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This paper reports a theory for the dielectric relaxation of dimeric mesogenic molecules in a nematic liquid crystal phase. Liquid crystal dimers consist of two mesogenic groups linked by a flexible chain. Recent experimental studies [D. A. Dunmur, G. R. Luckhurst, M. R. de la Fuente, S. Diez, and M. A. Perez Jubindo, J. Chem. Phys. 115, 8681 (2001)] of the dielectric properties of polar liquid crystal dimers have found unexpected results for both the static (low frequency) and variable frequency dielectric response of these materials. The theory developed in this paper provides a quantitative model with which to understand the observed experimental results. The mean-square dipole moments of α,ω-bis[(4-cyanobiphenyl-4′-yl]alkanes in a nematic phase have been calculated using both the rotational isomeric state model and a full torsional potential for the carbon-carbon bonds of the flexible chain. The orienting effect of the nematic phase is taken into account by a parametrized potential of mean torque acting on the mesogenic groups and the segments in the flexible chain. Results of calculations using the full torsional potential are in excellent agreement with experimental results for comparable systems. The probability density peq(βA,βB) for the orientation of the mesogenic groups (A,B) along the nematic director is also calculated. The resultant potential of mean torque is a surface characterized by four deep energy wells or sites equivalent to alignment of the terminal groups A and B approximately parallel and antiparallel to the director; of course, the reversal of the director leads to equivalent sites. This potential energy surface provides the basis for a kinetic model of dielectric relaxation in nematic dimers. Solution of the Fokker-Planck equation corresponding to this four-site model gives the time dependence of the site populations, and hence the time-correlation functions for the total dipole moment along the director. In this model the end-over-end rotation of the molecule, corresponding to simulataneous reversal of both mesogenic groups, is excluded because the activation energy is too large. Results are presented for a number of cases, in which a dipole is located on one or both of the mesogenic groups, and additionally where the groups differ in size. For the latter, under particular conditions, the correlation function exhibits a biexponential decay, which corresponds to two low frequency absorptions in the dielectric spectrum. This is exactly what has been observed for nonsymmetric nematic dimers having different groups terminating a flexible chain. Experimental results over a range of temperature for the nonsymmetric dimer α-[(4-cyanobiphenyl)-4′-yloxy]-ω-(4-decylanilinebenzylidene-4′-oxy)nonane can be fitted precisely to the theory, which provides new insight into the orientational and conformational dynamics of molecules in ordered liquid crystalline phases. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

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.)

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.)

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.

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).)

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.