Cost-effectiveness of severe acute malnutrition treatment delivered by community health workers in the district of Mayahi, Niger.

BACKGROUND: A non-randomized controlled trial, conducted from June 2018 to March 2019 in two rural communes in the health district of Mayahi in Niger, showed that including community health workers (CHWs) in the treatment of severe acute malnutrition (SAM) resulted in a better recovery rate (77.2% vs. 72.1%) compared with the standard treatment provided solely at the health centers. The present study aims to assess the cost and cost-effectiveness of the CHWs led treatment of uncomplicated SAM in children 6-59 months compared to the standard national protocol. METHODS: To account for all relevant costs, the cost analysis included activity-based costing and bottom-up approaches from a societal perspective and on a within-trial time horizon. The cost-effectiveness analysis was conducted through a decision analysis network built with OpenMarkov and evaluated under two approaches: (1) with recovery rate and cost per child admitted for treatment as measures of effectiveness and cost, respectively; and (2) assessing the total number of children recovered and the total cost incurred. In addition, a multivariate probabilistic sensitivity analysis was carried out to evaluate the effect of uncertainty around the base case input data. RESULTS: For the base case data, the average cost per child recovered was 116.52 USD in the standard treatment and 107.22 USD in the CHWs-led treatment. Based on the first approach, the CHWs-led treatment was more cost-effective than the standard treatment with an average cost per child admitted for treatment of 82.81 USD vs. 84.01 USD. Based on the second approach, the incremental cost-effectiveness ratio of the transition from the standard to the CHWs-led treatment amounted to 98.01 USD per additional SAM case recovered. CONCLUSIONS: In the district of Mayahi in Niger, the CHWs-led SAM treatment was found to be cost-effective when compared to the standard protocol and provided additional advantages such as the reduction of costs for households. TRIAL REGISTRATION: ISRCTN with ID 31143316. https://doi.org/10.1186/ISRCTN31143316.

An Overview of the Sustainable Depolymerization/Degradation of Polypropylene Microplastics by Advanced Oxidation Technologies.

Plastics have become indispensable in modern society; however, the proliferation of their waste has become a problem that can no longer be ignored as most plastics are not biodegradable. Depolymerization/degradation through sustainable processes in the context of the circular economy are urgent issues. The presence of multiple types of plastic materials makes it necessary to study the specific characteristics of each material. This mini-review aims to provide an overview of technological approaches and their performance for the depolymerization and/or degradation of one of the most widespread plastic materials, polypropylene (PP). The state of the art is presented, describing the most relevant technologies focusing on advanced oxidation technologies (AOT) and the results obtained so far for some of the approaches, such as ozonation, sonochemistry, or photocatalysis, with the final aim of making more sustainable the PP depolymerization/degradation process.

Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend the disease's pathogenesis is crucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease's pathological processes. PURPOSE: To identify the immune and nervous system-derived EV profile from blood that could have a specific role as biomarker in MS and assess its possible correlation with disease state. RESULTS: Higher levels of T cell-derived EVs and smaller size of neuron-derived EVs were associated with clinical relapse. The smaller size of the oligodendrocyte-derived EVs was related with motor and cognitive impairment. The proteomic analysis identified mannose-binding lectin serine protease 1 and complement factor H from immune system cell-derived EVs as autoimmune disease-associated proteins. We observed hepatocyte growth factor-like protein in EVs from T cells and inter-alpha-trypsin inhibitor heavy chain 2 from neurons as white matter injury-related proteins. In patients with MS, a specific protein profile was found in the EVs, higher levels of alpha-1-microglobulin and fibrinogen ß chain, lower levels of C1S and gelsolin in the immune system-released vesicles, and Talin-1 overexpression in oligodendrocyte EVs. These specific MS-associated proteins, as well as myelin basic protein in oligodendrocyte EVs, correlated with disease activity in the patients with MS. CONCLUSION: Neural-derived and immune-derived EVs found in blood appear to be good specific biomarkers in MS for reflecting the disease state.

Nanosponge-C3N4 composites as photocatalysts for selective partial alcohol oxidation in aqueous suspension.

