Ultrametric identities in glassy models of natural evolution

Spin-glasses constitute a well-grounded framework for evolutionary models. Of particular interest for (some of) these models is the lack of self-averaging of their order parameters (e.g. the Hamming distance between the genomes of two individuals), even in asymptotic limits, much as like what happens to the overlap between the configurations of two replica in mean-field spin-glasses. In the latter, this lack of self-averaging is related to a peculiar behavior of the overlap fluctuations, as described by the Ghirlanda–Guerra identities and by the Aizenman–Contucci polynomials, that cover a pivotal role in describing the ultrametric structure of the spin-glass landscape. As for evolutionary mod- els, such identities may therefore be related to a taxonomic classification of individuals, yet a full investigation on their validity is missing. In this paper, we study ultrametric identities in simple cases where solely random mutations take place, while selective pressure is absent, namely in flat landscape models. In particular, we study three paradigmatic models in this setting: the one parent model (which, by construction, is ultrametric at the level of single individu- als), the homogeneous population model (which is replica symmetric), and the species formation model (where a broken-replica scenario emerges at the level of species). We find analytical and numerical evidence that in the first and in the third model nor the Ghirlanda–Guerra neither the Aizenman–Contucci constraints hold, rather a new class of ultrametric identities is satisfied; in the second model all these constraints hold trivially. Very preliminary results on a real biological human genome derived by The 1000 Genome Project Consortium and on two artificial human genomes (generated by two different types neural networks) seem in better agreement with these new identities rather than the classic ones

Tribological behaviour of Ti or Ti alloy vs. zirconia in presence of artificial saliva

Abutment is the transmucosal component in a dental implant system and its eventual appearance has a major impact on aesthetics: use of zirconia abutments can be greatly advantageous in avoiding this problem. Both in the case of one and two-piece zirconia abutments, a critical issue is severe wear between the zirconia and titanium components. High friction at this interface can induce loosening of the abutment connection, production of titanium wear debris, and finally, peri-implant gingivitis, gingival discoloration, or marginal bone adsorption can occur. As in vivo wear measurements are highly complex and time-consuming, wear analysis is usually performed in simulators in the presence of artificial saliva. Different commercial products and recipes for artificial saliva are available and the effects of the different mixtures on the tribological behaviour is not widely explored. The specific purpose of this research was to compare two types of artificial saliva as a lubricant in titanium-zirconia contact by using the ball on disc test as a standard tribological test for materials characterisation. Moreover, a new methodology is suggested by using electrokinetic zeta potential titration and contact angle measurements to investigate the chemical stability at the titanium-lubricant interface. This investigation is of relevance both in the case of using zirconia abutments and artificial saliva against chronic dry mouth. Results suggest that an artificial saliva containing organic corrosion inhibitors is able to be firmly mechanically and chemically adsorb on the surface of the Ti c.p. or Ti6Al4V alloy and form a protective film with high wettability. This type of artificial saliva can significantly reduce the friction coefficient and wear of both the titanium and zirconia surfaces. The use of this type of artificial saliva in standard wear tests has to be carefully considered because the wear resistance of the materials can be overestimated while it can be useful in some specific clinical applications. When saliva is free from organic corrosion inhibitors, wear occurs with a galling mechanism. The occurrence of a super-hydrophilic saliva film that is not firmly adsorbed on the surface is not efficient in order to reduce wear. The results give both suggestions about the experimental conditions for lab testing and in vivo performance of components of dental implants when artificial saliva is used

Resolving sphincter of Oddi incontinence for primary duodenal Crohn's disease with strictureplasty

AbstractINTRODUCTIONCrohn's involvement of duodenum is a rare event and may be associated to proteiform symptoms and uncommon pathological aspects which make diagnosis and treatment complex.PRESENTATION OF CASEThe peculiar aspect of this case was a suspected duodeno-biliary fistula. The patient (female, 22 years old) was affected by duodenal Crohn's disease. Magnetic resonance imaging showed a dilated common bile duct, whose final part linked to a formation containing fluid, and characterized by filling of the contrast medium in the excretory phase. Abdominal ultrasound showed intra-hepatic and intra-gallbladder aerobilia. At surgery, the duodenum was mobilized showing an inflammatory stricture and a slight dilatation of the common bile duct, with no signs of fistulas. The opened duodenum was anastomized side to side to a transmesocolic loop of the jejunum. After surgery, the general condition of the patient improved.DISCUSSIONOnly two cases of fistula between a narrow duodenal bulb and the common bile duct have been described in literature and the Authors were not be able to verify the occurrence of a duodenal biliary fistula at surgery. The association between duodenal Crohn's disease and Sphincter of Oddi incontinence is a very rare finding with different etiology: chronic intestinal pseudo-obstruction, common bile duct stones, progressive systemic sclerosis.CONCLUSIONThe treatment to resolve Sphincter of Oddi incontinence for primary duodenal Crohn's disease is not clear. Strictureplasty could be the treatment of choice, because, resolving the stricture, the duodenal pressure is likely to decrease and the reflux through the incontinent sphincter can be avoided

