Subclinical vascular, hemodynamic and arterial stiffness changes in adults with cystic fibrosis: cross-sectional observational study.

Cardiovascular diseases can be an emerging complication in cystic fibrosis (CF), as the median life expectancy has improved considerably. The objective of this study was to compare vascular, hemodynamic parameters and arterial stiffness in adult CF patients with healthy participants pared by sex and age, and to assess the factors associated with arterial stiffness in the CF group. This is a cross-sectional observational study. The evaluation of cardiovascular parameters was performed non-invasively using Mobil-O-Graph. 36 individuals with CF and 35 controls were evaluated. The mean arterial pressure (96.71 ± 10.98 versus 88.61 ± 7.40 mmHg, p = 0.0005), cardiac output (4.86 ± 0.57 versus 4.48 ± 0.44 L/min, p = 0.002) and systolic volume (64.30 ± 11.91 versus 49.02 ± 9.31 ml, p < 0.0001) were significantly lower in the CF group. The heart rate was higher in the CF when compared to the control (77.18 ± 10.47 versus 93.56 ± 14.57 bpm, p < 0.0001). The augmentation index (AIx@75) was higher in the CF than control (29.94 ± 9.37 versus 16.52 ± 7.179%, p < 0.0001). In the multivariate model controlled by body mass index and Forced Expiratory Volume in the first second, central systolic blood pressure and reflection coefficient directly related to AIx@75. Negatively related to AIx@75 were age and systolic volume. The adjusted determination coefficient was 87.40%. Individuals with CF presented lower arterial blood pressures and changes in cardiac function with lower stroke volume and cardiac output. The AIx@75, an indirect index of arterial stiffness and direct index of left ventricular overload, is increased in this population. The subclinical findings suggest the need for earlier cardiovascular assessment in this population due to increased risks of cardiovascular disease.

Aortic pulse wave analysis and functional capacity of heart transplantation candidates: a pilot study.

We compared cardiovascular parameters obtained with the Mobil-O-Graph and functional capacity assessed by the Duke Activity Status Index (DASI) before and after Heart Transplantation (HT) and also compared the cardiovascular parameters and the functional capacity of candidates for HT with a control group. Peripheral and central vascular pressures increased after surgery. Similar results were observed in cardiac output and pulse wave velocity. The significant increase in left ventricular ejection fraction (LVEF) postoperatively was not followed by an increase in the functional capacity. 24 candidates for HT and 24 controls were also compared. Functional capacity was significantly lower in the HT candidates compared to controls. Stroke volume, systolic, diastolic, and pulse pressure measured peripherally and centrally were lower in the HT candidates when compared to controls. Despite the significant increase in peripheral and central blood pressures after surgery, the patients were normotensive. The 143.85% increase in LVEF in the postoperative period was not able to positively affect functional capacity. Furthermore, the lower values of LVEF, systolic volume, central and peripheral arterial pressures in the candidates for HT are consistent with the characteristics signs of advanced heart failure, negatively impacting functional capacity, as observed by the lower DASI score.

Breast adiposity: Menopausal status impact and its influence on glycemic and anthropometric metabolic parameters.

CONTEXT: Ectopic fat depots are related to the deregulation of energy homeostasis, leading to diseases related to obesity and metabolic syndrome (MS). Despite significant changes in body composition over women's lifespan, little is known about the role of breast adipose tissue (BrAT) and its possible utilization as an ectopic fat depot in women of different menopausal statuses. OBJECTIVE: We aimed to assess the relationship between BrAT and metabolic glycemic and lipid profiles and body composition parameters in adult women. METHODS: In this cross-sectional study, we enrolled adult women undergoing routine mammograms to perform history and physical examination, body composition assessment, semi-automated assessment of breast adiposity (BA) from mammograms and fasting blood collection for biochemical analysis. Correlations and multivariate regression analysis were used to examine the associations of the BA with metabolic and body composition parameters. RESULTS: Of the 101 participants included in the final analysis, 76.2% were in menopause, and 23.8% were in premenopause. The BA was positively related with fasting plasma glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, body mass index, waist circumference, body fat percentage, abdominal visceral and subcutaneous fat when adjusted for age among women in postmenopause. Also, the BA was an independent predictor of hyperglycemia and metabolic syndrome. These associations were not present among women in premenopause. CONCLUSION: The BA was related to different adverse body composition and metabolic factors in women in postmenopause. The results suggest that there might be a relevant BrAT endocrine role during menopause, whose mechanisms are yet to be clarified, which thus opens up research perspectives on the subject as well as on clinical settings.

