Interhemispheric coherence of EEG rhythms in children: Maturation and differentiation in corpus callosum dysgenesis.

OBJECTIVES: To evaluate the evolution of interhemispheric coherences (ICo) in background and spindle frequency bands during childhood and use it to identify individuals with corpus callosum dysgenesis (CCd). METHODS: A monocentric cohort of children aged from 0.25 to 15 years old, consisting of 13 children with CCd and 164 without, was analyzed. The ICo of background activity (ICOBckgrdA), sleep spindles (ICOspindles), and their sum (sICO) were calculated. The impact of age, gender, and CC status on the ICo was evaluated, and the sICO was used to discriminate children with or without CCd. RESULTS: ICOBckgrdA, ICOspindles and sICO increased significantly with age without any effect of gender (p < 10-4), in both groups. The regression equations of the different ICo were stronger, with adjusted R2 values of 0.54, 0.35, and 0.57, respectively. The ICo was lower in children with CCd compared to those without CCd (p < 10-4 for all comparisons). The area under the precision recall curves for predicting CCd using sICO was 0.992 with 98.9 % sensitivity and 87.5 % specificity. DISCUSSION: ICo of spindles and background activity evolve in parallel to brain maturation and depends on the integrity of the corpus callosum. sICO could be an effective diagnostic biomarker for screening children with interhemispheric dysfunction.

Sustainable Development Goals' health-related indicators for Brazil and Ecuador: an analysis for the period of 1990-2019.

OBJECTIVE: This article aims to analyse the evolution of 40 Sustainable Development Goals' (SDGs) health-related indicators in Brazil and Ecuador from 1990 to 2019. STUDY DESIGN: Epidemiological study of long-term trends in 40 SDGs' health-related indicators for Brazil and Ecuador from 1990 to 2019, using estimates from the Global Burden of Disease Study. METHODS: Forty SDGs' health-related indicators and an index from 1990 to 2017 for Brazil and Ecuador, and their projections up to 2030 were extracted from the Institute for Health Metrics and Evaluation's Global Burden of Disease website and analysed. The percent annual change (PC) between 1990 and 2019 was calculated for both countries. RESULTS: Both countries have made progress on child stunting (Brazil: PC = -38%; Ecuador: PC = -43%) and child wasting prevalences (Brazil: PC = -42%; Ecuador: PC = -41%), percent of vaccine coverage (Brazil: PC = +215%; Ecuador: PC = +175%), under-5 (Brazil: PC = -75%; Ecuador: PC = -60%) and neonatal mortality rates (Brazil: PC = -69%; Ecuador: PC = -51%), health worker density per 1000 population (Brazil: PC = +153%; Ecuador: PC = +175%), reduction of neglected diseases prevalences (Brazil: PC = -40%; Ecuador: PC = -58%), tuberculosis (Brazil: PC = -27%; Ecuador: PC = -55%) and malaria incidences (Brazil: PC = -97%; Ecuador: PC = -100%), water, sanitation and hygiene mortality rates (Brazil and Ecuador: PC = -89%). However, both countries did not show sufficient improvement in maternal mortality ratio to meet SDGs targets (Brazil: PC = -37%; Ecuador: PC = -40%). Worsening of indicators were found for violence, such as non-intimate partner violence for both countries (Brazil: PC = +26%; Ecuador: PC = +18%) and suicide mortality rate for Ecuador (PC = +66%), child overweight indicator for Brazil (PC = -67%), disaster mortality rates (Brazil: PC = +100%; Ecuador: PC = +325%) and alcohol consumption (Brazil: PC = +46%; Ecuador: PC = +35%). CONCLUSIONS: Significant improvements are necessary in both countries requiring the strengthening of health and other policies, particularly concerning the prevention and management of violence and alcohol consumption, and preparedness for dealing with environmental disasters.

Undernutrition, and overweight and obesity: the two faces of malnutrition in Brazil, analysis of the Global Burden of Disease, 1990 to 2019.