MRP4 over-expression has a role on both reducing nitric oxide-dependent antiplatelet effect and enhancing ADP induced platelet activation

The impact of inhibition of multidrug resistance protein 4 (MRP4) on nitric oxide (NO) resistance and on ADP-induced platelet aggregation is unknown. The aim of this investigation was to verify whether platelet NO resistance correlates with MRP4 expression and evaluate whether this can be reduced by in vitro MRP4 inhibition mediated by cilostazol. Moreover, we assessed if inhibition of MRP4-mediated transport reduces ADP-induced platelet reactivity. The inhibitory effect of sodium nitroprusside (SNP), a NO-donor that enhances cyclic guanosine monophosphate (cGMP) cytosolic concentration, was assessed in platelets obtained from aspirin treated patients and in a control population. The inhibitory effect of SNP was evaluated by ADP-induced aggregation in SNP-treated platelets. The impact of MRP4 on ADP-induced platelet aggregation was performed in high on aspirin residual platelet reactivity (HARPR) patients and compared to healthy volunteers (HV), and a control cohort (CTR). In aspirin-treated patients with high levels of MRP4, reduced SNP inhibition was found compared to those with low levels of MRP4. MRP4 inhibition by cilostazol significantly reduced ADP-induced platelet aggregation in HARPR population, and to a lesser extent in HV and CTR populations. In conclusion, cilostazol can mitigate the hyper-reactive platelet phenotype of HARPR patients by reducing residual ADP-induced platelet aggregation and increasing NO-dependent endothelial antiplatelet effects

Pregnancy, Proteinuria, Plant-Based Supplemented Diets and Focal Segmental Glomerulosclerosis: A Report on Three Cases and Critical Appraisal of the Literature.

Chronic kidney disease (CKD) is increasingly recognized in pregnant patients. Three characteristics are associated with a risk of preterm delivery or small for gestational age babies; kidney function reduction, hypertension, and proteinuria. In pregnancy, the anti-proteinuric agents (ACE–angiotensin converting enzyme-inhibitors or ARBS -angiotensin receptor blockers) have to be discontinued for their potential teratogenicity, and there is no validated approach to control proteinuria. Furthermore, proteinuria usually increases as an effect of therapeutic changes and pregnancy-induced hyperfiltration. Based on a favourable effect of low-protein diets on proteinuria and advanced CKD, our group developed a moderately protein-restricted vegan-vegetarian diet tsupplemented with ketoacids and aminoacids for pregnant patients. This report describes the results obtained in three pregnant patients with normal renal function, nephrotic or sub-nephrotic proteinuria, and biopsy proven diagnosis of focal segmental glomerulosclerosis, a renal lesion in which hyperfiltration is considered of pivotal importance (case 1: GFR (glomerular filtration rate): 103 mL/min; proteinuria 2.1 g/day; albumin 3.2 g/dL; case 2: GFR 86 mL/min, proteinuria 3.03 g/day, albumin 3.4 g/dL; case 3: GFR 142 mL/min, proteinuria 6.3 g/day, albumin 3.23 g/dL). The moderately restricted diet allowed a stabilisation of proteinuria in two cases and a decrease in one. No significant changes in serum creatinine and serum albumin were observed. The three babies were born at term (38 weeks + 3 days, female, weight 3180 g-62th centile; 38 weeks + 2 days, female, weight 3300 g-75th centile; male, 38 weeks + 1 day; 2770 g-8th centile), thus reassuring us of the safety of the diet. In summary, based on these three cases studies and a review of the literature, we suggest that a moderately protein-restricted, supplemented, plant-based diet might contribute to controlling proteinuria in pregnant CKD women with focal segmental glomerulosclerosis. However further studies are warranted to confirm the potential value of such a treatment strategy

Evaluation of the diagnostic accuracy of three memory tests for early Alzheimer's disease (pe-2013-02356465) : a preliminary report