A set of four composite materials was prepared, consisting of a nanosponge matrix based on ß-cyclodextrin in which carbon nitride was dispersed. The materials were characterized by the presence of diverse cross-linker units joining the cyclodextrin moieties, in order to vary the absorption/release abilities of the matrix. The composites were characterized and used as photocatalysts in aqueous medium under UV, visible and natural solar irradiation for the photodegradation of 4-nitrophenol, and for the selective partial oxidation of 5-hydroxymethylfurfural and veratryl alcohol to the corresponding aldehydes. The nanosponge-C3N4 composites showed higher activity than the pristine semiconductor, which can probably be attributed to the synergic effect of the nanosponge, capable of increasing the substrate concentration near the surface of the photocatalyst.

Higher prevalence of LAP+ (Latency TGFß-Associated Peptide) T cells at the tissue level in patients with early gastric cancer.

The presence of cells with regulatory functions in patients with cancer is one of the mechanisms whereby the immune system cannot confront tumor growth. We sought to determine the prevalence of immunoregulatory T-cell subpopulations, expressing the latency TGFß-associated peptide (LAP), in patients with gastric adenocarcinoma. T cells were enriched from blood or gastric tissue (tumoral, TT or tumor-free, TF) samples from 22 patients, 6 with early (EGC) and 16 with advanced gastric cancer (AGC). CD4, CD8, LAP, FoxP3 and IFN-γ were measured by cytometry. CD8 + LAP + cells were increased at tumoral sites, especially in early stages of the disease, as compared to tumor-free explants (EGC 5.28 % [4.67-6.64]*; AGC 2.90 % [1.37-4.44]; TF 3.14 % [2.33-4.16]; *p < 0.05 vs TF). Likewise, the LAP+/CD8 + LAP- ratio is increased in gastric samples from patients with early disease (EGC 0.38 [0.30-0.45]*, AGC 0.12 [0.07-0.14]; TF 0.12 [0.09-0.31]; *p < 0.05 vs AGC).Disease progression is accompanied by decreased LAP membrane expression and, probably, increased LAP secretion, therefore limiting the response to the tumor.

Supported Poly(Ionic Liquid)-Heteropolyacid Based Materials for Heterogeneous Catalytic Fructose Dehydration in Aqueous Medium.

Two sets of four different supported catalyst materials were prepared. One set was obtained by polymerization of a bis-vinylimidazolium salt, which formed a poly(ionic liquid) coating on SiO2, TiO2, boron nitride BN, and carbon nitride C3N4. The other set was, instead, obtained by immobilizing Keggin heteropolyacid H3PW12O40 onto poly-imidazolium functionalized materials. All the catalysts, including the bare supports, were subjected to physical and chemical characterization by XRD, SEM, Specific Surface Area and pore size measurements, TGA, FTIR, and acidity-basicity measurements. The catalytic activity of the materials was tested versus the fructose dehydration in water solution at two different sugar initial concentrations (0.3 and 1 M). Tests lasted 3 h with an amount of catalyst of 2 g∙L−1. The presence of the poly-imidazolium on the surface of the supports increased the catalytic conversion of fructose to 5-hydroxymethylfurfural (the most abundant compound obtained) and was further improved by the contemporary presence of the heteropolyacid, at least for the highest initial fructose concentration. In the latter conditions, the highest yield of 5-hydroxymethylfurfural (>40%) was also obtained.

TGFB1 polymorphisms and TGF-ß1 plasma levels identify gastric adenocarcinoma patients with lower survival rate and disseminated disease.

TGF-ß1 is involved in tumour growth. Four TGFB1 SNPs and TGF-ß1 production by stimulated PBMC were determined in seventy-eight gastric adenocarcinoma patients. In addition, TGF-ß1 levels were measured in the plasma of further thirty patients. rs1800471-G/C genotype was prevalent in patients (20.7%) compared to controls (8.4%), as it also was the rs1800468 SNP-G/A genotype in stage IV patients (20.7%) compared to stage I, II and III patients, combined (10.3%). Conversely, the T/T rs1800469 SNP-T/T genotype was absent in the former group and present in 19.0% in the latter. Furthermore, the rs1800469-C/rs1800470-T (CT) haplotype was found in 15.0% of stage IV patients as compared to 3.0% of the remaining patients (3.0%) and also identifies patients with worse five-year life expectancy (P = .03). TGF-ß1 synthesis by stimulated PBMCs was significantly lower in patients with the risk SNPs or haplotype, compared to the alternative genotype. Finally, TGF-ß1 plasma levels were lower in patients with worse life expectancy. Analysis of TGFB1 SNPs and measurement of plasma TGF-ß1 levels serves to identify patients at risk of developing a more aggressive disease.