OBJECTIVES: The objective of this study was to analyse the global burden of disease attributable to undernutrition and high body mass index (BMI) in Brazil and its 27 states, as well as its association with the socio-demographic index (SDI) from 1990 to 2019. STUDY DESIGN: This is an epidemiological time-series study. METHODS: This study analysed the undernutrition and high BMI estimated by the Global Burden of Disease study conducted from 1990 to 2019 for Brazil and its states, using the following metrics: absolute number of deaths, standardised mortality rate, and disability-adjusted life years (DALYs). This study also analysed the correlation between the percentage variation of mortality rates and SDI. RESULTS: A decrease in the number of deaths (-75 %), mortality rate (-75.1 %), and DALYS (-72 %) attributable to undernutrition was found in Brazil and in all regions. As regarding the high BMI, an increase in the number of deaths was found (139.6 %); however, the mortality rate (-9.7) and DALYs (-6.4 %) declined in all regions, except in the North and Northeast regions, which showed an increase. A strong correlation was identified between undernutrition and high BMI with SDI. CONCLUSION: Our study observed a double burden of malnutrition in Brazil, with a reduction in the burden of diseases due to malnutrition in Brazil and variation in the burden due to high BMI according to the socioeconomic status of the region. Public policies are necessary in order to guarantee the human right to a healthy and sustainable diet, together with food and nutrition security and a diminishing of social inequality.

Mortality by avoidable causes in Brazil from 1990 to 2019: data from the Global Burden of Disease Study.

OBJECTIVES: The aim of this study was to analyse the trends of avoidable mortality in Brazil from 1990 to 2019 and its correlation with sociodemographic indexes (SDIs). STUDY DESIGN: Epidemiological mortality trends. METHODS: This study analysed data from the Global Burden of Disease database. The list of causes of avoidable death, as proposed by Nolte and McKee, was applied and included 32 causes. The current study used age-standardised mortality rates and the rates of change, in addition to a correlation analysis between avoidable death and the SDI. RESULTS: Mortality rates decreased from 343.90/100,000 inhabitants in 1990 to 155.80/100,000 inhabitants in 2019. Infectious diseases showed the largest decline in mortality rates, but notable decreases were also found for diarrhoeal diseases (-94.9%), maternal conditions (-66.5%) and neonatal conditions (-60.5%). Mortality rates for non-communicable diseases (NCDs) also decreased (-48%) but maintained a similar absolute number of deaths in 2019 compared with 1990. Decreased mortality rates were also found for ischaemic heart disease (-49.1%), stroke (-61.4%) and deaths due to adverse effects caused by medical treatments (-26.2%). Avoidable mortality rates declined in all of the 27 Brazilian states, and a high correlation was found between deaths and SDI (R = -0.74; P < 0.000001). CONCLUSIONS: A reduction in avoidable deaths was found throughout Brazil over the study period, although major regional inequalities were revealed. Richer states presented the best overall reduction in mortality rates. The biggest decreases in mortality were seen in maternal and paediatric infectious diseases in the poorest states due to the expansion of the Primary Health System and improvements in sanitation. Today, NCDs predominate and efforts should be made to formulate public policies for the prevention and control of NCDs.

A medication reconciliation failure: A case report and incident analysis.

BACKGROUND: Medication reconciliation is advocated to ensure the continuity, safety, and effective use of medicines across transitions of care. CASE REPORT: In this report, we describe the case of a 90-year-old female with previous diagnoses of atrial fibrillation and cutaneous metastatic breast cancer presenting with bilateral ulcerative lesions on the chest wall. The patient was diagnosed with Deep Vein Thrombosis at the Emergency Department and started on rivaroxaban, although the patient was already taking edoxaban. This therapeutic duplication was noticed only one week later, even though she was already experiencing significant bleeding managed through a prescribing cascade. Despite the technical error (action-based), it is possible to identify several weaknesses in the organisation's structure, which provided a trajectory of accident opportunity. CONCLUSION: Anticoagulants are ranked first for the highest priority to receive a medication reconciliation. To achieve an optimal level of medication reconciliation, we ought to recognise and correct latent failures.

