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BACKGROUND: Rib fractures are one of the most common traumatic injuries and may result in significant morbidity and mortality. Despite growing evidence, technological advances and increasing acceptance, surgical stabilization of rib fractures (SSRF) remains not uniformly considered in trauma centers. Indications, contraindications, appropriate timing, surgical approaches and utilized implants are part of an ongoing debate. The present position paper, which is endorsed by the World Society of Emergency Surgery (WSES), and supported by the Chest Wall Injury Society, aims to provide a review of the literature investigating the use of SSRF in rib fracture management to develop graded position statements, providing an updated guide and reference for SSRF. METHODS: This position paper was developed according to the WSES methodology. A steering committee performed the literature review and drafted the position paper. An international panel of experts then critically revised the manuscript and discussed it in detail, to develop a consensus on the position statements. RESULTS: A total of 287 studies (systematic reviews, randomized clinical trial, prospective and retrospective comparative studies, case series, original articles) have been selected from an initial pool of 9928 studies. Thirty-nine graded position statements were put forward to address eight crucial aspects of SSRF: surgical indications, contraindications, optimal timing of surgery, preoperative imaging evaluation, rib fracture sites for surgical fixation, management of concurrent thoracic injuries, surgical approach, stabilization methods and material selection. CONCLUSION: This consensus document addresses the key focus questions on surgical treatment of rib fractures. The expert recommendations clarify current evidences on SSRF indications, timing, operative planning, approaches and techniques, with the aim to guide clinicians in optimizing the management of rib fractures, to improve patient outcomes and direct future research.

Members of the Filoviridae family are negativesense, nonsegmented, single-stranded RNA viruses with the potential to cause hemorrhagic disease in humans and nonhuman primates. Lloviu virus (LLOV) is an emerging filovirus [...]

BACKGROUND: The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. METHODS: Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. RESULTS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patients directives, family feelings and representatives desires, and all decisions should be shared. CONCLUSIONS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

Endotracheal intubation is a medical procedure to secure a patient’s airways, which can be challenging in emergency situations due to an individual’s anatomy. Intubation blades can benefit from an adjustable design with shape memory alloys. We present a novel blade design with two degrees of freedom, continuously transforming a straight into a curved blade. Our demonstrators reached mean angular deflections up to 16∘ without exceeding outer blade temperatures of 40∘C. Mean forces of almost 24N were applicable. This approach has the potential to reduce the complexity of intubation procedures and increase the success rate, especially in time-critical emergency situations.

Limited or absent haptic feedback is reported as a factor hindering the continued adoption of surgical robots. This article presents a proof of concept for vibrotactile feedback integrated into a continuum robot to explore whether such feedback improves spatial perception in surgical settings. The robot is equipped with a capacitive sensor for noncontact endoscope localization, enabling spatial awareness of the robot’s tool center point (TCP) within the surgical environment. The data from the sensor is processed and transmitted to a bracelet worn by the user, which generates vibrotactile feedback. The bracelet contains four vibration motors providing tactile cues for navigation and positioning of the robot’s TCP. All subsystems are integrated into a unified system to deliver vibrotactile feedback to the user. When the user maneuvers the TCP of the robot near an object, they receive vibrotactile feedback via the bracelet. Thereby, the intensity of vibration increases as the TCP approaches the object, and the direction of the obstacle is mapped on the bracelet. Initial functional tests were performed and prove the functionality of the proposed system.

Enhanced perioperative care protocols become the standard of care in elective surgery with a significant improvement in patients outcome. The key element of the enhanced perioperative care protocol is the multimodal and interdisciplinary approach targeted to the patient, focused on a holistic approach to reduce surgical stress and improve perioperative recovery. Enhanced perioperative care in emergency general surgery is still a debated topic with little evidence available. The present position paper illustrates the existing evidence about perioperative care in emergency surgery patients with a focus on each perioperative intervention in the preoperative, intraoperative and postoperative phase. For each item was proposed and approved a statement by the WSES collaborative group.

