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Little is known about diabetes risk in adolescents and young adults with Fontan palliation. We sought to understand the prevalence of abnormal hemoglobin A1c (HbA1c) in the adolescent and young adult population with Fontan palliation. Between 2015 and 2021, 78 Fontan patients > 10 years of age were seen in our single ventricle clinic; 66 underwent screening with HbA1c. 50% of the study cohort (n = 33) had HbA1c ≥ 5.7%; 2% (n = 1) had HbA1c ≥ 6.5%. There was no correlation between BMI and HbA1c, with no difference in the prevalence of overweight or obesity (BMI ≥ 85th percentile) between those with and without abnormal HbA1c (31% versus 27%, p = 0.69). While 20% of the cohort had a family history of diabetes, there was no difference in family history between those with and without abnormal HbA1c (21% versus 19%, p = 0.85). There were no differences in other risk factors and characteristics (race, glomerular filtration rate, liver function, liver elastography, hematocrit, and years from Fontan surgery) between those with and without abnormal HbA1c. Our results highlight the importance of recognizing that abnormal HbA1c is highly prevalent in the Fontan population. Whether abnormal HbA1c in this population correlates with atherosclerotic cardiovascular disease in adulthood is not known. The mechanism for an abnormal HbA1c in the adolescent and young adult Fontan population remains unclear and further studies are needed.
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The coronavirus disease 2019 (COVID-19) pandemic necessitated using telehealth to bridge the clinical gap, but could increase health disparities. This article reports on a chart review of diabetes telehealth visits occurring before COVID-19, during shelter-in-place orders, and during the reopening period. Visits for children with public insurance and for those who were non-English speaking were identified. Telehealth visits for children with public insurance increased from 26.2% before COVID-19 to 37.3% during shelter-in-place orders and 34.3% during reopening. Telehealth visits for children who were non-English speaking increased from 3.5% before COVID-19 to 17.5% during shelter-in-place orders and remained at 15.0% during reopening. Pandemic-related telehealth expansion included optimization of workflows to include patients with public insurance and those who did not speak English. Increased participation by those groups persisted during the reopening phase, indicating that prioritizing inclusive telehealth workflows can reduce disparities in access to care.
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PURPOSE OF REVIEW: Osteoporosis is an under-recognized complication of chronic illness in childhood. This review will summarize recent literature addressing the risk factors, evaluation, and treatment for early bone fragility. RECENT FINDINGS: Criteria for the diagnosis of pediatric osteoporosis include the presence of low trauma vertebral fractures alone or the combination of low bone mineral density and several long bone fractures. Monitoring for bone health may include screening for vertebral fractures that are common but often asymptomatic. Pharmacologic agents should be offered to those with fragility fractures especially when spontaneous recovery is unlikely. Controversies persist about the optimal bisphosphonate agent, dose, and duration. Newer osteoporosis drugs have not yet been adequately tested in pediatrics, though clinical trials are underway. The prevalence of osteoporosis is increased in children with chronic illness. To reduce the frequency of fragility fractures requires increased attention to risk factors, early intervention, and additional research to optimize therapy and potentially prevent their occurrence.
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Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Densidade Óssea , Criança , Doença Crônica , Glucocorticoides/efeitos adversos , Humanos , Osteoporose/induzido quimicamente , Osteoporose/complicações , Osteoporose/diagnóstico , Fraturas da Coluna Vertebral/prevenção & controleRESUMO
This report identifies human skeletal diseases associated with mutations in WNT1. In 10 family members with dominantly inherited, early-onset osteoporosis, we identified a heterozygous missense mutation in WNT1, c.652TâG (p.Cys218Gly). In a separate family with 2 siblings affected by recessive osteogenesis imperfecta, we identified a homozygous nonsense mutation, c.884CâA, p.Ser295*. In vitro, aberrant forms of the WNT1 protein showed impaired capacity to induce canonical WNT signaling, their target genes, and mineralization. In mice, Wnt1 was clearly expressed in bone marrow, especially in B-cell lineage and hematopoietic progenitors; lineage tracing identified the expression of the gene in a subset of osteocytes, suggesting the presence of altered cross-talk in WNT signaling between the hematopoietic and osteoblastic lineage cells in these diseases.
