A Case of Childhood-Onset Bartter Syndrome Type 1 with Renal Dysfunction / 罕见病研究

Bartter syndrome (BS, OMIM #601678) is a rare inherited salt-losing tubulopathy characterized by hypokalemia metabolic alkalosis with secondary renin-angiotensin-aldosterone system activation. As reported, BS type 1 is generally presented prenatal and neonatal period, and symptoms usually appear before and after birth or in infancy, accompanied by severe salt loss, whilst kidney function remains mostly normal. In this study, we report a case of BS type 1 with childhood onset and proteinuria and renal impairment. The child was born preterm due to hyperamniotic fluid, but there were no apparent symptoms after birth until the age of 3 when the child began to present with polydipsia, polyuria and increased nocturnal uria. At the age of 5, she had elevated serum creatinine level and proteinuria. After admission, she was diagnosed with chronic tubulointerstitial disease and stage 2 chronic kidney disease(CKD). According to the chloride clearance test, the abnormal function of medullary thick ascending limb Henle′s loop, was confirmed and BS type 1 was diagnosed by gene sequencing. After active management of complications, kidney function of the child improved. In the long-term follow-up, the urinary protein amount of the child still increased, eGFR slowly decreased, and the child was currently in the CKD2 stage. Children with prenatal BS may not present typical clinical manifestations immediately after birth until the onset of relevant clinical symptoms in childhood. BS type 1 patients may have renal impairment, which needs to be identified in time. Clinical differentiation diagnosis between BS and Gitelman syndrome can be made by chloride clearance tests. Early diagnosis and treatment are critical to improve prognosis.

Functions of HIV-1 Tat and its association with diseases / 中国生物制品学杂志

@#Acquired immune deficiency syndrome,or AIDS,has been a major infectious disease that troubles the public health in a global scale. Human immunodeficiency virus type 1(HIV-1)is the causative reagent responsible for AIDS development. Even though the highly active anti-retroviral therapy(HAART,or the cocktail therapy)that has been widely applied could effectively suppress the infection and replication of HIV-1,the infected people suffer from other related diseases,such as the HIV-associated neurocognitive disorder(HAND). This paper mainly focused on the function of an important regulatory protein of HIV-1,trans-activator of transcription(Tat),and its correlation with HIV-1 replication and HAND development,so as to clarify the importance of developing anti-AIDS drugs targeting Tat protein

Modified Liuwei Dihuangtang Combined with Losartan Potassium Regulates ACE1/AngⅡ/AT1R Axis and Intestinal Flora in Rat Model of Diabetic Kidney Disease / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of modified Liuwei Dihuangtang in preventing and treating renal injury in diabetic kidney disease （DKD） via the angiotensin-converting enzyme 1 （ACE1）/angiotensin Ⅱ （AngⅡ）/angiotensin Ⅱ type 1 receptor （AT1R） axis. MethodFifty male SD rats were randomized into a normal group （n=8） and a modeling group （n=42）. The rats in the modeling group were fed with a high-sugar and high-fat diet for 6 weeks and intraperitoneally injected with 35 mg·kg-1 streptozotocin （STZ） to establish the model of DKD. After successful modeling， the rats were randomized into model， traditional Chinese medicine （modified Liuwei Dihuangtang granules 21 g·kg-1）， western medicine （losartan potassium， 33 mg·kg-1）， and integrated Chinese and western medicine （losartan potassium 33 mg·kg-1 combined with modified Liuwei Dihuangtang granules 21 g·kg-1） groups. The levels of fasting blood glucose （FBG）， urinary protein （Up）， blood urea nitrogen （Bun）， and serum creatinine （SCr） were measured in each group after 8 consecutive weeks of drug intervention. Enzyme-linked immunosorbent assay was employed to determine the serum levels of ACE1， AngⅡ， and AT1R. Western blot was employed to measure the protein levels of ACE1， AngⅡ， and AT1R in the renal tissue. The pathological and morphological changes of the renal tissue were observed after hematoxylin-eosin （HE） staining， Masson staining， and periodic acid Schiff 's （PAS） staining. The fecal samples of rats in each group were collected for 16S rDNA high-throughput sequencing. ResultCompared with the normal group， the model group showed elevated levels of Up， FBG， Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01）， serious lesions in the renal tissue， up-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.01）， increased Firmicutes/Bacteroidetes （F/B） ratio， decreased relative abundance of Lactobacillus， and increased relative abundance of Moralella and Bifidobacteria. Compared with the model group， drug intervention lowered the levels of Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01） and alleviated the pathological changes in the renal tissue. Chinese medicine and integrated Chinese and western medicine lowered the levels of Up and FBG （P<0.01）， and western medicine and integrated Chinese and western medicine down-regulated the protein levels of ACE1， AngⅡ， and AT1R. In addition， Chinese medicine down-regulated the protein levels of AngⅡ （P<0.01） as well as ACE1 and AT1R （P<0.05）. Chinese medicine and integrated Chinese and western medicine decreased the F/B ratio， and western medicine and Chinese medicine increased the relative abundance of Blautia. Chinese medicine and integrated Chinese and western medicine increased the relative abundance of Lactobacillus， Ruminococcus undetermined genera， and Bifidobacteria， decreased the relative abundance of Moralella， and increased the Chao 1 and Ace indexes （P<0.05）. Compared with the western medicine group， the integrated Chinese and western medicine group showed lowered levels of Up （P<0.01）， Bun （P<0.05）， and ACE1 and AT1R （P<0.01）， down-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.05）， alleviated pathological changes in the renal tissue， increased relative abundance of Bifidobacteria， and increased Chao 1 and Ace indexes （P<0.05）. ConclusionModified Liuwei Dihuangtang combined with losartan potassium can mitigate renal fibrosis by regulating the ACE1/AngⅡ/AT1R axis， increasing the relative abundance of Lactobacillus and Bifidobacterium， reducing the relative abundance of Moralella， improving the richness and evenness of intestinal flora， and alleviating pathological damage in the renal tissue.

