Induction of Heme Oxygenase-1, Biliverdin Reductase and H-Ferritin in Lung Macrophage in Smokers with Primary Spontaneous Pneumothorax: Role of HIF-1α

Few data concern the pathophysiology of primary spontaneous pneumothorax (PSP), which is associated with alveolar hypoxia/reoxygenation. This study tested the hypothesis that PSP is associated with oxidative stress in lung macrophages. We analysed expression of the oxidative stress marker 4-HNE; the antioxidant and anti-inflammatory proteins heme oxygenase-1 (HO-1), biliverdin reductase (BVR) and heavy chain of ferritin (H-ferritin); and the transcription factors controlling their expression Nrf2 and HIF-1alpha, in lung samples from smoker and nonsmoker patients with PSP (PSP-S and PSP-NS), cigarette smoke being a risk factor of recurrence of the disease.mRNA was assessed by RT-PCR and proteins by western blot, immunohistochemistry and confocal laser analysis. 4-HNE, HO-1, BVR and H-ferritin were increased in macrophages from PSP-S as compared to PSP-NS and controls (C). HO-1 increase was associated with increased expression of HIF-1alpha mRNA and protein in alveolar macrophages in PSP-S patients, whereas Nrf2 was not modified. To understand the regulation of HO-1, BVR and H-ferritin, THP-1 macrophages were exposed to conditions mimicking conditions in C, PSP-S and PSP-NS patients: cigarette smoke condensate (CS) or air exposure followed or not by hypoxia/reoxygenation. Silencing RNA experiments confirmed that HIF-1alpha nuclear translocation was responsible for HO-1, BVR and H-ferritin induction mediated by CS and hypoxia/reoxygenation.PSP in smokers is associated with lung macrophage oxidative stress. The response to this condition involves HIF-1alpha-mediated induction of HO-1, BVR and H-ferritin

The influence of contextual factors on healthcare quality improvement initiatives:what works, for whom and in what setting? Protocol for a realist review

Background  Context shapes the effectiveness of knowledge implementation and influences health improvement. Successful healthcare quality improvement (QI) initiatives frequently fail to transfer to different settings, with local contextual factors often cited as the cause. Understanding and overcoming contextual barriers is therefore crucial to implementing effective improvement; yet context is still poorly understood. There is a paucity of information on the mechanisms underlyinghowandwhyQI projects succeed or fail in given settings. A realist review of empirical studies of healthcare QI initiatives will be undertaken to examine the influence and impact of contextual factors on quality improvement in healthcare settings and explore whether QI initiatives can work in all contexts.  Methods  The review will explore which contextual factors are important, and how, why, when and for whom they are important, within varied settings. The dynamic nature of context and change over time will be explored by examining which aspects of context impact at key points in the improvement trajectory. The review will also consider the influence of context on improvement outcomes (provider- and patient-level), spread and sustainability. The review process will follow five iterative steps: (1) clarify scope, (2) search for evidence, (3) appraise primary studies and extract data, (4) synthesise evidence and draw conclusions and (5) disseminate findings. The reviewers will consult with experts and stakeholders in the early stages to focus the review and develop a programme theory consisting of explanatory ‘context–mechanism–outcome’ configurations. Searches for primary evidence will be conducted iteratively. Data will be extracted and tested against the programme theory. A review advisory group will oversee the review process. Review findings will follow RAMESES guidelines and will be disseminated via a report, presentations and peer-reviewed publications.  Discussion  The review will update and consolidate evidence on the contextual conditions for effective improvement and distil new knowledge to inform the design and development of context-sensitive QI initiatives. This review ties in with the study of improvement programmes as vehicles of change and the development of an evidence base around healthcare improvement by addressing whether QI initiatives can work in all contexts.  Systematic review registration  PROSPERO CRD4201706213

Patient-cooperative control increases active participation of individuals with SCI during robot-aided gait training