[Surgery in the dark - a case of Cardiac Ochronosis]. / Cirurgia no Escuro ­ Um Caso de Ocronose Cardíaca.

Alkaptonuria is a rare genetic disorder related to tyrosine metabolism. The cardiovascular manifestations are rare being the aortic stenosis the most commonly reported. We present a case of 72-year-old women who underwent aortic valve replacement with intraoperative findings in the aortic valve and the aortic wall suggestive of Cardiac Ochronosis. Once it is a rare disease there are issues related to the natural history of the disorder that still unknown, namely the type of aortic prothesis in use. For this reason, we find essential the documentation and follow-up of all these rare cases.

A Alcaptonúria é uma doença genética rara, relacionada com o metabolismo da tirosina. As manifestações cardiovasculares são a forma de apresentação menos comum da doença, sendo a estenose aórtica a patologia mais frequentemente encontrada. No presente artigo, apresentamos o caso de uma doente do sexo feminino de 72 anos proposta para cirurgia eletiva de substituição valvular aórtica com alterações intraoperatórias sugestivas de Ocronose Cardíaca. Atendendo à raridade da doença, muito há por esclarecer acerca da sua história natural, nomeadamente no que se refere ao tipo de próteses utilizadas, motivo pelo qual é essencial a documentação e seguimento destes casos.

Confidence intervals for the symmetry point: an optimal cutpoint in continuous diagnostic tests.

Continuous diagnostic tests are often used for discriminating between healthy and diseased populations. For this reason, it is useful to select an appropriate discrimination threshold. There are several optimality criteria: the North-West corner, the Youden index, the concordance probability and the symmetry point, among others. In this paper, we focus on the symmetry point that maximizes simultaneously the two types of correct classifications. We construct confidence intervals for this optimal cutpoint and its associated specificity and sensitivity indexes using two approaches: one based on the generalized pivotal quantity and the other on empirical likelihood. We perform a simulation study to check the practical behaviour of both methods and illustrate their use by means of three real biomedical datasets on melanoma, prostate cancer and coronary artery disease.

Titania-Silica Materials for Enhanced Photocatalysis.

Mesoporous titania-organosilica nanoparticles comprised of anatase nanocrystals crosslinked with organosilica moieties have been prepared by direct co-condensation of a titania precursor, tetrabuthylortotitanate (TBOT), with two organosilica precursors, 1,4-bis(triethoxysilyl) benzene (BTEB) and 1,2-bis(triethoxysilyl) ethane (BTEE), in mild conditions and in the absence of surfactant. These hybrid materials show both high surface areas (200-360 m(2) g(-1) ) and pore volumes (0.3 cm(3) g(-1) ) even after calcination, and excellent photoactivity in the degradation of rhodamine 6G and in the partial oxidation of propene under UV irradiation, especially after the calcination of the samples. During calcination, there is a change in the Ti(IV) coordination and an increase in the content of SiOTi moieties in comparison with the uncalcined materials, which seems to be responsible for the enhanced photocatalytic activity of hybrid titania-silica materials as compared to both uncalcined samples and the control TiO2 .

Performance of students with different accessibility needs and preferences in "Design for All" MOOCs.

