A Comprehensive Approach to the Diagnosis of Leigh Syndrome Spectrum.

BACKGROUND: Leigh syndrome spectrum (LSS) is a novel nomenclature that encompasses both classical Leigh syndrome and Leigh-like phenotypes. Given the heterogeneity of disease presentation, a new consensus published recently addressed the main issues and proposed general guidelines towards diagnosis. Based on these recommendations, we developed a simple pipeline that can be useful in the diagnosis of LSS. METHODS: We combined previously published criteria with our own experience to achieve a diagnostic framework that can provide faster satisfactory results with fewer resources. RESULTS: We suggest adding basic biochemical tests for amino acids, acylcarnitine, and urinary organic acids as parallel investigations, as these results can be obtained in a short time. This approach characterized 80% of our cohort and promoted specific intervention in 10% of confirmed cases. CONCLUSIONS: Genetic studies are crucial in the diagnosis of LSS, but they are time-consuming and might delay tailored interventions. Therefore, we suggest adding more affordable and less complex biochemical studies as primary tests when investigating treatable causes of LSS.

Analysis of single vehicle noise emissions in the frequency domain for two different motorizations.

Environmental noise, primarily attributed to the road transportation system, poses a significant challenge in Europe, impacting the quality of life for millions. Therefore, a thorough characterization of noise emissions from road transportation sources is needed to stem this problem. This investigation aims to fill a gap in the literature regarding single-vehicle noise emissions in the frequency domain. The emphasis is on motorization (i.e., fuel type), with particular attention to Low-Frequency components, due to their potential impact on human health and ecosystems. Two probe vehicles, a diesel and a Liquefied Petroleum Gas-powered, were employed to collect data for noise emission curves in the frequency domain (from 63 to 8000 Hz) and compare them with those furnished in the CNOSSOS-EU, Harmonoise, and REMEL models. Moreover, data in terms of exhaust noise emissions (at the tailpipe) were also gathered and analyzed in the frequency domain. The analysis highlighted motorization's influence on noise emissions, revealing differences in frequency component contributions to the overall sound power level at different speeds. Low-frequency components were found to be predominant for both vehicles, especially at lower speeds, where the engine noise contribution dominates. This finds its endorsement in the frequency analysis on the noise emission curves provided in the examined models. The evaluation of the exhaust noise emissions revealed resonance phenomena at 63 Hz and showcased the dominance of low-frequency components in the exhaust spectrum (despite the penalization introduced by the A-weighting procedure), opening avenues for understanding and lowering noise emissions during vehicle idling and low-speed operations.

Phenotyping mitochondrial glutamyl-tRNA synthetase deficiency (EARS2): A case series and systematic literature review.

Mitochondrial glutamyl-aminoacyl tRNA synthetase deficiency, stemming from biallelic mutations in the EARS2 gene, was first described in 2012. With <50 cases reported globally, this condition exhibits a distinct phenotype of neonatal or childhood-onset, often referred to as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). It has also been one of the few reversible mitochondrial disorders described. The natural history of these patients is poorly documented, ranging from clinical and radiological improvement to early death. Herein, we detail three cases from our centre, including follow-up on the Portuguese patient reported by Steenweg et al., These cases illustrate the phenotypic spectrum: i) rapidly progressive neonatal presentation with lactic acidemia and corpus callosum agenesis, leading to early death; ii) early onset with a severe, slowly progressive course; iii) early onset with a milder phenotype, showing some improvement and mild neurological symptoms. Additionally, we conducted a systematic literature review on cases of EARS2-deficient patients, focusing on clinical manifestations, laboratory findings, radiological aspects, and disease progression over time, along with respective data analysis. "Patients with EARS2 deficiency typically present within the first year of life with a well-defined neurometabolic disorder picture, often including hypotonia and/or spasticity, along with neurodevelopmental delay or regression. There are no pathognomonic features specific to EARS2 deficiency, and no genotype-phenotype correlation has been identified." Comparing to initial characterization by Steenweg et al., this analysis reveals an expanded disease spectrum. We propose a novel strategy for clustering phenotypes into severe, moderate, or mild disease based on initial presentation, seemingly correlating with disease progression. The paucity of data on the disease's natural history highlights the need for a multicentric approach to enhance understanding and management. TAKE-HOME MESSAGE: Analysis of all cases published with EARS2 deficiency allows for establish disease spectrum and a novel strategy for clustering phenotypes which correlate to disease progression.

