At a glance: the largest Niemann-Pick type C1 cohort with 602 patients diagnosed over 15 years.

Niemann-Pick type C1 disease (NPC1 [OMIM 257220]) is a rare and severe autosomal recessive disorder, characterized by a multitude of neurovisceral clinical manifestations and a fatal outcome with no effective treatment to date. Aiming to gain insights into the genetic aspects of the disease, clinical, genetic, and biomarker PPCS data from 602 patients referred from 47 countries and diagnosed with NPC1 in our laboratory were analyzed. Patients' clinical data were dissected using Human Phenotype Ontology (HPO) terms, and genotype-phenotype analysis was performed. The median age at diagnosis was 10.6 years (range 0-64.5 years), with 287 unique pathogenic/likely pathogenic (P/LP) variants identified, expanding NPC1 allelic heterogeneity. Importantly, 73 P/LP variants were previously unpublished. The most frequent variants detected were: c.3019C > G, p.(P1007A), c.3104C > T, p.(A1035V), and c.2861C > T, p.(S954L). Loss of function (LoF) variants were significantly associated with earlier age at diagnosis, highly increased biomarker levels, and a visceral phenotype (abnormal abdomen and liver morphology). On the other hand, the variants p.(P1007A) and p.(S954L) were significantly associated with later age at diagnosis (p < 0.001) and mildly elevated biomarker levels (p ≤ 0.002), consistent with the juvenile/adult form of NPC1. In addition, p.(I1061T), p.(S954L), and p.(A1035V) were associated with abnormality of eye movements (vertical supranuclear gaze palsy, p ≤ 0.05). We describe the largest and most heterogenous cohort of NPC1 patients published to date. Our results suggest that besides its utility in variant classification, the biomarker PPCS might serve to indicate disease severity/progression. In addition, we establish new genotype-phenotype relationships for "frequent" NPC1 variants.

Razões para viver e risco do suicídio em graduandos de uma universidade pública de Pernambuco / Reasons for living and the meaning of suicide in graduandos of a public university of Pernambuco / Razões para vivir y el significado del suicidio en graduandos de una universidad pública de Pernambuco

Objetivo: Investigar as Razões para Viver e os riscos da ideação suicida para os graduandos da Universidade de Pernambuco. Métodos: Trata-se de uma pesquisa quantitativa com caráter descritivo realizada nas instituições do Campus Santo Amaro com 359 acadêmicos. A coleta de dados foi realizada através de dois instrumentos autoaplicáveis: um questionário sociodemográfico e a Escala de Razões para Viver. Os dados foram digitalizados em planilhas eletrônicas, o tratamento estatístico foi realizado no programa Excel. Resultados: Constatou-se que 46,52% dos acadêmicos possuem risco médio para a ideação suicida, ressalta-se ainda que um percentual de 3,62% dos estudantes teve risco elevado para o pensamento suicida. Conclusão: Tais achados constituem tanto como um diagnóstico situacional, para que as instituições de ensino superior promovam programas e estratégias voltados para a prevenção da ideação suicida e a redução de fatores de risco, tal como para que os docentes atuantes, dentro do campus ou os que assistem os estudantes fora dele, tenham conhecimento da importância de medidas que visem identificar e minimizar tal situação, melhorando assim o ambiente acadêmico. (AU)

Objective: To investigate the meaning of suicidal ideation for undergraduate at the University of Pernambuco. Methods: This is a quantitative research with descriptive character carried out in the institutions of the Campus Santo Amaro with 359 academics. Data collection was performed through two self-applied instruments: a sociodemographic questionnaire and the Scale of reasons to live. The data were scanned in spreadsheets, the statistical treatment was performed in the Excel program. Results: It was found that 46.52% of the students had a moderate risk for suicidal ideation. It was also noted a percentage of 3.62% of the students risk for suicidal thoughts. Conclusion: These findings constitute both a situational diagnosis, so that higher education institutions promote programs and strategies aimed at the prevention of suicidal ideation and the reduction of risk factors, such as for active teachers, on campus or which assist students outside of it, are aware of the importance of measures aimed at identifying and minimizing such situation, thus improving the academic environment. (AU)

Objetivo: Investigar el significado de laideación suicida para los graduandos de laUniversidad de Pernambuco. Métodos: Se trata de una investigacióncuantitativacon carácter descriptivo realizada enlasinstitucionesdel Campus Santo Amaro con 359 académicos. La recolección de datosfue realizada a través de dos instrumentos autoaplicables: uncuestionario sociodemográfico y la Escala De Razones para Vivir. Los datosfueron digitalizados enhojas de cálculo, eltratamiento estadístico fue realizado enel programa Excel. Resultados: Se constató que el 46,52% de los académicos poseenriesgopromedio para laideación suicida, se resaltaaún que unporcentajedel 3,62% de losestudiantestuvieronunriesgo elevado para elpensamiento suicida. Conclusión: Tales hallazgosconstituyen tanto como un diagnóstico situacional, para que lasinstituciones de enseñanza superior promuevan programas y estrategias dirigidos a laprevención de laideación suicida y lareducción de factores de riesgo, tal como para que los docentes actuantes, dentro del campus o que asisten a losestudiantesfuera de él, tenganconocimiento de laimportancia de medidas que apunte a identificar y minimizar tal situación, mejorandoasíel ambiente académico. (AU)

