Source Attribution of Antibiotic Resistance Genes in Estuarine Aquaculture: A Machine Learning Approach.

Aquaculture located in urban river estuaries, where other anthropogenic activities may occur, has an impact on and may be affected by the environment where they are inserted, namely by the exchange of antimicrobial resistance genes. The latter may ultimately, through the food chain, represent a source of resistance genes to the human resistome. In an exploratory study of the presence of resistance genes in aquaculture sediments located in urban river estuaries, two machine learning models were applied to predict the source of 34 resistome observations in the aquaculture sediments of oysters and gilt-head sea bream, located in the estuaries of the Sado and Lima Rivers and in the Aveiro Lagoon, as well as in the sediments of the Tejo River estuary, where Japanese clams and mussels are collected. The first model included all 34 resistomes, amounting to 53 different antimicrobial resistance genes used as source predictors. The most important antimicrobial genes for source attribution were tetracycline resistance genes tet(51) and tet(L); aminoglycoside resistance gene aadA6; beta-lactam resistance gene blaBRO-2; and amphenicol resistance gene cmx_1. The second model included only oyster sediment resistomes, amounting to 30 antimicrobial resistance genes as predictors. The most important antimicrobial genes for source attribution were the aminoglycoside resistance gene aadA6, followed by the tetracycline genes tet(L) and tet(33). This exploratory study provides the first information about antimicrobial resistance genes in intensive and semi-intensive aquaculture in Portugal, helping to recognize the importance of environmental control to maintain the integrity and the sustainability of aquaculture farms.

Body Composition Evaluation and Clinical Markers of Cardiometabolic Risk in Patients with Phenylketonuria.

Cardiovascular diseases are the main cause of mortality worldwide. Patients with phenylketonuria (PKU) may be at increased cardiovascular risk. This review provides an overview of clinical and metabolic cardiovascular risk factors, explores the connections between body composition (including fat mass and ectopic fat) and cardiovascular risk, and examines various methods for evaluating body composition. It particularly focuses on nutritional ultrasound, given its emerging availability and practical utility in clinical settings. Possible causes of increased cardiometabolic risk in PKU are also explored, including an increased intake of carbohydrates, chronic exposure to amino acids, and characteristics of microbiota. It is important to evaluate cardiovascular risk factors and body composition in patients with PKU. We suggest systematic monitoring of body composition to develop nutritional management and hydration strategies to optimize performance within the limits of nutritional therapy.

Dihydropteridine Reductase Deficiency - A Rare and Potentially Treatable Cause Mimicking Cerebral Palsy.

INTRODUCTION: Dihydropteridine reductase deficiency (DHPRD) is a rare genetic disorder of tetrahydrobiopterin (BH4) regeneration, a cofactor for several enzymes, including phenylalanine hydroxylase. Due to hyperphenylalaninemia (HPA), patients can be detected by the newborn metabolic screening, when available. The most common symptoms of DHPRD may mimic cerebral palsy: developmental/cognitive impairment, hypotonia, peripheral hypertonia, dystonia, feeding difficulties, epilepsy, and microcephaly. The long-term neurodevelopmental outcome is strongly influenced by the early initiation of effective treatment. CASE REPORT: A 2-year-old boy, born in Guinea, was evaluated in our center with the diagnosis of "cerebral palsy". He was born after a prolonged labor, and had feeding difficulties and severe developmental delay. Examination revealed microcephaly, axial hypotonia, and dyskinetic movements without hypertension. No seizures or oculogyric crisis were reported. Brain MRI showed slight brain atrophy and hyperintensity T2/FLAIR in basal ganglia. The diagnosis of cerebral palsy was questioned, and further investigation was carried out. HPA raised the possibility of BH4 deficiency, supported by increased biopterin in urine, decreased neurotransmitters in CSF, and low DHPR enzyme activity. A variant (128_130del (p.(Val43del)) in apparent homozygosity was later detected in the QPDR gene. At 4 years old, he started L-dopa/carbidopa, oxitriptan, and a phenylalanine-restrictive diet with moderate clinical improvement. CONCLUSION: When the diagnosis of "cerebral palsy" is questionable, other etiologies should be investigated, particularly disorders that have specific disease-modifying treatment. In our patient, the atypical constellation of neurological signs, brain MRI findings, and the nonexistence of newborn metabolic screening in the country of origin supported additional investigation. The presence of HPA-associated dystonia was crucial to the investigation and was later confirmed as DHPRD. Unfortunately, at this stage, the reversibility of the neurological damage in response to treatment is doubtful.

