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Electrode miniaturization has profoundly revolutionized the field of electrochemical sensing, opening up unprecedented opportunities for probing biological events with a high spatial and temporal resolution, integrating electrochemical systems with microfluidics, and designing arrays for multiplexed sensing. Several technological issues posed by the desire for downsizing have been addressed so far, leading to micrometric and nanometric sensing systems with different degrees of maturity. However, there is still an endless margin for researchers to improve current strategies and cope with demanding sensing fields, such as lab-on-a-chip devices and multi-array sensors, brain chemistry, and cell monitoring. In this review, we present current trends in the design of micro-/nano-electrochemical sensors and cutting-edge applications reported in the last 10 years. Micro- and nanosensors are divided into four categories depending on the transduction mechanism, e.g., amperometric, impedimetric, potentiometric, and transistor-based, to best guide the reader through the different detection strategies and highlight major advancements as well as still unaddressed demands in electrochemical sensing. [ABSTRACT FROM AUTHOR]

Background: The incidence of cancer is increasing globally, and a greater number of patients will receive treatments though central vascular access devices (CVADs). Only a few qualitative studies describe the experience of adult oncology patients living with CVADs, and no systematic review of literature has been published on this topic. We therefore aimed to systematically synthesize the evidence of the qualitative studies on the experience of adult oncology patients with CVADs to report the implications of living with this device, and to inform healthcare professionals (HCPs) about problematic aspects of care for this population.Methods: A comprehensive literature review was conducted on PUBMED, MEDLINE, SCOPUS, COCHRANE, and WEB OF SCIENCE, and was updated on May 25, 2021. Nine studies fulfilled the inclusion criteria. The evidence was synthesized using the meta-aggregation approach proposed by the Joanna Briggs Institute.Results: Four themes emerged: During catheter implantation oncology patients typically experience reluctance, apprehension and acceptance; The nature of the information, knowledge transmission and HCPs' competence all influence the patient's confidence; How the presence of a catheter impacts the patient's daily life, their self-perception and their social behavior; The catheter is a symbol of disease, a friend that helps prevent problems, and its removal is perceived as physical and psychological liberation.Conclusion: This systematic review evidenced some problematic aspects related to patient information, education and device management, and gaps in nursing skills on handling the device. The results of this review should be used as a framework for improvement interventions. [ABSTRACT FROM AUTHOR]

Seminal plasma (SP) of donkey stallions was evaluated using various oxidative stress parameters as well as protease and protease inhibitor activities. SP was obtained by nine donkey stallions. In addition, one donkey stallion with non-obstructive azoospermia was enrolled in this study. Free radical scavenging activity (FRSA), the ferric reducing ability of plasma (FRAP), total antioxidant capacity (TAC), and total thiol level (TTL) were highly correlated with each other and with the protease inhibitor activity. However, only FRAP, TAC, and the nitrate/nitrite concentration (NOx) were significantly correlated with sperm concentration, production, and kinetics. Protease inhibitor activity was highly correlated with sperm concentration and production; however, it did not correlate with sperm kinetics. The azoospermic stallion produced a lower amount of semen than the normospermic stallions and its SP showed a lower antioxidant activity when evaluated with FRAP, TAC, and TTL as well as a higher NOx and a lower protease inhibitor activity. In conclusion, the evaluation of SP oxidative profile by FRAP, TAC, and NOx may provide reliable information on donkey sperm quality whereas protease inhibitor activity may play a role as a marker of the sperm concentration in this species. [ABSTRACT FROM AUTHOR]

In this study, we model geodetic strain accumulation along the Cascadia subduction zone between 2007.0 and 2017.632 using position time series from 352 continuous GPS stations. First, we use the secular linear motion to determine interseismic locking along the megathrust. We determine two end member models, assuming that the megathrust is either a priori locked or creeping, which differ essentially along the trench where the inversion is poorly constrained by the data. In either case, significant locking of the megathrust updip of the coastline is needed. The downdip limit of the locked portion lies ∼ 20–80 km updip from the coast assuming a locked a priori, but very close to the coast for a creeping a priori. Second, we use a variational Bayesian Independent Component Analysis (vbICA) decomposition to model geodetic strain time variations, an approach which is effective to separate the geodetic strain signal due to non-tectonic and tectonic sources. The Slow Slip Events (SSEs) kinematics is retrieved by linearly inverting for slip on the megathrust the Independent Components related to these transient phenomena. The procedure allows the detection and modelling of 64 SSEs which spatially and temporally match with the tremors activity. SEEs and tremors occur well inland from the coastline and follow closely the estimated location of the mantle wedge corner. The transition zone, between the locked portion of the megathrust and the zone of tremors, is creeping rather steadily at the long-term slip rate and probably buffers the effect of SSEs on the megathrust seismogenic portion. [ABSTRACT FROM AUTHOR]

A critical point in the analysis of ground displacement time series, as those recorded by space geodetic techniques, is the development of data-driven methods that allow the different sources of deformation to be discerned and characterized in the space and time domains. Multivariate statistic includes several approaches that can be considered as a part of data-driven methods. A widely used technique is the principal component analysis (PCA), which allows us to reduce the dimensionality of the data space while maintaining most of the variance of the dataset explained. However, PCA does not perform well in finding the solution to the so-called blind source separation (BSS) problem, i.e., in recovering and separating the original sources that generate the observed data. This is mainly due to the fact that PCA minimizes the misfit calculated using an $$L_{2}$$ norm ( $$\chi ^{2})$$ , looking for a new Euclidean space where the projected data are uncorrelated. The independent component analysis (ICA) is a popular technique adopted to approach the BSS problem. However, the independence condition is not easy to impose, and it is often necessary to introduce some approximations. To work around this problem, we test the use of a modified variational Bayesian ICA (vbICA) method to recover the multiple sources of ground deformation even in the presence of missing data. The vbICA method models the probability density function (pdf) of each source signal using a mix of Gaussian distributions, allowing for more flexibility in the description of the pdf of the sources with respect to standard ICA, and giving a more reliable estimate of them. Here we present its application to synthetic global positioning system (GPS) position time series, generated by simulating deformation near an active fault, including inter-seismic, co-seismic, and post-seismic signals, plus seasonal signals and noise, and an additional time-dependent volcanic source. We evaluate the ability of the PCA and ICA decomposition techniques in explaining the data and in recovering the original (known) sources. Using the same number of components, we find that the vbICA method fits the data almost as well as a PCA method, since the $$\chi ^{2}$$ increase is less than 10 % the value calculated using a PCA decomposition. Unlike PCA, the vbICA algorithm is found to correctly separate the sources if the correlation of the dataset is low ( $$<$$ 0.67) and the geodetic network is sufficiently dense (ten continuous GPS stations within a box of side equal to two times the locking depth of a fault where an earthquake of $$M_\mathrm{{w}} >6$$ occurred). We also provide a cookbook for the use of the vbICA algorithm in analyses of position time series for tectonic and non-tectonic applications. [ABSTRACT FROM AUTHOR]