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Mutação , Osteogênese Imperfeita/genética , Osteoporose/genética , Proteína Wnt1/genética , Adolescente , Adulto , Idade de Início , Idoso , Animais , Criança , Feminino , Genes Dominantes , Genes Recessivos , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Linhagem , Proteína Wnt1/metabolismo , Adulto JovemRESUMO
Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by Losartan, suggesting a convergence of RANKL and angiotensin signaling at the level of ERK1/2 regulation. To assess the effect of Losartan on cartilage development, we examined the cartilage phenotype of wild type mice treated with Losartan in utero from conception to 1 day of age. Growth plates of these mice showed an elongated hypertrophic chondrocyte zone and increased Col10a1 expression level, with minimal changes in chondrocyte proliferation. Altogether, inhibition of the angiotensin pathway by Losartan increases bone mass and accelerates chondrocyte hypertrophy in growth plate during skeletal development.
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Densidade Óssea/efeitos dos fármacos , Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Losartan/farmacologia , Angiotensinas/efeitos dos fármacos , Angiotensinas/metabolismo , Animais , Densidade Óssea/fisiologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/ultraestrutura , Cartilagem/efeitos dos fármacos , Diferenciação Celular , Condrócitos/fisiologia , Feminino , Lâmina de Crescimento/efeitos dos fármacos , Hipertrofia/etiologia , Losartan/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/fisiologia , Fosforilação , Ligante RANK/antagonistas & inibidores , Ligante RANK/metabolismo , Células RAW 264.7 , RadiografiaRESUMO
OBJECTIVE: The objective of this study is to study if involuntary detention criteria in legal certificates filed by psychiatry residents and faculty psychiatrists are consistent with observations in clinical documentation. METHODS: Eighty-nine involuntarily hospitalized patients were retrospectively selected from medical records; eight patients were excluded due to change in involuntary status or immediate discharge on clinical grounds. Medical certificates filed by the residents and faculty psychiatrists were compared with clinical documentation of the same day for consistency in criteria for detention (substantial risk of harm to self or others and/or inability to care for self). RESULTS: Of 81 included patients, 38.3 % lacked sufficient documentation of clinical justification for involuntary hospitalization. The rate of inconsistency of documented clinical justification showed a greater trend among psychiatry residents compared to faculty psychiatrists (p = 0.069, not statistically significant). CONCLUSIONS: Inconsistency of documented clinical justification for involuntarily detention was higher among residents compared to faculty. There is a need for structured training and supervision of psychiatry residents as well as updated training for faculty psychiatrists with regard to involuntary detention procedures.
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Internação Compulsória de Doente Mental/estatística & dados numéricos , Docentes de Medicina/estatística & dados numéricos , Internato e Residência/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Psiquiatria/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Psiquiatria/métodos , Texas/epidemiologia , Adulto JovemRESUMO
Metabolic bone disease of prematurity (MBDP) is defined by undermineralization of the preterm infant skeleton arising from inadequate prenatal and postnatal calcium (Ca) and phosphate (PO4) accretion. Severe MBDP can be associated with rickets and fractures. Despite advances in neonatal nutrition, MBDP remains prevalent in premature infants due to inadequate mineral accretion ex-utero. There also remain significant knowledge gaps regarding best practices for monitoring and treatment of MBDP among neonatologists and pediatric endocrinologists. Preventing and treating MBDP can prevent serious consequences including rickets or pathologic fractures. Postnatal monitoring to facilitate early recognition of MBDP is best done by first-tier laboratory screening by measuring serum calcium, phosphorus, and alkaline phosphatase to identify infants at risk. If these labs are abnormal, further studies including assessing parathyroid hormone and/or tubular resorption of phosphate can help differentiate between Ca and PO4 deficiency as primary etiologies to guide appropriate treatment with mineral supplements. Additional research into optimal mineral supplementation for the prevention and treatment of MBDP is needed to improve long-term bone health outcomes and provide a fuller evidence base for future treatment guidelines.