BackgroundActive commuting to school (e.g., walking or cycling) can contribute to an increase in daily physical activity time of adolescents which is associated with positive health effects. However, it is known that the perceived barriers related to the physical and social environment hinder adolescents in participating in active commuting. To obtain more information about these barriers, and therefore be able to address them in the future, the present study aims to investigate how parents’ and adolescents’ perception of the physical and social environment is associated with (active) commuting to school.MethodsThe ARRIVE study consists of a quantitative online survey with parent-adolescent dyads (N = 517) followed by qualitative interviews with adolescents and parents (N = 32). The quantitative part examined adolescents’ travel behaviour to and from school and its predictors. The qualitative part sought to explore the decision-making process in families regarding transport mode choice. To evaluate predictors of active commuting to and from school binary logistic regression analysis and qualitative content analysis were performed.ResultsIn the quantitative part, we found that adolescents and parents perceive especially having much luggage to carry as crucial for adolescents’ active travel. Besides this barrier on active commuting to and from school found in the questionnaires, parents and adolescents reported lack of social support, weather, convenience, lack of traffic safety and getting a lift as barriers in the interviews.ConclusionWe found differences and similarities in the perceived barriers of active commuting regarding the physical and social environment between adolescents and parents. To encourage adolescents to actively commute to school, the perception of the physical and social environment, especially from parents, be taken into account.

Background and aims: Celiac disease (CeD) affects 1–2% of the world's population. The aim of this study was to relate the incidence of CeD-related serological markers to symptoms, pathologies, and environmental exposure to wheat flour, given the number of flour mills present in the region. Materials & methods: Serum samples were collected from 537 inhabitants from a rural city. Levels of anti-transglutaminase (a-tTg), anti-gliadin, anti-DGP antibodies and total IgA levels were measured. Volunteers completed a questionnaire covering environmental factors, demographics, pregnancies, other diseases, symptoms, and CeD diagnosis. Geo-referencing of volunteers' homes and mills in the city was performed, and correlations between the different parameters assessed were analysed. Results: A CeD incidence of 1.76 % was found. However, a-tTg and a-gliadin levels were elevated in the population without CeD diagnosis (9.6 % and 30.1 %). Subjects with CD diagnosis showed diarrhoea and colic pain. Women with CeD had fewer pregnancies. Positive a-tTg and number of CeD-associated symptoms appear to correlate with proximity to flour mills. Conclusion: A high prevalence of CeD-related specific antibody positivity in a rural population was found, possibly due to environmental factors related to flour mills. Further research is needed to better understand CeD's pathogenesis and its health implications.

The transgenerational effects of exposing male mice to chronic social instability (CSI) stress are associated with decreased sperm levels of multiple members of the miR-34/449 family that persist after their mating through preimplantation embryo (PIE) development. Here we demonstrate the importance of these miRNA changes by showing that restoring miR-34c levels in PIEs derived from CSI stressed males prevents elevated anxiety and defective sociability normally found specifically in their adult female offspring. It also restores, at least partially, levels of sperm miR-34/449 normally reduced in their male offspring who transmit these sex-specific traits to their offspring. Strikingly, these experiments also revealed that inducing miR-34c levels in PIEs enhances the expression of its own gene and that of miR-449 in these cells. The same induction of embryo miR-34/449 gene expression likely occurs after sperm-derived miR-34c is introduced into oocytes upon fertilization. Thus, suppression of this miRNA amplification system when sperm miR-34c levels are reduced in CSI stressed mice can explain how a comparable fold-suppression of miR-34/449 levels can be found in PIEs derived from them, despite sperm containing ~50-fold lower levels of these miRNAs than those already present in PIEs. We previously found that men exposed to early life trauma also display reduced sperm levels of miR-34/449. And here we show that miR-34c can also increase the expression of its own gene, and that of miR-449 in human embryonic stem cells, suggesting that human PIEs derived from men with low sperm miR-34/449 levels may also contain this potentially harmful defect.

