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MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in regulating gene expression. Many studies, mostly conducted on pediatric patients, suggested that oxidative stress and several miRNAs may play an important role in coeliac disease (CeD) pathogenesis. However, the interplay between oxidative stress and miRNA regulatory functions in CeD remains to be clarified. In this review, we aimed to perform a literature review on the role of miRNAs and oxidative stress in adult CeD patients and to analyze their potential interactions. In this direction, we also reported the preliminary results of a pilot study we recently performed.

Background:The increase in life expectancy and in the number of individuals over 60 years old brings new demands to health professionals and services based on the physiological changes that occur in this population. The aging process results in changes in body composition, increasing body fat and reducing muscle mass, in addition to a reduction in bone mass. Aim:The aim of this study was to examine the effect of whey protein and vitamin D supplementation on body composition and skeletal muscle in older adults living in long-term care facilities. Methods:This study is a double-blind randomized controlled trial. Thirty older adults (>60 years old) were randomized and allocated in three groups: group receiving resistance training and supplementation receiving resistance training, whey protein and vitamin D; group received resistance and placebo training receiving resistance training and placebo, and control group without any intervention. Body composition was measured by dual-energy X-ray absorptiometry at baseline, 12 weeks, and 24 weeks. Results:The mean age was 74.87 (± 8.14) years. A significant difference (p= 0.042) was observed between the group receiving resistance training and supplementation and control groups in relation to lean mass increase (kg) at 24 weeks. After 24 weeks of intervention, there was a significant increase in Relative index of muscle mass for the two groups that underwent resistance training, group received resistance and placebo training (p= 0.042) and group receiving resistance training and supplementation (p= 0.045), in relation to the control. Conclusion:Combined supplementation of whey protein and vitamin D with resistance training can significantly improve lean mass, total mass, and relative index of muscle mass in institutionalized older adults.

The vibrational spectrum determines, to a large extent, a material’s thermal expansion. However, extracting information on the material’s vibrational spectrum from the measured thermal expansion is an ill-conditioned inverse problem whose solution generally involves regularization techniques. In this work, the procedure for extracting the vibrational density of states-weighted Grüneisen parameter spectra (Ga(Θ)and Gc(Θ)) from the temperature-dependent linear thermal expansion coefficients parallel to the crystallographic a- and c-axis of materials with a hexagonal Bravais lattice is described and then applied to graphite. The resulting spectra, obtained by solving an inverse problem consisting of a pair of coupled Fredholm integrals of the first kind, exhibit two main contributions to Ga(Θ), centered around Θ= 100 K and Θ= 1200 K, and one narrow peak in Gc(Θ)centered around Θ= 100 K. The low-energy, narrow peak of negative amplitude in Ga(Θ)is in good agreement with a large and negative Grüneisen parameter previously reported for transverse acoustic modes in graphite and accounts for the negative thermal expansion exhibited by graphite along the a-axis up to about 655 K. A simplified vibrational density of states-weighted Grüneisen parameter spectra of graphite, consisting of the two lowest energy, narrow peaks in Ga(Θ)and Gc(Θ), plus an asymmetric Gaussian peak with positive amplitude in Ga(Θ), is proposed which still captures the main features of graphite’s thermal expansion.

This paper introduces PolyWeight, a Python software featuring a user-friendly graphical user interface (GUI), which offers two distinct approaches for MWD determination: an analytical relation-based method and a parametric model-based method. By utilizing dynamic moduli, users can calculate MWD as well as molecular weight averages such as M n , M w , and M z. The functionality of PolyWeight is validated using synthetic data and real data obtained from the literature, exhibiting good agreement. Log files and datasets used in this work are available on GitHub. Program Title: PolyWeight CPC Library link to program files: https://doi.org/10.17632/rn8t4mmvyd.1 Developer's repository link: https://github.com/a-minotto/PolyWeight Licensing provisions: GPLv3 Programming language: Python 3.x Nature of problem: Analytical rheology enables the determination of molecular weight distribution (MWD) by solving inverse problems. The reptation theory establishes a liaison between the viscoelastic behavior and MWD, permitting the application of mathematical resolution methods like regularization and parameterization. PolyWeight offers two solutions: a parameterization-based method that assumes a generalized exponential distribution (GEX) for the MWD, and an analytical relationship-based method that utilizes the relaxation spectrum. Solution method: The analytical relationship-based solution incorporates a mathematical formulation that considers the relaxation spectrum obtained from the dynamic moduli using the NLREG software. The numerical integration of the relaxation spectrum is performed utilizing the integrate.quad function from the SciPy library. An optimization process is employed in the parametric solution to perform a multiobjective fit of the viscoelastic models to the dynamic moduli. The integrals in this case are also calculated using the integrate.quad package from the SciPy library. The optimization procedure utilizes the lmfit library, where a Minimizer object is created based on the optimization function and subsequently utilized with the minimize function, employing the default Levenberg-Marquardt algorithm for the fit. [ABSTRACT FROM AUTHOR]

