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The BXD recombinant inbred (RI) mouse strains are the largest and most deeply phenotyped inbred panel of vertebrate organisms. RIs allow phenotyping of isogenic individuals across virtually any environment or treatment. We performed whole genome sequencing and generated a compendium of SNPs, indels, short tandem repeats, and structural variants in these strains and used them to analyze phenomic data accumulated over the past 50 years.We show that BXDs segregate >6 million variants with high minor allele which are dervied from the C57BL/6J and DBA/2J founders and use this dense variant set to define ‘infinite’ marker maps and a novel family-level pangenome. We additionally characterize rates and spectra de novo variants which have accumulated over 20-200 generations of inbreeding, and have largely been ignored previously. Overall, the uniquely rich phenome when linked with WGS enables a new type of integrative modeling of genotype-to-phenotype relations.

BackgroundBesides the ability to induce antigen-specific responses, vaccines can be endowed with immunomodulatory properties including the capacity to induce or downregulate regulatory T cells (Treg) that suppress adaptative and autoreactive immune responses (1).ObjectivesWe asked if an anti-SARS-CoV-2 mRNA vaccine could also induce an accumulation of Treg cells in patients with mixed cryoglobulinemia vasculitis (MCV), who have a deficiency of Treg cells (2) and in healthy individuals. We also investigated immunologic variables possibly associated with a low immunogenicity of SARS-CoV-2 mRNA vaccine in patients with MCV (3).MethodsWe analyzed peripheral blood lymphocyte subpopulations and anti-SARS-CoV-2 serological response in 24 patients with MCV and 9 Healthy donors (HD) before and after 2 weeks after the second dose of the Pfizer/BioNTech vaccine.ResultsAmong MCV patients we found 15 serological responders and 9 non-responders. All 5 seronegative patients treated recently with rituximab had low B cells was significantly increased in seronegative patients.Before receiving the Pfizer/BioNTech vaccine, patients with MCV had a significantly reduced frequency of Treg cells among CD4+ T cells compared to HD. After the second dose of the vaccine, there was in MCV patients a significant increase in the percent and absolute count of Treg among CD4+ T cellsConcerning the pre-vaccination distribution of T cells subpopulations, including the percentages and absolute counts of total CD3+, CD4+, CD8+, HLA-DR+ activated, Treg or CD56+ natural killer T cells, we could not reveal any pattern significantly associated with lack of serological response to vaccine.ConclusionOur findings show that lack of immunoreactivity in patients with MCV may be associated with expansion of pathologic B cells and that anti-SARS-CoV2 mRNA vaccine may induce an increase of Treg cells.References[1]Krienke C. et al. A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science. 2021 Jan 8;371(6525):145-153.[2]Boyer O. et al. CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood. 2004 May 1;103(9):3428-30.[3]Visentini M. et al. Flares of mixed cryoglobulinaemia vasculitis after vaccination against SARS-CoV-2. Ann Rheum Dis. 2021 Nov 24:annrheumdis-2021-221248.Disclosure of InterestsNone declared

SARS-CoV-2 is a member of the family of coronaviruses. The first cases were recorded in Wuhan, China, between December 2019 and January 2020. Italy is one of the most affected countries in Europe. COVID-19 is a new challenge in modern dentistry. New guidelines are required in dental clinics to avoid contagion caused by cross-infections. A narrative review was performed using both primary sources, such as scientific articles and secondary ones, such as bibliographic indexes, web pages, and databases. The main search engines were PubMed, SciELO, and Google Scholar. Twelve articles were selected to develop the bibliographic review by applying pre-established inclusion and exclusion criteria. Precautionary measures should be applied to control COVID-19 in clinical practice. Several authors have highlighted the importance of telephone triage and/or clinic questionnaires, body temperature measurement, usage of personal protective equipment, surface disinfection with ethanol between 62% and 71%, high-speed instruments equipped with an anti-retraction system, four-handed work, and large-volume cannulas for aspiration. Clinically, the use of a rubber dam is essential. FFP2 (or N95) and FFP3 respirators, if compared to surgical masks, provide greater protection for health workers against viral respiratory infections. Further accurate studies are needed to confirm this.

