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Introduction: The reduction, stabilization, and maintenance of alignment are the main goals in the surgical treatment of unstable hangman's fractures. The choice of the surgical strategy remains poorly standardized; anterior and/or posterior fusion could be performed; and none of the available clinical studies in the literature have shown significant differences in outcomes or complication rates. Vertebral anatomy, age, comorbidities, patient factors, and surgical experience may guide the treatment choice., Methods: We present a case of a polytraumatized young woman with an unstable hangman's fracture type II, according to Levine-Edwards classification. We treated the fracture by using a plate with four holes to fix C2-C3 without discectomy and body fusion., Results: We performed a small incision, such as those used for the fixation of odontoid screws, where the working angle allowed us to easily and quickly position the plate by using a minimally invasive approach., Conclusion: The stabilization alone, without discectomy and body fusion with the cage, in the same way favored the natural healing of the bone fracture. In our opinion, in some select cases, fixation of C2-C3 alone through a minimally invasive approach allows for bone healing with fewer risks and an easier surgery., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The surgical technique and the intraoperative technology that support spinal pedicle screw placement have consistently evolved over the past decades to decrease the misplacement rate of pedicle screws. We retrospectively evaluated our case series by analyzing the period 2016-2020. Patients undergoing pedicle screw fixation for cervical, thoracic, or lumbar spine degenerative diseases have been included. Surgery was carried out with the aid of intraoperative 3D C-arm fluoroscopy to assess and optimize screw placement and/or correct possible mispositioning. Each patient underwent a postoperative CT scan. Our aim was to evaluate the safety and accuracy of pedicle screw placement and estimate the variation in mispositioning rates. We carried out 329 surgical procedures, as follows: 70 cervical, 78 thoracic spine, and 181 lumbar spine surgeries. An excellent overall pedicle screw positioning was obtained, with slight differences between the cervical (98.6%), thoracic (100%), and lumbar (98.9%) tracts. Accordingly, only three patients required a revision surgery owing to mispositioning (0.91%). In particular, intraoperative C-arm fluoroscopy significatively improved the accuracy of thoracic screw positioning, as shown by postoperative CT scans. Our experience proves the crucial role of intraoperative C-arm fluoroscopy in pursuing optimal technical results and improving patient outcomes at follow-up., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The EAT-Lancet Commission devised a sustainable reference diet with the aim of reducing the incidence of non-communicable diseases and mortality globally while improving food system sustainability. The extent to which the reference diet supports cognitive function across the life course, however, has not yet been evaluated. This Review assesses the evidence for diet supporting cognitive function from childhood into old age. A comprehensive but non-exhaustive literature search was done, synthesising studies that investigated the effect of whole foods on cognition in healthy, community-dwelling human participants. We found that the current evidence base is weak with mixed conclusions and multiple methodological caveats, which precludes strong conclusions pertaining to the suitability of dietary recommendations for each food group per age group. Long-term intervention and prospective cohort studies are needed to reduce this knowledge deficit. Revising dietary recommendations with the aim of maintaining an adequate nutrient intake to sustain healthy cognitive function across the life course could be worthwhile. This Review outlines recommendations for future work to help improve the current knowledge deficit regarding dietary intake and cognitive function across the life course and its implications for dietary guidelines such as the EAT-Lancet Commission., Competing Interests: Declaration of interests AC received consulting fees from UK Climate Change Risk Assessment. ERG received research grants from Enterprise Ireland and dairy companies as part of Food for Health Ireland Technology Centre (TC20180025) and from Aconsi. ERG is an academic supervisor for the Marie Curie Career-FIT programme; no funds were received from the commercial partner Marigot. The programme of work was developed in collaboration with the commercial partner Marigot. ERG received honoraria from Nestlé Research Centre to speak at a conference. She is a member and trustee of the Nutrition Society, Deputy Director of University College Dublin Institute of Food and Health, and a member of the governing authority the European Food Information Council. JMV is a former employee of Danone Nutricia. GLF is an employee of DSM. LG is a former employee of International Life Sciences Institute (ILSI Europe). The European branch of the International Life Sciences Institute paid the processing charges for this manuscript. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The gut and brain link via various metabolic and signalling pathways, each with the potential to influence mental, brain and cognitive health. Over the past decade, the involvement of the gut microbiota in gut-brain communication has become the focus of increased scientific interest, establishing the microbiota-gut-brain axis as a field of research. There is a growing number of association studies exploring the gut microbiota's possible role in memory, learning, anxiety, stress, neurodevelopmental and neurodegenerative disorders. Consequently, attention is now turning to how the microbiota can become the target of nutritional and therapeutic strategies for improved brain health and well-being. However, while such strategies that target the gut microbiota to influence brain health and function are currently under development with varying levels of success, still very little is yet known about the triggers and mechanisms underlying the gut microbiota's apparent influence on cognitive or brain function and most evidence comes from pre-clinical studies rather than well controlled clinical trials/investigations. Filling the knowledge gaps requires establishing a standardised methodology for human studies, including strong guidance for specific focus areas of the microbiota-gut-brain axis, the need for more extensive biological sample analyses, and identification of relevant biomarkers. Other urgent requirements are new advanced models for in vitro and in vivo studies of relevant mechanisms, and a greater focus on omics technologies with supporting bioinformatics resources (training, tools) to efficiently translate study findings, as well as the identification of relevant targets in study populations. The key to building a validated evidence base rely on increasing knowledge sharing and multi-disciplinary collaborations, along with continued public-private funding support. This will allow microbiota-gut-brain axis research to move to its next phase so we can identify realistic opportunities to modulate the microbiota for better brain health., (© 2022. The Author(s).)

