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Research on the cerebellum and its functional organization has significantly expanded over the last decades, expanding our comprehension of its role far beyond motor control, including critical contributions to cognition and affective processing. Notably, the cerebellar lateralization mirrors contralateral brain lateralization, a complex phenomenon that remains unexplored, especially across different stages of life. The present work aims to bridge this gap by providing a comprehensive scoping review of the lateralization of motor, cognitive, and affective functioning within the cerebellum across the lifespan. A methodical search in electronic databases (i.e., PubMed, Embase, and PsycINFO) was conducted up to October 2024, focusing on neuroimaging studies with healthy participants of all ages performing motor, cognitive, or affective tasks. Our selection process, which involved multiple independent reviewers, identified 128 studies reporting cerebellar asymmetries in individuals from early childhood to older age, with a significant portion of studies regarding young-middle adults (19–45 years old). The majority of the findings confirmed established lateralization patterns in motor and language processing, such as ipsilateral motor control and right-lateralized language functions. However, less attention has been paid to other cognitive functions and affective processing where more heterogeneous and less consistent asymmetries have been observed. To the best of our knowledge, this scoping review is the first to comprehensively investigate the motor, cognitive, and affective functional lateralization of the cerebellum across lifespan, highlighting previously overlooked dimensions of cerebellar contributions. [ABSTRACT FROM AUTHOR]

Background: Peritoneal dialysis (PD) catheter related infections continue to be a major cause of morbidity and transfer to hemodialysis (HD) in PD patients. The treatment of tunnel infection (TI) could be challenging, especially when the infection involves the superficial cuff requiring the removal of the catheter. To spare the patient the loss of the catheter and the transfer to HD, several mini-invasive surgical techniques have been proposed as rescue therapy. Furthermore, nowadays, the rapid growth of digital technology has enormously increased the diagnostic sensibility of the echo signal allowing to accurately defines the extent of the infectious process along the PD catheter tunnel. Methods: Between 1st January 2020 and 31st December 2021 seven patients who underwent exit-site relocation by external splicing and cuff removal at our institution due to refractory TI were included in the study. All patients were followed until 12 months after the procedure. As soon as TI was defined refractory to the medical therapy, an ultrasonographic examination of the catheter tunnel was performed to define the extent of the infectious episode. Results: Among the 7 infectious episodes, 4 were caused by P. aeruginosa, and 3 by S. aureus. Around the superficial cuff the hypo/anechoic collections detected by ultrasounds showed a mean diameter of 3.05 ± 0.79 mm. The exit-site relocation by external splicing and cuff removal was successful in all cases (7/7, 100%). Conclusions: In our experience the use of exit site relocation by external splicing and cuff removal as rescue therapy for TI with positive ultrasounds for TI limited to superficial cuff involvement and without secondary peritonitis, yielded to promising results with a success rate of 100%. This preliminary experience underlines the paramount usefulness of tunnel echography in accurately defining the extent of TI and, consequently, guiding the choice of the therapeutical approach in refractory TI. [ABSTRACT FROM AUTHOR]

In hospital environments, droplets generated by urination within shared toilets may represent a route of dissemination for bacteria such as vancomycin-resistant Enterococcus faecium (VREfm), which contributes significantly to the burden of hospital-acquired infections. We investigated the potential activity of a foam in preventing the generation of droplets containing Enterococcus spp. during urination. A uniform layer of foam was deposited in the inner walls and at the bottom of an experimental toilet contaminated with suspensions of Enterococcus strains (including a VREfm strain). Human urination was simulated, and colonies of Enterococcus were recovered through a toilet lid where agar plates had been placed. Results showed that the foam was able to suppress production of droplets containing Enterococcus spp. generated by a liquid hitting inner toilet walls. Conversely, Enterococcus colonies were recovered in absence of foam. Moreover, the foam did not show antibacterial activity. We propose a new non-antimicrobial approach aimed at limiting transmission of multidrug-resistant bacteria, particularly in healthcare settings. [ABSTRACT FROM AUTHOR]

Despite the study of subterranean biodiversity facing harsh sampling and mapping challenges, the huge diversity of taxa, ecological adaptations and evolutionary trajectories in subterranean environments is gaining increasing attention. Yet, the spatial and environmental factors driving the composition of groundwater communities are still poorly understood. To partially fill this knowledge gap, we collected copepod crustaceans from 12 caves along the Italian peninsula between 2019 and 2022, sampling each cave twice. The resulting presence-absence data were analysed to assess: (i) between-cave taxonomic beta diversity, also partitioning between turnover and nestedness-resultant dissimilarity; (ii) the relative weight of geographic distance and climatic differences in shaping observed beta diversity. Seventy-one species of copepods were collected overall. Pairwise beta diversity was high for most pairs of caves, with turnover being the major component. Geographic distance-decay models partially explained total beta diversity and turnover patterns. However, in Generalized Dissimilarity Models (GDM), including surface climatic conditions as predictors, the contribution of seasonal temperature averages was generally higher than that of geographic distance. Further, the explanatory and predictive performance of the GDMs notably increased, along with temperature contribution, when widening the spatial extent from which climate data were gathered. Our results confirmed a high spatial turnover in groundwater copepods' assemblages and strengthened the link between regional climate and subterranean biodiversity. [ABSTRACT FROM AUTHOR]

The freshwater resource in karst is subjected to both sea level rise and an increasing pressure caused by the high-water demand. Therefore, developing an understanding of the hydrogeological dynamics of the karst aquifer can be a useful tool for improving protection and management actions. Vora Bosco cave (Apulia, Southern Italy) was instrumented with a multi-parameter probe for groundwater level measurements, aimed at exploring the system behavior within the cave recharge area. To characterize and quantify the natural recharge and discharge behavior of the system, a simple reservoir model was developed, initially also with the intention of predicting groundwater dynamics. Based on the original time-series of water level observations, different calibration datasets were established using different split-sample and bootstrapping approaches, and a regional sensitivity analysis was executed. Furthermore, in addition to the original observation time-series, a 3-month extension was used as a model testing period. Using these analyses, the parameters identifiability and the predictions robustness for the model testing period were evaluated. Results reveal that while the calibration on the whole dataset, as well as the bootstrapping approaches, lead to better performances in the calibration and validation period of the original time-series, and to a higher model precision with smaller uncertainty ranges. their performance in the model testing period becomes very poor and the observed water level data no longer plots within the uncertainty bands. Based on this extensive analysis, the model is finally rejected. Our study therefore also confirms the importance of model validation, especially when only a short time-series of observations are available. [ABSTRACT FROM AUTHOR]