Isolation of bone marrow mesenchymal stem cells in transgenic pigs and co-culture with porcine islets / 器官移植

Objective To investigate the isolation and culture of porcine bone marrow mesenchymal stem cell (BMSC) with α-1, 3-galactosyltransferase (GGTA1) gene knockout (GTKO), GTKO/ human CD46 (hCD46) insertion and cytidine monopho-N-acetylneuraminic acid hydroxylase (CMAH)/GGTA1 gene knockout (Neu5GC/Gal), and the protective effect of co-culture with porcine islets on islet cells. Methods Bone marrow was extracted from different transgenic pigs modified with GTKO, GTKO/hCD46 and Neu5GC/Gal. Porcine BMSC were isolated by the whole bone marrow adherent method and then cultured. The morphology of BMSC was observed and the surface markers of BMSC were identified by flow cytometry. Meantime, the multi-directional differentiation induced by BMSC was observed, and the labeling and tracing of BMSC were realized by green fluorescent protein (GFP) transfection. The porcine BMSC transfected with GFP were co-cultured with porcine islet cells. Morphological changes of porcine islet cells were observed, and compared with those in the porcine islet cell alone culture group. Results BMSC derived from pigs were spindle-shaped in vitro, expressing biomarkers of CD29, CD44, CD73, CD90, CD105 and CD166 rather than CD34 and CD45. These cells were able to differentiate into adipocytes, osteoblasts and chondrocytes. Porcine BMSC with GFP transfection could be labeled and traced, which could be stably expressed in the daughter cells after cell division. Porcine BMSC exerted certain protective effect on islet cells. Conclusions GFP-labeled porcine BMSC modified with GTKO, GTKO/hCD46 and Neu5GC/Gal are successfully established, which exert certain protective effect upon islet cells.

The mechanism of chlorogenic acid against neuropathic pain induced by cisplatin / 药学学报

This study aimed to investigate the analgesic effect of chlorogenic acid on cisplatin-induced neuropathic pain and explored the underlying molecular mechanisms. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Xinxiang Central Hospital, in compliance with the Institutional Animal Care Guidelines. Von Frey hair and a radiant heat was employed to measure mechanical allodynia and thermal hyperalgesia; Western blot was used to examine transient receptor potential vanilloid type-1 (TRPV1) protein expression in the rat dorsal root ganglion (DRG); patch clamp was used to record TRPV1 currents in DRG neurons. The experimental results showed that chlorogenic acid could attenuate cisplatin-induce mechanical allodynia and thermal hyperalgesia in rats. The expression of TRPV1 protein in DRGs was increased in cisplatin-treated rats, while chlorogenic acid also could reverse cisplatin-induced the upregulation of TRPV1 protein. Forthermore, chlorogenic acid could attenuate cisplatin-mediated the upregulation of TRPV1 current density. These above results indicated that chlorogenic acid could alleviate cisplatin-induced pain hypersensitivity through inhibition of the expression and function of TRPV1 in rats.

Effects of metabolites of eicosapentaenoic acid on promoting transdifferentiation of pancreatic OL cells into pancreatic β cells / 中国药理学通报

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Application progress of mesenchymal stem cells in islet transplantation for type 1 diabetes mellitus / 器官移植

Islet transplantation is considered as one of the most effective approach for type 1 diabetes mellitus, although its efficacy is limited by several factors. Anoxia, stress and rejection occurring during the isolation, culturing and transplantation of islets may have impact on the outcome of the islet transplantation. Due to the biological properties such as anti-inflammation, angiogenetic promotion and immune regulation, mesenchymal stem cells (MSCs) are all the way focused by researchers. Additionally, exosome, a derivative of MSC, also plays an import role in regulating anoxia-induced oxidative stress modulation, angiogenetic promotion, and immune regulation. MSC-based islet transplantation may be a useful therapeutic tool in treating type 1 diabetes. Therefore, in this review, the potential effect of MSC prior and posterior to the operation of the islet transplantation, its clinical application as well as its limitations were reviewed, aiming to offer insights into the future application of islet transplantation in treating type 1 diabetes.

