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IntroductionThrombotic events in neonates and children represent a rare although severe occurrence in view of the associated risk of mortality and sequelae. Quality evidence is limited in this field, and registry studies provide an essential base for research. The aim of this paper is to present the new Italian Registry of Infantile Thrombosis (RITI), set it into the scene of international thrombosis and stroke registries, and provide some insight on the challenges associated with registry management.MethodsWe present the detailed structure and content of the new RITI registry, a brief overview of its main data, and a reflection on its features, pitfalls and the main challenges related to its management.ResultsThe RITI, initially started in 2007 and officially re-launched in 2017 after structural modifications, is a non-interventional retrospective and prospective registry study collecting data on neonatal and pediatric patients (0–18 years) who experienced a systemic or cerebral thrombotic event in Italy. The RITI is managed by a multidisciplinary team with expertise in pediatric thrombosis, and participation is open to all Italian physicians, on a voluntary basis. The overall aim of the registry is to acquire new evidence to better characterize the population of children with thrombotic events and improve their management and outcome. 48 Italian pediatric and intensive care units are actively involved in the RITI, including 85 medical doctors from 16 Italian regions. A total of 1,001 neonates and children affected by cerebral or systemic thrombosis have been enrolled.DiscussionThe RITI is one of the largest available European registries of neonatal and pediatric thrombosis. National registries like the RITI represent a model for the study of rare conditions based on multidisciplinary and multicenter collaboration, aimed at overcoming the limitations due to small populations of patients, and creating a network of experts for patient referral and continuous education. Moreover, registry studies have a pivotal role in the research on pediatric thrombosis, due to the limited feasibility of high-quality studies. In our experience, the main critical stages, pitfalls and challenges in registry management include adequate registry designing, diffusion, data completeness and quality control.

Mini-EUSO is the first mission of the JEM-EUSO program on board the International Space Station. It was launched in 2019 and it is currently located in the Russian section (Zvezda module) of the station and viewing our planet from a nadir-facing UV-transparent window. The instrument is based on the concept of the original JEM-EUSO mission and consists of an optical system employing two Fresnel lenses and a focal surface composed of 36 Multi-Anode Photomultiplier tubes, 64 channels each, for a total of 2304 channels with single photon counting sensitivity and an overall field of view of 44° × 44°. Mini-EUSO can map the night-time Earth in the near UV range (predominantly between 290 nm and 430 nm), with a spatial resolution of about 6.3 km and different temporal resolutions of 2.5 µ, 320 µs and 41 ms. Mini-EUSO observations are extremely important to better assess the potential of a space-based detector in studying Ultra-High Energy Cosmic Rays (UHECRs) such as K-EUSO and POEMMA. In this contribution we focus the attention on UV measurements, the observation of clouds and of certain categories of events that Mini-EUSO triggers with the shortest temporal resolution. We place them in the context of UHECR observations from space, namely the estimation of exposure and sensitivity to Extensive Air Showers.

To take up the challenge of understanding the origin of the ultra-high-energy cosmic rays (UHECRs), new observational means appear necessary. The JEM-EUSO Collaboration has undertaken to open the space road to UHECR studies. For more than a decade, it has been developing a realistic program to measure the UHECRs from space with unprecedented aperture, together with complementary scientific objectives in a broader multidisciplinary context. Several intermediate missions have already been completed (on the ground: EUSO-TA; under stratospheric ballons: EUSO-Balloon and EUSO-SPB1; in space: TUS, and on-board the ISS: MINI-EUSO), and others are in preparation for flight (EUSO-SPB2), under review (K-EUSO: currently on hold), or proposed for the next decade (POEMMA). We report on the general status of the JEM-EUSO program, underlining that its technology has now reached operational maturity, and is ready for actual cosmic-ray shower detection from above.

Mini-EUSO is a wide Field-of-View (FoV, 44°) telescope currently in operation from a nadir-facing UV-transparent window in the Russian Zvezda module on the International Space Station (ISS). It is the first detector of the JEM-EUSO program deployed on the ISS, launched in August 2019. The main goal of Mini-EUSO is to measure the UV emissions from the ground and atmosphere, using an orbital platform. Mini-EUSO is mainly sensitive in the 290–430 nm bandwidth. Light is focused by a system of two Fresnel lenses of 25 cm diameter each on the Photo-Detector-Module (PDM), which consists of an array of 36 Multi-Anode Photomultiplier Tubes (MAPMTs), arranged in blocks of 2 × 2 called Elementary Cells (ECs), for a total of 2304 pixels working in photon counting mode, in three different time resolutions of 2.5 µs (defined as 1 Gate Time Unit, GTU), 320 µs and 40.96 ms operating in parallel. In the longest time scale, the data is continuously acquired to monitor the UV emission of the Earth. It is best suited for the observation of ground sources and therefore has been used for the observational campaigns of the ground-based UV flasher in order to perform an end-to-end calibration of Mini-EUSO. In this contribution, the assembled UV flasher, the operation of the field campaign and the analysis of the obtained data are presented. The result is compared with the overall effi ciency computed from the expectations which takes into account the atmospheric attenuation and the parametrisation of different effects such as the optics effi ciency, the MAPMT detection effi ciency, BG3 filter transmittance and the transparency of the ISS window.

