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3.
Ultrasound Obstet Gynecol ; 64(3): 348-353, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39087927

RESUMEN

OBJECTIVE: To assess the capacity of fetal pancreatic size, before standard blood glucose testing for screening and diagnosis, to predict maternal gestational diabetes mellitus (GDM). METHODS: This was a retrospective cohort study of low-risk pregnant women recruited during routine second-trimester fetal anatomical screening at 20-25 weeks' gestation at two ultrasound units in Israel between 2017 and 2020. The predictive performance of fetal pancreatic circumference ≥ 80th and ≥ 90th centiles and glucose challenge test (GCT) was examined for the outcome of GDM. The independent-samples t-test was used to compare mean pancreatic circumference centile between pregnancies with GDM and those without GDM. Diagnostic performance was evaluated with 2 × 2 contingency tables and receiver-operating-characteristics (ROC) curves. RESULTS: Overall, 195 women were selected for statistical analysis. Twenty-four (12.3%) women were diagnosed subsequently with GDM. The mean ± SD fetal pancreatic circumference centile was significantly higher in the GDM group compared with the non-GDM group (82.4 ± 14.6 vs 62.8 ± 27.6; P < 0.001). The pancreatic circumference centile was correlated positively with the estimated fetal weight centile (Pearson's coefficient, 0.243; P = 0.001). The 80th centile cut-off for pancreatic circumference had the highest sensitivity (70.8%) and positive predictive value (23.3%) for future maternal GDM, with the best trade-off between sensitivity and specificity achieved at the 75th centile cut-off (sensitivity, 79%; specificity, 60%). The GCT had better specificity (90.2%) and negative predictive value (97.9%) compared with both cut-offs in pancreatic circumference. The area under the ROC curve was higher for pancreatic circumference compared with GCT (0.71 vs 0.64) and only the former was statistically significant (P = 0.001). CONCLUSIONS: Fetal pancreatic circumference has a higher positive predictive capacity compared with GCT. Measuring pancreatic circumference can identify pregnancies at high risk for maternal GDM, thereby promoting earlier diagnosis and treatment, decreasing the time period during which the fetus is exposed to high maternal glucose levels and improving infant outcome. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Asunto(s)
Diabetes Gestacional , Páncreas , Valor Predictivo de las Pruebas , Segundo Trimestre del Embarazo , Ultrasonografía Prenatal , Humanos , Femenino , Embarazo , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/diagnóstico por imagen , Estudios Retrospectivos , Adulto , Páncreas/diagnóstico por imagen , Páncreas/embriología , Israel , Curva ROC , Prueba de Tolerancia a la Glucosa , Tamaño de los Órganos , Sensibilidad y Especificidad , Edad Gestacional
5.
Hum Reprod ; 34(11): 2228-2243, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31734698