The global increases in life expectancy and population have resulted in a growing ageing population and with it a growing number of people living with age-related neurodegenerative conditions and dementia, shifting focus towards methods of prevention, with lifestyle approaches such as nutrition representing a promising avenue for further development. This overview summarises the main themes discussed during the 3 rd Symposium on "Nutrition for the Ageing Brain: Moving Towards Clinical Applications" held in Madrid in August 2018, enlarged with the current state of knowledge on how nutrition influences healthy ageing and gives recommendations regarding how the critical field of nutrition and neurodegeneration research should move forward into the future. Specific nutrients are discussed as well as the impact of multi-nutrient and whole diet approaches, showing particular promise to combatting the growing burden of age-related cognitive decline. The emergence of new avenues for exploring the role of diet in healthy ageing, such as the impact of the gut microbiome and development of new techniques (imaging measures of brain metabolism, metabolomics, biomarkers) are enabling researchers to approach finding answers to these questions. But the translation of these findings into clinical and public health contexts remains an obstacle due to significant shortcomings in nutrition research or pressure on the scientific community to communicate recommendations to the general public in a convincing and accessible way. Some promising programs exist but further investigation to improve our understanding of the mechanisms by which nutrition can improve brain health across the human lifespan is still required., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

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It has become increasingly evident in recent years that the gut microbiome and the brain communicate in a bidirectional manner, with each possibly affecting the other's functions. Substantial research has aimed to understand the mechanisms of this interaction and to outline strategies for preventing or treating nervous system-related disturbances. This review explores the evidence demonstrating how the gut microbiome may affect brain function in adults, thereby having an impact on stress, anxiety, depression, and cognition. In vitro, in vivo, and human studies reporting an association between a change in the gut microbiome and functional changes in the brain are highlighted, as are studies outlining the mechanisms by which the brain affects the microbiome and the gastrointestinal tract. Possible modes of action to explain how the gut microbiome and the brain functionally affect each other are proposed. Supplemental probiotics to combat brain-related dysfunction offer a promising approach, provided future research elucidates their mode of action and possible side effects. Further studies are warranted to establish how pre- and probiotic interventions may help to balance brain function in healthy and diseased individuals.

The gastrointestinal tract (GIT) represents the largest interface between the human organism and the external environment. In the lumen and upper part of the mucus layer, this organ hosts an enormous number of microorganisms whose composition affects the functions of the epithelial barrier and the gut immune system. Consequentially, the microorganisms in the GIT influence the health status of the organism. Probiotics are living microorganisms which, in specific conditions, confer a health benefit to the host. Among others, probiotics have immunomodulatory properties that usually act directly by (a) increasing the activity of macrophages or natural killer cells, (b) modulating the secretion of immunoglobulins or cytokines, or indirectly by (c) enhancing the gut epithelial barrier, (d) altering the mucus secretion, and (e) competitive exclusion of other (pathogenic) bacteria. This review focuses on specific bacteria strains with indirect immunomodulatory properties. Particularly, we describe here the mechanisms through which specific probiotics enhance the gut epithelial barrier and modulate mucus production. Moreover, we describe the antimicrobial properties of specific bacteria strains. Recent data suggest that multiple pathologies are associated with an unbalanced gut microflora (dysbiosis). Although the cause-effect relationship between pathology and gut microflora is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health.