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.

Global representativeness and impact of funding sources in cost-effectiveness research on systemic therapies for advanced breast cancer: A systematic review.

BACKGROUND: Breast cancer (BC) is the most incident tumor and, consequently, any new intervention can potentially promote a considerable budget impact if incorporated. Cost-effectiveness (CE) studies assist in the decision-making process but may be influenced by the country's perspective of analysis and pharmaceutical industry funding. METHODS: A systematic review of Medline, Scopus, and Web of Science from January 1st, 2012 to July 8th, 2022 was conducted to identify CE studies of tumor-targeted systemic-therapies for advanced BC. Articles without incremental cost-effectiveness ratio calculations were excluded. We extracted information on the country and class of drug studied, comparator type, authors' conflicts of interest (COI), pharmaceutical industry funding, and authors' conclusions. RESULTS: 71 studies comprising 204 CE assessments were included. The majority of studies were from the United States and Canada (44%), Asia (32%) and Europe (20%). Only 8% were from Latin America and none from Africa. 31% had pharmaceutical industry funding. The most studied drug classes were cyclin-dependent-kinase inhibitors (29%), anti-HER2 therapy (23%), anti-PD(L)1 (11%) and hormone therapy (11%). Overall, 34% of CE assessments had favorable conclusions. Pharmaceutical industry-funded articles had a higher proportion of at least one favorable conclusion (82% vs. 24%, p-value<0.001), European countries analyzed (45% vs. 9%, p-value = 0.003), and CE assessments with same class drug comparators (56% vs. 33%, p-value = 0.004). CONCLUSIONS: Breast cancer CE literature scarcely represents low-and-middle-income countries' perspectives and is influenced by pharmaceutical industry funding which targets European countries', frequently utilizes comparisons within same-drug class, and is more likely to have favorable conclusions.

Recurrent Plunging Ranula Due to a Sublingual Ectopic Gland: A Rare Clinical Entity.

Ranula is a benign cystic lesion caused by the escape and collection of salivary mucus. Classically, it is divided into simple ranulas, a cystic mass in the floor of the mouth, and diving/plunging/cervical ranulas, a submandibular mass without apparent intraoral involvement. Although plunging ranula is a well-documented cause of neck swelling, its association with the presence of ectopic sublingual glands is extremely rare, with less than five cases reported. Other cervical cystic lesions may have the same clinical aspect; therefore, advanced diagnostic techniques like a CT scan or MRI play a critical role in early diagnosis. Different approaches have been used to treat ranulas, including non-invasive, minimally invasive, and surgical techniques. The purpose of this paper is to highlight a case report of a giant plunging ranula due to an anatomical aberration of the right sublingual gland, along with a significant literature review.

Hereditary epidermolysis bullosa: clinical-epidemiological profile of 278 patients at a tertiary hospital in São Paulo, Brazil.

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare hereditary diseases, characterized by fragility of the skin and mucous membranes. Epidemiological data on EB in Brazil are scarce. OBJECTIVES: To describe epidemiological aspects of patients with EB diagnosed in the Dermatology Department of a tertiary hospital, from 2000 to 2022. METHODS: An observational and retrospective study was conducted through the analysis of medical records. The evaluated data included clinical form, sex, family history, consanguinity, age at diagnosis, current age, time of follow-up, comorbidities, histopathology and immunomapping, presence of EB nevi and squamous cell carcinomas (SCC), cause of and age at death. RESULTS: Of 309 patients with hereditary EB, 278 were included. The most common type was dystrophic EB (DEB), with 73% (28.4% dominant DEB, 31.7% recessive DEB and 12.9% pruriginous DEB). Other types were junctional EB with 9.4%, EB simplex with 16.5% and Kindler EB with 1.1%. Women accounted for 53% and men for 47% of cases. Family history was found in 35% and consanguinity in 11%. The mean age at diagnosis was 10.8 years and the current age was 26 years. The mean time of follow-up was nine years. Esophageal stenosis affected 14%, dental alterations affected 36%, malnutrition 13% and anemia 29%. During diagnostic investigation, 72.6% underwent histopathological examination and 92% underwent immunomapping. EB nevi were identified in 17%. Nine patients had SCC. Eleven patients died. STUDY LIMITATIONS: Insufficient data included to medical records, loss to follow-up, and unavailability of genetic testing. CONCLUSIONS: In this study, dystrophic EB predominated and the need for multidisciplinary care for comorbidities and complications was highlighted.

