A single dose of angiotensin-(1-7) resolves eosinophilic inflammation and protects the lungs from a secondary inflammatory challenge.

OBJECTIVE: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge. METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed. RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation. CONCLUSION: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.

Antimicrobial Resistance Laboratory Network's multisite evaluation of the ThermoFisher Sensititre GN7F broth microdilution panel for antimicrobial susceptibility testing.

In 2017, the Centers for Disease Control and Prevention (CDC) established the Antimicrobial Resistance Laboratory Network to improve domestic detection of multidrug-resistant organisms. CDC and four laboratories evaluated a commercial broth microdilution panel. Antimicrobial susceptibility testing using the Sensititre GN7F (ThermoFisher Scientific, Lenexa, KS) was evaluated by testing 100 CDC and Food and Drug Administration AR Isolate Bank isolates [40 Enterobacterales (ENT), 30 Pseudomonas aeruginosa (PSA), and 30 Acinetobacter baumannii (ACB)]. We assessed multiple amounts of transfer volume (TV) between the inoculum and tubed 11-mL cation-adjusted Mueller-Hinton broth: 1 µL [tribe Proteeae (P-tribe) only] and 10, 30, and 50 µL, resulting in respective CFU per milliter of 1 × 104, 1 × 105, 3 × 105, and 5 × 105. Four TV combinations were analyzed: standard (STD) [1 µL (P-tribe) and 10 µL], enhanced standard (E-STD) [1 µL (P-tribe) and 30 µL], 30 µL, and 50 µL. Essential agreement (EA), categorical agreement, major error (ME), and very major error (VME) were analyzed by organism then TVs. For ENT, the average EA across laboratories was <90% for 7 of 15 ß-lactams using STD and E-STD TVs. As TVs increased, EA increased (>90%), and VMEs decreased. For PSA, EA improved as TVs increased; however, MEs also increased. For ACB, increased TVs provided slight EA improvements; all TVs yielded multiple VMEs and MEs. For ENT and ACB, Minimum inhibitory concentrations (MICs) trended downward using a 1 or 10 µL TV; there were no obvious MIC trends by TV for PSA. The public health and clinical consequences of missing resistance warrant increased TV of 30 µL for the GN7F, particularly for P-tribe, despite being considered "off-label" use.

Multivariate optimization of a green procedure for determination of emerging polycyclic aromatic nitrogen heterocycles in PM2.5 from sites with different characteristics.

Emerging polycyclic aromatic nitrogen heterocycles (PANHs) contributes significantly to the health risk associated with inhaling polluted air. However, there is a lack of analytical methods with the needed performance to their determination. This study presents the optimization and validation for the first time of a green microscale extraction procedure for the determination of twenty-one PANHs, including carbazole, indole, and quinolone classes, in particulate matter (PM2.5) samples by gas chromatography-mass spectrometry. A simplex-centroid mixture design and full factorial design (23) were employed to optimize the following extraction parameters: type and volume of solvent, sample size, extraction time, and necessity of a cleanup step. Low limits of detection and quantification (LOD < 0.97 pg m-3 and LOQ < 3.24 pg m-3, respectively) were obtained in terms of matrix-matched calibration. The accuracy and precision of the method were adequate, with recoveries in three levels between 73 to 120% and intraday and interday relative standard deviations from 2.0 to 12.9% and 7.3 to 18.9%, respectively. The green character of the method was evaluated using the Analytical Greenness (AGREE) tool, where a score of 0.69 was obtained, indicating a great green procedure. The method was applied to PM2.5 samples collected from sites with different characteristics; the concentrations ranged from 69.3 pg m-3 (2-methylcarbazole) to 11,874 pg m-3 (carbazole) for individual PANHs and from 2306 to 24,530 pg m-3 for ∑21PANHs. Principal component analysis (PCA) and hierarchical clustering enabled discrimination of the sampling sites according to the PANHs concentrations. The score plots formed two distinct groups, one with samples containing higher concentrations of PANHs, corresponding to sites with a major influence from diesel emissions, and another group with minor PANH contents, corresponding to sites impacted by emissions from urban traffic and industrial activities.

Reconsidering frailty from a human and social sciences standpoint: towards an interdisciplinary approach to vulnerability.