Metabolic Myopathies: Experience of a Reference Center of Inherited Metabolic Diseases.

INTRODUCTION: Metabolic myopathies (MM) are a heterogeneous group of genetic disorders affecting metabolic pathways involved in energy production during rest, exercise and physiologic stress (fever, fasting, …). Impairments in the pathways of glycolysis/ glycogenolysis, fatty acid transport/oxidation or in the mitochondrial respiratory chain present primarily with exercise intolerance, myalgias, weakness, cramps, or rhabdomyolysis. Depending on aetiology, the diagnosis can be made through neonatal screening, pre-symptomatic or in the set of clinical manifestations for which a high level of suspicion is important. METHODS: Retrospective descriptive study of the clinical, biochemical, and molecular features of patients with a confirmed diagnosis of MM followed by the multidisciplinary team of the Reference Center of Inherited Metabolic Diseases of Centro Hospitalar Universitário de Lisboa Central from 2009 to 2022. RESULTS: Twenty-three patients with MM were included: 9 (39%) glycogen storage diseases (7 McArdle and 2 Pompe), 7 (30%) fatty acid oxidation disorders (3 CPT2, 3 LCHAD and 1 MAD deficiencies), 6 (26%) mitochondrial disease with significant muscle involvement (2 Pearson, 1 Kearns Sayre, 1 VARS2, 1 SUCLA2 and 1 MT-TL1 deficiencies), and 1 myoadenylate deaminase deficiency. Ages varied from 15 months to 35 years. Eighteen (78%) patients were diagnosed by clinical symptoms, 3 by newborn screening (LCHAD) and 2 were asymptomatic (1 Pompe and 1 McArdle). Frequent symptoms were rhabdomyolysis triggered by illness or exercise 12 (52%), fatigue 11 (48%), exercise intolerance 10 (43%), and myalgia 9 (43%). Eight (35%) patients (LCHAD and mitochondrial) had multisystemic involvement. In 20 (87%) patients, the diagnosis was confirmed by biochemical and/or genetic analysis and 3 (McArdle) by muscle biopsy. CONCLUSION: MM are a heterogeneous set of disorders, but a careful history may guide the differential diagnosis among biochemical pathways and other etiologies. Nowadays, molecular testing has become a powerful tool for diagnosis confirmation, surpassing muscular biopsy in most cases. Accurate diagnosis is important to identify who may benefit from specific therapeutic options, such as enzyme replacement therapy, restricted diets, emergency regime and cofactors. All patients benefit from adequate lifestyle modifications, individualized exercise prescription, nutritional intervention, and genetic counselling.

Clinical, Biochemical and Molecular Features of a Cohort of 8 Patients with Inherited Disorders of Vitamin B12 Metabolism in a Metabolic Reference Center.

BACKGROUND: Vitamin B12, or cobalamin (Cbl), undergoes a complex series of absorptive and intracellular processing steps before serving as a cofactor for the enzymes methylmalonyl-CoA mutase and methionine synthase. Disorders of intracellular cobalamin metabolism have variable phenotypes and age of onset related to the location of the defect in the metabolic pathway leading to a combined methylmalonic acidemia and homocystinuria (cblC, cblD, cblF and cblJ), Isolated methylmalonic acidemia (cblA, cblB and cblDv2) and isolated homocystinuria (cblDv1, cblE and cblG). OBJECTIVE AND METHODS: We conducted a retrospective study of the clinical biochemical and molecular features of a cohort of patients with disorders of intracellular Cbl metabolism followed in our Reference Centre of Inherited Metabolic Diseases (CR-IMD) for the last 23 years (2000-2023). RESULTS: CblC: P1 and P2, pré-newborn screening (NBS), had an early and severe presentation evolving to multiorgan failure and death. P3 was asymptomatic at NBS with an excellent evolution except for nystagmus and retinitis pigmentosa. P4 presented at 19Y with an atypical hemolytic uremic syndrome and is presently on hemodialysis. CblD: P5 had a developmental delay (DD) and hypotonia and presented at 14m with seizures. CblDv2: P6 had DD and failure to thrive (FTT) and presented at 4Y with acute metabolic acidosis. CblDv1: P7 had DD, FTT, and hypotonia and presented at 16m with seizures and anemia. CblG: P8 had DD and FTT and presented at 15m with macrocytic anemia. In all, characteristic biochemical profiles guided the diagnosis, afterward confirmed by genetic analysis (4 MMACHC, 3 MMADHC, 1 MTR). All patients received either betaine, hydroxycobalamin, or both (P3 is on a very high dosage). CONCLUSION: Our cohort of patients has similar clinical and biochemical characteristics to the ones described in the literature. Outcomes of patients reinforce the importance of newborn screening and the need for consensus guidelines for optimal doses of parenteral hydroxocobalamin.