RESUMEN

STUDY QUESTION: Does experimental manipulation of fibroblast growth factor 9 (FGF9)-signalling in human fetal gonads alter sex-specific gonadal differentiation? SUMMARY ANSWER: Inhibition of FGFR signalling following SU5402 treatment impaired germ cell survival in both sexes and severely altered the developing somatic niche in testes, while stimulation of FGF9 signalling promoted Sertoli cell proliferation in testes and inhibited meiotic entry of germ cells in ovaries. WHAT IS KNOWN ALREADY: Sex-specific differentiation of bipotential gonads involves a complex signalling cascade that includes a combination of factors promoting either testicular or ovarian differentiation and inhibition of the opposing pathway. In mice, FGF9/FGFR2 signalling has been shown to promote testicular differentiation and antagonize the female developmental pathway through inhibition of WNT4. STUDY DESIGN, SIZE, DURATION: FGF signalling was manipulated in human fetal gonads in an established ex vivo culture model by treatments with recombinant FGF9 (25 ng/ml) and the tyrosine kinase inhibitor SU5402 (10 µM) that was used to inhibit FGFR signalling. Human fetal testis and ovary tissues were cultured for 14 days and effects on gonadal development and expression of cell lineage markers were determined. PARTICIPANTS/MATERIALS, SETTING, METHODS: Gonadal tissues from 44 male and 33 female embryos/fetuses from first trimester were used for ex vivo culture experiments. Tissues were analyzed by evaluation of histology and immunohistochemical analysis of markers for germ cells, somatic cells, proliferation and apoptosis. Culture media were collected throughout the experimental period and production of steroid hormone metabolites was analyzed in media from fetal testis cultures by liquid chromatography-tandem mass spectrometry (LC-MS/MS). MAIN RESULTS AND THE ROLE OF CHANCE: Treatment with SU5402 resulted in near complete loss of gonocytes (224 vs. 14 OCT4+ cells per mm2, P < 0.05) and oogonia (1456 vs. 28 OCT4+ cells per mm2, P < 0.001) in human fetal testes and ovaries, respectively. This was a result of both increased apoptosis and reduced proliferation in the germ cells. Addition of exogenous FGF9 to the culture media resulted in a reduced number of germ cells entering meiosis in fetal ovaries (102 vs. 60 γH2AX+ germ cells per mm2, P < 0.05), while in fetal testes FGF9 stimulation resulted in an increased number of Sertoli cells (2503 vs. 3872 SOX9+ cells per mm2, P < 0.05). In fetal testes, inhibition of FGFR signalling by SU5402 treatment altered seminiferous cord morphology and reduced the AMH expression as well as the number of SOX9-positive Sertoli cells (2503 vs. 1561 SOX9+ cells per mm2, P < 0.05). In interstitial cells, reduced expression of COUP-TFII and increased expression of CYP11A1 and CYP17A1 in fetal Leydig cells was observed, although there were no subsequent changes in steroidogenesis. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Ex vivo culture may not replicate all aspects of fetal gonadal development and function in vivo. Although the effects of FGF9 were studied in ex vivo culture experiments, there is no direct evidence that FGF9 acts in vivo during human fetal gonadogenesis. The FGFR inhibitor (SU5402) used in this study is not specific to FGFR2 but inhibits all FGF receptors and off-target effects on unrelated tyrosine kinases should be considered. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study suggest that dysregulation of FGFR-mediated signalling may affect both testicular and ovarian development, in particular impacting the fetal germ cell populations in both sexes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by an ESPE Research Fellowship, sponsored by Novo Nordisk A/S to A.JØ. Additional funding was obtained from the Erichsen Family Fund (A.JØ.), the Aase and Ejnar Danielsens Fund (A.JØ.), the Danish Government's support for the EDMaRC programme (A.JU.) and a Wellcome Trust Intermediate Clinical Fellowship (R.T.M., Grant no. 098522). The Medical Research Council (MRC) Centre for Reproductive Health (R.T.M.) is supported by an MRC Centre Grant (MR/N022556/1). The authors have no conflict of interest to disclose.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Células Germinativas/efectos de los fármacos , Ovario/embriología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Testículo/embriología , Diferenciación Celular , Linaje de la Célula , Proliferación Celular , Supervivencia Celular , Femenino , Factor 9 de Crecimiento de Fibroblastos/metabolismo , Humanos , Células Intersticiales del Testículo/efectos de los fármacos , Masculino , Embarazo , Primer Trimestre del Embarazo , Pirroles/farmacología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Células de Sertoli/efectos de los fármacos , Transducción de Señal , Proteína Wnt4/metabolismo
6.
J Child Orthop ; 12(2): 173-180, 2018 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-29707057

RESUMEN

PURPOSE: Surgical site infection (SSI) caused by Propionibacterium acnes is an infrequent but devastating complication after spinal fusion. The purpose of this study was to identify risk factors for SSI with Propionibacterium acnes after spinal fusion for juvenile and adolescent idiopathic scoliosis (JIS and AIS). METHODS: A case-control study was performed. Each case was matched 2:1 for age, gender and diagnosis. Retrospective chart review was performed to obtain relevant demographic, surgical and clinical data for all cases and controls. Statistical analysis included paired t-test and McNemar test, as well as exact logistic regression and robust regression models. RESULTS: This study included ten infection cases (eight AIS, two JIS) and 20 controls (16 AIS, four JIS). In total, six infected cases presented within two weeks of the index procedure (acute infection) and four infected cases presented more than one year from the index procedure (delayed infection). The most common presentation for acute infections was wound drainage, while back pain was more common in delayed infections. All infections were successfully treated with surgical irrigation and debridement and postoperative antibiotics. Hardware was removed for patients with delayed infections. The strongest risk factor for infection was increased requirement for blood transfusion, but it did not reach statistical significance. CONCLUSION: SSI with Propionibacterium acnes is an important complication after spinal fusion for idiopathic scoliosis. These infections can be successfully treated, but larger studies are needed to further identify risk factors and establish standardized guidelines for the treatment and prevention of this complication.