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INTRODUCTION: Noonan syndrome (NS) is a disorder of RAS- mitogen activated protein kinase (MAPK) pathway with clinical features of skeletal dysplasia. This pathway is essential for regulation of cell differentiation and growth including bone homeostasis. Currently, limited information exists regarding bone mineralization in NS. MATERIALS AND METHODS: Using dual-energy X-ray absorptiometry (DXA), bone mineralization was evaluated in 12 subjects (mean age 8.7 years) with clinical features of NS. All subjects underwent genetic testing which showed mutations in PTPN11 gene (N=8) and SOS1 gene (N=1). In a subgroup of subjects with low bone mass, indices of calcium-phosphate metabolism and bone turnover were obtained. RESULTS: 50% of subjects had low bone mass as measured by DXA. Z-scores for bone mineral content (BMC) were calculated based on age, gender, height, and ethnicity. Mean BMC z-score was marginally decreased at -0.89 {95% CI -2.01 to 0.23; p=0.1}. Mean total body bone mineral density (BMD) z-score was significantly reduced at -1.87 {95% CI -2.73 to -1.0; p=0.001}. Mean height percentile was close to - 2 SD for this cohort, thus total body BMD z-scores were recalculated, adjusting for height age. Adjusted mean total body BMD z-score was less reduced but still significant at -0.82 {95% CI -1.39 to -0.25; p=0.009}. Biochemical evaluation for bone turnover was unremarkable except serum IGF-I and IGF-BP3 levels which were low-normal for age. DISCUSSION: Children with NS have a significantly lower total body BMD compared to age, gender, ethnicity and height matched controls. In addition, total BMC appears to trend lower in children with NS compared to controls. We conclude that the metabolic bone disease present resulted from a subtle variation in the interplay of osteoclast and osteoblast activity, without clear abnormalities being defined in the metabolism of either. Clinical significance of this finding needs to be validated by larger longitudinal studies. Also, histomorphometric analysis of bone tissue from NS patients and mouse model of NS may further elucidate the relationship between the RAS-MAPK pathway and skeletal homeostasis.
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Osso e Ossos/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Síndrome de Noonan/metabolismo , Proteína Oncogênica p21(ras)/metabolismo , Adolescente , Densidade Óssea , Osso e Ossos/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mutação , Síndrome de Noonan/genéticaRESUMO
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with skeletal involvement. It is caused by mutations in fibrillin1 (FBN1) gene resulting in activation of TGF-ß, which developmentally regulates bone mass and matrix properties. There is no consensus regarding bone mineralization in children with MFS. Using dual-energy X-ray absorptiometry (DXA), we evaluated bone mineralization in 20 children with MFS unselected for bone problems. z-Scores were calculated based on age, gender, height, and ethnicity matched controls. Mean whole body bone mineral content (BMC) z-score was 0.26±1.42 (P=0.41). Mean bone mineral density (BMD) z-score for whole body was -0.34±1.4 (P=0.29) and lumbar spine was reduced at -0.55±1.34 (P=0.017). On further adjusting for stature, which is usually higher in MFS, mean BMC z-score was reduced at -0.677±1.37 (P=0.04), mean BMD z-score for whole body was -0.82±1.55 (P=0.002) and for lumbar spine was -0.83±1.32 (P=0.001). An increased risk of osteoporosis in MFS is controversial. DXA has limitations in large skeletons because it tends to overestimate BMD and BMC. By adjusting results for height, age, gender, and ethnicity, we found that MFS patients have significantly lower BMC and BMD in whole body and lumbar spine. Evaluation of diet, exercise, vitamin D status, and bone turnover markers will help gain insight into pathogenesis of the reduced bone mass. Further, larger longitudinal studies are required to evaluate the natural history, incidence of fractures, and effects of pharmacological therapy.