O conhecimento dos profissionais da Atenção Básica em Saúde sobre o Vírus T-linfotrópico Humano / The knowledge of Primary Health Care professionals about the Human T-lymphotropic virus / El conocimiento de los profesionales de la Atención Primaria de Salud sobre el virus linfotrópico T humano

Objetivo: investigar o conhecimento de profissionais de saúde presentes em unidades básicas de saúde (UBS's) sobre o HTLV e as condutas tomadas em caso de infecção. Método:pesquisa quantitativa transversal de abordagem exploratória, sendo realizada por meio de entrevista, com preenchimento de formulário via Google Forms. Realizada em julho de 2023. Resultados:estudo composto por 33 profissionais de saúde, dentre os quais 39% afirmaram desconhecer o HTLV. Essa informação é preocupante, considerando que uma unidade de saúde representa a principal porta de entrada paraos indivíduos em busca de atendimento à saúde. A maioria expressiva, representando 70%, demonstrou conhecimento sobre os meios de prevenção da doença. Porém, a vacinação não foi identificada pela maioria como um método de prevenção, destacando uma percepção menos difundida sobre o papel da vacina nesse contexto. Conclusão:é crucial divulgar pesquisas sobre o tema, criando oportunidades estratégicas para aprimorar tanto a compreensão clínica quanto a empatia no atendimento aos portadores do HTLV, contribuindo assim para a melhoria do diagnóstico, tratamento e qualidade assistencia

Objective:To investigate the knowledge of health professionals present in primary health care units (BHUs) about HTLV and the procedures taken in case of infection. Method:cross-sectional quantitative research with an exploratory approach, carried out through interviews, filling out a form via Google Forms. Carried out in July 2023. Results:study composed of 33 health professionals, of which 39% said they were unaware of HTLV. This information is worrying, considering that a health unit represents the main gateway for individuals seeking health care. The significant majority, representing 70%, demonstrated knowledge about the means of preventing the disease. However, vaccination was not identified by the majority as a prevention method, highlighting a less widespread perception about the role of the vaccine in this context. Conclusion:it is crucial to disseminate research on the topic, creating strategic opportunities to improve both clinical understanding and empathy in the care of HTLV carriers, thus contributing to the improvement of diagnosis, treatment and quality of care.

Objective:To investigate the knowledge of health professionals present in primary health care units (BHUs) about HTLV and the procedures taken in case of infection. Method:cross-sectional quantitative research with an exploratory approach, carried out through interviews, filling out a form via Google Forms. Carried out in July 2023. Results:study composed of 33 health professionals, of which 39% said they were unaware of HTLV. This information is worrying, considering that a health unit represents the main gateway for individuals seeking health care. The significant majority, representing 70%, demonstrated knowledge about the means of preventing the disease. However, vaccination was not identified by the majority as a prevention method, highlighting a less widespread perception about the role of the vaccine in this context. Conclusion:it is crucial to disseminate research on the topic, creating strategic opportunities to improve both clinical understanding and empathy in the care of HTLV carriers, thus contributing to the improvement of diagnosis, treatment and quality of care.

Low back pain, pelvic pain, and associated factors in type 1 diabetic pregnant women

Abstract Introduction Pregnancy and diabetes mellitus promote several musculoskeletal changes predisposing this population to complaints of Lower Back (LB) and Pelvic Pain (PP). Objective To assess the frequency of LB and PP and associated factors in type 1 Diabetic (DM1) pregnant women. Method: An observational analytical cross-sectional study. Thirty-six pregnant women with DM1 were evaluated through a postural assessment with a focus on pelvic positioning and what patients reported. The associated factors were assessed using the State-Trait Anxiety Inventory (STAI), the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Female Sexual Function Index (FSFI). Results The frequency of LB and PP was 55.6 % and 30.6 %, respectively. The presence of anxiety was not associated with a higher prevalence of pain. The incidence of sexual dysfunctions was higher in the GD. DM1 duration had a mean of 14.9 years (± 8.2 SD) in the GD and 9.0 years (± 6.9 SD) in the GSD, which was statistically significant (p ≤ 0.050). In the multiple binary regression analysis for the occurrence of pain, the independent factor was DM1 duration ≥ 17 years (OR = 11.2; 95 % CI = 1.02‒124.75). The association between DM1 duration ≥ 17 years and being overweight showed a probability of 95 % for the studied population in the analysis of the probabilities of occurrence of the pain event. Conclusion There was a high frequency of LB and PP related to pregnancy in DM1 pregnant women in the second trimester of pregnancy. The incidence of sexual dysfunction and DM1 duration ≥ 17 years increases the chance that DM1 pregnant women will experience pain. There was no association between anxiety. urinary incontinence and pain in DM1 pregnant women.

Use of probiotics and similar in pediatric patients with Type 1 Diabetes Mellitus: a systematic review / Uso de probióticos e similares em pacientes pediátricos com Diabetes Mellitus tipo 1: uma revisão sistemática

ABSTRACT Objective: To perform a systematic review of randomized controlled trials, evaluating the effect of probiotics, prebiotics or symbiotics supplementation on glycemic and inflammatory control in children with Type 1 Diabetes Mellitus (T1DM). Data source: The Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Clinical Trials, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Electronic Library Online (SciELO) databases were searched. Randomized clinical trials of pediatric patients with DM1 using probiotics, prebiotics or symbiotics were included, regardless of year or language of publication. Studies that did not evaluate glycated hemoglobin (HbA1c) were excluded. Metabolic results (HbA1c, total insulin dose and C-peptide) and inflammatory control [interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)] during probiotic supplementation or similar, related to modification of the intestinal microbiota, were analyzed. PROSPERO ID: CRD42022384485. Data synthesis: Five studies were selected for a systematic review. Regarding metabolic markers, only one of the articles that analyzed HbA1c showed a significant decrease (p=0.03) in the intervention group. One study identified a reduction in the total dose of insulin and increased C-peptide levels. Regarding the evaluation of inflammatory parameters (IL-10, TNF-α, INF-γ), there were no statistical relevant modifications. Conclusions: Current data from the literature were not conclusive in identifying an improvement in glycemic control and did not observe changes in inflammatory parameters with the use of probiotics, prebiotics or symbiotics in pediatric patients with T1DM.

