Primary Renal Paragangliomas and Renal Neoplasia Associated with Pheochromocytoma/Paraganglioma: Analysis of von Hippel–Lindau ( VHL ), Succinate Dehydrogenase ( SDHX ) and Transmembrane Protein 127 ( TMEM127 )

Abstract

Alterations of von Hippel-Lindau (VHL), succinate dehydrogenase (SDHX), and TMEM127 have been associated with the development of pheochromocytomas (PCs) and paragangliomas (PGLs) and are also associated with the development of renal neoplasms. This study involved 2 primary renal PGL and 12 cases of PC/PGL with associated renal neoplasia with a mean follow up of 74 months. Germline VHL and SDHX mutation status was obtained from the medical record. Immunohistochemistry for SDHB and mutation analysis for TMEM127 was performed, in addition to analysis of The Cancer Genome Atlas datasets for SDHX and TMEM127 mutated renal cell carcinomas (RCCs). The spectrum of renal neoplasia included clear cell and tubulocystic and papillary RCC, as well as a case of multiple papillary adenomas. Three patients had metastatic PC/PGL and three patients had VHL syndrome. Previously unreported TMEM127 alterations were identified in two patients, both without evidence of VHL syndrome or SDH-deficiency, and were classified as variants of uncertain significance. Primary renal PGL and neoplasia was associated with about 2% of 710 cases of PC/PGL. These were diagnosed concurrently or on average 27 months prior to the PC/PGL, and most were low-grade, low-stage clear cell RCCs. Up to half of patients with PC/PGL and renal neoplasia had VHL syndrome, SDH deficiency, or alterations in TMEM127. One (of three) case of metastatic PC/PGL had SDHB mutation and loss of SDHB by immunohistochemistry. The other two cases had retained SDHB expression.

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Observational Learning During Simulation-Based Training in Arthroscopy: Is It Useful to Novices?

Publication date: Available online 23 June 2017
Source:Journal of Surgical Education
Author(s): Marie-Eve LeBel, John Haverstock, Sayra Cristancho, Lucia van Eimeren, Gavin Buckingham
ObjectiveObserving experts constitutes an important and common learning experience for surgical residents before operating under direct guidance. However, studies suggest that exclusively observing experts may induce suboptimal motor learning, and watching errors from non-experts performing simple motor tasks may generate better performance. We investigated whether observational learning is transferrable to arthroscopy learning using virtual reality (VR) simulation.Setting/DesignIn our surgical simulation laboratory, we compared students learning basic skills on a VR arthroscopy simulator after watching an expert video demonstration of VR arthroscopy tasks or a non-expert video demonstration of the same tasks to a Control group without video demonstration. Ninety students in 3 observing groups (expert, non-expert, and Control) subsequently completed the same procedure on a VR arthroscopy simulator. We hypothesized the non-expert-watching group would outperform the expert-watching group, and both groups to outperform the Control group. We examined performance pretest, posttest, and 1 week later.ParticipantsParticipants were recruited from the final year of medical school and the very early first year of surgical residency training programs (orthopaedic surgery, urology, plastic surgery, and general surgery) at Western University (Ontario, Canada).ResultsAll participants improved their overall performance from pretest to retention (p < 0.001). At initial retention testing, non-expert-watching group outperformed the other groups in camera path length p < 0.05 and time to completion, p < 0.05, and both the expert/non-expert groups surpassed the Control group in camera path length (p < 0.05).ConclusionWe suggest that error-observation may contribute to skills improvement in the non-expert-watching group. Allowing novices to observe techniques/errors of other novices may assist internalization of specific movements/skills required for effective motor performances. This study highlights the potential effect of observational learning on surgical skills acquisition and offers preliminary evidence for peer-based practice (combined non-experts and experts) as a complementary surgical motor skills training strategy.



