Quantitative Changes In Human Epithelial Cancers And Osteogenesis Imperfecta Disease Detected Using Nonlinear Multicontrast Microscopy.

We show that combined multimodal nonlinear optical (NLO) microscopies, including two-photon excitation fluorescence, second-harmonic generation (SHG), third harmonic generation, and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation during the progression of cancer and osteogenesis imperfecta (OI) disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for different types of human breast cancer, mucinous ovarian tumors, and skin dermis of patients with OI. Using a set of scoring methods (anisotropy, correlation, uniformity, entropy, and lifetime components), we found significant differences in the content, distribution and organization of collagen fibrils in the stroma of breast and ovary as well as in the dermis of skin. We suggest that our results provide a framework for using NLO techniques as a clinical diagnostic tool for human cancer and OI. We further suggest that the SHG and FLIM metrics described could be applied to other connective or epithelial tissue disorders that are characterized by abnormal cells proliferation and collagen assembly.17081407-

Avaliação metabólica em mulheres jovens com hiperplasia adrenal congênita

OBJECTIVE: To evaluate insulin resistance and lipid profile in women with congenital adrenal hyperplasia (CAH) caused by classical 21-hydroxylase deficiency (21OHD), and their association with body mass index (BMI) and corticosteroid dosage. SUBJECTS AND METHODS: We assessed BMI, waist circumference, current glucocorticoid dosage, glucose, insulin and lipid profile in eighteen young women (mean ± SD, 19.3 ± 3.0 years) with 21OHD CAH. RESULTS: BMI was normal in 12 patients, 5 of them were overweight, and 1 was obese. Waist circumference was high in 7 patients. Fasting insulin and HOMA-IR were elevated in seven and eight patients, respectively. Total cholesterol and triglycerides were high in only two patients, and HDL-cholesterol was low in four. Insulin resistance was not associated with BMI, waist circumference or glucocorticoid dose. CONCLUSIONS: Young women with 21OHD CAH had infrequent dyslipidemia, but had a higher prevalence of insulin resistance and central obesity, that were independent of BMI or corticosteroid dosage.OBJETIVO: Avaliar a presença de resistência insulínica e dislipidemia em mulheres com hiperplasia adrenal congênita (HAC) por deficiência da 21-hidroxilase (21OHD) e investigar a associação com índice de massa corporal (IMC) e dose de glicocorticoide prescrita. PACIENTES E MÉTODOS: Em 18 mulheres jovens (média ± DP, 19,3 ± 3,0 anos), avaliamos IMC, circunferência abdominal, dose de glicocorticoide, glicemia, insulinemia e perfil lipídico. RESULTADOS: O IMC foi normal em 12 pacientes; 5 apresentavam sobrepeso e 1 apresentou obesidade. Circunferência abdominal estava aumentada em 7 pacientes. Insulinemia de jejum e HOMA-IR estavam elevados em 7 e 8 pacientes, respectivamente. Apenas 2 pacientes apresentaram aumento de colesterol total ou de triglicérides e 4, diminuição dos níveis de HDL-colesterol. Resistência insulínica não apresentou associação com IMC, circunferência abdominal ou dose de glicocorticoide prescrita. CONCLUSÃO: Mulheres jovens com CAH 21OHD apresentaram pouca dislipidemia, mas tiveram alta prevalência de resistência insulínica e obesidade central, independentemente do IMC e da dose de glicocorticoide prescrita.64665

A ausência de mutações no gene PAX6 em três casos de síndrome de Morning Glory associada à deficiência isolada de hormônio do crescimento

