PER2 C111G polymorphism, cognitive reserve and cognition in subjective cognitive decline and mild cognitive impairment: a 10-year follow-up study.

BACKGROUND AND PURPOSE: CLOCK and PER2 genes have been implicated in sleep-wake cycle alterations and neurodegenerative diseases. Our aim was to evaluate the effect of CLOCK T3111C and PER2 C111G on cognitive functioning in subjective cognitive decline (SCD) patients and mild cognitive impairment (MCI) patients at the baseline of a longitudinal study, and the effect of these two polymorphisms on the progression to Alzheimer's disease (AD) of the two groups. METHODS: Sixty-eight subjects (41 SCD and 27 MCI) who underwent clinical evaluation, neuropsychological assessment, CLOCK and PER2 genotyping at baseline and neuropsychological follow-up every 2 years for a mean time of 10 years were included. Subjects who developed AD (SCD-c and MCI-c) and non-converters (SCD-nc, MCI-nc) were considered. RESULTS: CLOCK T3111C was detected in 47% of cases (21 SCD, 11 MCI) and PER2 C111G in 19% of cases (eight SCD and five MCI). PER2 G carriers presented lower premorbid intelligence score (P = 0.049), fewer years of education (P = 0.007) and a lower frequency of family history of AD (P = 0.04) than G non-carriers. MCI PER2 G carriers had worse performance in tests assessing memory, executive function, language and visuospatial abilities at baseline. During follow-up, two SCD and 15 MCI subjects progressed to AD: both of the SCD-c subjects presented the PER2 G allele, while none of the SCD PER2 G non-carriers converted to AD (P = 0.003). CONCLUSION: PER2 seems to have a role in cognitive reserve and cognition in SCD and MCI patients. Nevertheless, further studies are needed to assess the role of PER2 C111G on the risk of progression to AD.

Assessing the effectiveness of subjective cognitive decline plus criteria in predicting the progression to Alzheimer's disease: an 11-year follow-up study.

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests and has been shown to increase the risk of Alzheimer's disease (AD). SCD could also be related to other conditions such as normal aging, psychiatric, neurological or medical disorders. The SCD Initiative proposed a set of features (SCD-plus) that increase the likelihood of preclinical AD in individuals with SCD. Our aim was to assess the effect of these features on the risk of conversion from SCD to AD. METHODS: In total 150 SCD subjects who underwent extensive neuropsychological investigation, assessment of cognitive complaints and apolipoprotein E (ApoE) genotyping at baseline and clinical-neuropsychological follow-up for a mean time of 11 years were included. RESULTS: During the follow-up, 20 subjects developed AD. Considering SCD-plus features, age at onset ≥60 years and ApoE ε4 significantly increased the risk of conversion from SCD to AD. When our sample was stratified into three groups (no risk factor, one risk factor, two risk factors), the proportion of conversion was statistically significantly different between the three groups. CONCLUSIONS: Our model allows the risk of AD to be stratified in patients experiencing SCD according to age at onset and ApoE genotype.

Ateneo General de la Residencia de Psicopedagogía: Que no sea Tabú: La sexualidad en la práctica psicopedagógica / General athenaeum of the Psychopedagogy Residence: Not taboo: Sexuality in psychopedagogical practice

Ateneo basado en tres ejes principales: Concepción de sexualidad; Sexualidad a lo largo de la vida, especialmente en los primeros tiempos del sujeto, en la latencia y en la pubertad; y abordaje de la sexualidad en la escuela y en las familias. Este último eje toma en cuenta lineamientos legales, la aplicación de la ley de Educación Sexual Integral en la escuela, el trabajo del equipo de salud proveniente del Área programática del Hospital en los talleres, las representaciones sociales de docentes, padres y alumnos, la sexualidad y educación, y el rol importante de los medios masivos de comunicación.

Viral nano-hybrids for innovative energy conversion and storage schemes.

Typical rod-like viruses (the Tobacco Mosaic Virus (TMV) and the Bacteriophage M13) are biological nanostructures that couple a 1D mono-dispersed morphology with a precisely defined topology of surface spaced and orthogonal reactive domains. These biogenic scaffolds offer a unique alternative to synthetic nano-platforms for the assembly of functional molecules and materials. Spatially resolved 1D arrays of inorganic-organic hybrid domains can thus be obtained on viral nano-templates resulting in the functional arrangement of photo-triggers and catalytic sites with applications in light energy conversion and storage. Different synthetic strategies are herein highlighted depending on the building blocks and with a particular emphasis on the molecular design of viral-templated nano-interfaces holding great potential for the dream-goal of artificial photosynthesis.

