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This systematic review evaluates the scientific literature on pediatric periodic limb movement disorder (PLMD), adhering to PRISMA guidelines and utilizing PICOS criteria. The search across PubMed, EMBASE, and Scopus yielded 331 articles, with 17 meeting inclusion criteria. Diagnostic criteria evolved, with polysomnography and PLMS index ≥5 required since 2003. Also, PLMD diagnosis mandates clinical consequences like insomnia, hypersomnia, and fatigue, excluding comorbidities causing sleep disruption. Prevalence in children is low (0.3%), emphasizing the need for meticulous investigation. Comorbidities, particularly the bidirectional relationship with ADHD, were explored. Challenges in diagnosis and understanding arise from overlapping conditions such as sleep disordered breathing, psychotropic medication, and criteria non-adherence. Despite generally good study quality, weaknesses include sample size justification and biases. The periodic leg movement index shows high sensitivity but low specificity, underscoring strict diagnostic criteria adherence. Diverse metrics for symptoms necessitate standardized approaches. Family history of RLS in children with PLMD suggests unexplored aspects. Treatment, mainly iron supplementation, lacks standardized assessment metrics. The review emphasizes diagnostic and treatment challenges, recommending unbiased studies with precise techniques. Comprehensive research, quantifying PLMS and objectively assessing sleep parameters, is crucial for advancing understanding in pediatric PLMD. PROSPERO REGISTRATION NUMBER: CRD42021251406.
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Síndrome da Mioclonia Noturna , Polissonografia , Humanos , Síndrome da Mioclonia Noturna/diagnóstico , Criança , ComorbidadeRESUMO
Dairy foods contribute nine essential nutrients to the diet including calcium, potassium and vitamin D; nutrients identified by the 2010 Dietary Guidelines for Americans as being "of public health concern" within the U.S. population. Milk and milk product intake is associated with better diet quality and has been associated with a reduced risk of chronic diseases or conditions including hypertension, cardiovascular disease, metabolic syndrome, Type 2 Diabetes and osteoporosis. Some research also indicates dairy food intake may be linked to reduced body fat, when accompanied by energy-restriction. On average, both African Americans and Hispanic Americans consume less than the recommended levels of dairy foods, and perceived or actual lactose intolerance can be a primary reason for limiting or avoiding dairy intake. True lactose intolerance prevalence is not known because healthcare providers do not routinely measure for it, and no standardized assessment method exists. Avoiding dairy may lead to shortfalls of essential nutrients and increased susceptibility to chronic disease. This updated Consensus Statement aims to provide the most current information about lactose intolerance and health, with specific relevance to the African American and Hispanic American communities. Topics covered include diagnostic considerations, actual and recommended dairy food intake and levels of consumption of key dairy nutrients among African Americans and Hispanic Americans; prevalence of self-reported lactose intolerance among various racial/ethnic groups; the association between dairy food intake, lactose intolerance and chronic disease; and research-based management recommendations for those with lactose intolerance.
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Negro ou Afro-Americano , Consenso , Nível de Saúde , Hispânico ou Latino , Intolerância à Lactose/etnologia , Humanos , Morbidade/tendências , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: We have identified that a novel developmental gene and protein, SCUBE1, is expressed in endothelial cells and may play an important role in kidney regeneration. METHODS: The temporal and spatial expression of SCUBE1 was determined in a mouse model of ischaemia-reperfusion (IR) injury at 3 days and 1, 3 and 6 weeks post-injury by immunofluorescence microscopy. In vitro analysis was used to examine SCUBE1 signalling in endothelial cells under conditions of cell stress using quantitative real-time polymerase chain reaction and immunofluorescence labelling. The media from cultured endothelial cells following SCUBE1 small interfering RNA (siRNA) transfection was used to assess the proliferation capacity of epithelial cells. RESULTS: Immunofluorescence confocal microscopy demonstrated that the SCUBE1 protein was localized to CD31-positive endothelial cells in IR kidneys during the resolution of tissue damage (3 weeks), but not in control animals. The peak expression of SCUBE1 following 3 weeks of IR injury was confirmed by reverse transcription-polymerase chain reaction. SCUBE1 mRNA and protein expression were detected in cultured endothelial cells under hypoxic conditions or serum starving. Furthermore, there was a significant decrease in epithelial cell proliferation following the addition of a supernatant derived from cultured endothelial cells following SCUBE1 siRNA gene silencing compared to control media. CONCLUSIONS: Our results indicate that SCUBE1 may be involved in the regulation of tubular cell proliferation and re-epithelialization during the resolution of kidney injury.
