INSTRUCTIONAL SKILLS AND COMPETENCY SKILLS THEORY IN MODERN TEACHING

The study aims to identify the contribution of instructional skills and competency skills theory in modern teaching as to classroom management, instructional delivery, formative assessment, personal competency, flexibility and adaptability, facilitation and engagement, collaboration and teamwork, communication and interpersonal skills, caring and inclusiveness, and organization and planning. The research design utilizes the descriptive correlational method because it generates and refines knowledge on instructional skills and competency skills theory in modern teaching. Hence, convenience and non-probability sampling are employed in the study. It provides inclusion gathering of sample size instructional skills and competency skills theory in modern teaching. The study comprised sixty (60) respondents only. Results show that approaches and practices support the learning routine of students for dynamic behavior to minimize emotional exhaustion beneficial in fostering strategy for higher-quality classroom management. It influences and practices personal competency to support the development of learning process network, and resources. It provides changes and practices on the adjusted curriculum, instructional methods and modern teaching technology. It demonstrates understanding on proper plan, learning process, and pace time demand in prioritizing realistic instructional skills and competency skills to implement individualized instructional resources learning process. Findings show that there is a significant agreement on the contribution of instructional skills and competency skills theory in modern teaching as observed by the respondents.  Article visualizations

Um Caso Clínico de Lepra Multibacilar com Vários Surtos de Eritema Nodoso Leproso

Leprosy is a chronic granulomatous disease with a long incubation period caused by Mycobacterium leprae that mainly affects the skin, mucous membranes and the peripheral nervous system. It carries the risk of per-manent sequels with a significant impact on the patient’s quality of life. It has a considerable clinically diver-sity and possible atypical presentations. We present a case of a 31-year-old, skin phototype V woman with multibacillary leprosy characterized by multiple outbreaks of erythema nodosum leprosum, as an inaugural manifestation of the disease. The disease was acquired within a group of children and adolescents from an endemic region of Africa, evolved untreated for 3 years, and presented with unusual features and remarkable lymphatic involvement. We highlight the importance of building and maintaining collaboration between expert centers and institutional partnerships in order to provide the adequate diagnostic resources and appropriate care to the affected populations.A lepra é uma doença granulomatosa crónica com longo período de incubação causada pelo bacilo Mycobacte- -rium leprae que afeta principalmente a pele, mucosas e sistema nervoso periférico. Tem risco de sequelas permanentes e impacto significativo na qualidade de vida do paciente. É clinicamente heterogénea com possíveis apresentações atípicas. Descrevemos o caso de uma mulher de 31 anos, fototipo V, com lepra multibacilar caracterizada por múltiplos surtos de eritema nodoso leproso como manifestação inaugural. A doença foi adquirida num grupo de crianças e adolescentes de uma região endémica de África, evoluiu sem tratamento durante 3 anos, e manifestou-se com algumas características clínicas incomuns e notável envolvimento linfático. Destacamos a importância da colaboração entre centros especializados e parcerias institucionais, a fim de fornecer os recursos de diagnósti-co e os cuidados adequados às populações afetadas

Lower prevalence of congenital cytomegalovirus infection in Portugal: possible impact of COVID-19 lockdown?

Cytomegalovirus (CMV) is the most frequent cause of congenital infection all over the world. Its prevalence ranges from 0.2 to 2.2%. Transmission from children to their pregnant mothers is a well-known risk factor, particularly if they attend a childcare centre. This study aims to compare the prevalence of CMV congenital infection (CMV_CI) in Portugal (Lisbon) between two studies, performed respectively in 2019 and 2020. In the 2019 study, performed in two hospitals, we found a 0.67% CMV_CI prevalence, using a pool strategy previously tested with saliva samples. In the 2020 study, using the same pool approach in four hospitals (the previous and two additional), and based on 1277 samples, the prevalence was 0.078%.Conclusion: The close temporal coincidence with COVID-19 lockdown suggests that these measures may have had a significant impact on this reduction, although other explanations cannot be ruled-out. What is Known: • Cytomegalovirus is the leading cause of congenital infection. • Behavioural measures decrease cytomegalovirus seroconversion in pregnant women. What is New: • From 2019 to 2020 there was a significant reduction in the prevalence of congenital CMV infection.info:eu-repo/semantics/publishedVersio

The Newborn in the Emergency Department - What Triage?