We investigated the late Quaternary throw distribution of the main normal fault that ruptured during the Mw 6.5 2016 earthquake in central Italy by means of a high-resolution structure-from-motion (SfM)-derived Digital Surface Model (DSM). We focused on a key area along the Cordone del Vettore fault (CDV), which is part of the Vettore-Bove fault system (VBFS). The CDV displays a prominent compound post-glacial scarp that allowed the reconstruction of the along-strike cumulative throw distribution. We propose a geometric approach to calculate the CDV fault throw distribution from the reconstruction of a displaced glaciation-related erosional surface, used as a geomorphic marker, and a series of closely spaced cross profiles. The proposed calculation accounts for both the slip vector direction and the degraded scarp top, including field data on fault dip angles. Following this approach, we recognized two scarps with a minimum average fault throw of ~21 m and ~35 m for this section of the investigated fault strand. The correlation with the possible post-LGM (Last Glacial Maximum) deglaciation phases of the erosional surface suggests a minimum scarp age of 25–27 ka cal BP. Such an age provides a reasonable CDV fault throw rate of ~0.8 mm/a, comparable with known long-term throw rates of the VBFS and active Apennines normal faults. By comparing the reconstructed long-term Cordone del Vettore throw distribution with the 2016 coseismic one, ~24 2016-like surface faulting events are required to generate the main cumulative scarp, under the assumption of constant slip per event. This, along with the age of the scarp, yields an average earthquake recurrence time interval of ~1100 a. These results suggest the presence of multiple regional markers that correlates with different LGM (if not pre-LGM) major glacial phases, whose erosional processes allow the preservation of pre-existing bedrock fault scarp remnants.

We performed geophysical investigations in the northwestern sector of the island of Malta to reconstruct velocity-depth models and provide shear-wave velocity profiles. We have chosen two sites, one located in Rabat (Malta) and another in the Golden Bay area. We used both active (seismic and electrical 2D-tomography, Multichanel Analysis of Surface Waves – MASW) and passive (2D arrays and single-station measurements using ambient noise) geophysical methods. Consistently with previous studies performed in this part of Malta, we have found that both sites are characterized by site resonance in the frequency range 1–2 Hz as an effect of the local lithostratigraphic succession that shows an impedance contrast at about 60–90 m depth. This resonance effect can have important implications on both seismic hazard as well as seismic risk evaluation of the region since the amplified frequency range coincides with the resonance frequencies typical of 5–10 storey buildings which are very diffuse in the Maltese Islands, especially after intense recent urbanization. We also highlight the importance of performing seismic velocity measurements even at rock sites. As an example, the Golden Bay site would be classified as class “A” following the EuroCode EC8 when considering only the outcropping lithology represented by limestone rocks. Conversely the subsoil characterization provided by this study has revealed that this site falls in the EC8 class “B”, stressing the importance of direct geophysical measurements since the a-priori assignment to A-class could lead to wrong estimates in evaluating the site response.

On 24 August 2016, a Mw 6.0 normal faulting earthquake struck central Italy, causing about 300 fatalities and heavy damage. A geological survey collected the coseismic effects observed at the surface in order to evaluate two competing hypotheses about their nature: surface faulting versus gravitational deformation. We find that the most significant geological effect is a 5.2 km-long alignment of ground ruptures along the Mt. Vettore Fault-System. These ruptures are independent from lithology, topography, morphology and change in slope and exhibit an average dip slip displacement of ~13 cm. Geometry, kinematics and dimensional properties of this zone of deformation strongly lead us to favor the primary surface faulting hypothesis that fits well the predicted estimates from experimental scaling-law relationships. Our study provides relevant hints for surface faulting in extensional domains, contributing to implement the worldwide database of the moderate earthquakes.

International audience; We integrate paleoseismic data sets along the Mt. Vettore‐Mt. Bove normal fault system rupturing at the surface in the 30 October 2016 Norcia earthquake. Through the analysis of new trenches from this work and a review of the preexisting data, we correlate events among trench sites along antithetic and synthetic fault splays. We recognize seven M 6.5, 2016 Norcia‐type (or larger) surface‐faulting events in the last ~22 kyr, including 2016. Before 2016, one event occurred in the past two millennia (260–575 CE) and possibly corresponds to the event damaging Rome in 443 or 484/508 CE. Three previous events occurred between 10590 and 415 BCE, whereas the two oldest ones date between 19820 and 16540 BCE. The average recurrence time is 3,360–3,640 years for the last ~22 kyr and 1,220–1,970 years for the last ~4 kyr. We infer a minimum dip‐slip rate of 0.26–0.38 mm/year on the master fault in the central portion of the Mt. Vettore–Mt. Bove normal fault system and a dip‐slip rate of at least 0.10 mm/year on the southernmost portion. We infer a Middle–Late Pleistocene inception of the long‐term scarp of the investigated splays. The along‐strike variation of slip rates well reproduces the trend of the 2016 surface slip; thus, the time window exposed in the trenches is representative for the present fault activity. Based on trenching data, different earthquake rupture scenarios should be also considered for local hazard assessment.