Catalytic oxygen production mediated by smart capsules to modulate elastic turbulence under a laminar flow regime.

Liquid flow in microchannels is completely laminar and uniaxial, with a very low Reynolds number regime and long mixing lengths. To increase fluid mixing and solubility of reactants, as well as to reduce reaction time, complex three-dimensional networks inducing chaotic advection have to be designed. Alternatively, turbulence in the liquid can be generated by active mixing methods (magnetic, acoustic waves, etc.) or adding small quantities of elastic materials to the working liquid. Here, polyelectrolyte multilayer capsules embodying a catalytic polyoxometalate complex have been suspended in an aqueous solution and used to create elastic turbulence and to propel fluids inside microchannels as an alternative to viscoelastic polymers. The overall effect is enhanced and controlled by feeding the polyoxometalate-modified capsules with hydrogen peroxide, H2O2, thus triggering an on-demand propulsion due to oxygen evolution resulting from H2O2 decomposition. The quantification of the process is done by analysing some structural parameters of motion such as speed, pressure, viscosity, and Reynolds and Weissenberg numbers, directly obtained from the capillary dynamics of the aqueous mixtures with different concentrations of H2O2. The increases in fluid speed as well as the capsule-induced turbulence effects are proportional to the H2O2 added and therefore dependent on the kinetics of H2O2 dismutation.

Bromide ion exchange with a Keggin polyoxometalate on functionalized polymeric membranes: a theoretical and experimental study.

Noncovalent interactions between the polyoxometalate [PMo12O40](3-) and acryloyloxyundecyltrimethyl ammonium bromide surfactant, used during membrane preparation, were evaluated in the frame of density functional theory. The electronic solvation energy of [PMo12O40](3) and bromide anions was also evaluated, at the same level of theory, in order to predict a probable exchange on the polymeric surface between these anions at the water/polymer interface. Energy balances were theoretically assessed, showing that the bromide cannot be exchanged with this nanosized polyanion in large extent. In order to validate this theoretical conclusion, ad hoc and accurate measurements were carried out by using homemade polymeric membranes and by dipping them in an ca. 0.4 mM solution of Na3[PMo12O40] for 4 days. The Br(-) concentration, released in a polyoxometalate solution, was followed at different times during the test period by gravimetrical analysis. The agreement between the theoretical prediction and experimental data was remarkable, as the quantum calculations correctly accounted for the short-range intermolecular interactions involved in this phenomenon. Bearing in mind that the achieved conclusion is based on an ab initio quantum approach, the findings of this study can be considered rather general and then exploitable for other similar systems.

[Kidney diseases with chronic renal failure in the Italian renal biopsy registries]. / Le nefropatie con insufficienza renale cronica nei registri delle biopsie renali.

The prevalence of chronic renal failure (CRF) at the time of kidney biopsy ranges between 5% and 37% in different renal biopsy registries. This wide variability is mainly dependent on the different definitions of CRF. In the period 1998-2006, the Triveneto Renal Biopsy Registry recorded 816 cases with CRF (defined as serum creatinine persistently > or =1.5 mg/dL), accounting for a prevalence of 27%. At the time of biopsy, the average age and glomerular filtration rate were 54 years and 41 mL/min, respectively; 70% of CRF patients are men and the prevalence of CRF increases with age. IgA nephropathy (IgAN) is the main histological form of glomerulonephritis, accounting for 23% of all cases of CRF. However, in subjects older than 65 years, membranous glomerulonephritis (MG) exceeds IgAN, thus becoming the main diagnosis in elderly patients with renal impairment. With a cutoff value for proteinuria of 3 g/day, the main diagnoses in cases with proteinuria below and above the cutoff are IgAN and MG, respectively. IgAN remains the main histological form of nephropathy throughout all levels of renal failure. These data confirm the findings of the Italian Registry of Renal Biopsies, but correspond only in part with data from other registries. The differences can to a certain extent be explained by the different criteria for the definition of renal impairment, patient selection, and differences in diagnosis among registries.

Prescriptions of NSAIDs to patients undergoing third molar surgery : an observational, prospective, multicentre survey.

