Osteoimmunology: from mice to humans

The immune system has been recognized as one of the most important regulators of bone turnover and its deregulation is implicated in several bone diseases such as postmenopausal osteoporosis and inflammatory bone loss; recently it has been suggested that the gut microbiota may influence bone turnover by modulation of the immune system. The study of the relationship between the immune system and bone metabolism is generally indicated under the term ‘osteoimmunology'. The vast majority of these studies have been performed in animal models; however, several data have been confirmed in humans as well: this review summarizes recent data on the relationship between the immune system and bone with particular regard to the data confirmed in humans

Chaos at the Gates: The impacts of the COVID-19 pandemic and energy price shocks on South Korea's gas industry amid energy transition

South Korea was one of the first countries to be hit by the coronavirus infections. Having rapidly contained the health emergency in the immediate period, Seoul arguably mitigated the economic fallouts more successfully than the majority of advanced economies but could not avoid substantial losses. The far-reaching fallout of COVID-19 has been testing the country's energy transition pathway, as actors involved are facing difficult decisions amid more stringent financial constraints to deliver their ambitious targets, including achieving carbon neutrality by 2050. Amid the combined effects of the pandemic and the global energy prices shocks, addressing the nexus between energy security on the supply side, affordability, and the safety of people's lives and property, has become even more pressing. Against this backdrop, natural gas has tailored a special role to bridge the low carbon re-alignment of the entire Korean energy system, also in the face of the current and future challenges to Korea's energy security. But long-drawn hurdles stemming from rather unsuccessful efforts to reform the gas system risk weakening its ability to cope with present uncertainties and heightened volatilities

Association between Immunosenescence, Mitochondrial Dysfunction and Frailty Syndrome in Older Adults

Aging is associated with changes in the immune system, increased inflammation and mitochondrial dysfunction. The relationship between these phenomena and the clinical phenotype of frailty is unclear. Here, we evaluated the immune phenotypes, T cell functions and mitochondrial functions of immune cells in frail and robust older subjects. We enrolled 20 frail subjects age- and gender-matched with 20 robust controls, and T cell phenotype, response to immune stimulation, cytokine production and immune cell mitochondrial function were assessed. Our results showed that numbers of CD4+ and CD8+ T cells were decreased in frail subjects, without impairment to their ratios. Memory and naïve T cells were not significantly affected by frailty, whereas the expression of CD28 but not that of ICOS was decreased in T cells from frail subjects. T cells from robust subjects produced more IL-17 after CD28 stimulation. Levels of serum cytokines were similar in frail subjects and controls. Mitochondrial bioenergetics and ATP levels were significantly lower in immune cells from frail subjects. In conclusion, we suggest that changes in T cell profiles are associated with aging rather than with frailty syndrome; however, changes in T cell response to immune stimuli and reduced mitochondrial activity in immune cells may be considered hallmarks of frailty

Electrode displacement after intracerebral hematoma as a complication of a deep brain stimulation procedure

Domenico Servello1, Marco Sassi1, Stefano Bastianello2, Guy Umberto Poloni2, Francesca Mancini3, Claudio Pacchetti31Functional Neurosurgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico Galeazzi, Milan, Italy; 2Neuroradiology Unit; 3Parkinson Disease and Movement Disorder Unit, Istituto di Ricovero e Cura a Carattere Scientifico Mondino, Institute of Neurology, Pavia, Italy Objectives: Deep brain stimulation (DBS) is nowadays considered a safe and effective procedure for various movement disorders in which conservative treatments have failed to show significant therapeutic results. One of the most common complications of definitive electrode positioning is intraparenchymal hemorrhage.Materials and methods: Authors report the case of a 55-year-old female patient treated for Parkinson’s disease in which intraparenchymal hemorrhage developed after DBS procedure, leading to significant (about 8 mm at the neuroradiological controls) displacement of an otherwise correctly positioned DBS electrode.Results: After conservative management, the hematoma spontaneously resolved. Late neuroradiological controls documented correct, symmetrically positioned electrodes, comparable to the immediate postoperative controls.Conclusions: Six months follow-up endpoint results of the DBS treatment were considered satisfying by an independent neurologist, with modest residual neurological deficits, demonstrating that re-positioning of the electrode was unnecessary in this rare complication.Keywords: deep brain stimulation, electrodes, outcomes, implant, case repor

Alternative splicing of the angiogenesis associated extra-domain B of fibronectin regulates the accessibility of the B-C loop of the type III repeat 8