Repercussions of COVID-19 on the care and behavior of users of a Child and Adolescent Psychosocial Care Center / Repercussões da COVID-19 no cuidado e comportamento de usuários de um Centro de Atenção Psicossocial infantojuvenil

RESUMO Objetivo analisar, à luz da teoria de Callista Roy, as implicações pandêmicas da COVID-19 no comportamento e cuidado de usuários atendidos em um Centro de Atenção Psicossocial infantojuvenil. Métodos estudo qualitativo, no qual participaram 13 cuidadores familiares de usuários atendidos em um Centro de Atenção Psicossocial infantojuvenil. A coleta de dados ocorreu por entrevistas semiestruturadas. A análise dos dados foi realizada mediante a análise de conteúdo. Resultados surgiram três categorias: O impacto do distanciamento social no comportamento das crianças/adolescentes atendidos no Centro de Atenção Psicossocial infantojuvenil; Dificuldades vivenciadas pelos cuidadores familiares com as crianças/adolescentes no período da pandemia de COVID19; Acolhimento e suporte às crianças/adolescentes e familiares vinculados ao Centro de Atenção Psicossocial infantojuvenil durante a pandemia da COVID-19. Conclusão o cuidado e os comportamentos das crianças e adolescentes sofreram mudanças resultantes das alterações no convívio social e do atendimento no Centro de Atenção Psicossocial infantojuvenil. Esse cenário exigiu adaptação; e, por meio da Teoria de Callista Roy, foi possível entender melhor tal processo adaptativo. Contribuições para a prática: este estudo permite compreender melhor a problemática e, consequentemente, aprimorar o cuidado ofertado pela equipe considerando a realidade apresentada.

ABSTRACT Objective to analyze, in the light of Callista Roy's model, the pandemic implications of COVID-19 on the behavior and care of users assisted at a Child and Adolescent Psychosocial Care Center. Methods a qualitative study, in which 13 family caregivers of users assisted at a Child and Adolescent Psychosocial Care Center participated. Data collection occurred through semi-structured interviews. Data analysis was performed through content analysis. Results three categories emerged: The impact of social distancing on the behavior of children/adolescents assisted at the Child and Adolescent Psychosocial Care Center; Difficulties experienced by family caregivers with children/adolescents during the COVID 19 pandemic; Welcoming and support for children/adolescents and family members linked to the Child and Adolescent Psychosocial Care Center during the COVID-19 pandemic. Conclusion children's and adolescents' care and behavior have undergone changes resulting from changes in social interaction and care at the Child and Adolescent Psychosocial Care Center. This scenario required adaptation and, through Callista Roy's model, it was possible to better understand this adaptive process. Contributions to practice: this study allows us to better understand the problem and, consequently, improve the care offered by the team considering the reality presented.

Pessoas em situação de rua frente à COVID-19: Reflexões à luz de teorias de enfermagem / Homeless population and COVID-19: Reflections in light of nursing theories / Personas sin hogar frente a la COVID-19: Reflexiones desde las teorías de enfermería

Resumo Enquadramento: COVID-19 é uma doença respiratória aguda causada por um novo coronavírus humano. Devido à disseminação acelerada do vírus, as autoridades sanitárias preconizaram o distanciamento social. Neste sentido, a população em situação de rua vivencia dificuldades para atender a tal demanda, pela ausência de direitos básicos, como moradia, educação e saúde. Para a enfermagem, as bases epistemológicas guiadas por teorias de enfermagem contribuem para alicerçar o cuidado para essas pessoas. Objetivo: Refletir sobre o cuidado à saúde da população em situação de rua diante da pandemia de COVID-19 à luz de cinco teorias de enfermagem. Principais tópicos em análise: As teorías de Nightingale, Roy, Horta, Peplau e Henderson possuem abordagens para o cuidado pautado nas necessidades básicas das pessoas em situação de rua, que frente à COVID-19 requerem ações imediatas. Conclusão: o cuidado de enfermagem baseado nos aspetos físicos, biológicos e sociais encontram nas teorias de enfermagem suporte científico para o cuidado à população em situação de rua com parcerias intersetoriais que possam promover o cuidado durante e após pandemia.

Abstract Background: COVID-19 is an acute respiratory illness caused by a novel human coronavirus. Due to the accelerated spread of the virus, health authorities have advocated social distancing. Homeless people have difficulties meeting this requirement due to a lack of access to fundamental rights such as housing, education, and health. The epistemological bases of nursing theories contribute to underpinning the care provided to these people. Objective: To reflect on the health care of the homeless population during the COVID-19 pandemic in light of five nursing theories. Main topics under analysis: The theories of Nightingale, Roy, Horta, Peplau, and Henderson have care approaches focused on the basic needs of homeless people who require immediate interventions due to the COVID-19 pandemic. Conclusion: Nursing theories provide scientific support to caring for the homeless population based on physical, biological, and social aspects through intersectoral partnerships that can promote care during and after the pandemic.