BACKGROUND AND OBJECTIVES: Surgical extraction of an impacted third molar is generally followed by acute post-operative pain that has been shown to be primarily inflammatory. Thus, use of NSAIDs in this context is appropriate and has been shown to be effective. Several drugs are employed for this purpose, but no information exists on the reasons why preference is given to one rather than another. The principal objective of this study was to evaluate the pattern of administration of NSAIDs in patients undergoing surgery for impacted third molar extraction. The study also aimed to collect information on the efficacy, onset and duration of the analgesic effect of routinely prescribed NSAIDs and to assess the duration of treatment with these drugs and their tolerability. METHODS: This was an observational, multicentre, prospective survey. A total of 616 patients (38% male and 62% female) from the Italian Stomatology Clinics of the Universities of Bologna, Brescia, Cagliari, Chieti, Pavia, Pisa, Siena and Varese and from the Department of Oral and Maxillo-Facial Surgery of Semmelweis University, Budapest, were eligible for the study. Patients were evaluated over the 7 days following surgical extraction. NSAIDs were prescribed according to the normal prescribing habits of the centre and physician involved. The main outcomes of interest in the survey were the efficacy, onset and duration of analgesic effect, duration of therapy, and tolerability of the NSAIDs prescribed. RESULTS: Nimesulide was the most prescribed NSAID (68%), followed by diclofenac, ketoprofen and ibuprofen. Because of the low proportion of patients receiving other NSAIDs, these patients were considered a single treatment group for evaluation purposes. Nimesulide, especially when given before patients started experiencing pain after surgery, was more effective than other NSAIDs in reducing the severity of pain on the day of surgery, in delaying the time to maximum intensity of pain, in providing complete pain relief and in prolonging the duration of analgesic effect on the day of surgery. These results are consistent with the known anti-inflammatory and analgesic actions of nimesulide and with the important role of inflammation in the onset of pain after this type of surgery. CONCLUSION: These results confirm nimesulide as an effective reference drug for the treatment of post-operative dental pain and show that it has a positive benefit/risk profile in this setting.

[The pathogenetical mechanisms of glomerular proteinuria.]. / Meccanismi patogenetici della proteinuria glomerulare.

Although the pathologic mechanisms responsible for glomerular proteinuria have not been completely clarified, yet, it has become evident that structural and functional abnormalities of podocytes play an early and important role. These data come from recent studies analyzing podocyte behaviour in cell culture, in-depth clinical researches, the application of survey techniques on isolated glomeruli, proteomic studies on particular aspects of circulating factors. For most glomerulopathies, whether primary or secondary, podocytes are often the first target for many pathogenetic mechanisms, which, unexpectedly, have the common characteristic of inducing tropism in podocytes. Hopefully, advances in glomerular podocyte research will better define clinical diseases, which we now classify according to a static description of the histological damage, thus perhaps mistaking causes and effects.

Posttransplant recurrence of proteinuria in a case of focal segmental glomerulosclerosis associated with WT1 mutation.

Posttransplant recurrence of inherited focal segmental glomerulosclerosis (FSGS) is still an enigma owing to the evident paradox of the molecular origin of proteinuria. A young girl with FSGS for WT1 mutation (IVS9+4C>T) and Frasier syndrome received a renal transplant at the age of 11 years. After an initial good outcome with recovery of renal function, proteinuria re-appeared after 7 days and steadily increased up to a nephrotic range. Determination of plasma permeability activity showed concomitant high Palb (0.7). At this point, plasmapheresis was started and after nine cycles with 1500 mL exchange and albumin re-infusion, proteinuria decreased to normal range and is still normal after 3 years. This is the first description of posttransplant recurrence of proteinuria in Frasier syndrome that should be included in potential outcome of renal transplant in this category of patients. This observation confirms the concept that recurrence of proteinuria may occur in inherited forms of FSGS so far reported only for patients carrying NPHS2 mutations and reinforces the idea on multifactorial origin of the disease.

Circulating anti-actin and anti-ATP synthase antibodies identify a sub-set of patients with idiopathic nephrotic syndrome.

