogeneity observed in emphysema allows identification of areas of alveolar destruction and gas trapping and suggests that ΔSVg maps provide useful information for evaluation and planning of emerging treatments that target trapped gas for removal.
Sweet talk: insights into the nature and importance of glucose transport in lung epithelium
Authors: Garnett James P. , Baker Emma H. , Baines Deborah L.
Published: August 2012

For over 50 years, glucose has been recognised to cross the lung epithelial barrier and be transported by lung epithelial cells. However, until recently, research into these processes focused on their effects on lung liquid volume. Here, we consider a newly identified role for pulmonary glucose transport in maintaining low airway surface liquid (ASL) glucose concentrations and propose that this contributes to lung defence against infection.

Glucose diffuses into ASLviaparacellular pathways at a rate determined by paracellular permeability and the transepithelial glucose gradient. Glucose is removed from ASL in proximal airwaysviafacilitative glucose transporters, down a concentration gradient generated by intracellular glucose metabolism. In the distal lung, glucose transportviasodium-coupled glucose transporters predominates. These processes vary between species but universally maintain ASL glucose at 3–20-fold lower concentrations than plasma.

ASL glucose concentrations are increased in respiratory disease and by hyperglycaemia. Elevated ASL glucose in intensive care patients was associated with increasedStaphylococcus aureusinfection. Diabetic patients with and without chronic lung disease are at increased risk of respiratory infection. Understanding of mechanisms underlying lung glucose homeostasis could identify new therapeutic targets for control of ASL glucose and prevention and treatment of lung infection.
CFTR biomarkers: time for promotion to surrogate end-point
Authors: De Boeck K. , Kent L. , Davies J. , Derichs N. , Amaral M. , Rowe S.M. , Middleton P. , de Jonge H. , Bronsveld I. , Wilschanski M. , Melotti P. , Danner-Boucher I. , Boerner S. , Fajac I. , Southern K. , de Nooijer R.A. , Bot A. , de Rijke Y. , de Wachter E. , Leal T. , Vermeulen F. , Hug M.J. , Rault G. , Nguyen-Khoa T. , Barreto C. , Proesmans M. , Sermet-Gaudelus I.
Published: August 2012

In patients with cystic fibrosis, cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal potential difference, are used as end-points of efficacy in phase-III clinical trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren. The aim of this project was to review the literature on reliability, validity and responsiveness of nasal potential difference, sweat chloride and intestinal current measurement in patients with cystic fibrosis.

Data on clinimetric properties were collected for each biomarker and reviewed by an international team of experts. Data on reliability, validity and responsiveness were tabulated. In addition, narrative answers to four key questions were discussed and agreed by the team of experts.

The data collected demonstrated the reliability, validity and responsiveness of nasal potential difference. Fewer data were found on reliability of sweat chloride concentration; however, validity and responsiveness were demonstrated. Validity was demonstrated for intestinal current measurement, but further information is required on reliability and responsiveness. For all three end-points, normal values were collected and further research requirements were proposed.

This body of work adds useful information to support the promotion of CFTR biomarkers to surrogate end-points and to guide further research in the area.
SharedPseudomonas aeruginosagenotypes are common in Australian cystic fibrosis centres
Authors: Kidd Timothy J. , Ramsay Kay A. , Hu Honghua , Marks Guy B. , Wainwright Claire E. , Bye Peter T. , Elkins Mark R. , Robinson Philip J. , Rose Barbara R. , Wilson John W. , Grimwood Keith , Bell Scott C. ,   the ACPinCF Investigator Group
Published: August 2012

Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways forPseudomonas aeruginosain patients with cystic fibrosis (CF). In Australia, there is only limited evidence of unrelated patients sharing indistinguishableP. aeruginosastrains. We therefore examined the point-prevalence, distribution, diversity and clinical impact ofP. aeruginosastrains in Australian CF patients nationally.

983 patients attending 18 Australian CF centres provided 2887 sputumP. aeruginosaisolates for genotyping by enterobacterial repetitive intergenic consensus-PCR assays with confirmation by multilocus sequence typing. Demographic and clinical details were recorded for each participant.

Overall, 610 (62%) patients harboured at least one of 38 shared genotypes. Most shared strains were in small patient clusters from a limited number of centres. However, the two predominant genotypes, AUST-01 and AUST-02, were widely dispersed, being detected in 220 (22%) and 173 (18%) patients attending 17 and 16 centres, respectively. AUST-01 was associated with significantly greater treatment requirements than uniqueP. aeruginosastrains.

