Formation of an invasion-permissive matrix requires TGFß/SNAIL1-regulated alternative splicing of fibronectin.

BACKGROUND: As in most solid cancers, the emergence of cells with oncogenic mutations in the mammary epithelium alters the tissue homeostasis. Some soluble factors, such as TGFß, potently modify the behavior of healthy stromal cells. A subpopulation of cancer-associated fibroblasts expressing a TGFß target, the SNAIL1 transcription factor, display myofibroblastic abilities that rearrange the stromal architecture. Breast tumors with the presence of SNAIL1 in the stromal compartment, and with aligned extracellular fiber, are associated with poor survival prognoses. METHODS: We used deep RNA sequencing and biochemical techniques to study alternative splicing and human tumor databases to test for associations (correlation t-test) between SNAIL1 and fibronectin isoforms. Three-dimensional extracellular matrices generated from fibroblasts were used to study the mechanical properties and actions of the extracellular matrices on tumor cell and fibroblast behaviors. A metastatic mouse model of breast cancer was used to test the action of fibronectin isoforms on lung metastasis. RESULTS: In silico studies showed that SNAIL1 correlates with the expression of the extra domain A (EDA)-containing (EDA+) fibronectin in advanced human breast cancer and other types of epithelial cancers. In TGFß-activated fibroblasts, alternative splicing of fibronectin as well as of 500 other genes was modified by eliminating SNAIL1. Biochemical analyses demonstrated that SNAIL1 favors the inclusion of the EDA exon by modulating the activity of the SRSF1 splicing factor. Similar to Snai1 knockout fibroblasts, EDA- fibronectin fibroblasts produce an extracellular matrix  that does not sustain TGFß-induced fiber organization, rigidity, fibroblast activation, or tumor cell invasion. The presence of EDA+ fibronectin changes the action of metalloproteinases on fibronectin fibers. Critically, in an mouse orthotopic breast cancer model, the absence of the fibronectin EDA domain completely prevents lung metastasis. CONCLUSIONS: Our results support the requirement of EDA+ fibronectin in the generation of a metastasis permissive stromal architecture in breast cancers and its molecular control by SNAIL1. From a pharmacological point of view, specifically blocking EDA+ fibronectin deposition could be included in studies to reduce the formation of a pro-metastatic environment.

Cytotoxic and Antileishmanial Effects of the Monoterpene ß-Ocimene.

Leishmaniasis is a group of infectious-parasitic diseases with high mortality rates, and endemic in many regions of the globe. The currently available drugs present serious problems such as high toxicity, costs, and the emergence of drug resistance. This has stimulated research into new antileishmania drugs based on natural products and their derivatives. ß-Ocimene is a monoterpene found naturally in the essential oils of many plant species which presents antileishmanial activity, and which has not yet been evaluated for its potential to inhibit the etiological agent of leishmaniasis. The aim of this work was to evaluate the activity of ß-ocimene against Leishmania amazonensis, its cytotoxicity, and potential mechanisms of action. ß-Ocimene presented direct activity against the parasite, with excellent growth inhibition of promastigotes (IC50 = 2.78 µM) and axenic amastigotes (EC50 = 1.12 µM) at concentrations non-toxic to RAW 264.7 macrophages (CC50 = 114.5 µM). The effect is related to changes in membrane permeability and resulting abnormalities in the parasitic cell shape. These were, respectively, observed in membrane integrity and atomic force microscopy assays. ß-Ocimene was also shown to act indirectly, with greater activity against intra-macrophagic amastigotes (EC50 = 0.89 µM), increasing TNF-α, nitric oxide (NO), and reactive oxygen species (ROS), with lysosomal effects, as well as promoting decreases in IL-10 and IL-6. Against intra-macrophagic amastigote forms the selectivity index was higher than the reference drugs, being 469.52 times more selective than meglumine antimoniate, and 42.88 times more selective than amphotericin B. Our results suggest that ß-ocimene possesses promising in vitro antileishmania activity and is a potential candidate for investigation in in vivo assays.

Longitudinal assessment of the eating pattern of people with dementia and its association with problems for feeding and malnutrition: a prospective follow-up study protocol.

INTRODUCTION: Dementia conditions the patient's nutrition from the beginning and vice versa. Generating difficulties for feeding (FEDIF) will influence its evolution. There are currently few nutritional longitudinal studies in people with dementia. Most focus on problems already established. The Edinburgh Feeding Evaluation in Dementia (EdFED) Scale identifies FEDIF of patients with dementia by studying their behaviours while eating or being fed. It also indicates areas of potential clinical interventions. METHODS AND ANALYSIS: Prospective multicentre observational study carried out in nursing homes, Alzheimer's day care centres and primary healthcare centres. The study population will be dyads composed by the patient (diagnosed of dementia, over 65 years of age and who have feeding difficulties) and their family caregiver. Sociodemographic variables and nutritional status (body mass index, Mini Nutritional Assessment, blood test and calf and arm circumference) will be assessed. The Spanish version of the EdFED Scale will be completed and the presence of nursing diagnoses related to feeding behaviours will be collected. Follow-up will take place for 18 months. ETHICS AND DISSEMINATION: All data will be carried out respecting European legislation 2016/679 in data protection, and the Spanish 'Organic Law 3/2018 of December 2005'. The clinical data will be kept segregated and encrypted. The informed consent has been obtained. The research has been authorised by the Costa del Sol Health Care District on 27 February 2020 and the Ethics Committee on 2 March 2021. It has obtained funding from the Junta de Andalucía on 15 February 2021. Findings of the study will be presented at provincial, national and international conferences and published in peer-reviewed journals.