Background: A total colectomy and a frequent life-long endoscopic surveillance are guaranteed to patients with Familial Adenomatous Polyposis (FAP) to reduce their risk of duodenal and rectal stump cancers. However, after surgery, individuals with FAP suffer from an increased number of diarrheal discharges that force them to dietary restrictions. A non-randomized pilot study was conducted to assess whether a three-month low-inflammatory Mediterranean dietary intervention reduces gastro-intestinal markers of inflammation in FAP individuals. The aim of the present work is to evaluate the participant’s adherence to the proposed dietary recommendations and the change in their number of diarrheal discharges. Methods: 26 FAP individuals aged >18 years, who underwent a total colectomy with ileo-rectal anastomosis and were involved in the surveillance program at the Fondazione IRCCS Istituto Nazionale Tumori of Milan, were included in the present analysis. Results: FAP individuals significantly reduced the Not recommended foods (p-value: 0.002) and increased the consumption of the Recommended ones (p-value: 0.075). The adherence to the proposed dietary recommendations was accompanied by a significant decrease in the number of diarrheal discharges (p-value: 0.008). Conclusions: This study suggests that adhering to a low-inflammatory Mediterranean diet has a potential protective effect on the number of diarrheal discharges in FAP individuals.

Background: The current practice in medical education is to place students at off-site locations. The effectiveness of these students attending remote lectures using interactive videoconferencing needs to be evaluated. Purpose: To determine whether lecture content covering clinical objectives is learned by medical students located at remote sites. Methods: During the University of Vermont medicine clerkship, 52 medical students attended lectures both in person and via 2-way videoconferencing over a telemedicine network. The study used a crossover design, such that all students attended half of the lectures in person and half using videoconferencing. At the end of the clerkship, students were assessed via a Clinical Practice Examination (CPX), with each student completing 1 exam for material learned in person and 1 for material learned over telemedicine. Results: Exam scores did not differ for the 2 lecture modes, with a mean score of 76% for lectures attended in person and a mean score of 78% for lectures attended via telemedicine (p = 0.66). Conclusions: Students learn content focused on clinical learning objectives as well using videoconferencing as they do in the traditional classroom setting. [ABSTRACT FROM AUTHOR]

BACKGROUND: Interactive videoconferencing may be an effective way for medical students on remote rotations to attend teaching sessions at the main campus. PURPOSE: To compare medical student evaluations of lectures for those attending in person and those attending through interactive videoconferencing. METHODS: Lecture evaluations were completed by medical students on University of Vermont College of Medicine clinical clerkship rotations. Students on clerkships at rural sites attended lectures using our telemedicine network. Responses from in-person and remote attendees were compared. RESULTS: Evaluation forms for 110 lectures were received from 648 in-person and 255 remote attendees. All evaluation items were rated 'good' or 'excellent' by at least 95% of in-person attendees. Over 90% of remote attendees rated nontelemedicine evaluation items, such as appropriateness of lecture topic for students, as good or excellent. Ratings of telemedicine-specific questions, such as ability to hear the lecturer, were lower. CONCLUSIONS: Level of satisfaction was high for most aspects of remote lecture attendance, although not quite as high as for in-person attendance. Improved technical reliability would likely increase remote attendee satisfaction. Overall, lecture attendance using videoconferencing was found to be an acceptable alternative to travel for medical students in rural clerkships. [ABSTRACT FROM AUTHOR]

