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Background: Transcription in mammalian cells is a complex stochastic process involving shuttling of polymerase between genes and phase-separated liquid condensates. It occurs in bursts, which results in vastly different numbers of an mRNA species in isogenic cell populations. Several factors contributing to transcriptional bursting have been identified, usually classified as intrinsic, in other words local to single genes, or extrinsic, relating to the macroscopic state of the cell. However, some possible contributors have not been explored yet. Here, we focus on processes at the 3 ' and 5 ' ends of a gene that enable reinitiation of transcription upon termination., Results: Using Bayesian methodology, we measure the transcriptional bursting in inducible transgenes, showing that perturbation of polymerase shuttling typically reduces burst size, increases burst frequency, and thus limits transcriptional noise. Analysis based on paired-end tag sequencing (PolII ChIA-PET) suggests that this effect is genome wide. The observed noise patterns are also reproduced by a generative model that captures major characteristics of the polymerase flux between the ends of a gene and a phase-separated compartment., Conclusions: Interactions between the 3 ' and 5 ' ends of a gene, which facilitate polymerase recycling, are major contributors to transcriptional noise.

Background: Radiofrequency ablation (RFA) has gained ground as an effective and well-tolerated technique to treat benign thyroid nodules. Most of the available studies have described the short-term outcomes of RFA, whereas there is a limited number of studies evaluating long-term issues, such as regrowth and the likelihood of retreatments. In addition, risk markers of regrowth and retreatment remain to be defined. The initial ablation ratio (IAR) is an index that measures the amount of ablation after RFA, which has been associated with technique efficacy (i.e. volume reduction >50% after 1 year from the procedure). This study aimed at evaluating i) IAR reproducibility and ii) IAR predictive value for RFA 5-year outcomes., Materials and Methods: This is a retrospective single center study on patients with benign thyroid nodules treated with RFA and followed for 5 years after initial treatment. IAR interobserver reproducibility was evaluated with Bland-Altman method and Lin's concordance correlation coefficient (ρc). IAR predictive value for RFA 5-year outcomes was evaluated with linear and logistic regression models, as well as with Cox models, while receiver operating characteristic (ROC) analyses were used for cut-offs., Results: We selected 78 patients with 82 benign thyroid nodules. The procedure significantly reduced nodule volume and this reduction was generally maintained over time. Technique efficacy was achieved in 92% of patients, while 23% of nodules regrew and 12% of nodules were retreated. Median IAR was 83%. Lin's concordance and Pearson's correlation coefficients suggested a good interobserver reproducibility of this index, consistent with the limits of agreement of the Bland-Altman plot. IAR was significantly associated with technique efficacy, 1- and 5-year volume reduction ratio, and with the likelihood of a retreatment, but not with nodule regrowth. ROC analyses showed that IAR cut-off was 49% for technique efficacy and 73% for retreatment., Conclusions: Our results show for the first time that IAR is reproducible and that it predicts the volume reduction and the likelihood of a retreatment after 5 years from RFA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bernardi, Cavallaro, Colombin, Giudici, Zuolo, Zdjelar, Dobrinja, De Manzini, Zanconati, Cova, Stacul and Fabris.)

Background: Radiofrequency ablation (RFA) and laser ablation (LA) are effective treatments for benign thyroid nodules. Due to their relatively recent introduction into clinical practice, there are limited long-term follow-up studies. This study aimed to evaluate technique efficacy, rate of regrowth, and retreatment over 5 years after RFA or LA and to identify predictive factors of outcome. Methods: In this multicenter retrospective study, the rates of technique efficacy, regrowth, and retreatment were evaluated in 406 patients treated with either RFA or LA, and followed for 5 years after initial treatment. Propensity score matching was used to compare treatments. Cumulative incidence studies with hazard models were used to describe regrowth and retreatment trends, and to identify prognostic factors. Logistic regression models and receiver operating characteristic analyses were used for risk factors and their cutoffs. Results: RFA and LA significantly reduced benign thyroid nodule volume, and this reduction was generally maintained for 5 years. Technique efficacy (defined as a reduction ≥50% after 1 year from the treatment) was achieved in 74% of patients (85% in the RFA and 63% in the LA group). Regrowth occurred in 28% of patients (20% in the RFA and 38% in the LA group). In the majority of cases, further treatment was not required as only 18% of patients were retreated (12% in the RFA and 24% in the LA group). These data were confirmed by propensity score matching. Cumulative incidence studies showed that RFA was associated with a lower risk of regrowth and a lower risk of requiring retreatment over time. Overall, technique inefficacy and regrowth were associated with low-energy delivery. Retreatments were more frequent in young patients, in large nodules, in patients with lower volume reduction at 1 year, and in cases of low-energy delivery (optimal cutoff was 918 J/mL for RFA). Conclusions: Both thermal ablation techniques result in a clinically significant and long-lasting volume reduction of benign thyroid nodules. The risk of regrowth and needing retreatment was lower after RFA. The need for retreatment was associated with young age, large baseline volume, and treatment with low-energy delivery.

The Atlantic salmon (Salmo salar) is a freshwater and marine fish of the family Salmonidae, widely farmed in aquaculture facilities in several countries. The salmon are carnivorous, but in aquaculture, alternative foods have been experienced. It is well known that feeding in captivity should cause adaptation and modifications of the morphological characteristics of the oral cavity, especially of tongue; therefore, the aim of this study was to investigate, by light, laser confocal and scanning electron microscopy, the morphological characteristics of the tongue dorsal surface, considering the importance of the correlations between feeding habits and the anatomy of the tongue. Scanning electron microscopy demonstrates the presence of caniniform teeth with oro-aboral orientation surrounded by numerous filiform papillae, single, fused or arranged in row. Oro-aborally, the papillae show an appearance like a rosette and they disappear at level of the root. Light and laser confocal microscopy demonstrates that the mucosa is covered by a non-keratinized stratified pavement epithelium with, in the deepest layer, the presence of a triangular structure whose apex is cranially directed and base facing aborally. In this structure, spindle-shaped cells are present, with a vimentin immunoreactivity, that for their characteristics could be adult mesenchymal stem cells. The obtained data could be useful not only for further studies on the nutrition, but it is interesting the detection of tissues typical of the embryo-fetal phase in the adult specimens tongue, thus giving a basis for studies of potential applications, if any, regarding cell therapies for different clinical indications., (© 2020 Wiley-VCH GmbH.)

