Proteinuria in focal segmental glomerulosclerosis: role of circulating factors and therapeutic approach.

The clinical course of primary Focal Segmental Glomerulosclerosis (FSGS) is frequently complicated by nephrotic range proteinuria and progression to renal failure. The high recurrence rate of the disease in transplanted kidney suggests the hypothesis that such patients have a circulating factor that alters glomerular capillary permeability. In recent years some authors found that serum from patients with FSGS increases glomerular permeability to albumin and partially identified the permeability factor (PF) as a protein of 30-50 Kd m.w. The removal of this protein by means of Plasma Exchange (PE) or plasma Immunoadsorption by Protein A (IA) decreased proteinuria. In this report we provide preliminary data about the prevalence of PF and the therapeutic effect of its removal by IA, in 3 pts with recurrence in the transplanted kidney, and 4 with FSGS of the native kidneys. They were resistant to corticosteroids (CS) and immunosuppressive (IS) therapy. 10 IA sessions were performed in 4 weeks: if a remission was achieved IA was gradually tapered. The level of PF in the serum was measured by an in vitro assay to determine the glomerular permeability to albumin. The FSGS was histologically proven in all cases and the degree of evolution was evaluated. PF levels, serum creatinine, daily proteinuria and serum albumin were monitored. The 3 patients with recurrent FSGS had a normalization of the PF levels; 2 had a clinical remission. In FSGS of native kidneys PF was elevated in 3/4 cases; 1 had a clinical remission; 2 with extensive sclerohyalinosis and 1 without PF levels did not improve. Our results confirm that most patients with FSGS have high PF serum levels and suggest that its removal can be beneficial

Assessing the Personality Profile of Patients with Fibromyalgia Syndrome: A Rorschach Study

Background: The role that psychological factors and personality traits play in the pathogenesis of Fibromyalgia Syndrome (FMS) is currently controversial. Most of the studies on FMS used self-report measures, and to date only a doctoral dissertation was conducted to compare the Rorschach responses of patients with FMS to the normative sample. Aim and Method: By using the Rorschach Performance Assessment System (R-PAS), we compared the scores of 35 women with FMS with those of 35 women with rheumatoid arthritis (RA). R-PAS is a performance-based task able to provide information on psychological processes occurring in the context outside and beyond the test. Furthermore, we chose RA patients as a contrast group because they both share the same medical picture in terms of pain experiences. Results: Compared to the RA group, the FMS group seemed to experience considerable implicit distress (YTVC’) associated with a sense of helplessness and despair (Y) that interferes with coping and adaptive mechanisms. Moreover, we found that these patients showed a cognitive processing focused mostly on the straightforward components of the environment (SI and Sy), but the interpretation of the environment was more unconventional (FQo%). Finally, we observed that almost half of the FMS group exhibited an excessive worry on the body (An). Conclusions: Our study has two implications for practicing psychologists. First, by using a performance-based test such as the R-PAS, we were able to provide a different clinical picture than self-reports (e.g., we did not find alexithymia features in the FMS protocols) and to identify the problematic features even at different levels of Complexity. Second, the increased levels of implicit stress found in the FMS group require psychological interventions focused on empowering these patients with self-management, active coping strategies when dealing with stressors and pain, so to defy their sense of helplessness

Insight into the mechanism of ferroptosis inhibition by ferrostatin-1

Ferroptosis is a form of cell death primed by iron and lipid hydroperoxides and prevented by GPx4. Ferrostatin-1 (fer-1) inhibits ferroptosis much more efficiently than phenolic antioxidants. Previous studies on the antioxidant efficiency of fer-1 adopted kinetic tests where a diazo compound generates the hydroperoxyl radical scavenged by the antioxidant. However, this reaction, accounting for a chain breaking effect, is only minimally useful for the description of the inhibition of ferrous iron and lipid hydroperoxide dependent peroxidation. Scavenging lipid hydroperoxyl radicals, indeed, generates lipid hydroperoxides from which ferrous iron initiates a new peroxidative chain reaction. We show that when fer-1 inhibits peroxidation, initiated by iron and traces of lipid hydroperoxides in liposomes, the pattern of oxidized species produced from traces of pre-existing hydroperoxides is practically identical to that observed following exhaustive peroxidation in the absence of the antioxidant. This supported the notion that the anti-ferroptotic activity of fer-1 is actually due to the scavenging of initiating alkoxyl radicals produced, together with other rearrangement products, by ferrous iron from lipid hydroperoxides. Notably, fer-1 is not consumed while inhibiting iron dependent lipid peroxidation. The emerging concept is that it is ferrous iron itself that reduces fer-1 radical. This was supported by electroanalytical evidence that fer-1 forms a complex with iron and further confirmed in cells by fluorescence of calcein, indicating a decrease of labile iron in the presence of fer-1. The notion of such as pseudo-catalytic cycle of the ferrostatin-iron complex was also investigated by means of quantum mechanics calculations, which confirmed the reduction of an alkoxyl radical model by fer-1 and the reduction of fer-1 radical by ferrous iron. In summary, GPx4 and fer-1 in the presence of ferrous iron, produces, by distinct mechanism, the most relevant anti-ferroptotic effect, i.e the disappearance of initiating lipid hydroperoxides

