NETosis in Wound Healing: When Enough Is Enough

The neutrophils extracellular traps (NETs) are a meshwork of chromatin, histonic and non-histonic proteins, and microbicidal agents spread outside the cell by a series of nuclear and cytoplasmic events, collectively called NETosis. NETosis, initially only considered a defensive/apoptotic mechanism, is now considered an extreme defensive solution, which in particular situations induces strong negative effects on tissue physiology, causing or exacerbating pathologies as recently shown in NETs-mediated organ damage in COVID-19 patients. The positive effects of NETs on wound healing have been linked to their antimicrobial activity, while the negative effects appear to be more common in a plethora of pathological conditions (such as diabetes) and linked to a NETosis upregulation. Recent evidence suggests there are other positive physiological NETs effects on wound healing that are worthy of a broader research effort

Erythropoietin stimulation of human adipose tissue for therapeutic refilling releases protective cytokines

Apoptosis and inflammatory processes may be at the basis of reducing graft survival. Erythropoietin is a tissue-protective hormone with pleiotropic potential, and it interferes with the activities of pro-inflammatory cytokines and stimulates healing following injury, preventing destruction of tissue surrounding the injury site. It may represent a useful tool to increase the autograft integration. Through the use of multipanel kit cytokine analysis we have detected the cytokines secreted by human tissue adipose mass seeded in culture following withdrawal by Coleman's modified technique in three groups: control, after lipopolysaccharides stimulation and after erythropoietin stimulation. In the control group, we have observed expression of factors that may have a role in protecting the tissue homeostatic mechanism. But the same factors were secreted following stimulation with lipopolysaccharides combined with others factors that delineated the inflammatory state. Instead through erythropoietin stimulation, the factors known to exert tissue-protective action were secreted. Therefore, the use of a trophic factors such as erythropoietin may help to inhibit the potential inflammatory process development and stimulate the activation of reparative/regenerative process in the tissue graft

The influence of mechanogastric distension via autonomic nerve on hemodynamic outputs

The meal presence of carbohydrate, particularly glucose performs a loading of intraduodenal glucose that elicits blood pressure fall; but the gastric distension cooperate counterbalancing this visceral reflex slightly increasing heart rate and blood pressure mainly via orthosympathetic nerves. However in the elderly and in patients with autonomic dysfunction postprandial hypothension, became an important clinical problem [1]. We have previously observed that several hindbrain nuclei are involved in cardiovascular reflexes elicited by mechanogastric dilatation in which vagal parasympathetic and splanchnic sympathetic component participate to define their responses [2,3]. Therefore in the present work monolateral and bilateral vagotomy and splanchnotomy have been performed to assert the involvement of visceral nervous system hindbrain nuclei in hemodynamic control following gastric mechanical dilatation at high and low pressure. The mapping of c-Fos positive neurons have shown the occurrence of cooperative pathways between vagal and splanchnic component in several nuclei under analysis, similarly an integrated response between controlateral areas of single nuclei has been observed. In particular following mechanogastric experimental protocols adopted, the physiological response on blood pressure and heart rate, shows a preponderance effect of orthosympathetic component, but its plain functional expression need of parasympathetic component involvement

Delirium risk factors analysis post proximal femur fracture surgery in elderly

Background and aim: The increase in the average-age and in the percentage of elderly people implies an exponential increase in fractures of the proximal femur. A common consequence of hip fracture in elderly patients is delirium, characterized by cognitive confusion or a lethargic-type condition. Predisposing factors have been identified, but risk factors assessment useful for managing clinical intervention, has not received unanimous consent. This work aims to identify the potential risk factors for delirium in the elderly operated for hip fracture. Methods: In this prospective observational study, we included 83 patients aged ≥65 years. Patients undergoing osteosynthesis of the femur and hip replacement for fractures were included. Patients already delusional in the pre-operative period were excluded. At the time, deadlines T0 (pre-operative), and T1,T3,T7 post-operative day, delirium, hematic parameters, blood transfusions, were assessed. Results: Level of delirium was assessed obtaining 80% not delusional and 20% delusional. Glycemia and hemoglobin were not found to be risk factors, although they are known to influence cognitive status; we hypothesize they should be considered predisposing factors. Comorbidities such as atrial fibrillation and Chronic Obstructive Pulmonary Disease were found associated with delirium. The most advanced age, anxiolytic drugs, the use of benzodiazepine as anaesthetic, the time surgical waiting, were found significantly associated with delirium. Conclusions: Taken together, findings of this prospective observational study showed that environmental and metabolic risk factors might contribute to make elderly susceptible to develop postoperative delirium following hip surgery. Thus, these patients should be adequately assessed and monitored. (www.actabiomedica.it)

PROCESSING ADIPOSE TISSUE TO MAKE IT MORE STABLE WHEN USED FOR REFILLING. A MORPHOLOGIC AND IMMUNOHISTOCHEMISTRY EVALUATION