BackgroundExtracellular vesicles (EVs), a heterogeneous group of cell-derived, membrane-enclosed vesicles bearing cell-specific epitopes, have been demonstrated to play a crucial role in neuronal-glial communication and the orchestration of neuroinflammatory processes. However, the existing evidence regarding their function as biomarkers and their role in the pathobiology of traumatic spinal cord injuries (tSCI), particularly in humans, is scarce.ObjectiveThe primary goal of this study was to investigate whether a distinct pattern of EV surface epitopes detected in the plasma of individuals suffering from spinal cord injury is indicative of tSCI.MethodsThe study includes patients with isolated tSCI (n=8), polytrauma patients without tSCI (PT; ISS ≥16, n=8), and healthy volunteers (HV; n=8). Plasma samples from tSCI and PT patients were collected right after admission to the emergency room (ER), 24 hours (24h), and 48h after trauma. EVs were isolated via size exclusion chromatography, and EVs’ surface epitopes were quantified with MACSPlex EV Kit Neuro (prototype product, Miltenyi Biotec) and compared among the groups. Additionally, results were correlated with clinical parameters.ResultsIn total, 19 epitopes differed significantly between the tSCI and the HV groups. Out of these 19, four (CD47, CD56, CD68, and ADAM17) were found to differ significantly among tSCI and PT groups. The expression of the CD47 epitope was found to correlate positively with the American Spinal Injury Association (ASIA) impairment scale.ConclusionWe identified four potential EV-based tSCI biomarkers (CD47+, CD56+, CD68+, and ADAM17+ EVs) that differ in tSCI, with CD47+ EVs showing a strong correlation with the neurological function in tSCI. Thus, future studies might further specify the relevance of potential tSCI-specific biomarkers and investigate underlying mechanisms of tSCI.

BackgroundPolytrauma and hemorrhagic shock can lead to direct and indirect liver damage involving intricate pathophysiologic mechanisms. While hepatic function has been frequently highlighted, there is minimal research on how the receptor activator of the NF-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system is regulated in the liver following trauma. Furthermore, cross-talking complement and toll-like-receptor (TLR) systems can contribute to the posttraumatic response. Therefore, we investigated the hepatic consequences of polytrauma focusing on the RANK-RANKL-OPG axis, and evaluated the effects of a dual blockade of complement factor C5 and TLR-cofactor CD14 on hepatic features.MethodsThe established pig model of polytrauma (PT) and hemorrhagic shock included pulmonary contusion, hepatic dissection, and bilateral femur fractures, surgically addressed either by external fixation (Fix ex) or intramedullary nailing (Nail). Four groups were investigated: 1) sham animals; 2) PT treated by Fix ex (Fix ex); 3) PT by Nail (Nail); or 4) PT by Nail plus combined C5/CD14 inhibition (Nail+Therapy). Serum samples were obtained between 0 - 72 h, and liver samples at 72 h after PT. Liver tissues were histologically scored and subjected to RT-qPCR-analyses, immunohistochemistry and ELISAs to evaluate the posttraumatic hepatic response with a focus on the RANK-RANKL-OPG system.ResultsFollowing PT, the liver injury score of the Nail+Therapy group was significantly lower than in the Fix ex or Nail group without immunomodulation (p

Plasma membrane (PM) domains and order phases have been shown to play a key role in the assembly, release, and entry of several lipid-enveloped viruses. In the present study, we provide a mechanistic understanding of the Ebola virus (EBOV) matrix protein VP40 interaction with PM lipids and their effect on VP40 oligomerization, a crucial step for viral assembly and budding. VP40 matrix formation is sufficient to induce changes in the PM fluidity. We demonstrate that the distance between the lipid headgroups, the fatty acid tail saturation, and the PM order are important factors for the stability of VP40 binding and oligomerization at the PM. The use of FDA-approved drugs to fluidize the PM destabilizes the viral matrix assembly leading to a reduction in budding efficiency. Overall, these findings support an EBOV assembly mechanism that reaches beyond lipid headgroup specificity by using ordered PM lipid regions independent of cholesterol.

Background: Nutrition quality could be one of the reasons why, in the face of a Shiga toxin-producing enterohemorrhagic Escherichia coli outbreak, some patients experience more profound deleterious effects than others, including unfortunate deaths. Thus, the aim of this study was to determine whether high-fat and/or high-carbohydrate diets could negatively modulate the deleterious action of Shiga toxin 2 on ventral anterior and ventral lateral thalamic nuclei and the internal capsule, the neurological centers responsible for motor activity. Methods: Mice were fed a regular, high-fat, high-carbohydrate diet or a combination of both previous to the intravenous administration of Shiga toxin 2 or vehicle. Four days after intravenous administration, mice were subjected to behavioral tests and then sacrificed for histological and immunofluorescence assays to determine alterations in the neurovascular unit at the cellular and functional levels. Statistical analysis was performed using one-way analysis of variance followed by Bonferroni post hoc test. The criterion for significance was p = 0.0001 for all experiments. Results: The high-fat and the high-carbohydrate diets significantly heightened the deleterious effect of Stx2, while the combination of both diets yielded the worst results, including endothelial glycocalyx and oligodendrocyte alterations, astrocyte and microglial reactivity, neurodegeneration, and motor and sensitivity impairment. Conclusions: In view of the results presented here, poor nutrition could negatively influence patients affected by Stx2 at a neurological level. Systemic effects, however, cannot be ruled out.