The robe of the nurse in patients at risk of suicide

openQuesta tesi affronterá l'argomento del suicidio e dell'importanza del ruolo dell'infermiere nel prevenire tale azione

Acute coronary syndrome associated with alemtuzumab infusion in multiple sclerosis

no abstract availabl

Glutathione peroxidase 4-catalyzed reduction of lipid hydroperoxides in membranes: The polar head of membrane phospholipids binds the enzyme and addresses the fatty acid hydroperoxide group toward the redox center

GPx4 is a monomeric glutathione peroxidase, unique in reducing the hydroperoxide group (-OOH) of fatty acids esterified in membrane phospholipids. This reaction inhibits lipid peroxidation and accounts for enzyme's vital role. Here we investigated the interaction of GPx4 with membrane phospholipids. A cationic surface near the GPx4 catalytic center interacts with phospholipid polar heads. Accordingly, SPR analysis indicates cardiolipin as the phospholipid with maximal affinity to GPx4. Consistent with the electrostatic nature of the interaction, KCl increases the KD. Molecular dynamic (MD) simulation shows that a -OOH posed in the core of the membrane as 13 - or 9 -OOH of tetra-linoleoyl cardiolipin or 15 -OOH stearoyl-arachidonoyl-phosphaphatidylcholine moves to the lipid-water interface. Thereby, the -OOH groups are addressed toward the GPx4 redox center. In this pose, however, the catalytic site facing the membrane would be inaccessible to GSH, but the consecutive redox processes facilitate access of GSH, which further primes undocking of the enzyme, because GSH competes for the binding residues implicated in docking. During the final phase of the catalytic cycle, while GSSG is produced, GPx4 is disconnected from the membrane. The observation that GSH depletion in cells induces GPx4 translocation to the membrane, is in agreement with this concept

Teleradiology for remote consultation using iPad improves the use of health system human resources for paediatric fractures: prospective controlled study in a tertiary care hospital in Italy

Background The growing cost of health care and lack of specialised staff have set e-Health high on the European political agenda. In a prospective study we evaluated the effect of providing images for remote consultation through an iPad on the number of in-hospital orthopaedic consultations for children with bone fractures. Methods Children from 0 to 18 years diagnosed with a bone fracture by the radiologist during the hours when an orthopaedic service is provided only on-call were eligible for enrollment. Cases were enrolled prospectively during September and October 2013. A standard approach (verbal information only, no X-Ray provided remotely) was compared to an experimental approach (standard approach plus the provision of X-ray for remote consultation through an iPad). The primary outcome was the number of orthopaedic in-hospital consultations that occurred. Other outcomes included: immediate activation of other services; time needed for decision-making; technical difficulties; quality of images and diagnostic confidence (on a likert scale of 1 to 10). Results Forty-two children were enrolled in the study. Number of in-hospital consultancies dropped from 32/42 (76.1%) when no X-ray was provided to 16/42 (38%) when the X-rays was provided (p < 0.001). With remote X-ray consultation in 14/42 (33.3%) cases services such as surgery and plaster room could be immediately activated, compared to no service activated without teleradiology (p < 0.001). Average time for decision making was 23.4 \ub1 21.8 minutes with remote X-ray consultation, compared to 56.2 \ub1 16.1 when the X-ray was not provided (p < 0.001). The comparison between images on the iPad and on the standard system for X- Ray visualisation resulted in a non statistically significant difference in the quality of images (average score 9.89 \ub1 0.37 vs 9.91 \ub1 0.30; p =0.79), and in non statistically significant difference in diagnostic confidence (average score 9.91 \ub1 0.32 vs 9.92 \ub1 0.31; p = 0.88). Conclusions Remote X-ray consultation through Aycan OsiriX PRO and iPad should be considered as a means for reducing the need of in-hospital orthopaedic consultation during on-call times, and potentially decrease the cost of care for the health system. In the future, alternative systems less expensive than Aycan OsiriX PRO should be further developed and tested

Temperature behavior of the (sqrt3 x sqrt3)R30-1CO and the (2 x 2)-3CO overlayers on Rh(111): A combined HAS and LEED investigation

The order-disorder phase transition of the Rh(111)-(√3 x √3)R30°-CO phase was investigated by He scattering. The critical temperature turned out to be 330±5 K, while the critical exponents are consistent with a phase transition belonging to the 3-state Potts universality class. The temperature dependence below the critical temperature of both CO phases was studied using elastic He scattering and LEED. These measurements demonstrate that a simple Debye-Waller evaluation of the diffraction data is not appropriate to provide information on the vibrational properties of the CO molecules. From LEED measurements at low temperatures (<70 K) and various CO partial pressures there is evidence of the formation of a disordered second CO layer in equilibrium with the gas phase. The isosteric heat of CO adsorption in the second layer is about 6 kJ mol-