Breast reconstruction has gained from lipofilling the possibility to recover the aesthetic outcome of anatomical profile in a more natural appearance. However, until today, the long-term graft survival remains unpredictable, and sometimes it does not guarantee a well-adequate aesthetic result. In the present work, the morphological changes, occurring in fat mass used for refilling, harvested by the Coleman's procedure or through the washing/fragmenting procedure were analysed. Adipocyte size; immunohistochemistry against CD8, CD31, CD68 and M2-type macrophages and catalase enzyme, were analysed in vitro on fat mass cultured for 4 weeks. Our observation reveals an increase of connective tissue around the mass and a high number of immune cells occurrence in fat mass harvested by the Coleman's procedure. Instead, the washing/fragmented procedure would reduce the number of immune cells within the fat mass, increase the size of adipocytes, and cause a wider presence of active vessels profile and greater catalase expression. We hypothesize that the fat mass processed by the Coleman's procedure would remain more reactive due to a higher number of immune and macrophages cells, prone to develop cystic formation, leading to a suboptimal integration in the recipient site. On the other hand, the conditions more prone to realize an optimal integration would occur in the fat mass processed by the washing/fragmenting procedure: a reduced number of immune cells, low amount of connective tissue, presence of larger adipocytes. Follow-up monitoring did support our conclusion, as we observed a reduction of re-intervention for refilling procedure in patients treated with the washing/fragmenting procedure

The importance of gravity vector on adult mammalian organisms: Effects of hypergravity on mouse testis

In the age of space exploration, the effect of hypergravity on human physiology is a relatively neglected topic. However, astronauts have several experiences of hypergravity during their missions. The main disturbance of altered gravity can be imputed to cell cytoskeleton alteration and physiologic homeostasis of the body. Testis has proved to be a particularly sensible organ, subject to environmental alteration and physiological disturbance. This makes testis an organ eligible for investigating the alteration following exposure to altered gravity. In our study, mice were exposed to hypergravity (3g for 14 days) in the Large Diameter Centrifuge machine (ESA, Netherland). We have observed a morphological alteration of the regular architecture of the seminiferous tubules of testis as well as an altered expression of factors involved in the junctional complexes of Sertoli cells, responsible for ensuring the morpho-functional integrity of the organ. The expression of key receptors in physiological performance, such as Androgen Receptors and Interstitial Cells Stimulating Hormone receptors, was found lower expressed. All these findings indicate the occurrence of altered physiological organ performance such as the reduction of the spermatozoa number and altered endocrine parameters following hypergravity exposure

The Combination of Molnupiravir with Nirmatrelvir or GC376 Has a Synergic Role in the Inhibition of SARS-CoV-2 Replication In Vitro

Introduction: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic; however, the need for orally administered antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify the synergistic effect. Methods: The SARS-CoV-2 strains 20A.EU, BA.1 and BA.2 were used to infect Vero E6 in presence of antiviral compounds alone or in combinations using five two-fold serial dilution of compound concentrations <= EC90. After 48 and 72 h post-infection, viability was performed using MTT reduction assay. Supernatants were collected for plaque-assay titration. All experiments were performed in triplicate, each being repeated at least three times. The synergistic score was calculated using Synergy Finder version 2. Results: All compounds reached micromolar EC90. Molnupiravir and GC376 showed a synergistic activity at 48 h with an HSA score of 19.33 (p < 0.0001) and an additive activity at 72 h with an HSA score of 8.61 (p < 0.0001). Molnupiravir and nirmatrelvir showed a synergistic activity both at 48 h and 72 h with an HSA score of 14.2 (p = 0.01) and 13.08 (p < 0.0001), respectively. Conclusion: Molnupiravir associated with one of the two protease-inhibitors nirmatrelvir and GC376 showed good additive-synergic activity in vitro

Linear Accelerator Test Facility at LNF Conceptual Design Report

Test beam and irradiation facilities are the key enabling infrastructures for research in high energy physics (HEP) and astro-particles. In the last 11 years the Beam-Test Facility (BTF) of the DA{\Phi}NE accelerator complex in the Frascati laboratory has gained an important role in the European infrastructures devoted to the development and testing of particle detectors. At the same time the BTF operation has been largely shadowed, in terms of resources, by the running of the DA{\Phi}NE electron-positron collider. The present proposal is aimed at improving the present performance of the facility from two different points of view: extending the range of application for the LINAC beam extracted to the BTF lines, in particular in the (in some sense opposite) directions of hosting fundamental physics and providing electron irradiation also for industrial users; extending the life of the LINAC beyond or independently from its use as injector of the DA{\Phi}NE collider, as it is also a key element of the electron/positron beam facility. The main lines of these two developments can be identified as: consolidation of the LINAC infrastructure, in order to guarantee a stable operation in the longer term; upgrade of the LINAC energy, in order to increase the facility capability (especially for the almost unique extracted positron beam); doubling of the BTF beam-lines, in order to cope with the signicant increase of users due to the much wider range of applications.Comment: 71 page