Introdução: Os recém-nascidos que recorrem ao serviço de urgência pediátrico requerem uma triagem que priorize o seu atendimento. Os objetivos deste estudo foram caracterizar os recém-nascidos admitidos no serviço de urgência pediátrico, determinar se a triagem pelo Sistema de Triagem de Manchester se adequou à gravidade das condições apresentadas e, adicionalmente, calcular a sua sensibilidade e especificidade. Métodos: Estudo observacional transversal com colheita retrospetiva de dados de recém-nascidos no serviço de urgência pedi- átrico, triados com o Sistema de Triagem de Manchester entre agosto de 2011 e julho de 2012. Resultados: Os recém-nascidos constituíram 0,8% (n = 281) das admissões no serviço de urgência pediátrico. A maioria (81,1%) recorreu sem referenciação. Não se verificou uma associação entre referenciação e diagnóstico da alta. Os recém-nascidos foram maioritariamente triados com o nível “pouco / não urgente” (174/281; 61,9%) mas destes, 46 (27%) apresentavam “patologia com necessidade de cuidados médicos hospitalares” e 16 (9%) foram internados / transferidos. Não se verificou uma associação entre utilização de recursos hospitalares / destino da alta e prioridade atribuída pelo Sistema de Triagem de Manchester, tendo este uma sensibilidade e especificidade calculadas de 47,1% e 66,1%, respetivamente. Discussão: Aproximadamente 70% das idas ao serviço de urgência pediátrico foram consideradas clinicamente injustificadas. Deve ser fortalecida a relação dos cuidadores com os cuidados de saúde primários e enfatizada formação em perinatologia. A triagem efetuada pelo Sistema de Triagem de Manchester revelou uma baixa sensibilidade e especificidade, parecendo não estar adaptada à amostra de recém-nascidos. Deverá ser atribuído um fator diferenciador ao recém-nascido na triagem. São necessários mais estudos aleatorizados que testem a validação do Sistema de Triagem de Manchester nesta população

Prevention and contrast of child abuse and neglect in the practice of European paediatricians: a multi-national pilot study

Background: Child abuse and neglect, or maltreatment, is a serious public health problem, which may cause long-term effects on children's health and wellbeing and expose them to further adulthood vulnerabilities. Studies on child maltreatment performed in Europe are scarce, and the number of participants enrolled relatively small. The aim of this multi-national European pilot study, was to evaluate the level of understanding and perception of the concepts of child abuse and neglect by European paediatricians working in different medical settings, and the attitude toward these forms of maltreatment in their practice. Methods: The study was performed by a cross-sectional, descriptive, online survey, made available online to European paediatricians members of 50 national paediatric, who belonged to four different medical settings: hospital, family care, university centres and private practice. The questionnaire, designed as a multiple choice questions survey, with a single answer option consisted of 22 questions/statements. Frequency analyses were applied. Most of the data were described using univariate analysis and Chi-squared tests were used to compare the respondents and answers and a significance level of p ≤ 0.05 applied. Results: Findings show that European paediatricians consider the training on child maltreatment currently provided by medical school curricula and paediatric residency courses to be largely insufficient and continuing education courses were considered of great importance to cover educational gaps. Physical violence was recognized by paediatricians mostly during occasional visits with a significant correlation between detecting abuse during an occasional visit and being a primary care paediatrician. Results also showed a reluctance by paediatricians to report cases of maltreatment to the competent judicial authorities. Conclusions: Data of this study may provide useful contribution to the current limited knowledge about the familiarity of European paediatricians with child maltreatment and their skills to recognize, manage and contrast abusive childhood experiences in their practice. Finally, they could provide local legislators and health authorities with information useful to further improve public health approaches and rules able to effectively address shared risk and protective factors, which could prevent child abuse and neglect from ever occurring