Although frailty is an important, well-characterized concept in the provision of medical care to older adults, it has not been linked to the concept of vulnerability developed in the humanities and social sciences. Here, we distinguish between the two main dimensions of vulnerability: a fundamental, anthropological dimension in which people are exposed to a risk of injury, and a relational dimension in which people depend on each other and on their environment. The relational notion of vulnerability might provide healthcare professionals with a better understanding of frailty (and its potential interaction with precarity). Precarity situates people in their relationship with a social environment that might threaten their living conditions. Frailty corresponds to individual-level changes in adaptation to a living environment and the loss of ability to evolve or react in that environment. Therefore, we suggest that by considering the geriatric notion of frailty as a particular form of relational vulnerability, healthcare professionals could better understand the specific needs of frail, older people-and thus provide more appropriate care.

Arterial stiffness indices, pulse wave velocity and central systolic blood pressure, are able to discriminate between obese and non-obese children.

The objectives of this study were to verify, first, if arterial stiffness indices can discriminate between obese and healthy children. Second, to evaluate arterial stiffness index predictors and hemodynamic parameters in obese children. Arterial stiffness indices evaluated were pulse wave velocity (PWV), central systolic blood pressure (SBPc), and central pulse pressure (PPc). A cross-sectional, descriptive, comparative study design was used. The sample consisted of 78 normal-weight children (8.1 ± 1.96 years) and 58 obese children (9.0 ± 1.87 years). PWV, PPc, and SBPc were significantly higher in the group of obese children than in the control group. The ROC curve analysis showed that maximum PWV and SBPc sensitivity and specificity in differentiating obese from non-obese children occurred at 4.09 m/s and 86.17 mmHg, respectively. PPc did not exhibit a discriminatory capacity between the two groups. Peripheral systolic blood pressure (SBPp), peripheral pulse pressure (PPp), and PPc (R2 = 0.98) were predictors of increased PWV. Augmentation pressure, PPp, and reflection coefficient (R2 = 0.873) were predictors of PPc. Age, augmentation index, total vascular resistance, cardiac index, and mean fat percentage (R2 = 0.801) were predictors of SBPc. CONCLUSION: This study shows for the first time that PWV > 4.09 m/s and SBPc > 86.17 mmHg are cut-off points associated with a higher risk of obesity. These results indicate that the simple, rapid, and noninvasive measurement of arterial stiffness adds prognostic information regarding cardiovascular risk, in addition to increased body mass index. WHAT IS KNOWN: • Overweight and obesity are strongly associated with comorbidities que contribute to the development of cardiovascular diseases. WHAT IS NEW: • This is the first study to show that PWV and SBPc can discriminate obese from non-obese children. These results show that, in addition to an increased BMI, a simple, rapid, and noninvasive measurement of arterial stiffness adds prognostic information on cardiovascular risk.

Advanced Levels of Chronic Venous Insufficiency are Related to an Increased in Arterial Stiffness.

BACKGROUND: Chronic venous insufficiency (CVI) is characterized by progressive inflammatory changes. Inflammatory damage occurs in the veins, adjacent tissues, and can lead to structural changes in the arteries. The aim of this study is to analyze whether the degree of CVI is associated with arterial stiffness. METHODS: Cross-sectional study including patients with CVI classified by clinical, etiological, anatomical, and pathophysiological classification (CEAP) 1 to 6. We performed correlation between the degree of CVI, central and peripheral arterial pressure, and arterial stiffness measured by brachial artery oscillometry. RESULTS: We evaluated 70 patients, 53 of whom were women with a mean age of 54.7 years. Patients with advanced degrees of venous insufficiency CEAP 4,5,6, had higher levels of systolic, diastolic, central, and peripheral arterial pressures compared to those with early stages (CEAP 1,2,3). The CEAP 4,5,6 group had higher arterial stiffness indices than the CEAP 1,2,3 group: pulse wave velocity (PWV) 9.3 m/s vs. 7.0 m/s, P < 0.001; augmentation pressure (AP) 8.0 mm Hg vs. 6.3 mm Hg; P = 0.04. There was a positive correlation between the degree of venous insufficiency measured by the venous clinical severity score, villalta score and CEAP classification, and the arterial stiffness indices (Spearman's coefficient = 0.62 for PWV and CEAP, P < 0.01). The factors influencing PWV were age, peripheral systolic arterial pressure (SAPp), and AP. CONCLUSIONS: There is a correlation between the degree of venous disease and arterial structural changes characterized by arterial pressure and stiffness indices. Degenerative changes secondary to venous insufficiency are associated with impairment of the arterial system, which has implications for the development of cardiovascular disease.

