Uncontrolled diabetes and healthcare utilisation: a bivariate Latent Markov model

Although uncontrolled diabetes (UD) or poor glycaemic control is a widespread condition with potentially life‐threatening consequences, there is sparse evidence of its effects on health care utilisation. We jointly model the propensities to consume health care and UD by employing an innovative bivariate latent Markov model that allows for dynamic unobserved heterogeneity, movements between latent states and the endogeneity of UD. We estimate the effects of UD on primary and secondary health care consumption using a panel dataset of rich administrative records from Spain and measure UD using a biomarker. We find that, conditional on time‐varying unobservables, UD does not have a statistically significant direct effect on health care use (...

Uncontrolled diabetes and health care utilisation: a bivariate Latent Markov model approach [WP]

While uncontrolled diabetes (UD) or poor glycaemic control is a widespread condition with potentially life-threatening consequences, there is sparse evidence of its effects on health care utilisation. We model the propensities to consume health care and UD by employing an innovative bivariate Latent Markov model which allows for dynamic unobserved heterogeneity, movements between latent states and the endogeneity of UD. We estimate the effects of UD on primary and secondary Health care consumption using a panel dataset of rich administrative records from Spain and measure UD using a biomarker. We find that UD does not have a statistically significant effect on health care use. Furthermore, individuals appear to move across latent classes and increase their propensities to poor glycaemic control and health care use over time. Our results suggest that by ignoring time-varying unobserved heterogeneity and the endogeneity of UD, the effects of UD on health care utilisation might be overestimated and this could lead to biased findings. Our approach reveals heterogeneity in behaviour beyond standard groupings of frequent versus infreqüent users of health care services. We argue that this dynamic latent Markov approach could be used more widely to model the determinants of health care use

On the Oligomeric State of DJ-1 Protein and Its Mutants Associated with Parkinson Disease A COMBINED COMPUTATIONAL AND IN VITRO STUDY

Mutations in the DJ-1 protein are present in patients suffering from familial Parkinson disease. Here we use computational methods and biological assays to investigate the relationship between DJ-1 missense mutations and the protein oligomeric state. Molecular dynamics calculations suggest that: (i) the structure of DJ-1 wild type (WT) in aqueous solution, in both oxidized and reduced forms, is similar to the crystal structure of the reduced form; (ii) the Parkinson disease-causing M26I variant is structurally similar to the WT, consistent with the experimental evidence showing the protein is a dimer as WT; (iii) R98Q is structurally similar to the WT, consistent with the fact that this is a physiological variant; and (iv) the L166P monomer rapidly evolves toward a conformation significantly different from WT, suggesting a change in its ability to oligomerize. Our combined computational and experimental approach is next used to identify a mutant (R28A) that, in contrast to L166P, destabilizes the dimer subunit-subunit interface without significantly changing secondary structure elements

Characterisation of Formaggella della Valle di Scalve Cheese Produced From Cows Reared in Valley Floor Stall or in Mountain Pasture: Fatty Acids Profile and Sensory Properties

An important problem in mountain areas is the abandonment of pasture. This trend can be combated by the valorisation of typical dairy products, such as "Formaggella della Valle di Scalve", a semi-cooked traditional cheese made from whole milk in a mountain area in Italy. The aim of the present research was to compare the fatty acid (FA) profile and the sensory properties of this cheese as manufactured under different conditions: i) from the milk of cows grazing on mountain or valley pasture or fed indoors; ii) from the milk of cows fed hay or fed silage. In the first case, five cheesemaking trials were conducted during two years for each of the following situations: mountain pasture (A); pasture at the bottom of the valley (P) (about 1000m asl); stall (S). In the second case, three cheesemaking trials were conducted for each of the following situations: cows fed silage (I); cows fed hay (F). S cheese was richer in medium-chain FAs, while long-chain FAs were higher in P and A cheeses. On the other hand, long chain fatty acids (LCFA) were more abundant in P and A cheeses than in S. In general, MUFA, PUFA and, consequently, total unsaturated FA (UFA), were significantly higher in the P and A cheeses than S (UFA: 36.55 and 38.34, respectively, vs 31.13; p < 0.001), while SFA showed higher values in S (68.85 vs 63.41 and 61.68 in P and A, respectively; p < 0.001). Conjugated linoleic acid isomers (CLA) were more represented in the P and A samples (1.86 in P and 1.52 in A, vs 0.80 in S; p < 0.001); Omega 3 fatty acids, and in particular α-linolenic acid, were more abundant in P than in S cheese. In winter, the I sample (silage) presented higher percentages of myristic (C14), myristoleic (C14:1) and omega 6 acids, whereas F cheese (hay) contained higher concentrations of CLA. The triangular test of sensory analysis showed that, in general, F cheeses were judged as "sweeter" than I, with aromatic profiles characterized by higher content of 2- butanol and ethyl capronate