ABSTRACT: BACKGROUND: Manual body weight supported treadmill training and robot-aided treadmill training are frequently used techniques for the gait rehabilitation of individuals after stroke and spinal cord injury. Current evidence suggests that robot-aided gait training may be improved by making robotic behavior more patient-cooperative. In this study, we have investigated the immediate effects of patient-cooperative versus non-cooperative robot-aided gait training on individuals with incomplete spinal cord injury (iSCI). METHODS: Eleven patients with iSCI participated in a single training session with the gait rehabilitation robot Lokomat. The patients were exposed to four different training modes in random order: During both non-cooperative position control and compliant impedance control, fixed timing of movements was provided. During two variants of the patient-cooperative path control approach, free timing of movements was enabled and the robot provided only spatial guidance. The two variants of the path control approach differed in the amount of additional support, which was either individually adjusted or exaggerated. Joint angles and torques of the robot as well as muscle activity and heart rate of the patients were recorded. Kinematic variability, interaction torques, heart rate and muscle activity were compared between the different conditions. RESULTS: Patients showed more spatial and temporal kinematic variability, reduced interaction torques, a higher increase of heart rate and more muscle activity in the patient-cooperative path control mode with individually adjusted support than in the non-cooperative position control mode. In the compliant impedance control mode, spatial kinematic variability was increased and interaction torques were reduced, but temporal kinematic variability, heart rate and muscle activity were not significantly higher than in the position control mode. CONCLUSIONS: Patient-cooperative robot-aided gait training with free timing of movements made individuals with iSCI participate more actively and with larger kinematic variability than non-cooperative, position-controlled robot-aided gait training

Is salinity the main ecologic factor that shapes the distribution of two endemic Mediterranean plant species of the genus Gypsophila?