RESUMO Objetivo: Realizar uma revisão sistemática de ensaios clínicos randomizados controlados avaliando o efeito da suplementação de probióticos, prebióticos ou simbióticos no controle glicêmico e inflamatório em crianças com diabetes mellitus tipo 1 (DM1). Fontes de dados: As bases Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Clinical Trials, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Scientific Electronic Library Online (SciELO) foram pesquisadas. Foram incluídos ensaios clínicos randomizados de pacientes pediátricos com DM1 em uso de probióticos, prebióticos ou simbióticos, independentemente de ano ou idioma de publicação. Foram excluídos os trabalhos que não avaliaram hemoglobina glicada (HbA1c). Os resultados metabólicos (HbA1c, dose de insulina total e peptídeo C) e o controle inflamatório [interleucina-10 — IL-10), fator de necrose tumoral-alfa (TNF-α) e interferon-gama (IFN-γ)] durante a suplementação de probióticos ou similares, relacionados à modificação da microbiota intestinal, foram analisados. ID PROSPERO: CRD42022384485. Síntese dos dados: Cinco estudos foram selecionados para revisão sistemática. Com relação aos marcadores metabólicos, apenas um dos artigos que analisaram a HbA1c apresentou diminuição significativa (p=0,03) no grupo intervenção. Um estudo identificou redução da dose total de insulina e aumento dos níveis de peptídeo C. Quanto à avaliação dos parâmetros inflamatórios (IL-10, TNF-α, INF-γ), não houve modificações de relevância estatística. Conclusões: Os dados atuais da literatura não foram conclusivos em identificar melhora no controle glicêmico e não observaram mudanças nos parâmetros inflamatórios com o uso de probióticos, prebióticos ou simbióticos em pacientes pediátricos com DM1.

A novel spot mutation leading to sialidosis type 1-myoclonus syndrome and optical coherence tomography findings / Uma nova mutação pontual levando à sialidose tipo 1 - síndrome mioclônica e seus achados na tomografia de coerência óptica

ABSTRACT This report presents the optical coherence tomography findings and a new NEU1 mutation in bilateral macular cherry-red spot syndrome associated with sialidosis type 1. A 19-year-old patient with a macular cherry-red spot underwent metabolic and genetic analyses supported by spectral-domain optical coherence tomography. Fundus examination revealed bilateral macular cherry-red spot. Spectral-domain optical coherence tomography revealed increased hyperreflectivity in the retinal inner layers and the photoreceptor layer in the foveal region. The genetic analysis detected a new NEU1 mutation, which caused type I sialidosis. In cases with a macular cherry-red spot, sialidosis should be included in the differential diagnosis, and NEU1 mutation should be screened. Spectral-domain optical coherence tomography alone is not sufficient in the differential diagnosis because childhood metabolic diseases may exhibit similar signs.

RESUMO Neste artigo, objetivamos apresentar os achados da tomografia de coerência óptica em uma nova mutação detectada no gene NEU1 em um caso de síndrome macular vermelho-cereja bilateral associada à sialidose tipo 1. Um paciente de 19 anos com um achado de mancha macular vermelho-cereja foi submetido a análises metabólicas e genéticas, apoiadas por imagens de tomografia de coerência óptica de domínio espectral (SD-OCT). Ao exame de fundo de olho, foi observada uma mancha macular vermelho-cereja bilateral. Nas imagens de SD-OCT, observou-se hiper-refletividade nas camadas internas da retina e na camada fotorreceptora na região foveal. Foi realizada uma análise genética e uma nova mutação foi detectada no gene NEU1, resultando em sialidose tipo 1. Nos casos em que é detectada uma mancha vermelho-cereja na mácula, o diagnóstico diferencial de sialidose deve ser feito e mutações do gene NEU1 devem ser rastreadas. A SD-OCT por si só não é suficiente para o diagnóstico diferencial, porque achados de aparência semelhante podem se manifestar em casos de doenças metabólicas da infância.