Burden of non-communicable diseases and the achievement of the sustainable development goals in 2030 in Mercosur countries.

OBJECTIVES: The aims of this article were to analyse the burden of NCDs and their RFs in the Mercosur countries between 1990 and 2019 and to project mortality trends for 2030. STUDY DESIGN: Epidemiological study of time series. METHODS: The present study used data from the Global Burden of Disease study. The absolute number of deaths, mortality rates, disability-adjusted life years, years of life lost, years lived with disability and the burden of premature mortality by NCD attributable to the RFs were evaluated. Projections were made up to 2030. Age-standardised rates were used to draw comparisons by years and by countries. The analysis was conducted using the RStudio software. RESULTS: Between 1990 and 2019, a decrease was found in the premature mortality rates caused by NCDs in all the countries, except for Paraguay, which remained stable. When analysing premature mortality rates due to NCDs up to 2030, it was predicted that none of the countries would achieve the sustainable development goal of a one-third reduction in premature mortality by NCDs. Regarding the impacts of the RFs for NCDs, smoking, dietary risks, high blood pressure (BP) and high body mass index (BMI) were the main risks attributable to premature deaths due to NCDs. CONCLUSIONS: The results showed that mortality rates are declining in Mercosur countries; however, none of the countries are predicted to achieve the sustainable development goal of a one-third reduction in mortality due to NCDs by 2030. In addition to access to adequate treatment, progress is required in public regulation actions to reduce RFs, such as smoking, dietary risks, high BP and high BMI.

Evaluating H295R steroidogenesis assay data for robust interpretation.

The in vitro H295R steroidogenesis assay (OECD TG 456) is used to determine a chemical's potential to interfere with steroid hormone synthesis/metabolism. As positive outcomes in this assay can trigger significant higher tiered testing, we compiled a stakeholder database of reference and test item H295R data to characterize assay outcomes. Information concerning whether a Level 5 reproductive toxicity study was triggered due to a positive outcome in the H295R assay was also included. Quality control acceptance criteria were not always achieved, suggesting this assay is challenging to conduct within the guideline specifications. Analysis of test item data demonstrated that pairwise significance testing to controls allowed for overly sensitive statistically significant positive outcomes, which likely contribute to the assay's high positive hit rate. Complementary interpretation criteria (e.g., 1.5-fold change threshold) markedly reduced the rate of equivocal and positive outcomes thus improving identification of robust positive effects in the assay. Finally, a case study (positive H295R outcome and no endocrine adversity in vivo) is presented, which suggests that stricter data interpretation criteria could refine necessary in vivo follow-up testing. Overall, the described additional criteria could improve H295R data interpretation and help inform on how to best leverage this assay for regulatory purposes.

Management and outcomes of obturator hernias: a systematic review and meta-analysis.

PURPOSE: Obturator Hernia (OH) is a rare type of abdominal wall hernia. It usually occurs in elderly women with late symptomatic presentation, increasing mortality rates. Surgery is the standard of care for OH, and laparotomy with simple suture closure of the defect is commonly used. Given the rarity of this disease, large studies are lacking, and data to drive management are still limited. This systematic review and meta-analysis aimed to describe current surgical options for OHs, with a focus on comparing the effectiveness and safety of mesh use with primary repair. METHODS: PubMed, EMBASE, and Cochrane were searched for studies comparing mesh and non-mesh repair for OH. Postoperative outcomes were assessed by pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. RESULTS: One thousand seven hundred and sixty studies were screened and sixty-seven were thoroughly reviewed. We included 13 observational studies with 351 patients surgically treated for OH with mesh or non-mesh repair. One hundred and twenty (34.2%) patients underwent mesh repair and two hundred and thirty-one (65.81%) underwent non-mesh repair. A total of 145 (41.3%) underwent bowel resection, with the majority having a non-mesh repair performed. Hernia recurrence was significantly higher in patients who underwent hernia repair without mesh (RR 0.31; 95% CI 0.11-0.94; p = 0.04). There were no differences in mortality (RR 0.64; 95% CI 0.25-1.62; p = 0.34; I2 = 0%) or complication rates (RR 0.59; 95% CI 0.28-1.25; p = 0.17; I2 = 50%) between both groups. CONCLUSION: Mesh repair in OH was associated with lower recurrence rates without an increase in postoperative complications. While mesh in clean cases is more likely to offer benefits, an overall recommendation regarding its use in OH repair cannot be made due to potential bias across studies. Given that many OH patients are frail and present emergently, the decision to use mesh is complex and should consider the patient's clinical status, comorbidities, and degree of intraoperative contamination.

