Phenotypic and Functional Properties of Helios+ Regulatory T Cells

Helios, an Ikaros family transcription factor, is preferentially expressed at the mRNA and protein level in regulatory T cells. Helios expression previously appeared to be restricted to thymic-derived Treg. Consistent with recent data, we show here that Helios expression is inducible in vitro under certain conditions. To understand phenotypic and functional differences between Helios+ and Helios− Treg, we profiled cell-surface markers of FoxP3+ Treg using unmanipulated splenocytes. We found that CD103 and GITR are expressed at high levels on a subset of Helios+ Treg and that a Helios+ Treg population could be significantly enriched by FACS sorting using these two markers. Quantitative real-time PCR (qPCR) analysis revealed increased TGF-β message in Helios+ Treg, consistent with the possibility that this population possesses enhanced regulatory potential. In tumor-bearing mice, we found that Helios+ Treg were relatively over-represented in the tumor-mass, and BrdU studies showed that, in vivo, Helios+ Treg proliferated more than Helios− Treg. We hypothesized that Helios-enriched Treg might exert increased suppressive effects. Using in vitro suppression assays, we show that Treg function correlates with the absolute number of Helios+ cells in culture. Taken together, these data show that Helios+ Treg represent a functional subset with associated CD103 and GITR expression

Probing the hydrothermal system of the Chicxulub impact crater

The ~180-km-diameter Chicxulub peak-ring crater and ~240-km multiring basin, produced by the impact that terminated the Cretaceous, is the largest remaining intact impact basin on Earth. International Ocean Discovery Program (IODP) and International Continental Scientific Drilling Program (ICDP) Expedition 364 drilled to a depth of 1335 m below the sea floor into the peak ring, providing a unique opportunity to study the thermal and chemical modification of Earth’s crust caused by the impact. The recovered core shows the crater hosted a spatially extensive hydrothermal system that chemically and mineralogically modified ~1.4 × 105 km3 of Earth’s crust, a volume more than nine times that of the Yellowstone Caldera system. Initially, high temperatures of 300° to 400°C and an independent geomagnetic polarity clock indicate the hydrothermal system was long lived, in excess of 106 years

VACCELERATE Site Network: Real-time definition of clinical study capacity in Europe

Background: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. Methods: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. Results: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. Conclusions: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.The VACCELERATE Site Network has received funding from the European Union’s Horizon 2020 research and innovation pro gramme (grant agreement No 101037867) and the German Federal Ministry of Education and Research (Bundesministerium für Bil dung und Forschung [BMBF]) (grant agreement No BMBF01KX2040).S

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Global alliance for the promotion of physical activity : the Hamburg declaration

Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the ‘Hamburg Declaration’. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the ‘Global Alliance for the Promotion of Physical Activity’ to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The ‘Hamburg Declaration’ calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings.https://drc.bmj.com/am2024Sports MedicineSDG-03:Good heatlh and well-beingSDG-17:Partnerships for the goal

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Males and females have similar mortality after thoracic endovascular aortic repair for blunt thoracic aortic injury

Objective: Prior literature has demonstrated worse outcomes for female patients after abdominal aortic aneurysm repair. Also, prior studies in the context of thoracic endovascular aneurysm repair (TEVAR) for thoracic aortic aneurysms have reported conflicting results regarding sex-related outcomes. Because the influence of sex on the outcomes after TEVAR for blunt thoracic aortic injuries (BTAIs) remains understudied, we evaluated the association between sex and outcomes after TEVAR for BTAI. Methods: We identified patients who had undergone TEVAR for BTAIs in the Vascular Quality Initiative registry from 2013 to 2022 and included those who had undergone TEVAR within zones 2 to 5 of the thoracic aorta. Patients with missing information regarding the aortic injury grade (Society for Vascular Surgery aortic injury grading system) were excluded. We performed multivariable logistic regression and Cox regression to determine the influence of sex on the perioperative outcomes and long-term mortality, respectively. Results: We identified 1311 patients, of whom 27% were female. The female patients were significantly older (female, 47 years [interquartile range (IQR), 30-63 years]; male, 38 years [IQR, 28-55 years]; P < .001) with higher rates of comorbidities. Although the female patients had had higher Glasgow coma scale scores (median, 15 [IQR, 11-15]; vs 14 [IQR, 8-15]; P = .028), no differences were found in the aortic injury grade or other coexisting traumatic injuries between the sexes. Apart from the longer procedure duration for the female patients (median, 79 minutes [IQR, 52-119 minutes]; vs 69 minutes [IQR, 48-106 minutes]; P = .008), the procedural characteristics were comparable. After adjustment, no significant association was found between female sex and perioperative mortality (7.1% vs 8.1%; odds ratio, 0.76; 95% confidence interval [CI], 0.43-1.3; P = .34). The male and female patients had had comparable rates of postoperative complications (26% vs 29%; odds ratio, 0.89; 95% CI: 0.52-1.5]; P = .26) including access-related complications (0.5% vs 0.8%; P=.83). However, females had a significantly higher risk for reintervention during the index admission (odds ratio, 2.5; 95% CI, 1.1-5.5; P = .024). No significant difference was found between the male and female patients with respect to 5-year mortality (hazard ratio, 0.87; 95% CI, 0.57-1.35; P = .50). Conclusions: Unlike the sex-based outcome disparities observed after thoracic aortic aneurysm repair, we found no significant association between sex and perioperative outcomes or long-term mortality after TEVAR for BTAIs. This contrast in the sex-related outcomes after other vascular pathologies might be explained by differences in the pathology, demographics, and anatomic factors in these patients