Cultural competence of undergraduate student nurses: a multicenter study.

OBJECTIVE: to evaluate the level of cultural competence of an undergraduate nursing students' population from four European higher education institutions. METHOD: a total of 168 nursing students from four different countries were included in our study. The study methodology involved a cross-sectional assessment of cultural competence among undergraduate nursing students from four European universities. Data collection included sociodemographic variables, as well as the following validated tools: the Intercultural Sensitivity Scale, the Cultural Competence Assessment Tool (student version) and the Cultural Awareness Scale. RESULTS: our results indicated that students demonstrated a high level of intercultural sensitivity but a moderate level of cultural competence and cultural awareness. Variations existed among students from different countries, suggesting potential differences in educational approaches. Despite expectations that higher-level students would exhibit greater cultural competence, no significant differences were found by year of study, indicating a lack of effective integration of cultural competence into nursing curricula. CONCLUSION: nurse educators should consider the students' cultural competence before designing related study programmes. Training programmes related to cultural competence should include elements which have been associated with enhanced cultural competence, including language skills, cultural encounter, and opportunities for internationalisation.

Unusual presentation of pancreatitis: Inguinoscrotal edema mimicking an incarcerated hernia - a case report.

INTRODUCTION: In rare instances, pancreatitis can manifest as inguinal edema without typical abdominal symptoms, posing diagnostic challenges. CASE PRESENTATION: We report a case of a man in his 40s, with alcohol addiction, who presented with left inguinal pain and swelling but no other abdominal complaints. Physical examination revealed inguinal tenderness and edema, with no hernia signs. Laboratory results showed leukocytosis and elevated C-reactive protein, inconsistent with the patient's symptoms. Abdominopelvic CT scan revealed peripancreatic fat densification and retroperitoneal fluid extending into the inguinal area. No hernia was evident. Extended analysis revealed elevated amylase and lipase levels, sustaining the diagnosis of pancreatitis. The patient responded well to supportive care and was discharged symptom-free. DISCUSSION: Acute pancreatitis emerging as an inguinoscrotal swelling, in the absence of any abdominal symptoms or signs, is extremely rare and can mimic more common causes of inguinoscrotal swellings, such as incarcerated hernias. This case highlights the ability of leaking pancreatic juice to track widely in the retroperitoneal tissues, particularly on the left side. A high level of suspicion, in combination with a CT scan, is essential for achieving an accurate diagnosis and determining the disease's extent. Failure to diagnose correctly could lead to unnecessary surgical procedures and inappropriate/delayed medical care. CONCLUSION: Inguinal edema as the sole presentation of acute pancreatitis is extremely rare. Therefore, it is essential to maintain a high index of suspicion, especially in patients with a history of alcohol consumption, in order to proceed with prompt treatment and avoid unnecessary surgery.

Pancreaticopleural fistula as the inaugural presentation of chronic pancreatitis: A case report.

INTRODUCTION: Pancreaticopleural fistula is a rare complication most associated with alcohol-induced chronic pancreatitis. This usually presents with chest symptoms instead of abdominal ones. Diagnosis requires a high index of suspicion in patients with pancreatitis and persistent pleural effusions. PRESENTATION OF CASE: We present a case of an 81-years-old man admitted in the emergency department with a one week complaints of productive cough, fever, dyspnea and left-side chest pain. The chest X-ray revealed a moderated-volume left-side pleural effusion. The pleural fluid analysis was consistent with an exsudative pleural effusion with high levels of amylase. The thoracoabdominal CT raised the suspicion of a pancreaticopleural fistula, confirmed by ERCP. A pancreatic main duct stenting was performed with good results. The patient was discharged asymptomatic after 18 days of hospitalization. DISCUSSION: Because of PPF insidious presentation it poses a great number of differential diagnosis, so pleural fluid analysis is of paramount importance with high levels of amylase confirming the diagnosis. MRCP and ERCP may establish the fistulous tract between the pancreatic duct and the pleural cavity, with the latter being also therapeutic. CONCLUSION: The rarity of this complication related to pancreatitis and the seldomly presence of abdominal pain in contrast with chest symptoms poses a diagnostic challenge.