Reacting, Sharing, and Commenting: How Many Facebook Users Are Engaging with Posts Related to Dental Caries That Contain Misinformation?

Recent studies have been concerned about the vast amount of misinformation detected on social media that directly hampers the prevention and control of chronic diseases. Based on these facts, the aim of this study was to identify and characterize misinformation about dental caries-related content found on Facebook, regarding the predictive factors of user interaction with posts. Then, CrowdTangle retrieved 2,436 posts published in English, ordered by the total interaction of the highest users. A total of 1,936 posts were selected for inclusion and exclusion criteria to select a sample of 500 posts. Subsequently, two independent investigators characterized the posts by their time of publication, author's profile, motivation, the aim of content, content facticity, and sentiment. The statistical analysis was performed using Mann-Whitney U and χ2 tests and multiple logistic regression models to determine differences and associations between dichotomized characteristics. p values <0.05 were considered significant. In general, posts were predominantly originated from the USA (74.8%), related to business profiles (89%), presented preventive content (58.6%), and noncommercial motivation (91.6%). Furthermore, misinformation was detected in 40.8% of the posts and was positively associated with positive sentiment (OR = 3.43), business profile (OR = 2.22), and treatment of dental caries (OR = 1.60). While the total interaction was only positively associated with misinformation (OR = 1.44), the overperforming score was associated with posts from the business profile (OR = 5.67), older publications (OR = 1.57), and positive sentiment (OR = 0.66). In conclusion, misinformation was the unique predictive factor of increased user interaction with dental caries-related posts on Facebook. However, it did not predict the performance of the diffusion of posts such as business profiles, older publications, and negative/neutral sentiment. Therefore, it is essential to promote the development of specific policies toward good quality information on social media, which includes the production of adequate materials, the increase of the critical sense of consuming health content, and information filtering mediated by digital solutions.

Eating behaviour, quality of life and cardiovascular risk in obese and overweight children and adolescents: a cross-sectional study.

BACKGROUND: Childhood obesity is a major cardiovascular risk factor because it predisposes individuals to comorbidities that are implicated in an increased risk of cardiovascular events. Its origin may be related to poor eating habits, such as the intake of foods of low nutritional value or inadequate eating behaviours related to emotional factors. This work aims to evaluate the relationship between the total body mass of children and adolescents and its association with eating habits, quality of life (QoL), and possible changes in early markers of cardiovascular risk. METHODS: This was a cross-sectional observational study that evaluated anthropometric and cardiovascular parameters, QoL, and eating behaviour in 181 children and adolescents aged between 5 and 13 years. Participants were stratified according to BMI/age into three groups (Adequate Weight, Overweight, and Obesity). Anthropometry included weight, height, waist and hip circumferences, waist-hip ratio, and waist-height ratio. QoL was assessed using the Peds-QL 4.0 questionnaire, and eating behaviour was assessed using the Children's Eating Behaviour Questionnaire (CEBQ). Cardiovascular parameters were assessed using the Mobil-O-Graph® device, which measures the pulse wave velocity (PWV) and augmentation index (AIx@75) to estimate arterial stiffness (AS), which is considered an early marker of cardiovascular disease. RESULTS: In addition to the increase in anthropometric measurements (p < 0.001), the Obesity group exhibited behaviour related to food intake (p < 0.05). When analysing QoL, a worsening in the social domain was also observed in the Obesity group (p < 0.05). However, PWV and AIx@75 did not differ between groups. CONCLUSIONS: Eating behaviour is related to the development of childhood obesity. However, early markers of cardiovascular risk related to AS did not change as a function of total body mass in the children evaluated.

Factors associated with arterial stiffness assessed by pulse pressure amplification in healthy children and adolescents: a cross-sectional study.