Eugenia piauhiensis Vellaff. essential oil and γ-elemene its major constituent exhibit antileishmanial activity, promoting cell membrane damage and in vitro immunomodulation.

Leishmaniasis is considered as one of the most Neglected Tropical Diseases (NTDs) in the world, caused by protozoan parasites of the genus Leishmania. Treatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. The search for new therapeutic agents from natural sources has been a constant for the treatment of diseases such as leishmaniasis. The objective of this study was to evaluate the biological activity of Eugenia piauhiensis Vellaff. essential oil (EpEO) and its major constituent γ-elemene on promastigote and amastigote forms of Leishmania (Leishmania) amazonensis, its cytotoxicity, and possible mechanisms of action. EpEO was more active (IC50 6.43 ± 0.18 µg/mL) against promastigotes than γ-elemene [9.82 ± 0.15 µg/mL (48.05 ± 0.73 µM)] and the reference drug miltefosine [IC50 17.25 ± 0.26 µg/mL (42.32 ± 0.64 µM)]. EpEO and γ-elemene exhibited low cytotoxicity against J774.A1 macrophages, with CC50 225.8 ± 3.57 µg/mL and 213.21 ± 3.3 µg/mL (1043 ± 16.15 µM), respectively. Additionally, EpEO and γ-elemene present direct activity against the parasite, decreasing plasma membrane integrity. EpEO and γ-elemene also proved to be even more active against intracellular amastigotes of the parasite [IC50 4.59 ± 0.07 µg/mL and 8.06 ± 0.12 µg/mL (39.44 ± 0.59 µM)], respectively), presenting indirect effects through macrophage activity modulation. Anti-amastigote activity was associated with increased TNF-α, IL-12, NO, and ROS levels. In conclusion, our results suggest EpEO and γ-elemene as promising candidates for new drug development against leishmaniasis.

Health, longevity, infrastructure and competitiveness: The Four Horsemen of COVID-19.

Many researchers around the world are working to reach a general framework to provide solutions for COVID-19 in different ways. From our economic and business orientation, "Health, Longevity, Infrastructure and Competitiveness" are presented in this paper as the Four Horsemen of COVID-19. Our aim is to analyse the relationship between these proposed four factors and their influence on COVID-19. Using the Global Competitive Index (GCI), Health Systems in Transition (HiT) and the System of Health Accounts (SHA), we complete a database for a total of 28 countries of the European Union, including the United Kingdom and using variables related to the environment of each region (competitiveness, security, infrastructure, population and health system). Our study is focused on a descriptive analysis and a binary logistic model (logit), trying to distinguish between countries with more and less incidence of COVID-19. According to the results, the presence of these four factors - which are desirables for any country - implies a greater transmission of the virus in these regions. However, a higher annual expenditure in the health system is related to a lower incidence of COVID-19.

[Prevalence of SARS-CoV-2 coronavirus infection in patients and professional staff at a medium or long-stay hospital in Spain]. / Prevalencia de infección por coronavirus SARS-CoV-2 en pacientes y profesionales de un hospital de media y larga estancia en España.

BACKGROUND AND GOALS: The aim of the study is to know the prevalence of SARS-CoV-2 infection in patients and professional staff of a medium or long-stay hospital during the peak period of the pandemic in Spain, spring 2020. MATERIAL AND METHODS: At the end of February 2020, we developed at the hospital a strategy to diagnose the SARS-CoV-2 infection consisting of complementing the realization of PCR tests at real time with a quick technique of lateral flow immunochromatography to detect IgG and IgM antibodies against the virus. We also developed a protocol to realize those diagnostic tests and considered an infection (current or past) a positive result in any of the above tests. We included 524 participants in the study (230 patients and 294 hospital staff), and divided them into hospital patients and Hemodialysis outpatients. Furthermore, we divided the hospital staff into healthcare and non-healthcare staff. The documented period was from March, 20th to April, 21st, 2020. RESULTS: 26 out of 230 patients tested positive in any of the diagnostic techniques (PCR, antibodies IgG, IgM) with a 11.30% prevalence. According to patients groups, we got a 14.38% prevalence in hospital patients vs. 5.95% in outpatients, with a significantly higher risk in admitted patients after adjustment for age and gender (OR=3,309, 95%CI: 1,154-9,495). 24 out of 294 hospital staff tested positive in any of the diagnostic techniques, with a 8.16% prevalence. According to the groups, we got a 8.91% prevalence in healthcare staff vs. 4.26% in non-healthcare staff. Thus, we do not see any statistically significant differences between hospital staff and patients as far as prevalence is concerned (P=0,391), (OR=2,200, 95%CI: 0,500-9,689). CONCLUSIONS: The result of the study was a quite low prevalence rate of SARS-CoV-2 infection, in both patients and hospital staff, being the hospital patients' prevalence rate higher than the outpatients', and the healthcare staff higher than the non-healthcare's. Combining PCR tests (gold standard) with antibodies tests proved useful as a diagnostic strategy.

