Versatility and modifications of the cross-finger flap in reconstruction of digital soft tissue defect

Background: Hand injuries can cause major functional and cosmetic concerns. The cross-finger flap (CFF) is an effective treatment for complex finger defects. While CFF has typically been employed to treat volar aspect abnormalities, new versions now address a larger variety of digital soft tissue defects. The aim of the study was to evaluate the clinical outcome of various modified techniques of cross-finger flap which are used to reconstruct different soft tissue defect of fingers. Methods: This was a prospective observational study carried out in the department of Burn and Plastic Surgery at Dhaka Medical College Hospital, Dhaka from September 2018 to February 2020. Forty (40) patients who presented with different soft tissue defect of fingers included in this study according to inclusion and exclusion criteria. Results: The study involved predominantly male participants (80%), with a mean age of 31.70±14.28 years. The most common soft tissue defect site was the volar area (47.5%), and various modified cross-finger flap techniques were employed. The majority of patients achieved excellent functional outcomes, with 82.5% classified as good, 12.5% as satisfactory, and 5.0% as poor. Conclusions: The modifications of the cross-finger flap are versatile and useful for different sites of digital injuries with good functional outcome

The In Vivo Role of the RP-Mdm2-p53 Pathway in Signaling Oncogenic Stress Induced by pRb Inactivation and Ras Overexpression

The Mdm2-p53 tumor suppression pathway plays a vital role in regulating cellular homeostasis by integrating a variety of stressors and eliciting effects on cell growth and proliferation. Recent studies have demonstrated an in vivo signaling pathway mediated by ribosomal protein (RP)-Mdm2 interaction that responds to ribosome biogenesis stress and evokes a protective p53 reaction. It has been shown that mice harboring a Cys-to-Phe mutation in the zinc finger of Mdm2 that specifically disrupts RP L11-Mdm2 binding are prone to accelerated lymphomagenesis in an oncogenic c-Myc driven mouse model of Burkitt's lymphoma. Because most oncogenes when upregulated simultaneously promote both cellular growth and proliferation, it therefore stands to reason that the RP-Mdm2-p53 pathway might also be essential in response to oncogenes other than c-Myc. Using genetically engineered mice, we now show that disruption of the RP-Mdm2-p53 pathway by an Mdm2C305F mutation does not accelerate prostatic tumorigenesis induced by inactivation of the pRb family proteins (pRb/p107/p130). In contrast, loss of p19Arf greatly accelerates the progression of prostate cancer induced by inhibition of pRb family proteins. Moreover, using ectopically expressed oncogenic H-Ras we demonstrate that p53 response remains intact in the Mdm2C305F mutant MEF cells. Thus, unlike the p19Arf-Mdm2-p53 pathway, which is considered a general oncogenic response pathway, the RP-Mdm2-p53 pathway appears to specifically suppress tumorigenesis induced by oncogenic c-Myc

Al/Fe isomorphic substitution versus Fe2O3 clusters formation in Fe-doped aluminosilicate nanotubes (imogolite)

Textural, magnetic and spectroscopic properties are reported of Fe-doped aluminosilicate nanotubes (NTs) of the imogolite type, IMO, with nominal composition (OH)3Al2−x Fe x O3SiOH (x = 0, 0.025, 0.050). Samples were obtained by either direct synthesis (Fe-0.025-IMO, Fe-0.050-IMO) or post-synthesis loading (Fe-L-IMO). The Fe content was either 1.4 wt% (both Fe-0.050-IMO and Fe-L-IMO) or 0.7 wt% (Fe-0.025-IMO). Textural properties were characterized by High-Resolution Transmission Electron Microscopy, X-ray diffraction and N2 adsorption/desorption isotherms at 77 K. The presence of different iron species was studied by magnetic moment measurements and three spectroscopies: Mössbauer, UV-Vis and electron paramagnetic resonance, respectively. Fe3+/Al3+ isomorphic substitution (IS) at octahedral sites at the external surface of NTs is the main process occurring by direct synthesis at low Fe loadings, giving rise to the formation of isolated high-spin Fe3+ sites. Higher loadings give rise, besides IS, to the formation of Fe2O3 clusters. IS occurs up to a limit of Al/Fe atomic ratio of ca. 60 (corresponding to x = 0.032). A fraction of the magnetism related to NCs is pinned by the surface anisotropy; also, clusters are magnetically interacting with each other. Post-synthesis loading leads to a system rather close to that obtained by direct synthesis, involving both IS and cluster formations. Slightly larger clusters than with direct synthesis samples, however, are formed. The occurrence of IS indicates a facile cleavage/sealing of Al-O-Al bonds: this opens the possibility to exchange Al3+ ions in pre-formed IMO NTs, a much simpler procedure compared with direct synthesi

Seduced by the dark side: integrating molecular and ecological perspectives on the influence of light on plant defence against pests and pathogens.