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Densidade Óssea , Síndrome de Marfan/fisiopatologia , Absorciometria de Fóton , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fibrilina-1 , Fibrilinas , Humanos , Masculino , Síndrome de Marfan/genética , Proteínas dos Microfilamentos/genéticaRESUMO
Pathogenic variants in RPS6KA3 are associated with Coffin-Lowry syndrome (CLS), an X-linked semidominant disorder characterized by intellectual disability, stimulus-induced drop attacks, distinctive facial features, progressive kyphoscoliosis, and digit anomalies in hemizygous males. Heterozygous females may also have features of CLS; however, there can be considerable phenotypic variation, often attributed to ratios of X-inactivation in various tissue types. Although skeletal anomalies and short stature are hallmarks of CLS, hypercalcemia has not been reported. Here we describe a 30-month-old girl with gross motor delays, short stature, dysmorphic features, bilateral duplicated renal collecting systems, and no family history of hypercalcemia who required multiple admissions for idiopathic hypercalcemia necessitating bisphosphonate infusions at 12.5 and 15 months of age. A maternally inherited likely-pathogenic variant in RPS6KA3 was identified by trio exome sequencing, consistent with the diagnosis of CLS in the proband and her mother. Maternal history was notable only for decreased height compared to first-degree relatives, bilateral genu valgum, and a bicornuate uterus; she was later found to also have a partially duplicated left renal collecting system. Subsequent X-inactivation studies in blood aligned with the phenotypic variation between mother and daughter. Although hypercalcemia is not a reported feature in CLS, there is evidence of interrupted osteoblast differentiation, providing a potential mechanism for hypercalcemia in this genetic condition. The hypercalcemia in this case may represent a severe presentation of an unrecognized clinical feature in CLS that resolves with age. This case further highlights the intrafamilial phenotypic variation of CLS among females, suggesting X-inactivation as the underlying mechanism, and demonstrates the value of exome sequencing in patients for whom a genetic disorder is highly suspected but not identified despite thorough evaluation.
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Síndrome de Coffin-Lowry , Nanismo , Hipercalcemia , Deficiência Intelectual , Pré-Escolar , Síndrome de Coffin-Lowry/genética , Feminino , Humanos , Hipercalcemia/etiologia , Hipercalcemia/genética , Masculino , Proteínas Quinases S6 Ribossômicas 90-kDa/genéticaRESUMO
CONTEXT: The ketogenic diet is associated with progressive skeletal demineralization, hypercalciuria, and nephrolithiasis. Acute hypercalcemia has been described as a newly recognized complication of this treatment. OBJECTIVE: To describe the clinical characteristics of acute hypercalcemia in children on the ketogenic diet through analysis of the presentation, response to treatment, and natural history in a large cohort of patients. DESIGN: A multicenter case series was performed including children who developed acute hypercalcemia while treated with the ketogenic diet. Information on clinical presentation, treatment, and course of this complication was collated centrally. RESULTS: There were 14 patients (median (range) age 6.3 (0.9 to 18) years) who developed hypercalcemia 2.1 (range, 0.2-12) years after starting the ketogenic diet. All had low levels of parathyroid hormone and levels of 1,25-dihydroxyvitamin D were low in all except one. Seven (50%) had impaired renal function at presentation. All except the 2 oldest had low alkaline phosphatase levels for age. Once normocalcemia was achieved, hypercalcemia recurred in only 2 of these patients over observation of up to 9.8 years. One patient discontinued the ketogenic diet prior to achieving normocalcemia while 4 more stopped the diet during follow-up after resolution of hypercalcemia. CONCLUSIONS: Ketotic hypercalcemia can occur years after starting the ketogenic diet, especially in the setting of renal impairment. The mechanism is unknown but appears to be due to reduced osteoblast activity and impaired bone formation. We recommend close attention to optimizing bone health in these children, and screening for the development of ketotic hypercalcemia.