Laparotomy incisions provide easy and rapid access to the peritoneal cavity in case of emergency surgery. Incisional hernia (IH) is a late manifestation of the failure of abdominal wall closure and represents frequent complication of any abdominal incision: IHs can cause pain and discomfort to the patients but also clinical serious sequelae like bowel obstruction, incarceration, strangulation, and necessity of reoperation. Previous guidelines and indications in the literature consider elective settings and evidence about laparotomy closure in emergency settings is lacking. This paper aims to present the World Society of Emergency Surgery (WSES) project called ECLAPTE (Effective Closure of LAParoTomy in Emergency): the final manuscript includes guidelines on the closure of emergency laparotomy.

Abstract The biology underlying proton minibeam radiation therapy (pMBRT) is not fully understood. Here we aim to elucidate the biological effects of pMBRT using Fourier Transform Infrared Microspectroscopy (FTIRM). In vitro (CTX-TNA2 astrocytes and F98 glioma rat cell lines) and in vivo (healthy and F98-bearing Fischer rats) irradiations were conducted, with conventional proton radiotherapy and pMBRT. FTIRM measurements were performed at ALBA Synchrotron, and multivariate data analysis methods were employed to assess spectral differences between irradiation configurations and doses. For astrocytes, the spectral regions related to proteins and nucleic acids were highly affected by conventional irradiations and the high-dose regions of pMBRT, suggesting important modifications on these biomolecules. For glioma, pMBRT had a great effect on the nucleic acids and carbohydrates. In animals, conventional radiotherapy had a remarkable impact on the proteins and nucleic acids of healthy rats; analysis of tumour regions in glioma-bearing rats suggested major nucleic acid modifications due to pMBRT.

Due to the dynamic nature of nitrate in fresh vegetables and the presence of multiple inaccurate detection techniques, quantifying nitrate concentration remains more challenging than detecting other pollutants. This study evaluated the effectiveness of three common methods, namely high-performance liquid chromatography (HPLC) and two spectrophotometric methods (ISO 6635 and Cadmium-Column Reduction) for measuring nitrate in vegetables. For this purpose, 11 vegetables with varying nitrate accumulation potentials were analyzed. It was observed that the nitrate concentration in onions, as measured by spectrophotometric methods, was lower than the results obtained by HPLC. Consequently, the spectrophotometric methods were modified to improve nitrate measurement in onion samples. The results demonstrated that the average nitrate concentration in leafy vegetables was higher than in tuberous, root, and fruit vegetables. Among the vegetables, spinach, lettuce, and celery, respectively, exhibited the highest nitrate concentrations, while watermelon, tomato, and onion had the lowest levels. A strong correlation was observed across all three methods for determining nitrate content. The HPLC method demonstrated the highest accuracy in samples with high nitrate content, while the spectrophotometric methods were more accurate for samples with low nitrate content. Although the HPLC method incurs higher equipment costs, it is faster, more accurate, and safer than the spectrophotometric methods. Since both Cd-Column reduction and ISO 6635 are based on the Griess reaction, their accuracy depends on factors such as pH, temperature, time, and sample matrix. Therefore, each method can be selected based on laboratory equipment, costs, and specific advantages or limitations.

Background: The increased hypertonicity or activity of pelvic floor muscles can lead to chronic pelvic pain (CPP). It represents an aspecific and persistent pain with no apparent clinical reason, affecting an estimated 6% to 16% of women worldwide. This study aimed to evaluate with validated questionnaires the efficacy and the safeness of a new device that uses Top flat Magnetic Stimulation for the management of muscular hypertonia in women with CCP. Methods: All patients underwent 8 treatments with a non-invasive electromagnetic therapeutic device. The device produces a TOP Flat Magnetic Stimulation with a uniform profile so, the muscle work aims to reduce pain while also inhibiting muscle activity. The PISQ-12 questionnaire was used for the evaluation of improvements. Side effects were monitored. Results: The PISQ-12 total mean score decreases from 29,2 (±3.3) to 17 (±2). Regarding the behavioural–emotive items (1-4), a decrease from 12 (±2) to 7 (±0.9) was visible. Physical items (5-9) decrease from 10,6 (±1.8) to 6 (±1.4) and the Partner Related items (10-12) from 6,6 (±1.6) to 3,9 (±0.4). Conclusions: The device we used in this research demonstrated to be a valid solution for the treatment of chronic pelvic pain in female patients.