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Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Rim/fisiologia , Regeneração , Animais , Proteínas de Ligação ao Cálcio , Hipóxia Celular , Proliferação de Células , Células Cultivadas , Células Endoteliais/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , RNA Interferente Pequeno/genética , Traumatismo por Reperfusão/patologiaRESUMO
INTRODUCTION: The International Restless Legs Study Group (IRLSSG) has developed the IRLS (International Restless Legs Syndrome Severity Scale) and validated it as a clinician/researcher administered scale to be used when both patient and examiner are present. The IRLSSG recognized the need for a self-completing scale that can be used economically in clinical practice and in large population-based studies. In this study the validity and the reliability of the IRLS as a self-administered scale (sIRLS) is assessed. METHODS: Established RLS patients were recruited by eight centers in four countries and consented to participate in this study. The validity of the sIRLS was assessed by patients completing the sIRLS before a clinician administered the IRLS. The reliability of the sIRLS was assessed by patients completing the sIRLS again, two weeks after the first one, provided no change had occurred. RESULTS: Overall, 173 patients were recruited and 164 of them were included in the analyses. The sIRLS showed satisfactory scaling assumptions and no relevant floor or ceiling effect. One factor explained 61.3% of the variance. Cronbach's alpha was 0.93 and the item homogeneity index was 0.59. Intraclass correlation coefficient between the sIRLS and the IRLS was 0.94. The sIRLS standard error of measurement was 3.61 (½ SD at baseline = 4.11). The results mostly overlapped those of the IRLS analyzed in parallel. DISCUSSION: The sIRLS is a reliable, valid and precise instrument that showed tight association with the IRLS. These findings support the use of the sIRLS for self-evaluation of RLS severity. The responses obtained on the sIRLS and the IRLS scale varied slightly. Therefore, we recommend that either the sIRLS or the IRLS scale be used as the only scale for serial measures over time.
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Autoavaliação Diagnóstica , Cooperação Internacional , Síndrome das Pernas Inquietas/diagnóstico , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos TestesRESUMO
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is one of the most sensitive, economical and widely used methods for evaluating gene expression. However, the utility of this method continues to be undermined by a number of challenges including normalization using appropriate reference genes. The need to develop tailored and effective strategies is further underscored by the burgeoning field of extracellular vesicle (EV) biology. EVs contain unique signatures of small RNAs including microRNAs (miRs). In this study we develop and validate a comprehensive strategy for identifying highly stable reference genes in a therapeutically relevant cell type, cardiosphere-derived cells. Data were analysed using the four major approaches for reference gene evaluation: NormFinder, GeNorm, BestKeeper and the Delta Ct method. The weighted geometric mean of all of these methods was obtained for the final ranking. Analysis of RNA sequencing identified miR-101-3p, miR-23a-3p and a previously identified EV reference gene, miR-26a-5p. Analysis of a chip-based method (NanoString) identified miR-23a, miR-217 and miR-379 as stable candidates. RT-qPCR validation revealed that the mean of miR-23a-3p, miR-101-3p and miR-26a-5p was the most stable normalization strategy. Here, we demonstrate that a comprehensive approach of a diverse data set of conditions using multiple algorithms reliably identifies stable reference genes which will increase the utility of gene expression evaluation of therapeutically relevant EVs.