Recent research has shown that Massive Open Online Courses (MOOCs) create barriers for students with disabilities. Not taking into account their needs in the design, production or delivery of MOOCs may be one of the main causes behind this. It leads to poor compliance with suitable learning designs and web accessibility standards, as well as a lack of knowledge about the students' needs. The objective of our research is to analyze the learning performance of the students in MOOCs on topics related to Design for All, offered in an Open edX-based platform. Accessibility support was conceived from the outset, including compliance of both the platform and the learning resources with the WCAG 2.1 accessibility standard, and with a subset of the principles of Universal Design for Learning. Additionally, students were consulted on their accessibility needs and preferences, following publicly available modeling schemes and previous research. From a sample of 765 students, who completed at least one of the graded assessment activities of the course, a multilevel multiple logistic regression model was fitted. Based on that model, the results indicate that: a) users of screen readers and users of captions show a statistically significant positive association with a good performance when compared to students with no preferences, with an odds ratio of, respectively, OR = 13.482 and OR = 13.701; b) students who have low vision or very low vision show a significant negative association with a good performance when compared to users of screen readers and to users of captions, with OR = 26.817 and OR = 27.254, respectively.

The impact of experimental diabetes on intracerebral haemorrhage. A preclinical study.

Although diabetes mellitus negatively affects post-ischaemic stroke injury and recovery, its impact on intracerebral haemorrhage (ICH) remains uncertain. This study aimed to investigate the effect of experimental diabetes (ED) on ICH-induced injury and neurological impairment. Sprague-Dawley rats were induced with ED 2 weeks before ICH induction. Animals were randomly assigned to four groups: 1)Healthy; 2)ICH; 3)ED; 4)ED-ICH. ICH and ED-ICH groups showed similar functional assessment. The ED-ICH group exhibited significantly lower haemorrhage volume compared with the ICH group, except at 1 mo. The oedema/ICH volume ratio and cistern displacement ratio were significantly higher in the ED-ICH group. Vascular markers revealed greater expression of α-SMA in the ED groups (ED and ED-ICH) compared with ICH. Conversely, the ICH groups (ED-ICH and ICH) exhibited higher levels of VEGF compared to the healthy and ED groups. An assessment of myelin tract integrity showed an increase in fractional anisotropy in the ED and ED-ICH groups compared with ICH. The ED group showed higher cryomyelin expression than the ED-ICH and ICH groups. Additionally, the ED groups (ED and ED-ICH) displayed higher expression of MOG and Olig-2 than ICH. As for inflammation, MCP-1 levels were significantly lower in the ED-ICH groups compared with the ICH group. Notably, ED did not aggravate the neurological outcome; however, it results in greater ICH-related brain oedema, greater brain structure displacement and lower haemorrhage volume. ED influences the cerebral vascularisation with an increase in vascular thickness, limits the inflammatory response and attenuates the deleterious effect of ICH on white matter integrity.

Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke: The ARIES Study.

BACKGROUND: Unknown cardioembolic sources are frequent causes of cryptogenic stroke. We analyzed the risk of atrial fibrillation (AF) or high burden of ectopic atrial activity (HBEA) in patients with cryptogenic stroke, assessing atrial function and 1-year outcomes. METHODS AND RESULTS: The ARIES (Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke) study is an observational study including patients with cryptogenic stroke. We analyzed the frequency of AF and HBEA (>3000 atrial ectopic beats/day or >2 bursts or atrial tachycardia between 3 beats and ≤30 seconds) in two 30-day Holter-ECGs, comparing advanced echocardiography signs of left atrial (LA) dysfunction according to rhythm: AF, HBEA, and normal sinus rhythm. We also evaluated 1-year stroke recurrence and mortality. The study included 109 patients; 35 (32.1%) patients had AF, 27 (24.8%) HBEA, and 47 (43.1%) normal sinus rhythm. Compared with those with normal sinus rhythm, patients with AF presented higher 2-dimensional and 3-dimensional LA indexed volumes (38.8±11.2 versus 27.3±11.8 mL/m2, and 50.6±17.2 versus 34.0±15.4 mL/m2, respectively, P<0.001), lower 3-dimensional LA ejection fraction (50±14.6 versus 62.7±11.8, P=0.001), LA reservoir strain (22.0±8.6 versus 30.4±10.5, P<0.001), and LA contraction strain (10.5±8.18 versus 17.1±7.5, P<0.001), remaining significant in multivariate analysis. Patients with HBEA showed higher LA indexed volumes and lower LA reservoir strain than patients with normal sinus rhythm only in univariate analysis. There were no differences in ischemic recurrence or mortality among the groups. CONCLUSIONS: Patients with cryptogenic stroke showed a high incidence of AF and HBEA. AF is strongly related to LA volume, LA function, and LA reservoir and contraction strain, whereas HBEA showed milder structural changes. Advanced LA echocardiography could help patient selection for long-term ECG monitoring in suspected cardiac sources.

