[Nirsevimab effectiveness against hospital admission for respiratory syncytial virus bronchiolitis in infants]. / Efectividad de nirsevimab en la prevención de los ingresos por bronquiolitis por virus respiratorio sincitial en lactantes.

OBJECTIVE: Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalization in infants. This season, a long half-life monoclonal antibody (Nirsevimab) is available to prevent this disease for all infants born from 1 April-30 September to 2023 and all those born during RSV season (October2023- March 2024). The aim of this study was to evaluate the impact of the implementation of this antibody on RSV admissions in a tertiary hospital. METHODS: Observational, retrospective and analytical study. All patients <6 months in October admitted for bronchiolitis at 2 time points were included: T1 or Pre-nirsevimab time: 1 September 2015-30 September 2023 and T2 or Nirsevimab time: 1 October-31 December 2023. Total admissions due to any cause of infants <6 months in the same period were used as the reference population. To assess the impact of the implementation of nirsevimab, we calculated the reduction in the percentage of admissions due to RSV with respect to total admissions in both periods, and also in the 2023-2024 season we calculated the double negative test to calculate the effectiveness of the intervention (1-Odds ratio) x 100. RESULTS: In infants under 6 months of age, we found significant differences in the number of admissions for RSV bronchiolitis between the last season and the previous 7 seasons [574/1195 (48%) vs 6/138 (4.3%); p<0.01, RPI: 91%). In the 2023/2024 season, the effectiveness of nirsevimab in preventing admission for RSV bronchiolitis in children under 6 months of age was 85% (CI 95%: 32-97%). CONCLUSIONS: The implementation of nirsevimab has had an important impact on the number of hospital admissions for RSV bronchiolitis. There were no differences in the severity of bronchiolitis.

The interplay of shape and catalyst distribution in the yield of compressible flow microreactors.

We develop a semi-analytical model for transport in structured catalytic microreactors, where both reactant and product are compressible fluids. Using lubrication and Fick-Jacobs approximations, we reduce the three-dimensional governing equations to an effective one-dimensional set of equations. Our model captures the effect of compressibility, corrugations in the shape of the reactor, and an inhomogeneous catalytic coating of the reactor walls. We show that in the weakly compressible limit (e.g., liquid-phase reactors), the distribution of catalyst does not influence the reactor yield, which we verify experimentally. Beyond this limit, we show that introducing inhomogeneities in the catalytic coating and corrugations to the reactor walls can improve the yield.

The fecal microbiota of Holstein cows is heritable and genetically correlated to dairy performances.

The fecal microbiota of ruminants constitutes a diversified community that has been phenotypically associated with a variety of host phenotypes, such as production and health. To gain a better understanding of the complex and interconnected factors that drive the fecal bacterial community, we have aimed to estimate the genetic parameters of the diversity and composition of the fecal microbiota, including heritabilities, genetic correlations among taxa, and genetic correlations between fecal microbiota features and host phenotypes. To achieve this, we analyzed a large population of 1,875 Holstein cows originating from 144 French commercial herds and routinely recorded for production, somatic cell score, and fertility traits. Fecal samples were collected from the animals and subjected to 16S rRNA gene sequencing, with reads classified into Amplicon Sequence Variants (ASVs). The estimated α- and ß-diversity indices (i.e., Observed Richness, Shannon index, Bray-Curtis and Jaccard dissimilarity matrices) and the abundances of ASVs, genera, families and phyla, normalized by centered-log ratio (CLR), were considered as phenotypes. Genetic parameters were calculated using either univariate or bivariate animal models. Heritabilities estimates, ranging from 0.08 to 0.31 for taxa abundances and ß-diversity indices, highlight the influence of the host genetics on the composition of the fecal microbiota. Furthermore, genetic correlations estimated within the microbial community and between microbiota features and host traits reveal the complex networks linking all components of the fecal microbiota together and to their host, thus strengthening the holobiont concept. By estimating the heritabilities of microbiota-associated phenotypes, our study quantifies the impact of the host genetics on the fecal microbiota composition. In addition, genetic correlations between taxonomic groups and between taxa abundances and host performance suggest potential applications for selective breeding to improve host traits or promote a healthier microbiota.

Analysis of the effect of citrate on radionuclide retention on portlandite.