Prevalencia de infección por coronavirus SARS-CoV-2 en pacientes y profesionales de un hospital de media y larga estancia en España / Prevalence of SARS-CoV-2 coronavirus infection in patients and professional staff at a medium or long-stay hospital in Spain

ANTECEDENTES Y OBJETIVO: El objetivo de este estudio fue conocer la prevalencia de la infección por SARS-CoV-2 en pacientes y profesionales de un hospital de media y larga estancia en el periodo del pico de la pandemia en España en la primavera de 2020. MATERIAL Y MÉTODOS: A finales de febrero del 2020, se diseñó en el hospital una estrategia para el diagnóstico de la infección por SARS-CoV-2 consistente en complementar la realización de PCR a tiempo real con una técnica rápida de inmunocromatografía de flujo lateral para la detección de anticuerpos IgG e IgM frente al virus. Se protocolizó la realización de dichas pruebas diagnósticas y se consideró como infección (actual o pasada) un resultado positivo de alguna de ellas. Se incluyeron en el estudio a 524 participantes (230 pacientes y 294 profesionales). Los pacientes se agruparon en ingresados y en ambulatorios para terapia de hemodiálisis. Los trabajadores se agruparon en asistenciales y no asistenciales. El periodo que se documenta es el comprendido entre el 20 de marzo y el 21 de abril del 2020. RESULTADOS: En 26 de los 230 pacientes el resultado fue positivo en alguna de las técnicas, con una prevalencia del 11,30%. Por grupos, en ingresados fue del 14,38% frente al 5,95% de los ambulatorios (p = 0,055), siendo significativamente superior el riesgo en pacientes ingresados tras ajustar por sexo y edad (OR = 3,309; IC del 95%: 1,154-9,495). En 24 de los 294 profesionales el resultado fue positivo en alguna de las técnicas, con una prevalencia del 8,16%. Por grupos, en asistenciales fue del 8,91% frente al 4,26% de los no asistenciales (p = 0,391), OR ajustada = 2,502 (IC del 95%: 0,559-11,202). CONCLUSIONES: Se ha encontrado una tasa de prevalencia baja frente a SARS-CoV-2 tanto en pacientes como en profesionales. La prevalencia en pacientes hospitalizados es mayor que en ambulatorios, también es superior la prevalencia de sanitarios asistenciales respecto a los no asistenciales

BACKGROUND AND GOALS: The aim of the study is to know the prevalence of SARS-CoV-2 infection in patients and professional staff of a medium or long-stay hospital during the peak period of the pandemic in Spain, spring 2020. MATERIAL AND METHODS: At the end of February 2020, we developed at the hospital a strategy to diagnose the SARS-CoV-2 infection consisting of complementing the realization of PCR tests at real time with a quick technique of lateral flow immunochromatography to detect IgG and IgM antibodies against the virus. We also developed a protocol to realize those diagnostic tests and considered an infection (current or past) a positive result in any of the above tests. We included 524 participants in the study (230 patients and 294 hospital staff), and divided them into hospital patients and Hemodialysis outpatients. Furthermore, we divided the hospital staff into healthcare and non-healthcare staff. The documented period was from March, 20th to April, 21st, 2020. RESULTS: 26 out of 230 patients tested positive in any of the diagnostic techniques (PCR, antibodies IgG, IgM) with a 11.30% prevalence. According to patients groups, we got a 14.38% prevalence in hospital patients vs. 5.95% in outpatients, with a significantly higher risk in admitted patients after adjustment for age and gender (OR=3,309, 95%CI: 1,154-9,495). 24 out of 294 hospital staff tested positive in any of the diagnostic techniques, with a 8.16% prevalence. According to the groups, we got a 8.91% prevalence in healthcare staff vs. 4.26% in non-healthcare staff. Thus, we do not see any statistically significant differences between hospital staff and patients as far as prevalence is concerned (P=0,391), (OR=2,200, 95%CI: 0,500-9,689). CONCLUSIONS: The result of the study was a quite low prevalence rate of SARS-CoV-2 infection, in both patients and hospital staff, being the hospital patients' prevalence rate higher than the outpatients', and the healthcare staff higher than the non-healthcare's. Combining PCR tests (gold standard) with antibodies tests proved useful as a diagnostic strategy

Description of frail older people profiles according to four screening tools applied in primary care settings: a cross sectional analysis.