Conjugated polymers with intense solid-state emission are vital for the development of next-generation optoelectronic devices. In particular, it remains extremely challenging to construct π-conjugated systems that emit in the red region of the electromagnetic spectrum and also retain their optical properties and intense photoluminescence in the solid state. In this article we report the synthesis and characterization of three novel diketopyrrolopyrrole-based conjugated polymers, with systematic variation of the covalent encapsulation density. Through control of the distance and density of encapsulation, our red-emitting polymers demonstrate that aggregation-caused quenching can be mostly eliminated, culminating in the most efficient solid-state photoluminescence from red conjugated polymers to date.

Intermolecular interactions play a fundamental role on the performance of conjugated materials in organic electronic devices, as they heavily influence their optoelectronic properties. Synthetic control over the solid state properties of organic optoelectronic materials is crucial to access real life applications. Perylene diimides (PDIs) are one of the most highly studied classes of organic fluorescent dyes. In the solid state, π–π stacking suppresses their emission, limiting their use in a variety of applications. Here, we report the synthesis of a novel PDI dye that is encapsulated by four alkylene straps. X-ray crystallography indicates that intermolecular π–π stacking is completely suppressed in the crystalline state. This is further validated by the photophysical properties of the dye in both solution and solid state and supported by theoretical calculations. However, we find that the introduction of the encapsulating “arms” results in the creation of charge-transfer states which modify the excited state properties. This article demonstrates that molecular encapsulation can be used as a powerful tool to tune intermolecular interactions and thereby gain an extra level of control over the solid state properties of organic optoelectronic materials.

In this article, we experimentally demonstrate a novel expanded nonorthogonal multiband super-Nyquist carrier-less amplitude and phase (m-ESCAP) modulation for bandlimited organic visible light communication (VLC) systems. The proposed scheme has the same bandwidth requirement as the conventional m-CAP while breaking the orthogonality between subcarriers by purposely overlapping them. We compare m-ESCAP with the conventional m-CAP and a compressed nonorthogonal version of m-CAP (m-SCAP) in terms of measured bit error rate (BER) performance, bit rates, and spectral efficiencies. We show that the m-ESCAP system offers improvement in the bit rate of $\sim$10% and 20% compared to the m-CAP and m-SCAP, respectively, and in the spectral efficiency of $\sim$20% compared to m-CAP. These gains are achieved at the cost of increased BER, which, however, remains below the 7% forward error correction limit.

ABSTRACTIn the present work, we investigate the usefulness of a new representation of the results obtained by fMRI data analysis, named weighted activation vector (WAV), built based on statistical parametric mapping. A software package for the generation and management of WAVs is illustrated. It is designed to support single-subject, multi-temporal and collective brain tumour studies. As seen in our experimental context, the combined use of WAVs and statistical parametric maps (SPMs) improves the quality of medical decisions before and after neurosurgical practice. Clustering techniques applied to WAVs can be efficiently analysed and optimised in an attempt to discover relevant properties of collective data.

The aggregation-induced emission (AIE) phenomenon provides a new direction for the development of organic light-emitting devices. Here, we present a new class of emitters based on 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY), functionalized at different positions with tetraphenylethylene (TPE), which is one of the most famous AIE luminogens. Thanks to this modification, we were able to tune the photoluminescence of the BODIPY moiety from the green to the near-infrared (NIR) spectral range and achieve PL efficiencies of ~50% in the solid state. Remarkably, we observed an enhancement of the AIE and up to ~100% photoluminescence efficiencies by blending the TPE-substituted BODIPY fluorophores with a poly[(9,9-di-n-octylfluorene-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,7-diyl)] (F8BT) matrix. By incorporating these blends in organic light-emitting diodes (OLEDs), we obtained electroluminescence peaked in the range 650–700 nm with up to 1.8% external quantum efficiency and ~2 mW/cm2radiance, a remarkable result for red/NIR emitting and solution-processed OLEDs.