BackgroundThe one-step membrane technique, using a human acellular dermal matrix (hADM), is an experimental method for treating large bone defects. This eliminates the need for the Masquelet membrane induction step, shortening the procedure while maintaining effectiveness. However, previous studies showed that colonizing hADM with bone marrow mononuclear cells (BMC) worsens healing, likely due to the presence of CD8+ lymphocytes, which negatively affect bone regeneration. This study aims to investigate whether the negative impact of BMC on bone healing in this technique is due to the CD8+ cell population.Materials and methodsA 5 mm femoral defect was created in 25 male Sprague-Dawley rats, divided into three groups (G1-G3). BMC were isolated from syngenic donor rats, with CD8+ lymphocytes removed magnetically from the BMC fraction in one group. The defects were filled with bone chips and wrapped with differently treated hADM: G1 received native hADM, G2 received hADM+BMC, and G3 received hADM+BMC-CD8. After 8 weeks, the femurs were evaluated through radiological, biomechanical, and histological examinations.ResultsBone defects and bone mineral density (BMD) were significantly improved in G3 (hADM+BMC-CD8) compared to G2 (hADM+BMC). Bone volume, bone formation, and median bending stiffness were higher in G3. Immunohistological analysis showed a significant decrease in CD8 cell count in G3, with a lower percentage of IFNγ-producing cells compared to G2.ConclusionDepleting CD8+ cells from BMC before colonizing hADM significantly improved bone healing, likely due to changes in the local mediator environment. This suggests that preoperative colonization with CD8+-depleted BMC could enhance the one-step membrane technique.

ABSTRACT Filoviruses produce viral particles with characteristic filamentous morphology. The major viral matrix protein, VP40, is trafficked to the plasma membrane and promotes viral particle formation and subsequent viral egress. In the present study, we assessed the role of the small GTPase Rab11-mediated endocytic pathway in Marburg virus (MARV) particle formation and budding. Although Rab11 was predominantly localized in the perinuclear region, it exhibited a more diffuse distribution in the cytoplasm of cells transiently expressing MARV VP40. Rab11 was incorporated into MARV-like particles. Expression of the dominant-negative form of Rab11 and knockdown of Rab11 decreased the amount of VP40 fractions in the cell periphery. Moreover, downregulation of Rab11 moderately reduced the release of MARV-like particles and authentic MARV. We further demonstrated that VP40 induces the distribution of the microtubule network toward the cell periphery, which was partly associated with Rab11. Depolymerization of microtubules reduced the accumulation of VP40 in the cell periphery along with viral particle formation. VP40 physically interacted with α-tubulin, a major component of microtubules, but not with Rab11. Taken together, these results suggested that VP40 partly interacts with microtubules and facilitates their distribution toward the cell periphery, leading to the trafficking of transiently tethering Rab11-positive vesicles toward the cell surface. As we previously demonstrated the role of Rab11 in the formation of Ebola virus particles, the results here suggest that filoviruses in general exploit the vesicle-trafficking machinery for proper virus-particle formation and subsequent egress. These pathways may be a potential target for the development of pan-filovirus therapeutics.IMPORTANCEFiloviruses, including Marburg and Ebola viruses, produce distinct filamentous viral particles. Although it is well known that the major viral matrix protein of these viruses, VP40, is trafficked to the cell surface and promotes viral particle production, details regarding the associated molecular mechanisms remain unclear. To address this knowledge gap, we investigated the role of the small GTPase Rab11-mediated endocytic pathway in this process. Our findings revealed that Marburg virus exploits the Rab11-mediated vesicle-trafficking pathway for the release of virus-like particles and authentic virions in a microtubule network-dependent manner. Previous findings demonstrated that Rab11 is also involved in Ebola virus-particle production. Taken together, these data suggest that filoviruses, in general, may hijack the microtubule-dependent vesicle-trafficking machinery for productive replication. Therefore, this pathway presents as a potential target for the development of pan-filovirus therapeutics.

