Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause

BACKGROUND: The association that exists between livedo reticularis (LR) and stroke is known as Sneddon's syndrome (SnS). The disorder is classified as primary SnS (PSnS), if the cause remains unknown and secondary SnS. The condition is rare and it occurs mainly sporadically. In 2014, 2 independent teams described a new genetic disorder with childhood-onset, which was called deficiency of adenosine deaminase 2 (DADA2), characterized by recurrent fevers and vascular pathologic features that included LR and stroke. All the patients carried recessively inherited mutations in cat eye syndrome chromosome region candidate 1 gene (CECR1), encoding the adenosine deaminase 2 (ADA2) protein. Genetic testing is the standard for the diagnosis of DADA2. However, the diagnostic accuracy of more affordable laboratorial analysis in CECR1-mutated individuals remains to be established. We aim to determine whether plasma ADA2 activity and serum immunoglobulin M (IgM) levels can distinguish (1) DADA2 from other adult patients within the SnS spectrum, and (2) healthy CECR1 heterozygous (HHZ) from healthy controls (HC). METHODS: ADA2 activity in plasma and serum IgM concentrations was measured in adult patients within the SnS spectrum, healthy first-degree relatives and HC. Genetic results were used as the reference standard. The primary outcome measures were sensitivity and specificity derived from receiver operating curve analysis. RESULTS: A total of 73 participants were included in the study: 26 patients with PSnS with no CECR1 mutation (PSnS), 6 bi-allelic (DADA2 patients) and 7 HHZ CECR1 mutations and 34 HC. Plasma ADA2 activity and serum IgM levels were significantly lower in DADA2 patients than in PSnS. With the use of the best indexes, plasma ADA2 activity differentiated PSnS from DADA2 with a sensitivity and specificity of 100.0% and HHZ from HC with a sensitivity of 97.1% and specificity of 85.7%. Serum IgM levels also differentiated PSnS from DADA2 with a sensitivity of 85.2% and specificity of 83.3%. CONCLUSION: Serum IgM levels might be used as a triage tool and plasma ADA2 activity performs perfectly as a diagnostic test for DADA2 in adult patients within the SnS spectrum. ADA2 activity in plasma also reliably distinguishes HHZ from HC.info:eu-repo/semantics/publishedVersio

Loss of 5'-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness.

The 5'-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients' clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients' clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP's role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas

Phenomenological Consequences of sub-leading Terms in See-Saw Formulas

Several aspects of next-to-leading (NLO) order corrections to see-saw formulas are discussed and phenomenologically relevant situations are identified. We generalize the formalism to calculate the NLO terms developed for the type I see-saw to variants like the inverse, double or linear see-saw, i.e., to cases in which more than two mass scales are present. In the standard type I case with very heavy fermion singlets the sub-leading terms are negligible. However, effects in the percent regime are possible when sub-matrices of the complete neutral fermion mass matrix obey a moderate hierarchy, e.g. weak scale and TeV scale. Examples are cancellations of large terms leading to small neutrino masses, or inverse see-saw scenarios. We furthermore identify situations in which no NLO corrections to certain observables arise, namely for mu-tau symmetry and cases with a vanishing neutrino mass. Finally, we emphasize that the unavoidable unitarity violation in see-saw scenarios with extra fermions can be calculated with the formalism in a straightforward manner.Comment: 22 pages, matches published versio

Phenomenology of event shapes at hadron colliders

We present results for matched distributions of a range of dijet event shapes at hadron colliders, combining next-to-leading logarithmic (NLL) accuracy in the resummation exponent, next-to-next-to leading logarithmic (NNLL) accuracy in its expansion and next-to-leading order (NLO) accuracy in a pure alpha_s expansion. This is the first time that such a matching has been carried out for hadronic final-state observables at hadron colliders. We compare our results to Monte Carlo predictions, with and without matching to multi-parton tree-level fixed-order calculations. These studies suggest that hadron-collider event shapes have significant scope for constraining both perturbative and non-perturbative aspects of hadron-collider QCD. The differences between various calculational methods also highlight the limits of relying on simultaneous variations of renormalisation and factorisation scale in making reliable estimates of uncertainties in QCD predictions. We also discuss the sensitivity of event shapes to the topology of multi-jet events, which are expected to appear in many New Physics scenarios.Comment: 70 pages, 25 figures, additional material available from http://www.lpthe.jussieu.fr/~salam/pp-event-shapes

Testing and comparing two self-care-related instruments among older Chinese adults