BACKGROUND: Regarding the health care of older populations, WHO recommends shifting from disease-driven attention models towards a personalized, integrated and continuous care aimed to the maintenance and enhancement of functional capacities. Impairments in the construct of functional intrinsic capacity have been understood as the condition of frailty or vulnerability. No consensus has been yet reached regarding which tools are the most suitable for screening this kind of patients in primary care settings. Tools based on the measurement of functional performance such as Timed up and go test (TUG), Short Physical Performance battery (SPPB), self-completed questionnaires like Tilburg Frailty Indicator (TFI) and clinical judgement, as the Gerontopole Frailty Scale (GFS) may be adequate. The objective of this work is to describe and compare characteristics of community-dwelling individuals identified as vulnerable or frail by four tools applied in primary care settings. METHODS: Cross sectional analysis developed in primary care services in two regions of Spain. Community-dwelling independent individuals aged 70 or more willing to participate were recruited and data was collected via face-to-face interviews. Frailty was assessed by TUG, SPPB, TFI and GFST. Also socio-demographic characteristics, lifestyle habits and health status data (comorbidities, polypharmacy, self-perceived health), were collected. Multiple correspondence analysis (MCA) and cluster analysis were used to identify groups of individuals with similar characteristics. RESULTS: Eight hundred sixty-five individuals were recruited, 53% women, with a mean age of 78 years. Four clusters of participants emerge. Cluster 1 (N = 263) contained patients categorized as robust by most of the studied tools, whereas clusters 2 (N = 199), 3 (N = 183) and 4 (N = 220) grouped patients classified as frail or vulnerable by at least one of the tools. Significant differences were found between clusters. CONCLUSIONS: The assessed tools identify different profiles of patients according to their theoretical construct of frailty. There is a group of patients that are identified by TUG and SPPB but not by GFS or TFI. These tools may be useful in primary care settings for the implementation of a function- driven clinical care of older patients.

Cardiovascular risk in children and adolescents with end stage renal disease.

OBJECTIVES: To evaluate cardiovascular involvement in children and adolescents with End Stage Renal Disease (ESRD) and to characterize the main risk factors associated with this outcome. METHODS: Cross-sectional study of 69 children and adolescents at renal transplantation and 33 healthy individuals matched by age and gender. The study outcomes were left ventricular mass z-score (LVMZ) and carotid artery intima-media thickness (CIMT). The potential risk factors considered were age, gender, CKD etiology, use of oral vitamin D and calcium-based phosphate binders, systolic and diastolic blood pressure, body mass index z-score, time since diagnosis, dialysis duration, serum levels of ionic calcium, phosphorus, parathyroid hormone, fibroblast growth factor (FGF 23), uric acid, homocysteine, cholesterol, triglycerides, C-reactive protein (CRP), vitamin D and hemoglobin. RESULTS: In the multivariate analysis, the factors associated with LVMZ were dialysis duration, age, systolic blood pressure, serum hemoglobin and HDL cholesterol levels. Regarding CIMT, in the multivariate analysis, systolic blood pressure was the only factor associated with the outcome. CONCLUSION: Children exhibited important cardiovascular involvement at the time of the renal transplantation. Both of the studied outcomes were independently associated with systolic blood pressure. For this reason, controlling blood pressure seems to be the main therapy to minimize cardiovascular involvement in children with ESRD.

No toda escoliosis idiopática es lo que parece / Not all scoliosis are what they seem

No disponible

Is arterial calcification in children and adolescents with end-stage renal disease a rare finding?

AIM: To investigate if calcification and intimal media thickness (IMT) of arteries are present in children and adolescents with end-stage renal disease and to describe the risk factors associated with these alterations. METHODS: In an observational, cross-sectional prospective study, 68 patients were evaluated at the time of renal transplantation. A fragment of the inferior epigastric artery was removed during surgery for histopathological analysis to verify the presence or not of arterial calcification. Two outcomes were considered: the presence of calcium deposition and the measurement of the IMT of the artery. The potential exposure variables were: age, chronic kidney disease aetiology, diagnosis time, systolic blood pressure (SBP), use of oral active vitamin D, homocysteine and C-reactive protein. RESULTS: No arterial calcification was observed in the studied sample. The median value of the IMT of the inferior epigastric artery was 166 µm (interquartile range = 130-208). SBP standard deviation score and age were the only factors associated with this outcome. There was no statistical interaction between SBP and age with the IMT (P = 0.280). CONCLUSION: Arterial calcification is rare in children and adolescents with end-stage renal disease. The factors associated with IMT were age and SBP.

Cardiovascular risk in children and adolescents with end stage renal disease

OBJECTIVES: To evaluate cardiovascular involvement in children and adolescents with End Stage Renal Disease (ESRD) and to characterize the main risk factors associated with this outcome. METHODS: Cross-sectional study of 69 children and adolescents at renal transplantation and 33 healthy individuals matched by age and gender. The study outcomes were left ventricular mass z-score (LVMZ) and carotid artery intima-media thickness (CIMT). The potential risk factors considered were age, gender, CKD etiology, use of oral vitamin D and calcium-based phosphate binders, systolic and diastolic blood pressure, body mass index z-score, time since diagnosis, dialysis duration, serum levels of ionic calcium, phosphorus, parathyroid hormone, fibroblast growth factor (FGF 23), uric acid, homocysteine, cholesterol, triglycerides, C-reactive protein (CRP), vitamin D and hemoglobin. RESULTS: In the multivariate analysis, the factors associated with LVMZ were dialysis duration, age, systolic blood pressure, serum hemoglobin and HDL cholesterol levels. Regarding CIMT, in the multivariate analysis, systolic blood pressure was the only factor associated with the outcome. CONCLUSION: Children exhibited important cardiovascular involvement at the time of the renal transplantation. Both of the studied outcomes were independently associated with systolic blood pressure. For this reason, controlling blood pressure seems to be the main therapy to minimize cardiovascular involvement in children with ESRD.