Suppression of exciton–vibration coupling yields organic light-emitting diodes that emit at 1,000 nm in the NIR-II spectral region, which is important for biological imaging.

The widespread application of quantum dots greatly profits from their broad absorption band. However, the variable nature of excitations within these bands is expected to result in undesired excitation energy dependence of steady state emission properties. We demonstrate the different role played by hot and cold carrier trapping in determining fluorescence quantum yields. Our analysis relates the energetic parameters with the available knowledge on the dynamics of charge trapping. It turns out that detrapping processes play a pivotal role in determining steady state emission properties. We studied excitation dependent photoluminescence quantum yields (PLQY) in different CdSe/CdxZn1–xS (x= 0, 0.5, and 1) quantum dots to identify best performing heterostructures in terms of shell thickness and composition. Our rationalization of the observed behavior is focused on the modulation of trapping and detrapping rates. The combination of experimental results and PLQY kinetics modeling reveals the need to consider hot-carrier trapping, supporting recent dynamics observations. This work provides a deeper insight into the trapping process in quantum dots, relating its energetics and dynamics.

Melanocytic nevi result from the proliferation of melanocytes at the dermal-epidermal junction and/or in the dermis and very rarely affect the nail matrix and bed. Intradermal nevi are tumors often diagnosed in routine clinical dermatological practice, with typical clinical and histopathologic aspects, and found in a wide variety of skin sites. We report a case of intradermal melanocytic nevus of the proximal nail fold with uncommon intraoperative gross findings and without involvement of the nail bed or matrix, showing intradermal component only, which draws our attention to the possible different presentation of melanocytic lesions. No description of intradermal nevi at this site has been reported in the literature so far.

The ability to control the properties of organic thin films is crucial for obtaining highly performant thin-film devices. However, thin films may experience post-growth processes, even when the most sophisticated and controlled growth techniques such as organic molecular beam epitaxy (OMBE) are used. Such processes can modify the film structure and morphology and, thus, the film properties ultimately affecting device performances. For this reason, probing the occurrence of post-growth evolution is essential. Equally importantly, the processes responsible for this evolution should be addressed in view of finding a strategy to control and, possibly, leverage them for driving film properties. Here, nickel-tetraphenylporphyrin (NiTPP) thin films grown by OMBE on highly oriented pyrolytic graphite (HOPG) are selected as an exemplary system exhibiting a remarkable post-growth morphology evolution consistent with Ostwald-like ripening. To quantitatively describe the growth, the height–height correlation function (HHCF) analysis of the atomic force microscopy (AFM) images is carried out, clarifying the role of the post-growth evolution as an integral part of the whole growth process. The set of scaling exponents obtained confirms that the growth is mainly driven by diffusion combined with the presence of step-edge barriers, in agreement with the observed ripening phenomenon. Finally, the results together with the overall approach adopted demonstrate the reliability of the HHCF analysis in systems displaying post-growth evolution.

This paper is a case report of a young patient after a major head trauma causing multiple skull base fractures. The trauma occasioned pseudoaneurysm (PSA) from intracavernous C4 segment of left internal carotid artery (ICA) protruding in the sphenoidal sinus. After two months, two episodes of massive epistaxis occurred. Consequently, the post-traumatic PSA was treated, after carotid occlusion test, with flow-diverter stent positioning. A computed tomography angiography study performed in the following days showed complete resolution of the post-traumatic PSA lesion and ICA patency.

The use of flow-diverter (FD) stents in recent years has positively changed the therapeutic approach to some vascular diseases, especially of certain types of aneurysms. This paper describes the case of a young patient after a major head trauma causing multiple skull fractures. The trauma occasioned two pseudoaneurysms from the A1 segment of the right anterior cerebral artery and from the A2 segment of the left anterior cerebral artery.Both lesions were treated with two Pipeline devices (ev3, Irvine, CA, USA) in two different sessions. The CT study and angiographic investigations performed in the following month showed a complete resolution of the post-traumatic pseudoaneurysmal lesions.Although the use of FD stents is described in the literature, particularly in the treatment of selected aneurysms, this paper shows good technical results in the use of these stents in cases of intracranial post-traumatic pseudoaneurysms with clinical improvement.