Bone density and proximal support effects on dental implant stability - Finite element analysis and in vitro experiments.

OBJECTIVES: The application of dental implants presents the occurrence of implant failures associated with bone proximal support. This study aims to assess implant behavior, in particular implant stability and strain distribution in the bone at different bone densities, and the effect of proximal bone support. MATERIAL AND METHODS: Three bone densities (D20, D15, and D10) were considered in the experimental in vitro study, represented by solid rigid polyurethane foam and two conditions of bone support in the proximal region. A finite element model was developed and validated experimentally and a Branemark model at a 3:1 scale was implanted in the experiments; the model was loaded and extracted. RESULTS: The results of the experimental models validate the finite element models with a correlation R2 equal to 0.899 and NMSE of 7%. The implant extraction tests for the effect of bone properties in the maximum load were 2832 N for D20 and 792 N for D10. The effect of proximal bone support changes the implant stability was observed experimentally; at 1 mm less bone support decreases by 20% of stability and at 2 mm by 58% for D15 density. CONCLUSIONS: Bone properties and bone quantity are important for the initial stability of the implant. A bone volume fraction of less than 24 g/cm3 exhibits poor behavior and is not indicated for implantation. Proximal bone support reduces the primary stability of the implant and the effect is critical in lower bone density.

[Use of neurodevelopmental disorder screening tool in primary care : A multicenter observational study]. / Utilisation en soins primaires d'un outil de repérage des troubles du neurodéveloppement : étude multicentrique observationnelle.

INTRODUCTION: Neurodevelopmental disorders (NDD) affect 5 to 15% of the population. Improved management largely depends on early detection in primary care. A screening tool was developed by an expert consensus and its use has been recommended since 2019. This tool has never been evaluated to date. The aim of this study was to investigate the prevalence and factors associated with the identification of neurodevelopmental disorders in primary care in children aged 6 months to 5 years. METHOD: This work is a multicentric observational study carried out in general practice in two regions of France: Île-de-France and Auvergne-Rhône-Alpes. A multivariate analysis was performed to identify the factors associated with the presence of abnormal signs on the grid. RESULTS: Five hundred and sixty-four (564) children aged 6 months to 4 years were included. The prevalence of children identified on the grid was 3.9%. The factors associated with the neurodevelopmental disorders identified in multivariate analysis were: low socio-professional status of the mother, male gender and parental concern about the child's neurodevelopment. Factors associated with identifying a developmental trajectory gap were male gender (OR = 2.10 (1.22-3.62)) and low socio-professional status of the mother (OR = 2.23 [1.05-4.70]). CONCLUSION: This original work allowed us to carry out first-line testing of a tool for the identification of NDD in primary care and to evaluate the prevalence of identification of these disorders. A complementary cohort study will be necessary to evaluate the sensitivity and specificity of this identification tool.

The Vacinómetro® initiative: an eleven-year monitorization of influenza vaccination coverage rates among risk groups in Portugal.