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Dieta Cetogênica/efeitos adversos , Hipercalcemia/etiologia , Doença Aguda , Adolescente , Fatores Etários , Síndrome de Aicardi/complicações , Síndrome de Aicardi/dietoterapia , Síndrome de Aicardi/epidemiologia , Cálcio/urina , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia Resistente a Medicamentos/dietoterapia , Epilepsia Resistente a Medicamentos/epidemiologia , Feminino , Humanos , Hipercalcemia/epidemiologia , Hipercalciúria/epidemiologia , Hipercalciúria/etiologia , Lactente , Recém-Nascido , Síndrome de Lennox-Gastaut/complicações , Síndrome de Lennox-Gastaut/dietoterapia , Síndrome de Lennox-Gastaut/epidemiologia , Masculino , Nefrocalcinose/epidemiologia , Nefrocalcinose/etiologia , Hormônio Paratireóideo/sangue , Estados Unidos/epidemiologiaRESUMO
Previous studies have shown that nitric oxide (NO) supplements may prevent bone loss and fractures in preclinical models of estrogen deficiency. However, the mechanisms by which NO modulates bone anabolism remain largely unclear. Argininosuccinate lyase (ASL) is the only mammalian enzyme capable of synthesizing arginine, the sole precursor for nitric oxide synthase-dependent (NOS-dependent) NO synthesis. Moreover, ASL is also required for channeling extracellular arginine to NOS for NO production. ASL deficiency (ASLD) is thus a model to study cell-autonomous, NOS-dependent NO deficiency. Here, we report that loss of ASL led to decreased NO production and impairment of osteoblast differentiation. Mechanistically, the bone phenotype was at least in part driven by the loss of NO-mediated activation of the glycolysis pathway in osteoblasts that led to decreased osteoblast differentiation and function. Heterozygous deletion of caveolin 1, a negative regulator of NO synthesis, restored NO production, osteoblast differentiation, glycolysis, and bone mass in a hypomorphic mouse model of ASLD. The translational significance of these preclinical studies was further reiterated by studies conducted in induced pluripotent stem cells from an individual with ASLD. Taken together, our findings suggest that ASLD is a unique genetic model for studying NO-dependent osteoblast function and that the NO/glycolysis pathway may be a new target to modulate bone anabolism.
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Acidúria Argininossuccínica/metabolismo , Osso e Ossos/metabolismo , Diferenciação Celular , Glicólise , Ácido Nítrico/metabolismo , Osteoblastos/metabolismo , Adolescente , Adulto , Animais , Acidúria Argininossuccínica/genética , Acidúria Argininossuccínica/patologia , Osso e Ossos/patologia , Criança , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Osteoblastos/patologiaRESUMO
The simultaneous occurrence of prepubertal Graves' disease, type 1 Diabetes Mellitus (DM), and Growth hormone deficiency (GHD) is uncommon. GHD has been reported in Autoimmune Polyglandular Syndrome (APS) Type 1 and Type 2 but not in APS Type 3. We report a 3-yr-old boy who presented simultaneously with type 1 DM and Graves' disease. After he developed urticarial rash to Propylthiouracil and Methimazole with persistent thyrotoxicosis, he received 8 millicuries of (131)I at 5 yr of age. We diagnosed GHD at age 8 yr 8 months because of growth deceleration (from 95 to 25%) and abnormal growth rate (3 cm/yr) despite euthyroidism, fair glycemic control, and normal weight gain. Both insulin-like growth factor (IGF) 1 (90 ng/mL; normal 113-261 ng/mL) and IGFBP3 (1.3 mcg/mL; normal 2.1-4.2 mcg/mL) levels were low and peak growth hormone level measured by RIA was 5.2 ng/mL after L-Dopa and insulin tolerance test. The rest of his pituitary functions and magnetic resonance imaging of the pituitary gland were normal. Growth hormone treatment (0.3 mg/kg/wk) was administered at 8 yr 9 months until near final adult height (FAH). Near FAH (172 cm) was close to midparental target height of 180 cm. GHD may be a component of all APS even though it is rare. Growth in treated children with Graves' disease should be followed closely as catch down growth below genetic height potential may be a harbinger of underlying GHD.