Aims: The main aim of this multicentric longitudinal project is to investigate the specificity and sensitivity of three memory tests (FCSRT, STMBT, DMS48) proposed as cognitive marker for Alzheimer's disease (AD). Here, we report preliminary baseline data on healthy controls, people with MCI and patients with AD. Subjects and methods: Data collected on 13 AD, 16 MCI, 16 healthy older (HO) and 16 healthy younger (HY) adults were analysed. All participants underwent the three experimental tests along with a standard neuropsychological evaluation in one single session. Results: For the FCSRT, a three-way ANOVA with GROUP as the between-subjects factor and TASK (free, cued) and TIME (immediate, delayed) as within-subjects measures revealed a significant effect of GROUP (HY = HO > MCI > AD; p free, ; p delayed; p MCI > AD; p paired = abstract; p HO > MCI > AD; p 3; p binding; p< .001) and a significant interaction between STIMULUS and GROUP (p= .003). Discussion: The present report study shows reports for the first time a comparison across Controls, MCI and AD on three memory tests proposed as cognitive markers for AD. For the FCSRT both the timing of recall and the presence of a cue are relevant factors to influence patient performances. For the DMS48 the most sensitive indexes to differentiate between controls and patients are the unpaired and abstract items, while for the STMBT the binding condition is more affected in patients are regardless of the number of items presented are. These preliminary data are encouraging in confirming that these tests may offer an aid to diagnosis of early AD, but a larger sample and longitudinal data are needed to address the main research question of this planned study. *** References: Barbeau, E, Didic, M, Tramoni, E, Felician, O, Joubert, S, Sontheimer, A, Ceccaldi, M, Poncet, M. (2004). Evaluation of visual recognition memory in MCI patients. Neurology 62, 1317-1322. Frasson P, Ghiretti R, Catricala E, Pomati S, Marcone A, Parisi L, Rossini PM, Cappa SF, Mariani C, Vanacore N, Clerici F (2011) Free and cued selective reminding test: an Italian normative study. Neurological Sciences 32:1057-1062 Parra MA, Abrahams S, Fabi K, Logie R, Luzzi S, Della Sala S (2009) Short-term memory binding deficits in Alzheimer's disease. Brain 132:1057-106

Vegan-vegetarian low-protein supplemented diets in pregnant CKD patients: fifteen years of experience

Background: Pregnancy in women with advanced CKD becoming increasingly common. However, experience with low-protein diets in CKD patients in pregnancy is still limited. Aim of this study is to review the results obtained over the last 15 years with moderately restricted low-protein diets in pregnant CKD women (combining: CKD stages 3-5, proteinuria: nephrotic at any time, or &gt; =1 g/24 at start or referral; nephrotic in previous pregnancy). CKD patients on unrestricted diets were employed for comparison. Methods: Study period: January, 2000 to September, 2015: 36 on-diet pregnancies (31 singleton deliveries, 3 twin deliveries, 1 pregnancy termination, 1 miscarriage); 47 controls (42 singleton deliveries, 5 miscarriages). The diet is basically vegan; since occasional milk and yoghurt are allowed, we defined it vegan-vegetarian; protein intake (0.6-0.8 g/Kg/day), keto-acid supplementation, protein-unrestricted meals (1-3/week) are prescribed according to CKD stage and nutritional status. Statistical analysis was performed as implemented on SPSS. Results: Patients and controls were similar (p: ns) at baseline with regard to age (33 vs 33.5), referral week (7 vs 9), kidney function (CKD 3-5: 48.4 % vs 64.3 %); prevalence of hypertension (51.6 % vs 40.5 %) and proteinuria &gt;3 g/24 h (16.1 % vs 12.2 %). There were more diabetic nephropathies in on-diet patients (on diet: 31.0 % vs controls 5.3 %; p 0.007 (Fisher)) while lupus nephropathies were non-significantly higher in controls (on diet: 10.3 % vs controls 23.7 %; p 0.28 (Fisher)). The incidence of preterm delivery was similar (&lt;37 weeks: on-diet singletons 77.4 %; controls: 71.4 %). The incidence of other adverse pregnancy related outcomes was non-significantly lower in on-diet patients (early preterm delivery: on diet: 32.3 % vs controls 35.7 %; birth-weight = &lt;1.500 g: on diet: 9.7 % vs controls 23.8 %). None of the singletons in the on-diet series died, while two perinatal deaths occurred among the controls (p = 0.505). The incidence of small for gestational age (SGA &lt;10th centile) and/or extremely preterm babies (&lt;28th week) was significantly lower in singletons from on-diet mothers than in controls (on diet: 12.9 % vs controls: 33.3 %; p: 0.04 (Fisher)). Conclusion: Moderate protein restriction in the context of a vegan-vegetarian supplemented diet is confirmed as a safe option in the management of pregnant CKD patients