The shell thickness and composition of CdSe–CdxZn1–xS core–shell quantum dots (QDs) are defining parameters for the efficiency of such materials as light emitters. In this work we present a detailed study into the optical absorption and fluorescence properties of CdSe–CdS, CdSe–Cd0.5Zn0.5S, and CdSe–ZnS QDs as a function of shell thickness. Moreover, the single-exciton recombination dynamics of these systems are analyzed by means of a time-correlated single-photon counting technique and directly related to the specific core–shell interfaces of the various QDs studied using a phenomenological kinetic model. The findings from this model highlight the strong role of the core–shell interface on both steady state photoluminescence and exciton recombination dynamics in these systems.

Pituitary apoplexy is a rare endocrine emergency that occurs in a small number of patients with a pituitary tumor. It is a clinical syndrome characterized by the sudden onset of headache, nausea, vomiting, visual impairment, and decreased consciousness, caused by hemorrhage and/or infarction of the pituitary gland. Pituitary apoplexy has very rarely been described during pregnancy, when it is potentially life-threatening to both the mother and the fetus, if unrecognized. Only a few cases have been published to date. The review of the existing literature underlines that pituitary apoplexy, although rare, should be borne in mind when a pregnant woman presents with severe headache and visual defects of sudden onset. After initial management, which includes intravenous glucocorticoid therapy, fluid and electrolyte replacement, the final selection of medical or surgical treatment should result from a multidisciplinary approach involving expert specialists, keeping into account both severity of clinical presentation and gestational week.

Lhermitte-Duclos disease is a rare pathologic condition consisting of a dysplastic gangliocytoma of the cerebellum. Its association with phacomatosis and an autosomal dominant neoplastic syndrome, Cowden's syndrome is also known. Modern neuroimaging contributes to a correct diagnosis and pre- and postoperative evaluation. Here we describe the morphologic and metabolic aspects of the disease as shown by conventional MRI, diffusion imaging and spectroscopy in a 31-year-old woman. In addition, the specific neuroradiologic characteristics are presented and discussed in the light of the main pathologic and clinical features, such as hypertrophy of the cerebellar folia associated with white matter atrophy.

The structural nature of heterointerfaces in core–shell semiconductor quantum dots (QDs) plays a crucial role in tailoring their optical properties. In this work we have focused on using surface-enhanced Raman spectroscopy as a nondestructive tool to investigate the structural evolution of such interfaces in CdSe/CdS and CdSe/Cd0.5Zn0.5S colloidal QDs. A comparison between the two systems shows significant structural variation across the core–shell interfaces for the two different materials: a smooth interface for the former and an abrupt interface for the latter. This structural difference modifies the electronic structure within the QDs, which directly dictates the confinement behavior of the electrons and holes. The implications of this translate to a better understanding of why graded CdSe/CdS/Cd0.5Zn0.5S/ZnS QDs are so lucrative for linear and nonlinear fluorescence-based applications.

While several studies have been conducted on the antioxidant properties of the P-amino acid taurine, these studies all used concentrations lower than what is found physiologically. This study investigates the scavenging and antioxidant properties of physiological taurine concentrations against different reactive species. No reactivity between taurine and hydrogen peroxide was found; however, taurine exhibited significant scavenging potential against peroxyl radical, nitric oxide, and superoxide donors. This study also evaluated if taurine was able to minimize the in vitroCuZn-superoxide dismutase damage (SOD) induced by peroxynitrite. Taurine prevented both the formation of nitrotyrosine adducts and the decrease in SOD activity caused by peroxynitrite. In addition, taurine prevented the ex vivodamage caused by tert-butyl hydroperoxide in rat liver slices. These experimental data show that taurine, at different physiological concentrations efficiently scavenges many reactive oxygen and nitrogen species. This finding supports the hypothesis that the antioxidant properties of taurine may be critical for the maintenance of cellular functions, and it suggests a more important function of taurine that requires further investigation.