Resumen Marco contextual: La COVID-19 es una enfermedad respiratoria aguda causada por un nuevo coronavirus humano. Debido a la acelerada propagación del virus, las autoridades sanitarias han abogado por el distanciamiento social. En este sentido, la población sin hogar experimenta dificultades para responder a dicha demanda, debido a la ausencia de derechos básicos, como la vivienda, la educación y la salud. Para la enfermería, los fundamentos epistemológicos guiados por las teorías de enfermería contribuyen a fundamentar los cuidados a estas personas. Objetivo: Reflexionar sobre los cuidados de salud de las personas sin hogar ante la pandemia de la COVID-19 en función de cinco teorías de enfermería. Principales temas en análisis: Las teorías de Nightingale, Roy, Horta, Peplau y Henderson tienen enfoques de cuidado basados en las necesidades básicas de las personas sin hogar, quienes, frente a la COVID-19, requieren una acción inmediata. Conclusión: Los cuidados de enfermería basados en los aspectos físicos, biológicos y sociales encuentran apoyo científico en las teorías de enfermería para el cuidado de las personas sin hogar con asociaciones intersectoriales que pueden promover cuidados durante y después de la pandemia.

An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients.

To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). A cohort of 3720 patients from 62 countries was tested using a panel including 206 genes with single nucleotide and copy number variant (SNV/CNV) detection, followed by semi-automatic variant filtering and reflex biochemical testing (25 assays). In 1389 patients (37%), a genetic diagnosis was achieved. Within this cohort, the highest diagnostic yield was obtained for patients from Asia (57.5%, mainly from Pakistan). Overall, 701 pathogenic/likely pathogenic unique SNVs and 40 CNVs were identified. In 620 patients, the result of the biochemical tests guided variant classification and reporting. Top five diagnosed diseases were: Gaucher disease, Niemann-Pick disease type A/B, phenylketonuria, mucopolysaccharidosis type I, and Wilson disease. We show that integrated genetic and biochemical testing facilitated the decision on clinical relevance of the variants and led to a high diagnostic yield (37%), which is comparable to exome/genome sequencing. More importantly, up to 43% of these patients (n = 610) could benefit from medical treatments (e.g., enzyme replacement therapy). This multiomic approach constitutes a unique and highly effective tool for the genetic diagnosis of IMDs.

TLR4 Antagonism Reduces Movement-Induced Nociception and ATF-3 Expression in Experimental Osteoarthritis.

INTRODUCTION: Toll-like receptor 4 (TLR4) is a pattern recognition receptor involved in the detection of pathogen-associated molecular patterns (PAMPs), but also a "danger-sensing" receptor that recognizes host-derived endogenous molecules called damage-associated molecular patterns (DAMPs). The involvement of TLR4 in rheumatic diseases is becoming evident, as well as its potential role as a target for therapeutic intervention. Moreover, increasing evidence also suggests that TLR4 is implicated in chronic pain states. Thus, in this study, we evaluated whether a systemic administration of a synthetic antagonist of TLR4 (TLR4-A1) could decrease nociception and cartilage degradation in experimental osteoarthritis (OA). Furthermore, as the activation transcription factor (ATF)-3 serves as a negative regulator for TLR4-stimulated inflammatory response, we also evaluated the effect of TLR4 inhibition on ATF-3 expression in primary afferent neurons at the dorsal root ganglia (DRG). METHODS: OA was induced in adult male Wistar rats through an intra-articular injection of 2 mg of sodium mono-iodoacetate (MIA) into the left knee. From days 14 to 28 after OA induction, animals received an intraperitoneal injection of either TLR4-A1 (10 mg/kg) or vehicle. Movement- and loading-induced nociception was evaluated in all animals, by the Knee-Bend and CatWalk tests, before and at several time-points after TLR4-A1/vehicle administration. Immunofluorescence for TLR4 and ATF-3 was performed in L3-L5 DRG. Knee joints were processed for histopathological evaluation. RESULTS: Administration of TLR4-A1 markedly reduced movement-induced nociception in OA animals, particularly in the Knee-Bend test. Moreover, the increase of ATF-3 expression observed in DRG of OA animals was significantly reduced by TLR4-A1. However, no effect was observed in cartilage loss nor in the neuronal cytoplasmic expression of TLR4 upon antagonist administration. CONCLUSION: The TLR4 antagonist administration possibly interrupts the TLR4 signalling cascade, thus decreasing the neurotoxic environment at the joint, which leads to a reduction in ATF-3 expression and in nociception associated with experimental OA.

Amylin, a peptide expressed by nociceptors, modulates chronic neuropathic pain.