Annual vaccination is fundamental for individual and group protection against seasonal influenza infection. International and Portuguese healthcare organizations have established influenza vaccination coverage rate (VCR) targets for risk groups, namely 75% in people ≥ 65 years old. The Vacinómetro® initiative has been monitoring influenza VCR among target risk groups in Portugal since 2009,: Group 1, ≥ 65 years old; Group 2, patients with chronic conditions; Group 3, healthcare workers in direct contact with patients; and Group 4, 60-64 years old. Besides VCR, social-demographic and health-related variables have been evaluated. During the study period (2009/2010 - 2019/2020), the VCR increased in the 4 target risk groups: from 58.6% to 76.0% in Group 1 (reaching the WHO target); 33.3% to 72.0% in Group 2; 25.0% to 58.9% in Group 3; and 36.6% to 42.8% in Group 4. "Physician recommendation" was the main driver for vaccination whereas "lack of habit" was the main barrier to vaccination. Vacinómetro® data demonstrate that free-of-charge vaccination has a positive impact on VCR. The observed positive trends in influenza VCR demonstrate that public health measures implemented in Portugal to facilitate access to influenza vaccine result in increased vaccine uptake. Strategies to promote population literacy and the physician's awareness should be continued and reinforced. Free-of-charge vaccination criteria extended to more risk groups would also contribute to higher influenza VCR in Portugal.

Osimertinib and anti-HER3 combination therapy engages immune dependent tumor toxicity via STING activation in trans.

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR.

Hyperphosphatemia is associated with cardiac valve calcification in chronic hypoparathyroidism.

PURPOSE: To evaluate the association between metabolic abnormalities and cardiovascular risk factors in patients with chronic hypoparathyroidism (HPP). PATIENTS AND METHODS: Patients 18 years and older, glomerular filtration > 30 mL/min/1.73 m2 and no documented coronary artery disease were selected. Serum calcium, phosphorus, glucose, lipids, PTH, 25(OH)D and FGF23 were measured. Cardiovascular risk was estimated by the European Society of Cardiology (ESC) calculator. Transthoracic echocardiogram and carotid ultrasound were performed to detect carotid plaques (CP), carotid intima-media thickness (IMT), cardiac valve calcification (CVC), and left ventricular hypertrophy (LVH). RESULTS: Thirty-seven patients (94.6% female), aged 56.0 ± 13.5 years and HPP duration 7.0 (4.0; 11.3) years, were included. Fifteen were classified as low cardiovascular risk, 9 as intermediate risk, 9 as high risk and none as very high risk. The prevalence of CP, CVC and LVH was 24.3%, 24.3% and 13.5%, respectively. IMT values were within normal ranges in all cohort. FGF23 were not associated with CP, IMT, CVC or LVH. After logistic regression, phosphorus was the only significant metabolic variable impacting CVC in univariate analysis (OR 2.795; 95% CI 1.132-6.905; p = 0.026), as well as in the multivariate analysis (OR 3.572; 95% CI 1.094-11.665; p = 0.035). Analysis by ROC curve showed serum phosphorus > 5.05 mg/dL (AUC 0.748; CI 0.584-0.877; p = 0.05) as the best cutoff point associated with valve heart calcification (sensitivity 78%; negative predictive value 91.3%). CONCLUSION: Hyperphosphatemia was associated with CVC in HPP patients. Further studies are needed to investigate whether the control of hyperphosphatemia may reduce cardiovascular risk in this population.

HIV-related non-Hodgkin lymphomas affecting the oral cavity: a clinicopathologic study of 11 cases.

BACKGROUND: HIV-related non-Hodgkin lymphomas of the oral cavity are rare lesions with aggressive clinical behaviour. The aim of this study is to describe the clinicopathological features of a series of HIV-related oral non-Hodgkin lymphomas. MATERIAL AND METHODS: Eleven cases of oral lymphomas affecting HIV-positive patients were retrieved from 2012 to 2019. Clinicopathological features regarding age, sex, tumour location, clinical presentation, laboratory findings, disease stage and follow-up were obtained. Histologic, immunohistochemical and in situ hybridization for EBV detection were done for diagnosis confirmation. Overall survival was estimated by Kaplan-Meier curve. RESULTS: Males predominated, with a mean age of 40.3 years-old. Maxilla and mandible were the mostly affected. Plasmablastic lymphoma and diffuse large B-cell lymphoma not otherwise specified (NOS) were the main histological types. Lesions presented as reddish ulcerated swellings, representing the first sign of AIDS in six cases. Stage IV were common (7 cases) and the mean HIV viral load was 10,557 copies/mL, with a mean of 266 CD4+ cells/mm3, 1,278 CD8+ cells/mm3 and a CD4+/CD8+ ratio of 0.26. Eight patients died of the disease (72.7%). Overall survival revealed that 78.2% of the patients died after 21 months of follow-up. CONCLUSIONS: HIV-related oral lymphomas present a poor prognosis usually diagnosed in advanced stages and in our series plasmablastic lymphoma was the most common subtype.

