N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation.

An unmet clinical goal in demyelinating pathologies is to restore the myelin sheath prior to neural degeneration. N-acetylaspartate (NAA) is an acetylated derivative form of aspartate, abundant in the healthy brain but severely reduced during traumatic brain injury and in patients with neurodegenerative pathologies. How extracellular NAA variations impact the remyelination process and, thereby, the ability of oligodendrocytes to remyelinate axons remains unexplored. Here, we evaluated the remyelination properties of the oligodendroglial (OL) mouse cell line Oli-neuM under different concentrations of NAA using a combination of biochemical, qPCR, immunofluorescence assays, and in vitro engagement tests, at NAA doses compatible with those observed in healthy brains and during brain injury. We observed that oligodendroglia cells respond to decreasing levels of NAA by stimulating differentiation and promoting gene expression of myelin proteins in a temporally regulated manner. Low doses of NAA potently stimulate Oli-neuM to engage with synthetic axons. Furthermore, we show a concentration-dependent expression of specific histone deacetylases essential for MBP gene expression under NAA or Clobetasol treatment. These data are consistent with the idea that oligodendrocytes respond to lowering the NAA concentration by activating the remyelination process via deacetylase activation.

A child is not an adult: development of a new in vitro model of the toddler colon.

Early life is a critical period where gut ecosystem and functions are being established with significant impact on health. For regulatory, technical, and cost reasons, in vitro gut models can be used as a relevant alternative to in vivo assays. An exhaustive literature review was conducted to adapt the Mucosal Artificial Colon (M-ARCOL) to specific physicochemical (pH, transit time, and nutritional composition of ileal effluents) and microbial parameters from toddlers in the age range of 6 months-3 years, resulting in the Tm-ARCOL. In vitro fermentations were performed to validate this newly developed colonic model compared to in vivo toddler data. Results were also compared to those obtained with the classical adult configuration. Fecal samples from 5 toddlers and 4 adults were used to inoculate bioreactors, and continuous fermentations were performed for 8 days. Gut microbiota structure (lumen and mucus-associated microbiota) and functions (gas and short-chain fatty acids) were monitored. Clearly distinct microbial signatures were obtained between the two in vitro conditions, with lower α-diversity indices and higher abundances of infant-related microbial populations (e.g., Bifidobacteriaceae, Enterobacteriaceae) in toddler versus adult conditions. In accordance with in vivo data, methane was found only in adult bioreactors, while higher percentage of acetate but lower proportions of propionate and butyrate was measured in toddlers compared to adults. This new in vitro model will provide a powerful platform for gut microbiome mechanistic studies in a pediatric context, both in nutritional- (e.g., nutrients, probiotics, prebiotics) and health-related (e.g., drugs, enteric pathogens) studies. KEY POINTS: • Development of a novel in vitro colonic model recapitulating the toddler environment. • Specific toddler versus adult digestive conditions are preserved in vitro. • The new model provides a powerful platform for microbiome mechanistic studies.

In vitro models of gut digestion across childhood: current developments, challenges and future trends.

The human digestion is a multi-step and multi-compartment process essential for human health, at the heart of many issues raised by academics, the medical world and industrials from the food, nutrition and pharma fields. In the first years of life, major dietary changes occur and are concomitant with an evolution of the whole child digestive tract anatomy and physiology, including colonization of gut microbiota. All these phenomena are influenced by child exposure to environmental compounds, such as drugs (especially antibiotics) and food pollutants, but also childhood infections. Due to obvious ethical, regulatory and technical limitations, in vivo approaches in animal and human are more and more restricted to favor complementary in vitro approaches. This review summarizes current knowledge on the evolution of child gut physiology from birth to 3 years old regarding physicochemical, mechanical and microbial parameters. Then, all the available in vitro models of the child digestive tract are described, ranging from the simplest static mono-compartmental systems to the most sophisticated dynamic and multi-compartmental models, and mimicking from the oral phase to the colon compartment. Lastly, we detail the main applications of child gut models in nutritional, pharmaceutical and microbiological studies and discuss the limitations and challenges facing this field of research.

Assistive Technologies and Quadriplegia: A Map Point on the Development and Spread of the Tongue Barbell Piercing.