Predicting response to physiotherapy treatment for musculoskeletal shoulder pain : A systematic review

© 2013 Chester et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: People suffering from musculoskeletal shoulder pain are frequently referred to physiotherapy. Physiotherapy generally involves a multimodal approach to management that may include; exercise, manual therapy and techniques to reduce pain. At present it is not possible to predict which patients will respond positively to physiotherapy treatment. The purpose of this systematic review was to identify which prognostic factors are associated with the outcome of physiotherapy in the management of musculoskeletal shoulder pain. Methods. A comprehensive search was undertaken of Ovid Medline, EMBASE, CINAHL and AMED (from inception to January 2013). Prospective studies of participants with shoulder pain receiving physiotherapy which investigated the association between baseline prognostic factors and change in pain and function over time were included. Study selection, data extraction and appraisal of study quality were undertaken by two independent assessors. Quality criteria were selected from previously published guidelines to form a checklist of 24 items. The study protocol was prospectively registered onto the International Prospective Register of Systematic Reviews. Results: A total of 5023 titles were retrieved and screened for eligibility, 154 articles were assessed as full text and 16 met the inclusion criteria: 11 cohort studies, 3 randomised controlled trials and 2 controlled trials. Results were presented for the 9 studies meeting 13 or more of the 24 quality criteria. Clinical and statistical heterogeneity resulted in qualitative synthesis rather than meta-analysis. Three studies demonstrated that high functional disability at baseline was associated with poor functional outcome (p ≤ 0.05). Four studies demonstrated a significant association (p ≤ 0.05) between longer duration of shoulder pain and poorer outcome. Three studies, demonstrated a significant association (p ≤ 0.05) between increasing age and poorer function; three studies demonstrated no association (p > 0.05). Conclusion: Associations between prognostic factors and outcome were often inconsistent between studies. This may be due to clinical heterogeneity or type II errors. Only two baseline prognostic factors demonstrated a consistent association with outcome in two or more studies; duration of shoulder pain and baseline function. Prior to developing a predictive model for the outcome of physiotherapy treatment for shoulder pain, a large adequately powered prospective cohort study is required in which a broad range of prognostic factors are incorporated.Peer reviewe

Whole-genome multilocus sequence typing of extended-spectrum-beta-lactamase-producing enterobacteriaceae

Molecular typing has become indispensable in the detection of nosocomial transmission of bacterial pathogens and the identification of sources and routes of transmission in outbreak settings, but current methods are labor-intensive, are difficult to standardize, or have limited resolution. Whole-genome multilocus sequence typing (wgMLST) has emerged as a whole-genome sequencing (WGS)-based gene-by-gene typing method that may overcome these limitations and has been applied successfully for several species in outbreak settings. In this study, genus-, genetic-complex-, and species-specific wgMLST schemes were developed for Citrobacter spp., the Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, and Klebsiella pneumoniae and used to type a national collection of 1,798 extended-spectrum-beta-lactamase-producing Enterobacteriaceae (ESBL-E) isolates obtained from patients in Dutch hospitals. Genus-, genetic-complex-, and species-specific thresholds for genetic distance that accurately distinguish between epidemiologically related and unrelated isolates were defined for Citrobacter spp., the E. cloacae complex, E. Coli, and K. pneumoniae. wgMLST was shown to have higher discriminatory power and typeability than in silico MLST. In conclusion, the wgMLST schemes developed in this study facilitate high-resolution WGS-based typing of the most prevalent ESBL-producing species in clinical practice and may contribute to further elucidation of the complex epidemiology of antimicrobial-resistant Enterobacteriaceae. wgMLST opens up possibilities for the creation of a Web-accessible database for the global surveillance of ESBL-producing bacterial clones