In the last decades, the consolidation of 3D CFD approaches in the industrial design practices has progressively moved throughflow codes from the top of design systems to somewhere in between first development stages and the final aerodynamic optimizations. Despite this trend and the typical limitations of traditional throughflow methods, designers tend to still consider such methods as fundamental tools for drafting a credible aero-design in a short turnaround time. Recently a considerable attention has been devoted to CFDbased throughflow codes as suitable means to widen the range of applicability of these tools while smoothing the predictive gap with successive threedimensional flow analyses. The present paper retraces the development and some applications of a modern and complete CFD-based throughflow solver specifically tuned for multistage axial turbine design. The code solves the axisymmetric Euler equations with an original treatment of tangential blockage and body force. It inherits its numerical scheme from a state-of-the-art CFD solver (TRAF code) and incorporates real gas capabilities, three-dimensional flow features (e.g. secondary flows, tip leakage effects), coolant flow injections, and radial mixing models. Also geometric features of actual blades, like fillets, part-span shrouds, and snubbers, are accounted for by suitable models. The capabilities of the code are demonstrated by discussing a significant range of test cases and industrial applications. They include single stage configurations and entire multistage modules of steam turbines, with flow conditions ranging from subsonic to supersonic. Computational strategies for design and off-design analyses will be presented and discussed. The reliability and accuracy of the method is assessed by comparing throughflow results with 3D CFD calculations and experimental data. A good agreement in terms of overall performance and spanwise distributions is achieved in both design and off-design operating conditions.

Wartime injuries from explosive devices have created the need for atypical responses to devastating and unusual injuries. We report a case of an explosive abdominal injury that produced a huge defect in the posterior abdominal wall which was ultimately repaired with a rectus abdominus flap, an usual use of this versatile muscle flap. The rectus abdominus muscle may be another tool available for the repair of wartime injuries. [ABSTRACT FROM AUTHOR]

OBJETIVO: avaliar a taxa de recorrência local, regional e a distância de nova técnica cirúrgica para tratamento conservador do câncer de mama de estádio inicial. A técnica é baseada na ressecção segmentar com dissecção axilar e preservação de pele por incisão periareolar única. MÉTODOS: cento e dezenove pacientes com câncer de mama de estádio I e II foram incluídas neste estudo. O grupo estudo foi constituído por 57 pacientes que se submeteram à cirurgia pela técnica proposta e 62 pacientes submetidas a quadrantectomia clássica constituíram o grupo controle. A radioterapia pós-operatória e o boost foram realizados em ambos os grupos. A média de seguimento foi de 50,1 meses para o grupo estudo e 51,2 para o grupo controle. As taxas de recidiva, sobrevida global e sobrevida livre de doença foram analisadas e comparadas entre os dois grupos. RESULTADOS: a taxa de recidiva local no período foi de 3,5% para o grupo estudo e 4,8% para o grupo controle. Não houve diferença significativa entre os grupos nas taxas de sobrevida livre de doença e sobrevida global. CONCLUSÕES: a técnica de ressecção segmentar com dissecção axilar por incisão única periareolar, preservando pele, não mostrou diferença, em relação à quadrantectomia clássica, nas taxas de recidiva, sobrevida global e sobrevida livre de doença.

Abstract Myxomatous mitral regurgitation (type II Carpentier's functional classification) affects about 1-2% of the population. This represents a very common indication for valve surgery resulting in a low percentage of repairs compared to replacement which is actually performed. In the last decades, several methods for mitral valve repair have been developed, to make the surgical feasibility easier, improve the long-term follow-up thus avoiding the need for reoperations. A very interesting method is represented by the combination of various valve repair techniques, depending on the involvement of the anterior, posterior, or both leaflets, and the use of PTFE artificial chordae tendineae when excessive chordal elongation or rupture due to myxomatous degeneration co-exists. The aim of this review is to summarize the evolution of these techniques from the beginning till now.

Abstract A 48 year old man was transferred to our department with cardiogenic shock, pyrexia, a high white cell count and significant serum troponin T level. Clinical evaluation revealed severe mitral regurgitation secondary to a flail of both mitral valve leaflets. An emergency cardiac catheterisation did not reveal any significant coronary artery disease. Left ventricular angiogram and echocardiography demonstrated a good left ventricular function and massive mitral regurgitation. Blood cultures were negative for aerobics, anaerobics and fungi. The patient underwent emergency mitral valve replacement with a mechanical valve. Intraoperatively, the posteromedial papillary muscle was found to be ruptured. Histology of the papillary muscle revealed myocardial necrosis with no signs of infection. Cultures obtained from a mitral valve specimen were negative. The patient's recovery was uneventful and he was discharged on the 6th postoperative day.

Abstract This article details a case report of a traumatic aortic arch false aneurysm after blunt chest trauma. Thoracic aorta false aneurysms are a rare and life-threatening complication of aortic surgery, infection, genetic disorders and trauma.

Abstract Background The relation betweeen the structure of discotic molecules and columnar properties, a crucial point for the realization of new advanced materials, is still largely unknown. A paradigmatic case is that hexa-alkyl-thio substituted triphenylenes present mesogenic behavior while the corresponding azatriphenylenes, similar in shape and chemical structure, but with a different core charge distribution, do not form any liquid crystalline mesophase. This study is aimed at investigating, with the help of computer simulations techniques, the effects on phase behaviour of changes of the charge distribution in the discotic core. Results We described the shape and the pair, dispersive and electrostatic, interactions of hexa alkyl triphenylenes by uniaxial Gay-Berne discs with embedded point charges. Gay-Berne parameters were deduced by fitting the dispersive energies obtained from an atomistic molecular dynamics simulation of a small sample of hexa-octyl-thio triphenylene molecules in columnar phase, while a genetic algorithm was used to get a minimal set of point charges that properly reproduces the ab anitio electrostatic potential. We performed Monte Carlo simulations of three molecular models: the pure Gay-Berne disc, used as a reference, the Gay-Berne disc with hexa-thio triphenylene point charges, the Gay-Berne disc with hexa-thio azatriphenylene point charges. The phase diagram of the pure model evidences a rich polymorphism, with isotropic, columnar and crystalline phases at low pressure, and the appearance of nematic phase at higher pressure. Conclusion We found that the intermolecular electrostatic potential among the cores is fundamental in sta-bilizing/destabilizing columnar phases; in particular the triphenylene charge distribution stabilizes the columnar structure, while the azatriphenylene distribution suppresses its formation in favor of the nematic phase. We believe the present model could be successfully employed as the basis for coarse-grained level simulations of a wider class of triphenylene derivatives.

The incidence of thyroid nodules is rapidly increasing worldwide. Raman spectroscopy (RS) is a powerful label-free and non-invasive technique, successfully used for early stage diagnosis. Here, RS is proposed as a tool to investigate the thyroid disease, including neoplasms, through the study of cell oxidative stress (OS), which represents one of the main cancer risk factors. In this study, we enrolled 28 patients, submitted to a first and second thyroid fine needle aspiration (FNA) during follow up. The cytological samples were studied by RS and morphological examination. Typical Raman spectra of thyroid cytological samples are reported and the contribution of oxidized and reduced cytochrome b and c and carotenoids are discussed. On the basis of the evolution of the Raman features over the time lapse between the two FNAs, the 28 patients have been classified into 4 different categories and the most representative case for each category is reported and discussed in detail. For each category, the different Raman intensity ratio between oxidized and reduced cytochromes b and c is reported and associated to different cell OS status, along with the presence of carotenoids. Overall, our results support a correlation among changes in oxidative stress, carotenoids uptake and thyroid diseases, which could inspire new fundamental research on biomarkers and signaling pathways involved in thyroid OS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Among the thyroid cancers, papillary thyroid cancer (PTC) accounts for 90% of the cases. In addition to the necessity to identify new targets for PTC treatment, early diagnosis and management are highly demanded. Previous data indicated that the multivariate statistical analysis of the Raman spectra allows the discrimination of healthy tissues from PTC ones; this is characterized by bands typical of carotenoids. Here, we dissected the molecular effects of carotenoid accumulation in PTC patients by analyzing whether they were required to provide increased retinoic acid (RA) synthesis and signaling and/or to sustain antioxidant functions. HPLC analysis revealed the lack of a significant difference in the overall content of carotenoids. For this reason, we wondered whether the carotenoid accumulation in PTC patients could be related to vitamin A derivative retinoic acid (RA) biosynthesis and, consequently, the RA-related pathway activation. The transcriptomic analysis performed using a dedicated PCR array revealed a significant downregulation of RA-related pathways in PTCs, suggesting that the carotenoid accumulation in PTC could be related to a lower metabolic conversion into RA compared to that of healthy tissues. In addition, the gene expression profile of 474 PTC cases previously published in the framework of the Cancer Genome Atlas (TGCA) project was examined by hierarchical clustering and heatmap analyses. This metanalysis study indicated that the RA-related pathways resulted in being significantly downregulated in PTCs and being associated with the follicular variant of PTC (FV-PTC). To assess whether the possible fate of the carotenoids accumulated in PTCs is associated with the oxidative stress response, the expression of enzymes involved in ROS scavenging was checked. An increased oxidative stress status and a reduced antioxidant defense response were observed in PTCs compared to matched healthy thyroids; this was possibly associated with the prooxidant effects of high levels of carotenoids. Finally, the DepMap datasets were used to profile the levels of 225 metabolites in 12 thyroid cancer cell lines. The results obtained suggested that the high carotenoid content in PTCs correlates with tryptophan metabolism. This pilot provided novel possible markers and possible therapeutic targets for PTC diagnosis and therapy. For the future, a larger study including a higher number of PTC patients will be necessary to further validate the molecular data reported here.

In this work, an innovative analytical approach focused on the use of advanced imaging techniques for the chemical mapping of degradation and/or restoration products is proposed. A representative cross-section showing a very complex stratigraphy from the Saint Wilgefortis Triptych (Hieronymus Bosch), exhibited in the Galleria dell'Accademia di Venezia, was investigated. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) experiments were performed using a time-of-flight detector operating in the so-called delayed extraction mode. The time delay applied during the extraction of the secondary ions permitted mass spectra to be obtained with an excellent mass resolution and chemical maps with nanometer scale spatial resolution. The painting's cross-section was also analysed at the micrometer scale by micro-Fourier transform infrared spectroscopy (micro-FTIR). The combined analytical approaches highlighted the colocalization of lead chloride, oxychloride, and hydroxychloride ions, suggesting the transformation of lead white ((PbCO 3 ) 2 Pb(OH) 2 ) into laurionite (PbClOH). Furthermore, chlorine appears evenly diffused in the cinnabar (HgS) layer, inducing the alteration of its more external part into calomel (Hg 2 Cl 2 ). In fact, from the chemical maps the presence in the sample of an unaltered portion of the cinnabar layer is evident. Such degradation products were probably due to the exposure of the painting to a chloride-rich atmosphere for a long time. This led to a global blackening of the painting. To protect the painting from aggressive chemical species, siloxane compounds were probably used as a modern restorative treatment. ToF-SIMS chemical maps revealed permeation of the silicon-based consolidants within the sample's cracks and no interaction products with the other constitutive materials of the painting were found. Finally, the presence of different lead soaps was detected in correspondence with the lead white layer.

Among the different effects of bariatric surgery, here we focus on bone-derived inflammatory molecules, and in particular, sclerostin; an osteocyte product potentially associated with cardio-metabolic diseases. In 94 morbidly obese patients undergoing laparoscopic sleeve gastrectomy (SG), over-time changes in anthropometric and biochemical measures-including insulin resistance (IR) indexes-were correlated with serum sclerostin levels. Sclerostin was positively associated with anthropometric indexes of obesity, and inversely with IR, namely homeostatic model assessment for peripheral insulin sensitivity (HOMA2%S) (r = -0.218; p = 0.045). Sclerostin emerged as the only significant predictor of HOMA2-%S normalization, independently of demographic and anthropometric variables (OR 1.01 (95% CI 1.00-1.02); p = 0.024). We also identified two distinct patterns of serum sclerostin change: the higher/lower sclerostin levels at baseline, the greater their post-surgical reduction/increase ( p < 0.001 for all subgroups). Among those two patterns, especially the post-surgery increase in serum sclerostin was associated with lean mass reduction, without any association with IR indexes. Although counterintuitive, this change was likely dependent on the post-surgical increase in bone turnover. In conclusion, baseline serum levels of sclerostin correlate with anthropometric measures of obesity and IR, and the ability to predict glycemic improvements after SG. Specifically, serum sclerostin was closely associated with peripheral insulin sensitivity (HOMA2-%S), thus supporting the role of skeletal muscle/bone interactions in metabolic diseases.

Follicular patterned nodules are sometimes complex to be classified due to ambiguous nuclear features and/or questionable capsular or vascular invasion. In this setting, there is a poor inter-observer concordance even among expert pathologists. Raman spectroscopy was recently used to separate benign and malignant thyroid nodules based on their molecular fingerprint; anyway, some histologically proved follicular adenomas were clustered as having a characteristic profile of malignant lesions. In this study, we analyzed five follicular thyroid adenomas with a malignant spectroscopic profile compared to five follicular adenomas with a benign Raman spectrum in order to assess possible molecular differences between the two groups. Morphological, immunohistochemical, and molecular analyses evidenced expression of malignancy-associated proteins in four out of five malignant clustered adenomas. The remaining malignant clustered adenoma showed a TSHR mutation previously associated with autonomously functioning follicular carcinomas. In conclusion, thyroid follicular adenomas are a group of morphologically benign neoplasms that may have altered the mutational or expression profile; cases of adenomas with altered immunophenotype are recognized as showing a profile associated with malignancy by Raman spectroscopy. This correlation warrants a more extensive evaluation and suggests a potential predictive value of spectroscopic assessment in recognizing characteristics associated with tumor progression in follicular thyroid neoplasms.

Magnetic mesoporous silica (MS) nanocomposites provide the possibility of generating multi-functional objects for application in different technological areas. This paper focuses on the magnetic properties of nanocomposites constituted by spinel iron oxide nanoparticles (magnetic nanoparticles (MNPs), < D > ≈ 8-9 nm) embedded in an MS matrix. The mesoporous structure of the silica matrix and the presence of the nanoparticles inside clearly emerge from transmission electron microscopy (TEM) measurements. Low temperature (5 K) field-dependent magnetization measurements reveal saturation magnetization (M S ) close to bulk value (M S bulk ∼ 90 emu g -1 ) for both MNPs and MNP/MS nanocomposites, indicating that the presence of silica does not affect the magnetic features of the single MNPs. Moreover, the dependence of the remanent magnetization on field (i.e. δM plots) at low temperature has shown a small but evident decrease of interaction in an MNP/MS sample with respect to MNP samples A m 2 Kg -1 . Finally, a partial orientation of the easy axis is observed when the MNPs are embedded in the silica matrix.

Over the last 50 years, the incidence of human thyroid cancer disease has seen a significative increment. This comes along with an even higher increment of surgery, since, according to the international guidelines, patients are sometimes addressed to surgery also when the fine needle aspiration gives undetermined cytological diagnosis. As a matter of fact, only 30% of the thyroid glands removed for diagnostic purpose have a post surgical histological report of malignancy: this implies that about 70% of the patients have suffered an unnecessary thyroid removal. Here we show that Raman spectroscopy investigation of thyroid tissues provides reliable cancer diagnosis. Healthy tissues are consistently distinguished from cancerous ones with an accuracy of [Formula: see text] 90%, and the three cancer typology with highest incidence are clearly identified. More importantly, Raman investigation has evidenced alterations suggesting an early stage of transition of adenoma tissues into cancerous ones. These results suggest that Raman spectroscopy may overcome the limits of current diagnostic tools.

Background: Obesity is a risk factor for vitamin D deficiency and hyperparathyroidism. Hyperparathyroidism could exert a negative effect on glucose metabolism and vascular function. The aim of this study was to identify the determinants of hyperparathyroidism beyond vitamin D deficiency, whether hyperparathyroidism could have a negative impact on individual health and whether laparoscopic sleeve gastrectomy (LSG) negatively affects the levels of intact parathyroid hormone (iPTH) and 25(OH) vitamin D (25(OH)D)., Methods: We evaluated the levels of iPTH, 25(OH)D, and leptin, together with markers of insulin sensitivity and early cardiovascular disease, in a cohort of 160 patients with severe obesity before and after an LSG intervention., Results: Ninety-seven percent of subjects had vitamin D deficiency, and 72% of them had hyperparathyroidism. After correcting for possible confounders, we found a correlation between iPTH levels and carotid intima-media thickness, as well as with the HOMA index. After the LSG, 25(OH)D levels were significantly increased, while iPTH levels were significantly reduced. The reduction of iPTH was significantly correlated with the reduction of BMI, diastolic blood pressure, and leptin, which was the independent predictor of iPTH reduction., Conclusions: Our results suggest that vitamin D deficiency is not the sole determinant of hyperparathyroidism in severe obesity because visceral fat deposition and leptin could both play a role. Obesity-related hyperparathyroidism is associated with insulin resistance and atherosclerosis, although the results from previous studies were conflicting. Finally, LSG intervention does not negatively affect vitamin D status and improves hyperparathyroidism.

Previous studies showed a high prevalence of micronutrient deficiencies in obese subjects, with low folate and vitamin B12 serum levels and intakes. Correlations between vitamins and lipids have been investigated both in animal and human studies. The aim of our study is to evaluate the influence of dietetic and serum levels of folate and vitamin B12 on lipid pattern in morbidly obese subjects. We also analysed the relationship between serum concentrations and dietary intake of these micronutrients, and compared the intakes to the Recommended Levels of Nutrients and Energy Intakes (LARN). In 122 morbidly obese patients, mean BMI 45 ± 7 kg/m 2 , we evaluated anthropometric parameters, hepatic, glyco/lipid profile, total folate and vitamin B12, blood pressure, and finally nutritional intakes in a subgroup of 68 patients using a food frequency questionnaire about the frequency of food consumption and daily water intake. These values were determined in obese patients before and one year after sleeve gastrectomy. Both before and after surgery, levels of vitamins and minerals remained in normal range compared to LARN. According to univariate analysis, at baseline folate showed a significantly positive correlation with high-density lipoprotein cholesterol (p = 0.028, ρ = 0.204), apolipoprotein A-I (p = 0.006, ρ = 0.268) and vitamin B12 (p = 0.040, ρ = 0.192), and a significantly negative correlation with triglycerides (p = 0.049, ρ = -0.184). Folate and vitamin B12 levels do not correlate with their nutritional intakes, which remain within recommended range after surgery. In conclusion the correlation between folate and anti-atherogenic lipid profile is confirmed also in a large group of morbid obese patients.