Cultural competence of undergraduate student nurses: a multicenter study / Competencia cultural de estudiantes de pregrado en enfermería: estudio multicéntrico / Competência cultural de estudantes de graduação em enfermagem: um estudo multicêntrico

Objective: to evaluate the level of cultural competence of an undergraduate nursing students' population from four European higher education institutions. Method: a total of 168 nursing students from four different countries were included in our study. The study methodology involved a cross-sectional assessment of cultural competence among undergraduate nursing students from four European universities. Data collection included sociodemographic variables, as well as the following validated tools: the Intercultural Sensitivity Scale, the Cultural Competence Assessment Tool (student version) and the Cultural Awareness Scale. Results: our results indicated that students demonstrated a high level of intercultural sensitivity but a moderate level of cultural competence and cultural awareness. Variations existed among students from different countries, suggesting potential differences in educational approaches. Despite expectations that higher-level students would exhibit greater cultural competence, no significant differences were found by year of study, indicating a lack of effective integration of cultural competence into nursing curricula. Conclusion: nurse educators should consider the students' cultural competence before designing related study programmes. Training programmes related to cultural competence should include elements which have been associated with enhanced cultural competence, including language skills, cultural encounter, and opportunities for internationalisation.

Objetivo: evaluar el nivel de competencia cultural de una población de estudiantes de pregrado en enfermería de cuatro instituciones europeas de educación superior. Método: en nuestro estudio se incluyeron en total 168 estudiantes de enfermería de cuatro países diferentes. La metodología de estudio implicó una evaluación transversal de la competencia cultural de los estudiantes de pregrado en enfermería de cuatro universidades europeas. La recolección de datos incluyó variables sociodemográficas y las siguientes herramientas validadas: la Escala de Sensibilidad Intercultural, la Herramienta de Evaluación de la Competencia Cultural (versión para estudiantes) y la Escala de Conciencia Cultural. Resultados: los estudiantes demostraron un alto nivel de sensibilidad intercultural pero un nivel moderado de competencia y conciencia cultural. Hubo variaciones entre los estudiantes de diferentes países, lo que sugiere posibles diferencias en los enfoques educativos. A pesar de que se esperaba que los estudiantes de educación superior tuvieran mayor competencia cultural, no se encontraron diferencias significativas por año de estudio, lo que indica que la competencia cultural no se incluye de forma efectiva en los planes de estudio de las carreras de pregrado en enfermería. Conclusión: los educadores de enfermería deben considerar la competencia cultural de los estudiantes antes de diseñar programas de estudio relacionados con la misma. Los programas de formación relacionados con la competencia cultural deben incluir elementos que se hayan asociado con una mayor competencia cultural, eso incluye habilidades lingüísticas, encuentros culturales y oportunidades de internacionalización.

Objetivo: avaliar o nível de competência cultural de uma população de estudantes de graduação em enfermagem de quatro instituições europeias de ensino superior. Método: um total de 168 estudantes de enfermagem de quatro países diferentes foram incluídos em nosso estudo. A metodologia do estudo envolveu uma avaliação transversal da competência cultural entre estudantes de graduação em enfermagem de quatro universidades europeias. A coleta de dados incluiu variáveis sociodemográficas, bem como as seguintes ferramentas validadas: Escala de Sensibilidade Intercultural, Ferramenta de Avaliação de Competência Cultural (versão do aluno) e Escala de Consciência Cultural. Resultados: nossos resultados indicaram que os alunos demonstraram um alto nível de sensibilidade intercultural, mas um nível moderado de competência e consciência cultural. Houve variações entre os alunos de diferentes países, o que sugere possíveis diferenças nas abordagens educacionais. Apesar das expectativas de que os alunos de nível superior apresentariam maior competência cultural, não foram encontradas diferenças significativas por ano de estudo, indicando uma falta de integração eficaz da competência cultural nos currículos de enfermagem. Conclusão: os educadores de enfermagem devem considerar a competência cultural dos alunos antes de elaborar programas de estudo relacionados. Os programas de treinamento relacionados à competência cultural devem incluir elementos que tenham sido associados a uma maior competência cultural, incluindo habilidades linguísticas, encontros culturais e oportunidades de internacionalização.