CD112 Supports Lymphatic Migration of Human Dermal Dendritic Cells

Dendritic cell (DC) migration from peripheral tissues via afferent lymphatic vessels to draining lymph nodes (dLNs) is important for the organism’s immune regulation and immune protection. Several lymphatic endothelial cell (LEC)-expressed adhesion molecules have thus far been found to support transmigration and movement within the lymphatic vasculature. In this study, we investigated the contribution of CD112, an adhesion molecule that we recently found to be highly expressed in murine LECs, to this process. Performing in vitro assays in the murine system, we found that transmigration of bone marrow-derived dendritic cells (BM-DCs) across or adhesion to murine LEC monolayers was reduced when CD112 was absent on LECs, DCs, or both cell types, suggesting the involvement of homophilic CD112–CD112 interactions. While CD112 was highly expressed in murine dermal LECs, CD112 levels were low in endogenous murine dermal DCs and BM-DCs. This might explain why we observed no defect in the in vivo lymphatic migration of adoptively transferred BM-DCs or endogenous DCs from the skin to dLNs. Compared to murine DCs, human monocyte-derived DCs expressed higher CD112 levels, and their migration across human CD112-expressing LECs was significantly reduced upon CD112 blockade. CD112 expression was also readily detected in endogenous human dermal DCs and LECs by flow cytometry and immunofluorescence. Upon incubating human skin punch biopsies in the presence of CD112-blocking antibodies, DC emigration from the tissue into the culture medium was significantly reduced, indicating impaired lymphatic migration. Overall, our data reveal a contribution of CD112 to human DC migration

Therapy-induced tumour secretomes promote resistance and tumour progression.

Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer. Here we show that targeted therapy with BRAF, ALK or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed human and mouse melanoma and human lung adenocarcinoma cells. This therapy-induced secretome stimulates the outgrowth, dissemination and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, contributing to incomplete tumour regression. The tumour-promoting secretome of melanoma cells treated with the kinase inhibitor vemurafenib is driven by downregulation of the transcription factor FRA1. In situ transcriptome analysis of drug-resistant melanoma cells responding to the regressing tumour microenvironment revealed hyperactivation of several signalling pathways, most prominently the AKT pathway. Dual inhibition of RAF and the PI(3)K/AKT/mTOR intracellular signalling pathways blunted the outgrowth of the drug-resistant cell population in BRAF mutant human melanoma, suggesting this combination therapy as a strategy against tumour relapse. Thus, therapeutic inhibition of oncogenic drivers induces vast secretome changes in drug-sensitive cancer cells, paradoxically establishing a tumour microenvironment that supports the expansion of drug-resistant clones, but is susceptible to combination therapy

Key comparison CCQM-K73 amount content of H+ in hydrochloric acid (0.1 mol·kg-1)