Advantages of whole-exome sequencing over immunomapping in 67 Brazilian patients with epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) is characterized by skin fragility and blistering. In Brazil, the diagnosis is usually obtained through immunomapping, which involves a skin biopsy. Most recently, whole exome sequencing (WES) has become an important tool for the diagnosis of the subtypes of EB, providing information on prognosis as well as allowing appropriate genetic counseling for the families. OBJECTIVE: To compare the results of immunomapping and molecular analysis and to describe the characteristics of a Brazilian cohort of patients with EB. METHODS: Patients were submitted to clinical evaluation and WES using peripheral blood samples. WES results were compared to those obtained from immunomapping testing from skin biopsies. RESULTS: 67 patients from 60 families were classified: 47 patients with recessive dystrophic EB (DEB), 4 with dominant DEB, 15 with EB simplex (EBS), and 1 with junctional EB (JEB). Novel causative variants were: 10/60 (16%) in COL7A1 associated with recessive DEB and 3 other variants in dominant DEB; one homozygous variant in KRT5 and another homozygous variant in PLEC, both associated with EBS. Immunomapping was available for 59 of the 67 patients and the results were concordant with exome results in 37 (62%), discordant in 13 (22%), and inconclusive in 9 patients (15%). STUDY LIMITATIONS: Even though EB is a rare disease, for statistical purposes, the number of patients evaluated by this cohort can still be considered limited; other than that, there was a significant difference between the proportion of types of EB (only one case with JEB, against more than 50 with DEB), which unfortunately represents a selection bias. Also, for a small subset of families, segregation (usually through Sanger sequencing) was not an option, usually due to deceased or unknown parent status (mostly the father). CONCLUSION: Although immunomapping has been useful in services where molecular studies are not available, this invasive method may provide a misdiagnosis or an inconclusive result in about 1/3 of the patients. This study shows that WES is an effective method for the diagnosis and genetic counseling of EB patients.

Claudin 18.2 as a New Biomarker in Gastric Cancer-What Should We Know?

Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive. This review navigates the evolving landscape of GC biomarkers, with a specific focus on Claudin 18.2 (CLDN18.2) as an emerging and promising target. Recent phase III trials have unveiled the efficacy of Zolbetuximab, a CLDN18.2-targeting antibody, in combination with oxaliplatin-based chemotherapy for CLDN18.2-positive metastatic GC. As this novel therapeutic avenue unfolds, understanding the nuanced decision making regarding the selection of anti-CLDN18.2 therapies over other targeted agents in metastatic GC becomes crucial. This manuscript reviews the evolving role of CLDN18.2 as a biomarker in GC and explores the current status of CLDN18.2-targeting agents in clinical development. The aim is to provide concise insights into the potential of CLDN18.2 as a therapeutic target and guide future clinical decisions in the management of metastatic GC.