BACKGROUND: Increasing evidence suggests that reducing pulse pressure amplification (PPA) plays an important role in pathogenesis and progression of cardiovascular disease. This is a cross-sectional, observational, and analytical study in which we evaluated the associated factors with a greater chance of reducing PPA in 136 healthy children and adolescents aged 8 to 19 years old stratified by gender and age group. METHODS: Arterial stiffness and vascular and hemodynamic parameters were non-invasively measured using Mobil-O-Graph® (IEM, Stolberg, Germany), a cuff-based oscillometric device. PPA was expressed as the peripheral-to-central pulse pressure ratio (PPp / PPc). Participants with PPA < 1.49 were considered as part of the arterial stiffness group. RESULTS: In a univariate model, the increase in total vascular resistance, the reflection coefficient and the augmentation pressure were more likely to have arterial stiffness in all groups. The factors most likely to have arterial stiffness (as assessed by the reduction of the PPA) in the multivariate model were increasing age, the reflection coefficient and cardiac index in the total sample, male group and child and adolescent groups. In addition to age in the female group, cardiac output, stroke volume, and AIx@75 were the factors most likely to present arterial stiffness. CONCLUSIONS: The results show for the first time in children and adolescents that the factors most likely to reduce PPA are related to the reflection wave, which determines aortic pressures and, therefore, left ventricular afterload.

Competency profiles for evidence-informed policy-making (EIPM): a rapid review.

BACKGROUND: Evidence-informed policy-making (EIPM) requires a set of individual and organizational capacities, linked with background factors and needs. The identification of essential knowledge, skills and attitudes for EIPM can support the development of competency profiles and their application in different contexts. PURPOSE: To identify elements of competency (knowledge, skills and attitudes) for EIPM, according to different professional profiles (researcher, health professional, decision-maker and citizen). METHODS: Rapid umbrella review. A structured search was conducted and later updated in two comprehensive repositories (BVSalud and PubMed). Review studies with distinctive designs were included, published from 2010 onwards, without language restrictions. Assessment of the methodological quality of the studies was not performed. A meta-aggregative narrative synthesis was used to report the findings. RESULTS: Ten reviews were included. A total of 37 elements of competency were identified, eight were categorized as knowledge, 19 as skills and 10 as attitudes. These elements were aggregated into four competency profiles: researcher, health professional, decision-maker and citizen. The competency profiles included different sets of EIPM-related knowledge, skills and attitudes. STRENGTHS AND LIMITATIONS: This study is innovative because it aggregates different profiles of competency from a practical perspective, favouring the application of its results in different contexts to support EIPM. Methodological limitations are related to the shortcuts adopted in this review: complementary searches of the grey literature were not performed, and the study selection and data extraction were not conducted in duplicate. FINAL CONSIDERATIONS: CONCLUSIONS AND IMPLICATIONS OF THE FINDINGS: EIPM requires the development of individual and organizational capacities. This rapid review contributes to the discussion on the institutionalization of EIPM in health systems. The competency profiles presented here can support discussions about the availability of capacity and the need for its development in different contexts.

Strategies for communicating scientific evidence on healthcare to managers and the population: a scoping review.

BACKGROUND: Health evidence needs to be communicated and disseminated in a manner that is clearly understood by decision-makers. As an inherent component of health knowledge translation, communicating results of scientific studies, effects of interventions and health risk estimates, in addition to understanding key concepts of clinical epidemiology and interpreting evidence, represent a set of essential instruments to reduce the gap between science and practice. The advancement of digital and social media has reshaped the concept of health communication, introducing new, direct and powerful communication platforms and gateways between researchers and the public. The objective of this scoping review was to identify strategies for communicating scientific evidence in healthcare to managers and/or population. METHODS: We searched Cochrane Library, Embase®, MEDLINE® and other six electronic databases, in addition to grey literature, relevant websites from related organizations for studies, documents or reports published from 2000, addressing any strategy for communicating scientific evidence on healthcare to managers and/or population. RESULTS: Our search identified 24 598 unique records, of which 80 met the inclusion criteria and addressed 78 strategies. Most strategies focused on risk and benefit communication in health, were presented by textual format and had been implemented and somehow evaluated. Among the strategies evaluated and appearing to yield some benefit are (i) risk/benefit communication: natural frequencies instead of percentages, absolute risk instead relative risk and number needed to treat, numerical instead nominal communication, mortality instead survival; negative or loss content appear to be more effective than positive or gain content; (ii) evidence synthesis: plain languages summaries to communicate the results of Cochrane reviews to the community were perceived as more reliable, easier to find and understand, and better to support decisions than the original summaries; (iii) teaching/learning: the Informed Health Choices resources seem to be effective for improving critical thinking skills. CONCLUSION: Our findings contribute to both the knowledge translation process by identifying communication strategies with potential for immediate implementation and to future research by recognizing the need to evaluate the clinical and social impact of other strategies to support evidence-informed policies. Trial registration protocol is prospectively available in MedArxiv (doi.org/10.1101/2021.11.04.21265922).

