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Non-targeted NMR is widely accepted as a powerful and robust analytical tool for food control. Nevertheless, standardized procedures based on validated methods are still needed when a non-targeted approach is adopted. Interlaboratory comparisons carried out in recent years have demonstrated the statistical equivalence of spectra generated by different instruments when the sample was prepared by the same operator. The present study focused on assessing the reproducibility of NMR spectra of the same matrix when different operators performed individually both the sample preparation and the measurements using their spectrometer. For this purpose, two independent laboratories prepared 63 tomato samples according to a previously optimized procedure and recorded the corresponding 1D 1 H NMR spectra. A classification model was built using the spectroscopic fingerprint data delivered by the two laboratories to assess the geographical origin of the tomato samples. The performance of the optimized statistical model was satisfactory, with a 97.62% correct sample classification rate. The results of this work support the suitability of NMR techniques in food control routines even when samples are prepared by different operators by using their equipment in independent laboratories.

In this pilot study, a multi-parametric analysis comparing immune responses in sera of adult healthy subjects (HS) or people with type 2 diabetes mellitus (T2D) undergoing the single or simultaneous administration of mRNA-based COVID-19 and cellular quadrivalent inactivated influenza vaccines was conducted. While SARS-CoV-2 antibodies remains comparable, influenza antibody titers and seroconversion were significantly higher upon simultaneous vaccination. Magnitude of anti-influenza humoral response closely correlated with an early innate immune signature, previously described for the COVID-19 vaccine, composed of IL-15, IL-6, TNF-α, IFN-γ, CXCL-10 and here extended also to acute-phase protein Pentraxin 3. People with T2D receiving simultaneous vaccination showed a protective response comparable to HS correlating with the early induction of IFN-γ/CXCL10 and a significant reduction of the circulating glucose level due to increased oxidation of glucose digestion and consumption. These data, although preliminary and in-need of validation in larger cohorts, might be exploited to optimize future vaccination in people with chronic disorders, including diabetes.

Repressing BET proteins' function using bromodomain inhibitors (BETi) has been shown to elicit antitumor effects by regulating the transcription of genes downstream of BRD4. We previously showed that BETi promoted cell death of triple-negative breast cancer (TNBC) cells. Here, we proved that BETi induce altered mitochondrial dynamics fitness in TNBC cells falling in cell death. We demonstrated that BETi treatment downregulated the expression of BCL-2, and proteins involved in mitochondrial fission and increased fused mitochondria. Impaired mitochondrial fission affected oxidative phosphorylation (OXPHOS) inducing the expression of OXPHOS-related genes, SDHa and ATP5a, and increased cell death. Consistently, the amount of mitochondrial DNA and mitochondrial membrane potential (∆Ψm) increased in BETi-treated cells compared to control cells. Lastly, BETi in combination with Metformin reduced cell growth. Our results indicate that mitochondrial dynamics and OXPHOS metabolism support breast cancer proliferation and represent novel BETi downstream targets in TNBC cells., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Proton magnetic resonance spectroscopy ( 1 H-MRS) of surgically collected tumor specimens may contribute to investigating cancer metabolism and the significance of the "total choline" ( t Cho) peak (3.2 ppm) as malignancy and therapy response biomarker. To ensure preservation of intrinsic metabolomic information, standardized handling procedures are needed. The effects of time to freeze (cold ischemia) were evaluated in (a) surgical epithelial ovarian cancer (EOC) specimens using high-resolution (HR) 1 H-MRS (9.4 T) of aqueous extracts and (b) preclinical EOC samples (xenografts in SCID mice) investigated by in vivo MRI-guided 1 H-MRS (4.7 T) and by HR- 1 H-MRS (9.4 T) of tumor extracts or intact fragments (using magic-angle-spinning (MAS) technology). No significant changes were found in the levels of 27 of 29 MRS-detected metabolites (including the t Cho profile) in clinical specimens up to 2 h cold ischemia, besides an increase in lysine and a decrease in glutathione. EOC xenografts showed a 2-fold increase in free choline within 2 h cold ischemia, without further significant changes for any MRS-detected metabolite (including phosphocholine and t Cho) up to 6 h. At shorter times (≤1 h), HR-MAS analyses showed unaltered t Cho components, along with significant changes in lactate, glutamate, and glutamine. Our results support the view that a time to freeze of 1 h represents a safe threshold to ensure the maintenance of a reliable t Cho profile in EOC specimens.

Revision of anterior cruciate ligament reconstruction (ACL-R) presents many challenges that are not encountered in the primary setting and, therefore, requires thorough preoperative planning. Recently, there has been growing evidence showing that combining the anterolateral ligament (ALL) reconstruction with ACL-R revision reduces the risk of postoperative ACL rupture and meniscal tears, and therefore, the ALL reconstruction becomes essential to a complex ACL revision. The technique that we describe is mainly used in the setting of complex ACL revision with extensive tunnel osteolysis associated with rotational instability of the knee. This article presents a technique for a one-stage complex ACL-R revision combined with ALL reconstruction using an Achilles tendon allograft with a bone plug., Competing Interests: The authors report no conflicts of interest in the authorship and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (© 2023 The Authors.)

Cell outer membranes contain glycosphingolipids and protein receptors, which are integrated into glycoprotein domains, known as lipid rafts, which are involved in a variety of cellular processes, including receptor-mediated signal transduction and cellular differentiation process. In this study, we analyzed the lipidic composition of human Dental Pulp-Derived Stem Cells (DPSCs), and the role of lipid rafts during the multilineage differentiation process. The relative quantification of lipid metabolites in the organic fraction of DPSCs, performed by Nuclear Magnetic Resonance (NMR) spectroscopy, showed that mono-unsaturated fatty acids (MUFAs) were the most representative species in the total pool of acyl chains, compared to polyunsatured fatty acids (PUFAs). In addition, the stimulation of DPSCs with different culture media induces a multilineage differentiation process, determining changes in the gangliosides pattern. To understand the functional role of lipid rafts during multilineage differentiation, DPSCs were pretreated with a typical lipid raft affecting agent (MβCD). Subsequently, DPSCs were inducted to differentiate into osteoblast, chondroblast and adipoblast cells with specific media. We observed that raft-affecting agent MβCD prevented AKT activation and the expression of lineage-specific mRNA such as OSX, PPARγ2, and SOX9 during multilineage differentiation. Moreover, this compound significantly prevented the tri-lineage differentiation induced by specific stimuli, indicating that lipid raft integrity is essential for DPSCs differentiation. These results suggest that lipid rafts alteration may affect the signaling pathway activated, preventing multilineage differentiation., 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 © 2023 Santilli, Fabrizi, Martellucci, Santacroce, Iorio, Pisanu, Chirico, Lancia, Pulcini, Manganelli, Sorice, Delle Monache and Mattei.)

The weak acid sorbic acid is a common preservative used in soft drink beverages to control microbial spoilage. Consumers and industry are increasingly transitioning to low-sugar food formulations, but potential impacts of reduced sugar on sorbic acid efficacy are barely characterised. In this study, we report enhanced sorbic acid resistance of yeast in low-glucose conditions. We had anticipated that low glucose would induce respiratory metabolism, which was shown previously to be targeted by sorbic acid. However, a shift from respiratory to fermentative metabolism upon sorbic acid exposure of Saccharomyces cerevisiae was correlated with relative resistance to sorbic acid in low glucose. Fermentation-negative yeast species did not show the low-glucose resistance phenotype. Phenotypes observed for certain yeast deletion strains suggested roles for glucose signalling and repression pathways in the sorbic acid resistance at low glucose. This low-glucose induced sorbic acid resistance was reversed by supplementing yeast cultures with succinic acid, a metabolic intermediate of respiratory metabolism (and a food-safe additive) that promoted respiration. The results indicate that metabolic adaptation of yeast can promote sorbic acid resistance at low glucose, a consideration for the preservation of foodstuffs as both food producers and consumers move towards a reduced sugar landscape., Competing Interests: None., (© 2023 The Authors.)

Purpose: Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course., Methods: Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested., Results: Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC., Conclusion: Combined treatment improved RFS and PFS only in patients with Ta disease., (© 2023. The Author(s).)

Background: The main mechanism underlying cancer dissemination is the epithelial to mesenchymal transition (EMT). This process is orchestrated by cytokines like TGFβ, involving "non-canonical" AKT- or STAT3-driven pathways. Recently, the alteration of copper homeostasis seems involved in the onset and progression of cancer., Methods: We expose different breast cancer cell lines, including two triple negative (TNBC) ones, an HER2 enriched and one cell line representative of the Luminal A molecular subtype, to short- or long-term copper-chelation by triethylenetetramine (TRIEN). We analyse changes in the expression of EMT markers (E-cadherin, fibronectin, vimentin and αSMA), in the levels and activity of extracellular matrix components (LOXL2, fibronectin and MMP2/9) and of copper homeostasis markers by Western blot analyses, immunofluorescence, enzyme activity assays and RT-qPCR. Boyden Chamber and wound healing assays revealed the impact of copper chelation on cell migration. Additionally, we explored whether perturbation of copper homeostasis affects EMT prompted by TGFβ. Metabolomic and lipidomic analyses were applied to search the effects of copper chelation on the metabolism of breast cancer cells. Finally, bioinformatics analysis of data on breast cancer patients obtained from different databases was employed to correlate changes in kinases and copper markers with patients' survival., Results: Remarkably, only HER2 negative breast cancer cells differently responded to short- or long-term exposure to TRIEN, initially becoming more aggressive but, upon prolonged exposure, retrieving epithelial features, reducing their invasiveness. This phenomenon may be related to the different impact of the short and prolonged activation of the AKT kinase and to the repression of STAT3 signalling. Bioinformatics analyses confirmed the positive correlation of breast cancer patients' survival with AKT activation and up-regulation of CCS. Eventually, metabolomics studies demonstrate a prevalence of glycolysis over mitochondrial energetic metabolism and of lipidome changes in TNBC cells upon TRIEN treatment., Conclusions: We provide evidence of a pivotal role of copper in AKT-driven EMT activation, acting independently of HER2 in TNBC cells and via a profound change in their metabolism. Our results support the use of copper-chelators as an adjuvant therapeutic strategy for TNBC., (© 2022. The Author(s).)

Background: Triple-Negative Breast Cancer (TNBC) is a subtype of breast cancer that differs from other types of breast cancers in the faster spread and worse outcome. TNBC presented limited treatment options. BET (Bromodomain and extra-terminal domain) proteins are epigenetic readers that control the expression of different oncogenic proteins, and their inhibition (BETi) is considered a promising anti-cancer strategy. Recent evidence demonstrated the involvement of BET proteins in regulation of metabolic processes., Methods: MDA-MB231 cells treated with JQ1 followed by RNA-sequencing analysis showed altered expression of lipid metabolic genes; among these, we focused on ATGL, a lipase required for efficient mobilization of triglyceride. Different in vitro approaches were performed to validate the RNA-sequencing data (qRT-PCR, immunofluorescence and flow cytometry). NMR (Nuclear Magnetic Resonance) was used to analyze the lipid reprogramming upon treatment. ATGL expression was determined by immunoblot and qRT-PCR, and the impact of ATGL function or protein knockdown, alone and in combination with BETi, was assessed by analyzing cell proliferation, mitochondrial function, and metabolic activity in TNBC and non-TNBC cells culture models., Results: TNBC cells treated with two BETi markedly increased ATGL expression and lipolytic function and decreased intracellular lipid content in a dose and time-dependent manner. The intracellular composition of fatty acids (FAs) after BETi treatment reflected a significant reduction in neutral lipids. The short-chain FA propionate entered directly into the mitochondria mimicking ATGL activity. ATGL KD (knockdown) modulated the levels of SOD1 and CPT1a decreasing ROS and helped to downregulate the expression of mitochondrial ß-oxidation genes in favor of the upregulation of glycolytic markers. The enhanced glycolysis is reflected by the increased of the mitochondrial activity (MTT assay). Finally, we found that after BETi treatment, the FoxO1 protein is upregulated and binds to the PNPLA2 promoter leading to the induction of ATGL. However, FoxO1 only partially prompted the induction of ATGL expression by BETi., Conclusions: The anti-proliferative effect achieved by BETi is helped by ATGL mediating lipolysis. This study showed that BETi altered the mitochondrial dynamics taking advantage of ATGL function to induce cell cycle arrest and cell death. Schematic representation of BETi mechanism of action on ATGL in TNBC cells. BETi induce the expression of FoxO1 and ATGL, lowering the expression of G0G2, leading to a switch in metabolic status. The induced expression of ATGL leads to increased lipolysis and a decrease in lipid droplet content and bioavailability of neutral lipid. At the same time, the mitochondria are enriched with fatty acids. This cellular status inhibits cell proliferation and increases ROS production and mitochondrial stress. Interfering for ATGL expression, the oxidative phenotypic status mildly reverted to a glycolytic status where neutral lipids are stored into lipid droplets with a consequent reduction of oxidative stress in the mitochondrial., (© 2023. The Author(s).)

Bariatric surgery (BS) is an effective intervention for severe obesity and associated comorbidities. Although several studies have addressed the clinical and metabolic effects of BS, an integrative analysis of the complex body response to surgery is still lacking. We conducted a longitudinal data study with 36 patients with severe obesity who were tested before, 6 and 12 months after restrictive BS for more than one hundred blood biomarkers, including clinical, oxidative stress and metabolic markers, peptide mediators and red blood cell membrane lipids. By using a synthetic data-driven modeling based on principal component and correlation analyses, we provided evidence that, besides the early, well-known glucose metabolism- and weight loss-associated beneficial effects of BS, a tardive, weight-independent increase of the hepatic cholesterol metabolism occurs that is associated with potentially detrimental inflammatory and metabolic effects. Canonical correlation analysis indicated that oxidative stress is the most predictive feature of the BS-induced changes of both glucose and lipids metabolism. Our results show the power of multi-level correlation analysis to uncover the network of biological pathways affected by BS. This approach highlighted potential health risks of restrictive BS that are disregarded with the current practice to use weight loss as surrogate of BS success., (© 2022. The Author(s).)

hMTH1 protects against mutation during oxidative stress. It degrades 8-oxodGTP to exclude potentially mutagenic oxidized guanine from DNA. hMTH1 expression is linked to ageing. Its downregulation in cultured cells accelerates RAS-induced senescence, and its overexpression in hMTH1-Tg mice extends lifespan. In this study, we analysed the effects of a brief (5 weeks) high-fat diet challenge (HFD) in young (2 months old) and adult (7 months old) wild-type (WT) and hMTH1-Tg mice. We report that at 2 months, hMTH1 overexpression ameliorated HFD-induced weight gain, changes in liver metabolism related to mitochondrial dysfunction and oxidative stress. It prevented DNA damage as quantified by a comet assay. At 7 months old, these HFD-induced effects were less severe and hMTH1-Tg and WT mice responded similarly. hMTH1 overexpression conferred lifelong protection against micronucleus induction, however. Since the canonical activity of hMTH1 is mutation prevention, we conclude that hMTH1 protects young mice against HFD by reducing genome instability during the early period of rapid growth and maximal gene expression. hMTH1 protection is redundant in the largely non-growing, differentiated tissues of adult mice. In hMTH1-Tg mice, expression of a less heavily mutated genome throughout life provides a plausible explanation for their extended longevity., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Introduction: Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice., Method: In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group., Results: SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale., Conclusion: Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns., (© 2022. The Author(s).)

Background: Choline kinase alpha (CHKA), an essential gene in phospholipid metabolism, is among the modulated MALAT1-targeted transcripts in advanced and metastatic prostate cancer (PCa)., Methods: We analyzed CHKA mRNA by qPCR upon MALAT1 targeting in PCa cells, which is characterized by high dose-responsiveness to the androgen receptor (AR) and its variants. Metabolome analysis of MALAT1-depleted cells was performed by quantitative High-resolution 1 H-Nuclear Magnetic Resonance (NMR) spectroscopy. In addition, CHKA genomic regions were evaluated by chromatin immunoprecipitation (ChIP) in order to assess MALAT1-dependent histone-tail modifications and AR recruitment., Results: In MALAT1-depleted cells, the decrease of CHKA gene expression was associated with reduced total choline-containing metabolites compared to controls, particularly phosphocholine (PCho). Upon MALAT1 targeting a significant increase in repressive histone modifications was observed at the CHKA intron-2, encompassing relevant AR binding sites. Combining of MALAT1 targeting with androgen treatment prevented MALAT1-dependent CHKA silencing in androgen-responsive (LNCaP) cells, while it did not in hormone-refractory cells (22RV1 cells). Moreover, AR nuclear translocation and its activation were detected by confocal microscopy analysis and ChIP upon MALAT1 targeting or androgen treatment., Conclusions: These findings support the role of MALAT1 as a CHKA activator through putative association with the liganded or unliganded AR, unveiling its targeting as a therapeutic option from a metabolic rewiring perspective.