We analysed how citrate (CIT), a chelating agent potentially present in radioactive waste disposals, affects the mobility of four radionuclides (RN): 63Ni, 233U, 152Eu, 238Pu in portlandite, an important hydrated phase of cement, a commonly used material for waste isolation. Portlandite was synthetized in the laboratory and showed high purity and grain size of few µm. This solid, buffers the pH to 12.5 and shows high adsorption capability for the studied RNs: 152Eu and 238Pu exhibited the highest adsorption (Kd ∼1·105 mL g-1) and 233U the lowest (Kd ∼8·102 mL g-1). CIT adsorption was also experimentally evaluated by batch sorption experiments and electrophoretic (ζ-potential) measurements: a non-lineal sorption behaviour was observed, with Kd values decreasing (from ∼1·103 mL g-1) as CIT concentration increased up to 1·10-2 M, according to portlandite sorption sites saturation. In the presence of CIT, a marginal decrease for 233U adsorption in portlandite was observed, one order of magnitude reduction for 63Ni, while 238Pu and 152Eu adsorption decreased significantly. The calculated sorption reduction factors (SRF) for the four RN in the presence of CIT at a concentration of 5·10-3 M were: 2.4, 9.7, 37 and 50.9 for 233U, 63Ni, 238Pu, and 152Eu, respectively. According to the available thermodynamic databases, low complexation between CIT and RN is predicted at pH = 12.5, thus the RN adsorption decrease in the presence of CIT must be attributed to the organic adsorption on portlandite. However, current thermodynamic are still incomplete for this ligand and this pH range and this limits a precise interpretation of the experimental data.

Impact of triple transmembrane regulator therapy on glucose metabolism in cystic fibrosis related diabetes during clinical practice.

AIMS: To evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on Cystic Fibrosis Related Diabetes (CFRD) glycemic control and insulin treatment in patients with CFRD during clinical practice. METHODS: We carried out a retrospective observational study of 23 adult patients with CFRD who started treatment with ETI. They had, at least, one F508del mutation. Data were collected before ETI initiation and 3, 6, and 12 months after. RESULTS: Glycemic control measured by HbA1c significantly improved by 0.3 % (0.1-0.5) after 3 months of ETI therapy (p = 0.004) and kept this improvement during follow-up (p < 0.001). The proportion of patients needing multiple daily injections of insulin was reduced by 16 % (p = 0.023). Total daily insulin dose dropped by 0.12 (0.05-0.18) UI/kg/day (p < 0.001). Data derived from Flash Continuous Glucose Monitoring (CGM) for patients treated with insulin stayed unchanged after insulin reduction, except for a significant 8 % (0.3-15.6) increase in the Time In Tight Range (TITR) between 70 and 140 mg/dL (p = 0.043). CONCLUSION: ETI therapy impacted CFRD in clinical practice reducing insulin needs and improving glycemic control measured by HbA1c and CGM. The improvements can be observed from the first 3 months of treatment.

Dual therapy based on co-formulated darunavir/ritonavir plus lamivudine for initial therapy of HIV infection: The ANDES randomized controlled trial.

BACKGROUND: Tenofovir-containing antiretroviral therapy regimens may have long-term toxicity-related side effects. This study aimed to compare the virological efficacy of co-formulated darunavir/ritonavir plus lamivudine with darunavir/ritonavir plus tenofovir and emtricitabine or lamivudine. METHODS: The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in treatment-naïve adults living with human immunodeficiency virus (HIV). Patients were randomized on a 1:1 basis to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir/ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir/ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of <50 copies/mL at week 48 in the intention-to-treat population. The US Food and Drug Administration snapshot algorithm and a non-inferiority margin of -12% were used. The secondary objective was to analyse safety in the per-protocol population. This study has been registered at ClinicalTrials.gov (NCT02770508). RESULTS: Between November 2015 and 31 October 2020, 336 participants were assigned at random to the triple therapy arm (n=165) or the dual therapy arm (n=171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the dual therapy group (91%) achieved virological suppression (difference -2.1%, 95% confidence interval -7.0 to 2.9). Drug-related adverse events were more common in the triple therapy group (P=0.04). Two toxicity-related events led to discontinuation in each group. INTERPRETATION: Co-formulated darunavir/ritonavir plus lamivudine showed non-inferiority and a safer toxicity profile compared with the standard-of-care triple therapy regimen including tenofovir in treatment-naïve patients.