The frequent occurrence of chiral 1-substituted-1,2,3,4-tetrahydroisoquinoline ring systems in a large number of alkaloids, possessing a broad spectrum of biological and pharmaceutical properties, has prompted out a considerable interest in their synthesis. Economical and valuable stereoselective processes based on organocatalytic transformations represent a new avenue for approaching isoquinoline alkaloids with efficiency and creativity. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Organic-inorganic hybrid nanofibers obtained by electrospinning technology have experienced a growing interest in the last decade thanks to the versatility and the high productivity of the technique, compared to other technologies devoted to the fabrication of nanocomposites, and to the unique and numerous features displayed by the produced nanomaterials. In this review, we classify and highlight recent progress, as well as current issues, in the production of hybrid nanofibers by electrospinning and their related applications. In particular, the scientific literature has been classified by taking into account the different methodologies that have been developed to fabricate hybrid polymeric-inorganic nanofibers by making use of electrospinning technology in combination with additional specific synthetic and processing procedures. The following technological and synthetic strategies have been discussed in detail: (1) electrospinning of inorganic dispersions in polymer solutions, (2) post treatments of electrospun fibers, (3) electrospinning combined with sol–gel processes, (4) electrospinning combined with electrospraying, (5) coaxial electrospinning, and (6) electrospinning of hybrid polymers. The huge number of different fiber morphologies, structures, and properties that can be achieved by electrospinning is impressive. The power of this technology is even more evident if we take into account that innovative hybrid nanofibers can be fabricated with a simple, versatile, extremely cheap, and scalable technology that makes electrospinning the most interesting currently available technique for the production of nanocomposites. [ABSTRACT FROM AUTHOR]

This paper surveys recent applications and advances of the Constraint Programming-based Column Generation framework, where the master subproblem is solved by traditional OR techniques, while the pricing subproblem is solved by Constraint Programming. This framework has been introduced to solve crew assignment problems, where complex regulations make the pricing subproblem demanding for traditional techniques, and then it has been applied to other contexts. The main benefits of using Constraint Programming are the expressiveness of its modeling language and the flexibility of its solvers. Recently, the Constraint Programming-based Column Generation framework has been applied to many other problems, ranging from classical combinatorial problems such as graph coloring and two dimensional bin packing, to application oriented problems, such as airline planning and resource allocation in wireless ad-hoc networks. [ABSTRACT FROM AUTHOR]

Owing to an unfortunate oversight, the wrong figure 2 has been published. [ABSTRACT FROM AUTHOR]

Evans' syndrome, a combination of autoimmune haemolytic anaemia and autoimmune (idiopathic) thrombocytopenic purpura, is generally harder to treat and more refractory than the single entities. In a male patient with refractory disease, predominantly thrombocytopenic, an allogeneic reduced intensity BMT from his human leukocyte antigen (HLA)-identical sister was followed by a dramatic platelet peak while he was still experiencing initial engraftment (presumably of autologous origin), but subsequently by progressive relapse associated with mixed chimerism. Five gradually incremental DLI achieved complete donor chimerism, which was associated not only with grade II graft-versus-host disease (GVHD), but also with complete clinical and biological remission for 2 years post-transplant. Long-term FU is necessary before claiming that allogeneic stem cell transplantation (SCT) is capable of curing an autoimmune blood disease. However, there is evidence for a graft-versus-autoimmunity effect in this case.Bone Marrow Transplantation (2003) 31, 399-402. doi:10.1038/sj.bmt.1703833 [ABSTRACT FROM AUTHOR]

Recent data has suggested that familial recurrent hydatidiform mole is a rare autosomal recessive trait in women experiencing this gestational disease (MIM 231090). Here we provide molecular data on an additional family confirming that recurrent familial hydatidiform moles are diploid, biparental and arise from independent conceptions. A narrowing of the gene interval on chromosome 19q13.3-13.4 is suggested by haplotype analysis in two sisters. [ABSTRACT FROM AUTHOR]

A letter to the editor focusing on allogeneic bone marrow transplantation(BMT) is presented.

Donor–acceptor dyads based on BODIPYs have been recently employed to enhance the formation of triplet excited states with the process of spin–orbit charge transfer intersystem crossing (SOCT-ISC) which does not require introduction of transition metals or other heavy atoms into the molecule. In this work we compare two donor–acceptor dyads based on meso-naphthalenyl BODIPY by combining experimental and computational investigations. The photophysical and electrochemical characterization reveals a significant effect of alkylation of the BODIPY core, disfavoring the SOCT-ISC mechanism for the ethylated BODIPY dyad. This is complemented with a computational investigation carried out to rationalize the influence of ethyl substituents and solvent effects on the electronic structure and efficiency of triplet state population via charge recombination (CR) from the photoinduced electron transfer (PeT) generated charge-transfer (CT) state. Time dependent-density functional theory (TD-DFT) calculations including solvent effects and spin–orbit coupling (SOC) calculations uncover the combined role played by solvent and alkyl substitution on the lateral positions of BODIPY. [ABSTRACT FROM AUTHOR]

Surgical treatment of tendon lesions still yields unsatisfactory clinical outcomes. The use of bioresorbable scaffolds represents a way forward to improve tissue repair. Scaffolds for tendon reconstruction should have a structure mimicking that of the natural tendon, while providing adequate mechanical strength and stiffness. In this paper, electrospun nanofibers of two crosslinked PLLA/Collagen blends (PLLA/Coll-75/25, PLLA/Coll-50/50) were developed and then wrapped in bundles, where the nanofibers are predominantly aligned along the bundles. Bundle morphology was assessed via SEM and high-resolution x-ray computed tomography (XCT). The 0.4-micron resolution in XCT demonstrated a biomimetic morphology of the bundles for all compositions, with a predominant nanofiber alignment and some scatter (50-60% were within 12° from the axis of the bundle), similar to the tendon microstructure. Human fibroblasts seeded on the bundles had increased metabolic activity from day 7 to day 21 of culture. The stiffness, strength and toughness of the bundles are comparable to tendon fascicles, both in the as-spun condition and after crosslinking, with moderate loss of mechanical properties after ageing in PBS (7 and 14 days). PLLA/Coll-75/25 has more desirable mechanical properties such as stiffness and ductility, compared to the PLLA/Coll-50/50. This study confirms the potential to bioengineer tendon fascicles with enhanced 3D structure and biomechanical properties. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 29-year-old female patient who suffered from recurrent polyarthralgias and bouts of fever from infancy until developed exudative pericarditis. It discusses results of her electromyographic examinations and histology/cytology. The patient was diagnosed of Sjögren's syndrome associated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and treated with autologous and later on allogeneic hematopoietic stem cell transplantation (HSCT).