Morning glory syndrome (MGS) is a congenital optic disc dysplasia often associated with craniofacial anomalies, especially basal encephalocele and hypopituitarism. Clinical signs are varied and often occult. The PAX6 gene is involved in ocular morphogenesis and is expressed in numerous ocular tissues during development especially in the developing central nervous system. The aim of the present study is to evaluate PAX6 in MGS associated with isolated growth hormone deficiency. Three pre-pubertal males (A, B and C) with MGS and short stature due to growth hormone deficiency, treated with recombinant human growth hormone with limited response, were reported. Two of them had basal encephalocele. Coding and non-coding sequences corresponding of PAX6 different transcripts were analyzed by direct sequencing. Nucleotide variations causing putative aminoacid change were not observed. Patient A presented the new IVS2+9G>A transition, whereas patients A and C were heterozygous for known single nucleotide polymorphisms (SNP) within the intron 4. In addition, two SNP heterozygoses were observed for patient C in both intron 9 and 13. Sequencing also revealed several nucleotide variations in patient B. Two heterozygoses for known polymorphisms were identified along with a novel C>A nucleotide change in intron 4. This patient also presented a low number on the TG repeat in intron 9 and a new IVS11+33A>T transversion. Gene regulation and transcription of PAX6 are complex processes; there are two major protein isoforms, PAX6(-5a) and PAX6(+5a), and nine transcripts described. Furthermore, extra transcription regulatory elements have been postulated within PAX6 introns. Considering that neither population distributions on PAX6 polymorphism nor their linkeages with diseases have been reported, a functional effect due to alterations described here cannot be discarded.A síndrome de Morning Glory (SMG) é uma displasia óptica congênita associada a anomalias craniofaciais, principalmente encefalocele basal e hipopituitarismo. Os sinais clínicos são variados e muitas vezes ocultos. O gene PAX6 está envolvido na morfogênese ocular e se expressa em vários tecidos oculares durante o desenvolvimento do sistema nervoso central. O objetivo deste estudo foi avaliar o gene PAX6 na SMG associada com deficiência isolada de hormônio de crescimento. Foram relatados três pacientes pré-púberes (A, B e C) com SMG e baixa estatura por deficiência de hormônio de crescimento tratados com hormônio de crescimento recombinante humano. As seqüências codificadoras e não-codificadoras correspondentes ao PAX6 em diferentes transcritos foram analisadas por seqüenciamento direto. Variações nucleotídeas com trocas pontuais de aminoácidos não foram encontradas. O paciente A apresentou uma transição nova IVS2+9G>A, enquanto os pacientes A e C foram heterozigotos para um polimorfismo (SNP) no íntron 4. Ainda, dois SNPs em heterozigose nos íntrons 9 e 13 foram observados no paciente C. O seqüenciamento também mostrou várias variações nucleotídeas no paciente B. Dois SNPs conhecidos com a alteração nucleotídea nova C>A no íntron 4 foram observados em heterozigose. Este paciente também apresentou um baixo número de repetições TG no íntron 9 e uma nova transversão IVS11+33A>T. A regulação e a transcrição do gene PAX6 são um processo complexo; existem 2 isoformas principais da proteína, PAX6(-5a) e PAX6(+5a) e 9 transcritos descritos. Considerando que nem a distribuição de SNPs no PAX6 e nem as suas ligações com as doenças foram relatadas, um defeito funcional devido às alterações descritas não pode ser descartado.University of Campinas Faculty of Medical Sciences Pediatric Endocrinology UnitFederal University of São Paulo School of Medicine Pediatric Endocrinology UnitUNIFESP School of Medicine Department of RadiologyUnicamp Center of Molecular Biology and Genetic EngineeringUNIFESP, EPM, Pediatric Endocrinology UnitUNIFESP, School of Medicine Department of RadiologySciEL