Advanced ceramics printed with photon-based additive manufacturing deals with anisotropic mechanical properties from the layer-by-layer manufacturing. Motivated by the success in using highly filled transparent slurries containing nanoparticles for powder-based two-photon-polymerization (2PP) for advanced ceramic printing, this works approach is the transfer to Xolography, a volumetric additive manufacturing technology based on linear two-photon excitation and without recoating steps. This paper reports the results of a preliminary investigation optimizing the photocurable slurry to the requirements of Xolography in terms of transparency, over a significantly larger mean free path, compared to 2PP. A feedstock filled with 70 % weight fraction of ceramic particles (∼30 vol%) exhibiting an exceptionally high degree of transparency in the relevant wavelength range of 400–800 nm was prepared from 5 nm zirconia nanoparticles. The high transparency of the photocurable slurry is attributed to the near-monomodal particle size distribution of the zirconia nanoparticles used.

Additive manufacturing techniques have gone beyond their reputation for rapid prototype production and are increasingly adopted for the manufacture of functional components comprising high-end materials and intricate lattice structures. Silicon nitride, renowned for its exceptional mechanical properties and thermal stability, has emerged as a promising candidate for lightweight structural applications. Nonetheless, its high refractive index and density have limited the fabrication of highly complex structures using extrusion and photopolymerization based techniques. In this work, a highly reactive silicon nitride-based ink with high solid loading is developed for the fabrication of ultra-lightweight, truss-based structures. By employing a robot UV-assisted direct ink writing process, it is possible to control the printing head orientation, thus overcoming the limited curing depth of silicon nitride-based inks. The failure behavior of the sintered lattice beam structures under 4-point bending loading has been modeled by applying a linear elastic fracture mechanics (LEFM) based approach to the results of finite element (FE) simulations.

Previous studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4+ helper T (Th) cells induced by Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions. Furthermore, BCG vaccination also upregulated FcγR expression to potentially maximize antibody-dependent effector activities. Using a mouse model of Ebola virus (EBOV) infection, this vaccine strategy provided sustained antibody levels with strong IgG2c bias and protection against lethal challenge. This general approach can be easily adapted to other viruses, and may be a rapid and effective method of immunization against emerging pandemics in populations that routinely receive BCG vaccination.

Krippendorff's Alpha is a measure for assessing inter-rater reliability, facilitating triangulated evaluations among multiple raters. Indeed, Krippendorff's Alpha is key in validating the dependability of human assessments, thereby reinforcing the robustness of human-based choices in contexts where interpretive variability could otherwise undermine the research outcomes. Despite its versatility across various data types, the procedure for computing this coefficient might limit its applicability for researchers unfamiliar with specialised statistical software. Addressing this issue, this paper introduces the “K-Alpha Calculator”—Krippendorff's Alpha Calculator—a freely accessible, user-friendly, web application available at https://www.k-alpha.org designed for easy computation of Krippendorff's Alpha. By offering a web interface without any software dependency, the K-Alpha Calculator seeks to promote the broader integration of such a reliability metric in research processes. We envisage that the tool's contribution could support researchers in enhancing methodological rigour, fostering conclusions are rooted in triangulated interpretations and assessments. The K-Alpha Calculator is both a computational tool and an educational resource, encouraging more researchers to include reliability measures in their studies. • Development of the K-Alpha Calculator.The study centres on the introduction of a web-based application: the K-Alpha Calculator. The tool is developed to simplify the calculation of Krippendorff's Alpha without any required software dependency. • User-friendly interface for diverse data types.The K-Alpha Calculator is characterised by its accessibility and user-friendliness, designed to simplify the procedures for computing the Krippendorff's Alpha. Its utility extends to various data types, which aligns with the intrinsic versatility of this coefficient.

BackgroundExtracellular particles (EPs), particularly extracellular vesicles, play a crucial role in regulating various pathological mechanisms, including immune dysregulations post-trauma. Their distinctive expression of cell-specific markers and regulatory cargo such as cytokines or micro-ribonucleic acid suggests their potential as early biomarkers for organ-specific damage and for identifying patients at risk for complications and mortality. Given the critical need for reliable and easily assessable makers to identify at-risk patients and guide therapeutic decisions, we evaluated the early diagnostic value of circulating EPs regarding outcomes in severely injured multiple-trauma patients.MethodsPlasma samples were collected from 133 severely injured trauma patients (Injury Severity Score (ISS) ≥16) immediately upon arrival at the emergency department (ED). Patients were categorized into survivors and non-survivors. Injury characteristics and outcomes related to sepsis, pneumonia, or early (