Raquitismo hipofosfatêmico: relato de caso / Hypophosphatemic rickets: case report

RESUMO Objetivo: O raquitismo hipofosfatêmico precisa ser precocemente diagnosticado porque seu tratamento previne sequelas incapacitantes. Este relato alerta para a doença. Relato de caso: Relato de perfil metabólico, depuração de creatinina, estado nutricional e desenvolvimento pôndero-estatural de paciente com características clínico-laboratoriais de raquitismo hipofosfatêmico, atendido em ambulatório de tubulopatias por período de 12 meses. Chegou ao serviço após tempo prolongado acamado, dependente de ventilação mecânica e com perfil metabólico ósseo alterado. Terapêutica consistiu na administração de fósforo (inicial: 65 mg/kg/dia, final: 24,2 mg/kg/dia), cálcio (inicial: 127 mg/kg/dia, final: 48,4 mg/kg/dia) e calcitriol (inicial: 0,06 mcg/kg/dia, final: 0,03 mcg/kg/dia), e a análise constou da descrição das consultas, utilizando-se mediana de exames laboratoriais e dados antropométricos. Observou-se nítida melhora inicial do padrão respiratório do paciente, que evoluiu com ventilação espontânea e deambulação autônoma; com exames laboratoriais: cálcio (mg/dL) inicial 7,1, final 10,1; fósforo (mg/dL) inicial 1,7, final 3,2; magnésio (mg/dL) inicial 1,5, final 2,1; paratormônio (pg/L) inicial 85,8, final 52,7; fosfatase alcalina (UI/L) inicial 12660, final 938; e melhora do desenvolvimento pôndero-estatural (escore Z: E/I inicial: -6,05, final -3,64; P/I: inicial -2,92, final -1,57) com presença de litíase transitória. A depuração de creatinina (mL/min/1,73 m2sc) foi constante durante o seguimento. O tratamento propiciou benefícios clínicos, bioquímicos e nutricionais, mas, apesar da boa resposta inicial, a família abandonou o seguimento por dois anos, apresentando o paciente piora da deambulação e das deformidades esqueléticas. Comentários: Não apenas diagnóstico precoce é necessário, como também a adesão ao tratamento é fundamental para o sucesso na condução dessa patologia.

ABSTRACT Objective: Early diagnosis and immediate treatment of hypophosphatemic rickets is of utmost importance as it may prevent subsequent sequelae. This report aims at warning pediatricians to consider the presence of the disease. Case description: Description of the metabolic profile, creatinine clearance, nutritional status, weight and body structure of a patient who presented the clinical-laboratorial characteristics of hypophosphatemic rickets and was followed in an outpatient clinic for tubulopathies over the period of 12 months. The patient had been bedridden for some time, was dependent on mechanical ventilation and presented an altered metabolic bone condition. Treatment was phosphate (initial: 65 mg/kg/day and final: 24,2 mg/kg/day), calcium (initial: 127 mg/kg/day, final: 48,4 mg/kg/day) and calcitriol (initial: 0.06 mcg/kg/day, final: 0.03 mcg/kg/day). The patient improved, evolving into spontaneous breathing and walking unaided. Laboratory results: calcium (mg/dL) initial 7.1, final 10.1; phosphate (mg/dL) initial 1.7 final 3.2; magnesium (mg/dL) initial 1.5 final 2.1, parathyroid hormone (pg/l) initial 85.8, final 52.7, alkaline phosphatase (UI/l) initial 12660, final 938; there was also improvement in weight/structural development (Z score: H/A initial: -6.05, final -3.64; W/A: initial -2.92, final -1.57) with presence of transitory gallstones. Creatinine clearance (mL/min/1.73m2bsa) was constant. The medication improved his laboratory results and nutritional status, but the patient did not return for two years for follow-up and, during this period, his condition has noticeably deteriorated. Comments: Early diagnosis and follow-up are essential in dealing with this pathology.

HYPOPHOSPHATEMIC RICKETS: CASE REPORT. / RAQUITISMO HIPOFOSFATÊMICO: RELATO DE CASO.

OBJECTIVE: Early diagnosis and immediate treatment of hypophosphatemic rickets is of utmost importance as it may prevent subsequent sequelae. This report aims at warning pediatricians to consider the presence of the disease. CASE DESCRIPTION: Description of the metabolic profile, creatinine clearance, nutritional status, weight and body structure of a patient who presented the clinical-laboratorial characteristics of hypophosphatemic rickets and was followed in an outpatient clinic for tubulopathies over the period of 12 months. The patient had been bedridden for some time, was dependent on mechanical ventilation and presented an altered metabolic bone condition. Treatment was phosphate (initial: 65 mg/kg/day and final: 24,2 mg/kg/day), calcium (initial: 127 mg/kg/day, final: 48,4 mg/kg/day) and calcitriol (initial: 0.06 mcg/kg/day, final: 0.03 mcg/kg/day). The patient improved, evolving into spontaneous breathing and walking unaided. Laboratory results: calcium (mg/dL) initial 7.1, final 10.1; phosphate (mg/dL) initial 1.7 final 3.2; magnesium (mg/dL) initial 1.5 final 2.1, parathyroid hormone (pg/l) initial 85.8, final 52.7, alkaline phosphatase (UI/l) initial 12660, final 938; there was also improvement in weight/structural development (Z score: H/A initial: -6.05, final -3.64; W/A: initial -2.92, final -1.57) with presence of transitory gallstones. Creatinine clearance (mL/min/1.73m2bsa) was constant. The medication improved his laboratory results and nutritional status, but the patient did not return for two years for follow-up and, during this period, his condition has noticeably deteriorated. COMMENTS: Early diagnosis and follow-up are essential in dealing with this pathology.