ENAM gene polymorphisms associated with dental anomalies in individuals with cleft lip and palate

Aim: This study aimed to investigate the occurrence of enamelin gene (ENAM) single nucleotide polymorphisms (SNP) and ENAM polymorphism association with dental anomalies (DA) in individuals with unilateral or bilateral cleft lip and palate (CLP). Methods: Saliva samples were collected from 147 individuals aged between 6 and 15 years-old, both genders, and divided into 4 groups: Group 1 (G1) - CLP and DA; Group 2 (G2) - CLP without DA; Group 3 (G3) - without CLP with DA; Group 4 (G4) - without CLP and DA. The genomic DNA was extracted from saliva samples and the following ENAM SNPs markers were genotyped: rs3796703, rs3796704, rs3796705, rs7671281, rs2609428, and rs35951442. Fisher exact and Pearson's Chi-square tests statistically analyzed the results (α=5%). Results: Individuals without CLP with DA (Group 3 - 19.2%) showed statistically higher prevalence of SNP rs2609428 heterozygotes (p=0.006) than individuals with CLP and DA (Group 1 - 0%). Individuals without CLP (10%) exhibited statistically higher prevalence of mutated heterozygotes/homozygous (p=0.028) than in individuals with CLP (1.3%). Conclusion: SNP rs2609428 marker of ENAM gene may be associated with dental anomalies in individuals without cleft lip and palate

Undergraduate dental students and dentists' acceptability and knowledge about selective caries tissue removal / Aceitabilidade e conhecimento sobre remoção seletiva de tecido cariado de graduandos em odontologia e cirurgiões-dentistas

Objetivo: Avaliar a aceitabilidade e o conhecimento de estudantes de graduação em Odontologia e cirurgiões-dentistas sobre a remoção seletiva de tecido cariado (RSTC). Materiais e Métodos: Participaram do estudo graduandos do terceiro e quarto ano de Odontologia (Grupo 1) e egressos de um Centro Hospitalar de Odontologia (Grupo 2). Os participantes responderam de forma anônima e confidencial um questionário validado contendo onze questões sobre diagnóstico e manejo de lesões cariosas profundas. Teste qui-quadrado de Pearson e regressão logística multivariada foram aplicados (p<0.05). Resultados: A amostra total foi composta por 146 participantes. Destes, 81.5% eram do sexo feminino; 52.05% eram graduados e a faixa etária mais prevalente foi de 18 a 29 anos (85.62%). Sessenta e nove participantes escolheram o tratamento expectante (p=0.027). A análise de regressão logística mostrou diferenças estatisticamente significativas. Os participantes que consideraram a parede pulpar úmida têm aproximadamente oito vezes mais chances de escolha pelo tratamento invasivo (p=0.028). Aqueles que escolheram o tratamento endodôntico como opção de sobrevida em dois anos têm três vezes mais chances de optar pelo tratamento invasivo (p=0.032). Aqueles que afirmaram que a dentina cariada próxima à polpa não deveria ser removida tiveram quase três vezes mais chances de optar por tratamentos minimamente invasivos (p=0.031). Discussão: Estudos com questionários podem ser ferramentas úteis para detectar se estudantes e cirurgiões-dentistas estão seguindo as evidências mais atuais para o tratamento de lesões cariosas profundas. Conclusão: Os participantes tinham certo nível de conhecimento sobre RSTC, mas a aceitabilidade da técnica carecia de consenso.

Aim: The aim of this study was to evaluate the acceptability and knowledge of undergraduate dental students and dentists on selective caries tissue removal (SCTR). Materials and Methods: Third- and fourth-year Dentistry undergraduates (Group 1) and graduates working in a Hospital Dentistry Center (Group 2) were included in the study. Participants anonymously and confidentially answered a validated questionnaire containing eleven questions on the diagnosis and management of deep caries lesions. Pearson's Chi-square test and multivariate logistic regression compared the answers (p<0.05). Results: Total sample comprised 146 participants. Of these, 81.5% were female; 52.05% were graduates and the most prevalent age group was 18-29 years old (85.62%). Sixty-nine participants chose stepwise caries removal (p=0.027). The logistic regression analysis showed statistically significant differences. The participants who considered pulp wall moist have approximately eight times more likelihood to choose an invasive treatment (p=0.028). Those who chose endodontic treatment as an option for two-year survival have three times more likelihood to choose an invasive treatment (p=0.032). Those who affirmed that the carious dentin close to the pulp should not be removed had almost three times more likelihood to choose minimally invasive treatments (p=0.031). Discussion: Studies with questionnaires can be useful tools to detect whether the students and dentists are following the most current evidences to treat deep carious lesions. Conclusion: The participants had certain level of knowledge on SCTR, but the technique acceptability lacked consensus.