The final publication is available at Springer via http://dx.doi.org/10.1007/s11104-014-2218-2Aims Responses to salt stress of two Gypsophila species that share territory, but with different ecological optima and distribution ranges, were analysed. G. struthium is a regionally dominant Iberian endemic gypsophyte, whereas G. tomentosa is a narrow endemic reported as halophyte. Theworking hypothesis is that salt tolerance shapes the presence of these species in their specific habitats. Methods Taking a multidisciplinary approach, we assessed the soil characteristics and vegetation structure at the sampling site, seed germination and seedling development, growth and flowering, synthesis of proline and cation accumulation under artificial conditions of increasing salt stress and effect of PEG on germination and seedling development. Results Soil salinity was low at the all sampling points where the two species grow, but moisture was higher in the area of G. tomentosa. Differences were found in the species salt and drought tolerance. The different parameters tested did not show a clear pattern indicating the main role of salt tolerance in plant distribution. Conclusions G. tomentosa cannot be considered a true halophyte as previously reported because it is unable to complete its life cycle under salinity. The presence of G. tomentosa in habitats bordering salt marshes is a strategy to avoid plant competition and extreme water stressSoriano, P.; Moruno Manchón, JF.; Boscaiu Neagu, MT.; Vicente Meana, Ó.; Hurtado, A.; Llinares Palacios, JV.; Estrelles, E. (2014). Is salinity the main ecologic factor that shapes the distribution of two endemic Mediterranean plant species of the genus Gypsophila?. Plant and Soil. 384(1-2):363-379. doi:10.1007/s11104-014-2218-2S3633793841-2Alonso MA (1996) Flora y vegetación del Valle de Villena (Alicante). Instituto de Cultura Juan Gil-Albert, AlicanteAlvarado JJ, Ruiz JM, López-Cantarero I, Molero J, Romero L (2000) Nitrogen metabolism in five plant species characteristic of gypsiferous soils. Plant Physiol 156:612–616Ashraf M, Foolad MR (2007) Roles of glycine betaine and proline in improving plant abiotic stress resistance. Environ Exp Bot 59:206–216Ashraf MY (2009) Salt tolerance mechanisms in some halophytes from Saudi Arabia and Egypt. Res J Agric Biol Sci 5:191–206Bates LS, Waldren RP, Tear LD (1973) Rapid determination of free proline for water-stress studies. Plant Soil 39:205–207Ben-Gal A, Neori-Borochov H, Yermiyahu U, Shani U (2009) Is osmotic potential a more appropriate property than electrical conductivity for evaluating whole plant response to salinity? Environ Exp Bot 65:232–237Biondi E (2011) Phytosociology today: Methodological and conceptual evolution. Plant Biosyst 145:19–29Boscaiu M, Bautista I, Lidón A, Llinares J, Lull C, Donat P, Mayoral O, Vicente O (2013a) Environmental-dependent proline accumulation in plants living on gypsum soils. Acta Physiol Plant 35:2193–2204Boscaiu M, Llul C, Llinares J, Vicente O, Boira H (2013b) Proline as a biochemical marker in relation to the ecology of two halophytic Juncus species. J Plant Ecol 6:177–186Bradford KJ (1990) A water relations analysis of seed germination rates. Plant Physiol 94:840–849Breckle SW (1999) Halophytic and gypsophytic vegetation of the Ebro-Basin at Los Monegros. In: Melic A, Blasco-Zumeta J (eds) Manifiesto científico por Los Monegros, vol 24, Bol. SEA., pp 101–104Brenchley JL, Probert RJ (1998) Seed germination responses to some environmental factors in the sea grass Zoostera capricorni from eastern Australia. Aquat Bot 62:177–188Cañadas EM, Ballesteros M, Valle F, Lorite J (2013) Does gypsum influence seed germination? Turk J Bot 38:141–147Chen Z, Cuin TA, Zhou M et al (2007) Compatible solute accumulation and stress-mitigating effects in barley genotypes contrasting in their salt tolerance. J Exp Bot 58:4245–4255Chutipaijit S, Cha-Um S, Sompornailin K (2009) Differential accumulation of proline and flavonoids in Indica rice varieties against salinity. Pak J Bot 41:2497–2506Cushman JC (2001) Osmoregulation in plants: implications for agriculture. Am Zool 41:758–769Debussche M, Thompson JD (2003) Habitat differentiation between two closely related Mediterranean plant species, the endemic Cyclamen balearicum and the widespread C. repandum. Acta Oecol 24:35–45Eskandari H, Kazemi K (2011) Germination and seedling properties of different wheat cultivars under salinity conditions. Not Sci Biol 3:130–134FAO (2006) Guidelines for soil descriptions, 5th edn. Food and Agricultural Organization of United Nation, RomeFerrandis P, Herranz JM, Copete MA (2005) Caracterización florística y edáfica de las estepas yesosas de Castilla-La Mancha. Invest Agrar Sist Recur For 14:195–216Flowers TJ, Hall JL (1978) Salt tolerance in Suaeda maritima (L.) Dum. The effect of sodium chloride on growth and soluble enzymes in a comparative study with Pisum sativum L. J Exp Bot 23:310–321Flowers TJ, Colmer TD (2008) Salinity tolerance in halophytes. New Phytol 179:945–963Flowers TJ, Hajibagheri MA, Clipson NJW (1986) Halophytes. Q Rev Biol 61:313–335García-Fuentes A, Salazar C, Torres JA, Cano E, Valle F (2001) Review of communities of Lygeum spartum L. in the south-eastern Iberian Peninsula (western Mediterranean). J Arid Environ 48:323–339Géhu JM (2006) Dictionnaire de Sociologie et Synécologie Végétales. J. Cramer, Berlin-Stuttgart, p 899Géhu JM (2011) On the opportunity to celebrate the centenary of modern phytosociology in 2010. Plant Biosyst 145(suppl):4–8Ghassemi F, Jakeman AJ, Nix HA (1995) Salinisation of land and water resources: human causes, extent, management and case studies. Canberra, Australia. CAB International, The Australian National University, WallingfordGrigore MN, Boscaiu M, Vicente O (2011) Assessment of the relevance of osmolyte biosynthesis for salt tolerance of halophytes under natural conditions. Eur J Plant Sci Biotech 5:12–19Grigore MN, Villanueva M, Boscaiu M, Vicente O (2012a) Do halophytes really require salts for their growth and development? An experimental approach mitigation of