Whether performed as a primary procedure or used to augment and support osseous reconstruction, tendon transfers are a key skill for the foot and ankle surgeon. Understanding the biomechanics preoperative and postoperatively is essential in performing appropriate procedures and in supporting patients through the rehabilitation process. Often the complexity of tendon transfer surgery is lost because it is deemed a soft tissue procedure and in theory should be less complex than osseous procedures. However, the dynamic nature of musculature and tendons require a deeper understanding of surgical and biomechanical concepts.

We applied a joint survey approach integrating time-domain electromagnetic soundings and single-station ambient vibration surveys in the Middle Aterno Valley (MAV), an intermontane basin in central Italy and the locus of the 2009 L'Aquila earthquake. By imaging the buried interface between the infilling deposits and the top of the pre-Quaternary bedrock, we reveal the 3-D basin geometry and gain insights into the long-term basin evolution. We reconstruct a complex subsurface architecture, characterized by three main depocenters separated by thresholds. Basin infill thickness varies from ~200-300 m in the north to more than 450 m to the southeast. Our subsurface model suggests a strong structural control on the architecture of the basin and highlights that the MAV experienced considerable modifications in its architecture over time. The buried shape of the MAV suggests a recent and still ongoing predominant tectonic control by the NW-SE trending Paganica - San Demetrio Fault System (PSDFS), which cross-cuts older ca. ENE- and NNE- trending extensional faults. Furthermore, we postulate that the present-day arrangement of the PSDFS is the result of the linkage of two previously isolated fault segments. We provide constraints on the location of the southeastern boundary of the PSDFS, defining an overall ~19 km-long fault system. This allows for earthquakes larger than M6.5. This study emphasizes the benefit of combining two easily-deployable geophysical methods for reconstructing the 3-D geometry of a tectonically-controlled basin. Our joint approach provided us with a consistent match between these two independent estimations of the basin substratum depth within 15%.

Castanea sativa e? una specie di notevole importanza economica sia per l'alimentazione che per il legno, ed e? ampiamente distribuita in Europa occidentale e nella regione del Caucaso. La diversita? e la struttura genetica dei popolamenti Europei di castagno sono il risultato combinato di fattori naturali e antropici. Infatti l'uomo fin dall'antichita? ha gestito i boschi naturali e ha selezionato varieta? attraverso tecniche selvicolturali o propagazione per innesto. Attualmente si possono osservare nella stessa area geografica frutteti e boschi naturali. Pertanto un'adeguata valutazione e gestione delle risorse genetiche del castagno, soprattutto a livello locale, non puo? prescindere da un'analisi approfondita della relazione genetica tra le popolazioni naturali e coltivati. Negli ultimi decenni sono state effettuate molte ricerche per valutare la diversita? genetica di popolazioni naturali e varieta? coltivate (Mattioni et al 2013; Martin et al 2010), tuttavia, pochi studi hanno comparato la variabilita? genetica e il flusso genico tra popolamenti naturali e coltivati localizzati in siti adiacenti. Il nostro lavoro ha i seguenti scopi 1) comparare la diversita? genetica dei popolamenti naturali e coltivati su scala locale e europea, e stimarne il flusso genico 2) verificare la natura autoctona o alloctona del germoplasma dei popolamenti coltivati. Utilizzando 6 marcatori microsatellitari sono state analizzate 6 popolazioni di castagno da frutto e 8 popolazioni di castagno selvatico, localizzati in siti adiacenti e provenienti da differenti aree geografiche (Spagna, Italia, Grecia e Turchia). Mediante il software GenAlEx 6 e? stato possibile calcolare i principali indici di diversita? genetica e flusso genico. L'analisi della struttura della popolazione e? stata condotta utilizzando il software STRUCTURE 2.3.3 ed e? stata spazialmente visualizzata mediante ArcGIS 9.3. Dall'analisi dei dati emerge che le popolazioni di castagno da frutto mostrano valori molto variabili di diversita? e di divergenza genetica dalle popolazioni selvatiche adiacenti nelle diverse aree geografiche esaminate. Inoltre l'analisi della struttura genetica mostra che in alcune aree geografiche le popolazioni di castagno da frutto e selvatico condividono lo stesso pool genico, mentre in altre aree geografiche le popolazioni da frutto risultano chiaramente alloctone rispetto alle popolazioni selvatiche. Questo studio ha permesso di valutare il livello della pressione selettiva dovuta all'attivita? umana, il livello di scambio genico tra i popolamenti coltivati e quelli selvatici offrendo cosi? uno strumento per valutare in modo piu? approfondito le risorse genetiche del castagno in funzione di eventuali programmi di gestione e conservazione delle risorse genetiche.