We consider the problem of allocating students to project topics satisfying side constraints and taking into account students' preferences. Students rank projects according to their preferences for the topic and side constraints limit the possibilities to team up students in the project topics. The goal is to find assignments that are fair and that maximize the collective satisfaction. Moreover, we consider issues of stability and envy from the students' viewpoint. This problem arises as a crucial activity in the organization of a first year course at the Faculty of Science of the University of Southern Denmark. We formalize the student-project allocation problem as a mixed integer linear programming problem and focus on different ways to model fairness and utilitarian principles. On the basis of real-world data, we compare empirically the quality of the allocations found by the different models and the computational effort to find solutions by means of a state-of-the-art commercial solver. We provide empirical evidence about the effects of these models on the distribution of the student assignments, which could be valuable input for policy makers in similar settings. Building on these results we propose novel combinations of the models that, for our case, attain feasible, stable, fair and collectively satisfactory solutions within a minute of computation. Since 2010, these solutions are used in practice at our institution. [ABSTRACT FROM AUTHOR]

Background: Sporadic Hemiplegic Migraine is a rare form of migraine headache. Mutations in three different genes, two ion-channel genes and one encoding an ATP exchanger, CACNA1A, ATP1A2 and SCN1A are all responsible for the FHM phenotype, thus indicating a genetic heterogeneity for this disorder. Here, we described a de novo exonic duplication of ATP1A2 in an Italian patient with Hemiplegic Migraine. Case presentation: We describe the case of a young woman (33 year old) who suffered from the age of 8 years of episodic weakness of the limbs, associated to other subjective and objective features. From aged 25, she developed neurological symptoms, like dizziness, blurred vision and an MRI scan revealed aspecific peritrigonal white matter hyperintensities. Aged 32 she suffered of right hemisomatic sudden-onset paresthesias, hypoesthesia and hyposthenia and the patient was genetically investigated for sporadic hemiplegic migraine. Conclusions: Here we report, for the first time, an exonic duplication in the ATP1A2 associated with hemiplegic migraine. The variation identified involves exon 21 of the ATP1A2 and is expected to alter the function of the alpha(2) subunit of the Na(+)/K(+) pump; the de novo nature of the duplication further supports its pathogenic role. To date, no other CNVs have been described in the ATP1A2 but only point mutations are reported. The novel mutation may result impaired M9 transmembrane domain, in a loss-of-function of the alpha(2) Na(+)/K(+)-ATPase with glutamate accumulation, alteration of synaptic function and neurotransmission. [ABSTRACT FROM AUTHOR]

Objective: To verify the safety and potential effect on ALS progression of a low-intensity immunosuppressive regimen followed by autologous hematopoietic stem cell transplantation (aHSCT) in amyotrophic lateral sclerosis (ALS) patients. Methods: ALS eligible patients underwent a set of clinical and laboratory evaluations at T-4 (screening), T-1 (pre-treatment visit), and for the 12 consecutive months after treatment (T3, T6, T9, T12). We evaluated the tolerability of the procedure, its efficacy on clinical course and quality of life (QoL). Results: Eight of the 11 ALS patients enrolled received the established immunoablative protocol. The procedure was well tolerated and side effects were those expected. One patient died 4 months after the conditioning regimen and another patient underwent tracheotomy just before T3 for a sudden respiratory failure, but he is still alive 4 years after the procedure without being ventilated any more. A third patient died 10 months after conditioning. In the other cases, there was no statistical difference in all functional measures and QoL pre- and post-treatment; however, a transitory slopes' reduction of ALSFRS-R and seated SVC% after the conditioning procedures was reported. Moreover, although not statistically significant, trends of reduction of CD4 + and increment of CD8 + were found. Conclusions: aHSCT was overall well tolerated, but it was not followed by any significant modification in disease progression. Considering the negative results of this small trial, further studies aimed to evaluate the possible efficacy of the aHSCT using a higher-intensity regimen should be carefully and with caution evaluated. [ABSTRACT FROM AUTHOR]

Introduction: Biallelic intronic AAGGG repeat expansion in the replication factor C subunit 1 (RFC1) gene was recently identified in two/third of patients with cerebellar ataxia, sensory neuropathy, and bilateral vestibular areflexia syndrome (CANVAS). The phenotypic spectrum has expanded since (i.e., parkinsonism, motor neuron involvement, cognitive decline); no behavioral symptoms have been reported yet. Case report: We report an Italian family that met the diagnostic criteria for CANVAS, and RFC1-expansion was detected in five of seven. All the affected members presented behavioral-psychiatric symptoms (anxiety, panic attacks, alcohol abuse) before the multisystemic RFC1-expansion manifestation. The disease course was progressive, with ataxia and behavioral-cognitive aspects as the most disabling symptoms. Conclusion: These behavioral-cognitive observations may broaden the RFC1-expansion phenotypic spectrum and highlight the importance of investigating the whole non-motor symptoms in ataxic patients. [ABSTRACT FROM AUTHOR]

Poly(vinylidene fluoride) (PVDF) displays ferroelectric, piezoelectric and pyroelectric behavior and it is widely used in high-tech applications including sensors, transducers, energy harvesting devices and actuators. The crystallization of this polymer into highly polar β phase is desirable but is hard to achieve without applying specific thermo-mechanical treatments. Indeed, fabrication processes directly affect PVDF molecular chain conformation, inducing distinct polymorphs. In this paper, we present the fabrication of PVDF/BaTiO3 composite foams by thermally induced phase separation method (TIPS). Different compositions are tested and characterized. The crystallinity, and in particular the development of electroactive β crystal phase is monitored by FTIR, DSC and XRD measurements. Dielectric properties are also evaluated. It turns out that TIPS is a straightforward method that clearly promotes the spontaneous growth of the β phase in PVDF and its composite foams, without the need to apply additional treatments, and also significantly improves the degree of crystallinity. BaTiO3 content gives additional value to the development of β phase and total crystallinity of the systems. The low permittivity values (between 2 and 3), combined with the cellular morphology makes these materials suitable as lightweight components of microelectronic circuits. [ABSTRACT FROM AUTHOR]