BACKGROUND: Amylin is a calcitonin gene-related peptide family member expressed by nociceptors. Amylin's expression is down-regulated following nerve damage, and studies suggested it affects nociception. We aimed at clarifying amylin's effects on chronic neuropathic pain and investigating its site of action. METHODS: Chronic neuropathic pain was induced in rats by spared nerve injury (SNI) surgery. Mechanical allodynia/hyperalgesia and cold allodynia/hyperalgesia were assessed by the von Frey, pinprick, acetone and cold plate behavioural tests, respectively. Amylin, amylin-receptor antagonist (AC187) or vehicle solutions were delivered chronically, by a subcutaneous (SC) mini-osmotic pump, or acutely, by SC or intrathecal (IT) injections. Cellular and fibre markers were used to detect spinal cord alterations in SNI rats after chronic amylin administration. RESULTS: Continuous subcutaneous amylin administration aggravated cold allodynia in SNI animals, possibly via amylin-receptors (AmyR) in supraspinal areas. Acute intrathecal administration of amylin attenuated mechanical hyperalgesia, whereas AC187 reduced mechanical allodynia, suggesting distinct roles of endogenous amylin and of pharmacological amylin doses when targeting spinal cord amylin receptors. Chronic amylin administration promoted c-Fos activation only in the dorsal horn neurons of SHAM animals, suggesting a distinctive role of amylin in the activation of the spinal neuronal circuitry under neuropathic and physiological conditions. ERK1/2 phosphorylation increased in the dorsal horn neurons of SNI rats chronically treated with amylin. This ERK1/2 cascade activation may be related to amylin's effect on the aggravation of cold allodynia in SNI rats. CONCLUSIONS: Amylin's nociceptive effects seem to depend on the treatment duration and route of administration by acting at different levels of the nervous system. SIGNIFICANCE: Amylin modulated neuropathic pain by acting at different levels of the nervous system. Whereas supraspinal areas may be involved in amylin's induced pronociception, modulation of spinal cord amylin receptors by endogenous or pharmacological amylin doses triggers both pro- and antinociceptive effects.

EFFECT OF THE P.A.R.Q.V.E ON RHIZARTHRITIS.

OBJECTIVE: To evaluate the effect of a clinical management program involving education on hand function in patients with rhizarthritis. METHODS: One hundred and eight patients with rhizarthritis and multiple arthritis (191 hands with clinical and radiographic rhizarthritis) followed for two years as part of an educational program on osteoarthritis were administered the SF-36, DASH, and HAQ questionnaires and measured for the strength of their palmar grip, pulp to pulp pinch, key (lateral) pinch, and tripod pinch at the time of inclusion and after 24 months. Age, race, level and frequency of physical activity, sex, body mass index, percentage of body fat, and degree of osteoarthritis were correlated to the test outcomes. RESULTS: Women improved less than men on the HAQ (p=0.037). Each 1% reduction in fat percentage increased the chance of HAQ score improvement by 9.2% (p=0.038). Physical activity did not influence improvement in the parameters evaluated (p>0.05). Palmar grip improvement was affected by age and presence of rhizarthritis (p<0.05); patients with unilateral rhizarthritis improved 5.3 times more than patients without the disease (p=0.015), while improvement in palmar grip strength decreased 6.8% per year (p=0.004). Pulp pinch grip strength improved more in women than in men (p=0.018). CONCLUSION: Patients with rhizarthritis and multiple arthritis improved quality of life and grip strength through clinical treatment, an educational program, and fat loss. Level of Evidence II; Retrospective study.

OBJETIVO: Avaliar o efeito de um programa de tratamento clínico com ensino da função das mãos em pacientes com rizoartrite. MÉTODOS: Cento e oito indivíduos com rizoartrite e poliartrose (191 mãos com rizoartrite clínico-radiográfica) acompanhados por dois anos num programa educacional sobre osteoartrite responderam os questionários SF-36, DASH e HAQ e os testes de força de preensão palmar, pinça-polpa, pinça-chave e pinça-trípode no momento da inclusão e 24 meses depois. Idade, raça, nível e frequência de atividade física, sexo, índice de massa corporal, porcentagem de gordura corpórea, grau de osteoartrite foram correlacionados aos testes realizados. RESULTADOS: As mulheres melhoraram em menor grau que homens no HAQ (p = 0,037) e cada redução de 1% no percentual de gordura aumenta 9,2% a chance de melhora no HAQ (p = 0,038). A atividade física não influenciou a melhora dos parâmetros avaliados (p > 0,05). Idade e presença de rizoartrite influenciam a melhora da preensão palmar (p < 0,05), sendo que pacientes com rizoartrite unilateral melhoram 5,3 vezes mais que pacientes sem a doença (p = 0,015) e a melhora da preensão diminui 6,8% por ano (p = 0,004). As mulheres melhoraram em maior grau que homens na pinça-polpa (p = 0,018). CONCLUSÃO: Pacientes com rizoartrite e poliartrose têm melhor qualidade de vida e força de preensão com o tratamento clínico, programa educacional e perda de gordura. Nível de Evidência II; Estudo retrospectivo.