Plants frequently suffer attack from herbivores and microbial pathogens, and have evolved a complex array of defence mechanisms to resist defoliation and disease. These include both preformed defences, ranging from structural features to stores of toxic secondary metabolites, and inducible defences, which are activated only after an attack is detected. It is well known that plant defences against pests and pathogens are commonly affected by environmental conditions, but the mechanisms by which responses to the biotic and abiotic environments interact are only poorly understood. In this review, we consider the impact of light on plant defence, in terms of both plant life histories and rapid scale molecular responses to biotic attack. We bring together evidence that illustrates that light not only modulates defence responses via its influence on biochemistry and plant development but, in some cases, is essential for the development of resistance. We suggest that the interaction between the light environment and plant defence is multifaceted, and extends across different temporal and biological scales

Molecular Characterization of Leukemia Evolving from Paroxysmal Nocturnal Hemoglobinuria

Myeloid malignancies can evolve from prior hematologic disorders, most commonly AML evolving from MDS. AA and PNH are not malignant conditions but they can evolve to myeloid malignancies with a lower frequency compared to MDS and other myeloid and myeloproliferative diseases. PNH can evolve to myeloid disorders with an incidence rate of 4-10%. Here we aim to revisit the subject of malignant evolution of PNH to myeloid disorders by analyzing the molecular background of PNH using modern NGS technologies. Clinical characteristics, demographics and mutational profiles of patients were collected at The Cleveland Clinic Foundation. In total a cohort of 243 patients evaluated for hemolytic PNH (n=83), AA (39) and AA/PNH (n=121) followed for a period of 22 years was evaluated. Inclusion criteria were: complete flow cytometric panels of PNH cells, patients without antecedent AA (pPNH, 45), patients evolving from AA with PNH clone >20% (sPNH, 38), karyotype (at diagnosis of PNH and transformation), clinical parameters including time to malignant progression, and molecular characterization resulting from NGS performed using various library preparation systems (TruSeq, TruSight, Nextera), comparison of molecular mutations with control cohorts (AA, 160; MDS, 835). The incidence rate of myeloid disorders in our PNH cohort was 3% (7/243). Among hemolytic PNH patients, 7 patients progressed to AML (n=1), MDS (n=5) or myelofibrosis (n=1). Median age was 48 yr (range, 24-80); M/F, 5/2. Median PNH clone size was 71% (range, 29-99). Three progressors were in the pPNH and 4 in the sPNH group. Time to malignant diagnosis was <1-22 yr: 4 yr for 3 patients, 5 yr for 1 patient, <1 yr for 2 patients and 22 years for 1 patient. At the time of transformation, combination of karyotypic abnormalities and molecular lesions showed that 4 cases had abnormal karyotype (+8, -7, del13q) and 5 cases carried myeloid mutations (ASXL1, BCOR, NPM1, TET2, U2AF1, WT1). Normal karyotype was seen in 3 patients with ASXL1+U2AF1, U2AF1 and BCOR+NPM1+WT. In 2 patients, del13q and -7 were associated with BCOR and TET2. In 2 others, del(13q) and +8 were the only detected aberrancies. A total of 45 somatic mutations equally distributed in the 2 groups (pPNH, 22; sPNH, 23) and with similar VAFAVG (pPNH vs. sPNH 38% vs. 33%) were found. PNH showed a higher proportion of individuals with mutations compared to AA/PNH+AA (42 vs. 22% of cases with ≥1 mutation; P=.002) with a median VAF percentage significantly higher in PNH vs. AA/PNH+AA (40 vs. 19%; P55), 17% were equivocal (possibly hits biclonal with a VAFSUM between 45-55), while 13% were more likely a result of clonal chimerism (hits present in different clones; VAFSUM <45). Clonal evolution of hemolytic PNH to MDS/AML is rare, but still occurs and it is accompanied by mutations in typical myeloid genes (BCOR, NPM1, TET2, U2AF1) which in permissive circumstances are capable to change the cell's fate favoring clonal evolution. Our results suggest that most PNH cases can carry additional mutations in the same clone and these mutations can be secondary hits, with PIGA mutations being the founder lesions. However even when mutations in myeloid genes are dominant, the phenotype of the patients is inferred by PIGA. This observation supports the nature of PNH as a monogenic disease with clinical manifestations resulting by PIGA mutations rather than by myeloid genes. Disclosures Sekeres: Syros: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Novartis: Consultancy; Alexion: Consultancy