salt stress-induced inhibition of Plantago crassifolia reproductive development by supplemental calcium or magnesium. Not Sci Biol 4:23–29Grigore MN, Boscaiu M, Llinares J, Vicente O (2012b) Mitigation of salt stressed-induced Inhibition of Plantago crassifolia reproductive development by supplemental calcium or magnesium. Not Bot Horti Agrobo 40:58–66Hare PD, Cress WA (1997) Metabolic implications of stress-induced proline accumulation in plants. Plant Growth Regul 21:79–102Ishikawa SI, Kachi N (2000) Differential salt tolerance of two Artemisia species growing in contrasting coastal habitats. Ecol Res 15:241–247Kebreab E, Murdoch AJ (1999) Modelling the effects of water stress and temperature on germination rate of Orobanche aegyptiaca seeds. J Exp Bot 50:655–664Khan MA (2002) Halophyte seed germination: Success and Pitfalls. In: Hegazi AM, El-Shaer HM, El-Demerdashe S et al (eds) International symposium on optimum resource utilization in salt affected ecosystems in arid and semi arid regions. Desert Research Centre, Cairo, pp 346–358Khan MA, Gul B, Weber DJ (2000) Germination responses of Salicornia rubra to temperature and salinity. J Arid Environ 45:207–214Khan A, Rayner GD (2003) Robustness to non-normality of common tests for the many-sample location problem. J Appl Math Decis Sci 7:187–206Lidón A, Boscaiu M, Collado F, Vicente O (2009) Soil requirements of three salt tolerant, endemic species from south-east Spain. Not Bot Horti Agrobo 37:64–70López González G (1990) Gypsohila L. In: Castroviejo S, Laínz M, López G et al (eds) Flora Ibérica 2. Real Jardín Botánico, Madrid, pp 408–415Lutts S, Kinet JM, Bouharmont J (1996) Effects of salt stress on growth, mineral nutrition and proline accumulation in relation to osmotic adjustment in rice (Oryza sativa L.) cultivars differing in salinity resistance. Plant Growth Regul 19:207–218Madidi S, Baroudi B, Ameur FB (2004) Effects of salinity on germination and early growth of barley (Hordeum vulgare L.) cultivars. Int J Agric Biol 6:767–770Marchal FM, Lendínez ML, Salazar C, Torres JA (2008) Aportaciones al conocimiento de la vegetación gispsícola en el occidente de la provincia de Granada (sur de España). Lazaroa 29:95–100Médail F, Verlaque R (1997) Ecological characteristics and rarity of endemic plants from southern France and Corsica: implications for biodiversity conservation. Biol Conserv 80:269–281Meyer SE (1986) The ecology of gypsophile endemism in the Eastern Mojave desert. Ecology 67:1303–1313Moruno F, Soriano P, Oscar V, Boscaiu M, Estrelles E (2011) Opportunistic germination behaviour of Gypsophila (Caryophyllaceae) in two priority habitats from semi-arid Mediterranean steppes. Not Bot Horti Agrobo 9:18–23Mota JF, Sánchez Gómez P, Merlo Calvente ME, Catalán Rodríguez P, Laguna Lumbreras E, de la Cruz RM, Navarro Reyes FB, Marchal Gallardo F, Bartolomé Esteban C, Martínez Labarga JM, Sainz Ollero H, Valle Tendero F, Serra Laliga L, Martínez Hernández F, Garrido Becerra JA, Pérez García FJ (2009) Aproximación a la checklist de los gipsófitos ibéricos. An Biol 31:71–80Mota JF, Sola AJ, Jiménez-Sánchez ML, Pérez-García F, Merlo ME (2004) Gypsicolous flora, conservation and restoration of quarries in the southeast of the Iberian Peninsula. Biodivers Conserv 13:1797–1808Munns R (2002) Comparative physiology of salt and water stress. Plant Cell Environ 25:239–250Palacio S, Escudero A, Montserrat-Martí G, Maestro M, Milla R, Albert M (2007) Plants living on gypsum: beyond the specialist model. Ann Bot 99:333–343Peinado M, Martínez-Parras JM (1982) Sobre la posición fitosociológica de Gypsophila tomentosa L. Lazaroa 4:129–140Pueyo Y, Alados CL, Maestro M, Komac B (2007) Gypsophile vegetation patterns under a range of soil properties induced by topographical position. Plant Ecol 189:301–311Rasband WS (1997–2012) ImageJ. U S National Institutes of Health. http://rsb.info.nih.gov/ij/ , Bethesda, MarylandRivas-Martínez S (2005) Notions on dynamic-catenal phytosociology as a basis of landscape science. Plant Biosyst 139:135–144Rivas-Martínez S, Rivas-Saenz S (1996–2009) Worldwide bioclimatic classification system, Phytosociological Research Center, Spain. http://www.globalbioclimatics.org . Accessed 1 July 2013Rivas-Martínez S, Fernández-González F, Loidi J, Lousã M, Penas A (2001) Syntaxonomical checklist of vascular plant communities of Spain and Portugal to association level. Itinera Geobot 14:5–341Salmerón-Sánchez E, Martínez-Nieto MI, Martínez-Hernández F, Garrido-Becerra JA, Mendoza-Fernández AJ, Gil de Carrasco C, Ramos-Miras JJ, Lozano R, Merlo ME, Mota JF (2014) Ecology, genetic diversity and phylogeography of the Iberian endemic plant Jurinea pinnata (Lag.) DC. (Compositae) on two special edaphic substrates: dolomite and gypsum. Plant Soil 374:233–250Saradhi P, Alia P, Arora S, Prasad KV (1995) Proline accumulates in plants exposed to UV radiation and protects them against UV induced peroxidation. Biochem Biophys Res Commun 209:1–5Sekmen AH, Turkan I, Tanyolac ZO, Ozfidan C, Dinc A (2012) Different antioxidant defense responses to salt stress during germination and vegetative stages of endemic halophyte Gypsophila oblanceolata Bark. Environ Exp Bot 77:63–76Tipirdamaz R, Gagneul D, Duhaze C, Ainouche A, Monnier C, Ozkum D, Larher F (2006) Clustering of halophytes from an inland salt marsh in Turkey according to their ability to accumulate sodium and nitrogenous osmolytes. Environ Exp Bot 57:139–153Ungar IA (1996) Effect of salinity on seed germination, growth, and ion accumulation of Atriplex patula (Chenopodiaceae). Am J Bot 83:604–607USDA-ARS (2008) Research databases. Bibliography on salt tolerance. George E. Brown, Jr. Salinity Lab. US Dep. Agric., Agric. Res. Serv. Riverside, CA. http://www.ars.usda.gov/Services/docs.htm?docid=8908USSL Staff (1954) Diagnosis and improvement of saline and alkali soils. US Department of Agriculture Handbook no. 60, 160 ppVicente O, Boscaiu M, Naranjo M, Estrelles E, Bellés JM, Soriano P (2004) Responses to salt stress in the halophyte Plantago crassifolia (Plantaginaceae). J Arid Environ 58:463–48