An evidence-informed policymaking (EIPM) competency profile for the Brazilian Health System developed through consensus: process and outcomes.

BACKGROUND: Evidence-informed policymaking (EIPM) requires a set of individual and organizational knowledge, skills and attitudes that should be articulated with background factors and needs. In this regard, the development of an EIPM competency profile is important to support the diagnosis, planning and implementation of EIPM. PURPOSE: To present the process and outcomes of the development of an EIPM competency profile by an expert committee, to be applied in different contexts of the Brazilian Health System. METHODS: A committee of experts in EIPM shared different views, experiences and opinions to develop an EIPM competency profile for Brazil. In six consensus workshops mediated by facilitators, the committee defined from macro problems to key actions and performances essential for the competency profile. The development steps consisted of: (1) Constitution of the committee, including researchers, professionals with practical experience, managers, and educators; (2) Development of a rapid review on EIPM competency profiles; (3) Agreement on commitments and responsibilities in the processes; (4) Identification and definition of macro problems relating to the scope of the competency profile; and (5) Outlining of general and specific capacities, to be incorporated into the competency profile, categorized by key actions. RESULTS: The development of the EIPM competency profile was guided by the following macro problems: (1) lack of systematic and transparent decision-making processes in health policy management; (2) underdeveloped institutional capacity for knowledge management and translation; and (3) incipient use of scientific evidence in the formulation and implementation of health policies. A general framework of key actions and performances of the EIPM Competency Profile for Brazil was developed, including 42 specific and general key actions distributed by area of activity (Health Management, Scientific Research, Civil Society, Knowledge Translation, and Cross-sectional areas). CONCLUSIONS: The competency profile presented in this article can be used in different contexts as a key tool for the institutionalization of EIPM.

Aortic pulse wave morphology in individuals after chronic stroke: interarm comparison wave morphology after chronic stroke.

CONTEXT: Vascular changes can be a risk factor for recurrent and new events of stroke. However, few information is known regarding the variables related to aortic pulse wave morphology in stroke individuals. OBJECTIVE: To analyze aortic pulse wave morphology (arterial stiffness indices, hemodynamics and vascular variables) and to compare the paretic and non-paretic sides in individuals after chronic stroke. DESIGN: In this cross-sectional study stroke individuals had arterial stiffness indices, hemodynamics and vascular variables assessed with brachial artery oscillometry. T-test (CI95%) was used in order to compare the variables between the paretic and non-paretic sides. RESULTS: Twenty individuals were included, 65% men (60.3 SD 16.7 years). The following variables: (mean difference [CI95%]): coefficient of reflection (-2.33 [-4.60 to -0.07]), peak of ejection wave, P1 (5.32 [2.75 to 7.90] and peak of ejection wave, P2 (6.17 [2.55 to 9.78]), central diastolic blood pressure (mean difference [IC95%]): (-3.75 [-6.09 to -1.40]), central systolic blood pressure (-6.17 [-9.74 to -2.59]), mean arterial pressure (-4.46 [-7.08 to -1.84]), peripheral diastolic blood pressure (-3.48 [-5.94 to -1.02]) and peripheral systolic blood pressure (-5.53 [-9.54 to -1.52]) were higher in paretic than non-paretic side. Hemodynamics parameters were similar in both sides. CONCLUSIONS: In this study we demonstrated, for the first time, that many parameters from aortic pulse wave were higher in paretic compared with non-paretic side in individuals after chronic stroke, suggesting that peripheral vascular changes affect heart-vascular coupling in these individuals.