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Diabetes Mellitus Tipo 1/complicações , Doença de Graves/complicações , Hormônio do Crescimento Humano/deficiência , Poliendocrinopatias Autoimunes/complicações , Adolescente , Criança , Pré-Escolar , Seguimentos , Doença de Graves/radioterapia , Hormônio do Crescimento Humano/sangue , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , MasculinoRESUMO
BACKGROUND: The purpose of this study is to assess the impact of frequency and tone of parent-youth communication on glycemic control as measured by the Family Communication Inventory (FCI). Adolescence provides a unique set of diabetes management challenges, including suboptimal glycemic control. Continued parental involvement in diabetes management is associated with improved HbA1c outcomes; however, diabetes-related conflict within the family can have adverse effects. Although it is clear that communication plays an important role in diabetes outcomes, the specific impact of frequency and tone of such communication is largely understudied. METHODS: A total of 110 youths with type 1 diabetes and their parents completed questionnaires assessing diabetes-related adherence, family conflict, and family communication (i.e., frequency and tone) during a routine clinic visit. Routine testing of HbA1c was performed. RESULTS: Youth- and parent-reported frequency of communication were unrelated to HbA1c. Instead, greater discrepancies between parents and children on reported frequency of communication (most commonly parents reporting frequent and youth reporting less frequent communication) corresponded with poorer glycemic control and increased family conflict. More positive tone of communication as rated by youth was associated with lower HbA1c. CONCLUSIONS: Diabetes-related communication is more complex than conveyed simply by how often children and their parents communicate. Tone of communication and discrepancies in a family's perception of the frequency of communication were better than frequency as predictors of glycemic control. The FCI appears to capture the frequency and tone of diabetes-related communication, though larger-scale studies are warranted to inform future use of this scale.
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The 45,X disorder of sexual differentiation (DSD) is a rare disorder. We report long-term follow-up of a 5-year-old African-American male whose evaluation for short stature revealed a karyotype of 45,X der(X)t(X;Y)(p22.3;p11.2)(SRY+). Presence of the SRY (sex-determining region Y) gene resulted in his male development. His chromosome abnormality also resulted in a deletion of the SHOX (short stature homeobox-containing) gene, which partly contributed to his short stature and skeletal features. He underwent normal spontaneous pubertal development, but his final height remained compromised due to advanced bone age, non-optimal response to recombinant human growth hormone (rhGH) treatment during the period of compliance and ultimately non-compliance with rhGH therapy. To our knowledge, this is the first case report describing long-term follow-up of a 45,X male DSD which highlights the similarities and differences from Turner syndrome females.