OBJETIVO: O raquitismo hipofosfatêmico precisa ser precocemente diagnosticado porque seu tratamento previne sequelas incapacitantes. Este relato alerta para a doença. RELATO DE CASO: Relato de perfil metabólico, depuração de creatinina, estado nutricional e desenvolvimento pôndero-estatural de paciente com características clínico-laboratoriais de raquitismo hipofosfatêmico, atendido em ambulatório de tubulopatias por período de 12 meses. Chegou ao serviço após tempo prolongado acamado, dependente de ventilação mecânica e com perfil metabólico ósseo alterado. Terapêutica consistiu na administração de fósforo (inicial: 65 mg/kg/dia, final: 24,2 mg/kg/dia), cálcio (inicial: 127 mg/kg/dia, final: 48,4 mg/kg/dia) e calcitriol (inicial: 0,06 mcg/kg/dia, final: 0,03 mcg/kg/dia), e a análise constou da descrição das consultas, utilizando-se mediana de exames laboratoriais e dados antropométricos. Observou-se nítida melhora inicial do padrão respiratório do paciente, que evoluiu com ventilação espontânea e deambulação autônoma; com exames laboratoriais: cálcio (mg/dL) inicial 7,1, final 10,1; fósforo (mg/dL) inicial 1,7, final 3,2; magnésio (mg/dL) inicial 1,5, final 2,1; paratormônio (pg/L) inicial 85,8, final 52,7; fosfatase alcalina (UI/L) inicial 12660, final 938; e melhora do desenvolvimento pôndero-estatural (escore Z: E/I inicial: -6,05, final -3,64; P/I: inicial -2,92, final -1,57) com presença de litíase transitória. A depuração de creatinina (mL/min/1,73 m2sc) foi constante durante o seguimento. O tratamento propiciou benefícios clínicos, bioquímicos e nutricionais, mas, apesar da boa resposta inicial, a família abandonou o seguimento por dois anos, apresentando o paciente piora da deambulação e das deformidades esqueléticas. COMENTÁRIOS: Não apenas diagnóstico precoce é necessário, como também a adesão ao tratamento é fundamental para o sucesso na condução dessa patologia.

Manejo del dolor en edad pediátrica. Artículo de revisión / Handling of the pain in pediatric age. Review article

Se realizó una revisión teórica del manejo del dolor en el niño; un problema común entre los niños y adolescentes, tal y como han mostrado estudios epidemiológicos recientes. El tratamiento del dolor en el niño, durante muchos años, fue percibido como herramienta de segundo plano en las terapias pediátricas, que buscaban preferentemente la terapéutica basada en la etiología. Para poder medir el dolor con similar exactitud a la medición de la temperatura, el profesional de la salud debe proveerse de los medios posibles, para lo que se han creado escalas con las que el niño puede trasmitir diferente información sobre aspectos del dolor, como duración e intensidad del mismo. La Organización Mundial de la Salud definió una escalera del dolor, como una guía en la estructuración del tratamiento analgésico. Aliviar el dolor debe ser una tarea obligada para el pediatra de hoy. Para ello, debería desterrar algún error, sobre lo que es preciso insistir, al partir de algunos datos epidemiológicos y fisiopatológicos (AU)

A theoretical review of the pain handling in the child was carried out; a common problem between children and adolescents, as recent epidemiologic studies has showed. The treatment of the pain in the child, for many years, was perceived as a background tool in the pediatric therapies, which were looking preferably for the therapeutics based on the etiology. To be able to measure the pain with similar accuracy to the measurement of the temperature, the health professional must be provided with the possible means for what there have been created scales that child can transmit different information about pain aspects, like duration and intensity. The World Health Organization defined a pain stairs, as a guide in the structure of the analgesic treatment. To relieve the pain must be a task forced for pediatrician nowadays. For it, it should exile some error, on what it is necessary to insist, departing from some epidemiological and physiopathological information (AU)

Clinical utility of combined Placido-scanning-slit midperipheral and thinnest point pachymetry after corneal ablation for myopia.

PURPOSE: The aim of this study was to assess the random error of the thinnest point and midperipheral pachymetry with a combined Placido-scanning-slit system (Orbscan II) in the intermediate-term follow-up of excimer laser keratorefractive surgery for treating myopia. METHODS: Sixty-five patients who had undergone aspheric surface ablation for treating myopia with a minimum follow-up of 6 months, and showed no biomicroscopically detectable corneal haze, were subjected to 5 consecutive topographic examinations. All eyes underwent a complete ophthalmic examination before the surgery. The within-subject SD (Sw), repeatability (2.77 × Sw), coefficient of repeatability (2.77 × Sw/mean), and intraclass correlation coefficients of pachymetry at the thinnest point and in each 4 quadrants at a 6-mm diameter were calculated. RESULTS: The patients had a mean age of 31.9 ± 6.2 years, and the average follow-up was for 7.5 ± 2.6 months. The mean ablation depth for myopia was 63.6 ± 23.6 µm. The average pachymetry for the thinnest point and midperipheral superior, inferior, nasal, and temporal locations was 456.9, 602.0, 595.5, 609.7, and 566.1 µm, respectively. The repeatability (and coefficient of repeatability) for the thinnest point and midperipheral superior, inferior, nasal, and temporal locations was 26.5 (5.8%), 37.9 (6.3%), 31.0 (5.2%), 30.5 (5.0%), and 35.4 µm (6.2%), respectively. The intraclass correlation coefficients were 0.96, 0.88, 0.89, 0.97, and 0.91 for each location, respectively. CONCLUSIONS: This study provides the repeatability of the thinnest and midperipheral pachymetry using the combined Placido-scanning-slit system in transparent corneas after laser keratorefractive surgery for treatment of myopia. The test-retest reliability provided here will help differentiate real corneal thickness change from measurement noise. For this, only pachymetric changes >6% are likely to be real and therefore useful when evaluating postoperative keratectasia suspects.