An EEG-fMRI Study on the Termination of Generalized Spike-And-Wave Discharges in Absence Epilepsy

INTRODUCTION: Different studies have investigated by means of EEG-fMRI coregistration the brain networks related to generalized spike-and-wave discharges (GSWD) in patients with idiopathic generalized epilepsy (IGE). These studies revealed a widespread GSWD-related neural network that involves the thalamus and regions of the default mode network. In this study we investigated which brain regions are critically involved in the termination of absence seizures (AS) in a group of IGE patients. METHODS: Eighteen patients (6 male; mean age 25 years) with AS were included in the EEG-fMRI study. Functional data were acquired at 3T with continuous simultaneous video-EEG recording. Event-related analysis was performed with SPM8 software, using the following regressors: (1) GSWD onset and duration; (2) GSWD offset. Data were analyzed at single-subject and at group level with a second level random effect analysis. RESULTS: A mean of 17 events for patient was recorded (mean duration of 4.2 sec). Group-level analysis related to GSWD onset respect to rest confirmed previous findings revealing thalamic activation and a precuneus/posterior cingulate deactivation. At GSWD termination we observed a decrease in BOLD signal over the bilateral dorsolateral frontal cortex respect to the baseline (and respect to GSWD onset). The contrast GSWD offset versus onset showed a BOLD signal increase over the precuneus-posterior cingulate region bilaterally. Parametric correlations between electro-clinical variables and BOLD signal at GSWD offset did not reveal significant effects. CONCLUSION: The role of the decreased neural activity of lateral prefrontal cortex at GSWD termination deserve future investigations to ascertain if it has a role in promoting the discharge offset, as well as in the determination of the cognitive deficits often present in patients with AS. The increased BOLD signal at precuneal/posterior cingulate cortex might reflect the recovery of neural activity in regions that are "suspended" during spike and waves activity, as previously hypothesized

An integrated metabolomics approach for the research of new cerebrospinal fluid biomarkers of multiple sclerosis

(1) Lipid profiling in MuS and OND patients. (2) Search of alterations associated with MuS. (3) Characterization of differences

Eight Weddings and Six Funerals: An fMRI Study on Autobiographical Memories

“Autobiographical memory” (AM) refers to remote memories from one's own life. Previous neuroimaging studies have highlighted that voluntary retrieval processes from AM involve different forms of memory and cognitive functions. Thus, a complex and widespread brain functional network has been found to support AM. The present functional magnetic resonance imaging (fMRI) study used a multivariate approach to determine whether neural activity within the AM circuit would recognize memories of real autobiographical events, and to evaluate individual differences in the recruitment of this network. Fourteen right-handed females took part in the study. During scanning, subjects were presented with sentences representing a detail of a highly emotional real event (positive or negative) and were asked to indicate whether the sentence described something that had or had not really happened to them. Group analysis showed a set of cortical areas able to discriminate the truthfulness of the recalled events: medial prefrontal cortex, posterior cingulate/retrosplenial cortex, precuneus, bilateral angular, superior frontal gyri, and early visual cortical areas. Single-subject results showed that the decoding occurred at different time points. No differences were found between recalling a positive or a negative event. Our results show that the entire AM network is engaged in monitoring the veracity of AMs. This process is not affected by the emotional valence of the experience but rather by individual differences in cognitive strategies used to retrieve AMs

Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules

BACKGROUND: The mesencephalic dopaminergic (mDA) cell system is composed of two major groups of projecting cells in the Substantia Nigra (SN) (A9 neurons) and the Ventral Tegmental Area (VTA) (A10 cells). Selective degeneration of A9 neurons occurs in Parkinson's disease (PD) while abnormal function of A10 cells has been linked to schizophrenia, attention deficit and addiction. The molecular basis that underlies selective vulnerability of A9 and A10 neurons is presently unknown. RESULTS: By taking advantage of transgenic labeling, laser capture microdissection coupled to nano Cap-Analysis of Gene Expression (nanoCAGE) technology on isolated A9 and A10 cells, we found that a subset of Olfactory Receptors (OR)s is expressed in mDA neurons. Gene expression analysis was integrated with the FANTOM5 Helicos CAGE sequencing datasets, showing the presence of these ORs in selected tissues and brain areas outside of the olfactory epithelium. OR expression in the mesencephalon was validated by RT-PCR and in situ hybridization. By screening 16 potential ligands on 5 mDA ORs recombinantly expressed in an heterologous in vitro system, we identified carvone enantiomers as agonists at Olfr287 and able to evoke an intracellular Ca2+ increase in solitary mDA neurons. ORs were found expressed in human SN and down-regulated in PD post mortem brains. CONCLUSIONS: Our study indicates that mDA neurons express ORs and respond to odor-like molecules providing new opportunities for pharmacological intervention in disease

Observation of Exclusive Gamma Gamma Production in p pbar Collisions at sqrt{s}=1.96 TeV

We have observed exclusive \gamma\gamma production in proton-antiproton collisions at \sqrt{s}=1.96 TeV, using data from 1.11 \pm 0.07 fb^{-1} integrated luminosity taken by the Run II Collider Detector at Fermilab. We selected events with two electromagnetic showers, each with transverse energy E_T > 2.5 GeV and pseudorapidity |\eta| < 1.0, with no other particles detected in -7.4 < \eta < +7.4. The two showers have similar E_T and azimuthal angle separation \Delta\phi \sim \pi; 34 events have two charged particle tracks, consistent with the QED process p \bar{p} to p + e^+e^- + \bar{p} by two-photon exchange, while 43 events have no charged tracks. The number of these events that are exclusive \pi^0\pi^0 is consistent with zero and is < 15 at 95% C.L. The cross section for p\bar{p} to p+\gamma\gamma+\bar{p} with |\eta(\gamma)| < 1.0 and E_T(\gamma) > 2.5$ GeV is 2.48^{+0.40}_{-0.35}(stat)^{+0.40}_{-0.51}(syst) pb.Comment: 7 pages, 4 figure

Effects of Pin1 Loss in Hdh(Q111) Knock-in Mice

Huntington's disease (HD) is a fatal, dominantly inherited, neurodegenerative disorder due to a pathological expansion of the CAG repeat in the coding region of the HTT gene. In the quest for understanding the molecular basis of neurodegeneration, we have previously demonstrated that the prolyl isomerase Pin1 plays a crucial role in mediating p53-dependent apoptosis triggered by mutant huntingtin (mHtt) in vitro. To assess the effects of the lack of Pin1 in vivo, we have bred Pin1 knock-out mice with Hdh(Q111) knock-in mice, a genetically precise model of HD. We show that Pin1 genetic ablation modifies a portion of Hdh(Q111) phenotypes in a time-dependent fashion. As an early event, Pin1 activity reduces the DNA damage response (DDR). In midlife mice, by taking advantage of next-generation sequencing technology, we show that Pin1 activity modulates a portion of the alterations triggered by mHtt, extending the role of Pin1 to two additional Hdh(Q111) phenotypes: the unbalance in the "synthesis/concentration of hormones", as well as the alteration of "Wnt/\u3b2-catenin signaling". In aging animals, Pin1 significantly increases the number of mHtt-positive nuclear inclusions while it reduces gliosis. In summary, this work provides further support for a role of Pin1 in HD pathogenesis. \ua9 2016 Agostoni, Michelazzi, Maurutto, Carnemolla, Ciani, Vatta, Roncaglia, Zucchelli, Leanza, Mantovani, Gustincich, Santoro, Piazza, Del Sal and Persichetti