Multiple clusters of sharedP. aeruginosastrains are common in Australian CF centres. At least one of the predominant and widespread genotypes is associated with increased healthcare utilisation. Longitudinal studies are now needed to determine the infection control implications of these findings.
Airway epithelial cell apoptosis and inflammation in COPD, smokers and nonsmokers
Authors: Comer David M. , Kidney Joseph C. , Ennis Madeleine , Elborn J. Stuart
Published: August 2012

We hypothesised that primary bronchial epithelial cells (PBECs) from subjects with chronic obstructive pulmonary disease (COPD) respond differently toPseudomonas aeruginosalipopolysaccharide (LPS) after cigarette smoke extract (CSE) exposure than PBECs obtained from smokers without airflow obstruction and nonsmokers.

PBECs from 16 COPD subjects, 10 smokers without airflow obstruction and nine nonsmokers were cultured at air–liquid interface. Cultures were incubated with CSE prior to stimulation withP. aeruginosaLPS. Interleukin (IL)-6 and IL-8 were measured by ELISA and Toll-like receptor (TLR)-4 expression by fluorescence-activated cell sorter. Activation of nuclear factor (NF)-κB was determined by Western blotting and ELISA, and MAPK and caspase-3 activity by Western blotting. Apoptosis was evaluated using Annexin-V staining and the terminal transferase-mediated dUTP nick end-labelling methods.

Constitutive release of IL-8 and IL-6 was greatest from the COPD cultures. However, CSE pretreatment followed byP. aeruginosaLPS stimulation reduced IL-8 release from COPD PBECs, but increased it from cells of smokers without airflow obstruction and nonsmokers. TLR-4 expression, MAPK and NF-κB activation in COPD cultures were reduced after CSE treatment, but not in the smokers without airflow obstruction or nonsmoker groups, which was associated with increased apoptosis.

CSE attenuates inflammatory responses to LPS in cells from people with COPD but not those from nonsmoking individuals and those who smoke without airflow obstruction.
Transmission of multidrug-resistant and extensively drug-resistant tuberculosis in a metropolitan city
Authors: Leung Eric Chung Ching , Leung Chi Chiu , Kam Kai Man , Yew Wing Wai , Chang Kwok Chiu , Leung Wai Man , Tam Cheuk Ming
Published: August 2012

Multidrug-resistant (MDR)- tuberculosis (TB) and extensively drug resistant (XDR)-TB reportedly lead to increased household transmission.

This is a retrospective cohort study of active TB occurring among household contacts exposed to MDR-TB.

Of 704 contacts in 246 households, initial screening identified 12 (1.7%) TB cases (prevalent cases) and 17 (2.4%) contacts that subsequently developed active TB (secondary cases) after a median (range) duration of 17 (5–62.5) months. Eight prevalent cases and three secondary cases had MDR-TB. TB incidence rates per 100 000 person-years were 254.9 overall and 45.0 for MDR-TB. XDR-TB in the index MDR-TB patient significantly increased the odds of identifying a prevalent TB case to 4.8 (95% CI 1.02–22.5), and the hazard of finding a secondary TB case to 4.7 (95% CI 1.7–13.5). Molecular fingerprinting confirmed household transmission of MDR-TB. Of 20 retrievable isolates from 27 XDR-TB index cases, restriction fragment length polymorphism analysis showed clustering among 13 (65%), with 11 (55%) due to recent transmission by n-1 method and an identifiable household source in only three (27.2%) of the 11 cases.

XDR-TB relative to MDR-TB significantly increases household transmission of TB, probably reflecting prolonged/higher infectivity, and indicating a need for prolonged household surveillance. XDR-TB may largely transmit outside of the household settings.
Defining race/ethnicity and explaining difference in research studies on lung function
Authors: Braun Lundy , Wolfgang Melanie , Dickersin Kay
Published: August 2012

The 2005 guidelines of the American Thoracic Society/European Respiratory Society recommend the use of race- and/or ethnic-specific reference standards for spirometry. Yet definitions of the key variables of race and ethnicity vary worldwide. The purpose of this study was to determine whether researchers defined race and/or ethnicity in studies of lung function and how they explained any observed differences.

Using the methodology of the systematic review, we searched PubMed in July 2008 and screened 10 471 titles and abstracts to identify potentially eligible articles that compared “white” to “other racial and ethnic groups”.

Of the 226 eligible articles published between 1922 and 2008, race and/or ethnicity was defined in 17.3%, with the proportion increasing to 70% in the 2000s for those using parallel controls. Most articles (83.6%) reported that “other racial and ethnic groups” have a lower lung capacity compared to “white”; 94% of articles failed to examine socioeconomic status. In the 189 studies that reported lower lung function in “other racial and ethnic groups”, 21.8% and 29.4% of explanations cited inherent factors and anthropometric differences, respectively, whereas 23.1% of explanations cited environmental and social factors.