Glycaemia and ischaemia-reperfusion brain injury in patients with ischaemic stroke treated with mechanical thrombectomy (GLIAS-MT): an observational, unicentric, prospective study protocol.

INTRODUCTION: Poststroke hyperglycaemia is an independent risk factor for poorer outcomes in patients treated with mechanical thrombectomy (MT) and is associated with a lower probability of functional recovery and higher mortality at 3 months. This study aims to evaluate the association between glucose levels during cerebral reperfusion with MT and functional recovery at 3 months, measured by subcutaneous continuous glucose monitoring (CGM) devices. METHODS: This prospective observational study aims to recruit 100 patients with ischaemic stroke and large anterior circulation vessel occlusion, in whom MT is indicated. CGM will be performed using a Freestyle Libre ProIQ device (FSL-CGM, Abbott Diabetes Care, Alameda, California, USA), which will be implanted on admission to the emergency department, to monitor glucose levels before, during and after reperfusion. The study's primary endpoint will be the functional status at 3 months, as measured by the dichotomised modified Rankin Scale (0-2 indicating good recovery and 3-6 indicating dependency or death). We will analyse expression profiles of microRNA (miRNA) at the time of reperfusion and 24 hours later, as potential biomarkers of ischaemic-reperfusion injury. The most promising miRNAs include miR-100, miR-29b, miR-339, miR-15a and miR-424. All patients will undergo treatment according to current international recommendations and local protocols for the treatment of stroke, including intravenous thrombolysis if indicated. ETHICS AND DISSEMINATION: This study (protocol V.1.1, dated 29 October 2021, code 6017) has been approved by the Clinical Research Ethics Committee of La Paz University Hospital (Madrid, Spain) and has been registered in ClinicalTrials.gov (NCT05871502). Study results will be disseminated through peer-reviewed publications in Open Access format and at conference presentations. TRIAL REGISTRATION NUMBER: NCT05871502.

A systematic review of risk factors for mortality among tuberculosis patients in South Africa.

BACKGROUND: Tuberculosis (TB)-associated mortality in South Africa remains high. This review aimed to systematically assess risk factors associated with death during TB treatment in South African patients. METHODS: We conducted a systematic review of TB research articles published between 2010 and 2018. We searched BioMed Central (BMC), PubMed®, EBSCOhost, Cochrane, and SCOPUS for publications between January 2010 and December 2018. Searches were conducted between August 2019 and October 2019. We included randomised control trials (RCTs), case control, cross sectional, retrospective, and prospective cohort studies where TB mortality was a primary endpoint and effect measure estimates were provided for risk factors for TB mortality during TB treatment. Due to heterogeneity in effect measures and risk factors evaluated, a formal meta-analysis of risk factors for TB mortality was not appropriate. A random effects meta-analysis was used to estimate case fatality ratios (CFRs) for all studies and for specific subgroups so that these could be compared. Quality assessments were performed using the Newcastle-Ottawa scale or the Cochrane Risk of Bias Tool. RESULTS: We identified 1995 titles for screening, 24 publications met our inclusion criteria (one cross-sectional study, 2 RCTs, and 21 cohort studies). Twenty-two studies reported on adults (n = 12561) and two were restricted to children < 15 years of age (n = 696). The CFR estimated for all studies was 26.4% (CI 18.1-34.7, n = 13257 ); 37.5% (CI 24.8-50.3, n = 5149) for drug-resistant (DR) TB; 12.5% (CI 1.1-23.9, n = 1935) for drug-susceptible (DS) TB; 15.6% (CI 8.1-23.2, n = 6173) for studies in which drug susceptibility was mixed or not specified; 21.3% (CI 15.3-27.3, n = 7375) for people living with HIV/AIDS (PLHIV); 19.2% (CI 7.7-30.7, n = 1691) in HIV-negative TB patients; and 6.8% (CI 4.9-8.7, n = 696) in paediatric studies. The main risk factors associated with TB mortality were HIV infection, prior TB treatment, DR-TB, and lower body weight at TB diagnosis. CONCLUSIONS: In South Africa, overall mortality during TB treatment remains high, people with DR-TB have an elevated risk of mortality during TB treatment and interventions to mitigate high mortality are needed. In addition, better prospective data on TB mortality are needed, especially amongst vulnerable sub-populations including young children, adolescents, pregnant women, and people with co-morbidities other than HIV. Limitations included a lack of prospective studies and RCTs and a high degree of heterogeneity in risk factors and comparator variables. SYSTEMATIC REVIEW REGISTRATION: The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42018108622. This study was funded by the Bill and Melinda Gates Foundation (Investment ID OPP1173131) via the South African TB Think Tank.