Idiopathic nephrotic syndrome (iNS) with resistance or dependence to steroids is a common disease in children but in spite of an increasing clinical impact its pathogenesis is unknown. We screened for the presence of circulating antibodies against glomerular (podocytes, mesangium) and tubular cells (tubular epithelia) a cohort of 60 children with iNS including 8 patients with a familial trait of iNS or with proven mutation of NPHS1-NPHS2 and 12 with good sensitivity to steroids. Positive sera were found in 8 cases, all belonging to the category without familial trait/molecular defects. The targets of antibodies were characterized with Western blot and MALDI-Mass utilizing beta-hexyl cell extracts separated with two-dimensional electrophoresis. In all cases antibodies of the IgM class were directed against ATP synthase beta chain alone (4 cases) or in combination with actin (3 cases); one child presented IgG against aldose reductase. The clinical picture was nephrotic syndrome with steroid resistance or dependence and variable cyclosporin sensitivity; 3 patients developed end stage renal failure. The basic pathology picture was focal segmental glomerulosclerosis (FSGS) in 4 cases and mesangial proliferative glomerulonephrites with deposition of IgM in 2. Overall, patients with circulating auto-antibodies could not be readely differentiated on clinical grounds with the exception of 3 children who developed positivity for antinuclear antibodies during the follow-up. Affinity-purified IgM from one patient who underwent plasmapheresis for therapeutical pourposes (but not from a normal pool) induced proteinuria in Sprague-Dawley rats and concomitant human IgM deposition within glomeruli. This is the first report of circulating anti-actin/ATP synthase beta chain antibodies in a subset of patients with iNS. Both pathological significance and clinical impact given by the presence of these antibodies and the relationship with other conditions such as lupus-erythematosus, characterized by their presence, must be defined.

Modulation of incipient glomerular lesions in experimental diabetic nephropathy by hypotensive and subhypotensive dosages of an ACE inhibitor.

A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects of hypotensive and subhypotensive dosages of the ACE inhibitor quinapril ex vivo and of its active metabolite quinaprilat in vitro on the glomerular albumin permeability (P(alb)) defect in the early phases of experimental diabetes. For the ex vivo study, six groups of male Wistar rats were evaluated for 4 weeks. One group served as a nondiabetic control (C); the other five groups were rendered diabetic and included untreated diabetic rats (D) and diabetic rats receiving quinapril at the dosages of 5 (DQ1), 2.5 (DQ2), 1.25 (DQ3), and 0.625 (DQ4) mg. kg(-1). day(-1). Dosage-dependent effects of quinapril on systolic blood pressure and the glomerular filtration rate were observed. In contrast, control of P(alb) in isolated glomeruli exposed to oncotic gradients, proteinuria, and glomerular and tubular hypertrophy was obtained with subhypotensive dosages (DQ3 and DQ4 groups) of the ACE inhibitor. In the in vitro study, quinaprilat reduced P(alb) significantly in concentration ranges from 10(-6) to 10(-14) mol/l compared with results in control glomeruli. The effect on P(alb) may have occurred by mechanisms different from kidney ACE inhibitor. These study results indicated that ACE inhibitor treatment prevents the early onset of the P(alb) defect in experimental diabetes. This effect seemed to occur independently of systemic or glomerular hemodynamic changes and, at least partially, from kidney ACE inhibition.

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.

Inhibition of renal permeability towards albumin: a new function of apolipoproteins with possible pathogenetic relevance in focal glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a degenerative renal disease characterized by the accumulation of extracellular matrix and lipids within the glomerular tuft. It has been proposed that an abnormal renal permeabilization towards proteins induced by a putative plasma factor is, in some way, involved in the pathogenesis of the disease. In this paper, we measured the plasma permeability activity (Palb) in several sera of patients with FSGS and found a mean activity of 0.82+/-0.03 which means a marked increase compared to a mean Palb of 0.16+/-0.03 in normal controls. Coincubation of FSGS and normal serum reduced the permeability activity within the normal range; normal serum added to the incubation medium after the glomeruli had already been exposed to the FSGS serum had no effect, suggesting the presence of inhibitory substances with a direct effect on a circulating substrate. Finally, the antipermeability activity was retained when heated to 60 degrees C but not to 100 degrees C. By serial fractionations of normal serum and reported activity measurements at each step, five natural occurring inhibitors of albumin permeabilization were purified and characterized by matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS), as components of apolipoproteins (apo) (apo E2 and E4, apo L, the high Mr apo J and a 28 kDa fragment of apo A-IV). Coincubation of each apolipoprotein with FSGS serum inhibited permeability, but only apo J and apo E2 and E4 were found to be crucial for the process. In conclusion, we have purified from normal serum five inhibitors of permeability induced by FSGS serum, all corresponding to apolipoproteins. An imbalance between permeability factors and apolipoproteins may play a pathogenetic role in FSGS.