Nível de ruídos na unidade neonatal / Noise level in the neonatal unit / Nivel de ruido en la unidad neonatal

Objetivo: verificar os níveis de pressão sonora, a influência do turno e das ocorrências nesses níveis em uma unidade neonatal do Rio de Janeiro. Método: estudo longitudinal, exploratório, descritivo, com dados coletados entre novembro de 2021 e janeiro de 2022. As variáveis categóricas foram descritas por meio de frequências absoluta e relativa. A aderência à distribuição normal foi verificada pelo teste Shapiro-Wilk. Para a análise da associação entre variáveis de exposição e desfecho, utilizou-se teste Mann-Whitney, Kruskal Wallis e Qui-quadrado. Considerou-se estatisticamente significativos resultados de p<0,05. Resultados: foram coletados 10.122 registros de decibéis e 56 eventos relacionados as atividades, que ocorreram predominantemente no período diurno. Houve variação de 38,6 a 93,1 decibéis (dB). Em 96,3% do período observado, os níveis de pressão sonora estiveram acima do recomendado. Na comparação entre os períodos, o noturno apresentou menores níveis (p=0,000). Conclusão: os níveis de pressão sonora registrados estão acima do recomendado para um ambiente seguro(AU)

Objective: to verify the sound pressure levels (SPL) and the influence of the shift and the occurrences in these levels in a neonatal unit in Rio de Janeiro. Method: longitudinal, exploratory, descriptive study. Collected from November 2021 to January 2022. Categorical variables were described using absolute and relative frequencies. To verify adherence to the normal distribution, the Shapiro-Wilk test was used. For the association between exposure and outcome variables, the Mann-Whitney, Kruskal Wallis and Qui-square tests were used. Results of p < 0.05 were considered statistically significant. Results: 10,122 decibel records and 56 events related to activities were collected, these occurred predominantly during the day. There was a variation from 38.6 to 93.1 decibels (dB). In 96.3% of the observed period, the NPS were above the recommended. Comparing the periods, nighttime had lower SPL (p=0.000). Conclusion: the registered NPS are above the recommended for a safe environment(AU)

Objetivo: Verificar los niveles de presión sonora y la influencia del turno y de las incidencias en esos niveles en una unidad neonatal en Rio de Janeiro. Método: Estudio longitudinal, exploratorio, descriptivo, cuyos datos se recopilaron de noviembre de 2021 a enero de 2022. Las variables categóricas se describieron mediante frecuencias absoluta y relativa. Para verificar la adherencia a la distribución normal se utilizó la prueba de Shapiro-Wilk. Para el análisis de la asociación entre variables de exposición y de resultado se utilizaron las pruebas de Mann-Whitney, Kruskal Wallis y Qui-quadrado. Los resultados de p < 0,05 se consideraron estadísticamente significativos. Resultados: se recolectaron 10.122 registros de decibelios y 56 eventos relacionados con actividades, que ocurrieron predominantemente durante el día. Hubo una variación de 38,6 a 93,1 decibelios (dB). En el 96,3% del período observado, los niveles de presión sonora estuvieron por encima de lo recomendado. Comparando los períodos, el nocturno presentó niveles más bajos (p=0,000). Conclusión: Los niveles de presión sonora registrados están por encima de lo recomendado para un ambiente seguro(AU)

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.

Impact of social isolation during COVID-19 on anthropometric data, quality of life, baseline physical activity and aortic pulse wave parameters in children and adolescents in two independent samples.