Background: Patients with coronavirus infectious disease 2019 (COVID-19) and gastrointestinal symptoms showed increased values of fecal calprotectin (FC). Additionally, bowel abnormalities were a common finding during abdominal imaging of individuals with COVID-19 despite being asymptomatic. The current pilot study aims at evaluating FC concentrations in patients without gastrointestinal symptoms., Methods: we enrolled 25 consecutive inpatients with COVID-19 pneumonia, who were admitted without gastrointestinal symptoms and a previous history of inflammatory bowel disease., Results: At admission, 21 patients showed increased FC with median values of 116 (87.5; 243.5) mg/kg despite absent gastrointestinal symptoms. We found a strong positive correlation between FC and D-Dimer (r = 0.745, p < 0.0001). Two patients developed bowel perforation., Conclusion: our findings may change the current understanding of COVID-19 intestinal-related disease pathogenesis, shedding new light on the potential role of thrombosis and the consequent hypoxic intestinal damage.

Objective: Magnetic resonance enterography has achieved an increasingly importance in the evaluation of patients with Crohn's disease, although it is limited by high costs and prolonged scanning times. The aim of our work was to design a "fast" abbreviated MRE protocol and to compare it with the standard one., Materials and Methods: A single-center retrospective study was performed on 73 patients with Crohn's disease who underwent MRE with standard protocol over a 7-month period. The images of the standard protocol were separated from those included in the proposed abbreviated one and independently evaluated by two radiologists with different years of experience in MRE imaging. Statistical analysis was performed with the Cohen kappa (κ) value, used to assess the agreement in case of categorical variables, the Lin's concordance correlation coefficient and Bland-Altman plot, in assessing the degree of agreement between numerical measurements, while the non- parametric Mann-Whitney U-test was used in comparing the evaluation times of the two protocols., Results: The intraobserver evaluation showed a perfect agreement between the two protocols for presence, number and extension of lesions, abdominal complications, and excellent/perfect in identification of active inflammation.The interobserver reproducibility was excellent for overall presence and number of lesions, for the presence and number of lesions in any abdominal quadrant, inflammation, intestinal and extraintestinal complications, and lesions extension., Conclusion: The proposed protocol achieves comparable performance with standard MRE. Furthermore, it would carry potential benefits in terms of patient's comfort, time, and health-care costs savings., Competing Interests: There are no conflicts of interest., (© 2020 Published by Scientific Scholar on behalf of Journal of Clinical Imaging Science.)

Numerous data show that the chemosensory system seems to be modulated by changes in the circulating levels of different molecules such as ghrelin, orexin, leptin, NPY, CCK. The chemosensory system of the zebrafish is represented by the taste buds (skin, oral and oropharyngeal), the olfactory rosette and the solitary chemosensorial cells (SCCs). The purpose of our study was to analyze the distribution of two peripheral hormones such as ghrelin and leptin in the chemosensory organs of the zebrafish. Our results demonstrated the presence of immunoreaction for all antibodies used in the zebrafish chemosensory organs even if with different distribution. In particular, IR was observed for ghrelin in the olfactory rosette while IR for leptin was found in the olfactory rosette, in the skin and oropharyngeal taste buds and in the gills. Both these hormones were detected in the intestine, used as a control., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Unlike conventional computed tomography, dual-energy computed tomography is a relatively novel technique that exploits ionizing radiations at different energy levels. The separate radiation sets can be achieved through different technologies, such as dual source, dual layers or rapid switching voltage. Body tissue molecules vary for their specific atomic numbers and electron density, and the interaction with different sets of radiations results in different attenuations, allowing to their final distinction. In particular, iodine recognition and quantification have led to important information about intravenous contrast medium delivery within the body. Over the years, useful post-processing algorithms have also been validated for improving tissue characterization. For instance, contrast resolution improvement and metal artifact reduction can be obtained through virtual monoenergetic images, dose reduction by virtual non-contrast reconstructions and iodine distribution highlighting through iodine overlay maps. Beyond the evaluation of the abdominal organs, dual-energy computed tomography has also been successfully employed in other anatomical districts. Although lung perfusion is one of the most investigated, this evaluation has been extended to narrowly fields of application, such as musculoskeletal, head and neck, vascular and cardiac. The potential pool of information provided by dual-energy technology is already wide and not completely explored, yet. Therefore, its performance continues to raise increasing interest from both radiologists and clinicians.

Four specimens of Dosima fascicularis were collected from the Strait of Messina (Central Mediterranean Basin), representing the first record of the species from this locality, the second from Italian waters, and the most eastern indication of the species in the Mediterranean Sea.

The taxonomic, morphological and meristic features of a dark eel caught by commercial trawling off the Gulf of Patti, southern Tyrrhenian Sea, Mediterranean Sea, February 17, 2017, showed it to be a female Conger conger. Histological analysis of gonads demonstrated that the individual was in a post-spawning phase. X-ray radiographs showed widespread decalcification of skeleton and teeth loss, confirming a strong mobilisation of somatic energy reserves needed for reproductive development., (© 2019 The Fisheries Society of the British Isles.)