What Are the Effects on Palate of Early Lip Surgery in Children With Cleft Lip and Palate? Cross-Sectional Evaluation From 5-Year-Old.

This study aimed to evaluate the postsurgical effects from 5 years on the palate after surgical repair of the lip at 3 or 9 months of age in children with cleft lip and palate. Eighty-four digitized dental impressions were divided into the following groups: group 1 (G1): lip surgery at 3 months of life; group 2 (G2): lip surgery at 9 months of life; group 3 (G3): without orofacial cleft. Five angular (C'IC, ICM, IC'M', CMM', and C'M'M) and 3 linear parameters (C-C', c-c', and M-M') were evaluated. Statistical analysis was applied with α=5%. Intraclass Correlation Coefficient was significantly smaller in G1 than in G3 ( P =0.005), while IC'M' was significantly smaller in G3 than in G1 ( P <0.001). C'M'M was significantly smaller in G1 than in G2 and G3 ( P <0.001). The distances C-C' and c-c' were significantly smaller in G1 than in G2 and G3 ( P <0.001). There was a statistically significant difference in both G1 and G2 ( P <0.001, in all) in the analysis of palatal symmetry. Linear regression analysis showed that the, 11.2% of outcomes determined by c-c' distance can be explained by the age of lip repair ( P =0.013). In conclusion, lip surgery at 3 months of life showed a tendency toward more restriction in 5-year postsurgery palate development. The age of cheiloplasty is one of the factors that can influence palatal development; however, other factors may be associated and should be studied.

Customized Tray for Impression Taking in Children With Cleft Lip and Palate.

The assessment of rehabilitation outcomes requires a patient documentation protocol, including records obtained at standardized ages, to compare different types of surgeries, their effects, as well as between different rehabilitation centers. The aim of this paper was to present proper trays for babies with different types of cleft lip and palate, which are used in the outpatient routine at Hospital of Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP). The customized trays are made with self-curing acrylic resin. The tray must have suitable depth to copy the buccal sulcus, and wax is usually applied to contour the tray edge, and the adjustment of the tray to the fornix, making the tray specific for each child. The impression precludes the utilization of dental casts for diagnosis, treatment plan, and research measurements. In the clinical practice at HRAC-USP, it was observed that customized trays increased the quality of impression, accurately reproducing anatomical features of dental arches of babies with oral clefts.

In-vitro NLRP3 functional test assists the diagnosis of cryopyrin-associated periodic syndrome (CAPS) patients: A Brazilian cooperation.

OBJECTIVE: To report our five-years experience on the use of NLRP3 inflammasome functional assays in the differential diagnosis of Brazilian patients with a clinical suspicion of CAPS. PATIENTS AND METHODS: The study included 9 patients belonging to 2 families (I, II) and 7 unrelated patients with a clinical suspicion of AID according to Eurofever/PRINTO classification, recruited between 2017 and 2022. The control group for the NLRP3 functional assay consisted of 10 healthy donors and for the CBA cytokines measurement of 19 healthy controls. Patients underwent clinical evaluation, genetic and functional analysis. RESULTS: All members of the family I received the diagnosis of Muckle-Wells Syndrome (MWS), carried the NLRP3 Thr348Met variant and resulted positive for the functional assay. The 2 patients of the family II resulted negative for the mutational screening but positive for the functional assay compatible with a MWS clinical phenotype. In 2 unrelated patients with NLRP3 mutations, including a novel mutation (Gly309Val, Asp303His), a positive functional test confirmed the clinical diagnosis of NOMID. 3 unrelated MWS and 1 FCAS patients resulted negative to the genetic screening and positive for the functional test. One patient with a FCAS-like phenotype harbored the NLRP12 His304Tyr variant confirming the diagnosis of FCAS2. CONCLUSION: The NLRP3 inflammasome functional assay can assist the clinical diagnosis of CAPS even in patients with unknown genetic defects.

Analysis of Immune Landscape in Pancreatic and Ileal Neuroendocrine Tumours Demonstrates an Immune Cold Tumour Microenvironment.