Toll-like receptors (TLRs) are powerful molecular regulators by which the immune system may "sense" the environment and protect the host from pathogens or endogenous threats. In mammalian cells, several TLRs were identified with a tissue and cell type-specific distribution. Understanding the functions of specific TLRs is crucial for the development and discovery of compounds useful to maintaining or re-establishing homeostasis in the gastrointestinal tract (GIT). Due to their relevance in regulating the inflammatory response in the GIT, we will focus here on TLR2, TLR4, and TLR5. In particular, we describe (a) the molecular pathways activated by the stimulation of these receptors with their known bacterial ligands; (b) the non-bacterial ligands known to interact directly with TLR2 and TLR4 and their soluble forms. The scope of this minireview is to highlight the importance of bacterial and non-bacterial compounds in affecting the gut immune functions via the activation of the TLRs., Competing Interests: All authors are employees of DSM Nutritional Products.

A dietary prebiotic is defined as 'a substrate that is selectively utilized by host microorganisms conferring a health benefit'. Although this definition evolved concomitantly with the knowledge and technological developments that accrued in the last twenty years, what qualifies as prebiotic continues to be a matter of debate. In this statement, we report the outcome of a workshop where academic experts working in the field of prebiotic research met with scientists from industry. The workshop covered three main topics: (i) evolution of the prebiotic concept/definition; (ii) the gut modeling in vitro technology PolyFermS to study prebiotic effects; and (iii) the potential novel microbiome-modulating effects associated with vitamins. The future of prebiotic research is very promising. Indeed, the technological developments observed in recent years provide scientists with powerful tools to investigate the complex ecosystem of gut microbiota. Combining multiple in vitro approaches with in vivo studies is key to understanding the mechanisms of action of prebiotics consumption and their potential beneficial effects on the host., Competing Interests: G.L.F., M.H.M., P.W. and R.E.S. are employees of DSM Nutritional Products. H.J.M.H. received a research grant from DSM Nutritional Products. All remaining authors declare no conflict of interest.

Background: Aging is a highly complex biological process driven by multiple factors. Its progression can partially be influenced by nutritional interventions. Vitamin E is a lipid-soluble anti-oxidant that is investigated as nutritional supplement for its ability to prevent or delay the onset of specific aging pathologies, including neurodegenerative disorders., Purpose: We aimed here to investigate the effect of vitamin E during aging progression in a well characterized mouse model for premature aging., Method: Xpg-/- animals received diets with low (~2.5 mg/kg feed), medium (75 mg/kg feed) or high (375 mg/kg feed) vitamin E concentration and their phenotype was monitored during aging progression. Vitamin E content was analyzed in the feed, for stability reasons, and in mouse plasma, brain, and liver, for effectiveness of the treatment. Subsequent age-related changes were monitored for improvement by increased vitamin E or worsening by depletion in both liver and nervous system, organs sensitive to oxidative stress., Results: Mice supplemented with high levels of vitamin E showed a delayed onset of age-related body weight decline and appearance of tremors when compared to mice with a low dietary vitamin E intake. DNA damage resulting in liver abnormalities such as changes in polyploidy, was considerably prevented by elevated amounts of vitamin E. Additionally, immunohistochemical analyses revealed that high intake of vitamin E, when compared with low and medium levels of vitamin E in the diet, reduces the number of p53-positive cells throughout the brain, indicative of a lower number of cells dying due to DNA damage accumulated over time., Conclusions: Our data underline a neuroprotective role of vitamin E in the premature aging animal model used in this study, likely via a reduction of oxidative stress, and implies the importance of improved nutrition to sustain health., Competing Interests: G.L.F, S.E., E.C., C.G., N.S., P.W., and M.H.M. are employees of DSM Nutritional Products. All other authors declare no conflict of interests.