We analyzed individual VHgene rearrangements in 55 consecutive B-chronic lymphocytic leukemia (B-CLL) patients collected from a northeastern region of Italy, stressing the possible differences related to geographic characteristics of the cohorts studied. Considering the percentage of somatic mutations present in the VHgene sequences and using the 98 cut-off value, 38 of the 55 B-CLL (69) patients displayed somatic hypermutations and 17 (31) had a germline configuration. Our results confirm and extend the observations of a bias in the use of certain VH, DH, and JHgenes among B-CLL cells. The most frequently used VHgenes were VH1-69 (12.7) with VH3-23 (12.7) and VH4-34 (10.9). Collectively these genes accounted for 36.3 of the cases. In the mutated cases, the range of mutations varied from 2 to 15, with a median of 6.5. VH1-69 (7 cases, all unmutated) carried few mutations as opposed to VH3-23 (7 cases, 5 of which mutated), VH4-34 (6 cases, all mutated), and VH3-30 (5 cases, all mutated), which show a high load of mutations. D3 family genes were found frequently (38.1) followed by D2 (27.2) and D6 (18.1). The individual D segment most frequently used was D3-3, which was present in 16.3 of cases. There was predominance of the JH4 gene (49) followed by JH6 (40). Analysis of the distribution of replacement and silent mutations in the mutated sequences using the method of Lossos showed in 39.4 of cases evidence of antigen selection in the framework region andor complementary determining regions. In comparison with a recent study on B-CLL patients from the Mediterranean area, the VH4-34 gene was significantly overused in the mutated group at a percentage double that of the Italian cohort reported in this study (10.9 vs. 5), but at a frequency similar to the entire Mediterranean region (10.7). We also found an over-representation of VH1-69 usage in the germline group, at a frequency (12.7) higher than previously described by the same authors (Italian 8, Mediterranean 10.7). On the contrary, VH3-07 and VH3-49 were not much used in our study (5.4 and 1.8, respectively) compared with the Italian group (8 and 5.1). In our study, VH3-23 gene segment was frequently expressed, at frequency as high as that of VH1-69, a finding in keeping with reported B-CLL Italian data, but higher than the entire series of the Mediterranean area (12.7 vs. 9.2); VH3-21 gene, frequently expressed in northern European CLL but rarely in the Mediterranean area, was completely absent. This biased usage of VHfamily genes may reflect a geographic leukemic repertoire, perhaps owing to a peculiar genetic background, depending on variations in germline composition of the IgVH locus or to the effect of a potential environmental element less frequently encountered in different regions.

Background:If not diagnosed earlier, chromoblastomycosis has a chronic evolutional course that may cause several problems, such as difficulty in managing therapy because of the recrudescent character of the disease, potential association with the growth of epidermoid carcinoma in affected regions, and poor quality of life and work incapacity to the patient. Although infrequent, new cases are reported in the state of Rio Grande do Sul every year, ratifying the necessity for further studies on this disease. Objective:The purpose of this study was to review clinical features and response to therapy in patients with chromoblastomycosis and present data on the demography and history of this disease in the state of Rio Grande do Sul, Brazil. Methods:We reviewed case records of 100 patients with skin lesions caused by chromoblastomycosis, who were treated between 1963 and 1998. The cases were confirmed by the histopathologic and mycologic analyses made by the Dermatology Service of the Universidade Federal do Rio Grande do Sul at the Santa Casa de Misericórdia Hospital. Results:There was a predominance of male patients (4:1) and of white farmers whose ages ranged from 50 to 59 years, with lesions on their lower limbs. Most of them were from the northern regions of the state. The average time between the appearance of the disease and medical diagnosis was 14 years. The verrucous type proved to be the most frequently reported lesion (53%). Thorn wounds were associated with the disease in 16% of the cases. Lesions uncommon to some parts of the body were also reported. In two of the cases, cutaneous lesions caused by paracoccidioidomycosis and chromoblastomycosis were found in the same patient. Epidermoid carcinoma was found in the same parts of the body affected by chromoblastomycosis. Eumycotic mycetoma and chromoblastomycosis were associated. Fonsecaea pedrosoiwas found in 96% of the cases, and Phialophora verrucosa in 4% of the cases. Conclusion:In our study, we observed a predominance of cases in the regions of Missões and Alto Uruguay, followed by the upper and lower northeastern slopes and the lowlands. Severe cases of chromoblastomycosis with intense skin involvement (eg, lesions with carcinoma) were observed. Statistical analysis showed recrudescence of the disease in 43% of cases despite the treatment used. (J Am Acad Dermatol 2001;44:585-92.)