Killer-cell immunoglobulin-like receptor polymorphism is associated with COVID-19 outcome: Results of a pilot observational study.

The pathogenesis of COVID-19 warrants unravelling. Genetic polymorphism analysis may help answer the variability in disease outcome. To determine the role of KIR and HLA polymorphisms in susceptibility, progression, and severity of SARS-CoV-2 infection, 458 patients and 667 controls enrolled in this retrospective observational study from April to December 2020. Mild/moderate and severe/death study groups were established. HLA-A, -B, -C, and KIR genotyping were performed using the Lifecodes® HLA-SSO and KIR-SSO kits on the Luminex® 200™ xMAP fluoroanalyser. A probability score using multivariate binary logistic regression analysis was calculated to estimate the likelihood of severe COVID-19. ROC analysis was used to calculate the best cut-off point for predicting a worse clinical outcome with high sensitivity and specificity. A p ≤ 0.05 was considered statistically significant. KIR AA genotype protected positively against severity/death from COVID-19. Furthermore, KIR3DL1, KIR2DL3 and KIR2DS4 genes protected patients from severe forms of COVID-19. KIR Bx genotype, as well as KIR2DL2, KIR2DS2, KIR2DS3 and KIR3DS1 were identified as biomarkers of severe COVID-19. Our logistic regression model, which included clinical and KIR/HLA variables, categorised our cohort of patients as high/low risk for severe COVID-19 disease with high sensitivity and specificity (Se = 94.29%, 95% CI [80.84-99.30]; Sp = 84.55%, 95% CI [79.26-88.94]; OR = 47.58, 95%CI [11.73-193.12], p < 0.0001). These results illustrate an association between KIR/HLA ligand polymorphism and different COVID-19 outcomes and remarks the possibility of use them as a surrogate biomarkers to detect severe patients in possible future infectious outbreaks.

Characterization of bovine vaginal microbiota using 16S rRNA sequencing: associations with host fertility, longevity, health, and production.

Due to their potential impact on the host's phenotype, organ-specific microbiotas are receiving increasing attention in several animal species, including cattle. Specifically, the vaginal microbiota of ruminants is attracting growing interest, due to its predicted critical role on cows' reproductive functions in livestock contexts. Notably, fertility disorders represent a leading cause for culling, and additional research would help to fill relevant knowledge gaps. In the present study, we aimed to characterize the vaginal microbiota of a large cohort of 1171 female dairy cattle from 19 commercial herds in Northern France. Vaginal samples were collected using a swab and the composition of the microbiota was determined through 16S rRNA sequencing targeting the V3-V4 hypervariable regions. Initial analyses allowed us to define the core bacterial vaginal microbiota, comprising all the taxa observed in more than 90% of the animals. Consequently, four phyla, 16 families, 14 genera and a single amplicon sequence variant (ASV) met the criteria, suggesting a high diversity of bacterial vaginal microbiota within the studied population. This variability was partially attributed to various environmental factors such as the herd, sampling season, parity, and lactation stage. Next, we identified numerous significant associations between the diversity and composition of the vaginal microbiota and several traits related to host's production and reproduction performance, as well as reproductive tract health. Specifically, 169 genera were associated with at least one trait, with 69% of them significantly associated with multiple traits. Among these, the abundances of Negativibacillus and Ruminobacter were positively correlated with the cows' performances (i.e., longevity, production performances). Other genera showed mixed relationships with the phenotypes, such as Leptotrichia being overabundant in cows with improved fertility records and reproductive tract health, but also in cows with lower production levels. Overall, the numerous associations underscored the complex interactions between the vaginal microbiota and its host. Given the large number of samples collected from commercial farms and the diversity of the phenotypes considered, this study marks an initial step towards a better understanding of the intimate relationship between the vaginal microbiota and the dairy cow's phenotypes.

Observation of Strong Nuclear Suppression in Exclusive J/ψ Photoproduction in Au+Au Ultraperipheral Collisions at RHIC.

We report a measurement of exclusive J/ψ and ψ(2s) photoproduction in Au+Au ultraperipheral collisions at sqrt[s_{NN}]=200 GeV using the STAR detector. For the first time, (i) the ψ(2s) photoproduction in midrapidity at the Relativistic Heavy-Ion Collider has been experimentally measured; (ii) nuclear suppression factors are measured for both the coherent and incoherent J/ψ production. At average photon-nucleon center-of-mass energy of 25.0 GeV, the coherent and incoherent J/ψ cross sections of Au nuclei are found to be 71±10% and 36±7%, respectively, of that of free protons. The stronger suppression observed in the incoherent production provides a new experimental handle to study the initial-state parton density in heavy nuclei. Data are compared with theoretical models quantitatively.