Background: Bone age (BA) assessment performed by artificial intelligence (AI) is of growing interest due to improved accuracy, precision and time efficiency in daily routine. The aim of this study was to investigate the accuracy and efficiency of a novel AI software version for automated BA assessment in comparison to the Greulich-Pyle method., Methods: Radiographs of 514 patients were analysed in this retrospective study. Total BA was assessed independently by three blinded radiologists applying the GP method and by the AI software. Overall and gender-specific BA assessment results, as well as reading times of both approaches, were compared, while the reference BA was defined by two blinded experienced paediatric radiologists in consensus by application of the Greulich-Pyle method., Results: Mean absolute deviation (MAD) and root mean square deviation (RSMD) were significantly lower between AI-derived BA and reference BA (MAD 0.34 years, RSMD 0.38 years) than between reader-calculated BA and reference BA (MAD 0.79 years, RSMD 0.89 years; p < 0.001). The correlation between AI-derived BA and reference BA (r = 0.99) was significantly higher than between reader-calculated BA and reference BA (r = 0.90; p < 0.001). No statistical difference was found in reader agreement and correlation analyses regarding gender (p = 0.241). Mean reading times were reduced by 87% using the AI system., Conclusions: A novel AI software enabled highly accurate automated BA assessment. It may improve efficiency in clinical routine by reducing reading times without compromising the accuracy compared with the Greulich-Pyle method.

The leopard gecko is a crepuscular and insectivorous reptile. The role of the tongue in this reptile is fundamental for the prey capture and ingestion and is not related with eyes cleaning as usual in other geckos. The elongated tongue can be divided into a foretongue with a slightly bifurcated apex and a hindtongue. Scanning electron microscopy demonstrated that several different papillae are present on the dorsal surface, foliate and dome-shaped in the foretongue, becoming thicker and stouter with reduced interpapillary spaces in the lateral parts. The hindtongue is characterised by wide foliate papillae with indented margins and deep fissures of the mucosa. Light microscopy showed the presence of a stratified slightly keratinized squamous epithelium in the apex of the foretongue, a stratified non-keratinized squamous epithelium in the fore and in the hindtongue. In the foretongue, numerous muciparous caliciform cells were observed. Moreover, the presence of taste buds on the tongue ventral surface was demonstrated for the first time in this species and the confocal laser study revealed a strong immunoreactivity for the S-100 protein in the sensory cells. Therefore, the results obtained could give a contribution to the knowledge of the tongue anatomy and are a basis for eventual further studies regarding the feeding habits in a reptile become a popular pet., (© 2019 Blackwell Verlag GmbH.)

The distribution of floating litter in marine waters, influenced by currents and wind drag, often determines the dispersal of its encrusting fauna. In the present paper, we observed for the first time the colonization of rafting floats from abandoned, lost or derelict fishing gears (ALDFG) by the four protected deep-sea species: Errina aspera, Desmophyllum pertusum, Madrepora oculata Pachylasma giganteum. Overall, 41 floats, colonized by deep benthic species, were found stranded on the shore of the Sicilian coast of the Strait of Messina, between 2016 and 2019. Species composition, number and occurrence of colonizing organisms were analyzed. On the basis of the species composition (the association between E. aspera, P. giganteum and Megabalanus tulipiformis), the knowledge on their ecology, biogeography, path of local currents, it was possible to define that the area of origin of the most part of these fishing net floats was the Strait of Messina., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Abdominal aortic graft infections (AGIs) occur in 1-5% of aortic prosthetic placements. It can result in limb amputation, pseudo-aneurysm formation, septic emboli, aorto-enteric fistulae, septic shock and death. The most frequently involved pathogens are methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci, followed by Enterobacteriaceae and uncommon bacteria. In case of gut involvement the presence of fungi has to be considered. Computed tomography angiography is actually the gold standard diagnostic imaging but magnetic resonance is a valid alternative. Nuclear medicine imaging is commonly used to improve sensitivity and specificity. Signs and symptoms are often aspecific and blood cultures can be negative, requiring alternative ways to detect the microorganism responsible for infection, such as 16S rRNA gene sequencing and molecular rapid diagnostic tests. Curative surgical intervention is the first choice approach, with in-situ reconstruction providing by far the best outcome and xenopericardial bovine patch as a promising option. For patients unable to undergo major surgery, the outcome of conservative approach remains uncertain but usually provides for life-long suppressive therapy. However, in selected cases an attempt of stopping antibiotic treatment after 3-6 months can be done. Given the difficulty in their management, we performed a review of AGIs, in order to raise awareness on clinical presentation, current available diagnostic tools, prophylaxis, surgical and anti-infective treatment of AGIs., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

BACKGROUND Diagnosis and management of accidental or intentional ingestion of foreign bodies is a common problem at in emergency departments. This condition is generally observed in patients with limited consciousness or attention, such as children, elders, or psychiatric patients. Here, we report a case of intestinal perforation caused by ingestion of a foreign body that occurred during the performance of a contrast-enhanced CT scan. CASE REPORT A 73-year-old diabetic woman was admitted to the emergency room of our hospital with postprandial abdominal discomfort, nausea, and vomiting. Under the suspicion of bowel ischemia, the patient underwent a contrast-enhanced CT scan. A thickened ileal loop with an endoluminal bone-density foreign body was detected. The following contrast-enhanced acquisitions additionally showed air bubbles adjacent to the loop, as the sign of an intestinal perforation that occurred between the basal and the contrast-enhanced acquisitions. CONCLUSIONS Caution should be always exercised in patients with suspected gastrointestinal perforation, especially if caused by ingested foreign bodies. A high degree of suspicion and a CT scan may prevent delays in the diagnosis and clinical management of these patients.

Traumatic injury to limb peripheral nerves represents an important cause of morbidity and disability. Timely diagnosis and treatment are crucial to optimizing outcomes. The initial evaluation requires a careful history, a thorough physical examination, and electrodiagnostic tests, which lead in most cases to a diagnostic suspicion, but fail to provide an extensive qualitative and quantitative assessment of the nerve damage. Ultrasonography (US) is a low-cost, non-invasive technique which allows for direct visualization of nerve internal structure. It enables performing dynamic examinations and nerves can be followed over long distances in a limb in relatively short times, adding paramount information to extensively characterize the specific type of lesion, and to plan the appropriate treatment. Magnetic resonance imaging (MRI) is complementary to US, especially in examining deep-seated and proximal nerve segments, but is expensive, not available in all institutions and less accepted by patients. The purpose of this review is to describe the role of ultrasonography in the setting of traumatic injury to peripheral nerves, analyzing the main US features in specific types of trauma. Technical aspects with key considerations for optimization are discussed. A brief comparative evaluation between US and MRI is also provided.

Motivation: Transcription in single cells is an inherently stochastic process as mRNA levels vary greatly between cells, even for genetically identical cells under the same experimental and environmental conditions. We present a stochastic two-state switch model for the population of mRNA molecules in single cells where genes stochastically alternate between a more active ON state and a less active OFF state. We prove that the stationary solution of such a model can be written as a mixture of a Poisson and a Poisson-beta probability distribution. This finding facilitates inference for single cell expression data, observed at a single time point, from flow cytometry experiments such as FACS or fluorescence in situ hybridization (FISH) as it allows one to sample directly from the equilibrium distribution of the mRNA population. We hence propose a Bayesian inferential methodology using a pseudo-marginal approach and a recent approximation to integrate over unobserved states associated with measurement error., Results: We provide a general inferential framework which can be widely used to study transcription in single cells from the kind of data arising in flow cytometry experiments. The approach allows us to separate between the intrinsic stochasticity of the molecular dynamics and the measurement noise. The methodology is tested in simulation studies and results are obtained for experimental multiple single cell expression data from FISH flow cytometry experiments., Availability and Implementation: All analyses were implemented in R. Source code and the experimental data are available at https://github.com/SimoneTiberi/Bayesian-inference-on-stochastic-gene-transcription-from-flow-cytometry-data., Supplementary Information: Supplementary data are available at Bioinformatics online.

Silicon carbide (SiC) is a compound semiconductor, which is considered as a possible alternative to silicon for particles and photons detection. Its characteristics make it very promising for the next generation of nuclear and particle physics experiments at high beam luminosity. Silicon Carbide detectors for Intense Luminosity Investigations and Applications (SiCILIA) is a project starting as a collaboration between the Italian National Institute of Nuclear Physics (INFN) and IMM-CNR, aiming at the realization of innovative detection systems based on SiC. In this paper, we discuss the main features of silicon carbide as a material and its potential application in the field of particles and photons detectors, the project structure and the strategies used for the prototype realization, and the first results concerning prototype production and their performance.

BACKGROUND Superior mesenteric artery syndrome is caused by vascular compression of the third portion of the duodenum between the aorta and the superior mesenteric artery. It may occur with acute or chronic symptomatology, such as vomiting or postprandial abdominal pain, and it is usually caused by a lack of mesenteric fat pad under conditions of severe weight loss. Crohn's disease can be one of them. CASE REPORT We report 2 cases of Crohn's disease patients with clinical suspicion of jejunal stricture who underwent MR-enterography with a novel approach. In fact, the examinations were performed including prone position of the patients inside the scanner, drinking of contrast medium during the examination, and prompt acquisition of fluoroscopic sequences. Both the exams showed an abrupt termination of the duodenum on its third portion and a decreased aortomesenteric distance, allowing the diagnosis of superior mesenteric artery syndrome. CONCLUSIONS A correlation between Crohn's disease and superior mesenteric artery syndrome has never before been reported in the literature. The present study provides some practical steps that may be useful in order to improve MRE standard protocol in recognizing this condition while evaluating Crohn's disease bowel lesions.

In this work 437 fish samples of species belonging to the families Myctophidae (Electrona risso and Diaphus metopoclampus) and Phosichthyidae (Vinciguerria attenuata) were examined for the presence of Anisakidae larvae. The study was performed with fishes in the central Mediterranean Sea, particularly in the Strait of Sicily and in the Strait of Messina. The visual inspection and chloro-peptic analysis revealed the presence of nematode parasites with prevalence values between 2.9% in Electrona risso samples and 5.4% in Vinciguerria attenuata samples. A positive correlation was found between standard length (SL) and prevalence of infestation in D. metopoclampus samples (p<0.05). The larvae examined were morphologically ascribed, at genus level, to Anisakis morphotypes I and II and molecularly identified as Anisakis pegreffii, Anisakis ziphidarum and Anisakis physeteris, in 67%, 9% and 24% of the fish samples examined. Overall, A. pegreffii and A. ziphidarum larvae were isolated in 14 and 2 specimens of D. metopoclampus respectively, A. physeteris larvae were found in 3 E. risso and 2 V. attenuata. A positive correlation was found between standard length and prevalence of infestation in D. metopoclampus samples (p<0.05). First information is provided on the presence of Anisakis spp. larvae of the myctophid fish species E. risso, D. metopoclampus and V. attenuata from the Central Mediterranean. It is also confirmed the role of lanternfishes (Myctophidae) as paratenic hosts for Anisakis spp., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Swordfish (Xiphias gladius L. 1758) is a predatory and migratory fish. Its characteristic feature is a flat and sharp upper jaw forming a "sword". The adaptation of vertebrates, including fish, to their environment is strictly related to the capacity of feeding and is carried out by often severe modifications of the anatomy of the buccal cavity, especially of the tongue. The aim of this study is, using light and scanning electron microscopy and considering that no data are so far available about the morphology of the tongue in this species, to analyse the anatomical characteristics of the tongue, especially its dorsal surface. The tongue shows a triangular shape and an apex, a body and a root. By SEM the presence of several small denticles and filiform papillae on the latero-ventral body was demonstrated while no taste buds or other sensitive structures are observed. LM shows a squamous stratified epithelium, becoming simple cuboidal around the denticles. Therefore this study could add further data to the knowledges of the fish oral cavity morphology supporting the hypothesis that the modifications and evolution of the tongue anatomy are, also in fish, related to the environment and especially to the feeding habits., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The decay path of the Hoyle state in ^{12}C (E&#95;{x}=7.654  MeV) has been studied with the ^{14}N(d,α&#95;{2})^{12}C(7.654) reaction induced at 10.5 MeV. High resolution invariant mass spectroscopy techniques have allowed us to unambiguously disentangle direct and sequential decays of the state passing through the ground state of ^{8}Be. Thanks to the almost total absence of background and the attained resolution, a fully sequential decay contribution to the width of the state has been observed. The direct decay width is negligible, with an upper limit of 0.043% (95% C.L.). The precision of this result is about a factor 5 higher than previous studies. This has significant implications on nuclear structure, as it provides constraints to 3α cluster model calculations, where higher precision limits are needed.

Band 3 protein efficiency in mediating Cl - /HCO 3 - exchange through erythrocytes membrane is reduced by oxidative stress. The aim of the present study was to verify whether and how anion transport through band 3 protein may be useful in monitoring canine leishmaniasis (Leishmania infantum) development, a disease associated to membrane protein degradation and oxidative stress. To accomplish this aim, serological analysis to determine IFAT (immunofluorescence antibody test) titers against leishmaniasis has been performed and 1:160 and 1:540 titers, determined at diagnosis and after 6 months, were considered for experiments. Oxidative conditions have been assessed by estimating MDA (malondialdehyde) plasma levels, intracellular GSH (reduced glutathione) content, and membrane -SH groups. Band 3 protein anion exchange capability was evaluated by measuring the rate constant for SO 4 = uptake, and its expression levels, along with those of P-Tyr (phosphorylated tyrosine), involved in pathways underlying band 3 protein function, have been also determined. Our results show that, in infected dogs with 1:160 IFAT titer, high MDA plasma levels and oxidation of -SH groups are associated to increased P-Tyr expression levels, leading to a reduction in anion exchange capability throughout 6 months of diagnosis. On the other hand, infected dogs with 1:540 IFAT titer, exhibited oxidative conditions associated to an impaired anion exchange capability at diagnosis, were ameliorated after 6 months. Such findings suggest that (1) band 3 protein-mediated anion transport is reduced by oxidative conditions associated to leishmaniasis, putatively via phosphorylative pathways; (2) band 3 protein efficiency may account for canine leishmaniasis development; and (3) the assessment of band 3 protein function may represent an additional tool for canine leishmaniasis diagnosis and monitoring of its development, with potential application to humans, either in case of leishmaniasis or other oxidative-related pathologies.

The oral cavity of vertebrates has a very important role in many functions strictly related to the food processing. Two species, sea bass Dicentrarchus labrax and seabream Sparus aurata, are mainly involved in the aquaculture industry in the mediterranean area; moreover, the white seabream Diplodus sargus sargus was recently chosen as the best candidate for the diversification of species of commercial interest. This investigation was carried out, using the standard procedures for light and scanning electron microscopy, to analyse the morphology of the tongue dorsal surface in order to show whether relationships are present between the tongue morphology and the nutritional choices of these species. In all the three investigated species, three different areas were observed on the dorsal lingual surface: an apex, a body and a root. In the sea bass D. labrax, numerous caninelike teeth, organized in pads, were present along the dorsal surface. The presence of numerous taste buds, scattered on the tongue, was shown. In the seabream S. aurata, the apical part of the tongue is inserted in a pouch with a characteristic medial ridge on the body surface. Numerous taste buds were scattered on the whole surface. In the white seabream D. sargus sargus, a pouch partially covering the apex was clearly observed. In the pouch, filiform-like and foliate-like papillae can be distinguished. The results show the important role of the fish tongue in the food ingestion process, demonstrating the interaction of food processing, taste and morphological characteristics., (© 2016 Blackwell Verlag GmbH.)

Transcatheter aortic valve replacement (TAVR) has been validated as a new therapy for patients affected by severe symptomatic aortic stenosis who are not eligible for surgical intervention because of major contraindication or high operative risk. Patient selection for TAVR should be based not only on accurate assessment of aortic stenosis morphology, but also on several clinical and functional data. Multi-Imaging modalities should be preferred for assessing the anatomy and the dimensions of the aortic valve and annulus before TAVR. Ultrasounds represent the first line tool in evaluation of this patients giving detailed anatomic description of aortic valve complex and allowing estimating with enough reliability the hemodynamic entity of valvular stenosis. Angiography should be used to assess coronary involvement and plan a revascularization strategy before the implant. Multislice computed tomography play a central role as it can give anatomical details in order to choice the best fitting prosthesis, evaluate the morphology of the access path and detect other relevant comorbidities. Cardiovascular magnetic resonance and positron emission tomography are emergent modality helpful in aortic stenosis evaluation. The aim of this review is to give an overview on TAVR clinical and technical aspects essential for adequate selection., Competing Interests: Conflict-of-interest statement: The authors report no relevant conflicts of interest.

Objective: Sleep laboratory study to determine the dose-related efficacy and safety of almorexant in elderly patients with primary chronic insomnia., Methods: Patients aged ≥65 years with primary insomnia were enrolled into a prospective, randomized, double-blind, placebo-controlled, multicenter dose-finding study with a five-period, five-way Latin square cross-over design. Patients were randomized to one of 10 unique sequences of two-night treatment with oral almorexant 25, 50, 100, or 200 mg capsules, or matching placebo. The primary efficacy endpoint was polysomnography (PSG)-determined mean wake time after sleep onset (WASO). Secondary and exploratory efficacy endpoints were also assessed., Results: 112 patients were randomized (mean [SD] age 72.1 [5.0] years; 69.9% female). Significant, dose-related improvements (reductions) in mean WASO were observed with almorexant. Least-squares mean (95% CI) treatment effects in the almorexant 200, 100, 50, and 25 mg dose groups versus placebo were -46.5 minutes (-53.0, -39.9; p < .0001), -31.4 minutes (-38.0, -24.9; p < .0001), -19.2 minutes (-25.7, -12.6; p < .0001), and -10.4 minutes (-17.0, -3.9; p = .0018), respectively. Mean total sleep time was significantly increased with each almorexant dose (mean increases versus placebo ranged 55.1-14.3 minutes; p < .0001 for each dose). Latency to persistent sleep was statistically significantly reduced only with almorexant 200 mg versus placebo (mean [95% CI] treatment effect -10.2 minutes, [-15.4, -5.0]; p = .0001). No unexpected safety concerns were identified. Adverse events were similar between all almorexant dose groups and placebo., Conclusions: Two-night oral administration of almorexant was effective and well tolerated in treating primary insomnia in elderly patients., (© Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

This Letter reports a study of the highly debated ^{10}Li structure through the d(^{9}Li,p)^{10}Li one-neutron transfer reaction at 100 MeV. The ^{10}Li energy spectrum is measured up to 4.6 MeV and angular distributions corresponding to different excitation energy regions are reported for the first time. The comparison between data and theoretical predictions, including pairing correlation effects, shows the existence of a p&#95;{1/2} resonance at 0.45±0.03  MeV excitation energy, while no evidence for a significant s-wave contribution close to the threshold energy is observed. Moreover, two high-lying structures are populated at 1.5 and 2.9 MeV. The corresponding angular distributions suggest a significant s&#95;{1/2} partial-wave contribution for the 1.5 MeV structure and a mixing of configurations at higher energy, with the d&#95;{5/2} partial-wave contributing the most to the cross section.

Non-invasive Doppler ultrasonographic study of cerebral arteries [transcranial Doppler (TCD)] has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency (≤ 2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays the most widespread indication for TCD in outpatient setting is the research of right to left shunting, responsable of so called "paradoxical embolism", most often due to patency of foramen ovale which is responsable of the majority of cryptogenic strokes occuring in patients younger than 55 years old. TCD also allows to classify the grade of severity of such shunts using the so called "microembolic signal grading score". In addition TCD has found many useful applications in neurocritical care practice. It is useful on both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoidal haemorrhage (caused by aneurysm rupture or traumatic injury), traumatic brain injury, brain stem death. It is used also to evaluate cerebral hemodynamic changes after stroke. It also allows to investigate cerebral pressure autoregulation and for the clinical evaluation of cerebral autoregulatory reserve.

Transcranial Doppler (TCD) ultrasonography is a noninvasive ultrasound study, which has been extensively applied in both outpatient and inpatient settings. Its main use in current clinical practice is the research for "Paradoxical Embolism," due to migration of thromboembolic material from systemic venous circulation to the left cardiac chambers and arterial circulation through cardiopulmonary shunts such as patent foramen ovale which represents an important cause of cryptogenic stroke, especially in patients under 55 years of age. In this review, we shall describe the incremental diagnostic role in cryptogenic stroke for this imaging modality. TCD not only can be used to detect right-left cardiopulmonary shunts but it also allows to classify the grade of severity of such shunts using the so-called "Microembolic Signals grading score.", Competing Interests: There are no conflicts of interest.

Legionella quantification in environmental samples is overestimated by qPCR. Combination with a viable dye, such as Propidium monoazide (PMA), could make qPCR (named then vPCR) very reliable. In this multicentre study 717 artificial water samples, spiked with fixed concentrations of Legionella and interfering bacterial flora, were analysed by qPCR, vPCR and culture and data were compared by statistical analysis. A heat-treatment at 55 °C for 10 minutes was also performed to obtain viable and not-viable bacteria. When data of vPCR were compared with those of culture and qPCR, statistical analysis showed significant differences (P < 0.001). However, although the heat-treatment caused an abatement of CFU/mL ≤1 to 1 log10 unit, the comparison between untreated and heat-treated samples analysed by vPCR highlighted non-significant differences (P > 0.05). Overall this study provided a good experimental reproducibility of vPCR but also highlighted limits of PMA in the discriminating capability of dead and live bacteria, making vPCR not completely reliable., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Transcranial Doppler (TCD) ultrasonography is a noninvasive ultrasound study, which has been extensively applied on both outpatient and inpatient settings. It involves the use of a low-frequency (≤2 MHz) transducer, placed on the scalp, to insonate the basal cerebral arteries through relatively thin bone windows and to measure the cerebral blood flow velocity and its alteration in many different conditions. In neurointensive care setting, TCD is useful for both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, and brain stem death. It also allows to investigate the cerebrovascular autoregulation in setting of carotid disease and syncope. In this review, we will describe physical principles underlying TCD, flow indices most frequently used in clinical practice and critical care applications in Neurocritical Unit care., Competing Interests: There are no conflicts of interest.

We study an open-boundary version of the on-off zero-range process introduced in Hirschberg et al. [Phys. Rev. Lett. 103, 090602 (2009)]. This model includes temporal correlations which can promote the condensation of particles, a situation observed in real-world dynamics. We derive the exact solution for the steady state of the one-site system, as well as a mean-field approximation for larger one-dimensional lattices, and also explore the large deviation properties of the particle current. Analytical and numerical calculations show that, although the particle distribution is well described by an effective Markovian solution, the probability of rare currents differs from the memoryless case. In particular, we find evidence for a memory-induced dynamical phase transition.

Electrolyte alterations and extra-renal disorders are quite frequent in patients undergoing haemodialysis or peritoneal dialysis. The native kidneys may be the site of important pathologies in patients undergoing dialysis, especially in the form of acquired renal cystic disease with frequent malignant transformation. Renal neoplasms represents an important complication of haemodialysis-associated acquired cystic kidney disease and imaging surveillance is suggested. Extra-renal complications include renal osteodistrophy, brown tumours, and thoracic and cardiovascular complications. Other important fields in which imaging techniques may provide important informations are arteriovenous fistula and graft complications. Teaching points • Renal neoplasms represent a dreaded complication of haemodialysis.• In renal osteodystrophy bone resorption typically manifests along the middle phalanges.• Brown tumours are well-defined lytic lesions radiographically, possibly causing bone expansion.• Vascular calcifications are very common in patients undergoing haemodialysis.• Principal complications of the AV fistula consist of thrombosis, aneurysms and pseudoaneurysms.

Background: Following DIY (do it yourself) diets as well as consuming supplements exceeding by far the recommended daily intake levels, is common among athletes; these dietary habits often lead to an overconsumption of some macro and/or micronutrients, exposing athletes to potential health risks. The aim of this study is to document the development of possible adverse effects in a 33 year-old amateur bodybuilder who consumed for 16 years a DIY high protein diet associated to nutrient supplementation. Body composition, biochemical measures and anamnestic findings were evaluated. We present this case to put on alert about the possible risks of such behavior repeated over time, focusing on the adverse gastrointestinal effects. We discuss the energy and nutrient composition of his DIY diet as well as the use of supplements., Conclusion: This study provides preliminary data of the potential risks of a long-term DIY dietary supplementation and a high protein diet. In this case, permanent abdominal discomfort was evidenced in an amateur body builder with an intake exceeding tolerable upper limit for vitamin A, selenium and zinc, according to our national and updated recommendations. As many amateur athletes usually adopt self-made diets and supplementation, it would be advisable for them to be supervised in order to prevent health risks due to a long-term DIY diet and over-supplementation.