Proteomics Reveals mRNA Regulation and the Action of Annexins in Thyroid Cancer.

Differentiated thyroid cancer is the most common malignancy of the endocrine system. Although most thyroid nodules are benign, given the high incidence of thyroid nodules in the population, it is important to understand the differences between benign and malignant thyroid cancer and the molecular alterations associated with malignancy to improve detection and signal potential diagnostic, prognostic, and therapeutic targets. Proteomics analysis of benign and malignant human thyroid tissue largely revealed changes indicating modifications in RNA regulation, a common cancer characteristic. In addition, changes in the immune system and cell membrane/endocytic processes were also suggested to be involved. Annexin A1 was considered a potential malignancy biomarker and, similarly to other annexins, it was found to increase in the malignant group. Furthermore, a bioinformatics approach points to the transcription factor Sp1 as being potentially involved in most of the alterations seen in the malignant thyroid nodules.

Biomarkers of hypoxic-ischemic encephalopathy: a systematic review.

BACKGROUND: Current diagnostic criteria for hypoxic-ischemic encephalopathy in the early hours lack objective measurement tools. Therefore, this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice (PROSPERO ID: CRD42021272610). DATA SOURCES: Searches were performed in PubMed, Web of Science, and Science Direct databases until November 2020. English original papers analyzing samples from newborns > 36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were included. Bias was assessed by the Newcastle-Ottawa Scale. The search and data extraction were verified by two authors separately. RESULTS: From 373 papers, 30 met the inclusion criteria. Data from samples collected in the first 72 hours were extracted, and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal asphyxia. In addition, the levels of glial fibrillary acidic protein, ubiquitin carboxyl terminal hydrolase isozyme-L1, glutamic pyruvic transaminase-2, lactate, and glucose were elevated in newborns diagnosed with hypoxic-ischemic encephalopathy. Moreover, pathway analysis revealed insulin-like growth factor signaling and alanine, aspartate and glutamate metabolism to be involved in the early molecular response to insult. CONCLUSIONS: Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers, since they are correlated with an unfavorable outcome of hypoxic-ischemic encephalopathy newborns. However, more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.

Management of infantile hemangiomas-experience of a tertiary hospital.

The purpose of the study is to describe the experience of a multidisciplinary team in a tertiary hospital regarding the management of Infantile Hemangiomas (IH). The method employed is a retrospective analysis of patients with IH followed in a tertiary pediatric hospital between January 2010 and May 2022. A total of 393 IH were diagnosed (56.7% female), with a median age of 5 months (interquartile range (IQR), 3-10). Imaging investigation was necessary for diagnosis and for exclusion of other IH in 9.2% and 14.3%, respectively. Focal (74.0%) and superficial (59.7%) lesions were more frequent as was facial location (35.9%). Pre-treatment ulceration or hemorrhage occurred in 6.6%. At follow-up, 87.4% regressed partially and 12.6% completely; 2.7% relapsed. Propranolol was started in 30.0% of cases for a median period of 9 months (IQR, 6-12), mainly due to esthetic concerns (41.9%). Side effects occurred in 8.3% (sleep disturbance in 5.1%). Only 1.7% were refractory and 5.9% had a rebound effect. Eleven patients were treated with topical timolol and 41 underwent surgery. Patients that were treated with propranolol had more risk factors (p = 0.016) and presented deeper lesions (p < 0.001) with a larger diameter (p < 0.001); total IH regression was less frequent (p < 0.001). Since 2020, twice-daily dosage was more frequently prescribed than three times daily (p = 0.007) and inpatient initiation of propranolol decreased (p = 0.750), without significant difference in the incidence of adverse reactions, duration of treatment, and lesion evolution.  Conclusions: Our protocol proved to be safe and feasible in an outpatient setting and twice daily administration of propranolol was effective. The majority of IH showed at least partial regression. Early detection of high-risk IH is paramount and a multidisciplinary assessment by a specialized team is essential for adequate management. What is Known: • IH are the most common vascular tumors in childhood. Although the majority evolves favorably, treatment may be warranted in selected cases. • Early detection of high-risk IH is paramount, and a multidisciplinary assessment by a specialized team is essential for adequate management. What is New: • One-third of our sample was treated with propranolol. These patients had more risk factors and presented deeper lesions with a larger diameter, and tumor total regression was less frequent. • Our results reinforce safety and feasibility of propranolol initiation in an outpatient setting, including twice daily dosage.