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18F-FDG PET/CT in a cardiac metastasis in a patient with history of malignant neuroectodermal tumour of the chest wall: Case report and review of the literature

Publication date: Available online 23 June 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): J.A. Marroquín, A.C. Hernández, J.P. Pilkington, A. Saviatto, M.J. Tabuenca, J.M. Estenoz
The case presented is a 25-year-old male with a malignant neuroectodermal tumour on the left chest wall (Askin tumour), treated with surgery after neoadyuvant chemotherapy and followed by consolidation chemotherapy. After 9 years of disease free survival, the patient developed an acute pulmonary embolism. The echocardiogram, thoracic CT, and cardiac MRI scans revealed a mass in the right atrium. Recurrence of an Askin tumour versus an atrium myxoma was suspected. ¹⁸F-FDG PET/CT showed an intense hypermetabolic right atrium mass with extension to the right ventricle highly suggestive of malignancy. The result of the histopathology examination after biopsy and subsequently exeresis of the right atrium mass was consistent with a metastasis of the primary tumour.



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A New Algebraic Method for Quantitative Proton Density Mapping using Multi-Channel Coil Data

Publication date: Available online 23 June 2017
Source:Medical Image Analysis
Author(s): Dietmar Cordes, Zhengshi Yang, Xiaowei Zhuang, Karthik Sreenivasan, Virendra Mishra, Le H. Hua
A difficult problem in quantitative MRI is the accurate determination of the proton density, which is an important quantity in measuring brain tissue organization. Recent progress in estimating proton density in vivo has been based on using the inverse linear relationship between the longitudinal relaxation rate T1 and proton density. In this study, the same type of relationship is being used, however, in a more general framework by constructing 3D basis functions to model the receiver bias field. The novelty of this method is that the basis functions developed are suitable to cover an entire range of inverse linearities between T1 and proton density. The method is applied by parcellating the human brain into small cubes with size 30mm x 30mm x30mm. In each cube the optimal set of basis functions is determined to model the receiver coil sensitivities using multi-channel (32 element) coil data. For validation, we use arbitrary data from a numerical phantom where the data satisfy the conventional MR signal equations. Using added noise of different magnitude and realizations, we show that the proton densities obtained have a bias close to zero and also low noise sensitivity. The obtained root-mean-square-error rate is less than 0.2% for the estimated proton density in a realistic 3D simulation. As an application, the method is used in a small cohort of MS patients, and proton density values for specific brain structures are determined.

Graphical abstract

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Identifying major events in two sturgeons’ life using pectoral fin spine ring structure: exploring the use of a non-destructive method

Abstract

Maturation is one of the most important life history traits that influences on many ecological characteristics of animals. This study aimed to describe the indirect distinguish of first reproduction and habitat shift (transition from the pelagic to benthic environment), using the width of translucent and annuluses of the pectoral fin spine of two sturgeon species, Persian sturgeon, Acipenser persicus, and starry sturgeon, Acipenser stellatus. Interpretation of growth bands in pectoral fin sections was done objectively using direct reading of thin sections and image analysis. The results showed that changes in the profiles of translucent and annuluses occurred at the time of habitat shift and first reproduction. Females of both sturgeons move to the deeper waters earlier than males, which can be considered as strategy for the prolonged gonad development of female individuals. Estimated age at maturity for A. persicus (9 years for female and 7 years for male) was higher than A. stellatus (7 years for female and 6 years for male), which coincide with abrupt reduction in annuli width. Marks of habitat shift and first reproduction in the pectoral fin spine are species-specific characters and enable life history traits to be identified.

http://ift.tt/2tY8afM

Long-term follow-up of a child with Klinefelter syndrome and achondroplasia from infancy to 16 years

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Joint association of screen time and physical activity with anthropometric measures in Iranian children and adolescents: the weight disorders survey of the CASPIAN-IV study

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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High prevalence of organ specific autoantibodies in Indian type 1 diabetic patients

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Comparison of Tanner staging of HIV-infected and uninfected girls at the University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu, Nigeria

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Clinical, biochemical and genetic features with nonclassical 21-hydroxylase deficiency and final height

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Assessment of insulin like growth factor-1 and IGF binding protein-3 in healthy Indian girls from Delhi and their correlation with age, pubertal status, obesity and thyroid hormonal status

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Process intensification for high yield production of influenza H1N1 Gag virus-like particles using an inducible HEK-293 stable cell line

Publication date: Available online 22 June 2017
Source:Vaccine
Author(s): Alina Venereo-Sanchez, Melanie Simoneau, Stéphane Lanthier, Parminder Chahal, Lucie Bourget, Sven Ansorge, Rénald Gilbert, Olivier Henry, Amine Kamen
Influenza virus dominant antigens presentation using virus like particle (VLP) approach is attractive for the development of new generation of influenza vaccines. Mammalian cell platform offers many advantages for VLP production. However, limited attention has been paid to the processing of mammalian cell produced VLPs. Better understanding of the production system could contribute to increasing the yields and making large-scale VLP vaccine manufacturing feasible. In a previous study, we have generated a human embryonic kidney HEK-293 inducible cell line expressing Hemagglutinin (HA) and Neuraminidase (NA), which was used to produce VLPs upon transient transfection with a plasmid containing HIV-1 Gag. In this work, to streamline the production process, we have developed a new HEK-293 inducible cell line adapted to suspension growth expressing the three proteins HA, NA (H1N1 A/PR/8/1934) and the Gag fused to GFP for monitoring the VLP production. The process was optimized to reach higher volumetric yield of VLPs by increasing the cell density at the time of induction without sacrificing the cell specific productivity. A 5-fold improvement was achieved by doing media evaluation at small scale. Furthermore, a 3-L perfusion bioreactor mirrored the performance of small-scale shake flask cultures with sequential medium replacement. The cell density was increased to 14×10⁶ cells/ml at the time of induction which augmented by 60-fold the volumetric yield to 1.54×10¹⁰ Gag-GFP fluorescent events/ml, as measured by flow cytometry. The 9.5-L harvest from the perfusion bioreactor was concentrated by tangential flow filtration at low shear rate. The electron micrographs revealed the presence of VLPs of 100–150nm with the characteristic dense core of HIV-1 particles. The developed process shows the feasibility of producing high quantity of influenza VLPs from an inducible mammalian stable cell line aiming at large scale vaccine manufacturing.



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Post-vaccination serologic testing of infants born to hepatitis B surface antigen positive mothers in 4 provinces of China

Publication date: Available online 23 June 2017
Source:Vaccine
Author(s): Fuzhen Wang, Guomin Zhang, Hui Zheng, Ning Miao, Liping Shen, Feng Wang, Pumei Dong, Fei Du, Chao Chen, Xiaoshu Zhang, Fuqiang Cui
ObjectiveTo evaluate prenatal maternal hepatitis B virus (HBV) screening and post-vaccination hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs) status and titers of babies born to HBsAg positive mothers, and to provide evidence for development of standard postvaccination serologic testing (PVST) strategies for babies born to HBsAg positive mothers in China.MethodsIn 2014, we conducted a baseline survey of HBV mother to child transmission (MTCT) interruption strategy implementation and PVST for babies born to HBsAg positive mothers after received 3 doses of hepatitis B vaccine (HepB) in 8 counties in 4 Provinces. Bivariate analysis and multivariable analyses modeled statistically significant predictor variables associated with infant HBsAg, anti-HBs positive, anti-HBs titer.ResultsAmong the 1563 infants born to HBsAg positive mothers, 1025 (65.6%) maternal-infant pairs were enrolled in PVST after receiving 3 doses of HepB. 38 infants tested HBsAg positive for an HBsAg positive rate of 3.7%. Maternal hepatitis B e antigen (HBeAg) status and age of infant were significantly associated with infant HBsAg positivity. A total of 932 infants were anti-HBs positive when tested at 7–24months of age, yielding an anti-HBs positivity rate of 90.9%. Maternal HBeAg status was the factor associated with infant anti-HBs status. Amount of antigen of HepB and infant's age were most associated with anti-HBs titers. PVST performed 1–2months after the 3rd dose of HepB was associated with the highest anti-HBs level and the anti-HBs Geometric Mean Concentration (GMC) decreased as the PVST intervals prolonged.ConclusionsIn China, perinatal HBV transmission is approaching the theoretical minimum possible with the current strategy of HepB coupled with HBIG administration for HBV-exposed newborns. PVST of infants born to an HBsAg positive mother is an essential strategy to ensure full protection for vaccine non-responders and appropriate medical care for those infected.



