Exosome levels in human body fluids: A tumor marker by themselves?

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can provide several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may themselves represent a predictive/diagnostic of tumors, discriminating cancer patients from healthy subjects. The aim of this review is to highlight these latest challenging findings to provide novel and groundbreaking ideas for successful tumor early diagnosis and follow-up

A systematic investigation of production of synthetic prions from recombinant prion protein

According to the protein-only hypothesis, infectious mammalian prions, which exist as distinct strains with discrete biological properties, consist of multichain assemblies of misfolded cellular prion protein (PrP). A critical test would be to produce prion strains synthetically from defined components. Crucially, high-titre 'synthetic' prions could then be used to determine the structural basis of infectivity and strain diversity at the atomic level. While there have been multiple reports of production of prions from bacterially expressed recombinant PrP using various methods, systematic production of high-titre material in a form suitable for structural analysis remains a key goal. Here, we report a novel high-throughput strategy for exploring a matrix of conditions, additives and potential cofactors that might generate high-titre prions from recombinant mouse PrP, with screening for infectivity using a sensitive automated cell-based bioassay. Overall, approximately 20 000 unique conditions were examined. While some resulted in apparently infected cell cultures, this was transient and not reproducible. We also adapted published methods that reported production of synthetic prions from recombinant hamster PrP, but again did not find evidence of significant infectious titre when using recombinant mouse PrP as substrate. Collectively, our findings are consistent with the formation of prion infectivity from recombinant mouse PrP being a rare stochastic event and we conclude that systematic generation of prions from recombinant PrP may only become possible once the detailed structure of authentic ex vivo prions is solved

Long-term beneficial effect of islet transplantation on diabetic macro-/microangiopathy in type 1 diabetic kidney-transplanted patients

OBJECTIVE: Our aim was to evaluate the long-term effects of transplanted islets on diabetic macro-/microangiopathy in type 1 diabetic kidney-transplanted patients. RESEARCH DESIGN AND METHODS: A total of 34 type 1 diabetic kidney-transplanted patients underwent islet transplantation and were divided into two groups: successful islet-kidney transplantation (SI-K; 21 patients, fasting C-peptide serum concentration >0.5 ng/ml for >1 year) and unsuccessful islet-kidney transplantation (UI-K; 13 patients, fasting C-peptide serum concentration <0.5 ng/ml). Patients cumulative survival, cardiovascular death rate, and atherosclerosis progression were compared in the two groups. Skin biopsies, endothelial dependent dilation (EDD), nitric oxide (NO) levels, and atherothrombotic risk factors [von Willebrand factor (vWF) and D-dimer fragment (DDF)] were studied cross-sectionally. RESULTS: The SI-K group showed a significant better patient survival rate (SI-K 100, 100, and 90% vs. UI-K 84, 74, and 51% at 1, 4, and 7 years, respectively, P = 0.04), lower cardiovascular death rate (SI-K 1/21 vs. UI-K 4/13, chi(2) = 3.9, P = 0.04), and lower intima-media thickness progression than the UI-K group (SI-K group: delta1-3 years -13 +/- 30 micro m vs. UI-K group: delta1-3 years 245 +/- 20 micro m, P = 0.03) with decreased signs of endothelial injuring at skin biopsy. Furthermore, the SI-K group showed a higher EDD than the UI-K group (EDD: SI-K 7.8 +/- 4.5% vs. UI-K 0.5 +/- 2.7%, P = 0.02), higher basal NO (SI-K 42.9 +/- 6.5 vs. UI-K 20.2 +/- 6.8 micro mol/l, P = 0.02), and lower levels of vWF (SI-K 138.6 +/- 15.3 vs. UI-K 180.6 +/- 7.0%, P = 0.02) and DDF (SI-K 0.61 +/- 0.22 vs. UI-K 3.07 +/- 0.68 micro g/ml, P < 0.01). C-peptide-to-creatinine ratio correlated positively with EDD and NO and negatively with vWF and DDF. CONCLUSIONS: Successful islet transplantation improves survival, cardiovascular, and endothelial function in type 1 diabetic kidney-transplanted patient