INTRODUCTION: Neuroendocrine tumours (NETs) are rare tumours with an increasing incidence. While low- and intermediate-grade pancreatic NET (PanNET) and small intestinal NET (siNET) are slow growing, they have a relatively high rate of metastasizing to the liver, leading to substantially worse outcomes. In many solid tumours, the outcome is determined by the quality of the antitumour immune response. However, the quality and significance of antitumour responses in NETs are incompletely understood. This study provides clinico-pathological analyses of the tumour immune microenvironment in PanNET and siNETs. METHODS: Formalin-fixed paraffin-embedded tissue from consecutive resected PanNETs (61) and siNETs (131) was used to construct tissue microarrays (TMAs); 1-mm cores were taken from the tumour centre, stroma, tumour edge, and adjacent healthy tissue. TMAs were stained with antibodies against CD8, CD4, CD68, FoxP3, CD20, and NCR1. T-cell counts were compared with counts from lung cancers. RESULTS: For PanNET, median counts were CD8+ 35.4 cells/mm2, CD4+ 7.6 cells/mm2, and CD68+ macrophages 117.7 cells/mm2. For siNET, there were CD8+ 39.2 cells/mm2, CD4+ 24.1 cells/mm2, and CD68+ 139.2 cells/mm2. The CD8+ cell density in the tumour and liver metastases were significantly lower than in the adjacent normal tissues, without evidence of a cell-rich area at the tumour edge that might have suggested immune exclusion. T-cell counts in lung cancer were significantly higher than those in PanNET and siNETs: CD8+ 541 cells/mm2 and CD4+ 861 cells/mm2 (p ≤ 0.0001). CONCLUSION: PanNETs and siNETs are immune cold with no evidence of T cell exclusion; the low density of immune infiltrates indicates poor antitumour immune responses.

Pediatric obstructive sleep-disordered breathing is associated with arterial stiffness.

The association between obstructive sleep-disordered breathing (oSDB) and arterial stiffness, an independent predictor of cardiovascular outcomes, is not well established in children. This study compared cardiovascular parameters between healthy and oSDB children and aimed to identify predictors of arterial stiffness indices in children with oSDB. Cross-sectional study realized in a tertiary hospital from June 2018 to January 2020. Forty-eight children (3 to 10 years old) with clinical diagnosis of oSDB and indication for adenotonsillectomy and 24 controls were evaluated. Cardiovascular parameters were measured non-invasively by brachial artery oscillometry with a portable device. The main arterial stiffness indices assessed were augmentation index and pulse wave velocity, both derived from the aortic pulse wave. In the oSDB group, the questionnaires Obstructive Sleep Apnea-18 (OSA-18) and Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0) were applied. The oSDB group had higher values of reflection coefficient (p = 0.044) and augmentation index (p = 0.003) than the control group. Stepwise multiple regression analysis revealed that age, female sex, reflection coefficient, and systolic volume were independent predictors of augmentation index. Higher pulse wave velocity values were associated with worse quality of life assessed by PedsQL 4.0 questionnaire. There was no association with OSA-18. The vascular and hemodynamic parameters were similar in both groups.Conclusion: Children with oSDB have increased augmentation index, an independent predictor of cardiovascular outcomes. The early identification of subclinical cardiovascular changes reinforces the importance of treating the disease, as well as changing lifestyle habits, to prevent complications in adulthood. What is Known: • The association between oSDB and cardiovascular risk in adults is well described in the literature. • Children with oSDB, regardless of their weight or sex, have higher PWV values when compared to non-snoring children. What is New: • Children with oSDB have augmented arterial stiffness, evidenced by the increase in AIx@75, measured non-invasively by brachial artery oscillometry with a portable device. • Low quality of life and therefore a high disease burden in children with oSDB may be a risk factor for arterial stiffness.

Adolescent pregnancy in Sao Tome and Principe: are there different obstetric and perinatal outcomes?