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HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway

Publication date: Available online 23 June 2017
Source:Vaccine
Author(s): Berit Feiring, Ida Laake, Inger Johanne Bakken, Margrethe Greve-Isdahl, Vegard Bruun Wyller, Siri E. Håberg, Per Magnus, Lill Trogstad
BackgroundVaccination has been suggested to be involved in the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). HPV vaccine was introduced in the Norwegian Childhood Immunisation Programme and offered 12year old girls from 2009. We studied the association between HPV vaccination and risk of CFS/ME and also assessed medical history in relation to both risk of CFS/ME and HPV vaccine uptake.MethodsIndividual data from national registries, including the Norwegian Population Registry, the Norwegian Patient Registry and the Norwegian Immunisation Registry were linked using the unique personal identification number. Yearly incidence rates of CFS/ME for 2009–2014 were calculated among the 824,133 boys and girls, aged 10–17 living in Norway during these 6years. A total of 176,453 girls born 1997–2002 were eligible for HPV vaccination and included in further analyses. Hazard ratios (HRs) of CFS/ME were estimated using Cox regression. Risk differences (RDs) of vaccine uptake were estimated with binomial regression.ResultsA similar yearly increase in incidence rate of CFS/ME was observed among girls and boys, IRR=1.15 (95% confidence interval (CI) 1.10–1.19) and 1.15 (95% CI 1.09–1.22), respectively. HPV vaccination was not associated with CFS/ME, HR=0.86 (95% CI 0.69–1.08) for the entire follow-up period and 0.96 (95% CI 0.64–1.43) for the first two years after vaccination. The risk of CFS/ME increased with increasing number of previous hospital contacts, HR=5.23 (95% CI 3.66–7.49) for 7 or more contacts as compared to no contacts. Girls with 7 or more hospital contacts were less likely to be vaccinated than girls with no previous hospital contacts, RD=−5.5% (95% CI −6.7% to −4.2%).ConclusionsNo indication of increased risk of CFS/ME following HPV vaccination was observed among girls in the first 6 birth cohorts offered HPV vaccine through the national immunisation programme in Norway.



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Risk of intussusception following rotavirus vaccination: An evidence based meta-analysis of cohort and case-control studies

Publication date: Available online 22 June 2017
Source:Vaccine
Author(s): Priya Kassim, Guy D. Eslick
BackgroundInternational post-licensure studies on rotavirus vaccines have identified an increased risk of intussusception in infants after administration. The first developed rotavirus vaccine (Rotashield (RRV-TV)) was suspended post-licensure in 1999 after an association with intussusception was found. The currently available second-generation rotavirus vaccines (Rotateq (RV5) and Rotarix (RV1)), are recommended as a routine vaccine by the World Health Organisation (WHO). Post-licensure studies of these vaccines have shown a smaller but temporal increased risk for developing intussusception.MethodsA meta-analysis was performed to summarise available evidence and to give an overall risk of developing intussusception from case-control and cohort studies for all rotavirus vaccines that have been manufactured up to date. A search was conducted on MEDLINE, PubMed, EMBASE and Google Scholar up to May 2017. Eligible studies assessed the relationship between the rotavirus vaccine administration and subsequent development of intussusception both after receiving the first dose and after receiving all doses combined. Data was extracted on study characteristics, methods and outcomes. Results were pooled using the random-effect model.ResultsSix cohort studies involving 4506265 total first doses and five case-control studies involving a total sample of 9643 children were included in this analysis. The cohort data revealed that there was an associated increased risk of intussusception after the first 7days post first dose of the vaccine (RR:3.71, 95% CI:1.08–12.69) and after receiving all doses of the rotavirus vaccine (RR:3.47, 95% CI:1.23–9.78). Similarly, the case-control data found an increased risk of intussusception following the first dose (OR: 8.45, 95% CI: 4.08–17.50) and following all doses (OR: 1.59, 95% CI: 1.11–2.27).ConclusionsFindings of this meta-analysis suggest that the rotavirus vaccine is associated with an increased risk on the development of intussusception, principally seen after administration of the first dose of vaccine.



