Nerve Repair Using Decellularized Nerve Grafts in Rat Models. A Review of the Literature

Peripheral nerve regeneration after severe traumatic nerve injury is a relevant clinical problem. Several different strategies have been investigated to solve the problem of bridging the nerve gap. Among these, the use of decellularized nerve grafts has been proposed as an alternative to auto/isografts, which represent the current gold standard in the treatment of severe nerve injury. This study reports the results of a systematic review of the literature published between January 2007 and October 2017. The aim was to quantitatively analyze the effectiveness of decellularized nerve grafts in rat experimental models. The review included 33 studies in which eight different decellularization protocols were described. The decellularized nerve grafts were reported to be immunologically safe and able to support both functional and morphological regeneration after nerve injury. Chemical protocols were found to be superior to physical protocols. However, further research is needed to optimize preparation protocols, including recellularization, improve their effectiveness, and substitute the current gold standard, especially in the repair of long nerve defects

Reactive Deep Eutectic Solvents (RDESs): A New Tool for Phospholipase D-Catalyzed Preparation of Phospholipids

The use of Reactive Deep Eutectic Solvents (RDESs) in the preparation of polar head modified phospholipids (PLs) with phospholipase D (PLD)-catalyzed biotransformations has been investigated. Natural phosphatidylcholine (PC) has been submitted to PLD-catalyzed transphosphatidylations using a new reaction medium composed by a mixture of RDES/buffer. Instead of exploiting deep eutectic solvents conventionally, just as the reaction media, these solvents have been designed here in order to contribute actively to the synthetic processes by participating as reagents. RDESs were prepared using choline chloride or trimethyl glycine as hydrogen-bond acceptors and glycerol or ethylene glycol, as hydrogen-bond donors as well as nucleophiles for choline substitution. Specifically designed RDES/buffer reaction media allowed the obtainment of PLs with optimized yields in the perspective of a sustainable process implementation

Towards a Complete Exploitation of Brewers’ Spent Grain from a Circular Economy Perspective

In the present work, brewers’ spent grain (BSG), which represents the major by-product of the brewing industry, was recovered from a regional brewery and fractionated in order to obtain a complete valorization. In particular, the whole process was divided in two main parts. A first pretreatment with hot water in an autoclave allowed the separation of a solution containing the soluble proteins and sugars, which accounted for 25% of the total starting biomass. This first step allowed the preparation of a medium that was successfully employed as a valuable growing medium for different microbial fermentations, leading to valuable fungal biomass as well as triglycerides with a high content of linear or branched fatty acids, depending on the microorganism used. The solid water-insoluble residue was then submitted to a lignocellulose deep eutectic solvent-mediated fractionation, which allowed the recovery of two important main fractions: BSG cellulose and BSG lignin. The latter product was tested as potential precursor for the development of cement water reducers with encouraging results. This combination of treatments of the waste biomass appeared to be a promising sustainable strategy for the development of the full exploitation of BSG from a circular economy perspective

Microbial Fermentation of the Water-Soluble Fraction of Brewers’ Spent Grain for the Production of High-Value Fatty Acids

Brewers’ spent grain (BSG) constitutes the primary by-product of the brewing industry. The valorization of BSG from a circular economy perspective is of high industrial interest. The objective of this study was the exploitation of BSG for the microbial production of branched-chain fatty acids (BCFAs) and polyunsaturated fatty acids (PUFAs), representing two different classes of high-value fatty acids (FAs). In the present study, this waste material underwent treatment with hot water in an autoclave and the resultant extract was utilized for the preparation of a novel liquid medium (BSG medium) to be employed for microbial fermentation. Screening and subsequent scaling-up experiments confirmed the suitability of the BSG medium to support the microbial production of various high-value FAs. In particular, Streptomyces jeddahensis and Conidiobolus heterosporus could be employed for BCFAs production, Pythium ultimum and Mortierella alpina could be used to provide cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and arachidonic acid (ARA), whereas Mucor circinelloides, when grown in a BSG medium, was able to accumulate γ-linolenic acid (GLA)

Clinical, Cognitive and Behavioural Assessment in Children with Cerebellar Disorder