Perspectives and challenges for mother-to-child transmission of HIV, hepatitis B, and syphilis in Brazil.

Background: Eliminating mother-to-child transmission (MTCT) of HIV, hepatitis B, and syphilis is a challenge in Brazil. Many policies have been implemented since 1986, but important gaps remain. This study aimed to describe the trends of MTCT in Brazil and evaluate the gaps and perspectives in this scenario. Methods: This is a descriptive study conducted with secondary data publicly available in the information systems of the Brazilian Ministry of Health regarding data on HIV, syphilis, and hepatitis B in pregnant women and children from 2011 to 2021. Results: HIV and hepatitis B have had constant rates over the years in pregnant women, with the detection rates around 2.5/1,000 live birth (LB) and 0.5/1.000LB, respectively. The same did not happen with syphilis, which has shown an increasing line in the last decade. In 2011, the detection rate of syphilis in pregnancy was 4.7/1,000LB, and in 2021 it reached 27.1/1,000LB. Regarding the trends in children, an important decrease was observed in HIV/AIDS (incidence rate from 0.18/1,000 in 2011 to 0.04/1,000 in 2021) and Hepatitis B (incidence rate from 0.9/1,000LB in 2011 to 0.5/1,000LB in 2021). For congenital syphilis, there is a continuous increase, being 3.3/1,000LB in 2011 and 9.9/1,000LB in 2021. Data from the HIV clinical monitoring showed that antiretroviral treatment coverage among pregnant women identified increased slightly between 2011 and 2021, in Brazil, from 92.3% to 94.3%. For syphilis, 82.5% of pregnant women were treated with benzathine penicillin, and 88.7% in 2011. The historical series of hepatitis B vaccination coverage in children has decreased over the years; it was 96% in 2013 and 76% in 2021. Conclusion: These data show many gaps and some perspectives in the MTCT program in Brazil. The country is close to reaching MTCT HIV elimination, but there are many challenges regarding HBV and syphilis. These data can be used to organize the strategies to improve the Brazilian response to MTCT elimination of HIV, hepatitis B, and syphilis.

Paediatric Palliative Care in a Reference Centre of Inherited Metabolic Diseases.

INTRODUCTION: Paediatric palliative care (PPC) has a significant role in improving the quality of life of children with life-limiting or life-threatening illnesses, diminishing symptom burden, and providing holistic support to patients and families. Inherited metabolic diseases (IMD) are a group of heterogeneous diseases that often present with severe neurologic impairment, needing lifelong care and challenging symptom management. OBJECTIVE: Our aim was to characterize the cohort of patients with IMD followed by the paediatric palliative care team (PPCT) and to describe the provision of care provided. METHODS: The descriptive analysis of demographic, clinical, and care delivery data of a cohort of paediatric patients was carried out with a confirmed diagnosis of IMD, followed in a Reference Centre, in the care of PPCT between 2018 and 2023. RESULTS: Thirteen (10%) of a total of 134 patients in the care of PPCT had a confirmed diagnosis of an IMD: 6 mitochondrial, 3 peroxisomal, 3 lysosomal, and 1 pterin metabolism disorder. The median age at referral was 9 years (0-18), the median duration of care was 2 years [2-4], median number of home visits in the last year was 2 [1-4], and median number of outpatient consults was 4 [2 -8]. Twelve patients (92%) had no autonomy in their activities of daily living. Neurologic (100%), gastrointestinal (92%), and respiratory (69%) symptoms were the main focus of care. All patients were polymedicated (5 or more different drugs). Nine (69%) had percutaneous gastrostomy and 2 (15%) had noninvasive ventilation. Median hospital admissions before and after starting care by PPCT were 4 and 1. Moreover, three patients died and one was at home. CONCLUSION: Mitochondrial, lysosomal, and peroxisomal disorders are complex multisystemic diseases that very often have no treatment intended to cure. These patients have a heavy symptom burden and frequent intercurrences. Addressing these symptoms is challenging, but PPC has proven to reduce hospital admissions with consequent improvement in quality of life. In the future, PPC should be available for all children and families with life-threatening conditions.