Autogestão do diabetes na adolescência: experiência de jovens adultos e pais portugueses / Autogestión de la diabetes en la adolescencia: experiencias de jóvenes adultos y padres portugueses / Self-management of diabetes in adolescence: experience of Portuguese young adults and their parents

Resumo Objetivo Identificar os fatores que facilitam ou dificultam a construção da autonomia na adolescência através da experiência de jovens adultos com diabetes tipo 1 e seus pais. Métodos Estudo de natureza qualitativa, descritiva e exploratória. Foram realizadas duas entrevistas de grupo focal, uma com nove jovens adultos peritos na gestão de sua doença e outra com sete pais. Para análise dos dados, foram usados análise de conteúdo temática e categorial, com particularidades de entrevista de grupo focal, e recurso ao software NVIVO 12. Resultados Emergiram duas grandes categorias e dez subcategorias relativas aos fatores que facilitaram (sistemas de suporte, conhecimentos, alimentação, bomba de insulina, responsabilização precoce pela gestão da terapêutica, características dos jovens), e dificultaram (regime terapêutico, estigma, atitude dos profissionais de saúde, características dos jovens, conhecimento) o desenvolvimento da autonomia na gestão da doença. Conclusão A autonomia na gestão do diabetes envolve vários desafios aos adolescentes, o que requer adequação de atitudes e intervenções de profissionais. Além da gestão tradicional da condição de saúde, é essencial abordar temas relacionados com a socialização dos adolescentes, procurando estratégias inovadoras que promovam o coping e a qualidade de vida. Os resultados deste estudo possibilitam refletir sobre a relação terapêutica com os adolescentes, salientando a importância de individualizar cuidados e respostas inovadoras às suas necessidades específicas.

Resumen Objetivo Identificar los factores que facilitan o dificultan la construcción de la autonomía en la adolescencia a través de la experiencia de jóvenes adultos con diabetes tipo 1 y sus padres. Métodos: Estudio de naturaleza cualitativa, descriptiva y exploratoria. Se realizaron dos entrevistas de grupo focal, una con nueve jóvenes adultos expertos en la gestión de su enfermedad y otra con siete padres. Para el análisis de datos se utilizó el análisis de contenido temático y categorial, con particularidades de entrevista de grupo focal y recurso del software NVIVO 12. Resultados Surgieron dos grandes categorías y diez subcategorías relativas a los factores que facilitaron el desarrollo de la autonomía en la gestión de la enfermedad (sistemas de apoyo, conocimientos, alimentación, bomba de insulina, responsabilización temprana de la gestión de la terapéutica, características de los jóvenes) y los que la dificultaron (régimen terapéutico, estigma, actitudes de los profesionales de la salud, características de los jóvenes, conocimientos). Conclusión La autonomía en la gestión de la diabetes incluye muchos desafíos para los adolescentes, lo que requiere adaptación de actitudes e intervenciones de profesionales. Además de la gestión tradicional del estado de salud, es esencial abordar temas relacionados con la socialización de los adolescentes y buscar estrategias innovadoras que promuevan el coping y la calidad de vida. Los resultados de este estudio permiten reflexionar sobre la relación terapéutica con los adolescentes y destacar la importancia de individualizar los cuidados y las respuestas innovadoras para sus necesidades específicas.

Abstract Objective To identify the factors that facilitate or hinder the construction of autonomy in adolescence through the experience of young adults with type-1 diabetes and their parents. Methods This was a qualitative, descriptive, and exploratory study. Two focus group interviews were conducted: one with nine young adults who were experts in managing their illness and the other with seven parents. Thematic and categorical content analysis was used for data analysis, with particularities of a focus group interview and the use of the NVIVO 12 software. Results Two major categories and ten subcategories related to factors that facilitated (support systems, knowledge, diet, insulin pump, early responsibility for managing therapy, and characteristics of young people) and hindered (therapeutic regimen, stigma, attitude of health professionals, characteristics of young people, and knowledge) the development of autonomy in disease management emerged. Conclusion Autonomy in the management of diabetes involves several challenges for adolescents, which requires adaptation of attitudes and interventions by professionals. In addition to the traditional management of the health condition, addressing issues related to the socialization of adolescents is essential, looking for innovative strategies that promote coping and quality of life. The results of this study make it possible to reflect on the therapeutic relationship with adolescents, emphasizing the importance of individualizing care and innovative responses to their specific needs.

Type 1 diabetes care delivery in Yaoundé, Cameroon: Social and political representations

Background: Increasing chronic diseases challenges the health systems of low- and middleincome countries, including Cameroon. Type 1 diabetes (T1D), among the most common chronic diseases in children, poses particular care delivery challenges. Aim: We examined social representations of patients' roles and implementation of T1D care among political decision-makers, healthcare providers and patients within families. Setting: The study was conducted in Yaoundé, Cameroon. Methods: Eighty-two individuals were included in the study. The authors conducted semistructured interviews with policy makers (n = 5), healthcare professionals (n = 7) and patients 'parents (n = 20). Questionnaires were administered to paediatric patients with T1D (n = 50). The authors also observed care delivery at a referral hospital and at a T1D-focused nongovernmental organisation over 15 days. Data were analysed using thematic content analysis and descriptive statistics. Results: Cameroonian health policy portrays patients with T1D as passive recipients of care. While many practitioners recognised the complex social and economic determinants of adherence to T1D care, in practice interactions focused on specific biomedical issues and offered brief guidance. Cultural barriers and policy implementation challenges prevent patients and their families from being fully active participants in care. Parents and children prefer an ongoing relationship with a single clinician and interactions with other patients and families. Conclusion: Patients and families mobilise experience and lay knowledge to complement biomedical knowledge, but top-down policy and clinical practice limit their active engagement in T1D care. Contribution: Children with T1D and their families, policy makers, healthcare professionals, and civil society have new opportunities to contribute to person-centred care, as advocated by the Sustainable Development Goals.