Influência das orientações fisioterapêuticas na qualidade de vida e na sobrecarga de cuidadores / Influence of physiotherapeutic guidelines in the caregiver's quality of life and overload

INTRODUÇÃO: O despreparo do cuidador pode acarretar situações de risco para quem cuida e para quem recebe o cuidado. OBJETIVO: Avaliar a influência de orientações fisioterapêuticas na qualidade de vida e na sobrecarga de cuidadores informais de pacientes com disfunções decorrentes de acidente vascular encefálico (AVE) ou de trauma raquimedular (TRM). MATERIAIS E MÉTODOS: Doze cuidadoras informais, com idade média de 50,5 ± 16,5 anos, sendo 4 de pacientes com disfunções decorrentes de TRM e 8 de pacientes que sofreram AVE. Todos os pacientes estavam em atendimento fisioterapêutico. No primeiro encontro, as cuidadoras foram instruídas a anotar as dúvidas e dificuldades do dia a dia. Após uma semana, entregaram as anotações; na mesma ocasião, foi avaliada a qualidade de vida e a sobrecarga, utilizando o questionário SF-36 e o Questionário de Avaliação da Sobrecarga do Cuidador Informal, respectivamente. Duas semanas depois, foi realizada uma aula teórico-prática baseada nas dúvidas e nas respostas dos questionários. Após quatro semanas, foram reavaliadas. Para comparação pré e pós-intervenção, foi utilizado o teste t pareado (p < 0,05). RESULTADOS: As dúvidas anotadas estavam relacionadas ao banho do paciente e com a própria saúde física e mental. Não se observou incremento no índice geral da qualidade de vida (p = 0,1226). Apenas para os domínios dor (p = 0,0316) e saúde mental (p = 0,0029) observou-se diferença significativa. Não se observou diferença na sobrecarga do cuidador. CONCLUSÃO: Uma intervenção com orientações fisioterapêuticas repercutiu na redução da dor e melhora da saúde mental em cuidadores informais de pessoas com disfunções decorrentes de TRM ou AVE.

INTRODUCTION: The caregiver's unpreparedness can lead to risky situations for caregivers and for those who receive the care. OBJECTIVE: To assess the impact of the physiotherapeutic guidelines on quality of life and overload of informal caregivers of patients with spinal cord injury or stroke disabilities. MATERIALS AND METHODS: Twelve female informal caregivers, mean age 50,5 ± 16,5 years old. Four were caregiver from patients with disability caused by spinal cord injury and 8 by stroke. All patients were in physical therapy. At the first meeting, the caregivers received a notepad to write down their daily difficulties. After a week, they returned the notepads. On this day we assessed the quality of life, using the SF-36, and the overload, using the Questionnaire for Assessment to Informal Caregiver Overload. Two weeks later, we prepared a theoretical and practical class based on the notes and the questionnaires scores. After 4 weeks, the caregivers were assessed again using the baseline instruments. To compare pre and post intervention was used paired t-test (p < 0,05). RESULTS: The doubts were about the patient's bath and their own physical and mental health. There was no increase in quality of life (p = 0.1226). Only for the domains of pain (p = 0.0316) and mental health (p = 0.0029) was observed a significant difference. There was no difference in caregiver overload. CONCLUSIONS: An intervention with physical therapy guidelines reduced pain and improved mental health in informal caregivers of patients with spinal cord injury or stroke disabilities.

Síndrome de Bartter: avaliação do desenvolvimento estatural e perfil metabólico / Bartter's syndrome: evaluation of statural growth and metabolic profile