Leigh Syndrome Spectrum: A Portuguese Population Cohort in an Evolutionary Genetic Era.

Mitochondrial diseases are the most common inherited inborn error of metabolism resulting in deficient ATP generation, due to failure in homeostasis and proper bioenergetics. The most frequent mitochondrial disease manifestation in children is Leigh syndrome (LS), encompassing clinical, neuroradiological, biochemical, and molecular features. It typically affects infants but occurs anytime in life. Considering recent updates, LS clinical presentation has been stretched, and is now named LS spectrum (LSS), including classical LS and Leigh-like presentations. Apart from clinical diagnosis challenges, the molecular characterization also progressed from Sanger techniques to NGS (next-generation sequencing), encompassing analysis of nuclear (nDNA) and mitochondrial DNA (mtDNA). This upgrade resumed steps and favored diagnosis. Hereby, our paper presents molecular and clinical data on a Portuguese cohort of 40 positive cases of LSS. A total of 28 patients presented mutation in mtDNA and 12 in nDNA, with novel mutations identified in a heterogeneous group of genes. The present results contribute to the better knowledge of the molecular basis of LS and expand the clinical spectrum associated with this syndrome.

The emergence of Brucella canis as a public health threat in Europe: what we know and what we need to learn.

The zoonotic bacteria, Brucella canis, is becoming the leading cause of canine brucellosis in Europe. In dogs, it causes reproductive problems as well as non-specific lameness or discospondilitis. In humans, B. canis can be origin of chronic debilitating conditions characteristic to its genus such as undulant fever, splenomegaly, and lymphadenopathy. Although B. canis shows some pathogenic characteristics similar to B. abortus and B. melitensis, it lacks surface O-polysaccharide, like nonzoonotic B. ovis. This review shows that host-B. canis interactions are still poorly understood, with many knowledge and capability gaps, causing relatively poor sensitivity and specificity of existing diagnostic tools. Currently, there is no vaccine for this rough Brucella species. Besides, antimicrobial therapy does not guarantee bacterial elimination, and infection relapses are frequently reported, increasing the risks of antibiotic resistance development. B. canis has been detected in dogs in almost all European countries which increased human exposure, but currently there is no systematic surveillance. Moreover, B. canis caused brucellosis is not included in Animal Health Law, and therefore there is no legal framework to tackle this emerging infectious disease. To map out the diagnostic strategies, identify risks for human infections and propose management scheme for infected pet and kennel dogs, we present current understanding of canine B. canis caused brucellosis, outline major knowledge gaps and propose future steps. To address and highlight challenges veterinary and public health services encounter in Europe, we developed two B. canis infection scenarios: of a single household pet and of a kennel dog in larger group.

Impact of Latent M. tuberculosis Infection Treatment on Time to CD4/CD8 Recovery in Acute, Recent, and Chronic HIV Infection.

INTRODUCTION: In people living with HIV, active and latent tuberculosis (TB) coinfections are associated with immune activation that correlate with HIV progression and mortality. We investigated the effect of initiating antiretroviral therapy (ART) during acute (AHI), recent (RHI), or chronic HIV infection (CHI) on CD4/CD8 ratio normalization and associated factors, the impact of latent TB infection treatment, and prior/concomitant TB diagnosis at the time of ART initiation. METHODS: We included sex with men and transgender women individuals initiating ART with AHI, RHI and CHI between 2013 and 2019, from a prospective cohort in Brazil. We compared time from ART initiation to the first normal CD4/CD8 ratio (CD4/CD8 ≥1) using Kaplan-Meier curves and multivariable Cox proportional hazards models. Sociodemographic and clinical variables were explored. Variables with P -values <0.20 in univariable analyses were included in multivariable analyses. RESULTS: Five hundred fifty participants were included, 11.8% classified as AHI and 6.4% as RHI, 46.7% with CHI-CD4 cell counts ≥350 cells/mm 3 and 35.1% with CHI-CD4 cell counts <350 cells/mm 3 . Time to normalization was shortest among AHI patients, followed by RHI and CHI individuals with higher baseline CD4. In the multivariable model, AHI was associated with a six-fold increased likelihood of achieving a CD4/CD8 ratio ≥1 (hazard ratio [HR]: 6.03; 95% confidence interval [CI]: 3.70 to 9.82; P < 0.001), RHI with HR: 4.47 (95% CI: 2.57 to 7.76; P < 0.001), and CHI CD4 ≥350 cells/mm 3 with HR: 1.87 (95% CI: 1.24 to 2.84; P = 0.003). Latent TB infection treatment was significantly associated with a higher likelihood of the outcome (HR: 1.79; 95% CI: 1.22 to 2.62; P = 0.003). Previous history or concomitant active TB at ART initiation was associated with a lower likelihood of the outcome (HR: 0.41; 95% CI: 0.16 to 1.02; P = 0.054). CONCLUSIONS: Initiating ART early during AHI may offer an opportunity to mitigate immune damage. Efforts to implement HIV diagnosis and ART initiation during AHI are critical to amplify ART benefits.