Central precocious puberty as a sole manifestation of suprasellar arachnoid cyst

OBJECTIVE: Arachnoid cysts (AC) are a rare finding; 10% of them are suprasellar and occur almost exclusively in children. They are frequently associated with neurological and visual manifestations. Central precocious puberty as a sole manifestation is uncommon. CASE DESCRIPTION: Girl evaluated at the age of two years and seven months. She started breast development at the age of one year and eight months, pubic and axillary hair at the age of two years, with growth velocity acceleration (13cm/year) and increased bone age (seven years and one month). On exam: weight: 22.6kg (Z+4.0), height: 106cm (Z+3.5) and puberal stage of B3P2. The GnRH stimulus test was performed (basal LH 8.3 IU/L, at 30 minutes 94.3 IU/L; FSH basal=10.1 IU/L, at 30 minutes 29.5 IU/L). Nuclear Magnetic Resonance of the skull showed a suprasellar arachnoid cyst. Others stimulation tests were performed and excluded pituitary deficiencies. Treatment with a GnRH analog was started. At the age of four years and three months, she was B3P2, with normal growth velocity and neurologic development. COMMENTS: Central precocious puberty can be the only manifestation of AC. It is essential to establish early diagnosis and treatment. A prolonged follow up is recommended, since late pituitary dysfunctions can occur.OBJETIVO: Os cistos aracnoides são achados raros. Em 10% dos casos, sua localização é supraselar e ocorrem quase exclusivamente em crianças. Em geral, apresentam manifestações neurológicas e visuais, sendo incomum a puberdade precoce central como sinal clínico de sua presença. DESCRIÇÃO DO CASO: Menina avaliada aos dois anos e sete meses por telarca iniciada com um ano e oito meses e pubarca e axilarca com dois anos, com aumento da velocidade de crescimento (13cm/ano) e da idade óssea (sete anos e um mês). Ao exame, apresentou peso de 22,6kg (Z+4,0), estatura de 106cm (Z+3,5) e Tanner de M3P2. Exames realizados: teste de estímulo com GnRH (LH basal 8,3 UI/L, pico aos 30 minutos 94,3 UI/L; FSH basal=10,1 UI/L, pico aos 30 minutos 29,5 UI/L), ressonância nuclear magnética de crânio com cisto aracnoide supraselar e demais testes de função hipofisária normais. Foi iniciado tratamento com análogo de GnRH. Atualmente, aos quatro anos e três meses com estadio puberal M3P2, velocidade de crescimento e desenvolvimento neuropsicomotor normais para a idade. COMENTÁRIOS: A puberdade precoce central pode ser manifestação única de um cisto aracnoide, sendo essenciais o diagnóstico e o tratamento precoces, além de seguimento prolongado, uma vez que outras disfunções hipofisárias podem ocorrer tardiamente.12612

Long-term Follow-up Of An 8-year-old Boy With Insulinoma As The First Manifestation Of A Familial Form Of Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling.54754-6

A ausência de mutações no gene PAX6 em três casos de síndrome de Morning Glory associada à deficiência isolada de hormônio do crescimento

Morning glory syndrome (MGS) is a congenital optic disc dysplasia often associated with craniofacial anomalies, especially basal encephalocele and hypopituitarism. Clinical signs are varied and often occult. The PAX6 gene is involved in ocular morphogenesis and is expressed in numerous ocular tissues during development especially in the developing central nervous system. The aim of the present study is to evaluate PAX6 in MGS associated with isolated growth hormone deficiency. Three pre-pubertal males (A, B and C) with MGS and short stature due to growth hormone deficiency, treated with recombinant human growth hormone with limited response, were reported. Two of them had basal encephalocele. Coding and non-coding sequences corresponding of PAX6 different transcripts were analyzed by direct sequencing. Nucleotide variations causing putative aminoacid change were not observed. Patient A presented the new IVS2+9G>A transition, whereas patients A and C were heterozygous for known single nucleotide polymorphisms (SNP) within the intron 4. In addition, two SNP heterozygoses were observed for patient C in both intron 9 and 13. Sequencing also revealed several nucleotide variations in patient B. Two heterozygoses for known polymorphisms were identified along with a novel C>A nucleotide change in intron 4. This patient also presented a low number on the TG repeat in intron 9 and a new IVS11+33A>T transversion. Gene regulation and transcription of PAX6 are complex processes; there are two major protein isoforms, PAX6(-5a) and PAX6(+5a), and nine transcripts described. Furthermore, extra transcription regulatory elements have been postulated within PAX6 introns. Considering that neither population distributions on PAX6 polymorphism nor their linkeages with diseases have been reported, a functional effect due to alterations described here cannot be discarded.A síndrome de Morning Glory (SMG) é uma displasia óptica congênita associada a anomalias craniofaciais, principalmente encefalocele basal e hipopituitarismo. Os sinais clínicos são variados e muitas vezes ocultos. O gene PAX6 está envolvido na morfogênese ocular e se expressa em vários tecidos oculares durante o desenvolvimento do sistema nervoso central. O objetivo deste estudo foi avaliar o gene PAX6 na SMG associada com deficiência isolada de hormônio de crescimento. Foram relatados três pacientes pré-púberes (A, B e C) com SMG e baixa estatura por deficiência de hormônio de crescimento tratados com hormônio de crescimento recombinante humano. As seqüências codificadoras e não-codificadoras correspondentes ao PAX6 em diferentes transcritos foram analisadas por seqüenciamento direto. Variações nucleotídeas com trocas pontuais de aminoácidos não foram encontradas. O paciente A apresentou uma transição nova IVS2+9G>A, enquanto os pacientes A e C foram heterozigotos para um polimorfismo (SNP) no íntron 4. Ainda, dois SNPs em heterozigose nos íntrons 9 e 13 foram observados no paciente C. O seqüenciamento também mostrou várias variações nucleotídeas no paciente B. Dois SNPs conhecidos com a alteração nucleotídea nova C>A no íntron 4 foram observados em heterozigose. Este paciente também apresentou um baixo número de repetições TG no íntron 9 e uma nova transversão IVS11+33A>T. A regulação e a transcrição do gene PAX6 são um processo complexo; existem 2 isoformas principais da proteína, PAX6(-5a) e PAX6(+5a) e 9 transcritos descritos. Considerando que nem a distribuição de SNPs no PAX6 e nem as suas ligações com as doenças foram relatadas, um defeito funcional devido às alterações descritas não pode ser descartado.1221122