The detection of volatile organic compounds (VOCs) is an always current topic that widely attracts the scientific community for being crucial in several applications mainly related to environment, health and industrial processes monitoring. Among the VOCs, ethanol is a common organic vapour frequently employed as reference parameter for food quality control, fermentation process or human breath thus resulting in an increasing request of low-cost, eco-compatible ethanol sensors able to work at room temperature. Such objective can be pursued by merging new material sensing properties with eco-sustainable fabrication processes and substrates. In this framework, the inkjet printing (IJP) technology, a deposition method from liquid phase, well addresses this demand for its patterning capability, which permits an efficient use of different functional inks so reducing the amount of waste products, and the employable (nonflexible and flexible) substrates. The latter issue promotes the use of paper as low cost and eco-sustainable substrates. In this perspective, we fabricated an ethanol chemiresistor by IJP an aqueous suspension of graphene-like (GL) layers. The sensing ink was prepared through a two steps oxidation/reduction method starting from a nanostructured carbon black [1,2]. GL layers as other graphene related materials present interesting properties for sensing applications at room temperature: high conductivity and stability, large specific surface areas and tunable performances. The GL layers-based ink was deposited by IJP onto glossy paper where interdigitated Cr/Au electrodes were previously e-beam evaporated. The printing parameters were optimized in order to obtain uniform, conductive and reproducible sensing films. The final sensor device was exposed to 50 ppm of ethanol at RT in dry N2, setting the voltage at 1 V. Differently from pristine graphene that is completely insensitive to ethanol, GL material shows a conductance variation when exposed to this analyte. This sensitivity may be attributable to adsorption or desorption of molecules on the surface of the GL layers film assisted by the presence of residual oxygen functional groups, mainly carboxylic groups, as confirmed by X-ray Photoemission Spectroscopy.

Chestnut, as multipurpose tree species, is, among forest trees, a non classical model for population, evolutionary and ecological genomic studies. Because of its different domestication levels, it has undergone to both natural and artificial selection pressure which have shaped its present genetic and phenotypic variation. For this reason, understanding the genetic basis of its adaptive variation needs, necessarily, an integration of different disciplines and methods in order to develop appropriate strategies for conservation and utilization of its genetic resources for both ecological and economic purposes. During the last decades, traditional methods such as provenance tests and screening of molecular genetic markers have been used separately to study and measure adaptive genetic diversity in European chestnut. Recently, new approaches have been developed that combine the use of functional and neutral markers to define the genetic mechanisms of variation at landscape level. In the present paper, an overview of traditional and new approaches, used to study genetic and adaptive variation in Castanea sativa, are reported.

The Tomographic Gamma Scanning (TGS) technique is a relatively new method in the field of non-destructive assay (NDA) of radioactive waste. The TGS technique combines High Resolution Gamma Spectrometry (HRGS) with Three-Dimensional (3-D) low spatial resolution transmission and emission image reconstruction techniques to achieve assay goals. When compared to the traditional methods such as Segmented Gamma Scanning (SGS), the TGS technique can yield better accuracies for cases where the radionuclide is distributed non-uniformly in a heterogeneous matrix. The TGS technique is ideally suited for low-to-moderate density waste matrices, say 1.0 g cm −3 or below for 55 US gal. drums, although it can be extended to higher densities by using alternative approaches to the design or analyses. Recently Canberra Industries designed, built and characterized four such TGS systems for nuclear power plant applications. Many of the design features and the end application itself set these TGS systems apart from the others that had been built previously. The four TGS systems are the first commercial grade systems that could quantify radionuclides contained in nuclear power plant waste, using the TGS technique. The TGS systems featured two different combinations of collimator and source–detector distance; a “near” geometry with a collimator aperture of 50.8 mm and a “Far” geometry with a narrower collimator aperture of 40.6 mm. For assaying drums with matrix densities greater than 1.0 g cm −3 and/or dose rates greater than 6 mSv h −1 the system could be configured as a SGS. In the SGS mode, five different assay geometries could be configured using different collimator, source-to-detector distance and absorber combinations. During operation, the appropriate assay geometry was selected automatically based on the drum weight (density) and dose rate measurements. The characterization and performance of the one of the TGS systems are discussed in detail for both TGS and SGS modes of operation. Quantitative results are presented for point source and rod source nuclide distributions. Transmission and emission images obtained in the TGS assays will be presented.

The Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) presents an overview of the techniques and methodologies of presurgical evaluation and of the surgical treatment of epilepsies. This overview is the result of the experience developed in the past years in the major Italian centers where programs of epilepsy surgery have been established, and it has the aim of offering a quick and easy reference tool for those involved in the treatment of patients with epilepsy. The sharing of different experiences has the additional aim of conforming and disseminating the employed techniques as well as the methods of selection and evaluation of patients. The synthetic coverage of the main issues concerning the presurgical workup and the available surgical options will hopefully provide a framework that may integrate and develop the contributions of every single center, in one of the more complex, challenging, and dynamic areas of neurological sciences.

Introduction: Neuro-vascular rearrangement occurs in brain disorders, including epilepsy. Platelet-derived growth factor receptor beta (PDGFRβ) is used as a marker of perivascular pericytes. Whether PDGFRβ + cell reorganization occurs in regions of neuro-vascular dysplasia associated with seizures is unknown. Methods : We used brain specimens derived from epileptic subjects affected by intractable seizures associated with focal cortical dysplasia (FCD) or temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Tissues from cryptogenic epilepsy, non-sclerotic hippocampi or peritumoral were used for comparison. An in vivo rat model of neuro-vascular dysplasia was obtained by pre-natal exposure to methyl-axozy methanoic acid (MAM). Status epilepticus (SE) was induced in adult MAM rats by intraperitoneal pilocarpine. MAM tissues were also used to establish organotypic hippocampal cultures (OHC) to further assess pericytes positioning at the dysplastic microvasculature. PDGFRβ and its colocalization with RECA-1 or CD34 were used to segregate perivascular pericytes. PDGFRβ and NG2 or IBA1 colocalization were performed. Rat cortices and hippocampi were used for PDGFRβ western blot analysis. Results: Human FCD displayed the highest perivascular PDGFRβ immunoreactivity, indicating pericytes, and presence of ramified PDGFRβ + cells in the parenchyma and proximal to microvessels. Tissues deriving from human cryptogenic epilepsy displayed a similar pattern of immunoreactivity, although to a lesser extent compared to FCD. In TLE-HS, CD34 vascular proliferation was paralleled by increased perivascular PDGFRβ + pericytes, as compared to non-HS. Parenchymal PDGFRβ immunoreactivity co-localized with NG2 but was distinct from IBA1 + microglia. In MAM rats, we found pericyte-vascular changes in regions characterized by neuronal heterotopias. PDGFRβ immunoreactivity was differentially distributed in the heterotopic and adjacent normal CA1 region. The use of MAM OHC revealed microvascular-pericyte dysplasia at the capillary tree lining the dentate gyrus (DG) molecular layer as compared to control OHC. Severe SE induced PDGFRβ + immunoreactivity mostly in the CA1 region of MAM rats. Conclusion: Our descriptive study points to microvascular-pericyte changes in the epileptic pathology. The possible link between PDGFRβ + cells, neuro-vascular dysplasia and remodeling during seizures is discussed.

Castanea sativa is a multipurpose species widely distributed across Europe. Man has influenced the structural and genetic characteristics of chestnut populations through propagation and transplanting, intensive cultivation and selvicultural practices. The goals of this study were to 1) evaluate the genetic diversity and gene flow of wild and cultivated populations at wide and local scale 2) identify possible alloctonous material as a result of human domestication activities. Six natural and 8 orchard populations, were collected in three different geographical areas Six nuclear microsatellite markers were used for the molecular analysis. Observed (Na) and effective (Ne) number of alleles, observed (Ho) and expected (He) heterozygosity, were calculated using the program GeneAlEx 6. Population structure analysis was conducted using the software STRUCTURE 2.3.3. The geospatial structure of chestnut populations was visualized using ArcGIS 9.3 software Orchard populations compared to natural stands showed lower values for all gene diversity parameters. In some cases, the structure analysis reveals the same gene pools for natural and orchard populations collected in the same areas, in other cases the orchard populations are genetically similar to natural population collected in distant geographical areas. The results were discussed considering the human activity and the different management of genetic resources.