BACKGROUND: The social restrictions resulting from the COVID-19 pandemic had a great impact on the routine of children and adolescents, with important consequences such as sleep, eating, and psychological/psychiatric disorders. Even though there are no studies on the subject, it is possible that these changes in habit and routine have also affected arterial stiffness (AS) in this population, which is an important predictor of cardiovascular risk. This study aimed to assess possible changes in AS, anthropometry, and quality of life (QoL) resulting from the COVID-19 pandemic in children and adolescents. METHODS: A controlled observational cross-sectional study was performed with 193 children and adolescents aged 9 to 19 years, allocated into two groups: before the pandemic (BPG) and one year after the pandemic (APG), matched by age and sex. Cardiovascular parameters were measured non-invasively by brachial artery oscillometry with a portable device. The main AS indices evaluated were the augmentation index (AIx) and pulse wave velocity (PWV) derived from the aortic pulse wave. QoL was assessed using the Paediatric Quality of Life Inventory version 4.0 (PedsQL 4.0). RESULTS: Regarding QoL, the APG showed a worsening in emotional (p = 0.002) and school-related (p = 0.010) aspects. There was no statistically significant difference for most anthropometric parameters, except for the hip circumference, which was higher in the APG group (p < 0.001). The main predictor of AS in the paediatric population, AIx@75, was shown to be increased in the APG group (p < 0.001). Other cardiovascular parameters were also different, such as peripheral (p = 0.002) and central (p = 0.003) diastolic blood pressure, stroke volume (p = 0.010), and total vascular resistance (p = 0.002), which were shown to be decreased in the APG group, while the heart rate was increased (p < 0.001). CONCLUSIONS: Our results show that routine changes resulting from the period of social isolation increased cardiovascular risk in children and adolescents, evident by the increase in AIx@75, which is considered to be an important marker of cardiovascular risk in the paediatric population.

Targeting KRAS in Pancreatic Ductal Adenocarcinoma: The Long Road to Cure.

Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer-related mortality, and it is expected to play an even bigger part in cancer burden in the years to come. Despite concerted efforts from scientists and physicians, patients have experienced little improvement in survival over the past decades, possibly because of the non-specific nature of the tested treatment modalities. Recently, the discovery of potentially targetable molecular alterations has paved the way for the personalized treatment of PDAC. Indeed, the central piece in the molecular framework of PDAC is starting to be unveiled. KRAS mutations are seen in 90% of PDACs, and multiple studies have demonstrated their pivotal role in pancreatic carcinogenesis. Recent investigations have shed light on the differences in prognosis as well as therapeutic implications of the different KRAS mutations and disentangled the relationship between KRAS and effectors of downstream and parallel signaling pathways. Additionally, the recognition of other mechanisms involving KRAS-mediated pathogenesis, such as KRAS dosing and allelic imbalance, has contributed to broadening the current knowledge regarding this molecular alteration. Finally, KRAS G12C inhibitors have been recently tested in patients with pancreatic cancer with relative success, and inhibitors of KRAS harboring other mutations are under clinical development. These drugs currently represent a true hope for a meaningful leap forward in this dreadful disease.

Condições de trabalho e biossegurança dos profissionais de saúde e trabalhadores invisíveis da saúde no contexto da COVID-19 no Brasil / Work conditions and biosafety of health professionals and invisible health workers in the context of COVID-19 in Brazil

Resumo O artigo versa sobre as condições de trabalho na saúde no contexto da pandemia no Brasil. Trata-se de estudo transversal que utilizou dados de recorte das pesquisas "Condições de trabalho dos profissionais de saúde no contexto da Covid-19 no Brasil" e "Os Trabalhadores invisíveis da saúde: condições de trabalho e saúde mental no contexto da Covid-19 no Brasil", objetivando conhecer as condições de trabalho e a biossegurança desses dois contingentes profissionais distintos e desiguais, socialmente. A análise dos dados comprova que as condições de trabalho foram extremamente afetas em função da infraestrutura inadequada, trabalho extenuante, biossegurança em risco, exaustão, medo da contaminação e da morte, fortes sinais de esgotamento físico e mental entre os trabalhadores. Aponta também para discriminação e desigualdades de direitos sociais e de valorização profissional que demarcam os mundos do trabalho apontados nas pesquisas, enfatizando as profundas desigualdades existentes no Brasil e em suas regiões. Conclui-se mostrando a importância de formulação de políticas públicas no âmbito da gestão do trabalho no SUS que assegurem a proteção, valorização e redução das desigualdades apontadas no artigo.