[Lead Exposure as Cause of a Clinical Scenario of Cardiac Arrhythmias]. / A Exposição ao Chumbo na Base de um Quadro de Arritmias Cardíacas.

The recycling of used batteries has raised public health concerns as this activity is associated with occupational and environmental exposure to lead. We describe the case of a 26-year-old woman who experienced palpitations associated with headaches, fatigue and insomnia. Blood tests showed anemia (Hb 11.9 g/dL) and a lead concentration of 59 µg/dL. This was reported about four months after starting work in a battery recycling company. She left the company and, reported a gradual decrease in symptoms about one month later. The analytical study revealed a normalization of hemoglobin levels (12.2 g/dL) and a decrease in blood lead levels to 23.4 µg/dL. The health effects of lead exposure are nonspecific, and its diagnosis requires a high degree of suspicion. In this context, the collaboration between the Attending Physician and the Health and Safety Departments of companies is important.

A reciclagem de baterias usadas tem suscitado preocupações de saúde pública uma vez que esta atividade está associada à exposição ocupacional e ambiental ao chumbo. Descreve-se o caso de uma mulher de 26 anos que iniciou quadro de palpitações associado a cefaleias, fadiga e insónias, cerca de quatro meses após iniciar funções numa empresa de reciclagem de baterias. Analiticamente, observou-se anemia (Hb 11,9 g/dL) e plumbémia de 59 µg/dL. Cessou funções na empresa e, após um mês, referiu uma diminuição progressiva da sintomatologia. O estudo analítico revelou uma normalização dos valores da hemoglobina (12,2 g/dL) e uma diminuição do valor de chumbo no sangue para 23,4 µg/dL. Os efeitos na saúde da exposição ao chumbo são inespecíficos e o seu diagnóstico requer um alto grau de suspeição. Neste âmbito revela-se importante a articulação entre o médico assistente e os serviços de Saúde, Higiene e Segurança no Trabalho das empresas.

Enrichment of hepatic glycogen and plasma glucose from H218 O informs gluconeogenic and indirect pathway fluxes in naturally feeding mice.

Deuterated water (2 H2 O) is a widely used tracer of carbohydrate biosynthesis in both preclinical and clinical settings, but the significant kinetic isotope effects (KIE) of 2 H can distort metabolic information and mediate toxicity. 18 O-water (H2 18 O) has no significant KIE and is incorporated into specific carbohydrate oxygens via well-defined mechanisms, but to date it has not been evaluated in any animal model. Mice were given H2 18 O during overnight feeding and 18 O-enrichments of liver glycogen, triglyceride glycerol (TG), and blood glucose were quantified by 13 C NMR and mass spectrometry (MS). Enrichment of oxygens 5 and 6 relative to body water informed indirect pathway contributions from the Krebs cycle and triose phosphate sources. Compared with mice fed normal chow (NC), mice whose NC was supplemented with a fructose/glucose mix (i.e., a high sugar [HS] diet) had significantly higher indirect pathway contributions from triose phosphate sources, consistent with fructose glycogenesis. Blood glucose and liver TG 18 O-enrichments were quantified by MS. Blood glucose 18 O-enrichment was significantly higher for HS versus NC mice and was consistent with gluconeogenic fructose metabolism. TG 18 O-enrichment was extensive for both NC and HS mice, indicating a high turnover of liver triglyceride, independent of diet. Thus H2 18 O informs hepatic carbohydrate biosynthesis in similar detail to 2 H2 O but without KIE-associated risks.