Physical and biological processes are the main causes for spoilage. Many technological solutions have been developed to stabilize products, obtaining a shelf life suitable for marketing and distribution demands. A novel packaging technology (Modified Atmosphere Packaging - MAP) was proved to be quite useful for fresh horticultural product preservation, being capable to keep for a relative long time the original hygienic and sensory quality of these products, by simply modifying the gas composition in the package headspace. This research concerns the application of this packaging technology on melon slices (Cucumis melo L. var. reticulatus 'Zagar'): a ready to eat product, which before distribution and use, undergoes some preliminary processes (washing, peel and seeds elimination, cut and packaging). Melon samples were packaged in trays containing three different gas mixtures: A = 78% N 2 , 21% O 2 , 1% CO 2 (assumed as control); B = 90% N 2 , 5% O 2 , 5% CO 2 and C = 85% N 2 , 10% O 2 , 5% CO 2 . Each tray was stored at 4±1°C for 10 days. During this period, microbiological, sensory and instrumental analyses were performed after 4, 7 and 10 days of storage, so to get informations on product quality decay, its sensory profile evaluation and the nature of physical, chemical or biological degradative phenomena.

Purpose Radiation therapy (RT) alone can cure more than 80% of all patients with pathologic stage IA, IB, and IIA Hodgkin's disease, but some prognostic factors unfavorably affect treatment outcome. Combined-modality approaches improved results compared with RT, but the optimal extent of RT fields when combined with chemotherapy warranted additional evaluation. Patients and Methods In February 1990, we activated a prospective trial in patients with early, clinically staged Hodgkin's disease to assess efficacy and tolerability of four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by either subtotal nodal plus spleen irradiation (STNI) or involved-field radiotherapy (IFRT). Results Main patient characteristics were fairly well balanced between the two arms. Complete remission was achieved in 100% and in 97% of patients, respectively. The 12-year freedom from progression rates were 93% (95% CI, 83% to 100%) after ABVD and STNI, and 94% (95% CI, 88% to 100%) after ABVD and IFRT, whereas the figures for overall survival were 96% (95% CI, 91% to 100%) and 94% (95% CI, 89% to 100%), respectively. Apart from three patients who developed second malignancies in the STNI arm, treatment-related morbidities were mild. Conclusion Present long-term findings suggest that, after four cycles of ABVD, IFRT can achieve a worthwhile outcome. The limited size of our patient sample, however, had no adequate statistical power to test for noninferiority of IFRT versus STNI. Despite this, ABVD followed by IFRT can be considered an effective and safe modality in early Hodgkin's disease with both favorable and unfavorable presentation.

Purpose To analyze the genetic variability in a variable number of tandem repeats (VNTR) in the thymidylate synthase (TS) enhancer promoter region and assess the influence of functional alterations in mismatch repair genes by analyzing constitutional and tumoral DNA from patients with colorectal adenocarcinoma with a high microsatellite instability (MSI-H) or microsatellite stability (MSS) status. Patients and methods Patients who underwent surgery for colorectal adenocarcinoma were selected from the colorectal database of our institute and, on the basis of MSI status, assigned to a study group and a control group: group A, MSI-H; group B, MSS. Microsatellite status was investigated using the Bethesda recommended panel (BAT-26, BAT-25, D2S123, D5S346, D17S250). In MSI-H patients an additional analysis was made of the microsatellite loci D18S61 and D18S58, both mapping in the region containing the TS gene (18p11.2–11.32). Based on the number of altered microsatellites (≥2, 1, or 0), tumors were considered as having high (MSI-H) or low (MSI-L) instability or microsatellite stability (MSS), respectively. Genotyping for thymidylate synthase promoter polymorphism was carried out on constitutional and tumor DNA of each patient by PCR amplification of the polymorphic region. Results MSI-H was found in 55 patients (group A) and MSS in 50 patients (group B). In none of the MSI-H patients was microsatellite instability found in the additional D18S61 and D18S58 loci. In five group A and ten group B cases the analysis was not performed because constitutional DNA and/or tumoral DNA were not amplifiable. Homozygotes for the triple repeat variant (3R/3R) displayed only the large PCR product, homozygotes for the double repeat variant (2R/2R) displayed only the smaller PCR product, while heterozygotes (2R/3R) displayed both the larger and smaller PCR products. In 3/50 (6%) group A patients and 5/40 (12%) group B patients repeat variations were found in tumoral DNA. Conclusion Our findings demonstrate that there is genetic homogeneity between constitutional and tumoral DNA but do not support the hypothesis that mismatch repair genes are involved in VNTR recombinant events in TS gene variability.