Abstract The present article addresses the work conditions in health in the context of the COVID-19 pandemic in Brazil. This is a cross-sectional study that used data from the surveys "Working conditions of healthcare professionals in the context of Covid-19 in Brazil" and "Invisible healthcare workers: work conditions and mental health in the context of Covid-19 in Brazil", seeking to better understand the working conditions and biosafety of these two distinct and socially unequal professional contingents. Data analysis proves that work conditions were extremely affected due to inadequate infrastructures, strenuous work, biosecurity at risk, exhaustion, fear of contamination and death, strong signs of physical and mental exhaustion, among workers. It also points out the discrimination and inequalities of social rights and professional development that mark the worlds of work highlighted in the surveys, emphasizing the profound inequalities that exist in Brazil and in its regions. It concludes by showing the importance of formulating public policies within the scope of work management in SUS, which ensures the protection, appreciation and reduction of inequalities pointed out in this article.

Transformações no mundo do trabalho em saúde: os(as) trabalhadores(as) e desafios futuros / Transformations in the world of healthcare work: workers and future challenges

Resumo O artigo versa sobre o mundo do trabalho da saúde, especialmente no SUS no contexto da pandemia no Brasil. O artigo utilizou dados das pesquisas "Condições de trabalho dos profissionais de saúde no contexto da COVID-19 no Brasil" e "Os trabalhadores invisíveis da saúde: condições de trabalho e saúde mental no contexto da COVID-19 no Brasil". A análise dos dados comprova que a pandemia evidenciou problemas estruturais existentes no âmbito do Sistema Único de Saúde, envolvendo a gestão da FTS o que pode ser interpretado como mais um dos reflexos das desigualdades socioeconômicas já existentes no país. Destacam-se: a reduzida oferta de educação permanente, a regulação do cuidado híbrido, precarização, desproteção no ambiente de trabalho, frágil biossegurança levando a trágicas taxas de adoecimento e mortes de trabalhadores da saúde. Conclui mostrando a importância de formulação de políticas públicas no âmbito da gestão da educação e do trabalho no SUS que assegurem a discussão sobre cuidado híbrido como nova forma de atuar sem perder qualidade, a necessidade de se rever questões referentes a: educação permanente, proteção, valorização e redução das desigualdades apontadas entre os contingentes profissionais analisados nesse artigo.

Abstract This article addresses the world of healthcare work, especially in the Brazilian Unified Healthcare System (SUS) in the context of the COVID-19 pandemic in Brazil. This study used data from the following surveys: "Working conditions of health professionals in the context of COVID-19 in Brazil" and "The Invisible health workers: working conditions and mental health in the context of COVID-19 in Brazil". Data analysis proves that the pandemic highlighted existing structural problems within SUS, involving the issue of healthcare workforce (HWF) management, which can be interpreted as another reflection of the socioeconomic inequalities that already exist in the country. This article highlights: the reduced provision of permanent education, the regulation of hybrid care, precariousness, a lack of protection in the work environment, as well as fragile biosecurity leading to tragic rates of illness and death of health workers. Our study concludes by showing the importance of formulating public policies in the scope of education and work management in SUS that ensure the discussion on hybrid care as a new way of acting without losing quality, together with the need to review issues related to permanent education, protection, valuation, and reduction of inequalities pointed out among the professional contingents analyzed in this article.

A precarização jurídica das relações de trabalho como fator de sofrimento das(os) trabalhadoras(es) no setor da saúde durante a pandemia de COVID-19 / The legal precariousness of work relations in the health sector during the COVID-19 pandemic, as a factor of worker suffering

Resumo O artigo analisou o processo de precarização das relações de trabalho no setor da saúde, demonstrando como essa situação gerou sofrimento dos trabalhadores. O texto buscou registrar como a adoção institucional das concepções econômicas neoliberais, de redução das políticas sociais de Estado, acopladas a um histórico de rejeição cultural aos direitos trabalhistas, proporcionou a atração dos mecanismos de precarização do trabalho, notadamente, a terceirização da mão de obra e da prestação de serviços. No segundo momento, o texto aponta as impropriedades jurídicas cometidas, apresentando as consequências da fragilização do vínculo jurídico nas condições de trabalho desses trabalhadores, principalmente no que se refere às jornadas de trabalho e a remuneração, destacando-se, também, o quanto a disseminação desses vínculos representou um fator de rebaixamento geral dos salários e direitos trabalhistas e previdenciários no setor. Foram apresentados, ainda, dados das pesquisas da Fiocruz sobre condições de trabalho durante a pandemia. Conclui mostrando a urgência de se resgatarem os institutos jurídicos trabalhistas que foram abandonados no percurso histórico estudado, para direcionar a novo rumo as políticas públicas na saúde.