Cerebellar disorders are characterised clinically by specific signs and symptoms, often associated with neurodevelopmental disorder. While the clinical signs of cerebellar disorders are clearly recognisable in adults and have a precise anatomo-functional correlation, in children the semiotics are less clear and vary with age because of the particular nature of the cerebellum’s maturation. Unlike other structures of the central nervous system, this begins at a later stage of foetal development and extends over a longer period of time, even after birth. As a result, the typical signs of cerebellar dysfunction will only become evident when the cerebellar functions have become integrated into the complex circuits of the central nervous system. This means that poor motor coordination in the very early years of life may not necessarily correlate with cerebellar dysfunction, and this may also be encountered in healthy children. The cerebellum’s role in cognitive and emotional functions relies on its structure and the complexity of its connections. Cognitive and behavioral impairment in cerebellar disorders can be the results of acquired lesions or the action of genetic and environmental risk factors, to which the cerebellum is particularly vulnerable considering its pattern of development. In the pathological setting, early evidence of cerebellar damage may be very vague, due, partly, to spontaneous compensation phenomena and the vicarious role of the connecting structures (an expression of the brain’s plasticity). Careful clinical assessment will nonetheless enable appropriate instrumental procedures to be arranged. It is common knowledge that the contribution of neuroimaging is crucial for diagnosis of cerebellar conditions, and neurophysiological investigations can also have a significant role. The ultimate goal of clinicians is to combine clinical data and instrumental findings to formulate a precise diagnostic hypothesis, and thus request a specific genetic test in order to confirm their findings, wherever possible

Pediatric Slow-Progressive, but Not Non-Progressive Cerebellar Ataxia Delays Intra-Limb Anticipatory Postural Adjustments in the Upper Arm

We recently investigated the role of the cerebellum during development, reporting that children with genetic slow-progressive ataxia (SlowP) show worse postural control during quiet stance and gait initiation compared to healthy children (H). Instead, children with genetic non-progressive ataxia (NonP) recalled the behavior of H. This may derive from compensatory networks, which are hindered by disease progression in SlowP while free to develop in NonP. In the aim of extending our findings to intra-limb postural control, we recorded, in 10 NonP, 10 SlowP and 10 H young patients, Anticipatory Postural Adjustments (APAs) in the proximal muscles of the upper-limb and preceding brisk index finger flexions. No significant differences in APA timing occurred between NonP and H, while APAs in SlowP were delayed. Indeed, the excitatory APA in Triceps Brachii was always present but significantly delayed with respect to both H and NonP. Moreover, the inhibitory APAs in the Biceps Brachii and Anterior Deltoid, which are normally followed by a late excitation, could not be detected in most SlowP children, as if inhibition was delayed to the extent where there was overlap with a late excitation. In conclusion, disease progression seems to be detrimental for intra-limb posture, supporting the idea that inter- and intra-limb postures seemingly share the same control mechanism

Multiple Genetic Rare Variants in Autism Spectrum Disorders: A Single-Center Targeted NGS Study

Many studies based on chromosomal microarray and next-generation sequencing (NGS) have identified hundreds of genes associated with autism spectrum disorder (ASD) risk, demonstrating that there are several complex genetic factors that contribute to ASD risk. We performed targeted NGS gene panels for 120 selected genes, in a clinical population of 40 children with well-characterized ASD. The variants identified were annotated and filtered, focusing on rare variants with a minimum allele frequency <1% in GnomAD. We found 147 variants in 39 of the 40 patients. It was possible to perform family segregation analysis in 28 of the 40 patients. We found 4 de novo and 101 inherited variants. For the inherited variants, we observed that all the variants identified in the patients came equally from the paternal and maternal genetic makeup. We identified 9 genes that are more frequently mutated than the others, and upon comparing the mutational frequency of these 9 genes in our cohort and the mutational frequency in the GnomAD population, we found significantly increased frequencies of rare variants in our study population. This study supports the hypothesis that ASD is the result of a combination of rare deleterious variants (low contribution) and many low-risk alleles (genetic background), highlighting the importance of MET and SLIT3 and the potentially stronger involvement of FAT1 and VPS13B in ASD. Taken together, our findings reinforce the importance of using gene panels to understand the contribution of the different genes already associated with ASD in the pathogenesis of the disease