We describe a 64-year-old patient complaining of progressive gait disturbance, referred to the compressive effect of multiple discal protrusions, for about 3 years. At the age of 62 he presented epileptic seizures during a febrile episode. Cerebral MRI showed bilateral frontobasal T2-weighted hyperintensity involving cortex and white matter. Partial seizures reappeared one year later and a MRI revealed a mild frontobasal atrophy. At the moment of our observation, neurological examination showed waddling gait with bilateral foot drop, muscular atrophy and weakness limited to the gluteal muscles and widespread deep tendon areflexia. Nerve conduction studies showed absent F-waves at both upper and lower limb examination, with normal distal sensorimotor nerve conduction. Needle EMG examination detected mild chronic partial denervation, predominant in proximal muscles of lower limbs. Somatosensory evoked potentials recorded from upper extremities showed bilateral increase in early latencies (N9). Overall, neurophysiological findings indicated a widespread radiculopathy. Serum exams revealed positive anti-nucleus (1:640, granular). CSF examination detected increased IgG level and several oligoclonal bands. Chest radiogram was normal. Soon after our first observation, the patient showed symptoms of respiratory insufficiency. A CT scans revealed a thoracic mass compatible with microcytoma, whereas anti-Hu (3 +) antibodies and increased NSE (neuronal specific enolase) titer were found. In the following two weeks, the patient showed a progressive worsening of the general clinical conditions and died. We interpreted this complex neurological picture, which included an atypical limbic encephalitis and a slowly progressive polyradiculopathy, as a paraneoplastic syndrome. The almost complete resolution of the encephalitic process and the subtle chronic involvement of the peripheral nervous system, characterized by a limited, though widespread, radicular impairment, are rather peculiar features.

This study was carried out in order to analyze the effect of silvicultural treatment on the structure and productivity of the chestnut stands, on the disease evolution and on the genetic structure of the species. The study considered a coppice stand aged 35 years (1994), growing on Monte Amiata (Tuscany, Italy). In the winter of 1994–1995, a low thinning of moderate intensity was applied; all suppressed shoots were removed, the intermediate class was partially reduced while the dominant storey was lightly thinned. Before, and after thinning, a description of stand structure, evaluation of number and typology of cankers caused by Cryphonectria parasitica on each tree and characterization of genotypical profile of all stumps was carried out. The structural and pathological surveys were repeated in February 1997 in order to analyze the growth trend of the stand and to verify the incidence and the evolution of disease two years after thinning. The results show that the applied silvicultural system neither reduced the genetic variability nor influenced the genotypic distribution of the stand. The removal of virulent cankers and the reduction of the individual susceptibility by the selection of the most vigorous trees has a positive effect on pathogen evolution.

Resume Objectif L’objectif de cette etude etait d’evaluer la capacite de la greffe de peau a prevenir la recidive de formes agressives de maladie de Dupuytren. Patients et methode Dix-huit patients presentant une forme bilaterale et recidivante de maladie de Dupuytren et traites par dermofasciectomie, et greffe de peau sur au moins une main ont ete revus avec un delai moyen de 8,8 ans apres la greffe. Resultats Seuls deux patients (11 %) presentaient une diathese complete de maladie de Dupuytren, telle que definie par Hueston, confirmant le caractere difficilement previsible des formes recidivantes. Toutes interventions chirurgicales confondues, chaque patient a ete opere en moyenne 3,6 fois. Treize patients ont ete greffes d’un seul cote et cinq de facon bilaterale. La maladie a recidive sous la greffe dans trois cas (13 %) et dans tous les cas du cote non greffe. Enfin, huit complications ont ete notees, trois peroperatoires et cinq postoperatoires. Conclusion La greffe de peau a ete efficace dans la prevention des recidives sur 20 mains des 23 mains greffees (78 %), a plus de huit ans de recul. Ces formes etant difficiles a identifier lors de l’anamnese et de l’examen clinique initial, la realisation d’une greffe de peau en premiere intention reste discutee. Son indication semble pouvoir etre plus large lorsque la recidive est averee.

The helium jet system was designed to transfer different mass fission fragments with nearly equal efficiency. Relative efficiency measurements made with an X-ray detector comparing helium-jet transferred activity to “rabbit” -shuttle transferred activity verify that the transfer efficiency is essentially a constant except for isotopes of noble gases (krypton and xenon) which do not “stick” to the catcher at the exit of the He-jet.

