Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

The applications of Wearable Cardioverter Defibrillators in Heart Failure and beyond.

Abstract: Wearable cardioverter defibrillator has revealed a crucial device both in patients with a clear indication of ICD implantation but with temporary contraindications or in expectation of a diagnosis, considering that its use should be individualized.

Artificial intelligence-based radiomics on computed tomography of lumbar spine in subjects with fragility vertebral fractures.

PURPOSE: There is emerging evidence that radiomics analyses can improve detection of skeletal fragility. In this cross-sectional study, we evaluated radiomics features (RFs) on computed tomography (CT) images of the lumbar spine in subjects with or without fragility vertebral fractures (VFs). METHODS: Two-hundred-forty consecutive individuals (mean age 60.4 ± 15.4, 130 males) were evaluated by radiomics analyses on opportunistic lumbar spine CT. VFs were diagnosed in 58 subjects by morphometric approach on CT or XR-ray spine (D4-L4) images. DXA measurement of bone mineral density (BMD) was performed on 17 subjects with VFs. RESULTS: Twenty RFs were used to develop the machine learning model reaching 0.839 and 0.789 of AUROC in the train and test datasets, respectively. After correction for age, VFs were significantly associated with RFs obtained from non-fractured vertebrae indicating altered trabecular microarchitecture, such as low-gray level zone emphasis (LGLZE) [odds ratio (OR) 1.675, 95% confidence interval (CI) 1.215-2.310], gray level non-uniformity (GLN) (OR 1.403, 95% CI 1.023-1.924) and neighboring gray-tone difference matrix (NGTDM) contrast (OR 0.692, 95% CI 0.493-0.971). Noteworthy, no significant differences in LGLZE (p = 0.94), GLN (p = 0.40) and NGDTM contrast (p = 0.54) were found between fractured subjects with BMD T score < - 2.5 SD and those in whom VFs developed in absence of densitometric diagnosis of osteoporosis. CONCLUSIONS: Artificial intelligence-based analyses on spine CT images identified RFs associated with fragility VFs. Future studies are needed to test the predictive value of RFs on opportunistic CT scans in identifying subjects with primary and secondary osteoporosis at high risk of fracture.

Linac-based STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia: a treatment planning study.

OBJECT: To analyze geometrical approaches, prescription modalities, and delivery efficiency for linear accelerator (Linac)-based STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia. METHODS: The anatomy and planning target volume (PTV) of the first Italian STAR patient were used. To assess geometrical approaches, 3 plans prescribed to 75% isodose-line, differing for number, length of arcs, and couch rotations, were generated and compared (Plans#1-3). Volumetric-arc with 6-MV flattening-filter-free (FFF) was employed. To evaluate prescription modality and delivery, the best geometrical plan was compared with other plans prescribed on 70%, 65%, and 60% isodose-line and with another one using 10MV-FFF beams (Plans#4-7). RESULTS: For Plans#1-3, PTV coverage, mean cardiac dose, monitor units (MUs), and beam-delivery-time (BDT) were 96-98.5%, 4.9-5.2 Gy, 7047-7790, and 5-6 min, respectively. Plans#4-7 were similar in terms of mean cardiac dose, MUs and BDT to Plans#1-3, except in maximum dose and lower time for 10MV-FFF plan. CONCLUSION: Linac-based STAR is safe and efficient in terms of BDT and MUs. To ensure high dose to PTV, different dose prescription modalities should be evaluated. The 10FFF approach was the faster but not suitable in patient with cardiac implantable electronic devices.

Saccorhiza polyschides used to synthesize gold and silver nanoparticles with enhanced antiproliferative and immunostimulant activity.

Over the last years, there has been an increasing trend towards the use of environmentally friendly processes to synthesize nanomaterials. In the case of nanomedicine, the use of bionanofactories with associated biological properties, such as seaweed, has emerged as a promising field of work due to the possibility they open for both the preservation of those properties in the nanomaterials synthesized and/or the reduction of their toxicity. In the present study, gold (Au@SP) and silver (Ag@SP) nanoparticles were synthesized using an aqueous extract of Saccorhiza polyschides (SP). Several techniques showed that the nanoparticles formed were spherical and stable, with mean diameters of 14 ± 2 nm for Au@SP and 15 ± 3 nm for Ag@SP. The composition of the biomolecules in the extract and the nanoparticles were also analyzed. The analyses performed indicate that the extract acts as a protective medium, with the particles embedded in it preventing aggregation and coalescence. Au@SP and Ag@SP showed superior immunostimulant and antiproliferative activity on immune and tumor cells, respectively, to that of the SP extract. Moreover, the nanoparticles were able to modulate the release of reactive oxygen species depending on the concentration. Hence, both nanoparticles have a significant therapeutic potential for the treatment of cancer or in immunostimulant therapy.

High optical enhancement in Au/Ag alloys and porous Au using Surface-Enhanced Raman spectroscopy technique.

We report high optical enhancement in Ag/Au alloys and porous gold nanostructures using Surface Enhanced Raman Spectroscopy (SERS) technique. Scanning electron microscopy investigation shows the formation of Ag/Au alloys particles during irradiation of Ag-Au bilayer deposited on FTO (SnO2:F) substrate by laser fluency equal to 0.5 J/cm2 or 1.0 J/cm2 with 12 ns laser pulse duration. The dealloying process of these Au-Ag alloy particles leads to the formation of Au nanoporous particles. The obtained nanostructures were studied with SERS and revealed a promising enhancement factor in porous Au nanostructure and tunability of localized surface plasmon resonance. The highly dense strong hot spots and large specific area in porous structure of gold nanostructures is the origin of the highly enhancement factor observed experimentally and theoretically. A very good agreement between simulation and experimental results was found confirming the potential of Au/Ag alloys and particularly porous gold nanostructure in SERS application.

Re-do surgery after prosthetic abdominal wall repair: intraoperative findings of mesh-related complications.

INTRODUCTION: Mesh repair is one of the most popular technique for the treatment of abdominal wall hernias, resulting in lower recurrence rates. However, it is associated with a high risk of mesh-related complications. The aim of the present study is to assess the impact of biomaterials on the intra-abdominal organs, in terms of adhesions and visceral complications, in a series of patients undergoing re-do surgery at our abdominal wall unit. MATERIALS AND METHODS: We reviewed the clinical records of 301 patients who undergone laparotomy between June 2008 and May 2018, selecting 67 patients with one or more previous prosthetic abdominal wall repair (AWR). RESULTS: The average number of previous repairs was 1.6 with a mean time interval of 66 months from the last repair. Clinical presentation included hernia recurrence (69%), mesh infection (26%), infection and recurrence (10%), and fistula (1%). Adhesions were intraoperatively observed in all patients, except for eight cases. Mesh was completely removed in 43 patients, partially in four. Postoperative complications were observed in 39% of cases, including wound dehiscence, hematoma, seroma, and mesh infection. CONCLUSIONS: Long-term implant results in abdominal wall repair and are not completely known, and literature is still lacking on this topic. Re-do surgery for subsequent pathological events may represent a way to increase our knowledge.

Immunostimulant and biocompatible gold and silver nanoparticles synthesized using the Ulva intestinalis L. aqueous extract.

This is the first study to report on the biocompatible and immunogenic properties of one-pot synthesised gold and silver nanoparticles (Au@UI and Ag@UI) using the macroalgae Ulva intestinalis (UI). The UI aqueous extract, Au@UI, and Ag@UI were obtained under sterile conditions and fully characterized by UV-vis spectroscopy, TEM, HRTEM, STEM and FTIR spectroscopy. Moreover, for the first time, the composition of carbohydrates in the UI extract has been reported along with the changes observed after nanoparticle synthesis by size exclusion chromatography, in order to investigate their possible role in the biosynthetic process. This study suggested that the polysaccharide fraction of the extract is involved in the formation and stabilization of the nanoparticles. The potential toxicity of the samples was evaluated using different cell lines and the hemocompatibility was tested in mouse erythrocytes. In addition, ROS production, complement activation and cytokine release were evaluated to determine the immunogenicity. The results showed that Au@UI and Ag@UI exhibit good biocompatibility and hemocompatibility, with the exception of Ag@UI nanoparticles at high concentration, which were hemolytic. The samples induced ROS release and complement activation, two key mechanisms in innate immunity. The samples also induced the release of cytokines from Th1 and Th2 profiles, and other cytokines implicated in the activation of the immune system. Au@UI and Ag@UI were biocompatible and preserved the immunostimulant properties of the UI extract. Hence, Au@UI and Ag@UI could be useful as adjuvants in vaccine development and promote a balanced Th1 and Th2 immune response mediated by ROS production, cytokine release and complement activation.

Comparison of T1 mapping and fixed T1 method for dynamic contrast-enhanced MRI perfusion in brain gliomas.

OBJECTIVES: To compare dynamic contrast-enhanced MRI (DCE-MRI) data obtained using different prebolus T1 values in glioma grading and molecular profiling. METHODS: We retrospectively reviewed 83 cases of gliomas: 46 lower-grade gliomas (LGG; grades II and III) and 37 high-grade gliomas (HGG; grade IV). DCE-MRI maps of plasma volume fraction (Vp), extravascular-extracellular volume fraction (Ve), and tracer transfer constant from plasma to tissue (Ktrans) were obtained using a fixed T1 value of 1400 ms and a measured T1 obtained with variable flip angle (VFA). Tumour segmentations were performed and first-order histogram parameters were extracted from volumes of interest (VOIs) after co-registration with the perfusion maps. The two methods were compared using Wilcoxon matched-pairs signed-rank test and Bland-Altman analysis. Diagnostic accuracy was obtained and compared using ROC curve analysis and DeLong's test. RESULTS: Perfusion parameters obtained with the fixed T1 value were significantly higher than those obtained with the VFA. As regards diagnostic accuracy, there were no significant differences between the two methods both for glioma grading and molecular classification, except for few parameters of both methods. CONCLUSIONS: DCE-MRI data obtained with different prebolus T1 are not comparable and the definition of a prebolus T1 by T1 mapping is not mandatory since it does not improve the diagnostic accuracy of DCE-MRI. KEY POINTS: • DCE-MRI data obtained with different prebolus T1 are significantly different, thus not comparable. • The definition of a prebolus T1 by T1 mapping is not mandatory since it does not improve the diagnostic accuracy of DCE-MRI for glioma grading. • The use of a fixed T1 value represents a valid alternative to T1 mapping for DCE-MRI analysis.

Near-infrared modulation by means of GeTe/SOI-based metamaterial.

Today, nanophotonics still lacks components for modulation that can be easily implementable in existing silicon-on-insulator (SOI) technology. Chalcogenide phase change materials (PCMs) are promising candidates for tuning in the near infrared: at the nanoscale, thin layers can provide enough contrast to control the optical response of a nanostructure. Moreover, all-dielectric metamaterials allow for resonant behavior without having ohmic losses in the telecom range. Here, a novel hybridization of a SOI-based metamaterial with PCM GeTe is experimentally investigated. A metamaterial based on Si nanorods, covered by a thin layer of GeTe, is designed and fabricated. Switching GeTe from amorphous to crystalline leads to a rather high resonance-governed reflection contrast at 1.55 µm. Additional confocal Raman imaging is done to differentiate the crystallized zones of the metamaterials' unit cell. The findings are in good agreement with numerical analysis and show good perspectives of all-dielectric tunable near-infrared nanophotonics.

Mesh-related visceral complications following inguinal hernia repair: an emerging topic.

The use of meshes in inguinal hernia repair (IHR) has gained popularity but new complications have been observed. Mesh-related visceral complications (MRVCs) are generally considered rare and hence are not studied in depth. We carried out a thorough literature search and collected 101 clinical reports published from 1992 to 2018. The reported complications seem to have tripled in the last decade. Ninety-seven cases met the inclusion criteria and they were subdivided into four groups (group A-onlay IHR, group B-3-D IHR, group C-preperitoneal IHR, group D-laparoscopic IHR) to be analyzed, according to the herniorraphy technique. Every prosthetic IHR can be followed by MRVCs but, according to the present review, the highest incidence is related to laparoscopic repairs, the lowest to Lichtenstein technique. Time-to-event was shorter in case of preperitoneal position of the prosthesis than when the mesh was implanted over the transversalis fascia. Urinary bladder involvement predominantly occurred after laparosopic IHR. A pathogenic correlation between the most frequently complained clinical signs and the previous mesh herniorraphy was rarely reported. The diagnosis was generally made at laparotomy, which was usually performed as an emergency. Removing the infected mesh and resecting or suture repairing the involved viscera was the challenging surgical treatment. Prevention of MRVCs after inguinal hernia repair appears to be an important significant issue. It is important to pay attention to the choice of a proper implantation site, avoiding direct contact between the mesh and viscera, and to select a proper device.