7.
Ultrasound Obstet Gynecol ; 52(1): 91-96, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29155474

RESUMEN

OBJECTIVE: To assess the obstetric and psychological effects of visual biofeedback by transperineal ultrasound (TPU) during the second stage of labor. METHODS: This was a prospective, single-center observational study of low-risk nulliparous women with epidural analgesia undergoing vaginal delivery. Visual biofeedback using TPU was provided to 26 women during the second stage of labor. Pushing efficacy was assessed by the change in the angle of progression (AoP) at rest and during pushing efforts, before and after biofeedback. Obstetric outcomes included incidence of perineal tearing, mode of delivery and length of second stage of labor. Psychological outcomes were assessed by self-reported measures obtained during the postnatal hospital stay and included measures of perceived control and maternal satisfaction with childbirth, as well as level of maternal feelings of connectedness with the newborn. Obstetric and psychological results were compared with those of a control group of 69 women who received standard obstetric coaching from midwives. RESULTS: Pushing efficacy increased significantly following visual biofeedback by TPU (P = 0.01), as indicated by a significantly lower delta AoP before (mean, 22.2° (95% CI, 13.9-31.7°)) compared with after (mean, 35.2° (95% CI, 25.9-45.3°)) biofeedback. A significant association was found between visual biofeedback and an intact perineum following delivery (P = 0.03). No significant differences were found between the two groups with regard to mode of delivery or length of the second stage. Feelings of maternal connectedness with the newborn were significantly stronger (P = 0.003) in women who received visual biofeedback than in those who did not. However, perceived control during childbirth and maternal satisfaction with childbirth did not differ significantly between the biofeedback and control groups. CONCLUSIONS: This pilot study suggests that biofeedback using TPU may serve as a complementary tool to coached maternal pushing during the second stage of labor, with obstetric as well as psychological benefits. Further studies are required to confirm our findings and define the optimal duration of the intervention. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Asunto(s)
Biorretroalimentación Psicológica , Parto Obstétrico/métodos , Cabeza/diagnóstico por imagen , Segundo Periodo del Trabajo de Parto/fisiología , Perineo/diagnóstico por imagen , Ultrasonografía , Adulto , Femenino , Cabeza/embriología , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Autoinforme , Ultrasonografía/métodos
8.
J Evol Biol ; 30(6): 1185-1194, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28402000

RESUMEN

Selfish genes that bias their own transmission during meiosis can spread rapidly in populations, even if they contribute negatively to the fitness of their host. Driving X chromosomes provide a clear example of this type of selfish propagation. These chromosomes have important evolutionary and ecological consequences, and can be found in a broad range of taxa including plants, mammals and insects. Here, we report a new case of X chromosome drive (X drive) in a widespread woodland fly, Drosophila testacea. We show that males carrying the driving X (SR males) sire 80-100% female offspring and possess a diagnostic X chromosome haplotype that is perfectly associated with the sex ratio distortion phenotype. We find that the majority of sons produced by SR males are sterile and appear to lack a Y chromosome, suggesting that meiotic defects involving the Y chromosome may underlie X drive in this species. Abnormalities in sperm cysts of SR males reflect that some spermatids are failing to develop properly, confirming that drive is acting during gametogenesis. By screening wild-caught flies using progeny sex ratios and a diagnostic marker, we demonstrate that the driving X is present in wild populations at a frequency of ~ 10% and that suppressors of drive are segregating in the same population. The testacea species group appears to be a hot spot for X drive, and D. testacea is a promising model to compare driving X chromosomes in closely related species, some of which may even be younger than the chromosomes themselves.


