Neuroglobin Gene Therapy Prevents Optic Atrophy and Preserves Durably Visual Function in Harlequin Mice

Neuroglobin (NGB) is considered as an endogenous neuroprotective molecule against stroke, since the protein alleviates the adverse effects of hypoxic and ischemic insults. We previously demonstrated the functional link between NGB and mitochondria since it is required for respiratory chain function. Thus, here, we evaluated the relevance of this effect in the Harlequin (Hq) mouse strain, which exhibits retinal ganglion cell (RGC) loss and optic atrophy due to a respiratory chain complex I (CI) defect. A twofold decrease of NGB amounts was observed in Hq retinas. We constructed a recombinant adeno-associated virus which combines to the mouse NGB open reading frame, its 5′ and 3′UTR, for guarantying mRNA stability and translation capacity. The vector was administrated intravitreally to Hq mice and NGB expression was stable for up to 7 months without negative effect on retinal architecture or function. On the contrary, RGCs and their axons were substantially preserved from degeneration; consequently, CI activity in optic nerves was protected conferring improvements in vision. Hence, we established that NGB prevents respiratory chain impairment, therefore, protecting visual function otherwise compromised by mitochondrial energetic failure.     

Contrast-Enhanced Ultrasound Quantifies the Perfusion Within Tibial Non-Unions and Predicts the Outcome of Revision Surgery

Vascularity is one of the factors determining successful bone regeneration. This prospective study focused on quantifying the microperfusion of tibial non-unions with contrast-enhanced ultrasound (CEUS) 12?wk after revision surgery and comparing it with the osseous consolidation at a maximum of 24?mo assessed with standard radiography and computed tomography. Of 36 patients with tibial non-unions, 28 (77.8%) manifested consolidation, and 8 patients required further revision surgery. CEUS revealed significantly higher perfusion in consolidated versus persistent non-unions for all quantification parameters (e.g., wash-in perfusion index p?=?0.036). Receiver operating characteristic analysis revealed a sensitivity of 82.1% and specificity of 75.0% with a wash-in perfusion index cutoff at 19.9 a.u. for diagnosing persisting non-unions. More than 1 y ahead of the final radiologic diagnostic examination, CEUS could predict eventual consolidation based on the osseous perfusion as soon as 12?wk postoperatively. This information can be crucial for the decision-making process for re-revision at an early stage.     

Human Monocyte-Derived Dendritic Cells Exposed to Microorganisms Involved in Hypersensitivity Pneumonitis Induce a Th1-Polarized Immune Response

Hypersensitivity pneumonitis (HP) is an immunoallergic disease characterized by a prominent interstitial infiltrate composed predominantly of lymphocytes secreting inflammatory cytokines. Dendritic cells (DCs) are known to play a pivotal role in the lymphocytic response. However, their cross talk with microorganisms that cause HP has yet to be elucidated. This study aimed to investigate the initial interactions between human monocyte-derived DCs (MoDCs) and four microorganisms that are different in nature (Saccharopolyspora rectivirgula [actinomycetes], Mycobacterium immunogenum [mycobacteria], and Wallemia sebi and Eurotium amstelodami [filamentous fungi]) and are involved in HP. Our objectives were to determine the cross talk between MoDCs and HP-causative agents and to determine whether the resulting immune response varied according to the microbial extract tested. The phenotypic activation of MoDCs was measured by the increased expression of costimulatory molecules and levels of cytokines in supernatants. The functional activation of MoDCs was measured by the ability of MoDCs to induce lymphocytic proliferation and differentiation in a mixed lymphocytic reaction (MLR). E. amstelodami-exposed (EA) MoDCs expressed higher percentages of costimulatory molecules than did W. sebi-exposed (WS), S. rectivirgula-exposed (SR), or M. immunogenum-exposed (MI) MoDCs (P < 0.05, Wilcoxon signed-rank test). EA-MoDCs, WS-MoDCs, SR-MoDCs, and MI-MoDCs induced CD4⁺ T cell proliferation and a Th1-polarized immune response. The present study provides evidence that, although differences were initially observed between MoDCs exposed to filamentous fungi and MoDCs exposed to bacteria, a Th1 response was ultimately promoted by DCs regardless of the microbial extract tested.     

Elderly victims of gender violence in Portugal: Invisible and not heard?

In this article, we explore professionals' representations of elderly female victims of gender violence. Semi-structured interviews were used to explore seven professionals' work philosophies and intervention methodologies in their work with elderly female victims of violence, their main problems and difficulties, and their perspectives regarding shelters for elderly women. Results show that there are no specific philosophies and methodologies to intervene with these victims. There is a tendency to homogenize all the victims of gender violence, regardless of their age and specific needs. The professionals also tended to trivialize gender violence against elderly female victims, considering that these women tolerate violence.