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The nonpharmacologic management of patients with restless legs syndrome (RLS) is an important part of the treatment. It can represent the entire treatment or it can be used as an adjuvant to pharmacologic options. The limited number of controlled studies allowed for a plethora of pseudoprofessional recommendations. Some of these suggestions may have a grain of truth and some are utterly dangerous. This review discusses the different potential treatments for RLS to facilitate the design of a tailored program for specific patients. Another goal of this review is to prompt the researcher to investigate some of the laymen suggestions.
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Síndrome das Pernas Inquietas/terapia , Gerenciamento Clínico , Conhecimentos, Atitudes e Prática em Saúde , HumanosRESUMO
ABSTRACT: The American Academy of Sleep Medicine (AASM) commissioned several Workgroups to develop quality measures for the care of patients with common sleep disorders, including adults with restless legs syndrome (RLS). Using the AASM process for quality measure development, the RLS Work-group developed three target outcomes for RLS management, including improving the accuracy of diagnosis, reducing symptom severity, and minimizing treatment complications. Seven processes were developed to support these outcomes. To achieve the outcome of improving accuracy of diagnosis, the use of accepted diagnostic criteria and assessment of iron stores are recommended. To realize the outcome of decreasing symptom severity, routine assessment of severity and provision of evidence-based treatment are recommended. To support the outcome of minimizing treatment complications, counseling about potential side effects and assessing for augmentation and impulse control disorders, when indicated, are recommended. Further research is needed to validate optimal practice processes to achieve best outcomes in adult patients with RLS.
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Indicadores de Qualidade em Assistência à Saúde/normas , Qualidade da Assistência à Saúde/normas , Síndrome das Pernas Inquietas/terapia , Adulto , Humanos , Síndrome das Pernas Inquietas/diagnóstico , Índice de Gravidade de Doença , Medicina do Sono/normas , Resultado do TratamentoRESUMO
STUDY OBJECTIVES: To assess potential relationships between serum iron and ferritin levels and the severity of periodic limb movement in sleep (PLMS) in a pediatric population, and to evaluate the response to supplemental iron therapy. DESIGN: A prospective study of all consecutively diagnosed children with PLMS (periodic limb movement index [periodic limb movements per hour of total sleep time, [PLMI] > 5) who underwent overnight polysomnographic evaluation. In all patients, complete blood count and serum iron and ferritin levels were obtained. Patients with serum ferritin concentrations less than 50 microg/L were prescribed iron sulfate at 3 mg/kg of elemental iron per day for 3 months. At the end of treatment, serum iron and ferritin levels and sleep studies were repeated. SETTING: Comprehensive Sleep Medicine Center, Tulane University Health Sciences Center, and Kosair Children's Hospital Sleep Medicine and Apnea Center. PATIENTS: Twenty boys and 19 girls with PLMS with a mean age of 7.5 +/- 3.1 years. INTERVENTION: Iron therapy. RESULTS: Twenty-eight (71.8%) patients had ferritin levels less than 50 microg/L. There was no significant correlation between serum ferritin concentration and PLMS severity as indicated by the PLMI (r = -0.19). The PLMI in patients with serum ferritin levels less than 50 microg/L (29.9 +/- 15.5 PLM/h) was higher than in patients with serum ferritin levels greater than 50 microg/L (21.9 +/- 11.8 PLM/h); however, the difference did not achieve statistical significance (P = 0.09). In contrast, serum iron was significantly correlated with PLMI (r = -0.43, P < 0.01). Indeed, patients with serum iron concentrations less than 50 microg/dL had a higher PLMI compared to patients with serum iron concentrations greater than 50 microg/dL (42.8 +/- 18.3 PLM/h and 23.1 +/- 10.1 PLM/h, respectively; P = 0.02). Twenty-five out of the 28 PLMS patients with serum ferritin levels less than 50 microg/L received treatment with iron sulfate, and 19 (76%) responded favorably. Among the responders to iron therapy, PLMI decreased from 27.6 +/- 14.9 PLM per hour to 12.6 +/- 5.3 PLM per hour after 3 months of iron supplements (P < 0.001) and coincided with increases in serum ferritin levels (pre: 40.8 +/- 27.4 microg/L vs post: 74.1 +/- 13.0 microg/L; P < 0.001). CONCLUSIONS: In children, the presence of PLMS is frequently associated with low serum iron and a tendency toward low serum ferritin levels. In addition, iron therapy is associated with clinical improvement in most of these patients.