Asunto(s)
Drosophila/genética , Tecnología de Genética Dirigida , Razón de Masculinidad , Cromosoma X , Cromosoma Y , Animales , Femenino , Bosques , Masculino , Meiosis
9.
Psychol Med ; 47(8): 1357-1369, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27998326

RESUMEN

BACKGROUND: Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth. METHOD: LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables. RESULTS: Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%. CONCLUSIONS: These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.


Asunto(s)
Conducta del Adolescente/fisiología , Síntomas Afectivos/fisiopatología , Corteza Cerebral , Depresión/fisiopatología , Problema de Conducta , Recompensa , Trastornos Relacionados con Sustancias/diagnóstico , Adolescente , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiología , Corteza Cerebral/fisiopatología , Niño , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos Relacionados con Sustancias/diagnóstico por imagen , Trastornos Relacionados con Sustancias/patología , Trastornos Relacionados con Sustancias/fisiopatología
10.
Qual Life Res ; 25(10): 2441-2455, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27522213

RESUMEN

PURPOSE: Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content. METHODS: New item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD. RESULTS: Moderate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between Neuro-QoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose. CONCLUSIONS: HDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.


Asunto(s)
Enfermedad de Huntington/psicología , Perfil de Impacto de Enfermedad , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
11.
Insect Mol Biol ; 25(5): 604-16, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27286234

RESUMEN

One of the most striking host range transitions is the evolution of plant parasitism from animal parasitism. Parasitoid wasps that have secondarily evolved to attack plants (ie gall wasps and seed-feeders) demonstrate intimate associations with their hosts, yet the mechanism of plant-host manipulation is currently not known. There is, however, emerging evidence suggesting that ovipositional secretions play a role in plant manipulation. To investigate whether parasites have modified pre-existing adaptations to facilitate dramatic host shifts we aimed to characterize the expression of venom proteins in a plant parasite using a collection of parasitoid venom sequences as a guide. The transcriptome of a seed-feeding wasp, Megastigmus spermotrophus, was assembled de novo and three putative venoms were found to be highly expressed in adult females. One of these putative venoms, aspartylglucosaminidase, has been previously identified as a major venom component in two distantly related parasitoid wasps (Asobara tabida and Leptopilina heterotoma) and may have originated via gene duplication within the Hymenoptera. Our study shows that M. spermotrophus, a specialized plant parasite, expresses putative venom transcripts that share homology to venoms identified in Nasonia vitripennis (both superfamily Chalcidoidea), which suggests that M. spermotrophus may have co-opted pre-existing machinery to develop as a plant parasite.


Asunto(s)
Evolución Biológica , Transcriptoma , Venenos de Avispas/genética , Avispas/fisiología , Animales , Perfilación de la Expresión Génica , Especificidad del Huésped , Filogenia , Semillas
12.
AJNR Am J Neuroradiol ; 37(7): 1359-66, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27032974

RESUMEN

BACKGROUND AND PURPOSE: Normal biometry of the fetal posterior fossa rules out most major anomalies of the cerebellum and vermis. Our aim was to provide new reference data of the fetal vermis in 4 biometric parameters by using 3 imaging modalities, 2D ultrasound, 3D ultrasound, and MR imaging, and to assess the relation among these modalities. MATERIALS AND METHODS: A retrospective study was conducted between June 2011 and June 2013. Three different imaging modalities were used to measure vermis biometry: 2D ultrasound, 3D ultrasound, and MR imaging. The vermian parameters evaluated were the maximum superoinferior diameter, maximum anteroposterior diameter, the perimeter, and the surface area. Statistical analysis was performed to calculate centiles for gestational age and to assess the agreement among the 3 imaging modalities. RESULTS: The number of fetuses in the study group was 193, 172, and 151 for 2D ultrasound, 3D ultrasound, and MR imaging, respectively. The mean and median gestational ages were 29.1 weeks, 29.5 weeks (range, 21-35 weeks); 28.2 weeks, 29.05 weeks (range, 21-35 weeks); and 32.1 weeks, 32.6 weeks (range, 27-35 weeks) for 2D ultrasound, 3D ultrasound, and MR imaging, respectively. In all 3 modalities, the biometric measurements of the vermis have shown a linear growth with gestational age. For all 4 biometric parameters, the lowest results were those measured by MR imaging, while the highest results were measured by 3D ultrasound. The inter- and intraobserver agreement was excellent for all measures and all imaging modalities. Limits of agreement were considered acceptable for clinical purposes for all parameters, with excellent or substantial agreement defined by the intraclass correlation coefficient. CONCLUSIONS: Imaging technique-specific reference data should be used for the assessment of the fetal vermis in pregnancy.


