Antifungal agents for preventing fungal infections in non-neutropenic critically-ill patients

Background Invasive fungal infections, important causes of morbidity and mortality in critically ill patients, may be preventable with the prophylactic administration of antifungal agents

Measures Matter: Scales for Adaptation, Cultural Distance, and Acculturation Orientation Revisited

Building upon existing measures, four new brief acculturation scales are presented, measuring sociocultural adaptation, psychological adaptation, perceived cultural distance, and acculturation orientation. Following good scale reliability in initial samples, the English scales were translated into nine different languages (Chinese, French, German, Italian, Japanese, Portuguese, Spanish, Thai, and Turkish). The translated scales were administered to a large sample of sojourners (N = 1,929), demonstrating good reliability and adequate structural equivalence across languages. In line with existing theory, sociocultural adaptation and psychological adaptation were positively correlated, and showed a negative association with perceived cultural distance. General measures of well-being were correlated with adaptation and distance, with better adaptation relating to higher well-being, and more distance relating to lower well-being. Acculturation orientation toward the home and host culture were measured separately and a weak negative correlation was found between the two, supporting their independence. Arguing against dichotomization, these subscales were analyzed as continuous variables. Regression analysis showed sojourners to be better adapted, if they were oriented more toward the host culture and less toward the home culture. These new scales are proposed as alternatives to existing measures

Тепловой баланс помещения с электрической кабельной системой отопления

Solvothermal oxidation of metallic gallium in monoethanolamine for 72 h at 240 °C yields a crystalline sample of γ-Ga₂O₃ (∼30 nm crystallites). While Rietveld refinement (cubic spinel structure, <i>Fd</i>3̅<i>m</i>; <i>a</i> = 8.23760(9) Å) reveals that Ga occupies two pairs of octahedral and tetrahedral sites (ideal spinel and nonspinel), it provides no information about their local distribution, which cannot be statistical owing to the short Ga–Ga contacts produced if neighboring ideal spinel and nonspinel sites are simultaneously occupied. To create an atomistic model to reconcile this situation, a 6 × 6 × 6 supercell of the crystal structure is constructed and refined against neutron total scattering data using a reverse Monte Carlo (RMC) approach. This accounts well for the local as well as long-range structure and reveals significant local distortion in the octahedral sites that resembles the structure of thermodynamically stable β-Ga₂O₃. ⁷¹Ga solid-state NMR results reveal a octahedral:tetrahedral Ga ratio that is consistent with the model obtained from RMC. Nanocrystalline samples of γ-Ga₂O₃ are produced by either a short solvothermal reaction (240 °C for 11 h in diethanolamine; ∼15 nm crystallites) or by precipitation from an ethanolic solution of gallium nitrate (∼5 nm crystallites). For these samples, the Bragg scattering profile is broadened by their smaller crystallite size, consistent with transmission electron microscopy results, and analysis of the relative Bragg peak intensities provides evidence that a greater proportion of tetrahedral versus octahedral sites are filled. In contrast, neutron total scattering shows the same average Ga–O distance with decreasing particle size, consistent with ⁷¹Ga solid-state NMR results that indicate that all samples contain the same overall proportion of octahedral:tetrahedral Ga. It is postulated that increased occupation of tetrahedral sites within the smaller crystallites is balanced by an increased proportion of octahedral surface Ga sites, owing to termination by bound solvent or hydroxide

Prophylactic Intra-Aortic Balloon Counterpulsation in High Risk Cardiac Surgery: The PINBALL Pilot Multicentre, Registry-Linked, Randomised, Controlled Feasibility Trial