Edge and face linear vibration welding of wood panels

Edge-to-edge linear vibration welding of particle- board, OSB, MDF and plywood gives better strength than face-to-face panel welding. In general, the edge-to-edge weldline is slightly weaker than the panels itself. The face- to-face weldline is stronger than the strength of the material in the same direction

Surface finishes by mechanically induced wood surface fusion

Mechanically induced vibration wood fusion welding techniques can also be used to obtain wood surface finishes of increased surface hardness and performance in presence of polymerizing unsaturated oils such as sunflower oil, or other polymerizing finishes. Wood surface hardness values more than double than those for the untreated control timber can be obtained by this method. This result is obtained due to two effects induced by the sharp increase in temperature induced by the mechanical welding vibration (i) the polymerization to a hardened network of the unsaturated oil and (ii) the densification proven to occur in the surface layer of the timber during mechanically-induced vibration-welding. The first of these effects predominates at shorter welding times while at slightly longer welding times both effects occur with the second one progressively becoming the bigger contributor. In the latter case the some μm thin densified surface is a surface composite formed by the networked unsaturated oil permeating the wood fibre/fused lignin composite. © Springer-Verlag 2005

Evaluation of the Iatrogenic Sciatic Nerve Injury following Double Pelvic Osteotomy Performed with Piezoelectric Cutting Tool in Dogs

(1) Background: The double pelvic osteotomy (DPO) is a prophylactic surgical procedure associated with 0.4% incidence of sciatic nerve injury. The piezoelectric cutting tool is a surgical device able to involve only mineralized tissue avoiding neurovascular tissue and other soft tissue. This study aimed to evaluate the sciatic nerve injury observed in dogs underwent iliac osteotomy performed using the piezoelectric cutting tool. (2) Methods: Dogs underwent DPO performed with piezoelectric cutting tool were included. Neurological assessment was performed 6 and 24 h after surgery and then repeated 12 days, 4 and 8 weeks after surgery. Temporary and or permanent sciatic nerve injury were recorded. (3) Results: 84 DPOs performed in fifty dogs were included. No temporary/permanent neurological disease associated with iatrogenic damage of the sciatic nerve were observed. (4) Conclusions: The iliac osteotomy performed with piezoelectric cutting tool was not associated to iatrogenic sciatic nerve injury

Case Report: Late-Onset Congenital Adrenal Hyperplasia and Acute Covid-19 Infection in a Pregnant Woman: Multidisciplinary Management

Background The impact of the Covid-19 infection on patients with chronic endocrine disease is not fully known. We describe here the first case of a pregnant woman with Covid-19 acute infection and non-classical congenital adrenal hyperplasia (NCAH). Case description A woman at 36 weeks of gestation was referred to our Maternity Hospital for premature rupture of membranes (PROM). Her medical history was positive for NCAH on chronic steroid replacement till the age of 17 years (cortisone acetate and dexamethasone, both in the morning). At admission, her naso-oro-pharyngeal swab resulted positive for SARS-CoV-2. Due to hyperpyrexia and late preterm PROM, cesarean section was planned, and she was started on a 100 mg-bolus of hydrocortisone, followed by continuous infusion of 200 mg/24 h. A female neonate in good clinical condition and with a negative nasopharyngeal Covid-19 swab was delivered. On second postpartum day, the mother was in good condition and was switched to oral steroid therapy. On third postpartum day she worsened, with radiological signs of acute pulmonary embolism. Oro-tracheal intubation and mechanical ventilation were started, and she was switched back to intravenous steroid therapy. On April 30, pulmonary embolism was resolved, and on May 13th she was discharged in good condition. Conclusions We report the first case of Covid-19 acute infection that occurred in late-pregnancy in a woman with NCAH on chronic steroid replacement. The management of the patient in a reference center with early involvement of a multidisciplinary team granted prompt care and adequate protection for all the involved sanitary operators