The barbell piercing can be used as an assistive device that allows people with severe disabilities, such as tetraplegia, to control their environments using the movement of the tongue. The human tongue can move rapidly and accurately, such that the tip can touch every tooth. Lingual control systems allow people with disabilities to take advantage of their residual skills for easier communication and to improve the control of mobility and the surrounding environment. The aim of this study was to conduct a narrative review of the development and dissemination of the assistive technologies based on tongue control by means of the barbell piercing. The design of the study was based on: (I) an overview of Pubmed complemented with other databases and Web searches (also institutional); (II) an organization according to a standardized checklist for narrative reviews; (III) an arrangement with four different perspectives: the trends in the scientific literature, technological evolution and categorization, dominant approaches, issues of incorporation into the health domain-such as acceptance, safety, and regulations. The results have highlighted: (1) that the volume of scientific productions, which started in this sector before the smartphone expansion, has not increased; (2) that it is possible to make a map point of the technological evolution and categorization; (3) that these assistive technologies have a high degree of acceptance and performance, especially when integrated with aid tools with mechatronics; (4) and the complexity of the regulatory framework in this area. The study, from a general point of view, highlighted the high potential of these systems and we suggest investing the energy into agreement tools for assistive technologies (AT)s, such as health technology assessment studies, comparative assessment analysis, or consensus conferences that could allow a better diffusion and use of ATs, including these systems.

Dermopigmentation of the nipple-areola complex in a dedicated breast cancer centre, following the Treviso Hospital (Italy) LILT model.

BACKGROUND: Dermopigmentation, also known as medical tattooing, is a complementary technique in the reconstruction of the nipple-areola and an adjuvant procedure to improve colour mismatch. In 2009, tattooing of the nipple-areola complex (NAC) was introduced by Treviso Hospital through a project conducted in cooperation with the local section of the Italian Anti-Cancer League (LILT). METHODS: From 2010 to 2016, 169 patients treated for breast cancer underwent dermopigmentation treatments. Patients were selected by the hospital plastic and breast surgeons. Dermopigmentation was performed at the LILT (Lega Italiana per la Lotta contro i Tumori, Italian Cancer League) facility following a specific procedure to ensure safety. A sterile disposable surgical set was used. RESULTS: Of 169 patients treated in 309 treatment sessions, no serious complications were reported after tattooing, with only three cases seen of minor complications. Patients expressed a high level of satisfaction (90%) with the aesthetic results. CONCLUSION: The study found that dermopigmentation of the NAC is a safe approach, providing benefits both to the patients and the hospital itself. Medical tattooing of the NAC is a simple and safe nonsurgical technique that reduces missed workdays and increases the time available for other commitments. This ultimately translates into savings for society and the healthcare system.

Seroprevalence of Hepatitis E Virus in Forestry Workers from Trentino-Alto Adige Region (Northern Italy).

People with some occupational or recreational activities, such as hunters and veterinarians, may have increased risk to be infected by the hepatitis E virus (HEV). The aim of the present study was to establish whether forestry workers could be considered at a higher risk of HEV infection than a control group. One hundred and fifty sera from forestry workers and a control group of 85 sera were analysed by anti-HEV IgG antibodies detection using a commercial ELISA kit. The anti-HEV IgG seroprevalence was 14% for forestry workers and 9.4% for the control group. Comparing the risk of HEV infection in the two groups, there was no difference in the odds ratio. However, the seroprevalence in older subjects was higher in the forestry workers than in the control group. Two sera from forestry workers were also positive for anti-HEV IgM, and, in one of them, HEV-RNA was detected. Our findings showed an increase of seroprevalence with age, which is likely to reflect cumulative exposure to HEV over time. The occupation of forestry workers did not seem to be associated with a higher risk of HEV infection. The study provided new insights into the risk of acquiring HEV in occupational exposure workers with open-air activities.

Mechanism of action at the molecular level of the antiviral drug 3(2H)-isoflavene against type 2 poliovirus.

The mechanism of action of the antiviral compound 3(2H)-isoflavene against Sabin type 2 poliovirus has been studied, and interference with virus uncoating was demonstrated. Isolation and sequencing of drug-resistant variants revealed single amino acid substitutions (I194M or D131V) in the VP1 capsid protein. While M194 is located in a hydrophobic pocket and should partially fill the space occupied by the isoflavene ring, V131 is exposed on the VP1 surface, forming a contact with VP4. The D131V mutation most likely induces local conformational changes in VP1 and/or VP4 that affect viral flexibility. Two dependent variants, N53S of VP1 and K58E of VP4, both located on the inner surface of the capsid, near the threefold axis of symmetry, were also selected. Both mutations affected viral stability, allowing the transition to 135S particles in the absence of drug, without the involvement of the viral receptor.