McCune Albright Syndrome: A Diagnosis to be Kept in Mind

Precocious puberty, defined as the development of secondary sexual characteristics before the age of 8, often leads to anxiety in patients and their families but also in clinicians searching for the final diagnosis. After adequate investigation, the majority of the cases in girls turn out to be idiopathic. The authors present a case of McCune Albright syndrome in order to call attention to a rare cause of sexual precocity and the value of ultrasound in the evaluation of these situations. 10 years old infant girl admitted in our department due to irregular menstrual bleeding. She experienced a vaginal bleeding by the age of 3 which led to the diagnosis of McCune Albright Syndrome after a complete evaluation. Pubertal assessment revealed a reversed sequence in the remaining events with adrenarche at 5 and thelarche at 8. Hormonal evaluation demonstrated low FSH and LH levels (11,2 and 6,72 respectively) with high estrogen (204). Pelvic ultrasound showed a normal sized uterus (73x 29x32 mm), endometrial thickness of 5 mm and ovaries with several microfollicles and a copus luteum measuring 23 mm in the right ovary. McCune Albright syndrome is a very uncommon cause of sexual precocity that should, however, be suspected in all infant girls who present with vaginal bleeding. It is characterized by a triad: polyostotic fibrous dysplasia, gonadotropin-independent precocious puberty and café-au-lait skin spots. Due to autonomous production of estrogen by the ovaries, ultrasound image of the female reproductive tract is inconsistent with chronologic age. Pelvic ultrasound demonstrates a normal sized uterus with a well defined cervix and clearly identified ovaries with several follicles, similar to adult women of reproductive age. Ultrasonography of the pelvis has also an important role excluding other causes of GnRH-independent precocious puberty conditions like ovarian cysts or tumors

Different levels of cardiometabolic indicators in multiple vs. singleton children

Background We aimed to compare cardiometabolic indicators in singletons and multiples at age 7 and explore the birthweight mediation effect. Methods We studied 5431 singletons and 103 sets of multiples from Generation XXI birth cohort. Anthropometric measurements, body composition, and fasting blood samples were obtained. Age- and sex-specific z-scores were calculated (additionally height-specific for blood pressure). Adjusted regression coefficients and respective 95% confidence intervals [β (95%CI)] were computed using path analysis. Results Multiples had lower weight [− 0.419 (− 0.616;-0.223)], height [− 0.404 (− 0.594;-0.213)], BMI [− 0.470 (− 0.705;-0.234)], fat mass index [− 0.359 (− 0.565;-0.152)], waist circumference [− 0.342 (− 0.537;-0.147)], and waist-to-height ratio [− 0.165 (− 0.326;-0.003)] z-scores. These results were explained by the indirect effect via birthweight, which was also negative and significant for all the aforementioned cardiometabolic indicators, while no direct effect was present. There were also significant indirect effects regarding fat-free mass index, glucose, insulin, and blood pressure, though the total effects were not significant, due to the balance between direct and indirect effects. The only significant direct effect was regarding diastolic blood pressure [− 0.165 (− 0.302;-0.028)]. Conclusions At age 7, multiples presented better cardiometabolic indicators explained by lower weight at birth, except for the lower blood pressure which was independent of an effect via birthweight.Generation XXI was funded by Programa Operacional de Saúde – Saúde XXI, Quadro Comunitário de Apoio III and Administração Regional de Saúde Norte (Regional Department of Ministry of Health); FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) (POCI-01- 0145-FEDER-016837), under the project “PathMOB: Risco cardiometabólico na infância: desde o início da vida ao fim da infância” (Ref. FCT PTDC/DTP-EPI/3306/2014), the Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013), and ACS holds a FCT Investigator contract IF/01060/2015; and by the project DOCnet (NORTE-01-0145-FEDER-000003), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by European Commission [project reference FP7-ENV-2013-603946]

A hybrid analytical-numerical method for solving advection-dispersion problems on a half-line