Peptidomics Unveils Distinct Acetylation Patterns of Histone and Annexin A1 in Differentiated Thyroid Cancer.

Thyroid cancer is a common malignancy of the endocrine system. Nodules are routinely evaluated for malignancy risk by fine needle aspiration biopsy (FNAB), and in cases such as follicular lesions, differential diagnosis between benign and malignant nodules is highly uncertain. Therefore, the discovery of new biomarkers for this disease could be helpful in improving diagnostic accuracy. Thyroid nodule biopsies were subjected to a precipitation step with both the insoluble and supernatant fractions subjected to proteome and peptidome profiling. Proteomic analysis identified annexin A1 as a potential biomarker of thyroid cancer malignancy, with its levels increased in malignant samples. Also upregulated were the acetylated peptides of annexin A1, revealed by the peptidome analysis of the supernatant fraction. In addition, supernatant peptidomic analysis revealed a number of acetylated histone peptides that were significantly elevated in the malignant group, suggesting higher gene transcription activity in malignant tissue. Two of these peptides were found to be robust malignancy predictors, with an area under the receiver operating a characteristic curve (ROC AUC) above 0.95. Thus, this combination of proteomics and peptidomics analyses improved the detection of malignant lesions and also provided new evidence linking thyroid cancer development to heightened transcription activity. This study demonstrates the importance of peptidomic profiling in complementing traditional proteomics approaches.

Migrant and ethnic minority nurses' experience of working in European health services: a qualitative study.

OBJECTIVE: To analyze the perception of culture and experience of working in European health services of a purposive sample of qualified migrant and ethnic minority nurses currently living in Belgium, Portugal, Spain and Turkey. METHOD: A qualitative phenomenological method was chosen. Individual interviews took place with 8 qualified migrant and ethnic minority nurses currently living in four European countries. Thematic analysis was conducted using Braun and Clark's stages after qualitative data had been verbatim transcribed, translated into English, and analyzed. RESULTS: Four themes and 4 subthemes emerged from thematic analysis of the transcripts. CONCLUSION: Migrant and ethnic minority nurses working in the European Union experience and witness discrimination and prejudice from patients and colleagues due to cultural differences. European health services should closely monitor and address discrimination and prejudice towards migrant and ethnic minority staff and patients, and take initiatives to reduce and, eventually, eradicate them.

Qualified Nurses' Perceptions of Cultural Competence and Experiences of Caring for Culturally Diverse Patients: A Qualitative Study in Four European Countries.

BACKGROUND: European nurses are expected to provide appropriate care for patients from diverse cultural backgrounds. However, there is limited knowledge and understanding of this process. The aim of this study was to analyse the perceptions of culture and experiences of caring for patients from diverse cultural backgrounds of a purposive sample of qualified nurses from four European countries, namely Belgium, Portugal, Spain and Turkey. METHODS: A qualitative phenomenological approach was selected in order to understand complex phenomena through the participants' lived experiences, meanings and perspectives. Individual interviews and focus groups took place with 28 staff nurses and 11 nurse managers from four European countries. The sociodemographic and cultural characteristics of the sample were described and analysed using descriptive statistics. Qualitative data were transcribed verbatim, translated into English and analysed following Braun and Clark's phases for thematic analysis. RESULTS: Five themes and twelve subthemes emerged from thematic analysis of the transcripts. The themes included: (1) relevance of culture for nursing; (2) culture in the healthcare service; (3) qualities of the healthcare professionals; (4) challenges to culturally competent care; (5) becoming a culturally competent nurse. CONCLUSIONS: There are challenges to the delivery of culturally congruent care, namely language and communication difficulties, prejudices and stereotyping in the health service, a tendency for ethnocentrism, a lack of education and training in cultural competence and a lack of support from the health service to facilitate new ways of acting.