Asunto(s)
Vermis Cerebeloso/diagnóstico por imagen , Vermis Cerebeloso/embriología , Neuroimagen/métodos , Biometría/métodos , Femenino , Feto , Edad Gestacional , Humanos , Imagen por Resonancia Magnética/métodos , Embarazo , Valores de Referencia , Estudios Retrospectivos , Ultrasonografía , Ultrasonografía Prenatal/métodos
13.
Mol Psychiatry ; 21(9): 1194-201, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26903272

RESUMEN

Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0 (s.d.=2.0) from three clinical sites. Linear regression using the LASSO (Least Absolute Shrinkage and Selection Operator) method for variable selection was used to predict severity of future behavioral and emotional dysregulation measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)) at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained ~1/3 of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions.


Asunto(s)
Síntomas Afectivos/fisiopatología , Sustancia Blanca/fisiopatología , Adolescente , Síntomas Afectivos/genética , Trastorno Bipolar/diagnóstico , Encéfalo/fisiopatología , Niño , Emociones/fisiología , Femenino , Predicción/métodos , Humanos , Estudios Longitudinales , Masculino , Padres/psicología , Escalas de Valoración Psiquiátrica , Recompensa , Resultado del Tratamiento
14.
Hum Reprod ; 30(10): 2351-63, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26251460

RESUMEN

STUDY QUESTION: What are the effects of experimentally manipulating meiosis signalling by addition of retinoic acid (RA) in cultured human fetal gonads? SUMMARY ANSWER: RA-treatment accelerated meiotic entry in cultured fetal ovary samples, while addition of RA resulted in a dysgenetic gonadal phenotype in fetal testis cultures. WHAT IS KNOWN ALREADY: One of the first manifestations of sex differentiation is the initiation of meiosis in fetal ovaries. In contrast, meiotic entry is actively prevented in the fetal testis at this developmental time-point. It has previously been shown that RA-treatment mediates initiation of meiosis in human fetal ovary ex vivo. STUDY DESIGN, SIZE, DURATION: This was a controlled ex vivo study of human fetal gonads treated with RA in 'hanging-drop' tissue cultures. The applied experimental set-up preserves germ cell-somatic niche interactions and the investigated outcomes included tissue integrity and morphology, cell proliferation and survival and the expression of markers of meiosis and sex differentiation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Tissue from 24 first trimester human fetuses was included in this study, all from elective terminations at gestational week (GW) 7-12. Gonads were cultured for 2 weeks with and without addition of 1 µM RA. Samples were subsequently formalin-fixed and investigated by immunohistochemistry and cell counting. Proteins investigated and quantified included; octamer-binding transcription factor 4 (OCT4), transcription factor AP-2 gamma (AP2γ) (embryonic germ cell markers), SRY (sex determining region Y)-box 9 (SOX9), anti-Müllerian hormone (AMH) (immature Sertoli cell markers), COUP transcription factor 2 (COUP-TFII) (marker of interstitial cells), forkhead box L2 (FOXL2) (granulosa cell marker), H2A histone family, member X (γH2AX) (meiosis marker), doublesex and mab-3 related transcription factor 1 (DMRT1) (meiosis regulator), cleaved poly ADP ribose polymerase (PARP), cleaved Caspase 3 (apoptosis markers) and Ki-67 antigen (Ki-67) (proliferation marker). Also, proliferation was determined using a 5'-bromo-2'-deoxyuridine (BrdU) incorporation assay. MAIN RESULTS AND THE ROLE OF CHANCE: A novel ex vivo 'hanging-drop' culture model for human fetal gonads was successfully established. Continued proliferation of cells without signs of increased apoptosis was observed after 2 weeks of culture. In cultured fetal ovaries treated with RA, an increased number of meiotic germ cells (P < 0.05) and DMRT1-positive oogonia initiating meiosis (P < 0.05) was observed, which is in agreement with a previous study. In fetal testes, RA-treatment resulted in a decreased number of gonocytes (P < 0.05), a reduced percentage of proliferating gonocytes (P < 0.05), altered expression pattern of the somatic cell markers AMH and COUP-TFII, as well as disrupted seminiferous cord structure and testis morphology. LIMITATIONS, REASONS FOR CAUTION: The number of samples included in this study was relatively small due to the limited availability of human fetal tissue. WIDER IMPLICATIONS OF THE FINDINGS: The hanging-drop culture, similarly to other organ culture approaches, allows studies of germ cell-somatic niche interactions and determination of effects after manipulating specific signalling pathways. Our novel finding of disrupted fetal testis development after treatment with RA indicates that abnormal meiosis regulation can potentially cause gonadal dysgenesis. Further studies will elucidate the exact mechanisms and timing of observed effects. STUDY FUNDING/COMPETING INTERESTS: This work was supported in part by an ESPE Research Fellowship, sponsored by Novo Nordisk A/S to A.Jø. Additional funding for this project was obtained from The Research Council of the Capital Region of Denmark (E.R.-D.M.), The Research Fund at Rigshospitalet (A.Ju. and J.E.N.), Familien Erichssens Fund (A.Jø.), Dagmar Marshalls Fund (A.Jø.) and Aase & Ejnar Danielsens Fund (A.Jø.). The authors have no conflicts of interest.