Effect of the p.a.r.q.v.e on rhizarthritis / Efeito do p.a.r.q.v.e sobre a rizoartrite

ABSTRACT Objective: To evaluate the effect of a clinical management program involving education on hand function in patients with rhizarthritis. Methods: One hundred and eight patients with rhizarthritis and multiple arthritis (191 hands with clinical and radiographic rhizarthritis) followed for two years as part of an educational program on osteoarthritis were administered the SF-36, DASH, and HAQ questionnaires and measured for the strength of their palmar grip, pulp to pulp pinch, key (lateral) pinch, and tripod pinch at the time of inclusion and after 24 months. Age, race, level and frequency of physical activity, sex, body mass index, percentage of body fat, and degree of osteoarthritis were correlated to the test outcomes. Results: Women improved less than men on the HAQ (p=0.037). Each 1% reduction in fat percentage increased the chance of HAQ score improvement by 9.2% (p=0.038). Physical activity did not influence improvement in the parameters evaluated (p>0.05). Palmar grip improvement was affected by age and presence of rhizarthritis (p<0.05); patients with unilateral rhizarthritis improved 5.3 times more than patients without the disease (p=0.015), while improvement in palmar grip strength decreased 6.8% per year (p=0.004). Pulp pinch grip strength improved more in women than in men (p=0.018). Conclusion: Patients with rhizarthritis and multiple arthritis improved quality of life and grip strength through clinical treatment, an educational program, and fat loss. Level of Evidence II; Retrospective study.

RESUMO Objetivo: Avaliar o efeito de um programa de tratamento clínico com ensino da função das mãos em pacientes com rizoartrite. Métodos: Cento e oito indivíduos com rizoartrite e poliartrose (191 mãos com rizoartrite clínico-radiográfica) acompanhados por dois anos num programa educacional sobre osteoartrite responderam os questionários SF-36, DASH e HAQ e os testes de força de preensão palmar, pinça-polpa, pinça-chave e pinça-trípode no momento da inclusão e 24 meses depois. Idade, raça, nível e frequência de atividade física, sexo, índice de massa corporal, porcentagem de gordura corpórea, grau de osteoartrite foram correlacionados aos testes realizados. Resultados: As mulheres melhoraram em menor grau que homens no HAQ (p = 0,037) e cada redução de 1% no percentual de gordura aumenta 9,2% a chance de melhora no HAQ (p = 0,038). A atividade física não influenciou a melhora dos parâmetros avaliados (p > 0,05). Idade e presença de rizoartrite influenciam a melhora da preensão palmar (p < 0,05), sendo que pacientes com rizoartrite unilateral melhoram 5,3 vezes mais que pacientes sem a doença (p = 0,015) e a melhora da preensão diminui 6,8% por ano (p = 0,004). As mulheres melhoraram em maior grau que homens na pinça-polpa (p = 0,018). Conclusão: Pacientes com rizoartrite e poliartrose têm melhor qualidade de vida e força de preensão com o tratamento clínico, programa educacional e perda de gordura. Nível de Evidência II; Estudo retrospectivo.

Glial activation in the collagenase model of nociception associated with osteoarthritis.

Background Experimental osteoarthritis entails neuropathic-like changes in dorsal root ganglia (DRG) neurons. Since glial activation has emerged as a key player in nociception, being reported in numerous models of neuropathic pain, we aimed at evaluating if glial cell activation may also occur in the DRG and spinal cord of rats with osteoarthritis induced by intra-articular injection of collagenase. Methods Osteoarthritis was induced by two injections, separated by three days, of 500 U of type II collagenase into the knee joint of rats. Movement-induced nociception was evaluated by the Knee-Bend and CatWalk tests during the following six weeks. Glial fibrillary acidic protein (GFAP) expression in satellite glial cells of the DRG was assessed by immunofluorescence and Western Blot analysis; the pattern of GFAP and activating transcription factor-3 (ATF-3) expression was also compared through double immunofluorescence analysis. GFAP expression in astrocytes and IBA-1 expression in microglia of the L3-L5 spinal cord segments was assessed by immunohistochemistry and Western Blot analysis. The effect of the intrathecal administration of fluorocitrate, an inhibitor of glial activation, on movement-induced nociception was evaluated six weeks after the first collagenase injection. Results GFAP expression in satellite glial cells of collagenase-injected animals was significantly increased six weeks after osteoarthritis induction. Double immunofluorescence showed GFAP upregulation in satellite glial cells surrounding ATF-3-positive neurons. In the spinal cord of collagenase-injected animals, an ipsilateral upregulation of GFAP and IBA-1 was also observed. The inhibition of glial activation with fluorocitrate decreased movement- and loading-induced nociception. Conclusion Collagenase-induced knee osteoarthritis leads to the development of nociception associated with movement of the affected joint and to the activation of glial cells in both the DRG and the spinal cord. Inhibition of glial cell activation by fluorocitrate decreases these osteoarthritis-associated nociceptive behaviours. These results suggest that glial cell activation may play a role in the development of chronic pain in this experimental model of osteoarthritis.

Clinical, biochemical, molecular, and histological features of 65 Portuguese patients with mitochondrial disorders.