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Ferritinas/deficiência , Síndrome da Mioclonia Noturna/metabolismo , Adolescente , Anemia Ferropriva/sangue , Anemia Ferropriva/complicações , Anemia Ferropriva/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Ferritinas/sangue , Humanos , Lactente , Ferro/uso terapêutico , Masculino , Síndrome da Mioclonia Noturna/etiologia , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a sensorimotor disorder that can result in considerable sleep disruption. This narrative review provides an overview of RLS diagnosis and reports epidemiologic evidence for an association between RLS and mood disorders. Possible links between RLS, sleep disturbances, and mood disorders are considered, and theoretical pathophysiologic pathways are discussed. Finally, pharmacologic therapies for RLS are summarized. DATA SOURCES: A PubMed search was performed using the search term restless legs syndrome in combination with affective/anxiety, antidepressants, anxiety/anxiety disorder, attention deficit hyperactivity disorder, depression/depressive disorder, mood/mood disorder, neuropsychiatric, panic/panic disorder, psychiatric disorder, and psychosis. English-language articles published between January 1993 and May 2013 were retrieved. Additional studies were identified from the reference lists of relevant publications. STUDY SELECTION: 173 publications were retrieved. Articles related to the association between idiopathic RLS and depression, anxiety, and mood disorders were reviewed. In total, 32 epidemiologic studies were identified. These studies were reviewed in detail and ranked according to quality. DATA EXTRACTION: Data were extracted on the basis of relevance to the topic. Epidemiologic studies were assessed using 3 parameters: methodology, data quality, and generalizability of the results. Each factor was scored from 1 (high quality) to 4 (low quality), giving a total score of between 3 and 12 for each study. RESULTS AND CONCLUSIONS: RLS and mood disorders are frequently comorbid. Recognition and appropriate treatment of comorbid RLS are particularly important in patients with psychiatric disorders, as RLS is a common medical reason for insomnia, and antidepressant use may exacerbate sensory symptoms.
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Comorbidade , Transtornos do Humor/epidemiologia , Síndrome das Pernas Inquietas/epidemiologia , Humanos , Transtornos do Humor/tratamento farmacológico , Síndrome das Pernas Inquietas/tratamento farmacológicoAssuntos
Transtornos dos Movimentos , Síndrome das Pernas Inquietas , História do Século XVII , História do Século XX , Humanos , Transtornos dos Movimentos/classificação , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/história , Transtornos dos Movimentos/terapia , Síndrome das Pernas Inquietas/classificação , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/história , Síndrome das Pernas Inquietas/terapia , Terminologia como AssuntoRESUMO
Inflammation and fibrogenesis are the two determinants of the progression of renal fibrosis, the common pathway leading to end-stage renal disease. The p38 mitogen-activated protein kinase (MAPK) and transforming growth factor (TGF)-beta1/Smad signaling pathways play critical roles in inflammation and fibrogenesis, respectively. The present study examined the beneficial renoprotective effect of combination therapy using the p38 MAPK pathway inhibitor (SB203580) and a TGF-beta receptor I (ALK5) inhibitor (ALK5I) in a mouse model of adriamycin (ADR) nephrosis. The p38 MAPK and TGF-beta1/Smad2 signaling pathways were activated in ADR-induced nephropathy in a sequential time course manner. Two weeks after ADR injection, the combined administration of SB203580 (1 mg/kg/24 hours) and ALK5I (1 mg/kg/24 hours) markedly reduced p38 MAPK and Smad2 activities. Moreover, the co-administration of SB203580 and ALK5I to ADR-injected mice resulted in a down-regulation of total and active TGF-beta1 production, reduced myofibroblast accumulation, and decreased expression of collagen type IV and fibronectin. In these mice, retardation in the development of glomerulosclerosis and interstitial fibrosis was observed. In conclusion, although p38 MAPK and TGF-beta1/Smad signaling pathways are distinct they coordinate the progression of renal fibrosis in ADR nephrosis. The co-administration of a p38 MAPK inhibitor and an ALK5 inhibitor may have potential applications in the treatment of renal fibrosis.