A new BODIPY derivative (o-I–BDP) containing an iodine atom in the ortho position of the meso-linked phenyl group was prepared. Photophysical and electrochemical properties of the molecule were compared to previously reported iodo BODIPY derivatives, as well as to the non-iodinated analog. While in the case of derivatives featuring iodine substituents in the BODIPY core, efficient population of the triplet state is accompanied by a substantial positive shift of the reduction potential compared to pristine BODIPY, o-I–BDP displays phosphorescence and simultaneously maintains the electrochemical properties of unsubstituted BODIPYs. A theoretical investigation was settled to analyze results and rationalize the influence of iodine position on electronic and photophysical properties, with the purpose of preparing a fully organic phosphorescent BODIPY derivative. TD-DFT and spin–orbit coupling calculations shed light on the subtle effects played by the introduction of iodine atom in different positions of BODIPY. [ABSTRACT FROM AUTHOR]

Forty-two patients relapsing after an unmanipulated haploidentical BM transplant and post-transplant CY (PT-CY), were given 108 DLI, with median interval from transplant of 266 days (range, 67-1372). DLI were given at escalating doses, expressed as CD3+ cells/kg, without GVHD prophylaxis, and ranged from 1 × 103 to 1 × 107 cells/kg (median 5 × 105 cells/kg). The average number of DLI per patient was 2.6 (range, 1-6). The diagnosis was leukemias (n=32) grafted with a myeloablative regimen and Hodgkin's disease (n=10), grafted with a nonmyeloablative regimen. Leukemic patients with molecular relapse (n=20), received DLI alone (n=17) or in association with azacytidine (n=3); leukemic patients with hematologic relapse (n=12) received chemotherapy followed by DLI (n=11) or DLI alone (n=1); Hodgkin patients received DLI following 1-3 courses of chemotherapy. In these three groups the incidence of acute GVHD II-III was 15%, 17% and 10%; response rate was 45%, 33% and 70%; 2-year actuarial survival was 43%, 19% and 80% respectively. This study confirms that escalating doses of DLI can be given in the haploidentical setting with PT-CY, with a relatively low risk of acute GVHD. Response rates and survival are dependent on the underlying disease. [ABSTRACT FROM AUTHOR]

In cutting plane methods, the question of how to generate the 'best possible' set of cuts is both central and crucial. We propose a lexicographic multi-objective cutting plane generation scheme that generates, among all the maximally violated valid inequalities of a given family, an inequality that is undominated and maximally diverse w.r.t. the cuts that were previously found. By optimizing a diversity measure, we introduce a form of coordination between successive cuts. Our focus is on valid inequalities with 0-1 coefficients in the left-hand side and a constant right-hand side, which encompasses several families of valid inequalities. As cut diversity measure, we consider an aggregate of the 1-norm distances w.r.t. the normal vectors of the previous cuts. In this case, our lexicographic multi-objective separation problem reduces to the standard separation problem with different values for the objective function coefficients. The impact of our coordinated cutting plane generation scheme is assessed in a pure cutting plane setting when separating stable set and cut set inequalities for, respectively, the max clique and min Steiner tree problems. Compared to the standard separation of undominated maximally violated cuts, we close the same fraction of the duality gap in a considerably smaller number of rounds and cuts. The potential of our scheme is also indicated by the results obtained in a cut-and-branch setting for max clique, where cut coordination allows for a substantial reduction, on average, of the number of branch-and-bound nodes. [ABSTRACT FROM AUTHOR]

Electrospinning technology is attracting increasing interest for the fabrication of several polymeric and inorganic nanofibrous materials useful for a wide range of applications. Although the intensive research performed to understand the physics of the electrospinning process, control of polymeric jet path and of fibre deposition still remains a challenge. In this work, micropatterned electrospun materials with tunable porosity are fabricated by using novel collector devices made up of a steel sheet coated with a vitreous enamel layer. The novel approach permits to modulate electrical properties of the collector, acting on charge distribution and charge diffusion properties of the vitreous enamel coating, without introducing substantial modification of the electrospinning apparatus. The proposed solution allows the achievement of novel electrospun products for all those advanced applications requiring materials with suited fibre deposition such as, microelectronics, optical and photonic devices, as well as scaffolds for tissue engineering. [ABSTRACT FROM AUTHOR]

Objective: In order to evaluate the prescribing pattern in the Italian paediatric population, prescriptions involving 923,353 children under 14 years old and dispensed during 2006 by the retail pharmacies of 22 Italian local health units were analysed.Materials and Methods: A total of 561,237 children (61%) received at least one drug prescription. The prescription prevalence rate was highest in children 3 years of age (78%), decreased with increasing age and was higher in boys than in girls (chi(2)=655; p<<0.001). Each treated child received an average of 3.2 prescriptions and 4.8 boxes.Results: Antibiotics and anti-asthmatics were the more prescribed therapeutic classes and represented 80% of prescriptions. Amoxicillin+clavulanic acid was the most prescribed drug (24% of the overall population; 17% of all boxes), followed by inhaled beclometasone and amoxicillin. A total of 620 different drugs were prescribed and the ten leading drugs represented 64% of the prescribed boxes. Six of the ten most prescribed drugs were the same in all age groups. Wide differences were found in the prevalence rate between the different local health units; these ranged between 50.1 and 68.4% (p<<0.001). The prescription prevalence increased in the 2000-2002 period (from 62.2 to 68.3%) and slightly decreased afterwards.Conclusion: Despite some limitations, the systematic monitoring of prescriptions is a valuable tool for evaluating the appropriateness of the care. [ABSTRACT FROM AUTHOR]