The southern Albania coast, about 147 km long, represents one of the fastest growing areas of the country for tourism and local economy, resulting in serious problems concerning water supply. Due the karst nature of the territory, groundwater is the only remaining promising resource. The aim of this research is to describe the main characteristics and influencing factors on karst groundwater quantity and quality and the drainage type in the study area. In general, the area is very rich in groundwater resources; the estimated total renewable karst water resources being about 20 m3/s. Based on the different geological-structural conditions and the development of karst processes, their drainage occurs in different ways. Five main types of drainage can be distinguished along the Southern Albanian coast: (a) overflowing springs, (b) descending springs, (c) coastal springs, (d) submarine spring, and (e) diffuse drainage. Regarding water quality, only the overflowing springs have a good quality, due to the presence of impervious rocks isolating freshwater from the sea water. Good-quality springs represent 28% of the total discharge of karst water resources drained to the Adriatic and Ionian Seas. In addition, the situation becomes more difficult, because about 83% of the fresh quality karst water resources drain along a 1.5 km-long coastal strip located in the northernmost sector of the studied area. Beside this, the strong increase in population, particularly during the summer due tourism activities, as well as construction of new urban areas, are the main sources of likely pollution for some of the good-quality springs. The high anthropic pressure on groundwater resources increases the seawater intrusion phenomena, reducing the availability of freshwater resource and in specific areas, contributing to spring salinization. [ABSTRACT FROM AUTHOR]

Lactic acidosis has been reported in solid tumor microenvironment (TME) including glioblastoma (GBM). In TME, several signaling molecules, growth factors and metabolites have been identified to induce resistance to chemotherapy and to sustain immune escape. In the early phases of the disease, microglia infiltrates TME, contributing to tumorigenesis rather than counteracting its growth. Insulin-like Growth Factor Binding Protein 6 (IGFBP6) is expressed during tumor development, and it is involved in migration, immune-escape and inflammation, thus providing an attractive target for GBM therapy. Here, we aimed at investigating the crosstalk between lactate metabolism and IGFBP6 in TME and GBM progression. Our results show that microglia exposed to lactate or IGFBP6 significantly increased the Monocarboxylate transporter 1 (MCT1) expression together with genes involved in mitochondrial metabolism. We, also, observed an increase in the M2 markers and a reduction of inducible nitric oxide synthase (iNOS) levels, suggesting a role of lactate/IGFBP6 metabolism in immune-escape activation. GBM cells exposed to lactate also showed increased levels of IGFBP6 and vice-versa. Such a phenomenon was coupled with a IGFBP6-mediated sonic hedgehog (SHH) ignaling increase. We, finally, tested our hypothesis in a GBM zebrafish animal model, where we observed an increase in microglia cells and igfbp6 gene expression after lactate exposure. Our results were confirmed by the analysis of human transcriptomes datasets and immunohistochemical assay from human GBM biopsies, suggesting the existence of a lactate/IGFBP6 crosstalk in microglial cells, so that IGFBP6 expression is regulated by lactate production in GBM cells and in turn modulates microglia polarization. [ABSTRACT FROM AUTHOR]

In a previous study we detected that a number of inquiry stages (data collection, analysis and conclusions) went unnoticed by the students of an in situ joint online/onsite master's degree via online teaching. In this paper we analyse the effect of improved instruction, in which students fully experienced and became aware of all the stages that comprise the inquiry-based teaching approach. In the article we show the differences between the initial and improved instruction. The comparison of student comments as exhibited in the online class diary forum between the initial and improved instruction has allowed us to analyse the influence of this improvement in the level of depth of the students' discourse. Two codings have been employed to analyse the forums: the first (deductive) detected which stages of inquiry appeared in the comments. The second (inductive) involved the recoding of each of the previously classified comments based on five levels of communicative quality that emerged. Our main finding was that as well as being more aware of the different stages of inquiry, the students of the improved investigation were able to explain and identify them with specific examples. In other words, the investment of time in developing each of the stages in question helped them to define, afford reality to, and increase the explicative quality of their comments. [ABSTRACT FROM AUTHOR]

Winnie, a mouse carrying a missense mutation in the MUC2 mucin gene, is a valuable model for inflammatory bowel disease (IBD) with signs and symptoms that have multiple similarities with those observed in patients with ulcerative colitis. MUC2 mucin is present in Winnie, but is not firmly compacted in a tight inner layer. Indeed, these mice develop chronic intestinal inflammation due to the primary epithelial defect with signs of mucosal damage, including thickening of muscle and mucosal layers, goblet cell loss, increased intestinal permeability, enhanced susceptibility to luminal inflammation-inducing toxins, and alteration of innervation in the distal colon. In this study, we show that the intestinal environment of the Winnie mouse, genetically determined by MUC2 mutation, selects an intestinal microbial community characterized by specific pro-inflammatory, genotoxic, and metabolic features that could imply a direct involvement in the pathogenesis of chronic intestinal inflammation. We report results obtained by using a variety of in vitro approaches for fecal microbiota functional characterization. These approaches include Caco-2 cell cultures and Caco-2/THP-1 cell co-culture models for evaluation of geno-cytotoxic and pro-inflammatory properties using a panel of 43 marker RNAs assayed by RT-qPCR, and cell-based phenotypic testing for metabolic profiling of the intestinal microbial communities by Biolog EcoPlates. While adding a further step towards understanding the etiopathogenetic mechanisms underlying IBD, the results of this study provide a reliable method for phenotyping gut microbial communities, which can complement their structural characterization by providing novel functional information. [ABSTRACT FROM AUTHOR]

Purpose: With the aim of characterizing the gastrointestinal (GI) microbiota and contextually determine how different prenatal, perinatal, and postnatal factors affected its composition in early childhood, infants were enrolled in a longitudinal-prospective study named "A.MA.MI." (Alimentazione MAmma e bambino nei primi MIlle giorni; NCT04122612, October 2019). Methods: Forty-five fecal samples were collected at 12 months of infants' age, identified as the 3rd follow-up (T3). The evaluated variables were pre-gestational weight and weight gain during pregnancy, delivery mode, feeding, timing of weaning, and presence/absence of older siblings. Fecal alpha and beta-diversities were analyzed. Noteworthy, to determine the impact of the influencing factors, multivariate analyses were conducted. Results: At T3, all prenatal and perinatal variables did not result to be significant whereas, among the postnatal variables, type of milk-feeding and weaning showed the greatest contribution in shaping the microbiota. Although aged 1 year, infants exclusively breastfed until 6 months were mainly colonized by Lactobacillaceae and Enterobacteriaceae. Differently, Bacteroidaceae characterized the microbiota of infants that were never breastfed in an exclusive way. Moreover, although an early introduction of solid foods determined higher values of Faith's PD, high abundances of Ruminococcaceae and Faecalibacterium mainly associated with infants weaned after the 4th month of age. Conclusion: The microbial colonization during the first year of life is likely affected by a simultaneous effect of multiple variables playing a significant role at different times. Therefore, these data contribute to add evidence concerning the complex multifactorial interaction between GI microbiota and various stimuli affecting infants during the early stages of life. [ABSTRACT FROM AUTHOR]

In this study we address the need to promote student engagement with school science and the need to measure a more comprehensive conception of engagement considering three dimensions of engagement: emotional, behavioural, and cognitive. We address the first issue by designing and implementing a model-based inquiry instructional sequence focused on fostering students' engagement with science. The second issue is addressed by developing and testing a heuristic that measures student engagement holistically by focusing on all three dimensions mentioned. The results report that our short MBI instructional sequence develop students' emotional engagement because most of them recognize to having felt interest, concentration, and satisfaction and few students reported boredom, shame, or rejection during the teaching. They spent most of the time working in small groups and sharing-discussing their hypothesis, planning and evaluating their experimental designs, and building models to explain acid-base phenomena together which highlight behavioural and cognitive dimension of students' engagement in our instructional sequence about chewing gum and pH of the mouth. The heuristic is designed to gather data continuously during instruction with minimal disruption to the learning and teaching sequence. The heuristic can be used by teachers, researchers, and also by students, to gain multi-level understandings about engagement by focusing on individual, group-level, or class-level analysis of responses. [ABSTRACT FROM AUTHOR]

A major risk factor of COVID-19 severity is the patient's health status at the time of the infection. Numerous studies focused on specific chronic diseases and identified conditions, mainly cardiovascular ones, associated with poor prognosis. However, chronic diseases tend to cluster into patterns, each with its particular repercussions on the clinical outcome of infected patients. Network analysis in our population revealed that not all cardiovascular patterns have the same risk of COVID-19 hospitalization or mortality and that this risk depends on the pattern of multimorbidity, besides age and sex. We evidenced that negative outcomes were strongly related to patterns in which diabetes and obesity stood out in older women and men, respectively. In younger adults, anxiety was another disease that increased the risk of severity, most notably when combined with menstrual disorders in women or atopic dermatitis in men. These results have relevant implications for organizational, preventive, and clinical actions to help meet the needs of COVID-19 patients. [ABSTRACT FROM AUTHOR]

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Introduction: Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder affecting multiple systems, due to inactivating mutations of TSC1 or TSC2 mTOR pathway genes. Neurological manifestations are observed in about 95% cases, representing the most frequent cause of morbidity and one of the most common causes of mortality. Background: Neuroimaging is crucial for early diagnosis, monitoring, and management of these patients. While computed tomography is generally used as first-line investigation at emergency department, magnetic resonance imaging is the reference method to define central nervous system involvement and investigate subtle pathophysiological alterations in TSC patients. Purpose: Here, we review the state-of-the-art knowledge in TSC brain imaging, describing conventional findings and depicting the role of advanced techniques in providing new insights on the disease, also offering an overview on future perspectives of neuroimaging applications for a better understanding of disease pathophysiology. [ABSTRACT FROM AUTHOR]

We propose explicit and implicit approaches for the teaching of acid-base chemistry based on research into the history and nature of science (NoS). To support these instructional proposals, we identify four rationales for students to understand acid-base processes: daily life, socio-scientific, curriculum, and history of science. The extensive bibliography on misconceptions at all educational levels justifies the need for a change from the usual pedagogical approaches to teaching the acid-base domain (traditionally involving conceptual-focused teaching) to a deeper and more meaningful approach that provides (implicitly or explicitly) a chance to reflect on how scientific knowledge is constructed. Controversial moments in science from 1923, when three researchers (Bronsted, Lowry, and Lewis) independently enunciated two theories from two different paradigms (dissociation and valence electron), underpin our first sequence with an explicit NoS approach for both lower secondary school and upper secondary or university levels. Our inquiry teaching cycle promotes the transformation of a hands-on activity (using cabbage as an indicator) into an inquiry, and subsequently, we use an historical model to propose a sequence of activities based on the modeling cycle of Couso and Garrido-Espeja for lower secondary school. Finally, we identify some implications for a model-focused teaching approach for upper secondary and university levels using more sophisticated models. [ABSTRACT FROM AUTHOR]

In this work, we use a proven model to study a dynamic duopolistic competition between an old technology and a new technology which through an improved technical performance—e.g. data transmission capacity—fight in order to conquer market share. The process whereby an old technology fights a new one off through own improvements has been named 'sailing-ship effect'. In the simulations proposed, intentional improvements of both the old technology and the new technology are affected by the values of three key parameters: scientific-technological, purely technological and purely economic. The interaction between these components gives rise to different outcomes in terms of prevalence of one technology over the other. [ABSTRACT FROM AUTHOR]

A complete CTA (computerized tomographic angiography) revealed a dilated right internal jugular vein (IJV) from the jugular foramen down to its confluence into the right brachiocephalic trunk. 1CTA. a Asterisk (*) indicates the internal jugular vein fully obstructing the right jugular foramen (horizontal line and blue arrow); b Asterisk (*) indicates the internal jugular vein. [Extracted from the article]

Small-size karst landforms may potentially provide very useful information to fully understand the behavior of karst systems and their dynamics. “Inghiottitoio della Masseria Rotolo,” located in a remarkable karst area of southeastern Italy, was originally a very small swallow hole, able to collect huge amount of water during rainstorms. After works of excavations, and the later caving explorations, it has become the deepest cave in Apulia, reaching the water table at depth of −264 m, with further exploration underwater that brought the depth to 324 m below the ground surface, for a total development of the system greater than 1800 m. This cave is described in the context of the possibility to define underground geosites and to promote speleotourism, with the main goal to spread among the great public information about karst processes and landscape evolution in Apulia. At this aim, the main historical and morphological features of the area where the cave is located (the Canale di Pirro polje) are also described. The karst system of the “Inghiottitoio della Masseria Rotolo” is being studied through a scientific project funded by the regional authority, and a great number of data is being collected, which could be extremely useful to reconstruct the different phases of cave development and to put this cave within the overall context of karst evolution in this sector of central Apulia. Transferring the scientific outcomes to the high number of tourists and visitors would be essential to spreading the main information about karst and to improve the level of knowledge on this remarkable karst system. [ABSTRACT FROM AUTHOR]

Background: The clinical relevance of Anxiety Sensitivity (AS) is well established, as well as the association between parents' and children's AS. However, there is little data data on the indirect relation between parents' AS and children's anxiety and somatic-hypochondriac symptoms through children's AS, and the few findings available are inconsistent.Objective: The study examined, in a community sample, whether children's AS was associated to their anxiety and somatic-hypochondriac symptoms, and tested whether children's AS mediated the link between parents' AS and children's anxiety and somatic-hypochondriac symptoms.Methods: A total of 392 children and one of their parents completed a battery of questionnaires.Results: Children's AS mediated the links between parents' AS and children's anxiety and somatic-hypochondriac symptoms. These pathways were moderated by the child's age, in that they were significant for older children (ages 11-17 years old), but not for younger ones (ages 8-10 years old).Conclusions: The findings advance understanding of how parental AS might be implicated in children's AS and clinical symptoms. [ABSTRACT FROM AUTHOR]

The aim of our study was to describe the clinical, electroencephalogram, molecular findings and the diagnostic and therapeutic flow-chart of children with pyridoxine-dependent epilepsies (PDEs). We performed a retrospective observational study on children with PDEs, diagnosed and followed-up in Italian Pediatric Departments. In each centre, the authors collected data from a cohort of children admitted for intractable seizures, responsive to pyridoxine administration and resistant to other anticonvulsant therapies. Data were retrospectively analysed from January 2016 to January 2017. Sixteen patients (13 males, and 3 females) were included. We found that 93.75% of patients underwent conventional anticonvulsant therapy before starting pyridoxine administration and 62.5% had ex-juvantibus diagnosis, as specific serum diagnostic tests had been performed in only 37.5% of patients by alpha-AASA and pipecolic acid blood and urine dosage. The most common type of seizure was generalized tonic-clonic in 7 patients and the most common EEG pattern was characterized by a 'burst suppression' pattern. Before pyridoxine administration, other anticonvulsant drugs were used in 93.75% of patients, with consequent onset of drug-resistance. Phenobarbital was the most frequently used drug as first-line treatment. The importance of our study relies on the need of a deeper knowledge of PDEs in terms of early diagnosis, avoiding incorrect treatment and related adverse events, clinical and EEG pathognomonic features, and genetic aspects of the disease. [ABSTRACT FROM AUTHOR]

Artificial recharge is used to increase the availability of groundwater storage and reduce saltwater intrusion in coastal aquifers, where pumping and droughts have severely impaired groundwater quality. The implementation of optimal recharge methods requires knowledge of physical, chemical, and biological phenomena involving water and wastewater filtration in the subsoil, together with engineering aspects related to plant design and maintenance operations. This study uses a novel Decision Support System (DSS), which includes soil aquifer treatment (SAT) evaluation, to design an artificial recharge plant. The DSS helps users make strategic decisions on selecting the most appropriate recharge methods and water treatment technologies at specific sites. This will enable the recovery of safe water using managed aquifer recharge (MAR) practices, and result in reduced recharge costs. The DSS was built using an artificial intelligence technique and knowledge-based technology, related to both quantitative and qualitative aspects of water supply for artificial recharge. The DSS software was implemented using rules based on the cumulative experience of wastewater treatment plant engineers and groundwater modeling. Appropriate model flow simulations were performed in porous and fractured coastal aquifers to evaluate the suitability of this technique for enhancing the integrated water resources management approach. Results obtained from the AQUASTRESS integrated project and DRINKADRIA IPA CBC suggest the most effective strategies for wastewater treatments prior to recharge at specific sites. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "The Establishment of the Gut Microbiota in 1-Year-Aged Infants: From Birth to Family Blood," which appeared in the 2022 issue of the magazine.

There are a number of intriguing reports of lymphoproliferative disorders (LPDs) diagnosed during immunosuppressive treatment for underlying autoimmune disease, and spontaneously abated shortly after treatment discontinuation. Such LPDs, completely or partially regressing, occur in the clinical setting of "Methotrexate (MTX)-associated LPDs", recognized by the World Health Organization (WHO) among the "Immunodeficiency-associated LPDs". We identified 26 literature patients achieving spontaneous complete remission (CR) of their LPD, and eight others showing partial remission (PR). Most of them were affected by rheumatoid arthritis, received low-dose and long-term pulsed MTX alone or combined with other immunosuppressants, and developed a lymphoma. By reviewing the patients achieving CR, the following can be drawn: the absence of a unique type of LPD, the occurrence of an increased incidence of diffuse large B cell lymphoma as well as of frequent extranodal involvement, and EBV-infection. Further, CR mostly occurred within 4 weeks after discontinuation of immunosuppressant, and appeared to be persistent overtime. Conversely in the patients experiencing PR, the interval between discontinuation of immunosuppressive treatment and clinical response was mostly reported as longer than 4 weeks; moreover, in many cases the persistence of LPD or its progression induced to start cytotoxic therapy. Increased awareness is needed on the possible occurrence of LPD spontaneous remission following immunosuppressant discontinuation, after that it is therefore advisable to have a careful monitoring of the patient for some weeks, before starting cytotoxic therapy. [ABSTRACT FROM AUTHOR]

The necessity of eliminating debris from a granite quarry has awakened an interest in applications of by-products, called “marginal arids”, in different fields, like construction and foundations for roadways, restoration, material for the manufacture of artificial rocks, and artesian products etc. Conclusions obtained from the results of tests carried out by X-ray diffraction of granite quarry by-products in Extremadura, Spain, submitted to different treatments, are established. Test pieces from two quarries are analyzed and compared generally and specifically, for commercial use. Finally, conclusions relating to essays in test pieces and mineral dynamics of marginal arid granite are exposed. [ABSTRACT FROM AUTHOR]

Haemopoietic stem cell therapy is an increasingly adopted procedure in the treatment of patients with malignant lymphoma. In this retrospective analysis, we evaluated 262 patients, 57 (22%) with Hodgkin's and 205 (78%) with non-Hodgkin's lymphomas (NHL), and 665 harvesting procedures in order to assess the impact of poor mobilization on survival and to determine the factors that may be predictive of CD34+ poor mobilization. The mobilization chemotherapy regimens consisted of high-dose cyclophosphamide in 92 patients (35.1%) and a high-dose cytarabine-containing regimen (DHAP in 87 patients –(33.2%), MAD in 83 (31.7%)). The incidence of poor mobilizers (<2 × 106 CD34+ cells/kg) was 17.9% overall, with a 10% of very poor mobilizers (1 × 106/kg). Refractory disease status and chemotherapeutic load (>3 regimens) before mobilization played a negative role and were associated with poor mobilization. Survival analysis of all harvested patients showed an overall survival at 3 years of 71% in good mobilizers vs 33% in poor mobilizers (P=0.002). The event-free survival at 3 years was 23% in poor mobilizers and 58% in good mobilizers (P=0.04). We conclude that in NHL patients, poor mobilization status is predictive of survival.Bone Marrow Transplantation (2006) 37, 719–724. doi:10.1038/sj.bmt.1705298; published online 6 March 2006 [ABSTRACT FROM AUTHOR]

Relapsed or refractory adult acute lymphoblastic leukemias (ALL) have poor prognosis. The strategy for treating these patients is through reinduction chemotherapy followed by allogeneic stem cell transplantation, provided that the toxicity of the salvage regimen is acceptable. Twenty three patients with relapsed/refractory adult ALL were treated with fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA). Five patients had primary refractory disease, and 18 were in first relapse. Nine (39.1%) patients achieved complete remission (CR) following salvage therapy, whereas 13 (56.5%) patients were refractory, and one patient died in aplasia due to infection. In patients achieving remission, the median time to reach absolute neutrophil count (ANC) more than 0.5×109/l and 1×109/l was 20 (range 16–25) and 24 (range 20–28) days from the start of chemotherapy, respectively. Platelet levels of more than 20×109/l and 100×109/l were achieved in a median time of 23 (range 19–25) and 33 (range 28–39) days, respectively. Fever more than 38.5°C was observed in 18 of 23 patients (78.2%), 13 had fever of unknown origin, and 5 had documented infections. Nonhematological side effects, consisting mainly of mucositis (18/23 or 78.2%) and transient liver toxicity increase (10/23 or 43.4%), were generally tolerated. All nine patients who achieved CR received a second course with FLAG-IDA, and seven patients underwent allogeneic stem cell transplantation (four from a matched donor, one from a mismatched donor, and two from an unrelated donor), while two did not reach that stage due to early relapse from CR. The median overall survival (OS) for all 23 patients was 4.5 (range 1–38) months; for the nine responders, the disease-free survival (DFS) and the OS were 6 (range 3–38) and 9 (7–38) months, respectively; the seven patients who received allogeneic stem cell transplantation had a DFS of 10 (range 7–38) months. In our experience, FLAG-IDA is a well-tolerated regimen in relapsed/refractory ALL patients; the toxicity is acceptable, enabling patients who have achieved CR to receive allogeneic transplantation. [ABSTRACT FROM AUTHOR]

In the present paper we report pericentric chromosome 8 inversions in two (2.4%) of 82 acute myeloid leukemia (AML) cases characterized by the 5'RUNX1/3'CBFA2T1fusion gene. Molecular cytogenetic characterization was achieved using appropriate bacterial artificial chromosome (BAC) and P1 artificial chromosome (PAC) probes in fluorescence in situ hybridization (FISH) experiments. In these two cases the fusion gene was detected on the der(8) short arm, resulting from a pericentric chromosome 8 inversion followed by a t(8;21) rearrangement. These results suggest that heterogeneous mechanisms can lead to the generation of the 5'RUNX1/3'CBFA2T1chimeric gene. [ABSTRACT FROM AUTHOR]

The factors possibly affecting the collection of peripheral blood stem cells (PBSC) were evaluated in 104 de novo acute leukemia patients (66 myeloid and 38 lymphoblastic leukemias) in first cytological complete remission (CR); all patients achieved CR after first-line induction chemotherapy. The acute myeloid leukemia patients (AML) were given consolidation—mobilization chemotherapy with cytarabine, and daunoblastin or mitoxantrone or idarubicin; the acute lymphoblastic leukemia patients (ALL) were given consolidation—mobilization chemotherapy with cytarabine and etoposide. In all patients, the collection of PBSC was performed during recovery after giving consolidation chemotherapy and granulocyte colony-stimulating factor (G-CSF). Two main groups were considered according to the CD34+ cells 106/kg b.w. collected, that is, poor mobilizers (PM), with a collection of <2 106/kg and good mobilizers, with a collection of >2 106/kg. Of 104 patients, 27 (25.9%) were PM; 20/27 had AML and 7/27 had ALL. At multivariate analysis, a lower CD34+ cells count premobilization chemotherapy (CD34 steady state), the presence of FUO (fever of unknown origin) or infection, and a lower number of CD34+ cells on the first day of collection correlated with poor mobilization. These results may enable early recognition of patients who may have poor mobilization, and aid selection of patients for different mobilization regimens. [ABSTRACT FROM AUTHOR]

We report the use of Alemtuzumab (Campath-1H) as salvage treatment in three patients with advanced mycosis fungoides/Sézary syndrome who had previously been treated with conventional chemotherapy. Two patients (case 1 and case 2), aged 42 and 68 yr, respectively, were heavily pretreated (more than three prior therapy regimens, including autologous transplant in case 2) and refractory to conventional chemotherapy, and the third patient (case 3), aged 80 yr, who had refused any chemotherapy, had been resistant to treatment with cyclosporine and steroids. Campath-1H was administered intravenously, after an escalating dose from 3 to 10 mg, at the dose of 30 mg, three times weekly, to a total dose of 1080, 223, and 480 mg, respectively. The patients with Sézary syndrome (case 2 and case 3) showed clearance of circulating Sézary cells and clinical improvement of the skin lesions after 2 wk of treatment. Two patients (case 1 and case 3) completed the treatment (12 and 6 wk) without significant toxicity, the former achieving a partial response and the latter a clinical complete response. The patient (case 2), who suffered from ischemic cardiopathy and diabetes, quickly achieved a clinical improvement of the Sézary syndrome, but he died because of a myocardial infarction after 3 wk of treatment. Our report shows that the treatment with Campath-1H is active even in patients with advanced refractory mycosis fungoides/Sézary syndrome. Further clinical observations on a larger cohort of patients are needed to establish if Campath-1H may have a role as first line therapy in addition to conventional therapy including chemotherapy. [ABSTRACT FROM AUTHOR]

We report the use of Alemtuzumab (Campath-1H) as salvage treatment in three patients with advanced mycosis fungoides/Sézary syndrome who had previously been treated with conventional chemotherapy. Two patients (case 1 and case 2), aged 42 and 68 yr, respectively, were heavily pretreated (more than three prior therapy regimens, including autologous transplant in case 2) and refractory to conventional chemotherapy, and the third patient (case 3), aged 80 yr, who had refused any chemotherapy, had been resistant to treatment with cyclosporine and steroids. Campath-1H was administered intravenously, after an escalating dose from 3 to 10 mg, at the dose of 30 mg, three times weekly, to a total dose of 1080, 223, and 480 mg, respectively. The patients with Sézary syndrome (case 2 and case 3) showed clearance of circulating Sézary cells and clinical improvement of the skin lesions after 2 wk of treatment. Two patients (case 1 and case 3) completed the treatment (12 and 6 wk) without significant toxicity, the former achieving a partial response and the latter a clinical complete response. The patient (case 2), who suffered from ischemic cardiopathy and diabetes, quickly achieved a clinical improvement of the Sézary syndrome, but he died because of a myocardial infarction after 3 wk of treatment. Our report shows that the treatment with Campath-1H is active even in patients with advanced refractory mycosis fungoides/Sézary syndrome. Further clinical observations on a larger cohort of patients are needed to establish if Campath-1H may have a role as first line therapy in addition to conventional therapy including chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate if advanced neuroimaging research is mainly conducted by imaging specialists, we investigated the number of first authorships by radiologists and non-radiologist scientists in articles published in the field of advanced neuroimaging in the past 10 years. Methods: Articles in the field of advanced neuroimaging identified in this retrospective bibliometric analysis were divided in four groups, depending on the imaging technique used. For all included studies, educational background of the first authors was recorded (based on available online curriculum vitae) and classified in subgroups, depending on their specialty. Finally, journal impact factors were recorded and comparatively assessed among subgroups as a metric of research quality. Results: A total number of 3831 articles were included in the study. Radiologists accounted as first authors for only 12.8 % of these publications, while 56.9 % of first authors were researchers without a medical degree. Mean impact factor (IF) of journals with non-MD researchers as first authors was significantly higher than the MD subgroup ( p < 10), while mean IF of journals with radiologists as first authors was significantly lower than articles authored by other MD specialists ( p < 10). Conclusions: The majority of the studies in the field of advanced neuroimaging in the last decade is conducted by professional figures other than radiologists, who account for less than the 13 % of the publications. Furthermore, the mean IF value of radiologists-authored articles was the lowest among all subgroups. These results, taken together, should question the radiology community about its future role in the development of advanced neuroimaging. [ABSTRACT FROM AUTHOR]

We evaluated the efficacy and toxicity profiles of the combination of fludarabine, high-dose cytosine arabinoside (AraC), idarubicin, and granulocyte colony-stimulating factor (G-CSF) in refractory/relapsed acute myeloblastic leukemia (AML) patients. Between October 1998 and February 2002, 46 AML patients were treated with FLAG-IDA (fludarabine 30 mg/m2, AraC 2 g/m2 for 5 days, idarubicin 10 mg/m2 for 3 days, and G-CSF 5 µg/kg from day +6 until neutrophil recovery). Thirty patients were in relapse after conventional chemotherapy including cytarabine, etoposide, and daunorubicin or mitoxantrone according to the GIMEMA protocols. Four were in relapse after autologous peripheral stem cell transplantation and two after allogeneic bone marrow transplantation. Ten patients had refractory disease (after 10 days of standard doses of cytarabine, 3 days of mitoxantrone or daunorubicin, and 5 days of etoposide). Recovery of neutrophils and platelets required a median of 19 and 22 days from the start of therapy. Complete remission (CR) was obtained in 24 of 46 patients (52.1%) and 3 of 46 (6.6%) died during reinduction therapy: 2 due to cerebral hemorrhage and 1 due to fungemia (Candida tropicalis). Fever >38.5°C was observed in 40 of 46 patients (86.9%), 27 had fever of unknown origin (FUO) and 13 documented infections; 31 of 46 (67.3%) developed mucositis and 14 of 46 (30.4%) had grade 2 WHO transient liver toxicity. After achieving CR, 11 patients received allogeneic stem cell transplantation, 4 patients received autologous stem cell transplantation, 4 were judged unable to receive any further therapy, and 5 refused other therapy. Ten patients are at present in continuous CR after a median follow-up of 13 months (range: 4–24). In our experience, FLAG-IDA is a well-tolerated and effective regimen in relapsed/refractory AML. The toxicity is acceptable, enabling most patients to receive further treatment, including transplantation procedures. [ABSTRACT FROM AUTHOR]

Some cases of acute myeloid leukemia following organ transplant (PT-AML) have been published in the literature. We report the second case of acute promyelocytic leukemia (APL), which developed post-transplant and immunosuppressive treatment, in a 50-year-old male who had undergone a renal transplant. At diagnosis he presented typical t(15;17)(q12;q13) with additional abnormalities, including +8,t(13;22)(q12;q13) and an abnormal chromosome 1 which was better characterized by fluorescence in situ hybridization (FISH). He obtained cytological, karyotypic and molecular complete remission (CR) with induction treatment according to the all-trans retinoic acid + idarubican (AIDA) protocol; after 12 months, he relapsed (molecular relapse) and achieved molecular remission with all-trans retinoic acid (ATRA) plus mitoxantrone and cytosine arabinoside. After a further 14 months, he was treated with arsenic trioxide for cytological relapse and obtained a third CR; at the cytological relapse the karyotype showed 47,XY,+8, t(15;17)(q22;q21),t(13;22)(q12;q13),der(22)t(1;22)(p22;q13). He is alive 3.3 years after diagnosis of APL. Cyclosporin A (CsA) was given during all cycles of chemotherapy. We did not observe any severe infections or kidney failure during treatments. The use of conventional cytogenetic analysis plus FISH may identify complex karyotype also in transplanted patients receiving immunotherapy, and may also contribute to a better assessment of PT-AL. [ABSTRACT FROM AUTHOR]

Lucia Longhitano, Nunzio Vicario and Stefano Forte have contributed equally to this manuscript. The correct affiliations details for Authors' Stefano Forte, Cesarina Giallongo, Giuseppe Broggi, Rosario Caltabiano, Giuseppe Maria Vincenzo Barbagallo, Roberto Altieri, Giuseppina Raciti and Arcangelo Liso should be: 2 IOM Ricerca, 95029 Viagrande, CT, Italy 3 Department of Medical and Surgical Sciences and Advanced Technologies, F. Ingrassia, Anatomic Pathology, University of Catania, Catania, Italy 4 Department of Drug Sciences, University of Catania, Catania, Italy 5 Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. [Extracted from the article]

Sports-related concussions are currently diagnosed through multi-domain assessment by a medical professional and may utilize neurocognitive testing as an aid. However, these tests have only been able to detect differences in the days to week post-concussion. Here, we investigate a measure of brain function, namely resting state functional connectivity, which may detect residual brain differences in the weeks to months after concussion. Twenty-one student athletes (9 concussed within 6 months of enrollment; 12 non-concussed; between ages 18 and 22 years) were recruited for this study. All participants completed the Wisconsin Card Sorting Task and the Color-Word Interference Test. Neuroimaging data, specifically resting state functional Magnetic Resonance Imaging data, were acquired to examine resting state functional connectivity. Two sample t-tests were used to compare the neurocognitive scores and resting state functional connectivity patterns among concussed and non-concussed participants. Correlations between neurocognitive scores and resting state functional connectivity measures were also determined across all subjects. There were no significant differences in neurocognitive performance between concussed and non-concussed groups. Concussed subjects had significantly increased connections between areas of the brain that underlie executive function. Across all subjects, better neurocognitive performance corresponded to stronger brain connectivity. Even at rest, brains of concussed athletes may have to 'work harder' than their healthy peers to achieve similar neurocognitive results. Resting state brain connectivity may be able to detect prolonged brain differences in concussed athletes in a more quantitative manner than neurocognitive test scores. [ABSTRACT FROM AUTHOR]

Objective: We report synthesis of two carbon-11 labeled imidazopyridines TSPO ligands, [(11)C]CB184 and [(11)C]CB190, for PET imaging of inflammatory process along with neurodegeneration, ischemia or brain tumor. Biodistribution of these compounds was compared with that of [(11)C]CB148 and [(11)C](R)-PK11195.Methods: Both [(11)C]CB184 and [(11)C]CB190 having (11)C-methoxyl group on an aromatic ring were readily prepared using [(11)C]methyl triflate. Biodistribution and metabolism of the compounds were examined with normal mice. An animal PET study using 6-hydroxydopamine treated rats as a model of neurodegeneration was pursued for proper estimation of feasibility of the radioligands to determine neuroinflammation process.Results: [(11)C]CB184 and [(11)C]CB190 were obtained via O-methylation of corresponding desmethyl precursor using [(11)C]methyl triflate in radiochemical yield of 73 % (decay-corrected). In vivo validation as a TSPO radioligand was carried out using normal mice and lesioned rats. In mice, [(11)C]CB184 showed more uptake and specific binding than [(11)C]CB190. Metabolism studies showed that 36 % and 25 % of radioactivity in plasma remained unchanged 30 min after intravenous injection of [(11)C]CB184 and [(11)C]CB190, respectively. In the PET study using rats, lesioned side of the brain showed significantly higher uptake than contralateral side after i.v. injection of either [(11)C]CB184 or [(11)C](R)-PK11195. Indirect Logan plot analysis revealed distribution volume ratio (DVR) between the two sides which might indicate lesion-related elevation of TSPO binding. The DVR was 1.15 ± 0.10 for [(11)C](R)-PK11195 and was 1.15 ± 0.09 for [(11)C]CB184.Conclusion: The sensitivity to detect neuroinflammation activity was similar for [(11)C]CB184 and [(11)C](R)-PK11195. [ABSTRACT FROM AUTHOR]

Objective: We report synthesis of two carbon-11 labeled imidazopyridines TSPO ligands, [C]CB184 and [C]CB190, for PET imaging of inflammatory process along with neurodegeneration, ischemia or brain tumor. Biodistribution of these compounds was compared with that of [C]CB148 and [C] (R)-PK11195. Methods: Both [C]CB184 and [C]CB190 having C-methoxyl group on an aromatic ring were readily prepared using [C]methyl triflate. Biodistribution and metabolism of the compounds were examined with normal mice. An animal PET study using 6-hydroxydopamine treated rats as a model of neurodegeneration was pursued for proper estimation of feasibility of the radioligands to determine neuroinflammation process. Results: [C]CB184 and [C]CB190 were obtained via O-methylation of corresponding desmethyl precursor using [C]methyl triflate in radiochemical yield of 73 % (decay-corrected). In vivo validation as a TSPO radioligand was carried out using normal mice and lesioned rats. In mice, [C]CB184 showed more uptake and specific binding than [C]CB190. Metabolism studies showed that 36 % and 25 % of radioactivity in plasma remained unchanged 30 min after intravenous injection of [C]CB184 and [C]CB190, respectively. In the PET study using rats, lesioned side of the brain showed significantly higher uptake than contralateral side after i.v. injection of either [C]CB184 or [C]( R)-PK11195. Indirect Logan plot analysis revealed distribution volume ratio (DVR) between the two sides which might indicate lesion-related elevation of TSPO binding. The DVR was 1.15 ± 0.10 for [C]( R)-PK11195 and was 1.15 ± 0.09 for [C]CB184. Conclusion: The sensitivity to detect neuroinflammation activity was similar for [C]CB184 and [C]( R)-PK11195. [ABSTRACT FROM AUTHOR]

The aim of this study was to understand whether insulin-like growth factor-binding protein-6 (IGFBP-6) has functional effects on neutrophils, in particular when they cross epithelium during inflammation. We found that IGFBP-6 increased ROS production (cytofluorimetry), degranulation of primary and tertiary granules (ELISA) and transmigration through the epithelial monolayer. No priming by IGFBP-6 on neutrophils stimulated by either PMA or fMLP was observed. IGFBP-6 is an agonist of neutrophils' functions, most likely when these cells have been already activated by other stimuli. [ABSTRACT FROM AUTHOR]

Background:Month of birth influences the risk of developing several diseases. We investigated the influence of date of birth on melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC) incidence.Methods:Enhanced cancer registry data were analysed including 1751 MSC and 15 200 NMSC.Results:People born in February to April showed significantly elevated risks of NMSC compared with those born in summertime.Conclusions:We demonstrated seasonality by date of birth for skin cancer incidence. Neonatal UV exposure may explain this finding. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (HCT) activity significantly increased in the Eastern Mediterranean area over the past decade. However, comparative outcomes with longer established centers, especially European Blood and Marrow Transplantation (EBMT) centers, have not been reported. We compared outcomes of matched-sibling allogeneic HCT between East Mediterranean Blood and Marrow Transplantation (EMBMT) and EBMT centers for adult patients with AML in first CR using myeloablative conditioning. We matched 431 patients from EMBMT with 431 patients from EBMT centers according to patient, disease and transplant characteristics. EMBMT recipients and donors were more likely to be CMV seropositive. There were no significant differences in the incidence of acute or chronic GVHD, or the 3-year cumulative incidence of non-relapse mortality (NRM) and relapse incidence (RI) between the two groups (NRM: EMBMT=16% vs EBMT=11), (RI: EMBMT=13% vs EBMT=19%). Notably, the 3-year leukemia-free survival (LFS) and OS were similar between the groups (LFS: EMBMT=70±2% vs EBMT=69±3%), (OS: EMBMT=74±2% vs EBMT=73±2%). Despite differences in socioeconomics, health resources and transplant experience, matched-sibling allogeneic HCT outcomes in emerging centers in the EMBMT region appear similar to EBMT centers. [ABSTRACT FROM AUTHOR]

Background: Dhat syndrome (DS) consists of vague somatic symptoms and at times sexual dysfunction which the patient falsely attributes to involuntary emissions of semen outside of sexual relations. Objective: Describe and analyse the occurrences of DS in patients attending the clinic and clarify the existence of this condition within the Spanish Urological service. Materials and methods: Patients reporting semen loss in urine or involuntarily outside of sexual relations were studied during a period from May 2006 to December 2007. Variables of age, nationality, marital status, family situation, medical history, reasons for the consultation, physical condition and additional tests were studied. All treatments and its effectiveness were also recorded. Results: DS affected predominantly southern Asian continent citizens ( n = 32). The average age was 35.44. Seventeen patients reported semen loss during urination; 20 at the end of urination; 11 spontaneously; 5 while sleeping; 4 during defecation; 1 while showering; 1 while eating meat; and 3 produced by noticing stained clothing. In 28 cases, the supposed loss of semen was linked to sex-related symptoms. All examinations and tests ruled out the existence of actual loss of semen. Conclusions: In urology consultations, we have been witnessing the unusual appearance of DS, a condition known by psychologists and psychiatrists and practically unheard of by urologists. A previously unknown condition in Spain, immigration from Asia, is causing the appearance of this syndrome. Its rapid identification will prevent patients from paying costly and unnecessary tests and provide alternative therapies, within a multidisciplinary approach involving psychologists and psychiatrists. [ABSTRACT FROM AUTHOR]

If a pelagic ecosystem is invaded by an efficient planktivorous fish, competition theory predicts that habitat and/or diet segregation should occur if the invader and native planktivores are to co-exist. We compared the diet and pelagic habitat use between invading vendace ( Coregonus albula) and two native morphs of whitefish ( Coregonus lavaretus) in three subarctic lakes located within the same watercourse. No clear vertical habitat segregation was found as vendace prevailed throughout the entire depth range. Zooplankton generally dominated the diet of all three coregonids. No obvious resource partitioning was found in two of the lakes, while in the third lake the diets of whitefish and vendace differed significantly from each other. Here, the predominant pelagic whitefish morph fed extensively on water mites whereas vendace mainly consumed surface insects and to some extent small fish, apparently as a result of highly depleted zooplankton resources. The results suggest that various levels of resource depletion following the vendace invasion caused the observed differences between the lakes, indicating that different levels of resource partitioning were associated with dissimilar competition intensities. At present, coexistence of these congeneric species seems to be possible, although the vendace invasion has apparently resulted in a challenging and unstable situation for the planktivorous whitefish. [ABSTRACT FROM AUTHOR]

OBJECTIVES:There are no established predictive markers of progression of gastric preneoplastic lesions. The aim of this study was to analyze the relationship between Helicobacter pylori cagA and vacA genotypes and progression of gastric preneoplastic lesions.METHODS:This was a follow-up study that carried out in a province of Spain with a high risk of gastric cancer. A total of 312 patients who underwent upper endoscopy with gastric biopsy in 1988-1994 with diagnoses of normal mucosa, non-atrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG), and complete or incomplete intestinal metaplasia (IM), and who accepted to undergo a new biopsy during 2005-2007 or had an end point during follow-up, were included in this study. Detection and characterization of H. pylori cagA and vacA genotypes was performed directly in baseline paraffin-embedded gastric biopsy specimens by PCR followed by reverse hybridization onto a line probe assay. Inter- and intra-observer variability of histological diagnosis was assessed. Analysis was done using unconditional logistic regression.RESULTS:The mean age of patients was 48.5 years (45% males) and the mean of follow-up was 12.8 years. H. pylori strains harboring cagA, vacA s1, and vacA m1 genotypes were more frequently found in patients with more advanced gastric preneoplastic lesions. Infection with cagA-positive, vacA s1, and vacA m1 strains was associated with progression of gastric preneoplastic lesions (multivariate odds ratio (OR)=2.28, 95% confidence interval (CI) 1.13-4.58; OR=2.90, 95% CI 1.38-6.13; and OR=3.38, 95% CI 1.34-8.53, respectively). Infection with strains that are simultaneously cagA positive and vacA s1/m1 was associated with progression of gastric precancerous lesions with an OR of 4.80 (95% CI 1.71-13.5) in relation to those infected with cagA-negative/vacA s2/m2 strains.CONCLUSIONS:H. pylori genotyping may be useful for the identification of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance. [ABSTRACT FROM AUTHOR]

Systemic AL amyloidosis is associated with nearly 15% of cases of multiple myeloma, but data on the frequency and significance of amyloid deposits in the bone marrow of patients affected by multiple myeloma without clinical signs of systemic amyloidosis are scanty. Bone marrow smears of 166 unselected patients affected by multiple myeloma (126 at diagnosis and 40 after treatment) were stained with Congo red and studied by transmission and birefringence microscopy. Both focal and diffuse storages were considered positive. Overall, 67 patients were positive and 99 were negative to Congo red and apple-green birefringence. In particular, 51 of the 126 patients studied at diagnosis and 16 of the 40 patients with advanced disease were positive. Seventeen patients were reassessed after a mean follow-up of 32 months (range: 6–91): disappearance of amyloid deposits was verified in three cases, all responsive to bortezomib-based regimens. The preliminary data available suggest that amyloid deposition in the marrow of myeloma patients is frequent, as it can be traced in nearly 40% of cases. We failed to find correlations between bone marrow amyloid deposits and immunoglobulin type, disease stage, plasma cells percentage, hemoglobin, calcium, creatinine, albumin, or β2microglobulin. Significantly higher incidence of moderate/severe peripheral neuropathy was found in patients with marrow amyloid exposed to potentially neurotoxic antineoplastic agents. Further studies and prolonged follow-up are needed to validate our findings and to define possible prognostic aspects. [ABSTRACT FROM AUTHOR]

A crucial role of segmental duplications (SDs) of the human genome has been shown in chromosomal rearrangements associated with several genomic disorders. Limited knowledge is yet available on the molecular processes resulting in chromosomal rearrangements in tumors. The t(9;22)(q34;q11) rearrangement causing the 5′BCR/3′ABL gene formation has been detected in more than 90% of cases with chronic myeloid leukemia (CML). In 10–18% of patients with CML, genomic deletions were detected on der(9) chromosome next to translocation breakpoints. The molecular mechanism triggering the t(9;22) and deletions on der(9) is still speculative. Here we report a molecular cytogenetic analysis of a large series of patients with CML with der(9) deletions, revealing an evident breakpoint clustering in two regions located proximally to ABL and distally to BCR, containing an interchromosomal duplication block (SD_9/22). The deletions breakpoints distribution appeared to be strictly related to the distance from the SD_9/22. Moreover, bioinformatic analyses of the regions surrounding the SD_9/22 revealed a high Alu frequency and a poor gene density, reflecting genomic instability and susceptibility to rearrangements. On the basis of our results, we propose a three-step model for t(9;22) formation consisting of alignment of chromosomes 9 and 22 mediated by SD_9/22, spontaneous chromosome breakages and misjoining of DNA broken ends. [ABSTRACT FROM AUTHOR]

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor superfamily, is known to be involved in cell survival and osteoclast (OC) formation. In this study, we show that malignant plasma cells and T lymphocytes from multiple myeloma (MM) bone disease patients, as well as Karpas 909, a human myeloma cell line, directly produce DcR3. By interacting with FasL, this molecule could inhibit OC apoptosis. In fact, the use of a neutralizing anti-DcR3 antibody induces a reduction of cell viability with a consequent increase of apoptotic cell number, the activation of caspase-8 and -3, and DNA fragmentation. Furthermore, we show that DcR3 supports OC formation in samples from MM patients through the upregulation of RANKL and TNFα by T lymphocytes and only TNFα by CD14+ cells. In conclusion, our data provide the first evidence of the expression of DcR3 in MM, and the involvement of this molecule in supporting the survival and formation of OCs from MM bone disease patients. The production of DcR3 by T lymphocytes confers these cells a role in the pathogenesis of bone disease associated with MM. [ABSTRACT FROM AUTHOR]