Abstract The present article analyzed the process of precarious work relations in the health sector, demonstrating how this situation generated illness and suffering among workers. The text sought to register how the institutional adoption of neoliberal economic conceptions, of the reduction of State social policies, coupled with a history of cultural rejection of labor rights, provided the attraction of mechanisms of precarious work for the public sector, notably, the outsourcing of labor and the provision of services. In a second moment, the text points out the legal improprieties committed, presenting the consequences of the weakening of the legal bond in the working conditions of these workers, mainly regarding working hours and remuneration, also highlighting how much the dissemination of these links represented a factor of a general reduction in wages and labor and social security rights in the sector. Data from Fiocruz surveys on working conditions during the pandemic were also presented. The article concludes by showing the urgency of rescuing the legal labor institutes that were abandoned in the historical path studied in order to guide the public health policies in a new direction.

Shaping ability of a pediatric motor-driven instrumentation system in primary molar root canal prototypes

Abstract Evaluate the shaping ability and preparation time using a pediatric motor-driven rotary instrumentation compared to other systems in resin prototypes of primary molars. Methods: Thirty specimens were scanned in micro-CT and divided into three groups according to the instrumentation type: pediatric motor-driven Sequence baby File (SBF); conventional motor-driven (Sequence Rotary File - SRF); manual K file. Instrumentation time was timed. After preparation, the specimens were scanned again. The pre- and post-instrumentation images were superimposed to measure the amount of root canal deviation and the resin remnant thickness. ANOVA followed by the Tukey test analyzed the comparisons between groups (p<0.05). Results: No statistically significant differences occurred in root canal deviation among groups (p>0.05). There were statistically significant differences in the comparison among root thirds (p<0.001) but without significant differences in the interaction group vs. root third (p>0.05). Both motor-driven instrumentations showed statistically greater weariness than manual instrumentation (p<0.001), without significant significant differences between SBF and SRF. Motor-driven instrumentation had a shorter working time than manual instrumentation (p<0.001). Conclusion: Pediatric motor-driven instrumentation demonstrated good outcomes in relation to root canal deviation and amount of remnant structure, with shorter instrumentation time. SBF can be a suitable alternative for endodontic instrumentation in primary molars.

Resumo Objetivo: Avaliar os resultados da instrumentação endodôntica e o tempo de preparo de lima odontopediátrica ativada por motor (Sequence Baby File- SBF) em canais de molares decíduos prototipados. Métodos: Trinta espécimes foram escaneados em micro-CT e divididos em três grupos de acordo com o tipo de instrumentação: mecanizada odontopediátrica (SBF); mecanizada convencional; lima K manual. O tempo de instrumentação foi cronometrado. Após o preparo, os espécimes foram escaneados novamente. As imagens pré e pós-instrumentação foram sobrepostas e a quantidade de desvio do canal radicular e a espessura de resina remanescente foram mensurados. Para as análises de comparações entre os grupos foram realizados teste ANOVA seguido do teste de Tukey (p<0,05). Resultados: Não ocorreram diferenças estatisticamente significativas entre os grupos no desvio do canal radicular (p>0,05). Houve diferenças estatisticamente significativas na comparação entre terços radiculares (p<0,001), mas sem diferenças significativas na interação grupo vs. terço radicular (p>0,05). A instrumentação mecanizada apresentou desgaste estatisticamente maior do que a instrumentação manual (p<0,001), sem diferenças estatísticas entre a SBF e a lima mecanizada convencional. A instrumentação mecanizada teve menor tempo de trabalho quando comparado a instrumentação manual (p<0,001). Conclusão: A instrumentação mecanizada odontopediátrica demonstrou bons resultados em relação ao desvio do canal radicular e quantidade de estrutura remanescente, com menor tempo de instrumentação. A SBF pode ser uma alternativa adequada para a instrumentação endodôntica em molares decíduos.