Background: Prophylactic intra-aortic balloon counterpulsation (IABC) is commonly used in selected patients undergoing coronary artery bypass graft (CABG) surgery, but definitive evidence is lacking. The aim of the multicentre PINBALL Pilot randomised controlled trial (RCT) was to assess the feasibility of performing a definitive trial to address this question. Methods: Patients listed for CABG surgery with impaired left ventricular function and at least one additional risk factor for postoperative low cardiac output syndrome were eligible for inclusion if the treating surgical team was uncertain as to the benefit of prophylactic IABC. The primary outcome of feasibility was based on exceeding a pre-specified recruitment rate, protocol compliance and follow-up. Results: The recruitment rate of 0.5 participants per site per month did not meet the feasibility threshold of two participants per site per month and the study was stopped early after enrolment of 24 out of the planned sample size of 40 participants. For 20/24 (83%) participants, preoperative IABC use occurred according to study assignment. Six (6)-month follow-up was available for all enrolled participants, [IABC 1 death (8%) vs. control 1 death (9%), p = 0.95]. Conclusion: The PINBALL Pilot recruitment rate was insufficient to demonstrate feasibility of a multicentre RCT of prophylactic IABC in high risk patients undergoing CABG surgery

White book on physical and rehabilitation medicine (PRM) in Europe. Chapter 10. Science and research in PRM: Specificities and challenges

In the context of the White Book of Physical and Rehabilitation Medicine (PRM), this paper deals with Research, the future of PRM. PRM students and specialists are mainly involved in biomedical research, investigating the biological processes, the causes of diseases, their medical diagnosis, the evaluation of their consequences on functioning, disability and health and the effects of health interventions at an individual and a societal level. Most of the current PRM research, often interdisciplinary, originates from applied research which, using existing knowledge, is directed towards specific goals. Translational medical research, research and development, implementation research and clinical impact research are in this field. PRM physicians, mainly master or PhD students, are nowadays increasing their participation in basic research and in pre-clinical trials. PRM physicians are involved in primary research, which is an original first hand research, but also in secondary research, which is the analysis and interpretation of primary research publications in a field, with a specific methodology. Secondary research remains an important activity of the UEMS PRM section and it will be the field of the new created Cochrane Rehabilitation. Secondary research with interest for persons with disabilities, will be developed world wide on the basis of evidence based medicine, with the participation of PRM physicians and of all other health and social professionals involved in rehabilitation. The development of research activities with interest for PRM in Europe is a challenge for the future, which has to be faced now. The European PRM schools, the European master and PhD program with their supporting research and clinical facilities, the European PRM organizations with their websites, the PRM scientific journals and European congresses are a strong basis to develop research activities, together with the development of Cochrane Rehabilitation field and of our cooperation with European high level research facilities, European and international scientific societies in different fields. PRM will be a leader in this field of research

Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial.

Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6-59 months and hospitalised with SAM (using WHO definitions: WLZ <-3, and/or MUAC <11.5 cm, and/or bilateral pedal oedema), with written, informed consent from the primary caregiver. We randomised 125 children hospitalised with complicated SAM to 14 days treatment with (i) bovine colostrum (n = 25), (ii) N-acetyl glucosamine (n = 24), (iii) subcutaneous teduglutide (n = 26), (iv) budesonide (n = 25) or (v) standard care only (n = 25). The primary endpoint was a composite of faecal biomarkers (myeloperoxidase, neopterin, α1-antitrypsin). Laboratory assessments, but not treatments, were blinded. Per-protocol analysis used ANCOVA, adjusted for baseline biomarker value, sex, oedema, HIV status, diarrhoea, weight-for-length Z-score, and study site, with pre-specified significance of P < 0.10. Of 143 children screened, 125 were randomised. Teduglutide reduced the primary endpoint of biomarkers of mucosal damage (effect size -0.89 (90% CI: -1.69,-0.10) P = 0.07), while colostrum (-0.58 (-1.4, 0.23) P = 0.24), N-acetyl glucosamine (-0.20 (-1.01, 0.60) P = 0.67), and budesonide (-0.50 (-1.33, 0.33) P = 0.32) had no significant effect. All interventions proved safe. This work suggests that treatment of enteropathy may be beneficial in children with complicated malnutrition. The trial was registered at ClinicalTrials.gov with the identifier NCT03716115

Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus

Funder: NHLI FoundationFunder: NIHR Imperial Biomedical Research Centre; FundRef: http://dx.doi.org/10.13039/501100013342Funder: National Heart Lung and Blood InstituteFunder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Funder: National Institute of Biomedical Imaging and Bioengineering; FundRef: http://dx.doi.org/10.13039/100000070Funder: Gates Cambridge ScholarshipFunder: NIH/OXCAM FellowshipObjectives: Low-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking and immune function are intimately linked to cellular biophysical properties. This study used proteomic, biomechanical and functional analyses to further define neutrophil heterogeneity in the context of SLE. Methods: Proteomic/phosphoproteomic analyses were performed in healthy control (HC) normal density neutrophils (NDNs), SLE NDNs and autologous SLE LDGs. The biophysical properties of these neutrophil subsets were analysed by real-time deformability cytometry and lattice light-sheet microscopy. A two-dimensional endothelial flow system and a three-dimensional microfluidic microvasculature mimetic (MMM) were used to decouple the contributions of cell surface mediators and biophysical properties to neutrophil trafficking, respectively. Results: Proteomic and phosphoproteomic differences were detected between HC and SLE neutrophils and between SLE NDNs and LDGs. Increased abundance of type 1 interferon-regulated proteins and differential phosphorylation of proteins associated with cytoskeletal organisation were identified in SLE LDGs relative to SLE NDNs. The cell surface of SLE LDGs was rougher than in SLE and HC NDNs, suggesting membrane perturbances. While SLE LDGs did not display increased binding to endothelial cells in the two-dimensional assay, they were increasingly retained/trapped in the narrow channels of the lung MMM. Conclusions: Modulation of the neutrophil proteome and distinct changes in biophysical properties are observed alongside differences in neutrophil trafficking. SLE LDGs may be increasingly retained in microvasculature networks, which has important pathogenic implications in the context of lupus organ damage and small vessel vasculopathy

Using shared goal setting to improve access and equity : a mixed methods study of the Good Goals intervention in children's occupational therapy

Peer reviewedPublisher PD

Influenza Outbreaks during World Youth Day 2008 Mass Gathering

Novel viruses were introduced and seasonal viruses were amplified

Rac1 and Rac3 isoform activation is involved in the invasive and metastatic phenotype of human breast cancer cells

INTRODUCTION: The metastatic progression of cancer is a direct result of the disregulation of numerous cellular signaling pathways, including those associated with adhesion, migration, and invasion. Members of the Rac family of small GTPases are known to act as regulators of actin cytoskeletal structures and strongly influence the cellular processes of integrin-mediated adhesion and migration. Even though hyperactivated Rac proteins have been shown to influence metastatic processes, these proteins have never been directly linked to metastatic progression. METHODS: To investigate a role for Rac and Cdc42 in metastatic breast cancer cell invasion and migration, relative endogenous Rac or Cdc42 activity was determined in a panel of metastatic variants of the MDA-MB-435 metastatic human breast cancer cell line using a p21-binding domain-PAK pull down assay. To investigate the migratory and invasive potential of the Rac isoforms in human breast cancer, namely Rac1 and the subsequently cloned Rac3, we stably expressed either dominant active Rac1 or dominant active Rac3 into the least metastatic cell variant. Dominant negative Rac1 or dominant negative Rac3 were stably expressed in the most metastatic cell variant. Cell lines expressing mutant Rac1 or Rac3 were analyzed using in vitro adhesion, migration and invasion assays. RESULTS: We show that increased activation of Rac proteins directly correlates with increasing metastatic potential in a panel of cell variants derived from a single metastatic breast cancer cell line (MDA-MB-435). The same correlation could not be found with activated Cdc42. Expression of a dominant active Rac1 or a dominant active Rac3 resulted in a more invasive and motile phenotype. Moreover, expression of either dominant negative Rac1 or dominant negative Rac3 into the most metastatic cell variant resulted in decreased invasive and motile properties. CONCLUSION: This study correlates endogenous Rac activity with high metastatic potential and implicates Rac in the regulation of cell migration and invasion in metastatic breast cancer cells. Taken together, these results suggest a role for both the Rac1 and Rac3 GTPases in human breast cancer progression