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Nefrose/induzido quimicamente , Nefrose/patologia , Transdução de Sinais , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Actinas/metabolismo , Receptores de Ativinas Tipo I/antagonistas & inibidores , Animais , Doxorrubicina/farmacologia , Ativação Enzimática/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibrose , Imidazóis/farmacologia , Rim/citologia , Rim/patologia , Rim/fisiopatologia , Testes de Função Renal , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Musculares/efeitos dos fármacos , Nefrose/fisiopatologia , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases , Piridinas/farmacologia , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Fator de Crescimento Transformador beta1/biossíntese , Regulação para Cima/efeitos dos fármacosRESUMO
Thirty-two outpatients with a mean age of 68 years were observed in a naturalistic study of outpatient electroconvulsive therapy (ECT) for the management of recurrent mood disorder. Sixty-nine percent of the patients responded favorably to ECT and were either discharged well from therapy or continue in treatment. A rehospitalization rate of 9% supports the efficacy of this treatment. We find outpatient ECT safe for the long-term management of recurrent depressive illness in elderly patients. The low dropout rate demonstrates that patient acceptance is equal to that of other outpatient treatments.
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OBJECTIVE: To investigate the effect of low-flow supplemental oxygen (SupOx) on sleep architecture and cardiorespiratory events in asymptomatic preterm infants. METHODS: An overnight polysomnographic evaluation was conducted prospectively in 23 premature infants who were born at 30.0 +/- 3.2 (standard deviation) weeks' gestational age and studied at 38.1 +/- 4.4 weeks' postconceptional age. Infants were free of any adverse events, including cardiorespiratory monitor alarms in the nursery for at least 1 week before the study. Infants received room air (RA) or SupOx via nasal cannula at 0.25 L/min. RESULTS: Quiet sleep density was increased during SupOx (33.3 +/- 10.8% vs 26.6 +/- 10.0% total sleep time [TST] in RA), and a reciprocal decrease in active sleep density was observed (61.5 +/- 11.1% vs 68.4 +/- 9.9% TST in RA). No differences in sleep efficiency emerged (69.7 +/- 10.6% SupOx vs 69.7 +/- 8.8% RA). SupOx elicited significant decreases in apnea index (3.8 +/- 2.4 events/h vs 11.1 +/- 6.4 events/h in RA) and in the percentage of time spent in periodic breathing (1.8 +/- 2.9% vs 6.7 +/- 8.9% in RA). In addition, SupOx decreased the frequency of bradycardic events (0.3 +/- 0.8 events vs 2.5 +/- 0.03 events in RA) and improved overall oxygen saturation (98.7 +/- 1.1% vs 96.4 +/- 2.2%). No changes in alveolar ventilation, as derived from end-tidal CO2 measurements, was detected (38.6 +/- 5.8 mm Hg in SupOx vs 38.4 +/- 5.4 mm Hg in RA). CONCLUSIONS: Asymptomatic preterm infants exhibit frequent and potentially clinically adverse cardiorespiratory events when assessed in the sleep laboratory. Administration of SupOx to these infants is associated with an increase in the overall duration and percentage TST spent in quiet sleep with reciprocal changes in active sleep. In addition, improvement in respiratory stability is observed with the use of low-flow SupOx, as evidenced by a decrease in apnea, periodic breathing, and bradycardia, without adverse effects on alveolar ventilation.