Dual role of peripheral B cells in multiple sclerosis: emerging remote players in demyelination and novel diagnostic biomarkers.

Introduction: Multiple sclerosis is an inflammatory and demyelinating disease caused by a pathogenic immune response against the myelin sheath surfaces of oligodendrocytes. The demyelination has been classically associated with pathogenic B cells residing in the central nervous system that release autoreactive antibodies against myelin. The aim of the present study was to investigate whether extracellular vesicles (EVs) mediate delivery of myelin autoreactive antibodies from peripheral B cells against oligodendrocytes in multiple sclerosis (MS) and to analyze whether these EVs could mediate demyelination in vitro. We also studied the role of these EV-derived myelin antibodies as a diagnostic biomarker in MS. Methods: This is a prospective, observational, and single-center study that includes patients with MS and two control groups: patients with non-immune white matter lesions and healthy controls. We isolated B-cell-derived EVs from the blood and cerebrospinal fluid (CSF) and analyzed their myelin antibody content. We also studied whether antibody-loaded EVs reach oligodendrocytes in patients with MS and the effect on demyelination of B-cell-derived EVs containing antibodies in vitro. Results: This study enrolled 136 MS patients, 23 white matter lesions controls, and 39 healthy controls. We found autoreactive myelin antibodies in EVs that were released by peripheral B cells, but not by populations of B cells resident in CSF. We also identified a cut-off of 3.95 ng/mL of myelin basic protein autoantibodies in EVs from peripheral B cells, with 95.2% sensitivity and 88.2% specificity, which allows us to differentiate MS patients from healthy controls. EV-derived myelin antibodies were also detected in the oligodendrocytes of MS patients. Myelin antibody-loaded EVs from B cells induced myelin markers decrease of oligodendrocytes in vitro. Discussion: Peripheral reactive immune cells could contribute remotely to MS pathogenesis by delivering myelin antibodies to oligodendrocytes. EV-derived myelin antibodies could play a role as diagnostic biomarker in MS.

The prognostic impact of SIGLEC5-induced impairment of CD8+ T cell activation in sepsis.

BACKGROUND: Sepsis is associated with T-cell exhaustion, which significantly reduces patient outcomes. Therefore, targeting of immune checkpoints (ICs) is deemed necessary for effective sepsis management. Here, we evaluated the role of SIGLEC5 as an IC ligand and explored its potential as a biomarker for sepsis. METHODS: In vitro and in vivo assays were conducted to both analyse SIGLEC5's role as an IC ligand, as well as assess its impact on survival in sepsis. A multicentre prospective cohort study was conducted to evaluate the plasmatic soluble SIGLEC5 (sSIGLEC5) as a mortality predictor in the first 60 days after admission in sepsis patients. Recruitment included sepsis patients (n = 346), controls with systemic inflammatory response syndrome (n = 80), aneurism (n = 11), stroke (n = 16), and healthy volunteers (HVs, n = 100). FINDINGS: SIGLEC5 expression on monocytes was increased by HIF1α and was higher in septic patients than in healthy volunteers after ex vivo LPS challenge. Furthermore, SIGLEC5-PSGL1 interaction inhibited CD8+ T-cell proliferation. Administration of sSIGLEC5r (0.8 mg/kg) had adverse effects in mouse endotoxemia models. Additionally, plasma sSIGLEC5 levels of septic patients were higher than HVs and ROC analysis revealed it as a mortality marker with an AUC of 0.713 (95% CI, 0.656-0.769; p < 0.0001). Kaplan-Meier survival curve showed a significant decrease in survival above the calculated cut-off (HR of 3.418, 95% CI, 2.380-4.907, p < 0.0001 by log-rank test) estimated by Youden Index (523.6 ng/mL). INTERPRETATION: SIGLEC5 displays the hallmarks of an IC ligand, and plasma levels of sSIGLEC5 have been linked with increased mortality in septic patients. FUNDING: Instituto de Salud Carlos III (ISCIII) and "Fondos FEDER" to ELC (PIE15/00065, PI18/00148, PI14/01234, PI21/00869), CDF (PI21/01178), RLR (FI19/00334) and JAO (CD21/00059).