'I believe that the staff have reduced their closeness to patients': an exploratory study on the impact of HIV/AIDS on staff in four rural hospitals in Uganda

<p>Abstract</p> <p>Background</p> <p>Staff shortages could harm the provision and quality of health care in Uganda, so staff retention and motivation are crucial. Understanding the impact of HIV/AIDS on staff contributes to designing appropriate retention and motivation strategies. This research aimed 'to identify the influence of HIV/AIDS on staff working in general hospitals at district level in rural areas and to explore support required and offered to deal with HIV/AIDS in the workplace'. Its results were to inform strategies to mitigate the impact of HIV/AIDS on hospital staff.</p> <p>Methods</p> <p>A cross-sectional study with qualitative and quantitative components was implemented during two weeks in September 2005. Data were collected in two government and two faith-based private not-for-profit hospitals purposively selected in rural districts in Uganda's Central Region. Researchers interviewed 237 people using a structured questionnaire and held four focus group discussions and 44 in-depth interviews.</p> <p>Results</p> <p>HIV/AIDS places both physical and, to some extent, emotional demands on health workers. Eighty-six per cent of respondents reported an increased workload, with 48 per cent regularly working overtime, while 83 per cent feared infection at work, and 36 per cent reported suffering an injury in the previous year. HIV-positive staff remained in hiding, and most staff did not want to get tested as they feared stigmatization. Organizational responses were implemented haphazardly and were limited to providing protective materials and the HIV/AIDS-related services offered to patients. Although most staff felt motivated to work, not being motivated was associated with a lack of daily supervision, a lack of awareness on the availability of HIV/AIDS counselling, using antiretrovirals and working overtime. The specific hospital context influenced staff perceptions and experiences.</p> <p>Conclusion</p> <p>HIV/AIDS is a crucially important contextual factor, impacting on working conditions in various ways. Therefore, organizational responses should be integrated into responses to other problematic working conditions and adapted to the local context. Opportunities already exist, such as better use of supervision, educational sessions and staff meetings. However, exchanges on interventions to improve staff motivation and address HIV/AIDS in the health sector are urgently required, including information on results and details of the context and implementation process.</p