Short communication: Bifidobacterium abundance in the faecal microbiota is strongly associated with milk traits in dairy cattle.

The performance of dairy cows is influenced by the microbial communities hosted within their digestive tract. While the rumen microbiota has long been associated with host phenotypes, the impact of the faecal microbiota remains elusive. In this study, we collected 697 faecal samples from commercial Holstein cows and analysed them with 16S rRNA gene analyses. For each animal, routinely recorded data, i.e., milk yield, fat yield, protein yield, fat content, protein content, and an aggregate production trait (pINEL) based on the French economic dairy index, were available to assess the links between the faecal microbiota and host production. Our findings revealed a strong and significant association between the structure of the bacterial and prokaryote community (ß-diversity) and dairy production. In addition, differential abundance analyses identified 48 genera whose abundances were significantly associated with pINEL, milk, fat and protein yield. Among these genera, the increased abundance of Bifidobacterium, and particularly an amplicon sequence variant with a 16S rRNA V3-V4 gene region identical to B. globosum and B. pseudolongum, was found to be the most important for high-yielding animals. Bifidobacterium seemed to be a potential key member of the bovine faecal microbiota that should be further investigated. Conversely, the p-1088-a5 gut group genus was found more abundant in low-productive cows. In conclusion, this study demonstrates significant associations between the faecal microbiota and the performance of dairy cows at the whole lactation scale. A better understanding of the physiology of the gut microbiota could help to improve dairy cow production.

Atypical fundoscopic manifestation with good visual prognosis in familial hypomagnesemia with hypercalciuria and nephrocalcinosis.

PURPOSE: Pathogenic variants in the CLDN19 gene are responsible for Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC) with ocular pathology (MIM *248190). Our objective was to delineate the ophthalmological and genetic manifestations of a patient with FHHNC and a pathogenic variant in CLDN19. CASE REPORT: A 25-year-old woman presented with renal involvement and a best-corrected visual acuity of 20/25 in the right eye and finger-counting ability in the left eye. The patient exhibited high myopia, convergent strabismus, and chorioretinal atrophic plaques in the perifoveal and peripapillary areas. We conducted a comprehensive ophthalmological examination, including refraction, fundoscopy, color and autofluorescence retinography, optical coherence tomography, and electrophysiology tests. Additionally, next-generation sequencing was performed using Illumina NextSeq500. We identified a homozygous missense variant, c.59G>A p.Gly20Asp, in the CLDN19 gene as the cause of renal and ocular manifestations. CONCLUSION: FHHNC is associated with various ocular alterations. The unique retinal disorders described in this article suggest a more favorable visual prognosis compared to those previously reported in the literature. Determining the phenotypic diversity of this disease may aid in the diagnosis and management of future cases.

Development of burnout and moral distress in intensive care nurses: An integrative literature review.

AIMS: To describe, through an integrative literature review, the factors contributing to the development of burnout and moral distress in nursing professionals working in intensive care units and to identify the assessment tools used most frequently to assess burnout and moral distress. METHODS: An integrative literature review was carried out. PubMed, CINAHL, PsycINFO, SciELO, Dialnet, Web of Science, Scopus, and Cochrane databases were reviewed from January 2012 to February 2023. Additionally, snowball sampling was used. The results were analysed by using integrative synthesis, as proposed by Whittemore et al., the Critical Appraisal Skills Programme for literature reviews, the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for quantitative observational studies, and the Joanna Briggs Institute checklist for qualitative research were used to evaluate evidence quality. RESULTS: Forty-one articles were selected for review: 36 were cross-sectional descriptive articles, and five were literature reviews. The articles were grouped into five-factor categories: 1) personal factors, 2) organisational factors, 3) labour relations factors, 4) end-of-life care factors, and 5) factors related to coronavirus disease 2019 (COVID-19). The Maslach Burnout Inventory-Human Services Survey and the Moral Distress Survey-Revised instruments were the most commonly used to measure burnout and moral distress. CONCLUSIONS: This review highlights the multiple personal, organisational, relational, situational, and end-of-life factors promoting burnout and moral distress among critical care nurses. Interventions in these areas are necessary to achieve nurses' job satisfaction and retention while improving nurses' quality of care.