Abstract Background  Interest in cancer-related fatigue has been growing over the last two decades and efforts have been dedicated to investigate this topic. However, research addressing the adequacy of educational resources for patients with this distressing and common symptom is lacking. Only one study has been undertaken and this explored Swiss and British patients’ views. Materials and methods  The current study replicated and extended the study previously undertaken in the United Kingdom (UK) and Switzerland. It sought views on the adequacy of materials on cancer-related fatigue available to patients with cancer living in Italy, and to determine the educational preferences and needs of Italian patients with cancer-related fatigue. These were attained through conduct of two focus groups. One was undertaken with Italian patients and the other with a group of Italian nurses. Main results  Findings from this study supported patients’ desire for timely, accurate and individualised information. Barriers to effective fatigue education included the limited dialogue regarding fatigue initiated in clinical settings. It appeared that nurses and patients held different priorities in symptom management. Further, it was acknowledged that there was often insufficient time to inform patients adequately about fatigue. Participants considered written materials as helpful complements to oral information, thus supporting the provision of information in both forms. However, it was clear that fewer written resources concerning cancer-related fatigue were available in Italy compared to either in Switzerland or in the UK. Conclusion  The study supported the view within the current literature that whilst cancer-related fatigue is recognised as a frequent and disruptive symptom, patient education about this symptom and its management still needs to be enhanced. The resources available to educate patients about cancer-related fatigue should be improved and made more accessible to patients who experience it. [ABSTRACT FROM AUTHOR]

We assessed the outcome of 170 patients with AML in first complete remission, aged 1–47 years (median 29), who had undergone an allogeneic BMT before or after 1990 (n=80 and n=90, respectively); all patients were prepared with cyclophosphamide and TBI; the median follow-up for surviving patients was 13 years. The donor was an HLA-identical sibling in 164 patients. Transplant-related mortality (TRM) was 30% before and 7% after 1990 (P<0.001); relapse-related death (RRD) was 26 and 11% (P=0.002); and actuarial 10-year survival was 42 and 79% (P<0.00001). Patients transplanted after 1990 were older, had a shorter interval diagnosis-BMT, had less FAB-M3 cases, received a higher dose of TBI, a higher marrow cell dose and combined (cyclosporine+methotrexate) GVHD prophylaxis. Patients relapsing after transplant had an actuarial survival of 0 vs 31% if grafted before or after 1990 (P=0.01), and their median follow-up exceeds 10 years. In conclusion, the overall survival of first remission AML undergoing an allogeneic BMT has almost doubled in the past two decades, despite older age and fewer M3 cases. Improvement has come not only from changes in transplant procedures, but also from effective rescue of patients relapsing after transplant.Bone Marrow Transplantation (2007) 40, 349–354; doi:10.1038/sj.bmt.1705739; published online 25 June 2007 [ABSTRACT FROM AUTHOR]

We assessed the long-term outcome of patients with relapsed acute myeloid (n=86) or acute lymphoid leukemia (n=66), undergoing an allogeneic hemopoietic stem cell transplantation in our unit. The median blast count in the marrow was 30%. Conditioning regimen included total body irradiation (TBI) (10–12 Gy) in 115 patients. The donor was a matched donor (n=132) or a family mismatched donor (n=20). Twenty-two patients (15%) survive disease free, with a median follow-up of 14 years: 18 are off medications. The cumulative incidence of transplant related mortality is 40% and the cumulative incidence of relapse related death (RRD) is 45%. In multivariate analysis of survival, favorable predictors were chronic graft-versus-host disease (GvHD) (P=0.0003), donor other than family mismatched (P=0.02), donor age less than 34 years (P=0.02) and blast count less than 30% (P=0.07). Patients with all four favorable predictors had a 54% survival. In multivariate analysis of relapse, protective variables were the use of TBI (P=0.005) and cGvHD (P=0.01). This study confirms that a fraction of relapsed leukemias is cured with an allogeneic transplant: selection of patients with a blast count <30%, identification of young, human leukocyte antigen-matched donors and the use of total body radiation may significantly improve the outcome.Bone Marrow Transplantation (2007) 39, 341–346. doi:10.1038/sj.bmt.1705594; published online 5 February 2007 [ABSTRACT FROM AUTHOR]

Preparative regimens without total body irradiation (TBI) have been reported for alternative donor hemopoietic stem cell transplants (HSCT). Between 7 September 1994 and 7 June 1999 48 patients with advanced hematologic malignancies were conditioned with thiotepa (THIO) 15 mg/kg, cyclophosphamide (CY) 150 mg/kg and antithymocyte globulin (ATG). Donors were HLA mismatched family members (1–2 antigens) (FAM) (n = 24, median age 31 years) or HLA matched unrelated donors (UD) (n = 24, median age 34 years). GVHD prophylaxis was cyclosporine and methotrexate. Stem cell source was peripheral blood (n = 8) or bone marrow (n = 40). Hematologic recovery was seen in 42/46 (91%) evaluable patients and complete chimerism in 31/37 patients (85%). Acute GVHD grades III–IV were seen in 10/46 patients surviving 10 days (21%) and extensive chronic GVHD in 2/36 patients surviving 100 days (5%). Twenty-six patients died (54%), eight of recurrent disease (17%) and 18 of transplant-related complications (37%): main causes of TRM were GVHD (15%), infections (15%) and graft failure (4%). Twenty-two patients (46%) survive with a median follow-up of 877 days (287–1840). The actuarial 3-year survival is 49% for FAM and 42% for UD transplants. Results obtained with this regimen in unrelated grafts for advanced CML (n = 15) were not significantly different when compared to 21 concurrent UD grafts for advanced CML prepared with CY-TBI. In conclusion, the combination of THIO-CY-ATG allows engraftment of alternative donor hemopoietic stem cells. Results are similar when using unrelated matched donors or partially mismatched family donors, and not significantly different when compared to patients conditioned with CY-TBI. Bone Marrow Transplantation (2000) 26, 1305–1311. [ABSTRACT FROM AUTHOR]

Background: Myofibrillar myopathies (MFM) are a subgroup of protein aggregate myopathies (PAM) characterized by a common histological picture of myofibrillar dissolution, Z-disk disintegration, and accumulation of degradation products into inclusions. Mutations in genes encoding components of the Z-disk or Z-disk-associated proteins occur in some patients whereas in most of the cases, the causative gene defect is still unknown. We aimed to search for pathogenic mutations in genes not previously associated with MFM phenotype. Methods: We performed whole-exome sequencing in four patients from three unrelated families who were diagnosed with PAM without aberrations in causative genes for MFM. Results: In the first patient and her affected daughter, we identified a heterozygous p.(Arg89Cys) missense mutation in LMNA gene which has not been linked with PAM pathology before. In the second patient, a heterozygous p.(Asn4807Phe) mutation in RYR1 not previously described in PAM represents a novel, candidate gene with a possible causative role in the disease. Finally, in the third patient and his symptomatic daughter, we found a previously reported heterozygous p.(Cys30071Arg) mutation in TTN gene that was clinically associated with cardiac involvement. Conclusions: Our study identifies a new genetic background in PAM pathology and expands the clinical phenotype of known pathogenic mutations. [ABSTRACT FROM AUTHOR]