Risk factors for ketoacidosis in children/adolescents with type 1 diabetes mellitus and establishment of a predictive model / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for diabetic ketoacidosis (DKA) in children/adolescents with type 1 diabetes mellitus (T1DM) and to establish a model for predicting the risk of DKA.@*METHODS@#A retrospective analysis was performed on 217 children/adolescents with T1DM who were admitted to General Hospital of Ningxia Medical University from January 2018 to December 2021. Among the 217 children/adolescents,169 cases with DKA were included as the DKA group and 48 cases without DKA were included as the non-DKA group. The risk factors for DKA in the children/adolescents with T1DM were analyzed, and a nomogram model was established for predicting the risk of DKA in children/adolescents with T1DM.@*RESULTS@#For the 217 children/adolescents with T1DM, the incidence rate of DKA was 77.9% (169/217). The multivariate logistic regression analysis showed that high levels of random blood glucose, hemoglobin A1c (HbA1c), blood ketone body, and triglyceride on admission were closely associated with the development of DKA in the children/adolescents with T1DM (OR=1.156, 3.2031015, 20.131, and 9.519 respectively; P<0.05). The nomogram prediction model had a C-statistic of 0.95, with a mean absolute error of 0.004 between the risk of DKA predicted by the nomogram model and the actual risk of DKA, indicating that the model had a good overall prediction ability.@*CONCLUSIONS@#High levels of random blood glucose, HbA1c, blood ketone body, and triglyceride on admission are closely associated with the development of DKA in children/adolescents with T1DM, and targeted intervention measures should be developed to reduce the risk of DKA.

Gene therapy strategies and prospects for neurofibromatosis type 1 / 中国修复重建外科杂志

OBJECTIVE@#To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress.@*METHODS@#The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized.@*RESULTS@#NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety.@*CONCLUSION@#Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.

Percepción de apoyo social en padres de niños con diabetes mellitus tipo 1

Fundamento: el apoyo de familiares y del equipo de salud a los padres cuidadores de sus hijos diabéticos es fundamental para el afrontamiento a los cambios que provoca esta enfermedad en la dinámica familiar. Objetivo: describir la percepción de los padres cuidadores sobre el apoyo familiar y de los Sistemas de Salud en el comienzo de sus hijos con diabetes mellitus tipo 1. Métodos: estudio cualitativo descriptivo realizado mediante entrevista semiestructurada a cuatro padres cuidadores de niños con diagnóstico de diabetes tipo 1. El consentimiento informado fue realizado vía Google Forms y la entrevista fue vía plataforma ZOOM. Las entrevistas tuvieron una duración de 30 minutos. El análisis de las entrevistas se realizó utilizando el programa ATLAS.ti versión 22. Resultados: el comienzo de la enfermedad de los niños fue recibido por los padres con mucha confusión y falta de conocimiento. En cuanto a las redes de apoyo, los padres declararon la soledad como vivencia en el cuidado de los niños y, en relación a los equipos de salud, relataron que está enfocada en los cuidados básicos que tenían que cumplir, como la alimentación y el control glucémico, con ausencia de preocupación por el apoyo emocional. Conclusiones: las necesidades de apoyo desde los equipos de salud, a los padres cuidadores, más allá del control de la enfermedad, es una necesidad explícita desde la evidencia, que aún no ha sido considerada por los Sistemas de Salud. El apoyo debe trascender la familia, con una actuación importante de los profesionales de la salud y todo el contexto en que están insertos los niños, para contribuir a un manejo adecuado de la enfermedad.

Foundation: the support of family members and the health team for parents caring for their diabetic children is essential for facing with the changes that this disease causes in family dynamics. Objective: to describe the perception of parent caregivers about family support and Health Systems at the beginning of their children with type 1 diabetes mellitus. Methods: qualitative descriptive study carried out through semi-structured interviews with four parent caregivers of children with a diagnosis of type 1 diabetes. Informed consent was carried out via Google forms and the interview was via the ZOOM platform. The interviews lasted 30 minutes. The analysis of the interviews was carried out using the ATLAS.ti version 22 program. Results: the beginning of the children's illness was received by parents with much confusion and lack of knowledge. Regarding the support networks, the parents declared loneliness in the experience of caring for the children and, in relation to the health teams, they reported that it is focused on the basic care that they had to fulfill, such as food and hygiene, glycemic control, with absence of concern for emotional support. Conclusions: the support needs from health teams to parent caregivers, beyond disease control, is an explicit need from the evidence, which has not yet been considered by Health Systems. Support must go beyond the family, with important action by health professionals and the entire context in which children are inserted, to contribute to adequate management of the disease.