Enhancing interventions for prevention of mother-to-child- transmission of hepatitis B virus.

Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis. Current guidelines recommend maternal screening, antiviral therapy during the third trimester of high-risk pregnancies, universal and timely HBV birth dose vaccination, and post-exposure prophylaxis with hepatitis B immunoglobulin for selected neonates. However, serological and molecular diagnostic testing, treatment and HBV vaccination are not consistently deployed, particularly in many high endemicity settings, and models predict that global targets for reduction in paediatric incidence will not be met by 2030. In this article, we briefly summarise the evidence for current practice and use this as a basis to discuss areas in which prevention of mother-to-child transmission can potentially be enhanced. By reducing health inequities, enhancing pragmatic use of resources, filling data gaps, developing advocacy and education, and seeking consistent investment from multilateral agencies, significant advances can be made to further reduce vertical transmission events, with wide health, societal and economic benefits.

1-Year Incidence of Tuberculosis Infection and Disease Among Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis.

BACKGROUND: Tuberculosis infection (TBI) and TB disease (TBD) incidence remains poorly described following household contact (HHC) rifampin-/multidrug-resistant TB exposure. We sought to characterize TBI and TBD incidence at 1 year in HHCs and to evaluate TB preventive treatment (TPT) use in high-risk groups. METHODS: We previously conducted a cross-sectional study of HHCs with rifampin-/multidrug-resistant TB in 8 high-burden countries and reassessed TBI (interferon-gamma release assay, HHCs aged ≥5 years) and TBD (HHCs all ages) at 1 year. Incidence was estimated across age and risk groups (<5 years; ≥5 years, diagnosed with human immunodeficiency virus [HIV]; ≥5 years, not diagnosed with HIV/unknown, baseline TBI-positive) by logistic or log-binomial regression fitted using generalized estimating equations. RESULTS: Of 1016 HHCs, 850 (83.7%) from 247 households were assessed (median, 51.4 weeks). Among 242 HHCs, 52 tested interferon-gamma release assay-positive, yielding a 1-year 21.6% (95% confidence interval [CI], 16.7-27.4) TBI cumulative incidence. Sixteen of 742 HHCs developed confirmed (n = 5), probable (n = 3), or possible (n = 8) TBD, yielding a 2.3% (95% CI, 1.4-3.8) 1-year cumulative incidence (1.1%; 95% CI, .5-2.2 for confirmed/probable TBD). TBD relative risk was 11.5-fold (95% CI, 1.7-78.7), 10.4-fold (95% CI, 2.4-45.6), and 2.9-fold (95% CI, .5-17.8) higher in age <5 years, diagnosed with HIV, and baseline TBI high-risk groups, respectively, vs the not high-risk group (P = .0015). By 1 year, 4% (21 of 553) of high-risk HHCs had received TPT. CONCLUSIONS: TBI and TBD incidence continued through 1 year in rifampin-/multidrug-resistant TB HHCs. Low TPT coverage emphasizes the need for evidence-based prevention and scale-up, particularly among high-risk groups.

Mindful Self-Care, Self-Compassion, and Resilience Among Palliative Care Providers During the COVID-19 Pandemic.