PURPOSE To define the maximum-tolerated dose (MTD) and better tolerated sequence of paclitaxel by 3-hour infusion plus bolus doxorubicin (DOX) and to evaluate antitumor efficacy. PATIENTS AND METHODS Thirty-five women with metastatic breast cancer (dominant visceral metastases in 56%, and involvement of > or = three sites in 67%) who never received chemotherapy of any type were studied. Paclitaxel every 3 weeks (125 mg/m2 starting dose) was increased by 25-mg/m2 steps in subsequent cohorts of patients. DOX (60 mg/m2 fixed dose) was administered 15 minutes before the start of or after the end of paclitaxel for a maximum of eight cycles. Subsequently, patients in continuous response could receive single-agent paclitaxel (175 to 200 mg/m2 every 3 weeks). The drug sequence was alternated in consecutive patients and in the first two cycles. RESULTS Severe neutropenia that lasted greater than 7 days (n = 4), febrile neutropenia (n = 7) and grade III oral mucositis (n = 6) defined the MTD of paclitaxel at 200 mg/m2 in 34 assessable patients. Grade II peripheral neuropathy occurred in 33% of patients. Six women (18%) developed clinically reversible congestive heart failure (CHF) after a median of 480 mg/m2 total DOX. Drug sequence had no effect on toxicities. High efficacy on all metastatic sites in 32 assessable patients accounted for a 41% complete response (CR) rate (95% confidence interval [CI], 24% to 59%) and 94% overall-response rate (95% CI, 79% to 99%). After a median follow-up of 12 months (range 3 to 18), the median response duration is 8 months (range, 2+ to 18+) for complete responders and 11 months (range 1+ to 15+) for partial responders. CONCLUSION The rate of CR and incidence of CHF may be an expression of therapeutic and toxic enhancement due to the schedule used in this trial. Until clarification of this possibility, this promising combination should be used in investigational trials.

Treatment of painful neuromas of the upper limb has been largely debated. The current surgical treatments spare from simple neuroma excision to proximal nerve stump relocation (into muscles, veins, and bones). Perineural fat grafting consists of neuroma excision and the creation of an autologous adipose graft wrapped around the proximal nerve stump. This technique should be prescribed to those patients suffering from terminal neuromas or neuromas in which functional reconstruction is contraindicated. The effectiveness of this technique could be addressed both to the mechanical and biological properties of the fat graft. On one hand the graft creates a gliding layer and a protective barrier, thus allowing longitudinal excursion and protection against mechanical solicitations. On the other hand the autologous adipose tissue brings neoangiogenesis, modulates the inflammatory response, and avoids scar adherences. A retrospective analysis was performed on 7 neuromas in 7 patients, treated with perineural fat grafting from June 2009 to February 2010. Pain and limb functionality were measured, respectively, with a visual acuity scale and the "Disabilities of the Arm, Shoulder, and Hand score," preoperatively and 1 year after surgery. A mean pain reduction of 23% was recorded, without relevant complications. Improvements in limb functionality were also observed through the measurement of the Disabilities of the Arm, Shoulder, and Hand score, which improved to 18%. We believe that this technique represents a valuable and versatile option in the treatment of painful neuromas of the upper limb that could be hereafter performed for pain syndromes of neuropatic origin.

Trapeziometacarpal prosthesis by metallic implant is used to treat thumb carpometacarpal osteoarthritis. Many causes of failure have been described whereas revision techniques still remain a challenging surgery. In this article, we describe a revision strategy in a failed metallic cemented trapeziometacarpal implant with major first metacarpal shortening.

The aim of this study is to assess outcomes of a lateral surgical approach for proximal interphalangeal joint arthroplasty with NeuFlex® silicone implants for primary degenerative osteoarthritis. We reviewed 51 arthroplasties performed on 43 patients. The mean follow up period was 36 months (range 18–42). The average preoperative range of motion (ROM) was 38°. The average postoperative ROM was 63°. In 21/51 (41%) cases, there was an average axial deviation of 17° (range 10–30°). VAS and Quick DASH scores improved. In 5/51 (10%) cases, further surgery was required. Our lateral approach seems to be effective and minimally invasive, providing adequate exposure. Contralateral incision and contralateral ligament reinforcement should be performed, whenever necessary, to improve lateral stability.

We report an atypical presentation of squamous cell carcinoma (SCC) of the distal phalanx of the left thumb. On physical examination, there was no clinical evidence of a local lesion, but magnetic resonance imaging (MRI) showed multiple intraosseous cavities filled with fluid. A biopsy specimen showed a well-differentiated SCC, which was treated by amputation of the distal phalanx.