Early attentional processing and cortical remapping strategies of tactile stimuli in adults with an early and late-onset visual impairment: A cross-sectional study.

Neuroplastic changes appear in people with visual impairment (VI) and they show greater tactile abilities. Improvements in performance could be associated with the development of enhanced early attentional processes based on neuroplasticity. Currently, the various early attentional and cortical remapping strategies that are utilized by people with early (EB) and late-onset blindness (LB) remain unclear. Thus, more research is required to develop effective rehabilitation programs and substitution devices. Our objective was to explore the differences in spatial tactile brain processing in adults with EB, LB and a sighted control group (CG). In this cross-sectional study 27 participants with VI were categorized into EB (n = 14) and LB (n = 13) groups. They were then compared with a CG (n = 15). A vibrotactile device and event-related potentials (ERPs) were utilized while participants performed a spatial tactile line recognition task. The P100 latency and cortical areas of maximal activity were analyzed during the task. The three groups had no statistical differences in P100 latency (p>0.05). All subjects showed significant activation in the right superior frontal areas. Only individuals with VI activated the left superior frontal regions. In EB subjects, a higher activation was found in the mid-frontal and occipital areas. A higher activation of the mid-frontal, anterior cingulate cortex and orbitofrontal zones was observed in LB participants. Compared to the CG, LB individuals showed greater activity in the left orbitofrontal zone, while EB exhibited greater activity in the right superior parietal cortex. The EB had greater activity in the left orbitofrontal region compared to the LB. People with VI may not have faster early attentional processing. EB subjects activate the occipital lobe and right superior parietal cortex during tactile stimulation because of an early lack of visual stimuli and a multimodal information processing. In individuals with LB and EB the orbitofrontal area is activated, suggesting greater emotional processing.

[Outcomes of respiratory rehabilitation program in lung transplant recipients: a quasi experimental study]. / Resultados de un programa de rehabilitación respiratoria en pacientes receptores de trasplante pulmonar: estudio cuasiexperimental.

INTRODUCTION: Lung transplant (LT) is the ultimate option for end-stage lung diseases. Malnutrition and sarcopenia, common in LT recipients, can be reversible with adequate exercise and nutrition. This study aims to assess changes in physical performance and aerobic capacity after a 10-week rehabilitation program (RP) in LT recipients, as well as to describe the prevalence of sarcopenia and malnutrition before and after RP and their influence on clinically relevant outcomes. MATERIALS AND METHODS: Quasi-experimental study, before and after a 10-week PR in first-time TP recipients, aged over 18 years, from January 2022 to September 2023. Aerobic exercise capacity was assessed through the 6-minute walking test (6MWT) and peak oxygen consumption (VO2peak); and physical performance was measured using the Short Physical Performance Battery (SPPB). Additionally, the prevalence of sarcopenia was described according to the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2) and malnutrition according to the criteria of the Global Leadership Initiative on Malnutrition (GLIM). RESULTS: Of the 41 patients, 56% had sarcopenia and 80% had malnutrition. After RP, the distance walked in the 6MWT increased by 66.3m (p=0.004) in men and 61m (p=0.001) in women. VO2peak increased in men by a mean of 3.1ml/min/kg (p=0.024). Physical performance improved significantly in both men and women according to the Short Physical Performance Battery (SPPB), with clinically relevant differences of 1.6 pts (p<0.001) and 1.2 pts (p=0.012), respectively. The prevalence of sarcopenia decreased to 24% and malnutrition to 61%. CONCLUSIONS: RP proved to be an effective and safe intervention for LT recipients. In addition to improvements in skeletal muscle strength and exercise capacity, a reduction in the prevalence of sarcopenia and malnutrition was also observed.

Validation of an IMU-based Gait Analysis Method for Assessment of Fall Risk Against Traditional Methods.