Epidural Corticosteroids, Lumbar Spinal Drainage, and Selective Hemodynamic Control for the Prevention of Spinal Cord Ischemia in Thoracoabdominal Endovascular Aortic Repair: A New Clinical Protocol

Introduction: In patients undergoing thoracoabdominal aorta repair, spinal cord ischemia (SCI) remains one of the most common and important complications resulting in transient paraparesis through to permanent flaccid paraplegia. In this manuscript, after a brief introduction to spinal cord ischemia complication and its prevention in thoracoabdominal endovascular aortic repair (TEVAR), we propose a new clinical protocol potentially able to prevent such complication. Methods: The proposed protocol suggests the use of high dosages of corticosteroids by epidural route, along with drainage of cerebrospinal fluid and controlled vascular hypertension, to reduce the incidence of SCI in TEVAR. Moreover, we paid particular attention to the control of the hemodynamic parameters to obtain adequate peripheral tissue perfusion (oxygen delivery), including in the spinal cord. Results: We applied this new protocol in 50 consecutive patients treated with TEVAR for thoracoabdominal aortic aneurysms (TAAs); 47 patients completed the procedure: 27 patients Crawford type I and 20 Crawford type II. Three patients died during surgery because of untreatable aneurysm rupture. The results show that in all patients there were no cases of SCI, after 5 days from TEVAR. Discussion: To the best of our knowledge, there are no clinical studies on the use of epidural corticosteroids in patients undergoing treatment of aortic syndrome (both in "open surgery" and endovascular aortic repair). This initial study on 50 consecutive patients has shown that the clinical protocol used could be of great interest to prevent one of the worse complications of TEVAR. Its limitations are the low number of patients studied till now, and the non-randomized protocol adopted. Further studies would be necessary. Conclusion: Our experience and the results obtained with this new perioperative protocol with epidural corticosteroid and accurate hemodynamic control have been encouraging and it seems a valid proposal to be explored in future by well-structured prospective, randomized protocols.Introduction: In patients undergoing thoracoabdominal aorta repair, spinal cord ischemia (SCI) remains one of the most common and important complications resulting in transient paraparesis through to permanent flaccid paraplegia. In this manuscript, after a brief introduction to spinal cord ischemia complication and its prevention in thoracoabdominal endovascular aortic repair (TEVAR), we propose a new clinical protocol potentially able to prevent such complication. Methods: The proposed protocol suggests the use of high dosages of corticosteroids by epidural route, along with drainage of cerebrospinal fluid and controlled vascular hypertension, to reduce the incidence of SCI in TEVAR. Moreover, we paid particular attention to the control of the hemodynamic parameters to obtain adequate peripheral tissue perfusion (oxygen delivery), including in the spinal cord. Results: We applied this new protocol in 50 consecutive patients treated with TEVAR for thoracoabdominal aortic aneurysms (TAAs); 47 patients completed the procedure: 27 patients Crawford type I and 20 Crawford type II. Three patients died during surgery because of untreatable aneurysm rupture. The results show that in all patients there were no cases of SCI, after 5 days from TEVAR. Discussion: To the best of our knowledge, there are no clinical studies on the use of epidural corticosteroids in patients undergoing treatment of aortic syndrome (both in “open surgery” and endovascular aortic repair). This initial study on 50 consecutive patients has shown that the clinical protocol used could be of great interest to prevent one of the worse complications of TEVAR. Its limitations are the low number of patients studied till now, and the non-randomized protocol adopted. Further studies would be necessary. Conclusion: Our experience and the results obtained with this new perioperative protocol with epidural corticosteroid and accurate hemodynamic control have been encouraging and it seems a valid proposal to be explored in future by well-structured prospective, randomized protocols