CONTEXT: Given the adverse impact of COVID-19 on the wellbeing of palliative care providers, there is a growing need to better understand protective variables, such as self-care, mindfulness and self-compassion, as they relate to resilience. OBJECTIVE: To investigate mindful self-care, self-compassion, and resilience as reported by palliative care providers during the COVID-19 pandemic. METHODS: Descriptive, cross-sectional survey. An electronic questionnaire captured data from validated instruments measuring each study variable, as well as participant demographics and perceived impacts of COVID-19 on professional quality of life. RESULTS: Positive, statistically significant correlations were found between mindful self-care, self-compassion, and resilience. These variables were also associated with greater satisfaction with professional life and perceived lessened impairment in physical and/or mental health due to a decrease in self-care activities stemming from altered routines during COVID-19. Those with higher resilience had worked in palliative care longer and also reported higher levels of self-compassion and mindful self-care, explaining 50% of variance. Self-compassion, satisfaction with professional life, and changes in self-care routine due to professional activities in the pandemic explained 44.3% of variance in mindful self-care. Self-compassion, female gender, and working as a frontline responder to the COVID-19 pandemic accounted for 35% variance in resilience levels. CONCLUSIONS: Results from this study extend the currently limited knowledge of self-care, mindfulness and self-compassion, as protective variables related to resilience in palliative care providers during the COVID-19 pandemic. Further longitudinal studies into causal effects on health and wellbeing over time are needed.

Association of Discrimination, Violence, and Resilience with Depressive Symptoms Among Transgender Women in Rio de Janeiro, Brazil: A Cross-Sectional Analysis.

Transgender women experience violence and discrimination that lead to stress responses and contribute to poor mental health. In this analysis of baseline data from Transcendendo, a trans-specific open cohort in Rio de Janeiro, Brazil, we hypothesized that the experience of discrimination and violence would be associated with depressive symptoms and that resilience could mitigate this association. Results showed that prior experiences with discrimination and sexual and physical violence were associated with depressive symptoms, while resilience was inversely associated with depressive symptoms. Resilience did not moderate nor mediate the strong effects of discrimination and violence on depressive symptoms in adjusted models.

Translation, cultural adaptation, and validation of the mindful self-care scale among Brazilian palliative care providers.

OBJECTIVE: This study aimed to translate, culturally adapt, and validate the Mindful Self-Care Scale (MSCS, 33-item) in a Brazilian hospice and palliative care context. METHOD: This was a cross-sectional study with a sample of 336 Brazilian hospice and palliative care providers. The European Organisation for Research and Treatment of Cancer - Quality of Life Group Translation Procedure protocol was used for the translation and the cultural adaptation process. Psychometric properties supporting the use of the MSCS were examined through confirmatory factor analysis (CFA) and correlation analysis with other instruments to assess congruence to related constructs (resilience and self-compassion). The reliability of the Brazilian-Portuguese version of the MSCS was assessed using Cronbach's α and composite reliability coefficients. RESULTS: The six-factor (33-item) model showed a good fit to the data, with satisfactory reliability indices and adequate representation of the scale's internal structure. Further validity is evidenced in the significant, positive correlations found between the MSCS, and similar well-being constructs, namely the Self-Compassion and Resilience scales. SIGNIFICANCE OF RESULTS: The findings reveal that the MSCS (33-item) is a valid, reliable, and culturally appropriate instrument to examine the practice of mindful self-care by hospice and palliative care providers in Brazil. More broadly, it represents a promising instrument for future research into self-care practices and well-being among Brazilian healthcare providers.

Escala para Avaliação de Náuseas e Vômitos Relacionados à Quimioterapia: Tradução e Adaptação Transcultural / Scale for the Assessment of Chemotherpy-Induced Nausea and Vomits: Translation and Transcultural Adaptation / Escala de Evaluación de Náuseas y Vómitos Relacionados con la Quimioterapia: Traducción y Adaptación Cultural