INTRODUCTION: Mitochondrial disorders display remarkable genetic and phenotypic heterogeneity. METHODS: We performed a retrospective analysis of the clinical, histological, biochemical, and genetic features of 65 patients with molecular diagnoses of mitochondrial disorders. RESULTS: The most common genetic diagnosis was a single large-scale mitochondrial DNA (mtDNA) deletion (41.5%), and the most frequent clinical phenotype was chronic progressive external ophthalmoplegia (CPEO). It occurred in 41.5% of all patients, primarily in those with mtDNA deletions. Histological signs of mitochondrial dysfunction were found in 73.8% of patients, and respiratory chain enzyme assay (RCEA) abnormalities were detected in 51.9%. CONCLUSIONS: This study confirms the high relative frequency of single large-scale deletions among mitochondrial disorders as well as its particular association with CPEO. Muscle histology seems to be particularly useful in older patients and those with mtDNA deletions, whereas RCEA might be more helpful in young children or individuals with mtDNA depletion. Muscle Nerve 56: 868-872, 2017.

The impact of migration on women's mental health in the postpartum period.

OBJECTIVE: To assess the influence of I mmigration on the psychological health of women after childbirth. METHODS: In this cross-sectional study, immigrant and Portuguese-native women delivering in the four public hospitals of the metropolitan area of Porto, Portugal, were contacted by telephone between February and December 2012 during the first postpartum month to schedule a home visit and fill in a questionnaire. Most immigrant (76.1%) and Portuguese mothers (80.0%) agreed to participate and with the visits, thus a total of 89 immigrants and 188 Portuguese women were included in the study. The questionnaire included the application of four validated scales: Mental Health Inventory-5, Edinburgh Postpartum Depression Scale, Perceived Stress Scale, and Scale of Satisfaction with Social Support. Statistical analysis included t-test and Chi-square or Fisher's test, and logistic regression models. RESULTS: Immigrants had an increased risk of postpartum depression (OR = 6.444, 95%CI 1.858-22.344), and of low satisfaction with social support (OR = 6.118, 95%CI 1.991-18.798). We did not perceive any associations between migrant state, perceived stress, and impoverished mental health. CONCLUSIONS: Immigrant mothers have increased vulnerabilities in the postpartum period, resulting in an increased risk of postpartum depression and lesser satisfaction with the received social support.

The impact of migration on women's mental health in the postpartum period / O impacto da migração na saúde mental das mulheres no pós-parto

ABSTRACT OBJECTIVE To assess the influence of I mmigration on the psychological health of women after childbirth. METHODS In this cross-sectional study, immigrant and Portuguese-native women delivering in the four public hospitals of the metropolitan area of Porto, Portugal, were contacted by telephone between February and December 2012 during the first postpartum month to schedule a home visit and fill in a questionnaire. Most immigrant (76.1%) and Portuguese mothers (80.0%) agreed to participate and with the visits, thus a total of 89 immigrants and 188 Portuguese women were included in the study. The questionnaire included the application of four validated scales: Mental Health Inventory-5, Edinburgh Postpartum Depression Scale, Perceived Stress Scale, and Scale of Satisfaction with Social Support. Statistical analysis included t-test and Chi-square or Fisher's test, and logistic regression models. RESULTS Immigrants had an increased risk of postpartum depression (OR = 6.444, 95%CI 1.858-22.344), and of low satisfaction with social support (OR = 6.118, 95%CI 1.991-18.798). We did not perceive any associations between migrant state, perceived stress, and impoverished mental health. CONCLUSIONS Immigrant mothers have increased vulnerabilities in the postpartum period, resulting in an increased risk of postpartum depression and lesser satisfaction with the received social support.

RESUMO OBJETIVO Avaliar a influência da imigração na saúde psicológica da mulher após o parto. MÉTODOS Neste estudo transversal, mulheres imigrantes e portuguesas com partos nos quatro hospitais públicos da região metropolitana de Porto, Portugal, foram contatadas por telefone entre fevereiro e dezembro de 2012, durante o primeiro mês pós-parto, para agendar uma visita domiciliar e preencher um questionário. A maioria das mães imigrantes (76,1%) e das mães portuguesas (80,0%) aceitou participar e aceder a visitas domiciliares, totalizando 89 imigrantes e 188 mulheres portuguesas incluídas no estudo. O questionário incluiu a aplicação de quatro escalas validadas: Inventário de Saúde Mental-5, Escala de Depressão Pós-parto de Edimburgo, Escala de Stress Percebido e Escala de Satisfação com o Suporte Social. As análises estatísticas incluíram os testes t-student, Qui-quadrado ou teste de Fisher e o cálculo de modelos de regressão logística. RESULTADOS As imigrantes tiveram risco aumentado de depressão pós-parto (OR 6,444; IC95% 1,858-22,344) e de baixa satisfação com o suporte social (OR = 6,118; IC95% 1,991-18,798). Não houve associação entre migração, stress percebido e saúde mental empobrecida. CONCLUSÕES Mães imigrantes apresentam vulnerabilidades aumentadas no período pós-parto, aumentando o risco de depressão pós-parto e havendo menor satisfação com o apoio social recebido.

Clinical Severity of PGK1 Deficiency Due To a Novel p.E120K Substitution Is Exacerbated by Co-inheritance of a Subclinical Translocation t(3;14)(q26.33;q12), Disrupting NUBPL Gene.

