Skin manifestations among GATA2-deficient patients

International audienceGATA2 mutations have been identified in various diseases, such as MonoMAC syndrome, Emberger syndrome, familial myelodysplastic syndrome, acute myeloid leukaemia and dendritic cell, monocyte, B-cell and natural killer-cell deficiency. These syndromes present a wide range of clinical features, dominated by severe infections and haematological disorders such as myelodysplastic syndrome. Up to 70% of patients with GATA2 mutations have dermatological features, mainly genital or extragenital warts, panniculitis or erythema nodosum and lymphoedema. We report three patients presenting with common dermatological and haematological features leading to the diagnosis of GATA2 deficiency, but also with skin manifestations that have not been previously described gingival hypertrophy, macroglossitis and glossitis and granulomatous lupoid facial lesions. Dermatologists can encounter patients with GATA2 mutations and should recognize this disorder

Graphene-Enabled Optoelectronics on Paper

The realization of optoelectronic devices on paper has been an outstanding challenge due to the large surface roughness and incompatible nature of paper with optical materials. Here, we demonstrate a new class of optoelectronic devices on a piece of printing paper using graphene as an electrically reconfigurable optical medium. Our approach relies on electro-modulation of optical properties of multilayer graphene on paper via blocking the interband electronic transitions. The paper based devices yield high optical contrast in the visible spectrum with a fast response. Pattering graphene into multiple pixels, folding paper into three-dimensional shapes or printing colored ink on paper substrates enable us to demonstrate novel optoelectronic devices which cannot be realized with wafer-based techniques. © 2016 American Chemical Society

Building productive relationships with young people with SEBD in transition: the role of identity

This article reports a study of the experiences of school leavers with social, emotional and behavioural difficulties (SEBD), which identified supportive relationships as key elements in young people demonstrating resilience through this transitional period. Almost all the young people involved in the study had access to potential helpers, but few managed to establish productive relationships with them. Analysis of interviews, conducted over a 15 month period with a group of 15 school leavers, their parents and those who worked with them, suggested that barriers and facilitators to relationship development existed at two levels: institutional and individual. This article focuses on the individual level, in which identity processes appear to play a key role. These processes are used to explain why some school leavers built productive relationships and thrived, whilst many failed to do so, and struggled. These findings have implications for policy, practice and theory

Electrically switchable metadevices via graphene.

Metamaterials bring subwavelength resonating structures together to overcome the limitations of conventional materials. The realization of active metadevices has been an outstanding challenge that requires electrically reconfigurable components operating over a broad spectrum with a wide dynamic range. However, the existing capability of metamaterials is not sufficient to realize this goal. By integrating passive metamaterials with active graphene devices, we demonstrate a new class of electrically controlled active metadevices working in microwave frequencies. The fabricated active metadevices enable efficient control of both amplitude (>50 dB) and phase (>90°) of electromagnetic waves. In this hybrid system, graphene operates as a tunable Drude metal that controls the radiation of the passive metamaterials. Furthermore, by integrating individually addressable arrays of metadevices, we demonstrate a new class of spatially varying digital metasurfaces where the local dielectric constant can be reconfigured with applied bias voltages. In addition, we reconfigure resonance frequency of split-ring resonators without changing its amplitude by damping one of the two coupled metasurfaces via graphene. Our approach is general enough to implement various metamaterial systems that could yield new applications ranging from electrically switchable cloaking devices to adaptive camouflage systems

Laparoscopic Versus Robot-Assisted Versus Transanal Low Anterior Resection:3-Year Oncologic Results for a Population-Based Cohort in Experienced Centers