Circulating extracellular vesicles promote recovery in a preclinical model of intracerebral hemorrhage.

Circulating extracellular vesicles (EVs) are proposed to participate in enhancing pathways of recovery after stroke through paracrine signaling. To verify this hypothesis in a proof-of-concept study, blood-derived allogenic EVs from rats and xenogenic EVs from humans who experienced spontaneous good recovery after an intracerebral hemorrhage (ICH) were administered intravenously to rats at 24 h after a subcortical ICH. At 28 days, both treatments improved the motor function assessment scales score, showed greater fiber preservation in the perilesional zone (diffusion tensor-fractional anisotropy MRI), increased immunofluorescence markers of myelin (MOG), and decreased astrocyte markers (GFAP) compared with controls. Comparison of the protein cargo of circulating EVs at 28 days from animals with good vs. poor recovery showed down-expression of immune system activation pathways (CO4, KLKB1, PROC, FA9, and C1QA) and of restorative processes such as axon guidance (RAC1), myelination (MBP), and synaptic vesicle trafficking (SYN1), which is in line with better tissue preservation. Up-expression of PCSK9 (neuron differentiation) in xenogenic EVs-treated animals suggests enhancement of repair pathways. In conclusion, the administration of blood-derived EVs improved recovery after ICH. These findings open a new and promising opportunity for further development of restorative therapies to improve the outcomes after an ICH.

Computer-Assisted Surgery Enables Beginner Surgeons, Under Expert Guidance, to Achieve Long-Term Clinical Results not Inferior to Those of a Skilled Surgeon in Knee Arthroplasty.

Purpose: The purpose of this study is to determine whether the use of a surgical navigation system in total knee replacement (TKR) enables beginner and intermediate surgeons to achieve clinical PROM outcomes as good as those conducted by expert surgeons in the long term. Methods: We enrolled 100 consecutive patients whose total navigated knee arthroplasty (TKA) was performed in our institution from 2008 to 2010. According to the principal surgeon's surgical experience, the patients were divided into three groups: (1) beginner surgeons, with no more than 30 previous knee replacement performances, (2) intermediate surgeons, with more than 30 but not more than 300, and (3) expert surgeons, with more than 300 knee replacements. Demographic data collected on the cohort included gender, laterality, age, and body mass index (BMI). The outcome measures assessed were Forgotten Joint Score (FJS), implant positioning, limb alignment, and prosthesis survival rate. A margin of equivalence of ± 18.5 points in the FJS scale was prespecified in terms of the minimal clinically important difference (MCID) to compare the FJS results obtained in the long period between the groups of interest. Results: The mean follow-up was 11.10 ± 0.78, 10.86 ± 0.66, and 11.30 ± 0.74 years, respectively, for each of the groups. The long-term FJS mean score was 80.86 ± 21.88, 81.36 ± 23.87, and 90.48 ± 14.65 for each group. The statistical analysis proved noninferiority and equivalence in terms of the FJS results reported in the long term by patients in Groups 1 or 2 compared to those in Group 3. More specifically, it has been proved that the mean difference between groups is within the interval of equivalence defined in terms of the MCID. The overall prostheses survival rate was 93.7%. Conclusion: Navigated assisted TKA, under expert guidance, can be as effective when performed by beginner or intermediate surgeons as performed by senior surgeons regarding the accuracy of implant positioning, limb alignment, and long-term clinical outcome.