Even though researchers sought to determine differences in lung function by race/ethnicity, they typically failed to define their terms and frequently assumed inherent (or genetic) differences.
Effectiveness of sequential automatic-manual home respiratory polygraphy scoring
Authors: Masa Juan F. , Corral Jaime , Pereira Ricardo , Duran-Cantolla Joaquin , Cabello Marta , Hernández-Blasco Luis , Monasterio Carmen , Alonso-Fernandez Alberto , Chiner Eusebi , Vázquez-Polo Francisco-José , Montserrat Jose M. ,   the Spanish Sleep Group
Published: August 2012

Automatic home respiratory polygraphy (HRP) scoring functions can potentially confirm the diagnosis of sleep apnoea-hypopnoea syndrome (SAHS) (obviating technician scoring) in a substantial number of patients. The result would have important management and cost implications. The aim of this study was to determine the diagnostic cost-effectiveness of a sequential HRP scoring protocol (automatic and then manual for residual cases) compared with manual HRP scoring, and with in-hospital polysomnography.

We included suspected SAHS patients in a multicentre study and assigned them to home and hospital protocols at random. We constructed receiver operating characteristic (ROC) curves for manual and automatic scoring. Diagnostic agreement for several cut-off points was explored and costs for two equally effective alternatives were calculated.

Of 366 randomised patients, 348 completed the protocol. Manual scoring produced better ROC curves than automatic scoring. There was no sensitive automatic or subsequent manual HRP apnoea–hypopnoea index (AHI) cut-off point. The specific cut-off points for automatic and subsequent manual HRP scorings (AHI >25 and >20, respectively) had a specificity of 93% for automatic and 94% for manual scorings. The costs of manual protocol were 9% higher than sequential HRP protocol; these were 69% and 64%, respectively, of the cost of the polysomnography.

A sequential HRP scoring protocol is a cost-effective alternative to polysomnography, although with limited cost savings compared to HRP manual scoring.
Evaluation of QuantiFERON microtube, using 0.9 mL blood, for diagnosing tuberculosis infection
Authors: Rose Michala V. , Kimaro Godfather , Kroidl Inge , Hoelscher Michael , Bygbjerg Ib C. , Mfinanga Sayoki M. , Ravn Pernille
Published: August 2012

The performance of QuantiFERON microtube (QFT-MT), using 0.9 mL blood, and QuantiFERON-TB Gold in-tube test (QFT-IT) (3 mL blood), for diagnosing tuberculosis (TB) was compared in children and adults in an endemic setting.

In 152 children with suspected TB and 87 adults with confirmed TB, QFT-IT was compared with two QFT-MT concentrations (QFT-MT A and B). Proportions of positive and indeterminate results, interferon (IFN)-γ responses, interassay agreement and sensitivity were assessed.

We found similar proportions of indeterminate results, levels of IFN-γ and comparable sensitivity. The interassay agreement was moderate in all children (QFT-ITversusQFT-MT A: 85%, k=0.44 and QFT-ITversusQFT-MT B: 88%, k=0.50) and adults (QFT-ITversusQFT-MT A: 88%, k=0.50 and QFT-ITversusQFT-MT B: 89%, k=0.49). Sensitivity was low (QFT-IT 23%, QFT-MT A 18% and B 19%) in children with confirmed or highly probable TB compared with adults (83%, 86% and 88%, respectively).

The QFT-MT test can be reliably performed using less than one-third of the blood volume used in QFT-IT. The reduced volume may be useful for research and future diagnosis of paediatric TB. The poor sensitivity and high indeterminate rate of both IFN-γ release assays in severely ill children, with immature or impaired immunity in an endemic setting, warrants further investigations.
Hospital admissions of adults with community-acquired pneumonia in Portugal between 2000 and 2009
Authors: Froes Filipe , Diniz António , Mesquita Margarida , Serrado Margarida , Nunes Baltazar
Published: August 2012

Recent studies in the USA and northern Europe have shown an increase in community-acquired pneumonia (CAP). In southern Europe, this increase has not yet been documented.

We carried out a retrospective analysis from encoded information from the Portuguese database for hospital admissions that included all individuals aged ≥18 years, with a primary diagnosis of pneumonia, who were discharged between 2000 and 2009. We excluded patients infected with HIV, individuals immunocompromised as a result of anti-cancer or immunosuppressive treatment, and transplant recipients.

Of the 294 027 admissions for CAP, 56% were male. The mean age was 73.1 years and the median age 77 years. Between 2000 and 2009, there was a 5% increase in the average age of patients admitted with CAP.