This is a report on 60 consecutive patients with chronic myeloid leukemia (CML) who received an allogeneic bone marrow transplant (BMT) in this Unit. Donors were HLA-identical siblings (SIB) (n = 36) or unrelated donors (MUD) (n = 24) matched by serology for HLA A and B and by molecular biology for HLA DR. All patients were prepared with cyclophosphamide 120 mg/kg and fractionated total body irradiation 10–12 Gy. GVHD prophylaxis consisted of cyclosporin A (CsA) starting on day -7 and short-course methotrexate. Bone marrow was unmanipulated in all cases. Cytomegalovirus prophylaxis consisted of acyclovir for SIBs and foscarnet for MUDs. When compared to SIB transplants, MUD patients were younger (29 vs 36 years; P = 0.002), had younger donors (31 vs 39; P = 0.001), had a longer interval between diagnosis and BMT (1459 vs 263 days; P < 0.001) and received a smaller number of nucleated cells at transplant (3.3 vs 4.4 × 108/kg; P = 0.003). More MUDs had advanced disease (50 vs 17%, P = 0.005). The median day to 0.5 × 109/l neutrophils was similar in both groups (18 days for SIBs vs 17 days for MUDs; P = 0.06); the median platelet count on days +30, +50, +100 was significantly (P < 0.01) higher in sib than in mud patients (122 vs 38, 113 vs 50 and 97 vs 45 × 109/l, respectively). Acute GVHD was scored as absent-mild, moderate, or severe, in 36, 58 and 6% of SIBs vs 25, 42 and 33% in MUD patients (P = 0.01). Chronic GVHD was comparable (P = 0.1). The actuarial risk of CMV antigenemia at 1 year was 60% in both groups. There were six deaths in SIB patients (two leukemia, two infections, one GVHD, one pneumonitis) and four deaths in MUD patients (three acute GVHD and one infection). Fifty patients survive with a median follow-up of 656 days for SIBs and 485 for MUDs. The actuarial 3-year transplant-related mortality is 12% in SIBs and 17% in MUDs (P = 0.5); the actuarial relapse is 18% in SIBs vs 6% in MUDs (P = 0... [ABSTRACT FROM AUTHOR]

Autologous haematopoietic stem-cell transplantation has been evaluated over the last years as a possible new therapeutic strategy in severe forms of multiple sclerosis unresponsive to the approved therapies. Up to now, more than 400 patients have been treated and numerous are the phase I and phase II studies which addressed the feasibility of this treatment, the efficacy, side effects and transplant-related mortality. The clinical response is strongly related to the intensity of the conditioning regimen utilized as well as to the phase of the disease course in which the therapy is carried out. Rapidly evolving multiple sclerosis with a relapsing–remitting clinical course and MRI signs of activity are the cases that can take more advantage. The risk of mortality, which dropped in the last years to 2–3%, is still the main problem of this powerful therapy. [ABSTRACT FROM AUTHOR]

In this work, the advantages of carbon nanoelectrodes (CNEs) and orgonic electrochemical transistors (OECTs) were merged to realise nanometre-sized, spearhead OECTs based on single- and double-barrel CNEs functionalised with a conducting polymer film. The needle-type OECT shows a high aspect ratio that allows its precise positioning by means of a macroscopic handle and its size is compatible with single-cell analysis. The device was characterised with respect to its electrolyte-gated behaviour and was employed as electrochemical sensor for the proof-of-concept detection of dopamine (DA) over a wide concentration range (10−12—10−6 M). Upon application of fixed drain and gate voltages (Vd = − 0.3 V, Vg = − 0.9 V, respectively), the nano-sized needle-type OECT sensor exhibited a linear response in the low pM range and from 0.002 to 7 μM DA, with a detection limit of 1 × 10−12 M. [ABSTRACT FROM AUTHOR]

Objective: To study the evolution of sensory-motor nerves in the upper and lower limbs in neurologically healthy preterm infants and to use sensory-motor studies to compare the rate of maturation in preterm infants at term age and full-term healthy neonates.Methods: The study comprised 26 neurologically normal preterm infants born at 23-33 weeks of gestational age, who underwent sensory nerve conduction and motor nerve conduction studies from plantar medial and median nerves and from tibial and ulnar nerves, respectively. We repeated the same neurophysiological studies in 19 of the preterm infants every 2 weeks until postnatal term age. The data from the preterm infants at term was matched with a group of ten full-term babies a few days after birth.Results: The motor nerve conduction velocity of the tibial and ulnar nerves showed progressive increases in values in relation to gestational age, but there was a decrease of values in distal latencies and F wave latencies. Similarly, there was a gradual increase of sensory nerve conduction velocity values of the medial plantar and median nerves and decreases in latencies in relation to gestational age. At term age, the preterm infants showed significantly lower values of conduction velocities and distal latencies than the full-term neonates. These results were probably because the preterm infants had significantly lower weights, total length and, in particular, distal segments of the limbs at term age.Conclusion: The sensory-motor conduction parameters were clearly related to gestational age, but extrauterine life did not affect the maturation of the peripheral nervous system in the very preterm babies who were neurologically healthy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of a 55-year-old woman who suffered from systemic lupus erythematosus (SLE), thymoma, and pure red cell aplasia (PCRA).

Bulk heterojunction (BHJ) solar cells were fabricated employing different poly(3,4-ethylenedioxythiophene) (PEDOT) buffers: one deposited by electrochemical potentiostatic synthesis (perchlorate as counterion) and the other by casting a commercial polymer (polystyrene sulfonate, PSS, as counterion) on indium tin oxide (ITO) electrodes. The experimental conditions to electrosynthesize the PEDOT film and control its thickness were successfully investigated. [6,6]-phenyl-C butyric acid methyl ester (PCBM) was used as electron acceptor in the blend. As electron donor, either the regioregular poly(3-hexylthiophene) (P3HT) or a polythiophene copolymer, functionalized with a porphyrin derivative to improve the absorption of the layer in the visible range, was employed. The morphologies of the PEDOT and the photoactive layers were extensively investigated by atomic force microscopy. The performances of all devices were tested evaluating the power conversion efficiencies which resulted comparable when either PEDOT:ClO or PEDOT:PSS was used as buffer layer. That proves electrochemical deposition of PEDOT can represent a good alternative to casting for the production of solar cells, since it is less expensive and permits an excellent control of the layer thickness. [ABSTRACT FROM AUTHOR]