OBJETIVO: A síndrome de Bartter é uma doença rara, porém uma das mais frequentes condições congênitas perdedoras de cloro. Este trabalho teve como objetivo relatar a evolução de dez pacientes com a síndrome. MÉTODOS: Estudo observacional, descritivo, realizado pela análise de prontuários médicos relatando o perfil metabólico, a depuração de creatinina, o estado nutricional e pôndero-estatural de dez pacientes atendidos no Serviço de Nefrologia da Universidade Federal de São Paulo com características clínico-laboratoriais da síndrome de Bartter, seguidos por um período médio de 43 meses (3-76 meses). Durante o acompanhamento, o tratamento consistiu na administração de suplemento de potássio (100 por cento), magnésio (60 por cento), anti-inflamatórios não hormonais (90 por cento), inibidores de enzima conversora de angiotensina (40 por cento) e espironolactona (50 por cento). A análise estatística constou da comparação dos dados da primeira e da última consulta, utilizando-se o teste de Wilcoxon. RESULTADOSs: Observou-se melhora dos valores absolutos dos itens avaliados e do desenvolvimento pôndero-estatural com a terapêutica empregada, porém apenas a calemia [mediana inicial 3,05mEqL e final 3,25mEqL (p=0,01)] e o escore Z de peso idade [mediana inicial -2,47 e final -1,35 (p=0,02)] apresentaram melhora significante. Dos dez pacientes estudados, dois apresentavam diminuição da depuração de creatinina com doença renal crônica estágio 2 no final do acompanhamento (ambos tinham iniciado o acompanhamento com depuração renal comprometida). CONCLUSÕES: Há necessidade da instituição terapêutica precoce para melhorar os níveis séricos dos eletrólitos e o estado nutricional dos pacientes acometidos, sem comprometer a depuração de creatinina.

OBJECTIVE: Bartter's syndrome is one of the most important inherited diseases that cause chloride leak. The objective of this study was to report the follow-up of ten patients with the syndrome. METHODS: This observational study was based on the review of medical charts reporting the metabolic features, creatinine clearance, nutritional and anthropometric assessment of ten patients with Bartter's syndrome followed at the Nephrology Service of the Universidade Federal de São Paulo, in their first and last medical appointments, after a mean follow-up period of 43 months (3-76 months). During the follow-up, the management included the administration of potassium (100 percent) and magnesium (60 percent) supplements, non-steroidal anti-inflammatory agents (90 percent), angiotensin-converting enzyme inhibitors (40 percent) and spironolactone (50 percent). Statistical analysis was performed comparing the results of first versus last clinical appointment by non-parametric Wilcoxon test. RESULTS: Improvement of serum electrolytes and statural growth after the treatment was observed but only serum potassium [3.05mEq/L versus 3.25 mEq/L (p=0.01)] and weigh-for-age Z-score [initial median -2.47 versus -1.35 (p=0.02)] improved significantly. Out of the ten patients studied, two presented decrease of creatinine clearance with chronic kidney disease at stage 2 at the end of the follow-up. These patients had already started the follow-up with decreased creatinine clearance. CONCLUSIONS: There is a need of early treatment of patients with Bartter's syndrome in order to improve their electrolytes and nutritional condition without compromising the creatinine clearance.

OBJETIVO: El síndrome de Bartter (SB) es una enfermedad rara, pero una de las más frecuentes condiciones congénitas perdedoras de cloro. Este trabajo tiene por objetivo relatar la evolución de diez pacientes con SB. MÉTODOS: Estudio observacional, descriptivo, obtenido mediante análisis de prontuarios médicos. Relata el perfil metabólico, la depuración de creatinina, el estado nutricio-nal y ponderoestatural de los diez pacientes atendidos en el ambulatorio de Tubulopatías de Universidade Federal de São Paulo con características clínico-laboratoriales de SB, seguidos por un periodo mediano de 43 meses (3-76 meses). Durante el seguimiento se practicó protocolo de tratamiento que consistió en la administración de suplemento de potasio (100 por ciento), magnesio (60 por ciento), anti-inflamatorios no hormonales (90 por ciento), inhibidores de enzima convertidora de angiotensina (40 por ciento) y espironolactona (50 por ciento). Se consideraron criterios de exclusión la presencia de alteraciones séricas y urinarias no compatibles con SB. El análisis estadístico constó de la comparación de datos de la primera y la última consulta, utilizándose la prueba de Wilcoxon. RESULTADOS: Se observó mejora numérica de los valores absolutos de los ítems evaluados y del desarrollo ponderoestatural con la terapéutica utilizada, pero solamente la calemia [mediana inicial 3,05mEq/L y final 3,25mEq/L (p=0,01)] y el escore Z de peso/edad [mediana inicial -2,47 y final 1,35 (p=0,02)] presentaron mejora significante. De los 10 pacien-tes estudiados, dos presentaban reducción de la depuración de creatinina con enfermedad renal crónica etapa 2 y en el final del seguimiento (ambos habían iniciado el seguimiento con depuración renal comprometida). CONCLUSIONES: Los datos enfatizan la necesidad de la ins-titución terapéutica precoz para mejorar los niveles séricos de los electrólitos y el estado nutricional, sin comprometer la depuración de creatinina.

Siameses parapagus tetrabrachius dipus / Parapagus tetrabrachius dipus conjoined twins

Los gemelos siameses o gemelos unidos son gemelos monocigóticos, monoamnióticos, monocoriales, unidos entre sí por alguna región de su anatomía, como resultado de una división incompleta del disco embrionario que ocurre después del día 13 de la concepción. Presentamos el caso de unos siameses parapagus tetrabrachius dipus, diagnosticados de forma temprana mediante ecografía a la 11+5 semanas de gestación(AU)

Conjoined twins are defined as monozygotic, monochorionic and monoamniotic twins fused at any portion of their body as a result of an incomplete division of the embryonic disk, which occurs after the 13th day of conception. We present a case report describing the first trimester ultrasound diagnosis of Parapagus Tetrabrachius Dipus twins(AU)