This key comparison (KC), CCQM-K73, was performed to demonstrate the capability of the participating National Metrology Institutes (NMIs) to measure the amount content of H+ , νH + , in an HCl solution with a nominal νH + of 0.1 mol·kg-1 . A parallel Pilot Study, CCQM-P19.2, was performed for NMIs that did not desire to participate in the KC. The comparison was a joint activity of the Electrochemical Working Group (EAWG) and Inorganic Analysis Working Group (IAWG) of the CCQM and was coordinated by NIST (USA) and CENAM (México). The method of determination of νH + was left to the individual participant. All participants used either coulometry or titrimetry with potentiometric determination of the endpoint. The agreement of the results was not commensurate with the claimed uncertainties of the subset of participants that claimed small uncertainties for this determination. A workshop on technical issues relating to the CCQM-K73 measurements was conducted at the joint IAWGEAWG meeting at the Bureau International des Poids et Mesures (BIPM), Paris (Sèvres) in April 2010. Several possible sources of bias were investigated, but none could explain the observed dispersion among the participants’ results. In the absence of a specific cause for the dispersion, the IAWG and EAWG decided to assign a Key Comparison Reference Value, KCRV, and standard uncertainty of the KCRV, uKCRV, based on the DerSimonian-Laird statistical estimator. The uKCRV is dominated by the between-laboratory scatter of results in CCQM-K73. The uncertainty estimates from the participants with the lowest reported uncertainties remain unsupported by this KC.Fil: Pratt, Kenneth W. National Institute of Standards and Technology (NIST); Estados UnidosFil: Ortiz-Aparicio, Jose Luis. Centro Nacional de Metrología (CENAM); MéxicoFil: Matehuala-Sanchez, Francisco Javier. Centro Nacional de Metrología (CENAM); MéxicoFil: Jakobsen, Pia Tønnes. Dansk Fundamental Metrology (DFM); DinamarcaFil: Pawlina, Monika. Główny Urząd Miar (GUM); PoloniaFil: Kozłowski, Władysław. Główny Urząd Miar (GUM); PoloniaFil: Borges, Paulo P. Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMetro); BrasilFil: da Silva Junior, Wiler B. Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMetro); BrasilFil: Borinsky, Mónica B. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Hernandez, Ana. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Puelles, Mabel. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Hatamleh, Nadia. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Acosta, Osvaldo. Instituto Nacional de Tecnología Industrial (INTI); ArgentinaFil: Nunes, João. Instituto Português da Qualidade (IPQ); PortugalFil: Guiomar Lito, M. J. Instituto Português da Qualidade (IPQ); PortugalFil: Camões, M. Filomena. Instituto Português da Qualidade (IPQ); PortugalFil: Filipe, Eduarda. Instituto Português da Qualidade (IPQ); PortugalFil: Hwang, Euijin. Korea Research Institute of Standards and Science (KRISS); Corea del SurFil: Lim, Youngran. Korea Research Institute of Standards and Science (KRISS); Corea del SurFil: Bing, Wu. National Institute of Metrology (NIM); ChinaFil: Qian, Wang. National Institute of Metrology (NIM); ChinaFil: Chao, Wei. National Institute of Metrology (NIM); ChinaFil: Hioki, Akiharu. National Metrology Institute of Japan (NMIJ); JapónFil: Asakai, Toshiaki. National Metrology Institute of Japan (NMIJ); JapónFil: Máriássy, Michal. Slovenský Metrologický Ústav (SMU); EslovaquiaFil: Hanková, Zuzana. Slovenský Metrologický Ústav (SMU); EslovaquiaFil: Nagibin, Sergey. Ukrainian State Research and Production Center of Standardization Metrology, Certification, and Consumers’ Rights Protection (UMTS); UcraniaFil: Manska, Olexandra. Ukrainian State Research and Production Center of Standardization Metrology, Certification, and Consumers’ Rights Protection (UMTS); UcraniaFil: Gavrilkin, Vladimir. Ukrainian State Research and Production Center of Standardization Metrology, Certification, and Consumers’ Rights Protection (UMTS); UcraniaFil: Kutovoy, Viatcheslav. All-Russian Scientific Institute for Physical-Technical and Radiological Measurements (VNIIFTRI); Rusi

Acquired Resistance to KRAS (G12C) Inhibition in Cancer

BACKGROUND: Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS(G12C)). The mechanisms of acquired resistance to these therapies are currently unknown. METHODS: Among patients with KRAS(G12C) -mutant cancers treated with adagrasib monotherapy, we performed genomic and histologic analyses that compared pretreatment samples with those obtained after the development of resistance. Cell-based experiments were conducted to study mutations that confer resistance to KRAS(G12C) inhibitors. RESULTS: A total of 38 patients were included in this study: 27 with non-small-cell lung cancer, 10 with colorectal cancer, and 1 with appendiceal cancer. Putative mechanisms of resistance to adagrasib were detected in 17 patients (45% of the cohort), of whom 7 (18% of the cohort) had multiple coincident mechanisms. Acquired KRAS alterations included G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, and high-level amplification of the KRAS(G12C) allele. Acquired bypass mechanisms of resistance included MET amplification; activating mutations in NRAS, BRAF, MAP2K1, and RET; oncogenic fusions involving ALK, RET, BRAF, RAF1, and FGFR3; and loss-of-function mutations in NF1 and PTEN. In two of nine patients with lung adenocarcinoma for whom paired tissue-biopsy samples were available, histologic transformation to squamous-cell carcinoma was observed without identification of any other resistance mechanisms. Using an in vitro deep mutational scanning screen, we systematically defined the landscape of KRAS mutations that confer resistance to KRAS(G12C) inhibitors. CONCLUSIONS: Diverse genomic and histologic mechanisms impart resistance to covalent KRAS(G12C) inhibitors, and new therapeutic strategies are required to delay and overcome this drug resistance in patients with cancer. (Funded by Mirati Therapeutics and others; ClinicalTrials.gov number, NCT03785249.)