Neoplasia endocrina múltiple tipo 1 en paciente con diagnóstico de nesidioblastosis. Presentación de un caso

Las neoplasias endocrinas múltiples engloban una serie de síndromes caracterizados por su origen genético y la afectación de una o más glándulas. Se describe el caso de un paciente masculino, de 23 años, con antecedentes de salud de nesidioblastosis diagnosticado a los 16 años de edad, quien acudió al Hospital General Docente Ambato por presentar convulsiones tónico clónicas, e hipoglucemia severa con posterior estatus epiléptico. Los estudios de laboratorio mostraron hiperparatiroidismo primario, y los de imagen identificaron lesiones sugerentes de adenoma paratiroideo e insulinoma de cabeza de páncreas. Después de analizar el caso, se identificaron dos criterios para plantear una neoplasia endocrina múltiple tipo 1: presencia de insulinoma e hiperparatiroidismo primario. Además de tratamiento con bifosfonato, se planificó interconsulta con el servicio de Genética, para estudio del paciente y familiares; y con Cirugía General, para programación de resolución quirúrgica. Debido a la poca frecuencia de esta enfermedad, resulta de interés describir el caso, con el objetivo de exponer las principales manifestaciones clínicas y conducta a seguir. Constituye una prioridad el diagnóstico de su causa en cada paciente.

Multiple endocrine neoplasias encompass a series of syndromes characterized by their genetic origin and the involvement of one or more glands. A 23-years-old male patient with a health history of nesidioblastosis diagnosed at 16 years of age, who attended the Ambato General Teaching Hospital with tonic-clonic seizures and severe hypoglycemia with subsequent epileptic status, is described. Laboratory studies showed primary hyperparathyroidism, and imaging identified lesions suggestive of parathyroid adenoma and insulinoma of the head of the pancreas. After analyzing the case, two criteria were identified to suggest multiple endocrine neoplasia type 1: presence of insulinoma and primary hyperparathyroidism. In addition to treatment with bisphosphonate, consultation with the Genetics service was planned for study of the patient and family members; and with General Surgery, for scheduling surgical resolution. Due to the infrequency of this disease, it is of interest to describe the case, with the aim of exposing the main clinical manifestations and conduct to follow. Diagnosing its cause in each patient is a priority.

Perfil das pessoas com diabetes que utilizaram a telefarmácia na pandemia de covid-19: resultados da DIABETES / Profile of people with diabetes who used telepharmacy during the covid-19 pandemic: results from DIABETES / Perfil de personas con diabetes que usaron telefarmacia durante la pandemia de covid-19: resultados de DIABETES

O objetivo foi analisar o perfil das pessoas com diabetes que utilizaram a telefarmácia na pandemia de covid-19. Trata-se de um estudo transversal com dados oriundos da websurvey DIABETESvid que ocorreu nos meses de setembro e outubro de 2020. Verificou-se que 45 participantes recorreram à telefarmácia, sendo que 55,6% eram do sexo masculino, 42,2% tinham idade compreendida entre 18 e 34 anos e 46,7% estudaram 12 ou mais anos. Além disso, 48,9% autorreferiram diabetes mellitus tipo 1. A maioria usava insulina (55,6%) e obteve os medicamentos para o diabetes em farmácias do sistema público de saúde (60%). Ademais, as pessoas que tiveram o diagnóstico de covid-19 buscaram mais pela telefarmácia (RP=2,20; IC95% 1,23­3,94). Sabe-se que os medicamentos são essenciais para o tratamento do diabetes. Logo, no período estudado em que se preconizava o distanciamento físico, os participantes apropriaram-se da telefarmácia a fim de obter a integralidade do cuidado

The objective was to analyze the profile of people with diabetes who used telepharmacy during the covid-19 pandemic. This is a cross-sectional study with data from the DIABETESvid websurvey that took place in September and October 2020. It was found that 45 participants used telepharmacy, 55.6% of whom were male, 42.2% were between 18 and 34 years-old and 46.7% studied 12 or more years. In addition, 48.9% self-reported type 1 diabetes mellitus. Most used insulin (55.6%) and obtained their diabetes medication from pharmacies in the public health system (60%). Also, people diagnosed with covid-19 used telephar-macy more often (PR=2.20; 95%CI 1.23­3.94). It is known that drugs are essential for the treatment of diabetes. Therefore, in the period studied in which physical distancing was advocated, the participants used telepharmacy to obtain comprehensive care

El objetivo fue analizar el perfil de las personas con diabetes que utilizaron la telefarmacia durante la pandemia del covid-19. Estudio transversal con datos de la encuesta por internet DIABETESvid realizada en septiembre y octubre de 2020. Se encontró que 45 participantes recurrieron a la telefarmacia, de los cuales el 55,6% eran hombres, el 42,2% tenían entre 18 y 34 años y el 46,7% estudiaban 12 o más años. Además, el 48,9% se autorrefirió diabetes mellitus tipo 1. La mayoría utilizaba insulina (55,6%) y recibía su medicación antidiabética en farmacias del sistema público (60%). Además, las personas diagnosticadas con covid-19 buscaron telefarmacia con más frecuencia (RP = 2,20; IC 95% 1,23­3,94). Los medicamentos son esenciales para el tratamiento de la diabetes. Por lo tanto, en el período estudiado en el que se propugnaba el distanciamiento físico, los participantes se apropiaron de la telefarmacia para la atención integral