Admissions for CAP represented 3.7% of total admissions of adult patients. The average annual rate of hospital admissions for adults with CAP was 3.61 per 1000 total population, rising to 13.4 for those aged ≥65 years. Between 2000–2004 and 2005–2009 the average annual rate of hospital admission for CAP per 1000 population increased by 28.2%.

Hospital admissions for CAP in Portugal increased between 2000 and 2009. It has grown consistently over time, varying according to age with males over-represented.
Distinct gene loci control the host response to influenza H1N1 virus infection in a time-dependent manner
Authors: Nedelko Tatiana , Kollmus Heike , Klawonn Frank , Spijker Sabine , Lu Lu , Heßman Manuela , Alberts Rudi , Williams Robert W , Schughart Klaus
Published: August 2012

Background

There is strong but mostly circumstantial evidence that genetic factors modulate the severity of influenza infection in humans. Using genetically diverse but fully inbred strains of mice it has been shown that host sequence variants have a strong influence on the severity of influenza A disease progression. In particular, C57BL/6J, the most widely used mouse strain in biomedical research, is comparatively resistant. In contrast, DBA/2J is highly susceptible.

Results

To map regions of the genome responsible for differences in influenza susceptibility, we infected a family of 53 BXD-type lines derived from a cross between C57BL/6J and DBA/2J strains with influenza A virus (PR8, H1N1). We monitored body weight, survival, and mean time to death for 13 days after infection. Qivr5 (quantitative trait for influenza virus resistance on chromosome 5) was the largest and most significant QTL for weight loss. The effect of Qivr5 was detectable on day 2 post infection, but was most pronounced on days 5 and 6. Survival rate mapped to Qivr5, but additionally revealed a second significant locus on chromosome 19 (Qivr19). Analysis of mean time to death affirmed both Qivr5 and Qivr19. In addition, we observed several regions of the genome with suggestive linkage. There are potentially complex combinatorial interactions of the parental alleles among loci. Analysis of multiple gene expression data sets and sequence variants in these strains highlights about 30 strong candidate genes across all loci that may control influenza A susceptibility and resistance.

Conclusions

We have mapped influenza susceptibility loci to chromosomes 2, 5, 16, 17, and 19. Body weight and survival loci have a time-dependent profile that presumably reflects the temporal dynamic of the response to infection. We highlight candidate genes in the respective intervals and review their possible biological function during infection.
GhWRKY15, a member of the WRKY transcription factor family identified from cotton (Gossypium hirsutumL.), is involved in disease resistance and plant development
Authors: Yu Feifei , Huaxia Yifeng , Lu Wenjing , Wu Changai , Cao Xuecheng , Guo Xingqi
Published: August 2012

Background

As a large family of regulatory proteins, WRKY transcription factors play essential roles in the processes of adaptation to diverse environmental stresses and plant growth and development. Although several studies have investigated the role of WRKY transcription factors during these processes, the mechanisms underlying the function of WRKY members need to be further explored, and research focusing on the WRKY family in cotton crops is extremely limited.

Results

In the present study, a gene encoding a putative WRKY family member, GhWRKY15, was isolated from cotton. GhWRKY15 is present as a single copy gene, and a transient expression analysis indicated that GhWRKY15 was localised to the nucleus. Additionally, a group of cis-acting elements associated with the response to environmental stress and plant growth and development were detected in the promoter. Consistently, northern blot analysis showed that GhWRKY15 expression was significantly induced in cotton seedlings following fungal infection or treatment with salicylic acid, methyl jasmonate or methyl viologen. Furthermore, GhWRKY15-overexpressing tobacco exhibited more resistance to viral and fungal infections compared with wild-type tobacco. The GhWRKY15-overexpressing tobacco also exhibited increased RNA expression of several pathogen-related genes, NONEXPRESSOR OF PR1, and two genes that encode enzymes involved in ET biosynthesis. Importantly, increased activity of the antioxidant enzymes POD and APX during infection and enhanced expression of NtAPX1 and NtGPX in transgenic tobacco following methyl viologen treatment were observed. Moreover, GhWRKY15 transcription was greater in the roots and stems compared with the expression in the cotyledon of cotton, and the stems of transgenic plants displayed faster elongation at the earlier shooting stages compared with wide type tobacco. Additionally, exposure to abiotic stresses, including cold, wounding and drought, resulted in the accumulation of GhWRKY15 transcripts.

Conclusion

Overall, our data suggest that overexpression of GhWRKY15 may contribute to the alteration of defence resistance to both viral and fungal infections, probably through regulating the ROS system via multiple signalling pathways in tobacco. It is intriguing that GhWRKY15 overexpression in tobacco affects plant growth and development, especially stem elongation. This finding suggests that the role of the WRKY proteins in disease resistance may be closely related to their function in regulating plant growth and development.