BACKGROUND: Fibronectin (FN) is a multi-domain molecule involved in many cellular processes, including tissue repair, embryogenesis, blood clotting, and cell migration/adhesion. The biological activities of FN are mediated by exposed loops located mainly at the interdomain interfaces that interact with various molecules such as, but not only, integrins. Different FN isoforms arise from the alternative splicing of the pre-mRNA. In malignancies, the splicing pattern of FN pre-mRNA is altered; in particular, the FN isoform containing the extra-domain B (ED-B), a complete FN type III repeat constituted by 91 residues, is undetectable in normal adult tissues, but exhibits a much greater expression in fetal and tumor tissues, and is accumulated around neovasculature during angiogenic processes, thus making ED-B one of the best markers and targets of angiogenesis. The functions of ED-B are still unclear; however, it has been postulated that the insertion of an extra-domain such as ED-B modifies the domain-domain interface and may unmask loops that are otherwise cryptic, thus giving FN new potential activities. METHODOLOGY: We used the mAb C6, which reacts with ED-B containing FN, but not with ED-B-free FN and various recombinant FN fragments containing mutations, to precisely localize the epitopes recognized by the mAb C6. CONCLUSION: We formally demonstrated that the inclusion of the alternatively spliced angiogenesis-associated ED-B leads to the unmasking of the FNIII 8 B-C loop that is cryptic in FN molecules lacking ED-B. Thus, the mAb C6, in addition to providing a new reagent for angiogenesis targeting, represents a new tool for the study of the potential biological functions of the B-C loop of the repeat FNIII 8 that is unmasked during angiogenic processes

Hip subluxation in Italian cerebral palsy children and its determinants: a retrospective cohort study

The study's aim was two-fold: to describe the trend of hip subluxation in the largest sample of Italian nonambulatory cerebral palsy (CP) children ever published; to investigate its determinants. This single-centre retrospective cohort study included patients with spastic or dyskinetic CP, Gross Motor Function Classification System (GMFCS) level IV or V, age 0-18 years, having been referred to our unit before March 2020. The hip subluxation was measured by means of the migration percentage (MP). Other data were gathered such as sex, CP subtype, GMFCS level, presence of drug-resistant epilepsy, age, use of walkers with weight relief or standing devices, previous botulinum injection or hip surgery, oral or intrathecal baclofen and hip pain. Multiple linear stepwise regression was performed and descriptive statistics are provided. Spastic CP had MP maximum increase in early ages, with GMFCS level V values persistently higher than level IV. The dyskinetic subtype showed a slower increase of the MP, with GMFCS level IV presenting similar or higher values, compared to level V. Age, CP severity and spastic subtype are the main determinants. The stepwise multiple regression analysis demonstrated that weight relief walking and standing assistive devices, combined with botulinum contributed to reduce the MP progression. Dyskinetic CP showed overall lower MP values and a more variable behaviour relative to age and GMFCS level, compared to the spastic subtype. Standing and walking assistive devices, with partial or total weight relief, combined with individually targeted botulinum injections, should be considered in the management of bilateral nonambulatory CP patients, to prevent hip subluxation or its recurrence after surgery

Targeting Taxanes to Castration-Resistant Prostate Cancer Cells by Nanobubbles and Extracorporeal Shock Waves

To target taxanes to castration-resistant prostate cancer cells, glycol-chitosan nanobubbles loaded with paclitaxel and docetaxel were constructed. The loaded nanobubbles were then combined with Extracorporeal Shock Waves, acoustic waves widely used in urology and orthopedics, with no side effects. Nanobubbles, with an average diameter of 353.3 ± 15.5 nm, entered two different castration-resistant prostate cancer cells (PC3 and DU145) as demonstrated by flow cytometry and immunofluorescence. The shock waves applied increased the amount of intracellular nanobubbles. Loading nanobubbles with paclitaxel and docetaxel and combining them with shock waves generated the highest cytotoxic effects, resulting in a paclitaxel GI50 reduction of about 55% and in a docetaxel GI50 reduction of about 45% respectively. Combined treatment also affected cell migration. Paclitaxel-loaded nanobubbles and shock waves reduced cell migration by more than 85% with respect to paclitaxel alone; whereas docetaxel-loaded nanobubbles and shock waves reduced cell migration by more than 82% with respect to docetaxel alone. The present data suggest that nanobubbles can act as a stable taxane reservoir in castration-resistant prostate cancer cells and shock waves can further increase drug release from nanobubbles leading to higher cytotoxic and anti-migration effect