This paper employs the unified transform, also known as the Fokas method, to solve the advection-dispersion equation on the half-line. This method combines complex analysis with numerics. Compared to classical approaches used to solve linear partial differential equations (PDEs), the unified transform avoids the solution of ordinary differential equations and, more importantly, constructs an integral representation of the solution in the complex plane which is uniformly convergent at the boundaries. As a consequence, such solutions are well suited for numerical computations. Indeed, the numerical evaluation of the solution requires only the computation of a single contour integral involving an integrand which decays exponentially fast for large values of the integration variable. A novel contribution of this paper, with respect to the solution of linear evolution PDEs in general, and the implementation of the unified transform in particular, is the following: using the advection-dispersion equation as a generic example, it is shown that if the transforms of the given data can be computed analytically, then the unified transform yields a fast and accurate method that converges exponentially with the number of evaluations N yet only has complexity O(N). Furthermore, if the transforms are computed numerically using M evaluations, the unified transform gives rise to a method with complexity O(NM). Results are successfully compared to other existing solutions.F.P.J. de B. acknowledges the support from the National Science Foundation Grant No. EAR-1654009. M.J.C. is supported by EPSRC Grant No. EP/L016516/1. A.S.F. is supported by EPSRC, UK, via the senior fellowship

Prevalence and duration of breast milk feeding in very preterm infants: A 3-year follow-up study and a systematic literature review

Background: The World Health Organization recommends exclusive breast milk feeding until 6 months and continuing up to 2 years of age; little is known about whether very preterm infants are fed in accordance with these recommendations. We aimed to describe the prevalence and duration of breast milk feeding in very preterm children and to systematically review internationally published data. Methods: We evaluated breast milk feeding initiation and duration in very preterm children born in 2 Portuguese regions (2011‐2012) enrolled in the EPICE cohort and followed‐up to the age of 3 (n = 466). We searched PubMed® from inception to January 2017 to identify original studies reporting the prevalence and/or duration of breast milk feeding in very preterm children. Results: 91.0% of children received some breast milk feeding and 65.3% were exclusively breast fed with a median duration of 2 months for exclusive and 3 months for any breast milk; only 9.9% received exclusive breast milk for at least 6 months, 10.2% received any breast milk for 12 months or more, and 2.0% for up to 24 months. The literature review identified few studies on feeding after hospital discharge (n = 9); these also reported a low prevalence of exclusive breast milk feeding at 6 months (1.0% to 27.0%) and of any breast milk at 12 months (8.0% to 12.0%). Conclusions: The duration of breast milk feeding among Portuguese very preterm infants was shorter than recommended. However, this appears to be common globally. Research is needed to inform strategies to promote continued breast milk feeding.This study was funded by the European Union Seventh Framework Programme (FP7/2007‐2013) under grant agreement no. 259882. This study was also funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education), under the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI‐01‐0145‐FEDER‐006862; Ref.UID/DTP/04750/2013); the PhD Grant SFRH/BD/111794/2015 (Carina Rodrigues) and the individual grant SFRH/BSAB/113778/2015 (Henrique Barros), co‐funded by the FCT and the POCH/FSE Program

Effect of maternal country of birth on breastfeeding practices: results from Portuguese GXXI birth cohort

Background: Maternal country of birth has been associated with perinatal health outcomes but less is known regarding breastfeeding practices in contemporary European settings. This study investigated effect of maternal country of birth on breastfeeding initiation and duration by comparing native Portuguese and migrant mothers. Methods: We analyzed data of 7065 children of the Generation XXI (GXXI) birth cohort recruited at birth (2005-06) and followed-up 4 years later. Logistic regression was used to assess the effect of maternal country of birth on breastfeeding initiation. Kaplan-Meier estimate was used to compare breastfeeding duration by maternal country of birth and length of residence by migrant mothers in Portugal. Results: Breastfeeding initiation and the type of breastfeeding practice were similar for native Portuguese and migrant mothers. The migrants had significantly higher median duration in months of any breastfeeding (Odds Ratio [OR] 6.0, 95% Confidence Interval [CI] 5.4,6.6) and exclusive breastfeeding (OR 4.0, 95% CI 3.8,4.2) than native Portuguese mothers (OR 4.0, 95% CI 3.8,4.2 and OR 3.0, 95% CI 2.9,3.0). Migrant mothers who resided in Portugal for either 5 years (OR 6.0, 95% CI 5.5,6.5 and OR 4.0, 95% CI 3.7,4.3) years had similar duration of any breastfeeding or exclusive breastfeeding, in both cases higher than the native Portuguese mothers. No significant differences were found when world regions were compared. Conclusions: Maternal country of birth does not influence breastfeeding initiation and type of feeding practice. However, migrant mothers have longer breastfeeding duration of either exclusive or any breastfeeding, which was not changed by length of residence in Portugal.GXXI was funded by Programa Operacional de Saude-Saude XXI, Quadro Comunitario de Apoio III and Administracao Regional de Saude Norte (Regional Department of Ministry of Health). It has support from Calouste Gulbenkian Foundation and Portuguese Foundation for Science and Technology. Precisely, EPIUnit-Instituto de Saude Publica da Universidade do Porto (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013); PhD Grant SFRH/BD/111794/2015 (Carina Rodrigues) as well as the individual grants IF/01060/2015 (Ana Cristina Santos) and SFRH/BSAB/113778/2015 (Henrique Barros), co-funded by the FCT and the POCH/FSE Program