Objectives The study aimed to test and compare the reliability and validity, including sensitivity and specificity of the two self-care-related instruments, the Self-care Ability Scale for the Elderly (SASE), and the Appraisal of Self-care Agency Scale-Revised (ASAS-R), among older adults in the Chinese context. Methods A cross-sectional design was used to conduct this study. The sample consisted of 1152 older adults. Data were collected by a questionnaire including the Chinese version of SASE (SASE-CHI), the Chinese version of ASAS-R (ASAS-R-CHI) and the Exercise of Self-Care Agency scale (ESCA). Homogeneity and stability, content, construct and concurrent validity, and sensitivity and specificity were assessed. Results The Cronbach's alpha (α) of SASE-CHI was 0.89, the item-to-total correlations ranged from r = 0.15 to r = 0.81, and the test-retest correlation coefficient (intra-class correlation coefficient, ICC) was 0.99 (95% CI, 0.99±1.00; P<0.001). The Cronbach's α of ASAS-R-CHI was 0.78, the item-to-total correlations ranged from r = 0.20 to r = 0.65, and the test-retest ICC was 0.95 (95% CI, 0.92±0.96; P<0.001). The content validity index (CVI) of SASE-CHI and ASAS-R-CHI was 0.96 and 0.97, respectively. The findings of exploratory and confirmatory factor analyses (EFA and CFA) confirmed a good construct validity of SASE-CHI and ASAS-R-CHI. The Pearson's rank correlation coefficients, as a measure of concurrent validity, between total score of SASE-CHI and ESCA and ASAS-R-CHI and ESCA were assessed to 0.65 (P<0.001) and 0.62 (P<0.001), respectively. Regarding ESCA as the criterion, the area under the receiver operator characteristic (ROC) curve for the cut-point of SASE-CHI and ASAS-R-CHI were 0.93 (95% CI, 0.91±0.94) and 0.83 (95% CI, 0.80±0.86), respectively. Conclusion There is no significant difference between the two instruments. Each has its own characteristics, but SASE-CHI is more suitable for older adults. The key point is that the users can choose the most appropriate scale according to the specific situation.publishedVersionNivå

Pamidronic acid and cabergoline as effective long-term therapy in a 12-year-old girl with extended facial polyostotic fibrous dysplasia, prolactinoma and acromegaly in McCune-Albright syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>McCune-Albright syndrome is a complex inborn disorder due to early embryonal postzygotic somatic activating mutations in the <it>GNAS</it>1 gene. The phenotype is very heterogeneous and includes polyostotic fibrous dysplasia, typically involving the facial skull, numerous café-au-lait spots and autonomous hyperfunctions of several endocrine systems, leading to hyperthyroidism, hypercortisolism, precocious puberty and acromegaly.</p> <p>Case presentation</p> <p>Here, we describe a 12-year-old Caucasian girl with severe facial involvement of fibrous dysplasia, along with massive acromegaly due to growth hormone excess and precocious puberty, with a prolactinoma. Our patient was treated with a bisphosphonate and the prolactin antagonist, cabergoline, resulting in the inhibition of fibrous dysplasia and involution of both the prolactinoma and growth hormone excess. During a follow-up of more than two years, no severe side effects were noted.</p> <p>Conclusion</p> <p>Treatment with bisphosphonates in combination with cabergoline is a suitable option in patients with McCune-Albright syndrome, especially in order to circumvent surgical interventions in patients suffering from polyostotic fibrous dysplasia involving the skull base.</p

Evapotranspiração e coeficientes de cultivo da beterraba orgânica sob cobertura morta de leguminosa e gramínea.

As práticas agrícolas que maximizam a produtividade e o uso da água são de vital importância para a agricultura. Assim, foram testados três tipos de manejo do solo com objetivo de determinar a evapotranspiração (ETc) e os coeficientes de cultivo (kc) da beterraba. Os tipos de manejo foram a utilização de coberturas mortas vegetais, denominadas capim cameroon (Pennisetum purpureum), gliricídia (Gliricidia sepium) e solo sem cobertura morta em área experimental do SIPA (Sistema Integrado de Produção Orgânica) localizado em Seropédica, Brasil. A lâmina de irrigação foi estimada com base no balanço de água no solo, cujo monitoramento foi realizado com a técnica da TDR. As ETc acumuladas para a cultura da beterraba foram 59,41; 55,31 e 119,62 mm, respectivamente, para capim cameroon, gliricídia e solo sem cobertura morta. A evapotranspiração de referência (ETo) foi obtida por meio do modelo de Penamn-Monteith. Os valores médios de kc obtidos para as fases inicial, média e final de desenvolvimento foram de 0,39; 0,42 e 1,02; 0,79; 0,76 e 1,18; e 0,56; 0,61 e 0,84, respectivamente, para capim cameroon, gliricídia e solo sem cobertura morta. O uso da cobertura do solo com gramínea ou leguminosa minimizou de forma expressiva a demanda hídrica da cultura da beterraba (Beta vulgaris)