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Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza hospitalizations – Latin America, 2013

Publication date: Available online 23 June 2017
Source:Vaccine
Author(s): Nathalie El Omeiri, Eduardo Azziz-Baumgartner, Mark G. Thompson, Wilfrido Clará, Mauricio Cerpa, Rakhee Palekar, Sara Mirza, Alba María Ropero-Álvarez
BackgroundDespite widespread utilization of influenza vaccines, effectiveness (VE) has not been routinely measured in Latin America.MethodsWe used a case test-negative control design to estimate trivalent inactivated influenza VE against laboratory-confirmed influenza among hospitalized children aged 6months-5years and adults aged ≥60years which are age-groups targeted for vaccination. We sought persons with severe acute respiratory infections (SARI), hospitalized at 71 sentinel hospitals in Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Honduras, Panama, and Paraguay during January–December 2013. Cases had an influenza virus infection confirmed by real-time reverse transcription PCR (rRT-PCR); controls had a negative rRT-PCR result for influenza viruses. We used a two-stage random effects model to estimate pooled VE per target age-group, adjusting for the month of illness onset, age and preexisting medical conditions.ResultsWe identified 2620 SARI patients across sites: 246 influenza cases and 720 influenza-negative controls aged ≤5years and 448 cases and 1206 controls aged ≥60years. The most commonly identified subtype among participants (48%) was the influenza A(H1N1)pdm09 virus followed by influenza A(H3N2) (34%) and influenza B (18%) viruses. Among children, the adjusted VE of full vaccination (one dose for previously vaccinated or two if vaccine naïve) against any influenza virus SARI was 47% (95% confidence interval [CI]: 14–71%); VE was 58% (95% CI: 16–79%) against influenza A(H1N1)pdm09, and 65% (95% CI: −9; 89%) against influenza A(H3N2) viruses associated SARI. Crude VE of full vaccination against influenza B viruses associated SARI among children was 3% (95% CI: −150; 63). Among adults aged ≥60years, adjusted VE against any influenza SARI was 48% (95% CI: 34–60%); VE was 54% (95% CI: 37–69%) against influenza A(H1N1)pdm09, 43% (95% CI: 18–61%) against influenza A(H3N2) and 34% (95% CI: −4; 58%) against B viruses associated SARI.ConclusionInfluenza vaccine provided moderate protection against severe influenza illness among fully vaccinated young children and older adults, supporting current vaccination strategies.



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Italy's response to vaccine hesitancy: An innovative and cost effective National Immunization Plan based on scientific evidence

Publication date: Available online 23 June 2017
Source:Vaccine
Author(s): C. Signorelli, R. Guerra, R. Siliquini, W. Ricciardi




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Progress and challenges in measles and rubella elimination in the WHO European Region

Publication date: Available online 23 June 2017
Source:Vaccine
Author(s): Siddhartha Sankar Datta, Patrick Michael O'Connor, Dragan Jankovic, Mark Muscat, Myriam Corrine Ben Mamou, Simarjit Singh, Theodoros Kaloumenos, Susan Reef, Mark Papania, Robb Butler
IntroductionDespite availability of safe and cost-effective vaccines to prevent it, measles remains one of the significant causes of death among children under five years of age globally. The World Health Organization (WHO) European Region has seen a drastic decline in measles and rubella cases in recent years, and a few of the once common measles genotypes are no longer detected. Buoyed by this success, all Member States of the Region reconfirmed their commitment in 2010 to eliminating measles and rubella, and made this a central objective of the European Vaccine Action Plan 2015–2020 (EVAP). Nevertheless, sporadic outbreaks continue, recently affecting primarily adolescents and young adults with no vaccination or an incomplete vaccination history. The European Regional Verification Commission for Measles and Rubella Elimination was established in 2011 to evaluate the status of measles and rubella elimination based on documentation submitted annually by each country's national verification committee.DiscussionEach country's commitment to eliminate measles and rubella is influenced by competing health priorities, and in some cases lack of capacity and resources. All countries need to improve case-base surveillance for both measles and rubella, ensure documentation of each outbreak and strengthen the link between epidemiology and laboratory data. Achieving high coverage with measles- and rubella-containing vaccines will require a multisectoral approach to address the root causes of lower uptake in identified communities including service delivery challenges or vaccine safety concerns caused by circulating myths about vaccination.ConclusionsThe WHO European Region has made steady progress towards eliminating measles and rubella and over half of the countries interrupted endemic transmission of both diseases by 2015. The programmatic challenges in disease surveillance, vaccination service delivery and communication in the remaining endemic countries should be addressed through periodic evaluation of the strategies by all stakeholders and exploring additional opportunities to accelerate the ongoing elimination activities.