The evolutionary significance of polyploidy

Polyploidy, or the duplication of entire genomes, has been observed in prokaryotic and eukaryotic organisms, and in somatic and germ cells. The consequences of polyploidization are complex and variable, and they differ greatly between systems (clonal or non-clonal) and species, but the process has often been considered to be an evolutionary 'dead end'. Here, we review the accumulating evidence that correlates polyploidization with environmental change or stress, and that has led to an increased recognition of its short-term adaptive potential. In addition, we discuss how, once polyploidy has been established, the unique retention profile of duplicated genes following whole-genome duplication might explain key longer-term evolutionary transitions and a general increase in biological complexity

Transcriptome Analysis of the Desert Locust Central Nervous System: Production and Annotation of a Schistocerca gregaria EST Database

) displays a fascinating type of phenotypic plasticity, designated as ‘phase polyphenism’. Depending on environmental conditions, one genome can be translated into two highly divergent phenotypes, termed the solitarious and gregarious (swarming) phase. Although many of the underlying molecular events remain elusive, the central nervous system (CNS) is expected to play a crucial role in the phase transition process. Locusts have also proven to be interesting model organisms in a physiological and neurobiological research context. However, molecular studies in locusts are hampered by the fact that genome/transcriptome sequence information available for this branch of insects is still limited. EST information is highly complementary to the existing orthopteran transcriptomic data. Since many novel transcripts encode neuronal signaling and signal transduction components, this paper includes an overview of these sequences. Furthermore, several transcripts being differentially represented in solitarious and gregarious locusts were retrieved from this EST database. The findings highlight the involvement of the CNS in the phase transition process and indicate that this novel annotated database may also add to the emerging knowledge of concomitant neuronal signaling and neuroplasticity events. EST data constitute an important new source of information that will be instrumental in further unraveling the molecular principles of phase polyphenism, in further establishing locusts as valuable research model organisms and in molecular evolutionary and comparative entomology

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe