Retinal and Circulating miRNAs in Age-Related Macular Degeneration: An In vivo Animal and Human Study

Age related macular degeneration (AMD) is the leading cause of blindness among people aged 50 and over. Retinal deposition of amyloid-β (Aβ) aggregates in AMD patients has suggested a potential link between AMD and Alzheimer's disease (AD). We have evaluated the differential retinal expression profile of miRNAs in a rat model of AMD elicited by Aβ. A serum profile of miRNAs in AMD patients has been also assessed using single TaqMan assay. Analysis of retina from rats intravitreally injected with Aβ revealed that miR-27a, miR-146a, and miR-155 were up-regulated in comparison to control rats. Seven miRNA (miR-9, miR-23a, miR-27a, miR-34a, miR-126, miR-146a, and miR-155) have been found to be dysregulated in serum of AMD patients in comparison to control group. Analysis of pathways has revealed that dysregulated miRNAs, both in the AMD animal model and in AMD patients, can target genes regulating pathways linked to neurodegeneration and inflammation, reinforcing the hypothesis that AMD is a protein misfolding disease similar to AD. In fact, miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 have been found to be dysregulated both in AMD and AD. In conclusion, we suggest that miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 represent potential biomarkers and new pharmacological targets for AMD

Unbalanced Immune System: Immunodeficiencies and Autoimmunity

Increased risk of developing autoimmune manifestations has been identified in different primary immunodeficiencies (PIDs). In such conditions, autoimmunity and immune deficiency represent intertwined phenomena that reflect inadequate immune function. Autoimmunity in PIDs may be caused by different mechanisms, including defects of tolerance to self-antigens and persistent stimulation as a result of the inability to eradicate antigens. This general immune dysregulation leads to compensatory and exaggerated chronic inflammatory responses that lead to tissue damage and autoimmunity. Each PID may be characterized by distinct, peculiar autoimmune manifestations. Moreover, different pathogenetic mechanisms may underlie autoimmunity in PID. In this review, the main autoimmune manifestations observed in different PID, including humoral immunodeficiencies, combined immunodeficiencies, and syndromes with immunodeficiencies, are summarized. When possible, the pathogenetic mechanism underlying autoimmunity in a specific PID has been explained

The prognostic value of the myeloid-mediated immunosuppression marker Arginase-1 in classic Hodgkin Lymphoma

Neutrophilia is hallmark of classic Hodgkin Lymphoma (cHL), but its precise characterization remains elusive. We aimed at investigating the immunosuppressive role of high-density neutrophils in HL

The short term debt vs. long term debt puzzle: a model for the optimal mix

This paper argues that the existing finance literature is inadequate with respect to its coverage of capital structure of small and medium sized enterprises (SMEs). In particular it is argued that the cost of equity (being both conceptually ill defined and empirically non quantifiable) is not applicable to the capital structure decisions for a large proportion of SMEs and the optimal capital structure depends only on the mix of short and long term debt. The paper then presents a model, developed by practitioners for optimising the debt mix and demonstrates its practical application using an Italian firm's debt structure as a case study

Impact of baryon physics on dark matter structures: a detailed simulation study of halo density profiles

The back-reaction of baryons on the dark matter halo density profile is of great interest, not least because it is an important systematic uncertainty when attempting to detect the dark matter. Here, we draw on a large suite of high resolution cosmological hydrodynamical simulations, to systematically investigate this process and its dependence on the baryonic physics associated with galaxy formation. The inclusion of baryons results in significantly more concentrated density profiles if radiative cooling is efficient and feedback is weak. The dark matter halo concentration can in that case increase by as much as 30 (10) per cent on galaxy (cluster) scales. The most significant effects occur in galaxies at high redshift, where there is a strong anti-correlation between the baryon fraction in the halo centre and the inner slope of both the total and the dark matter density profiles. If feedback is weak, isothermal inner profiles form, in agreement with observations of massive, early-type galaxies. However, we find that AGN feedback, or extremely efficient feedback from massive stars, is necessary to match observed stellar fractions in groups and clusters, as well as to keep the maximum circular velocity similar to the virial velocity as observed for disk galaxies. These strong feedback models reduce the baryon fraction in galaxies by a factor of 3 relative to the case with no feedback. The AGN is even capable of reducing the baryon fraction by a factor of 2 in the inner region of group and cluster haloes. This in turn results in inner density profiles which are typically shallower than isothermal and the halo concentrations tend to be lower than in the absence of baryons.Comment: 20 pages, 14 figures, 1 table. MNRAS in press. Version 2: added a few references

SARS-CoV-2 reinfection caused by the P.1 lineage in Araraquara city, Sao Paulo State, Brazil

Reinfection by the severe acute respiratory syndrome coronavirus type 2 (SARS-COV-2) has been reported in many countries, suggesting that the virus may continue to circulate among humans despite the possibility of local herd immunity due to massive previous infections. The emergence of variants of concern (VOC) that are more transmissible than the previous circulating ones has raised particular concerns on the vaccines effectiveness and reinfection rates. The P.1 lineage was first identified in December 2020 in Manaus city and is now globally spread. We report the first case of reinfection of SARS-CoV-2 caused by the P.1 variant outside of Manaus. The potential of these new variants to escape naturally and vaccine- induced immunity highlights the need for a global vigilance

Reshaping ophthalmology training after COVID-19 pandemic

Background The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on practical activities and didactic teaching of residents and fellows. This survey aimed to propose long-term changes for ophthalmology training based on the changes experienced by trainees and their perception of new training opportunities. Methods An online survey was distributed to ophthalmology trainees in multiple countries. Descriptive statistics were used to analyse the data. Results A total of 504 analyzable responses were collected from 32 different countries. The current impact of COVID-19 pandemic was described as "severe" by most trainees (55.2%); however, the future perspective was more optimistic as demonstrated by the greater number of responses reporting a presumed "moderate" (37.3%), "mild" (14.1%) or "slight" (4.2%) long-term impact. The vast majority of trainees reported a decrease >= 50% of clinical activity (76.4%) and >75% of surgical activity (74.6%). Although an initial gap in didactic teaching has been experienced by many (55.4%), regular web-based teaching was reportedly attended by 67.7% of the respondents. A strong agreement was found regarding the worthwhile role of web-based case-presentations in clinical training (91.7%), web-based discussion of edited surgical videos (85.7%) and simulation-based practice (86.9%) in surgical training. Conclusions This survey, focusing on trainees' perspective, strongly reinforces the need to promptly include new technology-based training tools, such as web-based teaching, virtual surgical simulators, and telementoring, in long-term reorganisation of ophthalmology training to ensure its continuity and effectiveness, which would remain available even in the face of another unpredictable crisis within the health system

Reshaping ophthalmology training after COVID-19 pandemic

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on practical activities and didactic teaching of residents and fellows. This survey aimed to propose long-term changes for ophthalmology training based on the changes experienced by trainees and their perception of new training opportunities. Methods: An online survey was distributed to ophthalmology trainees in multiple countries. Descriptive statistics were used to analyse the data. Results: A total of 504 analyzable responses were collected from 32 different countries. The current impact of COVID-19 pandemic was described as “severe” by most trainees (55.2%); however, the future perspective was more optimistic as demonstrated by the greater number of responses reporting a presumed “moderate” (37.3%), “mild” (14.1%) or “slight” (4.2%) long-term impact. The vast majority of trainees reported a decrease ≥50% of clinical activity (76.4%) and >75% of surgical activity (74.6%). Although an initial gap in didactic teaching has been experienced by many (55.4%), regular web-based teaching was reportedly attended by 67.7% of the respondents. A strong agreement was found regarding the worthwhile role of web-based case-presentations in clinical training (91.7%), web-based discussion of edited surgical videos (85.7%) and simulation-based practice (86.9%) in surgical training. Conclusions: This survey, focusing on trainees’ perspective, strongly reinforces the need to promptly include new technology-based training tools, such as web-based teaching, virtual surgical simulators, and telementoring, in long-term reorganisation of ophthalmology training to ensure its continuity and effectiveness, which would remain available even in the face of another unpredictable crisis within the health systempublishersversionPeer reviewe

Pediatric Gastrointestinal Endoscopy: European Society of Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and European Society of Gastrointestinal Endoscopy (ESGE) Guidelines

ABSTRACT: This Guideline refers to infants, children and adolescents aged 0–18 years. The areas covered include: indications for diagnostic and therapeutic esophagogastroduodenoscopy and ileo-colonoscopy; endoscopy for foreign body ingestion; corrosive ingestion and stricture/stenosis endoscopic management; upper and lower gastrointestinal bleeding; endoscopic retrograde cholangio-pancreatography and endoscopic ultrasonography. Percutaneous endoscopic gastrostomy and endoscopy specific to inflammatory bowel disease (IBD) has been dealt with in other Guidelines [1–3] and are therefore not mentioned in this Guideline. Training and ongoing skill maintenance are to be dealt with in an imminent sister publication to this