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Application of the revised WHO causality assessment protocol for adverse events following immunization in India

Publication date: Available online 22 June 2017
Source:Vaccine
Author(s): Awnish Kumar Singh, Abram L. Wagner, Jyoti Joshi, Bradley F. Carlson, Satinder Aneja, Matthew L. Boulton
BackgroundIn 2013, the World Health Organization (WHO) and CIOMS introduced a revised Causality Assessment Protocol (CAP) for Adverse Events following Immunization (AEFI). India is one of the first countries to adopt the revised CAP. This study describes the application of the revised CAP in India.MethodsWe describe use of CAP by India's AEFI surveillance program to assess reported AEFIs. Using publicly available results of causality assessment for reported AEFIs, we describe the results by demographic characteristics and review the trends for the results of the causality assessment.ResultsA total of 771 reports of AEFI between January 2012 and January 2015, completed causality review by August 2016. The cases were reported as belonging to a cluster (54%; n=302), hospitalized or requiring hospitalization (41%; n=270), death (25%; n=195), or resulting in disability (0.4%; n=3). The most common combinations of vaccines leading to report of an AEFI were DTwP, Hepatitis B, and OPV (14%; n=106), followed by Pentavalent and OPV (13%; n=103), and JE vaccine (13%; n=101). Using the WHO Algorithm, most AEFI reports (89%, n=683) were classifiable. Classifiable AEFI reports included those with a consistent causal association (53%; n=407), an inconsistent causal association (29%; n=226) or were indeterminate causal association with implicated vaccine(s) or vaccination process (6.5%; n=50) (Fig. 1); 88 reports remained unclassifiable.ConclusionsThe revised CAP was informative and useful in classifying most of the reviewed AEFIs in India. Unclassifiable reports could be minimized with more complete information from health records. Improvements in causality assessment, and standardization in reporting between countries, can improve public confidence in vaccine system performance and identify important vaccine safety signals.



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Brain state-dependent recruitment of high-frequency oscillations in the human hippocampus

Publication date: Available online 23 June 2017
Source:Cortex
Author(s): P. Billeke, T. Ossandon, M. Stockle, M. Perrone-Bertolotti, P. Kahane, J.P. Lachaux, P. Fuentealba
Ripples are high-frequency bouts of coordinated hippocampal activity believed to be crucial for information transfer and memory formation. We used intracortical macroelectrodes to record neural activity in the human hippocampus of awake subjects undergoing surgical treatment for refractory epilepsy and distinguished two populations of ripple episodes based on their frequency spectrum. The phase-coupling of one population, slow ripples (90-110 Hz), to cortical delta oscillations was differentially modulated by cognitive task; whereas the second population, fast ripples (130-170 Hz), was not seemingly correlated to local neural activity. Furthermore, as cognitive tasks changed, the ongoing coordination of neural activity associated to slow ripples progressively augmented along the parahippocampal axis. Thus, during resting states, slow ripples were coordinated in restricted hippocampal territories; whereas during active states, such as attentionally-demanding tasks, high frequency activity emerged across the hippocampus and parahippocampal cortex, that was synchronized with slow ripples, consistent with ripples supporting information transfer and coupling anatomically distant regions. Hence, our results provide further evidence of neural diversity in hippocampal high-frequency oscillations and their association to cognitive processing in humans.



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