Minotto, L., Edwards, M. R., and Bagnara, A. S. 2000. Trichomonas vaginalis: Characterization, expression, and phylogenetic analysis of a carbamate kinase gene sequence. Experimental Parasitology95, 54–62. The gene encoding carbamate kinase (CBK, ATP:carbamate phosphotransferase, EC 2.7.2.2) from Trichomonas vaginalis has been sequenced and its expression in this protozoon has been verified using reverse-transcription polymerase chain reaction. The codon usage and percentage nucleotide composition in the coding and noncoding regions are consistent with other genes isolated from this parasite. Phylogenetic analysis of this gene has suggested possible speciation events that are congruent with other studies, with suggestions of lateral gene transfer. The gene was expressed in Escherichia coli using the pQE-30 expression system, and the recombinant protein was purified using affinity chromatography. The expression of the recombinant protein was identified via Western blotting and matrix-assisted laser desorption ionization mass spectrometry of tryptic peptides. Preliminary kinetic assays have revealed that the recombinant enzyme has a Km similar to that of the native enzyme and size-exclusion chromatography has shown that the enzyme is active as the homodimer.

Minotto, L., Ko, G.-A., Edwards, M. R., and Bagnara, A. S. 1998.Trichomonas vaginalis: Expression and characterisation of recombinantS-adenosylhomocysteinase.Experimental Parasitology90, 175–180. The gene encodingS-adenosylhomocysteinase activity (S-adenosylhomocysteine hydrolase, SAHH; EC 3.3.1.1) inTrichomonas vaginalishas been expressed inEscherichia colito facilitate the characterisation of the enzyme. Expression of this gene using the pQE-30 (6xHis N-terminal tag) expression system (QIAGEN) has enabled the one-step purification of 6 mg of active recombinant enzyme from a 100-ml bacterial culture by affinity chromatography using a nickel-NTA matrix. The recombinant enzyme has a molecular weight of approximately 56,000 and identification of tryptic peptides by matrix-assisted laser desorption ionisation (MALDI) mass spectrometry has shown that the purified recombinant protein is identical in primary structure to the predicted sequence. The presence of the N-terminal 6xHis tag in the recombinant enzyme did not appear to affect its kinetic and other properties, which are similar to those exhibited by the “native” enzyme present in cell-free extracts ofT. vaginalis.These properties include a similar apparentKmfor adenosine (20–25 μM for the recombinant and 5–10 μM for the native enzymes, respectively) and similar inhibition/inactivation patterns exhibited by adenosine analogues such as arabinosyl adenine (ara-A).

Introduction:

Tiribelli: Bristol-Myers Squibb: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Ariad Pharmaceuticals: Consultancy, Speakers Bureau. Bonifacio:Ariad Pharmaceuticals: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Research Funding; Amgen: Consultancy. Fanin:Novartis: Speakers Bureau.

In this work a fully automatic algorithm to detect brain tumors by using symmetry analysis is proposed. In recent years a great effort of the research in field of medical imaging was focused on brain tumors segmentation. The quantitative analysis of MRI brain tumor allows to obtain useful key indicators of disease progression. The complex problem of segmenting tumor in MRI can be successfully addressed by considering modular and multi-step approaches mimicking the human visual inspection process. The tumor detection is often an essential preliminary phase to solvethe segmentation problem successfully. In visual analysis of the MRI, the first step of the experts cognitive process, is the detection of an anomaly respect the normal tissue, whatever its nature. An healthy brain has a strong sagittal symmetry, that is weakened by the presence of tumor. The comparison between the healthy and ill hemisphere, considering that tumors are generally not symmetrically placed in both hemispheres, was used to detect the anomaly. A clustering method based on energy minimization through Graph-Cut is applied on the volume computed as a difference between the left hemisphere and the right hemisphere mirrored across the symmetry plane. Differential analysis involves the loss the knowledge of the tumor side. Through an histogram analysis the ill hemisphere is recognized. Many experiments are performed to assess the performance of the detection strategy on MRI volumes in presence of tumors varied in terms of shapes positions and intensity levels. The experiments showed good results also in complex situations.

INTRODUCTION The impact on post-relapse survival of selected prognostic factors and salvage therapy (finalized to perform an allo-SCT) was retrospectively analyzed in 172 patients (patients) with relapsed non-APL AML, who had been initially treated with standard induction and risk-adapatiented consolidation. The aim was to identify factors associated with a better outcome at first relapse. METHODS All 172 patients were at first recurrence following consolidation of CR1 with high-dose Ara-C (HiDAC) multicycle therapy supported by blood stem cells (standard risk, as defined by mixed clinical-cytogenetic criteria) or allo-SCT in case of high-risk prognostic profile. Median age at relapse was 55 y (range 21–70). CR1 duration was <6 months in 50 patients (29%), ranging from 0.6 to 52,7 mo (median 9,1). High risk patients were 128/172 (74%) and 43/172 patients (25%) had an unfavourable cytogenetics (CG). One hundred-eleven patients (64%) received HiDAC and 24 (14%) an allo-SCT according to study design. RESULTS 140 patients (81%) received salvage treatment. The remaining 32 patients (19%) received palliation and all of them died. The median OS was 17.1 mo, with a 2yOS of 34%. Favorable prognostic factors identified by univariate analisys were: favourable or intermediate CG (p=0,007), standard risk category according to first line protocol (p=0.004), availibility of a HLA matched donor (p= 0.048), achievement of an early CR1(p=0,000), HiDAC as first line therapy(p=0,000), alloHSCT perfomed at relapse (p=0,000) and a DFS from CR1>12 mo (p=0,000). In multivariate analysis favourable or intermediate CG and DFS >12 mo were confirmed as independent prognostic factors (p=0,036 and p=0,001 respectively). Among the 140 patients, 50 received an allo-SCT following relapse (36%, group 1), and the remaining 90 (64%, group 2) received high dose chemotherapy alone (85), autologous SCT (2), or DLI (3, in case of previous alloSCT). Both groups were comparable regarding age >55 y, prior allo-SCT and risk class at diagnosis. After salvage therapy, 44 patients(88%) in the group 1 achieved CR2, compared to 26 patients (29%) in the group 2. The median duration of CR2 was 9 mo (range 2–64) and 3 mo (range 1–34) in group 1 and 2 respectively. NRM was 17/140: 12 patients (24%) in the allo-SCT group and 5 (6%) in group 2. The 2yOS was 57% and 23% respectively (p=0,000). Moreover, among 50 alloSCT patients, survival was affected by risk category at diagnosis: 2yOS of 19 (38%) standard risk patients was 83% compared to 42% in 31 high risk patients (62%) (p=0.01). This risk stratification has no impact on OS in the group 2. CONCLUSIONS DFS > 12 mo and standard risk category at diagnosis, according to NILG protocol, are the most important independent positive prognostic factors impacting OS of AML relapsed patients. The availibility of a HLA matched donor and a subsequent intensification with alloSCT may offer substantial salvage rates and its outcome is affected by the risk stratification at diagnosis. Nevertheless, high risk patients could benefit from alloSCT, reaching an 2yOS of 42%.

INTRODUCTION We retrospectively analyzed the impact on post-relapse survival of selected prognostic factors and salvage therapy (finalized to perform an allo-SCT) in 145 patients (pts) with non-APL AML who had been initially treated with standard induction and risk-adapted consolidation. The aim was to identify factors associated with a better outcome at first relapse. METHODS All pts were at first recurrence following consolidation of CR1 with (i) high-dose Ara-C (HiDAC) multicycle therapy supported by blood stem cells (standard risk, as defined by mixed clinico-cytogenetic criteria) or (ii) allo-SCT in case of high-risk prognostic profile. Median pt age was 55 y (range 21–68). CR1 duration was ≤ 6 months in 49 pts (34%), ranging from 0.6 to 6 mo (median 3.7). 25/68 pts (37%) had an unfavourable cytogenetics (CG), and 8.2 % had MDS-related AML. 96 pts (66%) had received HiDAC and 21 (15%) an allo-SCT according to study design. RESULTS 105 pts (72%) received salvage chemotherapy, 10 pts (7%) underwent directly allo-SCT, while the remaining 30 (21%) received palliation and all of them died. Salvage therapy consisted again of HiDAC alone or in combination with fludarabine or anthracyclines. After reinduction, 52/105 pts (49.5%) achieved CR2 and 15 (14%) died of complications. Altogether, 42 pts (29%, group 1) received an allo-SCT following relapse, 27 (64%) in CR2, 5 beyond CR2 and 10 soon after relapse. Of 20 more pts (14%, group 2) in CR2 but without HLA identical donor, 13 could be given further intensive consolidation therapy. Both groups were comparable regarding adverse prognostic features such as age >55 y, WBC count>50,000/μL, unfavourable CG, presence of FLT-3 ITD, prior allo-SCT and 1st CR lasting ≤ 6 mo. At the end of treatment, 37/42 pts (88%) receiving SCT and all 20 pts (100%) given only chemotherapy were in CR2. Logistic regression analysis showed that intensive treatment without HiDAC at induction (p=0.04) as well as CR1 lasting <6 mo (p=0.01) negatively affected CR2 rate. Median duration of CR2 was 7.5 mo (range 1–49) in group 1 compared to 4 mo (range 1–15) in group 2. Day 100 non-relapse mortality in the 2 groups was 7% and 10%. After a median follow-up of 9.4 mo in group 1 (range 3–49) and 10 mo in group 2 (range 2–65), 2-y OS was 24% and 15.5%, respectively. Notably, 2-y OS in allo-SCT group ranged from 42% in pts ≤ 45 years to 14% in older ones. Moreover, survival was affected by risk category. In fact 2-y OS of 14/37 (38%) standard risk pts undergoing allo-SCT at salvage was 41% vs 17% in 28/108 (26%) comparable high risk pts. Cox regression analysis revealed achievement of CR2 being the only independent prognostic factor related to overall survival (p=0.0001). CONCLUSIONS AML patients receiving intensive chemotherapy including HiDAC at 1st relapse reached a high CR2 rate, regardless of type of prior risk-adapted consolidation. Further intensification with allo-SCT may offer substantial salvage rates to younger standard risk patients, thus adding value to the underlying concept of a risk-oriented first-line therapy.

In adult ALL standard prognostic models do not predict relapse with great accuracy, which implies under-/over-exposure to a given therapy, especially transplants. A study is exploiting MRD as “best” predictive factor and decisional aid for therapy in unselected patients. Adults with ALL underwent induction-consolidation with IDR/V/ASP/P/CY (cycles 1–3,5,6,8), HD-MTX/Ara-C (cycles 4,7), and CNS prophylaxis. Imatinib was added in Ph+ ALL. For MRD, 3 marrow samples were taken before cycles 4, 6, 8, to be analyzed by PCR/RQ-PCR with case-specific probe(s) targeting fusion genes or Ig-H/TCR rearrangements. MRD negativity was defined as negative/low-positive (<10e-4) timepoint (TP) 2 and negative TP3. MRD- patients received standard maintenance (1st year 6MP/MTX and V/P or CY pulses; 2nd year 6MP/MTX); MRD+ ones were eligible to allogeneic SCT (related/unrelated donor) or alternatively, to autologous stem cell-supported “hypercycles” with MEL/VP/6MP (cycles 1,3) and HD-MTX/Ara-C (cycles 2,4) plus Rituximab if CD20+, and maintenance. Patients with Ph/t(4;11)+ ALL were eligible to early SCT regardless MRD study, and those with undefined MRD were treated by clinical risk class. MRD monitoring was planned at 6, 12 and 24 months since TP3. The trial was activated 05/’00, enrolling 215 ALLs and 15 lymphoblastic lymphomas. Diagnostic characteristics were: age 16–66 years (median 37), B-lin 182, T-lin 48, Ph+ 49, t(4;11)+ 11. CR rate was 84%. So far, 109 patients completed consolidation and were eligible to MRD-oriented therapy. The MRD study was informative in 80 (73%), 14 lacked a probe(s) and 15 were poorly sampled. Altogether, 36/80 were MRD− (45%), with few variations among subsets: B-lin low-risk 38%, high-risk 44%, Ph+ 25%, T-lin 54%. Only a WBC count >100 and adverse cytogenetics predicted to some extent an MRD+ result (P=0.05), while MRD negativity was always confirmed as early as TP1 (week 10). Only 6 MRD− cases relapsed (17%), 1 with a new clone and 4 with suboptimal MRD study, compared to 20/44 (45.5%) MRD+ (P=0.000). DFS at 4 years was 76% in MRD− vs. 24% in MRD+ vs. 54% in the unknown MRD group. In multivariate analysis MRD was stronly predictive for relapse (RR 5.51, P=0.000) followed by a WBC count >30 (RR 3.64, P=0.001), the latter effect being almost exclusively seen in MRD+ patients. As regards MRD monitoring, conversion rate from MRD+ to MRD− was similar after SCT and “hypercycles” in the few cases evaluable (4/6 in each group), with a strong correlation in every prognostic/treatment group between overt relapse and prior positive MRD test (2/35 MRD− vs. 9/20 MRD+; P=0.000). MRD is an invaluable prognostic tool for risk-oriented trials. Both an early analysis and monitoring support optimal therapeutic choices (with some reported exceptions), identify patients at greatest risk of relapse, and could allow comparative trials testing specific treatment elements in different ALL subsets.