Newborn weight change and childhood cardio-metabolic traits - a prospective cohort study

Background: Newborn weight change (NWC) in the first 4 days represents short-term adaptations to external environment. It may be a key developmental period for future cardio-metabolic health, but this has not been explored. We aimed to determine the associations of NWC with childhood cardio-metabolic traits. Methods: As part of Generation XXI birth cohort, children were recruited in 2005/2006 at all public units providing obstetrical and neonatal care in Porto. Birthweight was abstracted from clinical records and postnatal anthropometry was obtained by trained examiners during hospital stay. NWC was calculated as ((minimum weight - birthweight)/birthweight) x 100. At age 4 and 7, children were measured and had a fasting blood sample collected. Fasting glucose, LDL-cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressure were evaluated. This study included 312 children with detailed information on growth in very early life and subsequent cardio-metabolic measures. Path analysis was used to compute adjusted regression coefficients and 95% confidence intervals. Results: NWC was not associated with any cardio-metabolic traits at ages 4 or 7. Strong associations were observed between each cardio-metabolic trait at 4 with the same trait at 7 years. The strongest associations were found for waist circumference [0.725 (0.657; 0.793)] and LDL-cholesterol [0.655 (0.575; 0.735)]. Conclusions: No evidence that NWC is related to childhood cardio-metabolic traits was found, suggesting that NWC should be faced in clinical practice as a short-term phenomenon, with no medium/long term consequences, at least in cardio-metabolic health. Our results show strong tracking correlations in cardio-metabolic traits during childhood.This work was supported by Programa Operacional de Saude - Saude XXI, Quadro Comunitario de Apoio III and Administracao Regional de Saude Norte (Regional Department of Ministry of Health); FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology - FCT (Portuguese Ministry of Science, Technology and Higher Education) [POCI-01-0145-FEDER-016837], under the project PathMOB.: Risco cardiometabolico na infancia: desde o inicio da vida ao fim da infancia [Ref. FCT PTDC/DTP-EPI/3306/2014], and FCT Investigator contract [IF/01060/2015] - ACS; Unidade de Investigacao em Epidemiologia - Instituto de Saude Publica da Universidade do Porto (EPIUnit) [POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013]; Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) - DOCnet (NORTE-01-0145-FEDER-000003); UK Medical Research Council [MC_UU_12013/5] and UK National Institute of Health Research Senior Investigator [NF-SI-0611-10196] - DAL

Using nitrogen concentration and isotopic composition in lichens to spatially assess the relative contribution of atmospheric nitrogen sources in complex landscapes

Reactive nitrogen (Nr) is an important driver of global change, causing alterations in ecosystem biodiversity and functionality. Environmental assessments require monitoring the emission and deposition of both the amount and types of Nr. This is especially important in heterogeneous landscapes, as different land-cover types emit particular forms of Nr to the atmosphere, which can impact ecosystems distinctively. Such assessments require high spatial resolution maps that also integrate temporal variations, and can only be feasibly achieved by using ecological indicators. Our aim was to rank land-cover types according to the amount and form of emitted atmospheric Nr in a complex landscape with multiple sources of N. To do so, we measured and mapped nitrogen concentration and isotopic composition in lichen thalli, which we then related to land-cover data. Results suggested that, at the landscape scale, intensive agriculture and urban areas were the most important sources of Nr to the atmosphere. Additionally, the ocean greatly influences Nr in land, by providing air with low Nr concentration and a unique isotopic composition. These results have important consequences for managing air pollution at the regional level, as they provide critical information for modeling Nr emission and deposition across regional as well as continental scales.Supported by project GISA (funded by private companies: GALP, Repsol, APS, AdSA, AICEP, CARBOGAL, EDP, EuroResinas, KIMAXTRA, REN and GENERG; and managed by local authorities: CCDRA, ARSA and Municipalities of Sines, Santiago do Cacém, Grândola, Álcacer do Sal and Odemira. Further support for researchers from FCT-MCTES (SFRH/BPD/75425/2010, SFRH/BPD/109382/2015 and Investigador FCT contract) and EC-H2020 (NitroPortugal 692331)