Most mutations that truncate the reading frame of the DMD gene cause loss of dystrophin expression and lead to Duchenne muscular dystrophy. However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin. Here we demonstrate that this isoform results from usage of an internal ribosome entry site (IRES) within exon 5 that is glucocorticoid inducible. We confirmed IRES activity by both peptide sequencing and ribosome profiling in muscle from individuals with minimal symptoms despite the presence of truncating mutations. We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject-derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice. These results support a potential therapeutic approach for patients with mutations within the 5′ exons of DMD. [ABSTRACT FROM AUTHOR]

Abstract: Small molecule chemistry is of central importance to a number of R&D companies in diverse areas such as the pharmaceutical, nutraceutical, food flavoring, and cosmeceutical industries. In order to store and manage thousands of chemical compounds in such an environment, we have built a state-of-the-art master chemical database with unique structure identifiers. Here, we present the concept and methodology we used to build the system that we call the Unique Compound Database (UCD). In the UCD, each molecule is registered only once (uniqueness), structures with alternative representations are entered in a uniform way (normalization), and the chemical structure drawings are recognizable to chemists and to a cartridge. In brief, structural molecules are entered as neutral entities which can be associated with a salt. The salts are listed in a dictionary and bound to the molecule with the appropriate stoichiometric coefficient in an entity called "substance". The substances are associated with batches. Once a molecule is registered, some properties (e.g., ADMET prediction, IUPAC name, chemical properties) are calculated automatically. The UCD has both automated and manual data controls. Moreover, the UCD concept enables the management of user errors in the structure entry by reassigning or archiving the batches. It also allows updating of the records to include newly discovered properties of individual structures. As our research spans a wide variety of scientific fields, the database enables registration of mixtures of compounds, enantiomers, tautomers, and compounds with unknown stereochemistries. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed 55 patients given a fixed dose of rituximab (200 mg) on day+5 after an alternative donor transplant, to prevent EBV DNA-emia; 68 alternative transplants who did not receive prophylactic rituximab served as controls. The two groups were comparable for donor type, and all patients received anti-thymocyte globulin in the conditioning regimen. Rituximab patients had a significantly lower rate of EBV DNA-emia 56 vs 85% (P=0.0004), a lower number of maximum median EBV copies (91 vs 1321/105 cells, P=0.003) and a significantly lower risk of exceeding 1000 EBV copies per 105cells (14 vs 49%, P=0.0001). Leukocyte and lymphocyte counts were lower on day +50 and+100 in rituximab patients, whereas Ig levels were comparable. The cumulative incidence of grade II-IV acute GvHD was significantly reduced in rituximab patients (20 vs 38%, P=0.02). Chronic GvHD was comparable. There was a trend for a survival advantage for patients receiving rituximab (46 vs 40%, P=0.1), mainly because of lower transplant mortality (25 vs 37%, P=0.1). Despite the drawback of a retrospective study, these data suggest that a fixed dose of rituximab on day +5 reduces the risk of a high EBV load, and also reduces acute GvHD. [ABSTRACT FROM AUTHOR]

Potentially viable therapeutic approaches for Duchenne muscular dystrophy (DMD) are now within reach. Indeed, clinical trials are currently under way. Two crucial aspects still need to be addressed: maximizing therapeutic efficacy and identifying appropriate and sensible outcome measures. Nevertheless, the end point of these trials remains painful muscle biopsy to show and quantify protein restoration in treated boys. In this study we show that PMMA/N-isopropil-acrylamide+ (NIPAM) nanoparticles (ZM2) bind and convey antisense oligoribonucleotides (AONs) very efficiently. Systemic injection of the ZM2–AON complex restored dystrophin protein synthesis in both skeletal and cardiac muscles of mdx mice, allowing protein localization in up to 40% of muscle fibers. The mdx exon 23 skipping level was up to 20%, as measured by the RealTime assay, and dystrophin restoration was confirmed by both reverse transcription-PCR and western blotting. Furthermore, we verified that dystrophin restoration also occurs in the smooth muscle cells of the dorsal skin arrector pili, an easily accessible histological structure, in ZM2–AON-treated mdx mice, with respect to untreated animals. This finding reveals arrector pili smooth muscle to be an appealing biomarker candidate and a novel low-invasive treatment end point. Furthermore, this marker would also be suitable for subsequent monitoring of the therapeutic effects in DMD patients. In addition, we demonstrate herein the expression of other sarcolemma proteins such as α-, β-, γ- and δ-sarcoglycans in the human skin arrector pili smooth muscle, thereby showing the potential of this muscle as a biomarker for other muscular dystrophies currently or soon to be the object of clinical trials. [ABSTRACT FROM AUTHOR]

Following a previous preliminary report on a group of children suffering from partial epilepsies, we present the final considerations on the same group in order to evaluate the long-term efficacy, tolerability and safety of oxcarbazepine (OXC). We enrolled 36 patients (mean age 8.5), between January 2003 and December 2004, with new diagnosis of partial epilepsy: 25 patients were affected by idiopathic partial epilepsy, eight by symptomatic epilepsy and three by cryptogenic epilepsy. Each patient was scheduled to attend the center four times after the initial examination: 3 months (T1), 12 months (T2), 24 (T3) months and 36 (T4) months after the beginning of OXC-monotherapy (T0). At the end of our study, 20 patients were seizure free (SF): nine stopped OXC because of SF for at least 2 years, 11 were still on therapy. One patient showed a reduction of seizure frequency ≥50%, three were non responders (but still on therapy), nine stopped OXC due to a non-responder condition during follow-up before T4 and one because of adverse effects. At the end of the study no EEG focal abnormalities became generalized because of treatment. Normalization of EEG was observed in ten patients. Our preliminary findings have been confirmed. OXC can be considered an effective and well tolerated first line drug for long-term monotherapy in children with epilepsy, both for idiopathic and symptomatic/cryptogenic forms. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic SCT (HSCT) has been used as treatment for single patients with autoimmune diseases (AD). To summarise currently available information, we analyzed all patients who underwent allogeneic HSCT for AD and who reported to the European Group for Blood and Marrow Transplantation (EBMT) database. Thirty-five patients receiving 38 allogeneic transplantations for various hematological and non-hematological AD were identified. Four patients had had an allogeneic HSCT for a conventional hematological indication in the past. Fifty-five per cent of the transplantation procedures led to a complete clinical response of the refractory AD and 23% to at least a partial response. The median duration of response at the last follow-up was 70.7 (15.2–130) months. Three patients relapsed at a median of 12.3 months after HSCT. Treatment-related mortality at 2 years was 22.1% (95% CI: 7.3–36.9%). Two deaths were caused by progression of AD. The probability of survival at 2 years was 70%. No single factor predicting the outcome could be identified. The retrospective nature of this study and the heterogeneous, partly incomplete data are its limitations. However, allogeneic HSCT can induce remission in patients suffering from refractory AD. These data provide the basis for carefully conducted prospective trials.Bone Marrow Transplantation (2009) 44, 27–33; doi:10.1038/bmt.2008.424; published online 12 January 2009 [ABSTRACT FROM AUTHOR]