BACKGROUND: Laparoscopic, robot-assisted, and transanal total mesorectal excision are the minimally invasive techniques used most for rectal cancer surgery. Because data regarding oncologic results are lacking, this study aimed to compare these three techniques while taking the learning curve into account. METHODS: This retrospective population-based study cohort included all patients between 2015 and 2017 who underwent a low anterior resection at 11 dedicated centers that had completed the learning curve of the specific technique. The primary outcome was overall survival (OS) during a 3-year follow-up period. The secondary outcomes were 3-year disease-free survival (DFS) and 3-year local recurrence rate. Statistical analysis was performed using Cox-regression. RESULTS: The 617 patients enrolled in the study included 252 who underwent a laparoscopic resection, 205 who underwent a robot-assisted resection, and 160 who underwent a transanal low anterior resection. The oncologic outcomes were equal between the three techniques. The 3-year OS rate was 90% for laparoscopic resection, 90.4% for robot-assisted resection, and 87.6% for transanal low anterior resection. The 3-year DFS rate was 77.8% for laparoscopic resection, 75.8% for robot-assisted resection, and 78.8% for transanal low anterior resection. The 3-year local recurrence rate was in 6.1% for laparoscopic resection, 6.4% for robot-assisted resection, and 5.7% for transanal procedures. Cox-regression did not show a significant difference between the techniques while taking confounders into account. CONCLUSION: The oncologic results during the 3-year follow-up were good and comparable between laparoscopic, robot-assisted, and transanal total mesorectal technique at experienced centers. These techniques can be performed safely in experienced hands

Comparison of laparoscopic versus robot-assisted versus transanal total mesorectal excision surgery for rectal cancer:a retrospective propensity score-matched cohort study of short-term outcomes

BACKGROUND: Laparoscopic total mesorectal excision (TME) surgery for rectal cancer has important technical limitations. Robot-assisted and transanal TME (TaTME) may overcome these limitations, potentially leading to lower conversion rates and reduced morbidity. However, comparative data between the three approaches are lacking. The aim of this study was to compare short-term outcomes for laparoscopic TME, robot-assisted TME and TaTME in expert centres. METHODS: Patients undergoing rectal cancer surgery between 2015 and 2017 in expert centres for laparoscopic, robot-assisted or TaTME were included. Outcomes for TME surgery performed by the specialized technique in the expert centres were compared after propensity score matching. The primary outcome was conversion rate. Secondary outcomes were morbidity and pathological outcomes. RESULTS: A total of 1078 patients were included. In rectal cancer surgery in general, the overall rate of primary anastomosis was 39.4, 61.9 and 61.9 per cent in laparoscopic, robot-assisted and TaTME centres respectively (P < 0.001). For specialized techniques in expert centres excluding abdominoperineal resection (APR), the rate of primary anastomosis was 66.7 per cent in laparoscopic, 89.8 per cent in robot-assisted and 84.3 per cent in TaTME (P < 0.001). Conversion rates were 3.7 , 4.6 and 1.9 per cent in laparoscopic, robot-assisted and TaTME respectively (P = 0.134). The number of incomplete specimens, circumferential resection margin involvement rate and morbidity rates did not differ. CONCLUSION: In the minimally invasive treatment of rectal cancer more primary anastomoses are created in robotic and TaTME expert centres

Turner syndrome and associated problems in turkish children: A multicenter study

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population. Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014. Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosi) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto’s thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%. Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan. © Journal of Clinical Research in Pediatric Endocrinology

Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.

The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

Validation of the Decipher Genomic Classifier in Patients receiving Salvage Radiotherapy without Hormone Therapy after Radical Prostatectomy - An Ancillary Study of the SAKK 09/10 Randomized Clinical Trial.

BACKGROUND The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase 3 trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. PATIENTS AND METHODS A clinical grade whole-transcriptome assay was performed on RP samples obtained from patients enrolled in SAKK 09/10, a phase 3 trial of 350 men with biochemical recurrence post-radical prostatectomy randomized to 64Gy vs. 70Gy without concurrent hormonal therapy or pelvic nodal radiotherapy (RT). A pre-specified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, post-radical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. RESULTS The analytic cohort of 226 patients was representative of the overall trial, with median follow-up of 6.3 years (IQR 6.1-7.2). GC (high vs. low-intermediate) was independently associated with biochemical progression (subdistribution hazard ratio [sHR] 2.26 [95% CI 1.42-3.60], p<0.001), clinical progression (HR 2.29 [95% CI 1.32-3.98], p=0.003), and use of hormone therapy (sHR 2.99 [95% CI 1.55-5.76], p=0.001). GC high patients had 5-year freedom from biochemical progression of 45% vs. 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower vs. higher GC scores. CONCLUSIONS This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. This data confirms the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting

Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity