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Primary fallopian tube carcinoma (PFTC) is seldom diagnosed preoperatively and is often mistaken for epithelial ovarian carcinoma (EOC). This report details a case of primary high-grade serous carcinoma (HGSC) of the fallopian tube, highlighting radiological and clinical indicators to aid in accurate diagnosis and avoid misdiagnosis. A 46-year-old premenopausal woman presented with symptoms and a transvaginal ultrasound (TVUS) indicating a malignant ovarian tumor. Further imaging with CT and MRI revealed a solid-cystic mass suggestive of a fallopian tube tumor rather than an ovarian origin. Oncological surgery confirmed the presence of a high-grade serous carcinoma in the fallopian tube. This case underscores the diagnostic challenges of PFTC and the superior sensitivity and specificity of MRI over CT and US in distinguishing adnexal lesions. Key MRI features such as the sausage-shaped mass and associated hematosalpinx were crucial in differentiating PFTC from EOC. The report emphasizes the importance of considering PFTC in differential diagnoses of adnexal masses to ensure accurate preoperative identification.

The objective of the present study was to evaluate the effect of a precision biotic (PB; Symphiome®, dsm-firmenich) on the growth performance, nutrient digestibility, litter quality, blood uric acid (UA) concentration, cecal short-chain fatty acids (SCFA) concentration, and ileal and cecal microbiome of broiler chickens fed corn or wheat-based diets. One-day-old broiler chicks were placed in a completely randomized design (2 × 2 factorial scheme) in 4 treatments, 8 replicates/treatment, and 16 birds/replicate. The treatments were a corn or wheat and soybean meal-based diet without or with supplementation of 0.9 kg/MT of PB. All the birds were vaccinated against coccidiosis at the time of placement (Paracox 5). Growth performance was evaluated weekly and at the end of the experiment. At d 35, blood was collected to determine UA concentration and cecal content for SCFA concentration analysis. Ileal digesta was also collected for nutrient digestibility analysis, and ileal digesta and cecal content were collected for microbiome analysis. The data were submitted to two-way ANOVA (P ≤ 0.05), and LSM was used to separate the means in case of interaction. During the starter and grower phases of the study, a better body weight gain (P = 0.0008 and P = 0.04, respectively) was observed in birds fed wheat compared to corn-based diets. From 28 to 36 d of age, the supplementation of PB increased feed intake (P = 0.05), and tended (P = 0.06) to improve the feed conversion ratio by 4.3 points vs non-supplementated birds. Birds fed wheat-based diets had higher (P = 0.02) blood UA than corn based-diets fed birds, and the supplementation of PB led to a reduction (P = 0.02) of blood UA compared to non-supplemented birds. The supplementation of PB changed the abundance of core metabolic pathways of the microbiome, mostly related to protein metabolism, which led to a reduction in blood UA concentration and increase of cecal SCFA concentrations. In conclusion, by beneficially modulating the microbiome, the supplementation of PB was translated into improved growth performance of broiler chickens fed corn or wheat-based diets.

Background: Despite the implementation of specific exercises to reduce hamstrings strain injuries (HSI) risk, the incidence has remained unchanged over the past 30 years. Therefore, the purpose of the study was to analyze hamstrings muscle activation induced by a novel Flywheel Russian belt Deadlift (FRD) exercise, together with individual muscle-, region- and limb-specific differences. Methods: The activation of hamstring muscles before and immediately after a 10 × 10 FRD training session was assessed by the T2 shift technique through functional magnetic resonance imaging, in one international-level filed hockey male player. The individual use of the biceps femoris long head (BFLH) and short head (BFSH), semitendinosus (ST), and semimembranosus (SM) were analyzed, together with the region-specific activation for each muscle. Results: T2 values significantly increased immediately after exercise in all regions of the hamstring muscles in both dominant and non-dominant lower limb. However, the SM muscle showed a lesser activation, compared to BFLH, BFSH and ST muscles [F(3,106) = 9.557, p < 0.001]. Overall, the most activated muscle by the FRD training session was the biceps femoris (short head +13.8 %, long head, +12.7 %), followed by the ST (+11.3 %), and lastly the SM (+6.9 %). Conclusion: The novel FRD exercise triggers a homogeneous and consistent activation of hamstring muscles. Particularly, the lateral positioning muscles (i.e., BFLH and BFSH) were more activated than the medial positioning muscles (i.e., ST and SM). Therefore, the FRD exercise could enhance training programs to strengthen and activate the hamstring muscles, and specifically, the BFLH, in order to reduce HSI risk.

The overconsumption of conventional plastics has led to several environmental and social-economic issues related to plastic pollution, carbon emissions and resource depletion. Acknowledging these issues, the introduction of alternatives such as bioplastics has been promoted by national, supranational, and international organizations. However, the market for such materials is still niche, where businesses are uncertain about the benefits and costs associated with the use of these innovative materials. Successful (and sustainable) uptake of such alternatives will depend on public acceptance and changes in consumer behavior. Therefore, this study aims to explore how consumers' orientation towards environmental sustainability is related to consumer utilization of alternatives such as bio-based and biodegradable plastics. Consumer knowledge and performance expectations of these materials are also analyzed. This study employed a predominately quantitative research approach, where a self-administered online survey was used to collect the opinions of consumers across society using a snowball sampling technique. Results show continued consumer confusion, unrealistic expectations, and a value-action gap. These elements may have consequences for market uptake and broader implications across the value chain. A key implication is that both policy makers and businesses should address these barriers through enhanced communication of relevant information alongside improved consumer awareness and education.

An increasing number of patients experiences prolonged symptoms, whose profile and timeline remain uncertain, a condition that has been defined as post COVID. The majority of recovered hospitalized patients manifests at least one persistent symptom even sixty days after the first clinical manifestation's onset. Particularly, in light of the COVID-19-related symptomatology, it has been hypothesized that SARS-CoV-2 might affect the dopamine pathway. However, no scientific evidence has been produced so far.To this end, human iPSC-derived dopaminergic neurons were infected with EU, Delta and Omicron SARS-CoV-2 variants. The infection with EU and Delta variants, but not with Omicron, results in a reduced intracellular content and extracellular release of dopamine. Indeed, the tyrosine hydroxylase was found to be significantly upregulated at the mRNA level, while being greatly reduced at the protein level. The major downstream synthetic enzyme DOPA-decarboxylase and the dopamine transporter were significantly downregulated both at the mRNA and protein level. Notably, in vitro SARS-CoV-2 infection was also associated with an altered MAP2 and TAU expression and with an increased presence of neuronal stress markers.These preliminary observations suggest that the dopamine metabolism and production are affected by SARS-CoV-2, partially explaining some of the neurological symptoms manifested.

ABSTRACT: The objective of these studies was to evaluate the impact of dietary muramidase (MUR) on endogenous amino acids (AA) losses and digestibility of nutrients in wheat and corn-based broiler diets. In experiment 1, the effect of dietary MUR on the flow of endogenous AA (EAA) at the jejunum and terminal ileum of broilers were assessed using either the nitrogen (N) free diet method (NFD) or the highly digestible protein diet method (HDP; 100 g casein/kg diet). Sialic acid and muramic acid concentrations were measured in the jejunal content. In experiment 2, a 2x2x2 factorial arrangement of treatments with 2 base grains (wheat or corn), with low or high metabolizable energy (ME) levels, and without or with MUR supplementation was implemented. All diets contained phytase, xylanase, and cellulase. Apparent ileal digestibility (AID) of dry matter (DM), protein (CP), amino acids (AA), crude fat, and energy, as well as the apparent total tract metabolizability (ATTM) of DM, CP, and gross energy (GE) were determined. The standardized ileal digestibility (SID) of AA was obtained by correcting AID values for basal ileal EAA obtained from chicks fed with NFD or HDP in experiment 1, jejunal EAA flow of all AA was higher (P < 0.001) compared to the ileum, but this effect was method dependent. Jejunal, but not ileal, EAA flow measured with HDP was higher compared to NFD, as well as sialic acid (P < 0.001) and muramic acid (P < 0.004) concentrations. Muramidase inclusion had no effect on basal EAA flow, independently of the segment and the method used. In experiment 2, dietary MUR supplementation increased the AID of CP (P < 0.05), all AA, and tended (P = 0.07) to increase the AID of GE, independently of the cereal type used. However, ATTM of DM and GE, but not CP, increased with MUR inclusion compared with the control treatments, especially in wheat and low ME diets (P < 0.05). In conclusion, MUR supplementation improved AID of CP and AA without affecting EAA losses and increases energy utilization.

Genetic deficiency of β-N-acetylhexosaminidase (Hex) functionality leads to accumulation of GM2 ganglioside in Tay-Sachs disease and Sandhoff disease (SD), which presently lack approved therapies. Current experimental gene therapy (GT) approaches with adeno-associated viral vectors (AAVs) still pose safety and efficacy issues, supporting the search for alternative therapeutic strategies. Here we leveraged the lentiviral vector (LV)-mediated intracerebral (IC) GT platform to deliver Hex genes to the CNS and combined this strategy with bone marrow transplantation (BMT) to provide a timely, pervasive, and long-lasting source of the Hex enzyme in the CNS and periphery of SD mice. Combined therapy outperformed individual treatments in terms of lifespan extension and normalization of the neuroinflammatory/neurodegenerative phenotypes of SD mice. These benefits correlated with a time-dependent increase in Hex activity and a remarkable reduction in GM2 storage in brain tissues that single treatments failed to achieve. Our results highlight the synergic mode of action of LV-mediated IC GT and BMT, clarify the contribution of treatments to the therapeutic outcome, and inform on the realistic threshold of corrective enzymatic activity. These results have important implications for interpretation of ongoing experimental therapies and for design of more effective treatment strategies for GM2 gangliosidosis.

ABSTRACT: An experiment was conducted to compare the use of a total and digestible Ca formulation system in broilers from hatch to d 37 post-hatch. Ross 308 (n = 288) male broilers were obtained and allocated to one of 2 dietary treatments in floor pens. There were 18 birds per pen and 8 replicate pens per diet. One diet was formulated using ingredient and nutrient recommendations for total Ca and the second diet was formulated using ingredient and nutrient recommendations for standardized ileal digestible (SID) Ca. All diets were formulated to be nutrient adequate using a 2-phase feeding program and including 0.19% available P (avP) and 0.209% total Ca or 0.073% digestible Ca from 1,000 FYT/kg of phytase. On d 17 and 37, tibias and ileal contents were obtained. From hatch to d 37, birds fed diets formulated using digestible Ca gained (P < 0.05) more and were more efficient (P < 0.05) compared with birds fed diets formulated using total Ca. There was no impact of formulation system on tibia ash or minerals. Litter pH (P < 0.05) was greater and litter dry matter (P < 0.05) was lower in birds fed the diets formulated using digestible Ca compared with those fed diets formulated using total Ca. Apparent ileal digestibility (AID) of Ca (P < 0.05), AID of P (P < 0.05) and digestible P intake (P < 0.05) were lower in birds fed diets formulated using digestible Ca compared with those formulated using total Ca at d 17 or 37. However, apparent ileal digested Ca and digestible Ca intake were not different between the experimental diets on d 17 or 37. In conclusion, formulating diets using digestible Ca improved weight gain and feed conversion ratio, but reduced the AID of Ca and P compared with birds fed diets formulated using total Ca. These findings might be reflective of the higher total Ca concentration in the diets formulated using digestible Ca compared with those formulated using total Ca.

The spread of artificial intelligence (AI) technologies in ever-widening domains (e.g., virtual assistants) increases the chances of daily interactions between humans and AI. But can non-human agents influence human beings and perhaps even surpass the power of the influence of another human being? This research investigated whether people faced with different tasks (objective vs. subjective) could be more influenced by the information provided by another human being or an AI. We expected greater AI (vs. other humans) influence in objective tasks (i.e., based on a count and only one possible correct answer). By contrast, we expected greater human (vs. AI) influence in subjective tasks (based on attributing meaning to evocative images). In Study 1, participants (N = 156) completed a series of trials of an objective task to provide numerical estimates of the number of white dots pictured on black backgrounds. Results showed that participants conformed more with the AI's responses than the human ones. In Study 2, participants (N = 102) in a series of subjective tasks observed evocative images associated with two concepts ostensibly provided, again, by an AI or a human. Then, they rated how each concept described the images appropriately. Unlike the objective task, in the subjective one, participants conformed more with the human than the AI's responses. Overall, our findings show that under some circumstances, AI can influence people above and beyond the influence of other humans, offering new insights into social influence processes in the digital era.

ABSTRACT: Three independent trials were conducted to evaluate the efficacy of a novel phytase in laying hens. Trial 1 used a total of 90 laying hens (Lohmann Brown, 33-wk-old) fed either a negative control (NC) diet with 0.09% non-phytate P (NPP) or NC supplemented with 187.5 or 375 FYT phytase/kg feed for 4 d before collection of excreta and ileal digesta to measure ileal digestibility and retention of Ca and P. In trial 2 and 3, a total of 108 laying hens (Hy Line Brown, 25-wk-old) and 360 hens (Lohman Brown, 25-wk-old) were used, respectively. In both trials, the hens were randomly assigned to 3 dietary treatments: NC with 0.1% NPP, positive control (PC) and NC plus 187.5 FYT phytase/kg feed, the experimental diets were fed for 12 wk, and egg production and bone mineralization were measured. The results showed that the ileal digestibility of P increased both linearly (P = 0.012) and quadratically (P = 0.01) with increasing supplementation of phytase in trial 1. In trial 2, phytase supplementation significantly improved egg production, egg weight, and feed conversion ratio and reduced the percentage of broken eggs during the overall trial duration compared with NC. In trial 3, phytase significantly improved egg production, egg weight, and feed intake and reduced the percentage of broken eggs during the entire trial duration. In addition, percentage and weight of bone Ca and P increased significantly with added phytase. In trial 2 and 3, there was no significant difference between PC and the phytase treatment. In conclusion, the novel phytase significantly increased the ileal digestibility of P in a short-term digestibility study and improved egg production and bone mineralization in a 12-wk laying cycle. Ileal digestibility of P rather than P retention in short-term digestibility studies as well as egg production and whole tibia mineralization in long-term studies should be measured to demonstrate the efficacy of phytase in laying hens.

Among plastic additives, bisphenol A (BPA), used mainly in manufacturing objects of everyday use, has received considerable attention for acting as a xenoestrogen and causing endocrine disruption. We now observe its rapid replacement with analogue compounds with similar structures (BPs) whose safety is not fully demonstrated. The present paper investigates the possible adverse effects of BPA, BPF, and BPS on DNA integrity of two gammarid species, Echinogammarus veneris and Gammarus aequicauda, to assess the environmental risk posed by these compounds in the aquatic ecosystem. Moreover, we analysed the cell-specific sensitivity to BPs using somatic (hemocytes) and germ (spermatozoa) cells that could have wide-ranging implications for their reproductive biology and long-term adverse effects at the population level. Results demonstrate that BPA and its analogues caused a genotoxic impact and highlighted lower genotoxic damage induced in sperm cells in both species tested. The implications of the findings of this study on the aquatic ecosystem are discussed, taking into account the critical role of amphipods within the freshwater trophic chain.

Introduction: Silicon dioxide, produced as synthetic amorphous silica (SAS), is made of nanoparticles (NPs), either present as such or as agglomerates and aggregates, and is widely used in many types of food processes and products as an additive. To assess whether repeated, long-term exposure to SAS NPs may result in adverse effects, mice were exposed for 18 months via drinking water to NM-200, one of the reference nanostructured silica used for applications related to food, at 4.8 mg NM-200/kg body weight per day, a dose relevant to the estimated dietary exposure to SAS in humans. Methods: The experiment focused on the kidney and liver as target organs and was carried out in parallel using 3 mouse lines (wild type and transgenic) differing for the expression of α-synuclein, that is, murine and human mutated (A53T). Sensitive determination of silicon revealed higher contents in liver and kidneys of NM-200–exposed mice compared with unexposed aged-matched controls. Results: Histological abnormalities, such as vacuolization of tubular epithelial cells, were detected in all kidneys, as well as inflammatory responses that were also detected in livers of exposed animals. Less frequent but more deleterious, amyloidosis lesions were observed in glomeruli, associated with perivascular amyloid accumulation in liver. Conclusion: These histological findings, in conjunction with the observation of detectable deposition of silica, highlight that chronic oral intake of SAS may pose a health risk to humans and need to be examined further. Keywords: chronic oral exposure, E551, kidney, mice, nanoparticles, silica

Universities and other organizations providing higher level education are collectively called Higher Education Institutions. Their detail data, for instance number of students, number of graduates, etc., constitute the basis for several important analyses of the educational systems. This work provides data of the European Tertiary Education Register (ETER), which describes the Educational Institutions of Europe. These data have been gathered through the National Statistical Authorities of all the Countries participant in the ETER Project. However, they include many scattered missing values. Therefore, we have developed and applied an imputation methodology (see “Imputation Techniques for the Reconstruction of Missing Interconnected Data from Higher Educational Institutions, Bruni et al. [3]) to replace the missing values with feasible values being as similar as possible to the original values that have been lost and are now unknown. Thus, we also provide the imputed version of the same dataset, which allows more in-depth analyses of the European Higher Education Institutions. Both datasets (before and after imputation) are provided in two versions: with or without bibliometric information for the Institutions, so the user can also consider these additional information if interested.

The imputation of missing values in the detail data of Educational Institutions is a difficult task. These data contain multivariate time series, which cannot be satisfactory imputed by many existing imputation techniques. Moreover, almost all the data of an Institution are interconnected: the number of graduates is not independent from the number of students, the expenditure is not independent from the staff, etc. In other words, each imputed value has an impact on the whole set of data of the institution. Therefore, imputation techniques for this specific case should be designed very carefully. We describe here the methods and the codes of the imputation methodology developed to impute the various patterns of missing values which appear in similar interconnected data. In particular, a first part of the proposed methodology, called ``trend smoothing imputation'', is designed to impute missing values in time series by respecting the trend and the other features of an Institution. The second part of the proposed methodology, called ``donor imputation'', is designed to impute larger chunks of missing data by using values taken form similar Institutions in order to respect again their size and trend. • Trend smoothing imputation can handle missing subsequences in time series, and is given by a weighted combination of: (a) weighed average of the other available values of the sequence, and (b) linear regression. • Donor imputation can handle full sequence missing in time series. It imputes the Recipient Institution using the values taken from a similar institution, called Donor, selected using optimization criteria. • The values imputed by our techniques should respect the trend, the size and the ratios of each Institution.

The data described in this article are supplementary to our primary article “Platelet factor 4 regulates T cell effector functions in malignant pleural effusions”. Malignant pleural effusion (MPE) is a common complication of advanced lung adenocarcinoma (LAC) associated with a poor life expectancy [1]. Several challenges need to be addressed to identify non-invasive molecular biomarkers that help to predict the prognosis of LAC patients with MPE [2]. In the primary publication, we proposed that platelet-derived factors, especially platelet factor 4 (PF4), can negatively regulate T lymphocyte activation and granzyme B expression in pleural metastasis and its levels were associated with a worse prognosis. Here, we provide data on the influence of other platelet-derived factors, including transforming growth factor β (TGF-β), vascular endothelial factor (VEGF), and P-selectin on T lymphocyte response in MPE and their relevance as prognostic factors in lung cancer patients with pleural metastasis. Pleural fluids from 35 lung adenocarcinoma (LAC) and 20 heart failure (HF) patients were collected by thoracentesis and its platelet-derived factors’ content was measured by specific enzyme-linked immunosorbent assay (ELISAs). Correlations between pleural levels of platelet-derived factors and T cell functions were analyzed by Pearson coefficients. Kaplan-Meier curves were used to estimate the effect of pleural concentrations of platelet-derived factors on overall survival of LAC patients with pleural metastasis. These analyses showed that the concentration of platelet-derived factors was not associated with T cell proliferation and cytotoxicity. Furthermore, their levels do not predict the survival of LAC with MPE.

The favorable outcome of in vivo and ex vivo gene therapy approaches in several Lysosomal Storage Diseases suggests that these treatment strategies might equally benefit GM2 gangliosidosis. Tay-Sachs and Sandhoff disease (the main forms of GM2 gangliosidosis) result from mutations in either the HEXA or HEXB genes encoding, respectively, the α- or β-subunits of the lysosomal β-Hexosaminidase enzyme. In physiological conditions, α- and β-subunits combine to generate β-Hexosaminidase A (HexA, αβ) and β-Hexosaminidase B (HexB, ββ). A major impairment to establishing in vivo or ex vivo gene therapy for GM2 gangliosidosis is the need to synthesize the α- and β-subunits at high levels and with the correct stoichiometric ratio, and to safely deliver the therapeutic products to all affected tissues/organs.Here, we report the generation and in vitro validation of novel bicistronic lentiviral vectors (LVs) encoding for both the murine and human codon optimized Hexa and Hexb genes. We show that these LVs drive the safe and coordinate expression of the α- and β-subunits, leading to supranormal levels of β-Hexosaminidase activity with prevalent formation of a functional HexA in SD murine neurons and glia, murine bone marrow-derived hematopoietic stem/progenitor cells (HSPCs), and human SD fibroblasts. The restoration/overexpression of β-Hexosaminidase leads to the reduction of intracellular GM2 ganglioside storage in transduced and in cross-corrected SD murine neural progeny, indicating that the transgenic enzyme is secreted and functional. Importantly, bicistronic LVs safely and efficiently transduce human neurons/glia and CD34+ HSPCs, which are target and effector cells, respectively, in prospective in vivo and ex vivo GT approaches.We anticipate that these bicistronic LVs may overcome the current requirement of two vectors co-delivering the α- or β-subunits genes. Careful assessment of the safety and therapeutic potential of these bicistronic LVs in the SD murine model will pave the way to the clinical development of LV-based gene therapy for GM2 gangliosidosis.

Background: Transcranial direct current stimulation (tDCS) may promote the recovery of severely brain-injured patients with disorders of consciousness (DOC). Prior tDCS studies targeted single brain regions rather than brain networks critical for consciousness recovery. Objective: Investigate the behavioral and electrophysiological effects of multifocal tDCS applied over the frontoparietal external awareness network in patients with chronic acquired DOC. Methods: Forty-six patients were included in this randomized double-blind sham-controlled crossover trial (median [interquartile range]: 46 [35 – 59] years old; 12 [5 – 47] months post injury; 17 unresponsive wakefulness syndrome, 23 minimally conscious state (MCS) and 6 emerged from the MCS). Multifocal tDCS was applied for 20 min using 4 anodes and 4 cathodes with 1 mA per electrode. Coma Recovery Scale-Revised (CRS-R) assessment and 10 min of resting state electroencephalogram (EEG) recordings were acquired before and after the active and sham sessions. Results: At the group level, there was no tDCS behavioral treatment effect. However, following active tDCS, the EEG complexity significantly increased in low frequency bands (1–8 Hz). CRS-R total score improvement was associated with decreased baseline complexity in those bands. At the individual level, after active tDCS, new behaviors consistent with conscious awareness emerged in 5 patients. Conversely, 3 patients lost behaviors consistent with conscious awareness. Conclusion: The behavioral effect of multifocal frontoparietal tDCS varies across patients with DOC. Electrophysiological changes were observed in low frequency bands but not translated into behavioral changes at the group level.

This research introduces dynamic modeling and real-time control of fractal structure in particulate materials fabricated by the ball milling process, specifically addressing challenges of unavailable real-time non-destructive and non-invasive imaging measurements in the enclosed rotating vials. A description of the internal temperature dynamics in the container is established along with a thermal regulator based on external temperature feedback. The fractal dimension is introduced as a structural measure, and its dynamics is established via an analytical formulation through a lumped model, along with a full thermostructural computational model of the ball milling particulate microstructure. These models are used as real-time observers of inaccessible internal states during the process. In addition, they are used as model references in an adaptive control system, regulating the fractal structure with adaptation via external temperature measurements, available experimentally via an infrared thermocouple. The controller is designed on the basis of the dynamic models and is tested experimentally. The controller is demonstrated to command the duration of the process at steady conditions to obtain the necessary thermal exposure yielding the desired microstructure for the ball-milled particulates. Keywords: Ball milling, Adaptive control, Aluminum alloys, Fractal dimension

Summary: Multiple system atrophy (MSA) is a progressive neurodegenerative disease that affects several areas of the CNS, whose pathogenesis is still widely unclear and for which an effective treatment is lacking. We have generated induced pluripotent stem cell-derived dopaminergic neurons from four MSA patients and four healthy controls and from two monozygotic twins discordant for the disease. In this model, we have demonstrated an aberrant autophagic flow and a mitochondrial dysregulation involving respiratory chain activity, mitochondrial content, and CoQ10 biosynthesis. These defective mechanisms may contribute to the onset of the disease, representing potential therapeutic targets. : Monzio Compagnoni et al. present an iPSC-based neuronal in vitro model of multiple system atrophy. Patients' dopaminergic neurons display a dysregulation of mitochondrial functioning and autophagy, suggesting new hints for the comprehension of the pathogenesis of the disease. Keywords: multiple system atrophy, induced pluripotent stem cells, dopaminergic neurons, mitochondria, autophagy, MSA, neurodegeneration

The deoxynivalenol (DON) occurrence in durum wheat (Triticum durum Desf.) kernels is a key food safety issue, hence more and more attempts have been made to increase the availability of resistant cultivars. Within this framework, this work focused on the analysis of the behaviour of several durum wheat cultivars widely grown in Italy in relation to the level of deoxynivalenol contamination in whole milled kernels. A total of 2844 samples were submitted for deoxynivalenol analysis by enzyme-linked immuno-sorbent assay. The statistical analysis by generalised linear models provided a trend ranking of durum wheat cultivars on the basis of the deoxynivalenol contamination level, depending on each cultivation area assayed. This study provided a better understanding of cultivar susceptibility to mycotoxin accumulation in grains. The role of the factor cultivar has clearly emerged. However, other environmental factors, such as growing area, have a great influence on the DON concentration levels in the cultivars tested.

El Servicio de Atención Primaria de Santa Coloma de Gramenet ha diseñado un sistema que estandariza y automatiza la planificación de coberturas de personal sanitario. Está dividido en dos partes: una calculadora que en función de parámetros de actividad y presión asistencial orienta sobre el riesgo previsible derivado de nuestra planificación, y otra con indicadores centinela; el principal es el «nivel básico asistencial», definido como el porcentaje de usuarios atendidos a 2, 3 y 7 días naturales, y valora su repercusión en la asistencia a la población. Los resultados en el verano de 2010 muestran un aumento de la eficiencia al disminuir la plantilla presencial respecto al año 2009, conseguir una mejor distribución de ésta en el periodo acorde con la actividad realizada y mejorar la gestión presupuestaria. Puesto que los datos necesarios están disponibles y su cálculo es sencillo, puede ser exportable a todo nuestro ámbito.The Santa Coloma de Gramenet Primary Care Service has designed a new tool to standardize and automate the process of planning the number of needed health care workers. The tool is divided in two parts: a calculator, which gives guidance on the foreseeable risk depending on the activity and the health care workers' workload, and sentinel indicators; the main is the "welfare basic level", that is the percentage structure of visited patients and their delay at 2, 3 and 7 calendar days, assessing the impact on the care of the population. The results of its use in the summer of 2010 have demonstrated its efficiency by lowering the needed workers with respect to 2009, achieving a better distribution according to the workload and improving the economic management. Given that the necessary data are accessible through computerized databases and its simple use, we believe it to be exportable to other fields.

The dihydroceramide, ceramide, sphingomyelin, lactosylceramide, and ganglioside species of A2780 human ovarian carcinoma cells treated with the synthetic retinoids N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR) and 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) in culture were characterized by ESI-MS. We characterized 32 species of ceramide and dihydroceramide, 15 of sphingomyelin, 12 of lactosylceramide, 9 of ganglioside GM2, and 6 of ganglioside GM3 differing for the long-chain base and fatty acid structures. Our results indicated that treatment with both 4-HPR and 4-oxo-4-HPR led to a marked increase in dihydroceramide species, while only 4-oxo-4-HPR led to a minor increase of ceramide species. Dihydroceramides generated in A2780 cells in response to 4-HPR or 4-oxo-4-HPR differed for their fatty acid content, suggesting that the two drugs differentially affect the early steps of sphingolipid synthesis. Dihydroceramides produced upon treatments with the drugs were further used for the synthesis of complex dihydrosphingolipids, whose levels dramatically increased in drug-treated cells.

Human fibroblasts from normal subjects and Niemann-Pick A (NPA) disease patients were fed with two labeled metabolic precursors of sphingomyelin (SM), [3H]choline and photoactivable sphingosine, that entered into the biosynthetic pathway allowing the synthesis of radioactive phosphatidylcholine and SM, and of radioactive and photoactivable SM ([3H]SM-N3). Detergent resistant membrane (DRM) fractions prepared from normal and NPA fibroblasts resulted as highly enriched in [3H]SM-N3. However, lipid and protein analysis showed strong differences between the two cell types. After cross-linking, different patterns of SM-protein complexes were found, mainly associated with the detergent soluble fraction of the gradient containing most cell proteins. After cell surface biotinylation, DRMs were immunoprecipitated using streptavidin. In conditions that maintain the integrity of domain, SM-protein complexes were detectable only in normal fibroblasts, whereas disrupting the membrane organization, these complexes were not recovered in the immunoprecipitate, suggesting that they involve proteins belonging to the inner membrane layer. These data suggest that differences in lipid and protein compositions of these cell lines determine specific lipid-protein interactions and different clustering within plasma membrane. In addition, our experiments show that photoactivable sphingolipids metabolically synthesized in cells can be used to study sphingolipid protein environments and sphingolipid-protein interactions.

Objetivo: : Realizar una aproximación a la metodología de árboles de decisión tipo CART (Classification and Regression Trees) desarrollando un modelo para calcular la probabilidad de muerte hospitalaria en infarto agudo de miocardio (IAM). Método: Se utiliza el conjunto mínimo básico de datos al alta hospitalaria (CMBD) de Andalucía, Cataluña, Madrid y País Vasco de los años 2001 y 2002, que incluye los casos con IAM como diagnóstico principal. Los 33.203 pacientes se dividen aleatoriamente (70 y 30 %) en grupo de desarrollo (GD = 23.277) y grupo de validación (GV = 9.926). Como CART se utiliza un modelo inductivo basado en el algoritmo de Breiman, con análisis de sensibilidad mediante el índice de Gini y sistema de validación cruzada. Se compara con un modelo de regresión logística (RL) y una red neuronal artificial (RNA) (multilayer perceptron). Los modelos desarrollados se contrastan en el GV y sus propiedades se comparan con el área bajo la curva ROC (ABC) (intervalo de confianza del 95%). Resultados: En el GD el CART con ABC = 0,85 (0,86-0,88), RL 0,87 (0,86-0,88) y RNA 0,85 (0,85-0,86). En el GV el CART con ABC = 0,85 (0,85-0,88), RL 0,86 (0,85-0,88) y RNA 0,84 (0,83-0,86). Conclusiones: Los 3 modelos obtienen resultados similares en su capacidad de discriminación. El modelo CART ofrece como ventaja su simplicidad de uso y de interpretación, ya que las reglas de decisión que generan pueden aplicarse sin necesidad de procesos matemáticos.Objective: To provide an overview of decision trees based on CART (Classification and Regression Trees) methodology. As an example, we developed a CART model intended to estimate the probability of intrahospital death from acute myocardial infarction (AMI). Method: We employed the minimum data set (MDS) of Andalusia, Catalonia, Madrid and the Basque Country (2001-2002), which included 33,203 patients with a diagnosis of AMI. The 33,203 patients were randomly divided (70% and 30%) into the development (DS; n = 23,277) and the validation (VS; n = 9,926) sets. The CART inductive model was based on Breiman's algorithm, with a sensitivity analysis based on the Gini index and cross-validation. We compared the results with those obtained by using both logistic regression (LR) and artificial neural network (ANN) (multilayer perceptron) models. The developed models were contrasted with the VS and their properties were evaluated with the area under the ROC curve (AUC) (95% confidence interval [CI]). Results: In the DS, the CART showed an AUC = 0.85 (0.86-0.88), LR 0.87 (0.86-0.88) and ANN 0.85 (0.85-0.86). In the VS, the CART showed an AUC = 0.85 (0.85-0.88), LR 0.86 (0.85-0.88) and ANN 0.84 (0.83-0.86). Conclusions: None of the methods tested outperformed the others in terms of discriminative ability. We found that the CART model was much easier to use and interpret, because the decision rules generated could be applied without the need for mathematical cal

This work shows the results of trials carried out over three years (2006-2008) within the national networks of durum wheat grown under conventional and organic cropping systems in six representative locations of the main cultivation areas of Italy. The main aspects of grain yield and grain quality were analyzed, particularly assessing the hygienic health status of the grain in relation to the possible presence of deoxynivalenol (DON) contamination. DON is considered the most common trichothecene mycotoxin found in the wheat grain, causing significant reductions in grain yield and adverse effects for human or animal consumption. In the studied period the average grain yields were quite interesting both in conventional samples (5.85 t ha-1) and in organic ones (4.91 t ha-1). As expected, the organic yields were significantly different(-16%). However, in the southern locations the same differences were lower (-5%), thus emphasizing the limited impact of the higher inputs of the conventional cropping in these environments. The reduced nitrogen input is notoriously the most critical point of organic wheat, because the protein content is the most sensitive parameter of grain quality. The protein content was significantly different among year, fields location and cropping system, but not among their interactions. Grain protein content in organic wheat was lower than in conventional one all over the three years; anyway, differences were somewhat limited (only about 1% in the southern locations and 0.5% in central Italy). Among cultivars no significant differences in the protein content were recorded. Mean levels of DON contamination during the study period were generally lower, with only a sample exceeding the legal limit of 1750 ppb. Among the main factors, year and location (and their interaction) had a strong influence on DON contamination, accounting for 75% of the observed variability. DON levels in 2008 at Papiano-PG were dramatically high; the strong influence of the year-location interaction may be due to this fact. Cropping system and cultivar, although significant, had a low influence; however, their interaction accounted for 13% of total variance. Cropping system – location interaction accounted for 5% of the total variability. Very low levels of DON were detected in the southern locations with both cropping systems; the lower levels were recorded in organic wheat samples. In the central Italy areas DON could represent a potential hazard, but even in these organically cropped environments wheat gave the best results. Lower concentrations of DON were detected in organic wheat samples, either in less favourable years for the occurrence of Fusarium (2006 and 2007) and in the more favourable one (2008). Regarding the role of the varietal choice, Creso revealed to be the less susceptible to DON contamination, probably as it is the best adapted to the areas of the Central Italy, where Fusarium is more widespread.

The intestinal microbiota is an ecosystem formed by a variety of ecological niches, made of several bacterial species and a very large amount of strains. The microbiota is in close contact with the intestinal mucosa or epithelial interface which is, after the respiratory area, the largest surface of the body, occupying approximately 250-400 m(2). The physiological activities of the microbiota are manifold and are just being unraveled. Based on the observations of the multiple roles played by the microbiota in health and disease, the notion of modifying it with appropriate formulations, i.e. probiotics, is being tested in several settings. This review summarizes the current knowledge on probiotics and discusses both limitations and acquired evidence to support their use in preventive and therapeutic medicine., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This work was undertaken to study the serotypes and pulsotypes of 674 Listeria monocytogenes isolates from human (57), food (558) and environmental (59) sources, collected from different Italian geographical areas during 2002-2005, to determine whether certain subtypes were associated with certain foods and more often involved in cases of listeriosis, and to determine possible geographical or temporal associations. Eleven different L. monocytogenes serotypes were found in the food, environmental and human isolates. Most isolates belonged to only four serotypes (1/2a, 1/2b, 1/2c, 4b). The isolates were divided into 133 distinct AscI pulsotypes grouped into 26 pulsogroups. Pulsogroups ranged from a minimum of 2 up to 212 isolates, and contained 1-19 different pulsotypes. When associations between subtypes and isolates from specific foods selected as being most frequently involved in cases of listeriosis were tested some of these associations were highly significant but not exclusive, indicating that there was no close correlation between specific subtypes and specific food products. Despite the limitations of this study (few human isolates versus many food isolates prevalently collected from one food category), we believe that a large-scale database of L. monocytogenes subtypes and a timely epidemiological investigation can facilitate risk assessment and outbreak detection and control.

The importance of non-pharmacological control of plasma cholesterol levels in the population is increasing, along with the number of subjects whose plasma lipid levels are non-optimal, or frankly elevated, according to international guidelines. In this context, a panel of experts, organized and coordinated by the Nutrition Foundation of Italy, has evaluated the nutritional and lifestyle interventions to be adopted in the control of plasma cholesterol levels (and specifically of LDL cholesterol levels). This Consensus document summarizes the view of the panel on this topic, with the aim to provide an updated support to clinicians and other health professionals involved in cardiovascular prevention.

Recent genome sequencing of isolates of Listeria monocytogenes serotype 4b implicated in some major outbreaks of foodborne listeriosis has revealed unique genetic markers in these isolates. The isolates were grouped into two distinct epidemic clones, ECI and ECII. In the present study, selected ECI- and ECII-specific genetic markers were detected in 16 and 15 of 89 L. monocytogenes 4b isolates, respectively. The ECI markers were found in 6 of 34 clinical isolates, 9 of 50 food isolates, and 1 of 5 environmental isolates, and the ECII markers were detected in 7 of 34 clinical isolates, 7 of 50 food isolates, and 1 of 5 environmental isolates. Hence, of the isolates with the epidemic clonal genetic markers, 38% (13 of 34) were of clinical origin, 32% (16 of 50) were of food origin, and 40% (2 of 5) were of environmental origin. The predominance of the epidemic clonal markers among the clinical and environmental isolates supports the hypothesis that these markers are correlated with the pathogenic potential of strains and with their environmental persistence. Several isolates had only one epidemic clonal marker, either the ECI-specific marker 133 or the ECII-specific marker 4bSF18. Pulsed-field gel electrophoresis analysis revealed higher genomic diversity among the strains with ECII-like characteristics than among those strains carrying the ECI-specific genetic markers.

This study was undertaken to supplement existing information on the survival of Listeria monocytogenes in Italian salami. The fact that Italian salami is frequently consumed by a large number of people poses some serious health implications. Some raw materials have been found to be microbiologically contaminated, for their production occurs without any thermic treatment, and these are in circulation throughout Italy all year round. We selected the product for its microbiological, technological, and commercial characteristics. We analyzed 1,020 samples taken during the autumn and winter 2002 and spring and summer 2003 periods and immediately before selling. The samples were collected from 17 plants with an annual production of between 1 and 2000 metric tons and with a distribution of products in over 80% of Italy in geographic terms. To detect and enumerate L. monocytogenes, we followed International Organization for Standardization (ISO) 11290 part 1 and 2: 1996 (modified using chromogenic medium Agar Listeria according to Ottarviani and Agosti [ALOA]). L. monocytogenes was found in 22.7% of samples, but the contamination level was less than 10 CFU/g. Contamination prevalence ranged from 1.6 to 58.3% and was lower than 10% in 5 of the 17 plants checked. The most frequently isolated serotypes were 1/2c, 1/2a, 1/2b, and 4b. Additional studies are necessary to establish if the exposure to a small number of L. monocytogenes cells through the consumption of salami represents a significant health risk and, in light of the future introduction of the SANCO/4198/2001 revision 21 "Commission Regulation on Microbiological Criteria for Foodstuffs," is a necessary investigation.

Microbial strains traditionally used to ferment food have a long history of safe use and are, therefore, considered as generally recognised as safe. Many of these micro-organisms have also functional attributes and are included among probiotics. New species and strains of bacteria with desirable technological and functional properties are constantly being identified; in addition, micro-organisms can be engineered by recently developed biotechnological tools in order to accelerate strain improvement. Although the potentialities of novel micro-organisms with better probiotic and technological properties are promising, it cannot be assumed that they share the safety record of traditional micro-organisms, since they may pose unique challenges for human health. The risk assessment and safety evaluation of novel micro-organisms must focus, primarily, on their potential harmful effects, both direct and indirect, upon host resident intestinal microflora. Genetically modified micro-organisms need further assessment for the complete characterisation of the DNA rearrangement and of the final product, in order to establish the "substantial equivalence" with the parental strain.

Strains of Clostridium butyricum that produce botulinal toxin type E have been implicated in outbreaks of foodborne botulism in China, India, and Italy, yet the conditions that are favorable for the growth and toxinogenesis of these strains remain to be established. We attempted to determine the temperatures and pH levels that are most conducive to the growth of and toxin production by the six strains of neurotoxigenic C. butyricum that have been implicated in outbreaks of infective and foodborne botulism in Italy. The strains were cultured for 180 days on Trypticase-peptone-glucose-yeast extract broth at various pHs (4.6, 4.8, 5.0, 5.2, 5.4, 5.6, and 5.8) at 30 degrees C and at various temperatures (10, 12, and 15 degrees C) at pH 7.0. Growth was determined by checking for turbidity; toxin production was determined by the mouse bioassay. We also inoculated two foods: mascarpone cheese incubated at 25 and 15 degrees C and pesto sauce incubated at 25 degrees C. The lowest pH at which growth and toxin production occurred was 4.8 at 43 and 44 days of incubation, respectively. The lowest temperature at which growth and toxin production occurred was 12 degrees C, with growth and toxin production first being observed after 15 days. For both foods, toxin production was observed after 5 days at 25 degrees C. Since the strains did not show particularly psychrotrophic behavior, 4 degrees C can be considered a sufficiently low temperature for the inhibition of growth. However, the observation of toxin production in foods at room temperature and at abused refrigeration temperatures demands that these strains be considered a new risk for the food industry.

A total of 1,017 mascarpone cheese samples, collected at retail, were analyzed for Clostridium botulinum spores and toxin, aerobic mesophilic spore counts, as well as pH, a(w) (water activity), and Eh (oxidation-reduction potential). In addition 260 samples from other dairy products were also analyzed for spores and botulinum toxin. Experiments were carried out on naturally and artificially contaminated mascarpone to investigate the influence of different temperature conditions on toxin production by C. botulinum. Three hundred and thirty-one samples (32.5%) of mascarpone were positive for botulinal spores, and 7 (0.8%) of the 878 samples produced at the plant involved in an outbreak of foodborne botulism also contained toxin type A. The chemical-physical parameters (pH, a(w), Eh) of all samples were compatible with C. botulinum growth and toxinogenesis. Of the other milk products, 2.7% were positive for C. botulinum spores. Growth and toxin formation occurred in naturally and experimentally contaminated mascarpone samples after 3 and 4 days of incubation at 28 degrees C, respectively.

The maternal-fetal transfer of tobramycin (TBM) was investigated in the rat by means of a microbiological assay, to assess the presence and amount in the kidneys and placentae of fetuses at gestational day (GD) 20, in the kidneys of newborns 6 and 11 days after the end of treatment and in the kidneys of the dams. In the qualitative assay, pregnant rats were injected i.p. with 0, 30, 60 mg/kg b.w. of TBM on GD 10-19. A group of dams treated in parallel with 30 mg/kg b.w. was utilized for a microbiological semiquantitative assay. All litters contained some fetuses showing no detectable TBM accumulation in either kidney or in placentae: at 30 mg/kg/b.w. accumulation appeared more prevalent in placenta than in the kidneys of the corresponding fetuses, as confirmed also by the semiquantitative assay. Some newborns (about 6%) of both groups showed detectable renal TBM residues on the 6th and on the 11th day after the end of treatment. The frequency of newborns showing residues was not obviously related to the dose or the day of sampling, and the concentrations of TBM found were comparable to those observed in fetuses. It is possible that they represent a particularly sensitive subgroup.

The antimicrobial activity of 32 plant essential oils commonly used in food industry was examined against four strains of Listeria monocytogenes and one strain of Listeria innocua . Two different procedures were carried out to test the essential oils, a paper disc diffusion method and an inhibition curve. In the former procedure an absolute ethanolic solution (1:5 v/v) of each oil was tested on the plates inoculated with a bacterial concentration of 10 6 CFU/ml. Five of the 32 essential oils (cinnamon, clove, origanum, pimento, and thyme) showed antibacterial activity. Some of the five oils were also tested at lower concentration (1:50 v/v). The inhibition curve to study antilisteric efficacies of the five oils in a saline solution system was examined. Pimento oil showed marked and rapid activity (generally within 1 h of exposure), whereas clove, origanum, and thyme oils showed a more slow activity. The antilisteric activity of the tested oils seems to be strain dependent. A L. monocytogenes strain was also tested in a food matrix (minced pork meat) against thyme essential oil. Minced pork meat with thyme oil reduced the L. monocytogenes population by ca. 100-fold over the first week of storage.