Introdução: Náuseas e vômitos induzidos por quimioterapia acometem cerca de 70-80% dos pacientes com câncer. Assim, é importante a utilização de um instrumento para avaliar melhor esses sintomas, visando a um tratamento mais adequado. Objetivo: Traduzir e adaptar culturalmente a escala Morrow Assessment of Nausea and Emesis para o contexto brasileiro. Método: Estudo correlacional do tipo survey, com tradução e adaptação cultural da escala segundo o protocolo da European Organization for Research and Treatment of Cancer ­ Quality of Life Group (EORTC-QLG). A amostra foi constituída por 160 pacientes em tratamento quimioterápico em uma clínica de oncologia. No processo de validação, realizaram-se análises de correlação multimétodos entre os itens da escala Morrow Assessment of Nausea and Emesis e os escores das escalas visuais numéricas de náusea e vômito com nível de p<0,05. Resultados: O autor da escala autorizou a tradução. A escala Morrow Assessment of Nausea and Emesis e as escalas numéricas apresentaram correlações significativas (p<0,01; p<0,05), sendo que os itens que apresentaram correlação mais forte das escalas numéricas foram os que se referiram à avaliação de náusea e vômito pós-quimioterapia. Já os itens destinados à avaliação desses sintomas no momento pré-quimioterapia e ao uso da medicação antiemética e sua eficácia apresentaram associações fracas com as escalas numéricas. Conclusão: A escala Morrow Assessment of Nausea and Emesisapresentou-se adequada para a avaliação de náuseas e vômitos induzidos por quimioterapia no contexto brasileiro

Introduction: Chemotherapy-induced nausea and vomiting affects nearly 70-80% of patients with cancer. To achieve a better treatment it is important to utilize an adequate instrument to assess these symptoms. Objective:To translate and culturally adapt the Morrow Assessment of Nausea and Emesis Scale to the Brazilian context. Method: Survey and correlational study, with the translation and cultural adaptation of the scale according to the protocol of the European Organization for Research and Treatment of Cancer ­ Quality of Life Group (EORTC-QLG). The sample consisted of 160 patients undergoing chemotherapy treatment in an oncology clinic. In the validation process, multimethod correlation analyses were carried out among the items of the Morrow Assessment of Nausea and Emesis Scale items and the scores of the numerical visual scales of nausea and vomits at the level of p<0.05. Results: The author of the scale approved the translation process. The Morrow Assessment of Nausea and Emesis scale and the numerical scales presented significant correlations (p<0.01; p<0.05), considering that the items presenting stronger correlation with the numerical scales were those addressing post-chemotherapy assessment of nausea and vomit. On the other hand, the items for pre-chemotherapy assessment of these symptoms and use of the antiemetic drugs and their efficacy presented weak associations with the numerical scales. Conclusion: The Morrow Assessment of Nausea and Emesis scale was adequate for the assessment of chemotherapy-induced nausea and vomiting in the Brazilian context

Introducción: Las náuseas y vómitos inducidos por la quimioterapia afectan aproximadamente al 70-80% de los pacientes con cáncer. Por lo tanto, es importante utilizar un instrumento para evaluar mejor estos síntomas, con el objetivo de un tratamiento más adecuado. Objetivo: Traducir y adaptar culturalmente la escala de Morrow Assessment of Nausea and Emesisal contexto brasileño. Método: Estudio correlativo del tipo de encuesta, con la traducción y adaptación cultural de la escala según el protocolo de la European Organization for Research and Treatment of Cancer ­ Quality of Life Group (EORTC-QLG). La muestra consistió en 160 pacientes sometidos a quimioterapia en una clínica oncológica. En el proceso de validación, se realizaron análisis de correlación multimétodos entre los elementos de la escala de Morrow Assessment of Nausea and Emesis y las puntuaciones de las escalas visuales numéricas de náuseas y vómitos con nivel de p<0,05. Resultados: El autor de la escala autorizó la traducción. La Morrow Assessment of Nausea and Emesis y las escalas numéricas mostraron correlaciones significativas (p<0,01; p<0,05), y los elementos que presentaron una correlación más fuerte de las escalas numéricas fueron los que se refirieron a la evaluación de las náuseas y los vómitos después de la quimioterapia. Por otro lado, los elementos destinados a la evaluación de estos síntomas en el momento anterior a la quimioterapia y el uso de medicamentos antieméticos y su eficacia presentaron asociaciones débiles con escalas numéricas. Conclusión: La Morrow Assessment of Nausea and Emesis fue adecuada para la evaluación de náuseas y vómitos inducidos por quimioterapia en el contexto brasileño

Genetic Characterization of Brucella spp.: Whole Genome Sequencing-Based Approach for the Determination of Multiple Locus Variable Number Tandem Repeat Profiles.