Carriers of cytogenetically similar, apparently balanced familial chromosome translocations not always exhibit the putative translocation-associated disease phenotype. Additional genetic defects, such as genomic imbalance at breakpoint regions or elsewhere in the genome, have been reported as the most plausible explanation.By means of comprehensive molecular and functional analyses, additional to careful dissection of the t(3;14)(q26.33;q12) breakpoints, we unveil a novel X-linked PGK1 mutation and examine the contribution of these to the extremely severe clinical phenotype characterized by hemolytic anemia and neuromyopathy.The 3q26.33 breakpoint is 40 kb from the 5' region of tetratricopeptide repeat domain 14 gene (TTC14), whereas the 14q12 breakpoint is within IVS6 of nucleotide-binding protein-like gene (NUBPL) that encodes a mitochondrial complex I assembly factor. Disruption of NUBPL in translocation carriers leads to a decrease in the corresponding mRNA accompanied by a decrease in protein level. Exclusion of pathogenic genomic imbalance and reassessment of familial clinical history indicate the existence of an additional causal genetic defect. Consequently, by WES a novel mutation, c.358G>A, p.E120K, in the X-linked phosphoglycerate kinase 1 (PGK1) was identified that segregates with the phenotype. Specific activity, kinetic properties, and thermal stability of this enzyme variant were severely affected. The novel PGK1 mutation is the primary genetic alteration underlying the reported phenotype as the translocation per se only results in a subclinical phenotype. Nevertheless, its co-inheritance presumably exacerbates PGK1-deficient phenotype, most likely due to a synergistic interaction of the affected genes both involved in cell energy supply.

Inborn errors of metabolism in the biosynthesis and remodelling of phospholipids.

Since the proposal to define a separate subgroup of inborn errors of metabolism involved in the biosynthesis and remodelling of phospholipids, sphingolipids and long chain fatty acids in 2013, this group is rapidly expanding. This review focuses on the disorders involved in the biosynthesis of phospholipids. Phospholipids are involved in uncountable cellular processes, e.g. as structural components of membranes, by taking part in vesicle and mitochondrial fusion and fission or signal transduction. Here we provide an overview on both pathophysiology and the extremely heterogeneous clinical presentations of the disorders reported so far (Sengers syndrome (due to mutations in AGK), MEGDEL syndrome (or SERAC defect, SERAC1), Barth syndrome (or TAZ defect, TAZ), congenital muscular dystrophy due to CHKB deficiency (CHKB). Boucher-Neuhäuser/Gordon Holmes syndrome (PNPLA6), PHARC syndrome (ABHD12), hereditary spastic paraplegia type 28, 54 and 56 (HSP28, DDHD1; HSP54, DDHD2; HSP56, CYP2U1), Lenz Majewski syndrome (PTDSS1), spondylometaphyseal dysplasia with cone-rod dystrophy (PCYT1A), atypical haemolytic-uremic syndrome due to DGKE deficiency (DGKE).

Obstetric care in a migrant population with free access to health care.

OBJECTIVE: To evaluate differences in obstetric care between immigrant and native women in a country with free access to health care. METHODS: A cross-sectional study was carried out of immigrant mothers delivering in one of the four public hospitals in the Porto, Portugal, metropolitan area between February and December 2012. The comparison group included native Portuguese mothers who delivered in the same institutions. The participants (89 immigrant mothers and 188 Portuguese mothers) were recruited by telephone and completed a written questionnaire during a home visit. RESULTS: Immigrant women were more likely to have their first pregnancy appointment after 12 weeks of pregnancy (27.0% vs 14.4%, P = 0.011) and to have fewer than three prenatal visits (2.2% vs 0.0%, P < 0.001). They were also more likely to have had a cesarean delivery (48.3% vs 31.4%, P = 0.023), perineal laceration (48.8% vs 11.6%, P < 0.001), or postpartum hemorrhage (33.5% vs 12.3%, P < 0.001). CONCLUSION: Migrants were more prone to late prenatal care and to intrapartum complications. Unsatisfactory interactions with healthcare staff may play an important role in these findings.

Syndromes associated with mitochondrial DNA depletion.

Mitochondrial dysfunction accounts for a large group of inherited metabolic disorders most of which are due to a dysfunctional mitochondrial respiratory chain (MRC) and, consequently, deficient energy production. MRC function depends on the coordinated expression of both nuclear (nDNA) and mitochondrial (mtDNA) genomes. Thus, mitochondrial diseases can be caused by genetic defects in either the mitochondrial or the nuclear genome, or in the cross-talk between the two. This impaired cross-talk gives rise to so-called nuclear-mitochondrial intergenomic communication disorders, which result in loss or instability of the mitochondrial genome and, in turn, impaired maintenance of qualitative and quantitative mtDNA integrity. In children, most MRC disorders are associated with nuclear gene defects rather than alterations in the mtDNA itself.The mitochondrial DNA depletion syndromes (MDSs) are a clinically heterogeneous group of disorders with an autosomal recessive pattern of transmission that have onset in infancy or early childhood and are characterized by a reduced number of copies of mtDNA in affected tissues and organs. The MDSs can be divided into least four clinical presentations: hepatocerebral, myopathic, encephalomyopathic and neurogastrointestinal. The focus of this review is to offer an overview of these syndromes, listing the clinical phenotypes, together with their relative frequency, mutational spectrum, and possible insights for improving diagnostic strategies.