Vitamin E is an important antioxidant that protects cells from oxidative stress-induced damage, which is an important contributor to the progression of ageing. Ageing can be studied in vitro using primary cells reaching a state of irreversible growth arrest called senescence after a limited number of cellular divisions. Generally, the most utilized biomarker of senescence is represented by the expression of the senescence associated β-galactosidase (SA-β-gal). We aimed here to study the possible effects of vitamin E supplementation in two different human primary cell types (HUVECs and fibroblasts) during the progression of cellular senescence. Utilizing an unbiased automated system, based on the detection of the SA-β-gal, we quantified cellular senescence in vitro and showed that vitamin E supplementation reduced the numbers of senescent cells during progression of ageing. Acute vitamin E supplementation did not affect cellular proliferation, whereas it was decreased after chronic treatment. Mechanistically, we show that vitamin E supplementation acts through downregulation of the expression of the cycline dependent kinase inhibitor P21. The data obtained from this study support the antiageing properties of vitamin E and identify possible mechanisms of action that warrant further investigation.

Deficiencies in fragile X mental retardation protein (FMRP) are the most common cause of inherited intellectual disability, fragile X syndrome (FXS), with symptoms manifesting during infancy and early childhood. Using a mouse model for FXS, we found that Fmrp regulates the positioning of neurons in the cortical plate during embryonic development, affecting their multipolar-to-bipolar transition (MBT). We identified N-cadherin, which is crucial for MBT, as an Fmrp-regulated target in embryonic brain. Furthermore, spontaneous network activity and high-resolution brain imaging revealed defects in the establishment of neuronal networks at very early developmental stages, further confirmed by an unbalanced excitatory and inhibitory network. Finally, reintroduction of Fmrp or N-cadherin in the embryo normalized early postnatal neuron activity. Our findings highlight the critical role of Fmrp in the developing cerebral cortex and might explain some of the clinical features observed in patients with FXS, such as alterations in synaptic communication and neuronal network connectivity.

Vitamin E is an important antioxidant that primarily protects cells from damage associated with oxidative stress caused by free radicals. The brain is highly susceptible to oxidative stress, which increases during ageing and is considered a major contributor to neurodegeneration. High plasma vitamin E levels were repeatedly associated with better cognitive performance. Due to its antioxidant properties, the ability of vitamin E to prevent or delay cognitive decline has been tested in clinical trials in both ageing population and Alzheimer's disease (AD) patients. The difficulty in performing precise and uniform human studies is mostly responsible for the inconsistent outcomes reported in the literature. Therefore, the benefit of vitamin E as a treatment for neurodegenerative disorders is still under debate. In this review, we focus on those studies that mostly have contributed to clarifying the exclusive function of vitamin E in relation to brain ageing and AD.

The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS while a patient-case with FXS showed an unusual decrease of tumour brain invasiveness. However, a role for FMRP in regulating cancer biology, if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate with prognostic indicators of aggressive breast cancer, lung metastases probability and triple negative breast cancer (TNBC). We establish that FMRP overexpression in murine breast primary tumours enhances lung metastasis while its reduction has the opposite effect regulating cell spreading and invasion. FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression., (© 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.)

Brain metastases (BM) are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases are associated with a poor prognosis and a poor performance status. Metastasis development involves the migration of a cancer cell from the bulk tumor into the surrounding tissue, extravasation from the blood into tissue elsewhere in the body, and formation of a secondary tumor. In the recent past, important results have been obtained in the management of patients affected by BM, using surgery, radiation therapy, or both. Conventional chemotherapies have generally produced disappointing results, possibly due to their limited ability to penetrate the blood-brain barrier. The advent of new technologies has led to the discovery of novel molecules and pathways that have better depicted the metastatic process. Targeted therapies such as bevacizumab, erlotinib, gefitinib, sunitinib and sorafenib, are all licensed and have demonstrated improved survival in patients with metastatic disease. In this review, we will report current data on targeted therapies. A brief review about brain metastatic process will be also presented.

The complex of the yeast Lsm1p-7p proteins with Pat1p is an important mRNA decay factor that is involved in translational shutdown of deadenylated mRNAs and thus prepares these mRNAs for degradation. While the Lsm proteins are highly conserved, there is no unique mammalian homolog of Pat1p. To identify proteins that interact with human LSm1, we developed a novel immunoprecipitation technique that yields virtually pure immunocomplexes. Mass-spec analysis therefore identifies mostly true positives, avoiding tedious functional screening. The method unambiguously identified the Pat1p homolog in HeLa cells, Pat1b. When targeted to a reporter mRNA, Pat1b represses gene expression by inducing deadenylation of the mRNAs. This demonstrates that Pat1b, unlike yPat1p, acts as an mRNA-specific deadenylation factor, highlighting the emerging importance of deadenylation in the mRNA regulation of higher eukaryotes.