A mechanistic perspective on pex1 and pex6, two aaa+ proteins of the peroxisomal protein import machinery

In contrast to many protein translocases that use ATP or GTP hydrolysis as the driving force to transport proteins across biological membranes, the peroxisomal matrix protein import machinery relies on a regulated self-assembly mechanism for this purpose and uses ATP hydrolysis only to reset its components. The ATP-dependent protein complex in charge of resetting this machinery—the Receptor Export Module (REM)—comprises two members of the “ATPases Associated with diverse cellular Activities” (AAA+) family, PEX1 and PEX6, and a membrane protein that anchors the ATPases to the organelle membrane. In recent years, a large amount of data on the structure/function of the REM complex has become available. Here, we discuss the main findings and their mechanistic implications.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/BEX-BCM/2311/2014 (POCI-01-0145-FEDER-016613) and the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). This work is a result of the project NORTE-01-0145-FEDER-000008—Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). A.B.-B., A.G.P., M.J.F., T.F. and T.A.R. are supported by Fundação para a Ciência e Tecnologia, Programa Operacional Potencial Humano do QREN, and Fundo Social Europeu

Maternal smoking: a life course blood pressure determinant?

Introduction: Exposure to maternal smoking early in life may affect blood pressure (BP) control mechanisms. We examined the association between maternal smoking (before conception, during pregnancy, and 4 years after delivery) and BP in preschool children. Methods: We evaluated 4295 of Generation XXI children, recruited at birth in 2005–2006 and reevaluated at the age of 4. At birth, information was collected by face-to-face interview and additionally abstracted from clinical records. At 4-year follow-up, interviews were performed and children’s BP measured. Linear regression models were fitted to estimate the association between maternal smoking and children’s BP. Results: Children of smoking mothers presented significantly higher BP levels. After adjustment for maternal education, gestational hypertensive disorders, and child’s body mass index, children exposed during pregnancy to maternal smoking presented a higher systolic BP (SBP) z-score (β = 0.08, 95% confidence interval [CI] 0.04 to 0.14). In crude models, maternal smoking was associated with higher SBP z-score at every assessed period. However, after adjustment, an attenuation of the association estimates occurred (β = 0.08, 95% CI 0.03 to 0.13 before conception; β = 0.07, 95%CI 0.02 to 0.12; β = 0.04, 95%CI −0.02 to 0.10; and β = 0.06, 95%CI 0.00 to 0.13 for the first, second, and third pregnancy trimesters, respectively; and β = 0.07, 95%CI 0.02 to 0.12 for current maternal smoking). No significant association was observed for diastolic BP z-score levels. Conclusion: Maternal smoking before, during, and after pregnancy was independently associated with systolic BP z-score in preschool children. This study provides additional evidence to the public health relevance of maternal smoking cessation programs if early cardiovascular health of children is envisaged. Implications: Using observational longitudinal data from the birth cohort Generation XXI, this study showed that exposure to maternal smoking—before pregnancy, during pregnancy, and 4 years after delivery—was associated with a systolic BP-raising effect in children at the age of 4. The findings of this study add an important insight into the need to support maternal smoke-free environments in order to provide long-term cardiovascular benefit, starting as early as possible in life.Generation XXI has been funded by the Operational Health Programme XXI Health, Community support framework III (co-funded by Feder), Administração Regional de Saúde do Norte, Fundação Calouste Gulbenkian and Fundação para a Ciência e Tecnologia (SFRH/BSAB/113778/2015; PD/BD/105824/2014; PD/BD/105827/2014; F-COMP-01-0124-FEDER-011008; FCT—PTDC/SAU-ESA/105033/2008). Also, the Portuguese Foundation for Science and Technology funds the Epidemiology Research Unit of the Institute of Public Health of the University of Porto (UID/DTP/04750/2013). This article is a result of the project DOCnet (NORTE-01-0145-FEDER-000003), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)