Pan-Atlantic analysis of the overlap of a highly migratory species, the leatherback turtle, with pelagic longline fisheries

This is the final version of the article. Available from the publisher via the DOI in this record.Large oceanic migrants play important roles in ecosystems, yet many species are of conservation concern as a result of anthropogenic threats, of which incidental capture by fisheries is frequently identified. The last large populations of the leatherback turtle, Dermochelys coriacea, occur in the Atlantic Ocean, but interactions with industrial fisheries could jeopardize recent positive population trends, making bycatch mitigation a priority. Here, we perform the first pan-Atlantic analysis of spatio-temporal distribution of the leatherback turtle and ascertain overlap with longline fishing effort. Data suggest that the Atlantic probably consists of two regional management units: northern and southern (the latter including turtles breeding in South Africa). Although turtles and fisheries show highly diverse distributions, we highlight nine areas of high susceptibility to potential bycatch (four in the northern Atlantic and five in the southern/equatorial Atlantic) that are worthy of further targeted investigation and mitigation. These are reinforced by reports of leatherback bycatch at eight of these sites. International collaborative efforts are needed, especially from nations hosting regions where susceptibility to bycatch is likely to be high within their exclusive economic zone (northern Atlantic: Cape Verde, Gambia, Guinea Bissau, Mauritania, Senegal, Spain, USA and Western Sahara; southern Atlantic: Angola, Brazil, Namibia and UK) and from nations fishing in these high-susceptibility areas, including those located in international waters.Work in Gabon was financially supported by the Large Pelagics Research Center through National Oceanographic and Atmospheric Agency award no. NA04NMF4550391, the UK Defra Darwin Initiative, the Shellshock Campaign (European Association for Zoos and Aquaria) and the UK Natural Environment Research Council. Sea turtle monitoring programmes in Gabon were financially supported by the Wildlife Conservation Society and by the Gabon Sea Turtle Partnership with funding from the Marine Turtle Conservation Fund (United States Fish and Wildlife Service, US Department of the Interior). Four of the satellite tags were deployed in Canadian waters by M. James (Dalhousie University) and the Canadian Sea Turtle Network, with the funding support of Canadian Sea Turtle Network leatherback field research provided by R. A. Myers, the Canadian Wildlife Federation, Environment Canada and WWF-Canada. Work in French Guiana was financially supported by CNES, DEAL and the European Union.This study results from the collaborative effort of 10 data providers, which have satellite-tracked leatherback turtles in the Atlantic Ocean since 1995, through their voluntary participation in the Trans-Atlantic Leatherback Conservation Initiative (TALCIN), a WWF-led initiative. We thank C. Drews (WWF-International) and Jean-Yves Georges (IPHC-CNRS) for having initiated this project. Significant contributions were made by A. Fonseca and M. L. Felix and the WWF Guianas office in fostering this project to secure its continuation. We thank those involved in the sea turtle restoration plan in French Guiana (DEAL, ONCFS, Kulalasi NGO, Kwata, the Reserve Naturelle de l'Amana, Chiefs of Awala and Yalimapo), Yvon Le Maho (IPHC-CNRS) for having initiated the leatherback tracking programme in French Guiana, colleagues from the Regional Program for Sea Turtles Research and Conservation of Argentina–PRICTMA, Aquamarina and Fundación Mundo Marino, the onboard scientific observers from PNOFA-DINARA, the crew and owner of the F/V Torres del Paine, the artisanal fishermen from Kiyú, San José, Uruguay, D. del Bene (PROFAUMA), Z. Di Rienzo and colleagues from Karumbé, the University of Pisa for initiating the satellite tagging programmes in South Africa, and the South African Department of Environmental Affairs for continuing the work in cooperation with Dr Nel from the Nelson Mandela Metropolitan University, Port Elizabeth and Ezemvelo KZN Wildlife. We thank M. L. Felix for her efforts in the deployment of satellite tags in Suriname and the Nature Conservation Division Suriname for facilitating these research efforts. P.M. thanks C. Palma for his help in dealing with ICCAT's database, C. Ere, as well as the GIS training and support received from SCGIS and the ESRI Conservation Program, which allowed processing of fishing-effort data. We thank J. Parezo for her careful reading of the manuscript. All authors designed the study and contributed data; S.F, M.S.C., P.M. and M.J.W. compiled the data; S.F., M.A.N. and A.L. coordinated and supervised the project; S.F., M.J.W., P.M. and B.J.G. led the data analysis and interpretation with contributions from all authors; the manuscript was developed by S.F. and M.J.W. as lead authors, with contributions from all authors

Aerobic Exercise Training and In Vivo Akt Activation Counteract Cancer Cachexia by Inducing a Hypertrophic Profile through eIF-2α Modulation

Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-α. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt/mTORC1 pathway and the eIF-2α activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia