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Among flaviviruses, Zika virus (ZIKV) is the only arbovirus officially recognized as a teratogenic agent, as a consequence of its ability to infect and cross the placental barrier causing congenital malformation in the fetus. While many studies have focused on understanding ZIKV pathogenesis during pregnancy, the viral mechanisms affecting fetal development remain largely unclear. In this study, we investigated ZIKV virulence in placental trophoblasts, using viruses with distinct lipid profiles. Firstly, we propagated a ZIKV strain belonging to the Asian lineage in either mammalian or mosquito cells, obtaining two viral stocks, which were purified and analyzed to determine their genetic and lipid composition. Successively, we assessed the infectivity of the two stocks in placental cells using both immortalized cell lines and explants. We found that the two viral stocks displayed identical consensus sequences with homogeneous quasispecies composition. However, the lipid composition of their envelope significantly varied depending on the cell of origin, with the mammalian-derived viral stock characterized by a higher content of phosphatidylcholines compared to the virions originating from mosquito cells. Notably, ZIKV stock derived from mammalian cells showed a higher infectivity in immortalized villous trophoblasts and full-term placental explants of human origin. This increased infectivity was linked to enhanced fusion efficiency during the viral uncoating phase in trophoblast cells, as demonstrated using a lipophilic probe. Collectively, our data suggest a potential role of viral lipids as determinants of ZIKV infectivity in full-term placenta, underscoring the importance of lipidomic research in virology., 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. Published by Elsevier B.V.)

Objective: This study aimed at investigating implant survival rate and marginal bone loss (MBL) around extra-short implants. The impact of the loading protocol and of the use of an intermediate abutment was also evaluated, to explore possible differences in terms of the outcome measures., Materials and Methods: Patients with single or multiple mandibular or maxillary posterior edentulism rehabilitated using extra-short 5-6 mm long implants were included. Different prosthetic protocols were used. Clinical and radiological follow-up was 5 years. The outcomes measures were implant survival and MBL., Results: The analysis included 56 implants placed in 34 adults (12 males and 22 females; mean age 60 years, SD 11). Six implants failed during a median follow-up of 5 years and 4 of them were recorded in one patient at 2-year follow-up. The 5-year implant survival was 89% overall (87% in conventional and 94% in immediate loading). At univariate analysis, during follow-up immediate loading was associated with higher MBL (mean variation 0.21 mm, 95%CI 0.01 to 0.40; p = 0.02), while intermediate abutment was associated with lower MBL (mean variation -0.23 mm, 95%CI -0.39 to -0.09; p = 0.003). Multivariable analysis confirmed that immediate loading was associated with higher MBL., Conclusion: Within its limitations, this study showed that extra-short implants under immediate loading conditions can be a reliable solution. The application of horizontal and vertical platform switching with the use of intermediate abutments seems to be able to contribute to the reduction of MBL., Competing Interests: Declarations. Ethical approval: The protocol was approved by the Hospital of Padova Ethic Board (Protocol Nr. 4376/AO/17). Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: The incidence of adverse short-term outcomes for infants who undergo complex congenital heart disease (CHD) surgery with cardiopulmonary bypass (CPB) is still high. Early identification and treatment of high-risk patients remain challenging, especially because clinical risk factors often fail to explain the different outcomes of this vulnerable population. Metabolomics offers insight into the phenotype of the patient and the complex interplay between the genetic substrate and the environmental influences at the time of sampling. For these reasons, it may be helpful to identify the mechanisms of physio-pathological disruptions experienced in neonates undergoing congenital heart surgery and to identify potential therapeutic targets., Methods: We conducted a systematic review ( PROSPERO : ID 565112) of studies investigating the association between targeted or untargeted metabolomic analysis of infants undergoing elective surgery with CPB for CHD and clinical outcomes. The PRISMA guidelines were followed. We searched MEDLINE via PubMed, EMBASE via Ovid, the Cochrane Central Register of Controlled Trials, the Cochrane Library, ClinicalTrials.gov and the World Health Organization's International Trials Registry and Platform., Results: Seven studies involving 509 children (aged 1 day to 21.3 months), all of whom underwent cardiac surgery requiring CPB, were included for qualitative analysis. We found associations between metabolomic profiles and various clinical outcomes, such as mortality, acute kidney injury (AKI), and neurological outcomes. Specific metabolites (mainly amino acids, their metabolic products and fatty acids) were identified as potential biomarkers for these outcomes, demonstrating the utility of metabolomics in predicting certain postoperative complications., Conclusion: The quality of the evidence was limited due to heterogeneity in study designs and small sample sizes, but the findings are promising and suggest that further research is warranted to confirm these associations., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO ID 565112., 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., (© 2024 Meggiolaro, Moschino, Stocchero, Giordano, Vida, Di Salvo and Baraldi.)

Background: Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal (GI) emergency in preterm neonates. Untargeted metabolomics may allow the identification of biomarkers involved in NEC pathophysiology., Methods: We conducted a prospective study including preterm infants born at < 34 gestational weeks (GWs) whose urine was longitudinally collected at birth (< 48 h, T0) and at 14 (T1) and 28 days (T2). Neonates were followed for their development of NEC, spontaneous intestinal perforation (SIP), or other GI conditions and compared to those of matched healthy controls. Urine samples were investigated by untargeted metabolomic analysis based on mass-spectrometry., Results: Thirty-five patients with NEC, 5 patients with SIP, 14 patients with other GI diseases and 113 controls were enrolled and selected for metabolomic analysis on the basis of their clinical characteristics and available samples. Considering urine samples at T0, the one-class classification approach was able to correctly classify 16/20 subjects (80%) who developed NEC, 3/3 (100%) who developed SIP and 5/7 subjects (71.4%) with other GI pathologies as not belonging to the control group. Neonates with surgical NEC had higher N-acetylaspartic acid, butyrylcarnitine and propionylcarnitine levels than did those with medical NEC. Considering the time evolution of the urinary metabolome, the NEC and control groups showed differences independently of the time point., Conclusions: The urinary metabolome is closely associated with the underlying GI disease from birth. Urinary metabolic features characterize NEC patients from healthy controls until 28 days of life. The early urinary metabolome has the potential to predict surgical NEC. Future studies are needed to validate our results., (© 2024. The Author(s).)

We analyzed and compared variations in the urinary metabolome, as well as postnatal clinical outcomes among preterm infants, based on the timing of antenatal corticosteroid (ACS) administration in response to preterm labor onset in their mothers. This was a prospective observational study held in the Neonatal Intensive Care Unit, Department of Woman's and Child's Health, Padova University Hospital (Italy). A urine sample was obtained from each patient within 24 h of birth; Mass Spectrometry-based untargeted metabolomics analysis was then conducted. We searched for any significant disparities in the metabolomic profile of preterm newborns subjected to antenatal corticosteroid (ACS) treatment at varying timings; their correlation with clinical outcomes were also evaluated. The group receiving ACS within the optimal time window (1-7 days before delivery) exhibited elevated levels of cysteine, N-acetylglutamine, propionyl carnitine and 5-hydroxyindolacetic acid, coupled with a decrease in pipecolic acid. Clinically, this group demonstrated a reduced need for invasive ventilation ( p = 0.04). In conclusion, metabolomics analysis identified several metabolites that discriminated preterm infants whose mothers received ACS within the recommended time window. Elevated levels of cysteine and 5-Hydroxyindoleacetic acid, metabolites characterized by antioxidant and anti-inflammatory properties, were observed in these infants. This metabolic profile correlated with improved respiratory outcomes, as evidenced by a reduced necessity for invasive ventilation at birth.

Fresh-cut processing is a good strategy to enhance the commercialization of peaches and nectarines, which easily deteriorate during low-temperature storage mostly due to the occurrence of chilling injury. Although several studies have been performed to improve the shelf-life of fresh-cut stone fruit, the achievement of high-quality fresh-cut peaches and nectarines still constitutes a challenge. The present study aimed to gain insights into the evolution of the postharvest quality of fresh-cut nectarines ( Prunus persica L. Batsch) Big Bang, cold-stored at two different storage temperatures (4 and 8 °C) for up to 10 days. Several aspects influencing the quality traits (sensory and postharvest quality parameters; the profile of phenolic and volatile organic compounds (VOCs)) were explored to predict the marketable life of the fresh-cut nectarines. The respiration rate was higher in samples stored at 4 °C, while the browning process was more evident in fruit stored at 8 °C. Partial Least Squares Regression performed on VOCs showed that samples stored at 4 °C and 8 °C presented a different time evolution during the experiment and the trajectories depended on the interaction between time and temperature. Moreover, Multiple Linear Regression analysis discovered that the 17 VOCs affected by the storage conditions seemed to suggest that no chilling injury was detected for nectarines Big Bang. In conclusion, this approach could also be used with other nectarine cultivars and/or different stone fruits.

The RNA-binding protein LIN28B, identified as an independent risk factor in high-risk neuroblastoma patients, is implicated in adverse treatment outcomes linked to metastasis and chemoresistance. Despite its clinical significance, the impact of LIN28B on neuroblastoma cell metabolism remains unexplored. This study employs a multi-omics approach, integrating transcriptome and metabolome data, to elucidate the global metabolic program associated with varying LIN28B expression levels over time. Our findings reveal that escalating LIN28B expression induces a significant metabolic rewiring in neuroblastoma cells. Specifically, LIN28B prompts a time-dependent increase in the release rate of metabolites related to the glutathione and aminoacyl-tRNA biosynthetic pathways, concomitant with a reduction in glucose uptake. These results underscore the pivotal role of LIN28B in governing neuroblastoma cell metabolism and suggest a potential disruption in the redox balance of LIN28B-bearing cells. This study offers valuable insights into the molecular mechanisms underlying LIN28B-associated adverse outcomes in neuroblastoma, paving the way for targeted therapeutic interventions.

Introduction: Due to its peculiar anatomy and physiology, the pericardial fluid is a biological matrix of particular interest in the forensic field. Despite this, the available literature has mainly focused on post-mortem biochemistry and forensic toxicology, while to the best of authors' knowledge post-mortem metabolomics has never been applied. Similarly, estimation of the time since death or post-mortem interval based on pericardial fluids has still rarely been attempted., Objectives: We applied a metabolomic approach based on 1 H nuclear magnetic resonance spectroscopy to ascertain the feasibility of monitoring post-mortem metabolite changes on human pericardial fluids with the aim of building a multivariate regression model for post-mortem interval estimation., Methods: Pericardial fluid samples were collected in 24 consecutive judicial autopsies, in a time frame ranging from 16 to 170 h after death. The only exclusion criterion was the quantitative and/or qualitative alteration of the sample. Two different extraction protocols were applied for low molecular weight metabolites selection, namely ultrafiltration and liquid-liquid extraction. Our metabolomic approach was based on the use of 1 H nuclear magnetic resonance and multivariate statistical data analysis., Results: The pericardial fluid samples treated with the two experimental protocols did not show significant differences in the distribution of the metabolites detected. A post-mortem interval estimation model based on 18 pericardial fluid samples was validated with an independent set of 6 samples, giving a prediction error of 33-34 h depending on the experimental protocol used. By narrowing the window to post-mortem intervals below 100 h, the prediction power of the model was significantly improved with an error of 13-15 h depending on the extraction protocol. Choline, glycine, ethanolamine, and hypoxanthine were the most relevant metabolites in the prediction model., Conclusion: The present study, although preliminary, shows that PF samples collected from a real forensic scenario represent a biofluid of interest for post-mortem metabolomics, with particular regard to the estimation of the time since death., (© 2023. The Author(s).)

Low-field (LF) benchtop NMR is a new family of instruments available on the market, promising for fast metabolic fingerprinting and targeted quantification of specific metabolites despite a lack of sensitivity and resolution with respect to high-field (HF) instruments. In the present study, we evaluated the possibility to use the urinary metabolic fingerprint generated using a benchtop LF NMR instrument for an early detection of sepsis in preterm newborns, considering a cohort of neonates previously investigated by untargeted metabolomics based on Mass Spectrometry (MS). The classifier obtained behaved similarly to that based on MS, even if different classes of metabolites were taken into account. Indeed, investigating the regions of interest mainly related to the development of sepsis by a HF NMR instrument, we discovered a set of relevant metabolites associated to sepsis. The set included metabolites that were not detected by MS, but that were reported as relevant in other published studies. Moreover, a strong correlation between LF and HF NMR spectra was observed. The high reproducibility of the NMR spectra, the interpretability of the fingerprint in terms of metabolites and the ease of use make LF benchtop NMR instruments promising in discovering early-onset sepsis., Competing Interests: The authors declare no conflict of interest. Claire Cannet, Claudia Napoli and Elena Demetrio are employees of Bruker. The paper reflects the views of the scientists, and not the company.

Purpose: The aim of this study was to review the literature on current surface modification strategies used to improve the binding efficiency of an emerging biological material, polyetheretherketone (PEEK), with bone and soft tissues., Study Selection: This review was based on articles retrieved from PubMed, Google Scholar, Web of Science, and ScienceDirect databases. The main keywords used during the search were "polyetheretherketone (PEEK)," "implant," "surface modification," "biomaterials," "bone," "osseointegration," and "soft tissue.", Results: The suitability of PEEK surface modification strategies has been critically analyzed and summarized here. Many cell and in vivo experiments in small animals have shown that the use of advanced modification technologies with appropriate surface modification strategies can effectively improve the surface inertness of PEEK, thereby improving its binding efficiency with bone and soft tissues., Conclusions: Surface modifications of PEEK have revealed new possibilities for implant treatment; however, most results are based on in vitro or short-term in vivo evaluations in small animals. To achieve a broad application of PEEK in the field of oral implantology, more in vivo experiments and long-term clinical evaluations are needed to investigate the effects of various surface modifications on the tissue integration ability of PEEK to develop an ideal implant material.

Background: The pathobiological mechanisms associated with perinatal asphyxia and hypoxic-ischemic encephalopathy are complex and poorly understood. The metabolic effects of therapeutic hypothermia have been partially explored., Methods: We conducted a single-center longitudinal study to investigate the metabolic effects of perinatal asphyxia and hypoxic-ischemic encephalopathy on the urinary metabolome of a group of 12 asphyctic infants over time compared to 22 matched healthy newborns, using untargeted metabolomics based on mass spectrometry., Findings: Over-representation pathway analysis identified the steroidogenesis pathway as being significantly disrupted, with reduced steroid levels in the first three days of life despite treatment with hypothermia. Comparison with matched healthy newborns showed that the urinary steroid content was lower in asphyctic infants before hypothermia. The lysine degradation and carnitine synthesis pathways were also significantly affected., Interpretation: Steroidogenesis is significantly disrupted in asphyctic infants compared to healthy newborns. Given how neurosteroids are involved in neuromodulation and neuroprotection, translational research is warranted on the potential role of neurosteroid-based intervention in asphyctic infants., Funding: None., Competing Interests: Declaration of interests The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The estimation of post-mortem interval (PMI) remains a major challenge in forensic science. Most of the proposed approaches lack the reliability required to meet the rigorous forensic standards., Objectives: We applied 1 H NMR metabolomics to estimate PMI on ovine vitreous humour comparing the results with the actual scientific gold standard, namely vitreous potassium concentrations., Methods: Vitreous humour samples were collected in a time frame ranging from 6 to 86 h after death. Experiments were performed by using 1 H NMR metabolomics and ion capillary analysis. Data were submitted to multivariate statistical data analysis., Results: A multivariate calibration model was built to estimate PMI based on 47 vitreous humour samples. The model was validated with an independent test set of 24 samples, obtaining a prediction error on the entire range of 6.9 h for PMI < 24 h, 7.4 h for PMI between 24 and 48 h, and 10.3 h for PMI > 48 h. Time-related modifications of the 1 H NMR vitreous metabolomic profile could predict PMI better than potassium up to 48 h after death, whilst a combination of the two is better than the single approach for higher PMI estimation., Conclusion: The present study, although in a proof-of-concept animal model, shows that vitreous metabolomics can be a powerful tool to predict PMI providing a more accurate estimation compared to the widely studied approach based on vitreous potassium concentrations., (© 2023. The Author(s).)

Purpose: To determine the biologic and biomechanical effects of two implant drilling protocols on the cortical bone around implants subjected to immediate loading., Materials and Methods: A total of 48 implants were inserted into the mandibles of six sheep following one of two drilling protocols: undersized preparation (US; n = 24) and nonundersized preparation (NUS; n = 24). Immediately after implant insertion, an abutment was placed on each implant and 36 implants were subjected to 10 sessions of dynamic vertical loads (1,500 cycles, 1 Hz) of 25 N or 50 N. Insertion torque value (ITV) was recorded at implant installation. Resonance frequency analysis (RFA) was measured at implant insertion and at each loading session. Fluorochrome was administered at day 17, and the animals were euthanized after 5 weeks. The removal torque values (RTVs) were measured, and samples underwent histomorphometric, μCT (microcomputed tomography), and fluorescence image acquisition analyses. The bone volume density (BV/TV), bone-to-implant contact (BIC), bone area fraction occupancy (BAFO), and fluorochrome stained bone surface (MS) were calculated. A linear mixed model analysis was performed, and Pearson paired correlation was calculated., Results: Five implants from the NUS group failed, with a mean ITV of 8.8 Ncm and an RFA value of 57. The mean ITVs for US group and NUS group were 80.5 (± 14) Ncm and 45.9 (± 25) Ncm, respectively ( P < .001). No differences were noted in the RFA values from the time of implant insertion until the end of the study. No differences in RTV, BV/TV, BAFO, or MS were observed between the groups. Intense new bone formation took place in the NUS group implants that were subjected to load., Conclusions: Undersized preparation of cortical bone ensured a greater BIC compared to a nonundersized preparation. Moreover, this study demonstrated that immediate loading did not interfere with the osseointegration process, but loading induced intense new bone formation in the NUS group. It is not recommended to immediately load the implants when the clinically perceived primary stability is lower than an ITV of 10 Ncm and an RFA value of 60. Int J Oral Maxillofac Implants 2023;38:607-618. doi: 10.11607/jomi.9949.

Background: The biochemical variations occurring in intrauterine growth restriction (IUGR), when a fetus is unable to achieve its genetically determined potential, are not fully understood. The aim of this study is to compare the urinary metabolomic profile between IUGR and non-IUGR very preterm infants to investigate the biochemical adaptations of neonates affected by early-onset-restricted intrauterine growth., Methods: Neonates born <32 weeks of gestation admitted to neonatal intensive care unit (NICU) were enrolled in this prospective matched case-control study. IUGR was diagnosed by an obstetric ultra-sonographer and all relevant clinical data during NICU stay were captured. For each subject, a urine sample was collected within 48 h of life and underwent untargeted metabolomic analysis using mass spectrometry ultra-performance liquid chromatography. Data were analyzed using multivariate and univariate statistical analyses., Results: Among 83 enrolled infants, 15 IUGR neonates were matched with 19 non-IUGR controls. Untargeted metabolomic revealed evident clustering of IUGR neonates versus controls showing derangements of pathways related to tryptophan and histidine metabolism and aminoacyl-tRNA and steroid hormones biosynthesis., Conclusions: Neonates with IUGR showed a distinctive urinary metabolic profile at birth. Although results are preliminary, metabolomics is proving to be a promising tool to explore biochemical pathways involved in this disease., Impact: Very preterm infants with intrauterine growth restriction (IUGR) have a distinctive urinary metabolic profile at birth. Metabolism of glucocorticoids, sexual hormones biosynthesis, tryptophan-kynurenine, and methionine-cysteine pathways seem to operate differently in this sub-group of neonates. This is the first metabolomic study investigating adaptations exclusively in extremely and very preterm infants affected by early-onset IUGR. New knowledge on metabolic derangements in IUGR may pave the ways to further, more tailored research from a perspective of personalized medicine., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objectives: The aim of this study was to evaluate whether salivary contamination during placement of implants with different surface characteristics affects osseointegration in native and in augmented bone areas., Materials and Methods: Forty eight implants with machined surface (MS) and 48 implants with moderately rough surface (RS) were tested in the calvaria of 12 sheep. At the first surgery, 64 bony critical defects were randomly created and were subsequently augmented with two materials (autogenous or bovine bone). After 5 weeks of graft healing, 8 implants were placed per sheep, in native bone and in the centre of the augmented defects. Forty eight implants were soaked with saliva before placement (contaminated group [CG]), while 48 implants were not (non-contaminated group [NCG]). Five weeks after implant placement, bone-to-implant contact (BIC) and bone material area fraction occupancy (BMAFO) were calculated histomorphometrically., Results: Saliva contamination showed a significant negative effect (p = .000) on BIC, especially in augmented areas. RS showed significant positive effect on BIC, compared to MS (p = .000), while there were no significant differences for different bone conditions (p = .103). For BMAFO, the contamination showed a significantly negative affect (p = .000), while there were no significant differences for surface characteristics (p = .322) and for bone condition (p = .538)., Conclusion: Saliva contamination during dental implant placement has a negative effect on osseointegration in augmented areas. Moderately rough surface has a possible advantage in the aspect of initial bone to implant contact. However, it seems to be advisable to avoid saliva contamination especially for implants placed in augmented bone areas., (© 2023 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Purpose: There is no clinical consensus to determine the right balance between underpreparation and marginal bone level changes. The purpose of this systematic review and meta-regression was to investigate the influence of the type of drilling preparation of the implant site in relation to the bone mineral density on the clinical success, expressed in terms of the MBL and implant failure rate., Study Selection: A thorough search was performed using the digital databases MEDLINE PubMed, EMBASE, and Cochrane Central Register of Controlled Trials by entering research lines or various combinations of free words. The main keywords used were "dental implants", "bone density", and "torque"., Results: The mean bone resorption in the conventional preparation group was -0.43 (± 0.28) mm, whereas it was -0.80 (± 0.37) mm in the underprepared group. For the D1/D2/D3 bone group, the slope was significantly different from zero and linearity; the D4 bone group slope was not significantly different from zero and was almost parallel, although it was significantly different from linearity. The box and whiskers plot shows that the MBL in underprepared sites tended to be significantly higher with a higher variation than that in conventionally prepared sites., Conclusions: Within its limits, our meta-regression analysis showed that MBL is influenced by the type of drilling preparation and bone mineral density. In particular, a lower MBL was observed in the D1 bone with conventional preparation than with underpreparation. Moreover, a greater implant-to-osteotomy site mismatch was positively associated with greater MBLs in the bone densities of D1/D2/D3.

Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal emergency in preterm neonates. Research on early predictive biomarkers is fundamental. This is a systematic review of studies applying untargeted metabolomics and gut microbiota analysis to evaluate the differences between neonates affected by NEC (Bell’s stage II or III), and/or by spontaneous intestinal perforation (SIP) versus healthy controls. Five studies applying metabolomics (43 cases, 95 preterm controls) and 20 applying gut microbiota analysis (254 cases, 651 preterm controls, 22 term controls) were selected. Metabolomic studies utilized NMR spectroscopy or mass spectrometry. An early urinary alanine/histidine ratio >4 showed good sensitivity and predictive value for NEC in one study. Samples collected in proximity to NEC diagnosis demonstrated variable pathways potentially related to NEC. In studies applying untargeted gut microbiota analysis, the sequencing of the V3−V4 or V3 to V5 regions of the 16S rRNA was the most used technique. At phylum level, NEC specimens were characterized by increased relative abundance of Proteobacteria compared to controls. At genus level, pre-NEC samples were characterized by a lack or decreased abundance of Bifidobacterium. Finally, at the species level Bacteroides dorei, Clostridium perfringens and perfringens-like strains dominated early NEC specimens, whereas Clostridium butyricum, neonatale and Propionibacterium acnei those at disease diagnosis. Six studies found a lower Shannon diversity index in cases than controls. A clear separation of cases from controls emerged based on UniFrac metrics in five out of seven studies. Importantly, no studies compared NEC versus SIP. Untargeted metabolomics and gut microbiota analysis are interrelated strategies to investigate NEC pathophysiology and identify potential biomarkers. Expression of quantitative measurements, data sharing via biorepositories and validation studies are fundamental to guarantee consistent comparison of results.

Perinatal asphyxia (PA) still occurs in about three to five per 1,000 deliveries in developed countries; 20% of these infants show hypoxic-ischemic encephalopathy (HIE) on brain magnetic resonance imaging (MRI). The aim of our study was to apply metabolomic analysis to newborns undergoing therapeutic hypothermia (TH) after PA to identify a distinct metabotype associated with the development of HIE on brain MRI. We enrolled 53 infants born at >35 weeks of gestation with PA: 21 of them showed HIE on brain MRI (the "HIE" group), and 32 did not (the "no HIE" group). Urine samples were collected at 24, 48 and 72 hours of TH. Metabolomic data were acquired using high-resolution mass spectrometry and analyzed with univariate and multivariate methods. Considering the first urines collected during TH, untargeted analysis found 111 relevant predictors capable of discriminating between the two groups. Of 35 metabolites showing independent discriminatory power, four have been well characterized: L-alanine, Creatine, L-3-methylhistidine, and L-lysine. The first three relate to cellular energy metabolism; their involvement suggests a multimodal derangement of cellular energy metabolism during PA/HIE. In addition, seven other metabolites with a lower annotation level (proline betaine, L-prolyl-L-phenylalanine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E, 2,6 dimethylheptanoyl carnitine, Octanoylglucuronide, 19-hydroxyandrost-4-ene-3,17-dione) showed biological consistency with the clinical picture of PA. Moreover, 4 annotated metabolites (L-lysine, L-3-methylhistidine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E) retained a significant difference between the "HIE" and "no HIE" groups during all the TH treatment. Our analysis identified a distinct urinary metabotype associated with pathological findings on MRI, and discovered 2 putative markers (L-lysine, L-3-methylhistidine) which may be useful for identifying neonates at risk of developing HIE after PA., Competing Interests: The authors have declared that no competing interests exist.

Electronic nose (e-nose), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and image analysis (IA) were used to discriminate the ripening stage (half-red or red) of strawberries (cv Sabrosa, commercially named Candonga), harvested at three different times (H1, H2 and H3). Principal component analysis (PCA) performed on the e-nose, ATR-FTIR and IA data allowed us to clearly discriminate samples based on the ripening stage, as in the score space they clustered in distinct regions of the plot. Moreover, a correlation analysis between the e-nose sensor and 57 volatile organic compounds (VOCs), which were overall detected in all the investigated fruit samples by headspace solid-phase microextraction coupled to gas chromatography-mass spectrometry (HS-SPME/GC-MS), allowed us to distinguish half-red and red strawberries, as the e-nose sensors gave distinct responses to samples with different flavours. Three suitable broad bands were individuated by PCA in the ATR-FTIR spectra to discriminate half-red and red samples: the band centred at 3295 cm -1 is generated by compounds that decline, whereas those at 1717 cm -1 and at 1026 cm -1 stem from compounds that accumulate during ripening. Among the chemical parameters (titratable acidity, total phenols, antioxidant activity and total soluble solid) assayed in this study, only titratable acidity was somehow correlated to ATR-FTIR and IA patterns. Thus, ATR-FTIR spectroscopy and IA might be exploited to rapidly assess titratable acidity, which is an objective indicator of the ripening stage.

The aim of the present retrospective study was to assess marginal bone changes around implants restored with different prosthetic emergence profile angles. Patients were treated with implants supporting fixed dentures and were followed for 3 years. Marginal bone levels (MBL) measured at the prosthesis installation (t0) and at the 3-year follow-up visit (t1) were considered. The MBL change from t0 to t1 was investigated. Two groups were considered: Group 1 for restorations with an angle between implant axis and prosthetic emergence profile >30°, and Group 2 for those with an angle ≤30°, respectively. Moreover, peri-implant soft tissue parameters, such as the modified bleeding index (MBI) and plaque index (PI) were assessed. Seventy-four patients were included in the analysis and a total of 312 implants were examined. The mean EA in groups 1 and 2 was 45 ± 4 and 22 ± 7 degrees, respectively. The mean marginal bone level change (MBL change) of 0.06 ± 0.09 mm and 0.06 ± 0.10 mm were, respectively, in groups 1 and 2. The difference in the MBL change between the two groups was not statistically significant (p = 0.969). The MBL change does not seem to be influenced by the emergence angle for implants with a stable internal conical connection and platform-switching of the abutment diameter.

The witnesses of the millenary history of Campania felix in southern Italy highlighted that several fruit and vegetables cultivated in such territory could potentially be a treasure trove of important health elements. Our work evaluated the content of β-carotene, ascorbic acid, and total phenolics and the antioxidant activity of ten typical varieties of apricots cultivated in the Vesuvius area in the Campania region. The total polyphenols varied between 10.24 and 34.04 mg/100 g of a fresh sample. The amount of ascorbic acid also varied greatly, ranging from 2.65 to 10.65 mg/100 g of a fresh product. B-Carotene reached values up to 0.522 mg/100 g of the fresh sample. The correlation analysis performed, accounting for these parameters, showed that the antioxidant activity, calculated by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay) and azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) tests, was influenced mainly by the content of total polyphenols, with ρ = -0.762 and ρ = 0.875 when we considered DPPH and ABTS tests, respectively, slightly less by the content of ascorbic acid, and not by β-carotene. The dendrogram clustered eight varieties into two main groups; on the other hand, two varieties ("Vitillo" and "Preveta bella") seemed hierarchically distant. The gas chromatography-mass spectrometry (GC-MS) analysis of volatile organic compounds (VOCs), herein performed for the first time, demonstrated the influence of the varieties on the VOC profiles, both from a qualitative and semiquantitative perspective, discriminating the varieties in different clusters, each of which was characterized by specific notes. α-Terpinolene was the only terpene identified by GC-MS that appeared to affect the antioxidant activity., 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 © 2022 Fratianni, Cozzolino, d'Acierno, Ombra, Spigno, Riccardi, Malorni, Stocchero and Nazzaro.)

Purpose: Radiation-induced esophageal cancer (RIEC) is a rare but severe late consequence of radiotherapy. The literature regarding this topic is predominately limited in describing the risk of this disease. Tumor behavior, treatment strategies, and prognosis of this cancer remain poorly defined., Patients and Methods: We collected data of patients who were referred to our unit between 2000 and 2020 for RIEC. After tumor board discussion, upfront surgery or neoadjuvant therapy and surgery were indicated as the main treatment. Preoperative characteristics, long-term and short-term postoperative outcomes of RIEC patients were compared with a 1:1 clustering-matched cohort of patients affected by primary esophageal cancer (PEC)., Results: At pre-matching, 54 RIEC and 936 PEC patients were enrolled. The median time between primary irradiation and diagnosis of RIEC was 13.5 years, and the median primary radiation dose was 60 Gy. Compared to the unmatched cohort of PECs, RIEC patients were more frequently female (p = 0.0007), had earlier detection of disease (p = 0.03) and presented more frequently with upper esophageal cancers (p < 0.0001). Neoadjuvant treatment was used less frequently in RIEC patients (p < 0.0001). After matching, the 51 RIEC and 50 PEC patients showed comparable results in terms of exposure to neoadjuvant treatment, surgical radicality and survival outcomes. RIEC patients had more severe postoperative complications (p = 0.04) and a higher proportion of pulmonary complications (p = 0.04)., Conclusions: Curative treatments are feasible for RIEC. Neoadjuvant chemotherapy or chemoradiation can be used in this subgroup, treatment response and long-term outcomes are comparable to those of PEC. The risk of postoperative complications is probably related to the detrimental effect of primary irradiation on lung function., (Copyright © 2022. Published by Elsevier Ltd.)

Implant therapy for tooth loss in the molar area is challenging due to the anatomical limitations, requiring bone augmentation procedures that are associated with high surgical complexity and long postsurgical recovery. Recently, many studies have demonstrated the usefulness of short implants. However, few studies have been performed in Japanese patients to evaluate peri-implant bone changes, changes in peri-implant epithelial tissue, and patient satisfaction. The present study included 16 patients (5 men, 11 women; mean age: 60 years) who received 26 short (6-mm) implants. Changes in peri-implant bone and epithelial tissue were measured radiographically at superstructure loading and after 2 years. Peri-implant pocket probing depth was measured at the epithelial tissue and compared at both time points. Patient satisfaction was graded using the Oral Health Impact Profile (OHIP-14) before treatment and at follow-up. The mean mesial and distal bone levels were -0.05 mm and 0.37 mm at loading, respectively, and were 0.33 mm and 0.53 mm after 2 years, respectively. Significant peri-implant bone formation for mesial and distal bone levels at both time points were determined by Wilcoxon signed-rank test. Mean probing depth increased slightly, from 3.03 mm at loading to 3.33 mm after 2 years, but no significant difference was found. The OHIP-14 found that patient satisfaction levels increased after 2 years. Using 6-mm short implants in sites with insufficient bone levels can be a highly beneficial treatment option for patients, as it avoids the need for bone augmentation. However, more long-term and detailed studies on the clinical outcomes for these implants are required.