Mercury Isotopic Fractionation during Pedogenesis in a Tropical Forest Soil Catena (French Guiana): Deciphering the Impact of Historical Gold Mining.

We used natural mercury (Hg) stable isotopes to investigate the Hg cycle in a rainforest soil catena (French Guiana) partially gold-mined during the early 1950s. Litterfall showed homogeneous Δ199Hg values [-0.18 ± 0.05‰, i.e., a modern gaseous elemental Hg (GEM) isotopic signature]. After litter decomposition, Hg bound to organic matter (OM) is mixed with Hg from pristine (-0.55 ± 0.22‰) or gold-mined (-0.09 ± 0.16‰) mineral materials. Negative Δ199Hg values in deep pristine mineral horizons (-0.60 ± 0.16‰) suggest the transfer of Hg bound to dissolved OM depleted in odd isotopes due to mass-independent fractionation during Hg abiotic reduction. Perennial palm tree leaves collected above gold-mined and pristine soil recorded contrasting Δ199Hg signatures likely resulting from GEM re-emission processes from soils and leaf surfaces. Upslope, soil δ202Hg signatures showed a negative shift (ε ∼ -1‰) with depth attributed to mass-dependent fractionation during Hg sorption and complexation onto iron oxides and dissolved OM. Downslope, higher δ202Hg values in soils resulted from hydromorphy [lower humification, greater Hg(II) reduction, etc.]. The unique Hg isotopic signatures of Amazonian soils probably result in multistep fractionation processes during pedogenesis (millions of years) and in a potentially different Hg isotopic signature of preanthropogenic background GEM.

Effect of nutrient deprivation on the expression and the epigenetic signature of sirtuin genes.

BACKGROUND AND AIM: Over the last decades advances in understanding the molecular bases of the close relationship between nutrition, metabolism, and diseases have been impressive. However, there are always novel frontiers coming up and epigenetics is one of these. Sirtuins, are pivotal factors in the control of metabolic pathways according to nutrient availability. In the present study we evaluated the effect of nutrient deprivation on expression, DNA methylation and chromatin status of the sirtuin genes. METHODS AND RESULTS: We performed these studies in mouse hepatoma cells, that were grown in standard medium, or in media containing low glucose concentration, or no glucose, or no amino acids. We applied quantitative real-time PCR to cDNA, methylation-enriched DNA and nuclease-treated DNA in order to evaluate gene expression, DNA methylation, and chromatin condensation, respectively. This study shows that the expression of sirtuin genes varies following nutrient deprivation. Moreover, we observed that changes of DNA methylation and chromatin condensation occur at the transcription start site of sirtuin genes following nutrient deprivation. CONCLUSIONS: Epigenetic mechanisms may have a role in the sirtuin response to nutrient deprivations in cultured hepatoma cells. Replicating these results in vivo to achieve a comprehensive understanding of the epigenetic control of sirtuin expression following nutrient deprivations might open up novel therapeutic possibilities to cure metabolic diseases and promote human health.

Intensive dietary intervention promoting the Mediterranean diet in people with high cardiometabolic risk: a non-randomized study.

AIMS: Mediterranean diet (MD) is acknowledged to exert a number of beneficial health effects. We assessed the efficacy and the durability of a 3-month intensive dietary intervention aimed at implementing the MD on body weight and cardiometabolic risk factors in subjects at high risk. METHODS: One hundred and sixteen subjects participated in the study (71 assigned to the intensive intervention and 45 to the conventional intervention). The intensive intervention consisted of 12 weekly group educational meetings and a free-of-charge supply of meals prepared according to the MD model. The conventional intervention consisted of an individual education session along with monthly reinforcements of nutritional messages by the general practitioner. All participants were followed up for 9 months. RESULTS: The two groups had similar pre-intervention characteristics. After the intervention, mean body weight decreased significantly in both groups (p < 0.001). However, the intervention group lost more weight (6.8 ± 4.0 vs. 0.7 ± 1.3, p < 0.0001) and showed a greater reduction in plasma glucose, triglycerides, blood pressure and an increase in HDL cholesterol than the control group (p < 0.01-p < 0.002). In the subgroup of participants with type 2 diabetes, there was a significant reduction in HbA1c level following the intensive (p < 0.0001) but not the conventional intervention. At follow-up, weight loss still persisted in the intervention group (p < 0.0001), while it was lost in the control group. Both interventions significantly reduced blood pressure in the long term (p < 0.001). A significant reduction in daily total energy intake was observed in both groups with a greater reduction in saturated fat and a higher increase in fibre intake in the intervention than in the control group (p < 0.009 and p < 0.001, respectively). CONCLUSIONS: A 3-month intensive dietary intervention inspired to the traditional MD produced greater and more durable weight loss and improvement in cardiometabolic risk profile than the conventional intervention.

GPU-based computation for brain spatio-temporal networks definition.

Nowadays, with the increase of computational analysis in sciences such as biology and neuroscience, the computational aspect is one of the most challenging. The purpose of this work is the achieve the possibility to apply spatio-temporal networks inference techniques on brain to perform network analysis. One of the problems of spatio-temporal network applications is the computational time, and it becomes impractical to keep developing studies when it takes a long time to analyze and compute the results. We present a GPU-based system used to speed up the computation of spatio-temporal networks applied to different brain data; thanks to the architecture of these devices we are able to obtain an average increase in the performances of ~ 35× on a single GPU and ~ 78× on multi GPU with the respect of CPU execution.

An innovative chemical strategy for PCR-free genetic detection of pathogens by an integrated electrochemical biosensor.

An innovative chemical strategy integrated in a miniaturized electrochemical device was developed for sensitive detection of a pathogen genome (HBV virus) without any amplification step. The results show a limit of detection comparable to the standard qRT-PCR method (20 copies per reaction), paving the way to future development of genetic PoC devices addressing automatized and low-cost molecular diagnostics.

Candidate apoptotic and DNA repair gene approach confirms involvement of ERCC1, ERCC5, TP53 and MDM2 in radiation-induced toxicity in head and neck cancer.

INTRODUCTION: Single nucleotide polymorphisms (SNPs) of DNA repair and apoptosis genes have been associated with outcome in head and neck squamous cell carcinoma (HNSCC) patients receiving radiotherapy (RT). Our goal was to conduct a candidate gene study in HNSCC patients receiving RT or chemoRT. METHODS: 122 non-resectable HNSCC patients undergoing RT (N=38) or chemoRT (N=84) between 1992 and 2006 were retrospectively analyzed. ERCC1 Lys259Thr (rs735482), ERCC2 Lys751Gln (rs13181), ERCC5 His46His C>T (rs1047768), XRCC1 Arg399Gln (rs25487), TP53 Arg72Pro (rs1042522) and MDM2 309T>G (rs2279744) were analyzed on tumor DNA. SNP profile was considered to assess RT-related toxicity. RESULTS: All 120 evaluable patients experienced RT-related toxicity at any time. Among them, 83% had G3-4 acute side-effects during RT, mainly dysphagia, mucositis, epithelitis and/or xerostomia (DMEX). 28/105 patients (27%) had early G3-4 toxicity up to 3months after the end of RT. 29/96 patients (30%) had G3-4 late toxicity thereafter. The presence of G allele of MDM2 or Thr allele of ERCC1 was associated with a significantly higher risk of acute and/or early DMEX toxicity. The MDM2 309GG genotype was linked to a higher risk of acute G3-4 dermatitis. The ERCC5 TT genotype was associated with more frequent G3-4 late cervical skin fibrosis or xerostomia. Pro allele of TP53 72 was associated with a higher risk of G3-4 osteoradionecrosis. CONCLUSION: Relevant SNPs in DNA repair (ERCC1 and ERCC5) and apoptosis (MDM2 and TP53) genes might influence the severity of radiation-related side-effects in HNSCC patients. Prospective clinical SNP-based validation studies are needed on these bases.