Bullying Prevalence And Its Perception Of Students, Parents And Teachers

5821S76S7

The Future Of Screening, Brief Intervention And Referral To Treatment In Adolescent Primary Care: Research Directions And Dissemination Challenges

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Purpose of review screening, brief intervention and referral to treatment (SBIRT) offers a practical, integrated model for addressing substance use in primary care settings. This review provides an update of the research on SBIRT for adolescents in primary care, examines current dissemination challenges and suggests future research directions.Recent findingsA number of brief screening tools for adolescents have been developed and tested relative to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) substance use disorders. Computerized previsit screening promotes standardization and is a more time-efficient alternative to provider interview. The adolescent brief intervention literature is growing, particularly with respect to technology-based tools, but is still limited, with evidence greatest for alcohol, and for motivational enhancement therapy interventions. Increasing SBIRT implementation in pediatric primary care remains a challenge. Using nonphysician behavioral health providers to deliver SBIRT, and embedding a screener and decision support tool in electronic medical record systems are strategies being investigated to promote SBIRT implementation.SummarySubstance use begins in adolescence, and pediatric SBIRT could help to achieve a population-level reduction of substance use-related harms. With a growing number of available tools, adolescent SBIRT effectiveness and feasibility are increasing, but more studies are needed to grow its evidence base, and elucidate strategies to increase implementation.284434440Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior [CAPES - BEX 6951/14-7]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil [CNPq - 202418/2014]Divisions of Adolescent/Young Adult Medicine and Developmental Medicine at Boston Children's HospitalNational Institute on Alcohol Abuse and Alcoholism [5R01AA021904-03, 5R01AA022493-02, 5R34AA023026-02]Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Apoptosis through death receptors in temporal lobe epilepsy-associated hippocampal sclerosis

Seizure models have demonstrated that neuroinflammation and neurodegeneration are preponderant characteristics of epilepsy. Considering the lack of clinical studies, our aim is to investigate the extrinsic pathway of apoptosis in pharmacoresistant temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) patients, TLE(HS). By a specific death receptor-mediated apoptosis array plate, 31 upregulated targets were revealed in the sclerotic hippocampus from TLE(HS) patients. Amongst them are the encoding genes for ligands (FASLG, TNF, and TNFSF10) and death receptors (FAS, TNFRSF1A, TNFRSF10A, and TNFRSF10B). In addition, we evaluated the hippocampal relative mRNA expression of the two TNF receptors, TNFRSF1A and TNFRSF1B, in patients, being both upregulated (n = 14; n < 0.01 and n < 0.04, resp.) when compared to the post mortem control group (n. = 4). Our results have clearly suggested that three different death receptor apoptotic systems may be associated with the maintenance and progression of TLE-associated HS: (1) TNF-TNFRSF1A, (2) FASLG-FAS, and (3) TNFSF10-TNFRSF10A/B. Their effects on epilepsy are still scarcely comprehended. Our study points out to TNF and TNF receptor superfamily pathways as important targets for pharmacological studies regarding the benefits of an anti-inflammatory therapy in these patients2016COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informação2005/565778-