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Estatura/genética , Cromossomos Humanos X/genética , Transtornos do Desenvolvimento Sexual/genética , Haploinsuficiência/genética , Proteínas de Homeodomínio/genética , Pré-Escolar , Transtornos do Desenvolvimento Sexual/patologia , Feminino , Seguimentos , Humanos , Cariotipagem , Masculino , Prognóstico , Proteína de Homoeobox de Baixa EstaturaAssuntos
Osso e Ossos/patologia , Transtornos Cromossômicos/patologia , Doenças do Sistema Endócrino/patologia , Consolidação da Fratura/fisiologia , Fraturas Ósseas/patologia , Distúrbios Nutricionais/patologia , Osteoporose/patologia , Absorciometria de Fóton , Adolescente , Criança , Transtornos Cromossômicos/complicações , Suplementos Nutricionais , Doenças do Sistema Endócrino/complicações , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/etiologia , Fraturas Ósseas/terapia , Humanos , Avaliação Nutricional , Distúrbios Nutricionais/complicações , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Osteoporose/terapia , Guias de Prática Clínica como AssuntoRESUMO
Pediatric hematology oncology nurses face a variety of stressors while working in this specialty field. Through hematology oncology staff group discussions, nurses identified a myriad physical and emotional stressors they experienced, and expressed concern regarding possible burnout. They described facing stressors related to experiencing loss, grief, moral and ethical dilemmas, and administering complex treatment regimens. To address these concerns, a hematology oncology nursing supportive care committee envisioned and implemented 3 off-site self-care retreats. The committee's primary purpose was to create a therapeutic and supportive environment for all participants, while allowing time for relaxation, reflection, and serenity. The primary goals for the retreats were to heal nurses from their reported past trauma and stress and to provide them effective coping strategies for the ongoing stressors they will inevitably face. In a collaborative effort, the committee members developed an agenda including presentations, group discussions, and relaxation activities. Written evaluations were completed by each participant to assess the benefit of the retreat. Overall feedback was extremely positive, with the majority of the participants finding great value in this experience.
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Esgotamento Profissional/terapia , Neoplasias Hematológicas/enfermagem , Recursos Humanos de Enfermagem Hospitalar/psicologia , Enfermagem Oncológica , Autocuidado , Adaptação Psicológica , Humanos , Recursos HumanosRESUMO
Osteogenesis imperfecta (OI) is typically caused by mutations in type 1 collagen genes, but in recent years new recessive and dominant forms caused by mutations in a plethora of different genes have been characterized. OI type V is a dominant form caused by the recurrent (c.-14C > T) mutation in the 5'UTR of the IFITM5 gene. The mutation adds five residues to the N-terminus of the IFITM5, but the pathophysiology of the disease remains to be elucidated. Typical clinical features present in the majority of OI type V patients include interosseous membrane calcification between the radius and ulna and between the tibia and fibula, radial head dislocation, and significant hyperplastic callus formation at the site of fractures. We report a 5-year-old child with clinical features of OI type III or severe OI type IV (characteristic facies, gray sclerae, typical fractures) and absence of classical features of OI type V with a de novo recurrent IFITM5 mutation (c.-14C > T), now typical of OI type V. This highlights the variability of OI caused by IFITM5 mutations and suggests screening for mutations in this gene in most cases of OI where type 1 collagen mutations are absent.
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Proteínas de Membrana/genética , Mutação/genética , Osteogênese Imperfeita/genética , Sequência de Bases , Criança , Feminino , Antebraço/diagnóstico por imagem , Humanos , Masculino , Dados de Sequência Molecular , Osteogênese Imperfeita/diagnóstico por imagem , Linhagem , RadiografiaRESUMO
In a large cohort of osteogenesis imperfecta type V (OI type V) patients (17 individuals from 12 families), we identified the same mutation in the 5' untranslated region (5'UTR) of the interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.-14C > T) and provide a detailed description of their phenotype. This mutation leads to the creation of a novel start codon adding five residues to IFITM5 and was recently reported in several other OI type V families. The variability of the phenotype was quite large even within families. Whereas some patients presented with the typical calcification of the forearm interosseous membrane, radial head dislocation and hyperplastic callus (HPC) formation following fractures, others had only some of the typical OI type V findings. Thirteen had calcification of interosseous membranes, 14 had radial head dislocations, 10 had HPC, 9 had long bone bowing, 11 could ambulate without assistance, and 1 had mild unilateral mixed hearing loss. The bone mineral density varied greatly, even within families. Our study thus highlights the phenotypic variability of OI type V caused by the IFITM5 mutation.