Falls are a severe problem in older adults, often resulting in severe consequences such as injuries or loss of consciousness. It is crucial to screen fall risk in order to prescribe appropriate therapies that can potentially prevent falls. Identifying individuals who have experienced falls in the past, commonly known as fallers, is used to evaluate fall risk, as a prior fall indicates a higher likelihood of future falls. The methods that have the most support from evidence are Gait Speed (GS) and Time Up and Go (TUG), which use specific cut-off values to evaluate the fall risk. There have been proposals for alternative methods that use wearable sensor technology to improve fall risk assessment. Although these technological alternatives are promising, further research is necessary to validate their use in clinical settings. In this study, we propose a method for identifying fallers based on a Support Vector Machine (SVM) classifier. The inputs for the classifier are the gait parameters obtained from a 30-minute walk recorded using an Inertial Measurement Unit (IMU) placed at the foot of patients. We validated our proposed method using a sample of 157 patients aged over 70 years. Our findings indicate significant differences (p< 0.05) in stride speed, clearance, angular velocity, acceleration, and coefficient of variability among steps between fallers and non-fallers. The proposed method demonstrates the its potential to classify fallers with an accuracy of [79.6]%, slightly outperforming the GS method which provides an accuracy of [77.0]%, and also overcomes its dependency on the cut-off speed to determine fallers. This method could be valuable in detecting fallers during long-term monitoring that does not require periodic evaluations in a clinical setting.

Epidemiology of musculoskeletal tumors in a reference unit. / Epidemiología de los tumores musculoesqueléticos en una unidad de referencia.

OBJECTIVE: The objective of this study was to perform an epidemiological analysis of patients presented to the Musculoskeletal Tumors Committee of a reference hospital. MATERIAL AND METHOD: A retrospective analysis of patients with sarcomas treated in a reference Sarcoma Unit between 2009 and 2022 was carried out. RESULTS: A total of 1978 patients were analyzed, of which 1477 (74.67%) were diagnosed as sarcomas. They were divided into 446 (30.20%) bone tumors and 1.031 (69.80%) soft tissue tumors. The most common benign bone tumor was enchondroma (27.23%), giant cell tumor (59.21%) was the most common tumor of intermediate malignancy and the malignant one was osteosarcoma (24.78%). The most frequently observed benign soft tissue tumor was lipoma (50.74%), the atypical lipomatous tumor (53.25%) was the most frequent tumor of intermediate malignancy and the malignant one was sarcoma of uncertain differentiation (38.10%). CONCLUSION: Our study represents the first work on the epidemiology of sarcomas and other musculoskeletal tumors in our country, being very useful to adapt the resources destined for their diagnosis and treatment.

Impact in real-world of intermittent-scanned continuous glucose monitoring with alarms on hypoglycemia and its recognition in type 1 diabetes.

BACKGROUND: Recent studies have demonstrated that real-time CGM use reduce the incidence severe hypoglycemic events and impaired awareness of hypoglycemia (IAH) However, there are few real-world studies evaluating the effect of intermittently scanned continuous glucose monitoring (isCGM) on hypoglycemic episodes and hypoglycemia unawareness (IAH). The present study was designed to cover this research-practice gap. METHODS: This is a real-world, observational, prospective cohort study with 2 years of follow-up in which 60 subjects with T1D who experienced frequent hypoglycemic events were included. All the patients were invited to use isCGM type Abbott FreeStyle Libre 2® on a continuous basis for 2 years. Glucometric parameters were obtained during the initial 2 weeks using isCGM and compared with data collected for the same period at 1 year and at the end of follow-up. The IAH was evaluated using the Clarke questionnaire, and to assess psychological aspects related to hypoglycemia the Hypoglycemia Fear Survey (HFS) was used. RESULTS: After 2-years of follow-up using isCGM, we observed a decrease in glucose variability (40.3 ± 0.8 % vs. 37.1 ± 0.9 %, p = 0.003), time in low glucose range (54-69 mg/dL) (5.2 ± 0.4 % vs. 3.6 ± 0.3 %, p = 0.001), time in very low glucose range (<54 mg/dL) (3.2 ± 0.5 % vs. 0.8 ± 0.2 %, p < 0.001), less events related to low glucose levels (10.6 ± 1.1 vs 8.0 ± 1.0, p = 0.042) and a short duration of hypoglycemia episodes (106.1 ± 5.9 min vs. 85.7 ± 5.7 min, p = 0.008). In addition, participants presented a reduction of 47 % in the frequency of IAH, assessed by the Clarke questionnaire scores (24.6 % vs. 11.6 %, p = 0.034), as well as hypoglycemia fear (77.8 ± 2.4 vs 68.2 ± 2.1, p < 0.001). Furthermore, a reduction in total insulin dose was also observed (0.64 ± 0.30 UI/Kg/day vs 0.56 ± 0.11 UI/Kg/day, p = 0.018). CONCLUSIONS: In the real-world, long-term use of isCGM could reduce both hypoglycemic episodes and IAH in people with T1D.