On Earth, water plays an active role in cellular life, over several scales of distance and time. At a nanoscale, water drives macromolecular conformation through hydrophobic forces and at short times acts as a proton donor/acceptor providing charge carriers for signal transmission. At longer times and larger distances, water controls osmosis, transport, and protein mobility. Neutron diffraction experiments augmented by computer simulation, show that the three-dimensional shape of the hydration shell of carboxyl and carboxylate groups belonging to different molecules is characteristic of each molecule. Different hydration shells identify and distinguish specific sites with the same chemical structure. This experimental evidence suggests an active role of water also in controlling, modulating, and mediating chemical reactions involving carboxyl and carboxylate groups.

Background and Aims: Chemerin is an adipokine with an emerging role in the crosstalk between adipose tissue and immune system. It is overexpressed in severe obesity, affects adipogenesis and glucose homeostasis and it correlates with early vascular damage. The aim of this study is to investigate the correlation between circulating levels of chemerin and early vascular damage in subjects with severe obesity, before and after laparoscopic sleeve gastrectomy (LSG)., Methods: Fifty-six obese subjects eligible for LSG were enrolled in the study. The following parameters were evaluated: body mass index (BMI), glycemia, insulinemia, glycated haemoglobin, lipid profile, plasma chemerin levels and carotid intima-media thickness (cIMT). Fifty-four subjects were evaluated 1 year after the intervention., Results: Univariate analysis showed a direct and significant correlation between chemerin and waist circumference, insulin resistance, glycated haemoglobin and cIMT. Chemerin was a better predictor of intima-media thickening than waist circumference and glycated haemoglobin at the ROC curve analysis, with a cut-off value for chemerin of 140 ng/mL. The reduction of chemerin is independently associated with the reduction of cIMT and the improvement of insulin sensitivity after LSG., Conclusion: Chemerin is involved in the development and progression of early vascular damage and insulin resistance in subjects with severe obesity, and in their healing after bariatric surgery. Chemerin could also have a role in the assessment of cardiovascular risk in subjects with severe obesity., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation.)

Purpose: Recently, it has been demonstrated that Raman spectroscopy is able to differentiate between healthy parathyroid tissues and parathyroid adenoma based on the basis of a specific molecular fingerprint. However, to our knowledge, no previous studies have been performed to evaluate the metabolic profile of parathyroid adenoma. Therefore, we designed a proof of concept study aimed to investigate the glucose/fatty acid metabolisms, in addition to the mitochondrial changes, in solitary parathyroid adenoma and in healthy parathyroid glands., Methods: Nine females with primary hyperparathyroidism due to a solitary parathyroid adenoma and formal surgical indication for parathyroidectomy have been enrolled. At the time of surgery, the removed specimens were immediately submitted unfixed and a tissue slice of about 0.5 cm in diameter was obtained from the nodular lesion. The expression of selected metabolic enzymes and proteins has been evaluated by western blot analysis, using human parathyroid whole tissue lysates as control., Results: Data obtained highlighted an increase, compared with the healthy group, of: (i) the glucose uptake by the GLUT-1 receptor and its phosphorylation by hexokinase II (HXKII); (ii) the expression of 3-phosphoglycerate dehydrogenase (3-PGDH) and glucose-6-phosphate dehydrogenase (G6PD); (iii) lipids biosynthesis; and (iv) cytochrome c expression., Conclusions: Our findings highlight for the first time the parathyroid adenoma metabolic hallmarks that could represent potential molecular targets usable for the development of new pharmacological treatments, allowing to reduce surgical parathyroidectomy.

Natural sugars combine energy supply and, except a few cases, a pleasant taste. On the other hand, exaggerated consumption may impact population health. This has busted the research for the synthesis of increasingly cheaper artificial sweeteners, with low energy content and intense taste. Here, we suggest that studies of the hydration properties of three disaccharides, namely, the natural sucrose and lactose and the artificial sucralose, may explain the difference by orders of magnitude among their sweetness. This is done by analyzing via Monte Carlo simulations the neutron diffraction differential cross sections of aqueous solutions of the three sugars and their isotopes. Our results show that the strength of the sugar-water hydrogen bond interaction is one of the factors influencing sweetness, another being the number of water molecules within the first neighboring shell of the sugar whether bonded or not., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Neutrophil extracellular traps (NETs) are DNAs products involved in immune process. Obesity through a low-grade chronic inflammation determines neutrophil activation, but it is still unclear its role in NETs formation. Here we analyzed the NETs levels in healthy and morbid obese, their association with anthropometric and glyco-metabolic parameters and their changes after bariatric surgery. For this study, we enrolled 73 patients with morbid obesity (BMI ≥40 kg/m 2 or ≥35 kg/m 2  + comorbidity) eligible to sleeve gastrectomy. In parallel, 55 healthy subjects and 21 patients with severe coronary artery disease were studied as controls. We evaluated anthropometric parameters, peripheral blood pressure, biochemical and serum analysis at the enrollment and at twelve months after surgery. Plasmatic levels of MPO-DNA complexes were assessed by ELISA. NETs levels were higher in obese than in control group (p < 0.001) and correlated with the main anthropometric variable (BMI, waist, hip), glyco-metabolic variables and systolic blood pressure. NETs trend after intervention was uneven. The reduction of NETs correlated with the entity of reduction of BMI (ρ = 0.416, p < 0.05), visceral fat area (ρ = 0.351, p < 0.05), and glycemia (ρ = 0.495, p < 0.001). In medical history of patients in whom NETs increased, we observed a higher number of thromboembolic events. Our observations indicate that severe obesity is associated with increased generation of NETs, which in turn could influence the patients' systemic inflammatory state. Weight loss and in particular, loss of adipose tissue after bariatric surgery does not in itself correct NET's dysregulated production. Finally, patients in whom NETs accumulation persists after surgery are probably those at the highest risk of cardiovascular events.

Background and Aims: The rising prevalence of morbid obesity is increasing the demand for bariatric surgery. The benefits observed after bariatric surgery seems to be not fully explained by surgery-induced weight loss or traditional cardiovascular risk factors regression or improvement. Some evidences suggest that bile acid (BA) levels change after bariatric surgery, thus suggesting that BA concentrations could influence some of the metabolic improvement induced by bariatric surgery. In this report, we have characterized circulating BA patterns and compared them to metabolic and vascular parameters before and after sleeve gastrectomy (SG)., Patients and Methods: Seventy-nine subjects (27 males, 52 females, aged 45 ± 12 years, mean BMI 45 ± 7 kg/m 2 ) SG candidates were included in the study. Before and about 12 months after SG, all subjects underwent a clinical examination, blood tests (including lipid profile, plasma glucose and insulin, both used for calculating HOMA-IR, and glycated hemoglobin), ultrasound visceral fat area estimation, ultrasound flow-mediated dilation evaluation, and determination of plasma BA concentrations., Results: Before SG, both primary and secondary BA levels were higher in insulin-resistant obese subjects than in non-insulin resistant obese, and BA were positively associated with the markers of insulin-resistance. After SG, total (conjugated and unconjugated) cholic acids significantly decreased (p 0.007), and total lithocholic acids significantly increased (p 0.017). SG-induced total cholic and chenodeoxycholic acid changes were directly associated with surgery-induced glycemia (p 0.011 and 0.033 respectively) and HOMA-IR (p 0.016 and 0.012 respectively) changes., Conclusions: Serum BA are associated with glucose metabolism and particularly with markers of insulin-resistance. SG modifies circulating BA pool size and composition. SG-induced BA changes are associated with insulin-resistance amelioration. In conclusion, an interplay between glucose metabolism and circulating BA exists but further studies are needed.

The quest for a possible liquid-liquid coexistence line in supercooled water below its homogeneous nucleation temperature is faced by confining water within a porous silica substrate (MCM-41). This system is investigated by synchrotron radiation infrared spectroscopy, exploring both the intramolecular and the intermolecular vibrational dynamics, in the temperature range from ambient down to ∼120 K, along several isobaric paths between 0.7 kbar and 3.0 kbar. Upon lowering the temperature, the OH-stretching band shows that the intramolecular vibrational dynamics continuously evolves from predominantly liquidlike to predominantly icelike. An abrupt change in the line shape of the intermolecular vibrational band between 220 K and 240 K, depending on the pressure, is the signature of nucleation of ice within the MCM-41 pores. These findings do not support the presence of two liquid phases and provide evidence for the coexistence of liquid water and ice in water confined in MCM-41.

A very low carbohydrate ketogenic diet (VLCKD) is an emerging technique to induce a significant, well-tolerated, and rapid loss of body weight in morbidly obese patients. The low activity of lysosomal acid lipase (LAL) could be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is a common feature in morbidly obese patients. Fifty-two obese patients suitable for a bariatric surgery intervention underwent a 25-day-long VLCKD. The biochemical markers of glucose and lipid metabolism, and flow-mediated dilation (FMD) of the brachial artery were measured before and after VLCKD. LAL activity was measured using the dried blood spot technique in 20 obese patients and in a control group of 20 healthy, normal-weight subjects. After VLCKD, we observed a significant reduction in body mass index, fasting glucose, insulinemia, and lipid profile parameters. No significant variation in FMD was observed. The number of patients with severe liver steatosis significantly decreased. LAL activity significantly increased, although the levels were not significantly different as compared to the control group. In conclusion, VLCKD induces the activity of LAL in morbidly obese subjects and reduces the secretion of all circulating lipoproteins. These effects could be attributed to the peculiar composition of the diet, which is particularly poor in carbohydrates and relatively rich in proteins.