Brucellosis is an important zoonosis that is emerging in some regions of the world, gaining increased relevance with the inclusion of the causing agent Brucella spp. in the class B bioterrorism group. Until now, multi-locus VNTR Analysis (MLVA) based on 16 loci has been considered as the gold standard for Brucella typing. However, this methodology is laborious, and, with the rampant release of Brucella genomes, the transition from the traditional MLVA to whole genome sequencing (WGS)-based typing is on course. Nevertheless, in order to avoid a disruptive transition with the loss of massive genetic data obtained throughout the last decade and considering that the transition timings will vary considerably among different countries, it is important to determine WGS-based MLVA alleles of the nowadays sequenced genomes. On this regard, we aimed to evaluate the performance of a Python script that had been previously developed for the rapid in silico extraction of the MLVA alleles, by comparing it to the PCR-based MLVA procedure over 83 strains from different Brucella species. The WGS-based MLVA approach detected 95.3% of all possible 1,328 hits (83 strains×16 loci) and showed an agreement rate with the PCR-based MLVA procedure of 96.4% for MLVA-16. According to our dataset, we suggest the use of a minimal depth of coverage of ~50x and a maximum number of ~200 contigs as guiding "boundaries" for the future application of the script. In conclusion, the evaluated script seems to be a very useful and robust tool for the in silico determination of MLVA profiles of Brucella strains, allowing retrospective and prospective molecular epidemiological studies, which are important for maintaining an active epidemiological surveillance of brucellosis.

Utility of Gene Panels for the Diagnosis of Inborn Errors of Metabolism in a Metabolic Reference Center.

Next-generation sequencing (NGS) technologies have been proposed as a first-line test for the diagnosis of inborn errors of metabolism (IEM), a group of genetically heterogeneous disorders with overlapping or nonspecific phenotypes. Over a 3-year period, we prospectively analyzed 311 pediatric patients with a suspected IEM using four targeted gene panels. The rate of positive diagnosis was 61.86% for intermediary metabolism defects, 32.84% for complex molecular defects, 19% for hypoglycemic/hyperglycemic events, and 17% for mitochondrial diseases, and a conclusive molecular diagnosis was established in 2-4 weeks. Forty-one patients for whom negative results were obtained with the mitochondrial diseases panel underwent subsequent analyses using the NeuroSeq panel, which groups all genes from the individual panels together with genes associated with neurological disorders (1870 genes in total). This achieved a diagnostic rate of 32%. We next evaluated the utility of a tool, Phenomizer, for differential diagnosis, and established a correlation between phenotype and molecular findings in 39.3% of patients. Finally, we evaluated the mutational architecture of the genes analyzed by determining z-scores, loss-of-function observed/expected upper bound fraction (LOEUF), and haploinsufficiency (HI) scores. In summary, targeted gene panels for specific groups of IEMs enabled rapid and effective diagnosis, which is critical for the therapeutic management of IEM patients.

Caries prevalence using ICDAS visual criteria and risk assessment in children and adolescents with cerebral palsy: A comparative study.

AIMS: To compare the dental caries prevalence using the International Caries Detection and Assessment System (ICDAS) and the caries risk by Caries Management by Risk Assessment (CAMBRA) in individuals with cerebral palsy (CP) and normoactives (NAs). METHODS AND RESULTS: Sixty children and adolescents aged 6-12 years (30 CP/30 NA) were clinically evaluated by one calibrated examiner using two-digit ICDAS criteria and converted into components of dmf/DMF indices: d2mf2/D2MF2 (enamel and dentin lesions) and d3mf3/D3MF3 (dentin lesions). An adapted CAMBRA was used for risk classification. The mean d2mf2s/d2mf2t and D2MF2S/D2MF2T for CP were 17.0 ± 16.8/7.5 ± 4.3 and 10.7 ± 17.6/5.3 ± 5.8, respectively, and for NA were 17.2 ± 16.9 /6.9 ± 4.8 and 11.1 ± 11.7/5.5 ± 4.7, respectively. The mean d3mf3s/d3mf3t and D3MF3S/D3MF3T for CP were 10.1 ± 16.7/3.0 ± 4.1 and 4.9 ± 15.6/0.2 ± 0.4, respectively, while for NA the mean values were 9.8 ± 13.0/3.5 ± 3.8 and 2.1 ± 5.7/0.9 ± 2.0, respectively. There were no statistically differences for caries prevalence and risk in both groups (p > 0.05). CONCLUSIONS: Dental caries was highly prevalent in CP and NA children and adolescents. Enamel and dentin lesions and high caries risk were the most common condition.