The use of augmented reality (AR) and virtual reality (VR) for life support training is increasing. These technologies provide an immersive experience that supports learning in a safe and controlled environment. This review focuses on the use of AR and VR for emergency care training for health care providers, medical students, and nonprofessionals. In particular, we analyzed (1) serious games, nonimmersive games, both single-player and multiplayer; (2) VR tools ranging from semi-immersive to immersive virtual and mixed reality; and (3) AR applications. All the toolkits have been investigated in terms of application goals (training, assessment, or both), simulated procedures, and skills. The main goal of this work is to summarize and organize the findings of studies coming from multiple research areas in order to make them accessible to all the professionals involved in medical simulation. The analysis of the state-of-the-art technologies reveals that tools and studies related to the multiplayer experience, haptic feedback, and evaluation of user's manual skills in the foregoing health care-related environments are still limited and require further investigation. Also, there is an additional need to conduct studies aimed at assessing whether AR/VR-based systems are superior or, at the minimum, comparable to traditional training methods., (©Serena Ricci, Andrea Calandrino, Giacomo Borgonovo, Marco Chirico, Maura Casadio. Originally published in JMIR Serious Games (https://games.jmir.org), 23.03.2022.)

Background: Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer (NMIBC). The superiority of any BCG strain over another could not be demonstrated yet., Methods: Patients with NMIBCs underwent adjuvant induction ± maintenance schedule of intravesical immunotherapy with either BCG TICE or RIVM at two high-volume tertiary institutions. Only BCG-naïve patients and those treated with the same strain over the course of follow-up were included. One-to-one (1:1) propensity score matching (PSM) between the two cohorts was utilized to adjust for baseline demographic and tumor characteristics imbalances. Kaplan-Meier estimates and multivariable Cox regression models according to high-risk NMIBC prognostic factors were implemented to address survival differences between the strains. Sub-group analysis modeling of the influence of routine secondary resection (re-TUR) in the setting of the sole maintenance adjuvant schedule for the two strains was further performed., Results: 852 Ta-T1 NMIBCs ( n = 719, 84.4% on TICE; n = 133, 15.6% on RIVM) with a median of 53 (24-77) months of follow-up were reviewed. After PSM, no differences at 5-years RFS, PFS, and CSS at both Kaplan-Meier and Cox regression analyses were detected for the whole cohort. In the sub-group setting of full adherence to European/American Urology Guidelines (EAU/NCCN), BCG TICE demonstrated longer 5-years RFS compared to RIVM (68% vs. 43%, p = 0.008; HR: 0.45 95% CI 0.25-0.81)., Conclusion: When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to RIVM for RFS outcomes. However, no significant differences were detected for PFS and CSS, respectively.

Introduction: Sacrocolpopexy (SC) is the main treatment option for the repair of anterior and apical pelvic organ prolapse (POP). Indications and technical aspects are not standardized, and the question remains whether it is necessary to place a mesh on both anterior and posterior vaginal walls, particularly in cases with only minor or no posterior compartment prolapse. The present study aimed to compare the anatomical and functional outcomes of single anterior mesh only versus anterior and posterior mesh procedures in SC., Materials and Methods: Our prospectively maintained database on POP was used to identify patients who had undergone either abdominal or mini-invasive SC from January 2006 to October 2019. Patients with symptomatic or unmasked stress urinary incontinence (SUI) were not included in the study and were treated using the pubo-vaginal cystocele sling procedure. Objective outcomes included clinical evaluation of pre-existing or de novo POP by the halfway system and POP-q classifications, as well as the development of de novo SUI. Subjective outcomes were assessed using the Pelvic Floor Impact Questionnaire (PFIQ-7) with questions on bladder, bowel, and vaginal functions. Persistent or de novo constipation and overactive bladder were defined as bowel symptoms and urinary urgency/frequency/urinary incontinence after surgery., Results: Ninety-five women with symptomatic anterior and apical POP underwent SC. Forty-one patients were treated with only anterior vaginal mesh (group A), and 54 with anterior and posterior mesh (group B). There were no differences between the pre- and post-operative characteristics of the 2 groups. In group B, there were 2 blood transfusions, 1 wound dehiscence, and 3 mesh erosions/extrusion after abdominal SC (Clavien-Dindo II), and in group A, there was 1 ileal lesion after laparoscopic SC (Clavien-Dindo III). There were no differences between the 2 groups in either anatomical or functional outcomes during 3 years of follow-up., Conclusions: SC with single anterior vaginal mesh has similar results to SC with combined anterior/posterior mesh, regardless of the surgical approach. The single anterior mesh may reduce the risk of complications (mesh erosion/extrusion), and offers better subjective outcomes with improved quality of life. Anterior/posterior mesh may be justified in the presence of clinically significant posterior POP., (© 2021 S. Karger AG, Basel.)

Magnetic resonance imaging (MRI) offers excellent spatial and contrast resolution for evaluating a wide variety of pathologies, without exposing patients to ionizing radiations. Additionally, MRI offers reproducible diagnostic imaging results that are not operator-dependent, a major advantage over ultrasound. MRI is commonly used in pregnant women to evaluate, most frequently, acute abdominal and pelvic pain or placental abnormalities, as well as neurological or fetal abnormalities, infections, or neoplasms. However, to date, our knowledge about MRI safety during pregnancy, especially about the administration of gadolinium-based contrast agents, which are able to cross the placental barrier, is still limited, raising concerns about possible negative effects on both the mother and the health of the fetus. Contrast agents that are unable to cross the placenta in a way that is safe for the fetus are desirable. In recent years, some preclinical studies, carried out in rodent models, have evaluated the role of long circulating liposomal nanoparticle-based blood-pool gadolinium contrast agents that do not penetrate the placental barrier due to their size and therefore do not expose the fetus to the contrast agent during pregnancy, preserving it from any hypothetical risks. Hence, we performed a literature review focusing on contrast and non-contrast MRI use during pregnancy.

The first minute of life, the Golden Minute, has been defined as a critical window in which fundamental physiological processes occur for establishing spontaneous ventilation in a newborn. Resuscitation is more likely to succeed if it is performed properly and at the right time. In this scenario, simulation is an appropriate tool for training and evaluating the abilities of all staff working in the delivery room, as well as students. As simulations require a high degree of immersivity in order to be effective, the use of technologies like Virtual (VR) and mixed reality (MR) have garnered more interest in training. Currently, some VR and MR applications have been developed for adult life support training, but neonatal tools are still missing. To overcome this limitation, we present RiNeo MR, a prototype of a MR simulator for neonatal resuscitation training. The simulator consists of (i) a sensorized physical model of the newborn that allows monitoring chest compressions; (ii) a VR head mounted display that allows visualizing a virtual 3D model of the manikin and scenarios of the delivery and operating rooms. This enables students, and healthcare providers to be immersed in realistic hospital settings while performing life support procedures on the newborn manikin. Clinical Relevance-The newborn life support training (NLS) in facilities reduces term intrapartum-related deaths by 30%.

Massive hemorrhage remains the number one cause of preventable death in trauma worldwide. However, immediate intervention by a bystander can significantly improve the survival of the injured person. In this context, the tourniquets represent the most quick and effective devices for stopping arterial and venous blood flow. The aim of this study was to implement a system to detect the force applied by a tourniquet on a simulated limb, without blood flow. The system we designed is characterized by four low-cost force sensing resistors placed on each lower limb of a manikin, below the groin. Tests on 21 tourniquets, revealed that our system is able to detect the force applied for 60 minutes, also discriminating between turns. Hence, this system can be used to compare the performance of different types of devices, but also to assess proper tourniquet placement in trainees and trauma care providers, thus making it a versatile low-cost device.