Giant resonances are collective excitation modes for many-body systems of fermions governed by a mean field, such as the atomic nuclei. The microscopic origin of such modes is the coherence among elementary particle-hole excitations, where a particle is promoted from an occupied state below the Fermi level (hole) to an empty one above the Fermi level (particle). The same coherence is also predicted for the particle-particle and the hole-hole excitations, because of the basic quantum symmetry between particles and holes. In nuclear physics, the giant modes have been widely reported for the particle-hole sector but, despite several attempts, there is no precedent in the particle-particle and hole-hole ones, thus making questionable the aforementioned symmetry assumption. Here we provide experimental indications of the Giant Pairing Vibration, which is the leading particle-particle giant mode. An immediate implication of it is the validation of the particle-hole symmetry.

We explore micropatterned director structures of aqueous lyotropic chromonic liquid crystal (LCLC) films created on square-lattice cylindrical-micropost substrates. The structures are manipulated by modulating the LCLC mesophases and their elastic properties via concentration through drying. Nematic LCLC films exhibit preferred bistable alignment along the diagonals of the micropost lattice. Columnar LCLC films, dried from nematics, form two distinct director and defect configurations: a diagonally aligned director pattern with local squares of defects, and an off-diagonal configuration with zig-zag defects. The formation of these states appears to be tied to the relative splay and bend free energy costs of the initial nematic films. The observed nematic and columnar configurations are understood numerically using a Landau-de Gennes free energy model. Among other attributes, the work provide first examples of quasi-2D micropatterning of LC films in the columnar phase and lyotropic LC films in general, and it demonstrates alignment and configuration switching of typically difficult-to-align LCLC films via bulk elastic properties.

Purpose: To investigate whether contrast-enhanced ultrasound (CEUS) may help to diagnose retinal/choroidal detachment and may help to differentiate intraocular lumps in cases with equivocal features on conventional grayscale and Doppler modes., Materials and Methods: The institutional review board approved this retrospective study. The need for informed consent was waived. A computerized data search was performed in the database of our institution for patients with vitreous hemorrhage who underwent CEUS of the eye to assess retinal/choroidal detachment and/or associated masses. This process yielded a total of 31 patients (18 men, 13 women, age range: 39 - 88 years) in whom CEUS was performed because the findings on conventional grayscale and Doppler modes were equivocal. CEUS was performed using low acoustic power contrast-specific modes. A 2.4 - 4.8  mL bolus of SonoVue was injected, followed by a saline flush. All examinations were digitally recorded for retrospective analysis. Confirmation of CEUS findings was obtained at surgery (n = 20) or with binocular indirect fundoscopy performed after clearance of the ocular media (n = 11). Two readers with different levels of ultrasound experience independently reviewed the imaging features. A five-degree scale ranging from definitely absent (score 1) to definitely present (score 5) was used to assess the presence or absence of retinal/choroidal detachment on conventional ultrasound modes alone and with the addition of CEUS. ROC curve analysis was performed to assess the diagnostic accuracy of both methods. The inter-reader agreement was also evaluated. In patients with associated intraocular lumps, conventional Doppler modes and CEUS were used to differentiate non-tumor masses from tumor masses., Results: According to the reference standard, 13 patients had retinal detachment, 4 had choroidal detachment, and 3 had both retinal and choroidal detachment. There were 8 associated intraocular lumps (4 subretinal hemorrhages, 3 malignant melanomas, 1 metastasis). The inter-reader agreement was good (K = 0.644) and very good (K = 0.833) for conventional modes and CEUS, respectively. The diagnostic performance of CEUS was high for both readers (area ± standard error under the ROC curve: 0.966 ± 0.031 and 0.900 ± 0.055 for readers 1 and 2, respectively). There were 2 false-positive results and 1 false-negative result in patients with proliferative diabetic retinopathy. CEUS was effective in differentiating subretinal hemorrhage from hypovascular tumors., Conclusion: CEUS can be used as a problem-solving technique when conventional ultrasound modes are not diagnostic for retinal/choroidal detachment and when intraocular lumps cannot be characterized as tumor or non-tumor masses on conventional modes. The evaluation of patients with proliferative diabetic retinopathy, however, may be problematic., (© Georg Thieme Verlag KG Stuttgart · New York.)

Gastric neuroendocrine tumors (g-NETs), which originate from gastric enterochromaffin-like (ECL) mucosal cells and account for 2.4% of all carcinoids, are increasingly recognized due to expanding indications of upper gastrointestinal endoscopy. Often silent and benign, g-NETs may however, be aggressive and sometimes they mimic the course of gastric adenocarcinoma. Current nosography distinguishes those occurring in chronic conditions with hypergastrinemia, as the type 1 associated with chronic atrophic gastritis, and the type 2 associated with Zollinger-Ellison syndrome in MEN1. Conversely, type 3 and 4 (according to some authors) are unrelated to hypergastrinemia and are frequently malignant, with a propension to develop distant metastases. While there is a general agreement concerning the treatment of malignant gastric neuroendocrine tumors, for types 1 and 2, current possibilities include surveillance, endoscopic polypectomy, surgical excision, associated or not with surgical antrectomy, or total gastrectomy. This report, based on our clinical experience, discusses how the size, number, depth, histological grading, staging with CT, MRI, and the use of recently developed somatostatin receptor tracers (68Ga-DOTATATE, 68Ga-DOTA-TOC) could allow the correct identification of a benign or malignant propensity of an individual tumor, thus avoiding underestimation or overtreatment of these uncommon neoplasms., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Background/aims: The study objective was to investigate and compare the pharmacokinetics of a single oral dose of ACT-077825, a novel direct renin inhibitor, in young and elderly, male and female healthy subjects and to evaluate the safety and tolerability of ACT-077825 in these population groups., Methods: A total of 32 healthy subjects were included in this single-center, open-label study. The subjects were divided into 4 groups, including 8 young male, 8 young female, 8 elderly male and 8 elderly female subjects. Each participant received a single 200-mg dose of ACT-077825. Blood samples were taken over 5 days (120 h) to determine the plasma levels of ACT-077825. Safety and tolerability were monitored using standard assessments before drug administration, on the administration day and at the end of the blood sampling period., Results: Upon pooling male and female subjects, exposure was higher in elderly compared to young subjects, showing an increase of 65% for AUC0-∞, 40% for Cmax and 38% for t1/2. While young male and female subjects showed similar plasma profiles and exposure, a significant increase in exposure occurred with age in both sexes compared to younger subjects. The difference was largest between young and elderly females. Furthermore, the exposure to ACT-077825 was around 30% higher in elderly female compared to elderly male subjects. ACT-077825 was well tolerated by all groups, including the elderly females who showed the highest exposure., Conclusions: ACT-077825 exposure is moderately increased in elderly subjects. The clinical relevance of this observation should be explored in the context of further studies., (© 2014 S. Karger AG, Basel.)

Introduction. Aim of the present work is to review the literature to point out the role of laparoscopic reversal of Hartmann procedure. Material and Methods. Number of patients, age, sex, etiology, Hinchey classification, interval between procedure and reversal, position of the first trocars, mean operative time (min), number and causes of conversion, length of stay, mortality, complications, and quality of life were considered. Results. 238 males (52.4%) and 216 females (47.6%) between 38 and 67 years were analyzed. The etiology was diverticulitis in 292 patients (72.1%), carcinoma in 43 patients (10.6%), and other in 70 patients (17.3%). Only 7 articles (22.6%) reported Hinchey classification. The interval between initial procedure and reversal was between 50 and 330 days. The initial trocar was open positioned in 182 patients (43.2%) through umbilical incision, in 177 patients (41.9%) in right upper quadrant, and in 63 patients (14.9%) in colostomy site. The operative time was between 69 and 285 minutes. A total of 83 patients (12.1%) were converted and the causes were reported in 67.4%. The length of stay was between 3 and 12 days. 5 patients (0.7%) died. The complications concern 112 cases (16.4%). Conclusion. The laparoscopic Hartmann's reversal is safer and achieves faster positive results.

Introduction: Gallbladder cancer (GBC) is the fifth most common neoplasm of the gastrointestinal tract and the most common cancer of the biliary tract. GBC is suspected preoperatively in only 30-40% of patients. The other 60-70% are discovered incidentally (IGBC) by the pathologist on a gallbladder specimen following cholecystectomy for benign diseases such as polyps, gallstones, and cholecystitis., Materials and Methods: Between 1995 and 2011, 30 cases of GBC, who underwent resection with curative intent in our institutions, were retrospectively reviewed. They were analyzed for demographic data, and type of operation, surgical morbidity and mortality, histopathological classification, and survival. Incidental GBC was compared with suspected or preoperatively diagnosed GBC. Overall survival, disease-free survival (DFS) and the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention were analyzed. The authors also present a systematic review to evaluate the role of extended surgery in the treatment of the incidental GBC., Results: GBC was diagnosed in 30 patients, 16 women and 14 men. The M/F ratio was 1:1.14 and the mean age was 69.4 years (range 45-83 years). A preoperative diagnosis was possible only in 14 cases; fourteen of the incidental cases were diagnosed postoperatively after the pathological examination; two were suspected intraoperatively at the opening of the surgical specimen and then confirmed by frozen sections. The ratio between incidental and nonincidental cases was 1, 14/1, with twelve cases discovered after laparoscopic cholecystectomy. Eighty-one per cent of the incidental cases were discovered at an early stage (≤II). The preoperative diagnosis of the 30 patients with GBC was: GBC with liver invasion diagnosed by preoperative CT (nine cases); gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum (one case); porcelain gallbladder (three cases); gallbladder adenoma (four cases); and chronic cholecystolithiasis (thirteen cases). Every case, except one, with a T1b or more advanced invasion underwent IVb + V wedge liver resection and pericholedochic/hepatoduodenal lymphoadenectomy. One patient refused further surgery. Cases with Tis and T1a involvement were treated with cholecystectomy alone. Nine of the sixteen patients with incidental diagnosis reached 5-year DFS (56.25%) and eight of them are recurrence free. Surprisingly, one patient reached 38 mo survival despite a port-site recurrence (the only one in our experience) 2 years after the original surgery requiring further resection. Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5 years DFS (Tables 2 and 3)., Conclusion: Laparoscopic cholecystectomy does not affect survival if implemented properly. Reoperation should have two objectives: R0 resection and clearance of the lymph nodes., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Clonogenic neural stem (NS) cell lines grown in adherent cultures have previously been established from embryonic stem cells and fetal and adult CNS in rodents and from human fetal brain and spinal cord. Here we describe the isolation of a new cell line from human fetal striatum (hNS cells). These cells showed properties of NS cells in vitro such as monolayer growth, high proliferation rate and expression of radial glia markers. The hNS cells expressed an early neuronal marker while being in the proliferative state. Under appropriate conditions, the hNS cells were efficiently differentiated to neurons, and after 4 weeks about 50% of the cells were βIII tubulin positive. They also expressed the mature neuronal marker NeuN and markers of neuronal subtypes, GABA, calbindin, and DARPP32. After intrastriatal implantation into newborn rats, the hNS cells survived and many of them migrated outside the transplant core into the surrounding tissue. A high percentage of cells in the grafts expressed the neuroblast marker DCX, indicating their neurogenic potential, and some of the cells differentiated to NeuN+ mature neurons. The human fetal striatum-derived NS cell line described here should be a useful tool for studies on cell replacement strategies in models of the striatal neuronal loss occurring in Huntington's disease and stroke.