BACKGROUND: Adolescent childbirth is a major public health problem in Sao Tome and Principe (STP). Adolescent pregnancy and childbirth can carry a risk of morbidity associated with the physiological and sociological characteristics of teenage girls. This study aims to identify the main adverse obstetric and perinatal outcomes for adolescent pregnancies in the Hospital Dr. Ayres de Menezes (HAM), the only hospital in STP. METHODS: An institution-based cross-sectional study. Pregnant women ≤ 19 years of age (n = 104) were compared to non-adolescent women (n = 414). The obstetric and perinatal outcomes were compared between groups using the t test. Odds ratio (OR) were calculated through Cochran's and Mantel-Haenszel statistics test for odds ratio equal to 1, 95% confidence intervals (CI) and p values (p < 0.05) were considered significant. RESULTS: The adverse perinatal outcomes imputable to adolescent births were foetal distress with low first minute Apgar score < 7 (OR 1.94, 95% CI 1.18-3.18, p = 0.009) and performance of neonatal resuscitation manoeuvres (OR 2.4, 95% CI 1.07-5.38, p = 0.032). Compared to older mothers, teenage girls were likely to have a non-statistically significant threefold higher risk of having an obstructed labour (OR 3.40, 95% CI 0.89-12.94, p = 0.07). Other perinatal outcomes as neonatal asphyxia, risk for cerebral palsy, premature birth, early neonatal infection, and neonatal death were identical between groups as well as maternal anaemia, mode of delivery or other obstetrical outcomes. CONCLUSION: Adolescent pregnancies were associated with worse perinatal outcomes as foetal distress and higher need for neonatal resuscitation manoeuvres. This study may support STP health authorities in their efforts to make Sustainable Development Goals 3 (good health and wellbeing), 4 (quality education) and 5 (gender equality) a reality by 2030, since it identifies specific problems that need to be addressed to improve maternal adolescent health.

Adolescent pregnancy in Sao Tome and Principe: a cross-sectional hospital-based study.

BACKGROUND: Pregnancy starts early in Sao Tome and Principe (STP) and rates of adolescent pregnancy increased 16% in recent years reaching a 27.3% prevalence. This study aimed to understand the pregnant adolescents' characteristics and factors associated to early childbearing in STP. METHODS: A cross-sectional hospital-based study was undertaken in Hospital Dr. Ayres de Menezes between 2016 and 2018 with a randomly selected total sample size of 518 mothers. Mothers' clinical records and interviews were used to collect relevant data. The results among adolescent girls 19 years of age and younger (n=104) were compared to adult mothers (n=414). A subgroup analysis of adolescent pregnant girls was also conducted. Statistically significance was considered at a p-value ≤0.05. Data were analysed using SPSS software. RESULTS: The study revealed that 20.1% were adolescent mothers. Pregnancy at a very early age (≤15) was experienced by 7.7%. The characteristics founded to be positively associated with adolescent pregnancy were: 1) being single (OR 0.39, 95% CI=0.2-0.6, p≤0.001); 2) having a relationship with the baby´s father for a period of less than one year (OR 0.16, 95% CI=0.09-0.3, p≤0.001); 3) lack of the baby´s father support (OR 0.41, 95% CI=0.2-0.7, p=0.002); 4) not using a contraceptive method (OR 0.33, 95% CI=0.2-0.5, p≤0.001), and 5) inappropriate knowledge concerning the identification of the newborn's danger signs (OR 15.7, 95% CI= 9-26, p≤0.001). Comparing pregnancy at very early age (≤15) to late (>18 and ≤19) adolescents, main differences were that previous contraceptives were not used at all in girls ≤15 years compared to 9.8% of late childbearing subgroup. CONCLUSIONS: Unfavourable factors linked to adolescent pregnancies were absence of a contraceptive method, getting pregnant in the early first months of one relationship and to be single. Gap age difference between adolescents' partners, polygamous sexual relationships, previous abortion and having already other living children were also identified. Adolescents also had inappropriate knowledge of the identification of the newborns' danger signs. Before being sexually active, adolescents critically need sexual and reproductive health information provided by a healthy community and through school programmes on sexual education. Schools should promote girl's empowerment and awareness and, at the same time, reinforce boy's role in fatherhood and shared responsibilities. The government should work on the prevention of early sexual initiation, as well as on improving family planning programmes to protect them from pregnancy with special focus for the very early adolescent girls. None of these goals can be achieved if the government doesn't, simultaneously, improve educational and economic opportunities for girls.