Boliviadendron, a new segregate genus of mimosoid legume (Leguminosae, Caesalpinioideae, mimosoid clade) narrowly endemic to the interior Andean valleys of Bolivia.

Phylogenetic analyses of DNA sequence data sampling all species of Leucochloron alongside representatives of genera of the Inga and Albizia clades of the larger ingoid clade of mimosoid legumes (sensu Koenen et al. 2020) confirm the non-monophyly of the genus Leucochloron. We show that Leucochloronbolivianum is placed in the Albizia clade, while the remaining four species of Leucochloron are placed in the Inga clade, in line with previous results. To rectify this non-monophyly, L.bolivianum is segregated as the new genus, Boliviadendron, with a single species, Boliviadendronbolivianum, narrowly endemic to the interior Andean valleys of Bolivia. We illustrate this new segregate genus, present a map of its distribution and discuss the striking lack of morphological distinctions between Boliviadendron and Leucochloron, as well as the phylogenetic and morphological affinities of Boliviadendron to the genera Enterolobium and Albizia.

Fecal microbiota transplantation in hepatic encephalopathy : a review of the current evidence and future perspectives.

Hepatic encephalopathy (HE) is a leading cause of hospitalization and morbimortality in advanced cirrhosis with limited therapeutic options available. Given the paramount role of gut microbiota in HE, and the efficacy of fecal microbiota transplantation (FMT) in other diseases, this review intends to summarize the evidence supporting the safety, efficacy and future perspectives of FMT in HE. Current evidence, despite being scarce, points towards FMT being a safe, effective and tolerable procedure in HE. Some unanswered questions remain about the optimal dose, the administration route, the long term effects and the selection of the optimal donor. Future trials, some of which are already underway, will provide us additional evidence and hopefully the necessary answers.

Management and biosecurity practices by small to medium egg producers in Scotland.

1. Information about procedures and biosecurity practices used by small and medium egg producers (SMEPs) is scarce. Anecdotal evidence suggests that biosecurity in such enterprises may be poor, as personnel and equipment move freely between sites and this may be compounded by personnel working on commercial units who keep their own poultry.2. To fill this knowledge gap, a questionnaire was designed and implemented targeting SMEPs in Scotland. Small enterprises were defined as egg producers that have ≥50 laying hens but <350 laying hens; while medium enterprises were defined as egg producers that have ≥350 laying hens but ≤32 000 laying hens. The questionnaire consisted of a total of 56 questions divided into multiple sections, covering the characteristics of the primary keeper, location of the enterprise and size of the flocks, husbandry, marketing of products and health/biosecurity.3. The questionnaire was posted to 375 holdings at the beginning of March 2017 and the survey remained open until the end of May 2017. In total 90 questionnaires were received by the cut-off date of which 76 questionnaires were from SMEPs. Forty were small enterprises and 36 were medium enterprises. For three questionnaires, it was not possible to identify the enterprise type.4. Differences were observed between SMEPs in terms of reported biosecurity and management practices, with medium enterprises reporting the adoption of more biosecurity measures than small enterprises. Furthermore, SMEPs behave differently from backyard poultry keepers and large commercial companies in terms of disease risk.5. In conclusion, it is important to ensure that SMEPs are considered in contingency plans and disease control programmes and that engagement with them is promoted so that the uptake of relevant information, such as awareness of disease control programmes, is optimised.