Assessing maternal healthcare inequities among migrants: a qualitative study.

Considering pregnancy and motherhood as periods of increased vulnerability in migrant women, to characterize the healthcare provided to this collective, we sought to identify and understand patterns of satisfaction and demand of maternal and child healthcare, assessing women's perceptions about its quality. The study followed a qualitative methodology (semi-structured interviews) for collecting and analysing data (content analysis) and was conducted in Porto, the second largest city of Portugal. Participants were 25 recent immigrant mothers from Eastern European countries, Brazil, Portuguese-speaking African countries and six native Portuguese recent mothers (for comparison), contacted through social associations and institutions. Data suggests that healthcare depends not only on accessibility but especially on social opportunities. Equitable public health action must provide individuals and groups the equal opportunity to meet their needs, which may not be achieved by providing the same standard if care to all.

Assessing maternal healthcare inequities among migrants: a qualitative study / Avaliando desigualdades de saude materna em migrantes: um estudo qualitativo / Evaluacion de las inequidades en salud materna entre los inmigrantes: un estudio cualitativo

Considering pregnancy and motherhood as periods of increased vulnerability in migrant women, to characterize the healthcare provided to this collective, we sought to identify and understand patterns of satisfaction and demand of maternal and child healthcare, assessing women’s perceptions about its quality. The study followed a qualitative methodology (semi-structured interviews) for collecting and analysing data (content analysis) and was conducted in Porto, the second largest city of Portugal. Participants were 25 recent immigrant mothers from Eastern European countries, Brazil, Portuguese-speaking African countries and six native Portuguese recent mothers (for comparison), contacted through social associations and institutions. Data suggests that healthcare depends not only on accessibility but especially on social opportunities. Equitable public health action must provide individuals and groups the equal opportunity to meet their needs, which may not be achieved by providing the same standard if care to all.

Considerando a gravidez e a maternidade como períodos de maior vulnerabilidade em mulheres migrantes, a fim de caracterizar os cuidados de saúde prestados, procurou-se identificar e compreender padrões de satisfação e procura de cuidados de saúde materna e infantil, avaliando as suas percepções sobre a qualidade deles. O estudo seguiu uma metodologia qualitativa (entrevistas semiestruturadas) para a coleta e análise de dados (análise de conteúdo) e foi realizado no Porto, a segunda maior cidade de Portugal. As participantes foram 25 mães recém-imigradas do Leste Europeu, Brasil, e países africanos de língua portuguesa e seis Portuguesas (para comparação), contatadas pelas associações e instituições sociais. Os dados sugerem que a saúde depende não só da acessibilidade, mas especialmente das oportunidades sociais. Ações equitativas de saúde pública devem proporcionar aos indivíduos e grupos oportunidades iguais para satisfazer as suas necessidades, que podem não ser alcançadas fornecendo o mesmo tratamento padrão para todos.

Considerando el embarazo y maternidad como los períodos de mayor vulnerabilidad para las mujeres inmigrantes, y con el fin de caracterizar la asistencia sanitaria, se buscó identificar y comprender patrones de satisfacción y demanda de salud materno-infantil, así como la evaluación de las percepciones sobre la calidad de los mismos. El estudio siguió una metodología cualitativa (entrevistas semi-estructuradas) para la recogida y análisis de datos (análisis de contenido) y se llevó a cabo en Porto, la segunda ciudad más grande de Portugal. Las participantes fueron 25 madres, inmigrantes recientes de países de la Europa del Este, Brasil, países africanos de habla portuguesa y seis nativas portuguesas (para su comparación), contactadas a través de asociaciones e instituciones sociales. Los datos sugieren que la asistencia sanitaria no sólo depende de la accesibilidad, sino especialmente de las oportunidades sociales. Las acciones equitativas de salud pública deben proporcionar igualdad de oportunidades a las personas y grupos para satisfacer sus necesidades, que no se pueden lograr al ofrecer una misma atención estándar a todos.

Migrant women's perceptions of healthcare during pregnancy and early motherhood: addressing the social determinants of health.

Recent guidelines from the World Health Organization emphasize the need to monitor the social determinants of health, with particular focus on the most vulnerable groups. With this in mind, we evaluated the access, use and perceived quality of care received by migrant women during pregnancy and early motherhood, in a large urban area in northern Portugal. We performed semi-structured interviews in 25 recent mothers, contacted through welfare institutions, who had immigrated from Eastern European countries, Brazil, or Portuguese-speaking African countries. Six native-Portuguese women of equal economic status were also interviewed for comparison. Misinformation about legal rights and inadequate clarification during medical appointments frequently interacted with social determinants, such as low social-economic status, unemployment, and poor living conditions, to result in lower perceived quality of healthcare. Special attention needs to be given to the most vulnerable populations in order to improve healthcare. Challenges reside not only in assuring access, but also in promoting equity in the quality of care.