Asunto(s)
Técnicas de Cultivo de Embriones , Meiosis/efectos de los fármacos , Técnicas de Cultivo de Órganos/métodos , Testículo/efectos de los fármacos , Testículo/embriología , Tretinoina/química , Hormona Antimülleriana/metabolismo , Apoptosis , Factor de Transcripción COUP II/metabolismo , Proliferación Celular , Femenino , Feto/patología , Células Germinativas/citología , Células de la Granulosa/citología , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Células Intersticiales del Testículo/metabolismo , Masculino , Oocitos/citología , Oogonios/patología , Ovario/efectos de los fármacos , Ovario/embriología , Fenotipo , Diferenciación Sexual , Transducción de Señal , Testículo/patología , Factores de Transcripción/metabolismo
15.
J Clin Pediatr Dent ; 39(2): 91-3, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25951305
16.
Euro Surveill ; 19(23)2014 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-24957744

RESUMEN

The pseudoparticle virus neutralisation test (ppNT) and a conventional microneutralisation (MN) assay are specific for detecting antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV) when used in seroepidemiological studies in animals. Genetically diverse MERS-CoV appear antigenically similar in MN tests. We confirm that MERS-CoV was circulating in dromedaries in Saudi Arabia in 1993. Preliminary data suggest that feral Australian dromedaries may be free of MERS-CoV but larger confirmatory studies are needed.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Camelus/sangre , Infecciones por Coronavirus/epidemiología , Coronavirus/inmunología , Pruebas de Neutralización/métodos , Infecciones del Sistema Respiratorio/epidemiología , Animales , Australia/epidemiología , Bovinos/sangre , Coronavirus/aislamiento & purificación , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/virología , Humanos , Inmunoglobulina G/sangre , Prevalencia , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/virología , Arabia Saudita/epidemiología , Estudios Seroepidemiológicos
17.
Psychol Med ; 44(12): 2603-15, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24468022

RESUMEN

BACKGROUND: Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging. METHOD: A total of 61 youth (9-17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy. RESULTS: There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n=22) and low and decreasing (LowD; n=39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p<0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's<0.001, corrected). CONCLUSIONS: Patterns of function in lateral prefrontal cortical-amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.