OBJECTIVES:Little is known about the natural history and pathogenesis of small gallbladder polyps (<10 mm, usually of the cholesterol type), particularly in Western populations. It is unclear if these polyps and gallstones represent different aspects of the same disease. The aim of this study was to characterize the natural history and pathogenesis of small gallbladder polyps.METHODS:Fifty-six Caucasian patients with small gallbladder polyps, 30 matched gallstone patients, and 30 controls were enrolled in this 5-year prospective study. Patients underwent a symptomatic questionnaire, abdominal ultrasonography, and ultrasonographic evaluation of gallbladder motility at baseline and yearly intervals for 5 years. Cholesterol saturation index, cholesterol crystals in bile, and apolipoprotein E genotype were also determined.RESULTS:Most patients with polyps (mean size: 5.3 mm) were men (61%), asymptomatic, and had multiple polyps (57%). Polyps did not change in 91% of patients during follow-up. No subject experienced biliary pain or underwent cholecystectomy; four developed gallstones. Cholesterol saturation index was higher in patients with polyps or gallstones than in controls (P<0.05). Cholesterol crystals were more frequent in patients with polyps than in controls (P<0.0001) but less common than in gallstone patients (P<0.0001). Polyps and gallstones were associated with nonapolipoprotein E4 phenotypes.CONCLUSIONS:The natural history of small gallbladder polyps was benign, as no patient developed specific symptoms and/or morphological changes in polyps. Consequently, a “wait and see” policy is advisable in these patients. Polyps have some pathogenetic mechanisms in common with gallstones, but few patients developed gallstones.Am J Gastroenterol 2009; 104: 624–629; doi:10.1038/ajg.2008.99; published online 10 February 2009 [ABSTRACT FROM AUTHOR]

Extracorporeal photopheresis (ECP) was given to 23 patients with steroid-refractory acute GVHD (aGVHD, grade II (n=10), III (n=7) or IV (n=6)). The median duration of ECP was 7 months (1–33) and the median number of ECP cycles in each patient was 10. Twelve patients (52%) had complete responses. Eleven patients (48%) survived and 12 died, 10 of GVHD with or without infections and two of leukaemia relapse. The average grade of GVHD was reduced from 2.8 (on the first day of ECP) to 1.4 (on day +90 from ECP) (P=0.08), and the average dose of i.v. methylprednisolone from 2.17 to 0.2 mg/kg/d (P=0.004). Complete responses were obtained in 70, 42 and 0% of patients, respectively, with grades II, III and IV aGVHD; complete responses in the skin, liver and gut were 66, 27 and 40%. Patients treated within 35 days from onset of aGVHD had higher responses (83 vs 47%; P=0.1). A trend for improved survival was seen in grade III–IV aGVHD treated with ECP as compared to matched controls (38 vs 16%; P 0.08). ECP is a treatment option for patients with steroid refractory aGVHD and should be considered early in the course of the disease.Bone Marrow Transplantation (2008) 42, 609–617; doi:10.1038/bmt.2008.221; published online 28 August 2008 [ABSTRACT FROM AUTHOR]

We present new observations of seven late-type stars previously discovered in the First Byurakan Survey (FBS). These observations prove that they belong to the family of carbon (C) stars. Seventy-nine similar FBS C stars were previously known. The seven objects under analysis were presented in the FBS lists as M or C star candidates. Among the seven objects, six objects are confirmed by low-resolution spectra of the Hamburg Quasar Objective-Prism Survey. We also present for five of them moderate-resolution spectra obtained at optical wavelengths with a spectrograph equipped with a CCD detector. Three objects can be classified as N-type C stars. One object is an early CH-type C star. Most likely, the star FBS 1339+117 belongs to the group of carbon dwarfs. We estimate distances of these seven new C stars either by using their red-band magnitudes, or by using their near-infrared 2MASS J-KS color and KS-band magnitudes. [ABSTRACT FROM AUTHOR]

Aggressive forms of multiple sclerosis (MS) represent a limited group of demyelinating diseases that rapidly progress to severe disability. Currently available therapies are poorly effective against these clinical entities. Recently, it has been demonstrated that intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT) can affect the clinical course of individuals with severe MS and completely abrogate the inflammatory activity detected by MRI. We report the result of the Italian phase 2 GITMO study, a multicentre study in which 21 MS patients, who were rapidly deteriorating and not responding to the usual therapeutic strategies, were treated with this procedure. The clinical effect of the treatment is long lasting, with a striking abrogation of inflammation detected by MRI findings. These results support a role for intense immunosuppression followed by ASCT as treatment in rapidly evolving MS cases unresponsive to conventional therapies. [ABSTRACT FROM AUTHOR]

Summary:We have previously described a scoring system for patients undergoing hemopoietic stem cell transplantation (HSCT) based on day +7 blood urea nitrogen (BUN) and serum bilirubin levels. We have revised that scoring system using a formal multivariate approach based on a training phase (305 patients) and a validation phase (217 patients). Day +7 BUN, serum cholinesterase (CHE), total proteins (TP), gamma glutamyl transferase (?GT), donor type and cell dose at transplant were included in the new score. The score distribution identified three groups of patients in the training set (<25, 25-75, >75 percentile of the score) which were classified as low, intermediate and high risk. Their actuarial risk of transplant-related mortality (TRM) at 6 years was, respectively, 12, 38 and 60%. In the validation set the 6 year actuarial TRM was, respectively, 15, 40 and 69%. High risk patients had more graft-versus-host disease (GvHD) (P<0.0001) and lower platelet counts (P<0.0001). This study confirms that GvHD and TRM can be predicted on day +7 after HSCT: pre-emptive GvHD therapy may be one option for high-risk patients and is being tested in a prospective randomized trial. The score for single patients can be calculated on the web site http://213.26.110.20/lrm/day_seven_score.html.Bone Marrow Transplantation (2003) 32, 205-211. doi:10.1038/sj.bmt.1704085 [ABSTRACT FROM AUTHOR]