Biomarkers for personalised prevention of chronic diseases: a common protocol for three rapid scoping reviews.

INTRODUCTION: Personalised prevention aims to delay or avoid disease occurrence, progression, and recurrence of disease through the adoption of targeted interventions that consider the individual biological, including genetic data, environmental and behavioural characteristics, as well as the socio-cultural context. This protocol summarises the main features of a rapid scoping review to show the research landscape on biomarkers or a combination of biomarkers that may help to better identify subgroups of individuals with different risks of developing specific diseases in which specific preventive strategies could have an impact on clinical outcomes. This review is part of the "Personalised Prevention Roadmap for the future HEalThcare" (PROPHET) project, which seeks to highlight the gaps in current personalised preventive approaches, in order to develop a Strategic Research and Innovation Agenda for the European Union. OBJECTIVE: To systematically map and review the evidence of biomarkers that are available or under development in cancer, cardiovascular and neurodegenerative diseases that are or can be used for personalised prevention in the general population, in clinical or public health settings. METHODS: Three rapid scoping reviews are being conducted in parallel (February-June 2023), based on a common framework with some adjustments to suit each specific condition (cancer, cardiovascular or neurodegenerative diseases). Medline and Embase will be searched to identify publications between 2020 and 2023. To shorten the time frames, 10% of the papers will undergo screening by two reviewers and only English-language papers will be considered. The following information will be extracted by two reviewers from all the publications selected for inclusion: source type, citation details, country, inclusion/exclusion criteria (population, concept, context, type of evidence source), study methods, and key findings relevant to the review question/s. The selection criteria and the extraction sheet will be pre-tested. Relevant biomarkers for risk prediction and stratification will be recorded. Results will be presented graphically using an evidence map. INCLUSION CRITERIA: Population: general adult populations or adults from specific pre-defined high-risk subgroups; concept: all studies focusing on molecular, cellular, physiological, or imaging biomarkers used for individualised primary or secondary prevention of the diseases of interest; context: clinical or public health settings. SYSTEMATIC REVIEW REGISTRATION: https://doi.org/10.17605/OSF.IO/7JRWD (OSF registration DOI).

A new method based on dispersive solid phase microextraction with commercial MOFs coupled to LC-MS/MS for the determination of isoflavones in soy drinks.

For the first time, a method based on dispersive solid phase microextraction (D-µSPE) using commercial metal-organic frameworks coupled to liquid chromatography-triple quadrupole tandem mass spectrometry (LC-MS/MS) has been proposed for the determination of isoflavones in soy drinks. The use of commercial sorbents simplifies the sample treatment procedure and allows their application to routine analysis. Optimization of the parameters involved in the microextraction process was carried out using a Box-Behnken experimental design. Under the optimized conditions, the limits of detection ranged between 2 and 7 µg L-1; the intra-day and inter-day precision were <10 and 20%, respectively, and the recoveries were in the range of 61-120%. No significant matrix effect was found, which allowed the use of external standard calibration method. The method was successfully applied to the determination of isoflavones in commercial soy milk samples.

Engineering Mesoscale T Cell Receptor Clustering by Plug-and-Play Nanotools.

T cell receptor (TCR) clustering and formation of an immune synapse are crucial for TCR signaling. However, limited information is available about these dynamic assemblies and their connection to transmembrane signaling. In this work, TCR clustering is controlled via plug-and-play nanotools based on an engineered irreversible conjugation pair and a peptide-loaded major histocompatibility complex (pMHC) molecule to compare receptor assembly in a ligand (pMHC)-induced or ligand-independent manner. A streptavidin-binding peptide displayed in both tools enabled their anchoring in streptavidin-pre-structured matrices. Strikingly, pMHC-induced clustering in the confined regions exhibit higher density and dynamics than the ligand-free approach, indicating that the size and architecture of the pMHC ligand influences TCR assembly. This approach enables the control of membrane receptor clustering with high specificity and provides the possibility to explore different modalities of receptor activation.