Asunto(s)
Desarrollo del Adolescente/fisiología , Síntomas Afectivos/fisiopatología , Amígdala del Cerebelo/fisiopatología , Síntomas Conductuales/fisiopatología , Corteza Prefrontal/fisiopatología , Adolescente , Niño , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino
18.
AJNR Am J Neuroradiol ; 35(6): 1214-8, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24436347

RESUMEN

BACKGROUND AND PURPOSE: Accurate measurement of the lateral ventricles is of paramount importance in prenatal diagnosis. Possible conflicting classifications caused by their measurement in different sectional planes by sonography and MR imaging are frequently raised. The objective of our study was to evaluate the agreement between ultrasonography and MR imaging in the measurement of the lateral ventricle diameter in the customary sectional planes for each technique. MATERIALS AND METHODS: Measurement of both lateral ventricles was performed prospectively in 162 fetuses from 21 to 40 weeks of gestational age referred for evaluation due to increased risk for cerebral pathology. The mean gestational age for evaluation was 32 weeks. The measurements were performed in the customary plane for each technique: axial plane for sonography and coronal plane for MR imaging. RESULTS: The 2 techniques yielded results in substantial agreement by using intraclass correlation and κ coefficient score tests. When we assessed the clinical cutoff of 10 mm, the κ score was 0.94 for the narrower ventricle and 0.84 for the wider ventricle, expressing almost perfect agreement. The Bland-Altman plot did not show any trend regarding the actual width of the ventricle, gestational week, or interval between tests. Findings were independent for fetal position, sex, and indication for examination. CONCLUSIONS: Our study indicates excellent agreement between fetal brain ultrasonography and MR imaging as to the diagnosis of fetal ventriculomegaly in the customarily used sectional planes of each technique.


Asunto(s)
Ventrículos Cerebrales/diagnóstico por imagen , Ventrículos Cerebrales/patología , Hidrocefalia/diagnóstico , Hidrocefalia/embriología , Imagen por Resonancia Magnética/métodos , Ultrasonografía Prenatal/métodos , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
19.
J Clin Pediatr Dent ; 39(1): 9-11, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25631718

RESUMEN

National studies indicate that an increasing proportion of children are receiving needed oral health care. However, this increase is not uniform throughout all populations of youngsters. Overall national study findings regarding the use of dental services mask the fact that, a significant subset of low-income, minority, medically and developmentally compromised and socially vulnerable children continue to lack access to care and suffer significant and consequential dental and oral disease. In addition, these same children will face continued difficulties in securing needed care as they reach their early adult years.


Asunto(s)
Atención Dental para Niños/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Adolescente , Negro o Afroamericano/estadística & datos numéricos , Asiático/estadística & datos numéricos , Niño , Preescolar , Atención Dental para Enfermos Crónicos/estadística & datos numéricos , Atención Dental para la Persona con Discapacidad/estadística & datos numéricos , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Seguro de Salud/estadística & datos numéricos , Pacientes no Asegurados/estadística & datos numéricos , Grupos Minoritarios/estadística & datos numéricos , Pobreza/estadística & datos numéricos , Transición a la Atención de Adultos , Estados Unidos , Poblaciones Vulnerables/estadística & datos numéricos , Población Blanca/estadística & datos numéricos
20.
J Clin Pediatr Dent ; 37(4): 351-3, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24046980

RESUMEN

US. Census Bureau reports for the 2010 census detail the slowing overall growth of the number of children with specific emphasis on the increasing proportion of Hispanic children in the population. A review of these data is considered in terms of the potential impact on pediatric dental practices.


Asunto(s)
Distribución por Edad , Atención Dental para Niños/estadística & datos numéricos , Hispánicos o Latinos/estadística & datos numéricos , Odontología Pediátrica , Dinámica Poblacional/estadística & datos numéricos , Adolescente , Niño , Preescolar , Humanos , Lactante , Pobreza/estadística & datos numéricos , Estados Unidos , Población Urbana/estadística & datos numéricos , Población Blanca/estadística & datos numéricos
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