Diabetes mellitus tipo 1 de presentación súbita inducida por inhibidores del punto de control inmunitario en el tratamiento de cáncer avanzado. Serie de casos / Sudden onset type 1 diabetes mellitus induced by immune checkpoint inhibitors in the treatment of advanced cancer. Cases report

Tres pacientes con cáncer avanzado en tratamiento con inhibidores del punto de control inmunitario (inmune checkpoint inhibitors, ICIs), sin antecedentes de diabetes mellitus (DM), ingresaron al Servicio de Urgencias con poliuria, polidipsia y pérdida de peso, y diagnóstico de cetoacidosis diabética, sin evidencia clínica de infección. Fueron tratados con líquidos e infusión de insulina pasando luego a un régimen de insulina bolo basal que continuó después del alta. Las pruebas de detección de autoanticuerpos para DM resultaron negativas, y se les diagnosticó DM inducida por ICIs, pembrolizumab en dos de ellos y nivolumab en el otro. El propósito de esta serie de casos es demostrar el desarrollo de la DM1 en forma aguda en pacientes tratados con inhibidores de PD-1. Sobre la base de estos casos y la literatura revisada, se buscaron determinar las características clínicas, y sugerir estrategias para la identificación, control, tratamiento precoz y seguimiento de los pacientes tratados con ICIs a fin de minimizar el impacto de la disfunción autoinmune.

Three patients with advanced cancer, treated with inmune checkpoint inhibitors (ICIs), with no history of diabetes mellitus (DM), were admitted to the Emergency Department with polyuria, polydipsia, and weight loss and a diagnosis of diabetic ketoacidosis without clinical evidence of infection. They were treated with fluids and insulin infusion transitioning to a basal-bolus insulin regimen, which continued after discharge. Autoantibody detection tests for DM were negative and they were diagnosed with DM induced by ICIs, pembrolizumab in two of them, and nivolumab in another. The purpose of this case report is to show the development of DM1 in an acute form in patients treated with PD-1 inhibitors. Based on these cases and the reviewed literature, we seek to identify clinical characteristics and suggest strategies for the proper identification, control, treatment, and follow-up of patients treated with ICIs to minimize the impact of autoimmune dysfunction.

Presencia de autoanticuerpos anti islotes pancreáticos en diabetes tipo 1 durante la edad pediátrica / Presence of anti-pancreatic islet autoantibodies in type 1 diabetes in children

En la Diabetes tipo 1 (DM1) la pérdida de células ß pancreáticas es consecuencia de un proceso de autoinmunidad que cursa con la presencia de autoanticuerpos anti-islotes pancreáticos (AAPs). Estos AAPs son marcadores útiles para la clasificación de la enfermedad. En un centro pediátrico de tercer nivel se analizó la frecuencia de presentación de GADA, IA-2A, ZnT8A e IAA en un grupo con reciente debut entre enero 2018 y agosto 2021 (n= 90). Además, se investigó la frecuencia de presentación y relación de los AAPs con la edad, sexo y tiempo de evolución en pacientes en seguimiento (n= 240). En el grupo de debut se obtuvo positividad de GADA, IA-2A, ZnT8A y IAA en 77,8; 60; 62 y 47,8% de los pacientes respectivamente, un 4% no presentó AAPs. El 95,6% de los pacientes presentaron al menos un AAPs positivo. La frecuencia de IAA en el grupo en debut fue mayor en menores de 5 años. En el grupo en seguimiento el 75,2% resultaron GADA positivo (85,7% en mujeres y 62,8% en varones) p<0,05. IA-2A y ZnT8A fueron positivos en 45 y 51.7% respectivamente. El 91% presentaron al menos un AAP positivo. En este grupo se evidenció una menor positividad en función del tiempo de evolución. Se pudo determinar la frecuencia de presentación de los AAPs en un grupo en debut y la relación con la edad, sexo y tiempo de evolución en pacientes en seguimiento. La determinación de APPs facilita la correcta clasificación y elección de la terapia adecuada (AU)

In type 1 diabetes (DM1) the loss of pancreatic ß-cells is a consequence of an autoimmune process that results in the presence of pancreatic anti-islet autoantibodies (PAAs). PAAs are useful markers for the classification of the disease. The frequency of presentation of GADA, IA-2A, ZnT8A, and IAA in a group with recent debut seen between January 2018 and August 2021 (n= 90) was analyzed in a tertiary pediatric center. In addition, we investigated the frequency of presentation and association of PAAs with age, sex, and time of evolution in patients in follow-up (n= 240). In the debut group, GADA, IA2A, ZnT8A, and IAA positivity was found in 77.8, 60, 62, and 47.8% of patients, respectively; no PAAs were observed in 4% of the patients. Overall, 95.6% presented at least one positive PAA. The frequency of IAA in the debut group was higher in children younger than 5 years. In the follow-up group, 75.2% were GADA positive (85.7% of females and 62.8% of males) p<0.05. IA-2A and ZnT8A were positive in 45 and 51.7% respectively. Ninety-one percent presented with at least one positive PAA. In this group, a lower positivity was evidenced as a function of the time of evolution. The frequency of presentation of PAAs in a debut group and the relationship with age, sex, and time of evolution in patients in follow-up was demonstrated. The assessment of PAAs facilitates the correct classification and choice of adequate therapy (AU)