Efficacy of SSRIs on cognition of Alzheimer's disease patients treated with cholinesterase inhibitors.

Background: This study examines the joint effect on cognition of selective serotonin re-uptake inhibitors (SSRIs) and cholinesterase inhibitors (AChEIs) in depressed patients affected by Alzheimer’s disease (AD) living at home. Methods: The study was conducted in two different outpatient neurological clinics. 338 patients with probable ADwere treated with ChEis (donepezil, rivastigmine and galantamine) as per the clinician’s judgment and were observed for nine months. At study entry, participants underwent a multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All patients were evaluated at baseline, after one (T1), three (T2) and nine months (T3). Patients were grouped in three different categories (patients not depressed and not treated with SSRIs, patients depressed and treated with SSRIs, and patients depressed but not treated with SSRIs). Results: At baseline 182 were diagnosed as not depressed and not treated with SSRIs, 66 as depressed and treated with SSRIs, and 90 as depressed but not treated with SSRIs. The mean change in MMSE score from baseline to nine months showed that depressed patients not treated worsened in comparison with those not depressed and not treated with SSRIs (mean change −0.8±2.3 vs 0.04±2.9; p = 0.02) and patients depressed and treated with SSRI (mean change −0.8±2.3 vs 0.1±2.5; p = 0.03). Conclusions: In AD patients treated with AChEIs, SSRIs may exert some degree of protection against the negative effects of depression on cognition

Leading impactful research: applying platform thinking to drive collaborative inquiry in the innovation field

Purpose This study investigates the application of collaborative inquiry within innovation management, employing platform thinking to address challenges of generalizability and relevance. The aim is to integrate Collaborative Inquiry methods, characterized by participatory, diffuse, and reflective practices, to transform research into a tool for impactful change in organizations in the field of innovation management. Design/methodology/approach A longitudinal participatory case study approach focuses on the IDeaLs case—a research platform that collaborated with multiple companies over several years. The data gathered and analyzed comes from the research project within the research platforms over the first two editions and from the research platform management and coordination activities. Findings The study introduces the Collaborative Research Platform Approach (CRPA), demonstrating its effectiveness in addressing typical constraints of traditional research methodologies through a real-world application within the IDeaLs case. The findings highlight the CRPA's potential in fostering a dynamic, co-creative research environment that bridges theoretical knowledge with practical applications, thus enhancing both scholarly and organizational outcomes while pursuing a future change within the organizations. Research limitations/implications There are two main research implications. First, it proposes platform thinking as a theoretical lens to read a multi-stakeholder phenomenon in the research domain, confirming its nature of value-creation mechanisms, using it outside the business model and strategic space. Second, it offers a methodological contribution by presenting the CRPA framework. Practical implications The CRPA framework offers organizations a structured approach to managing collaborative research projects that align with both academic rigor and practical relevance. Companies engaged in the study reported enhanced ability to implement actionable insights from research, influencing real-time decision-making processes. Social implications By fostering collaborative engagements across multiple stakeholders, the CRPA promotes a research culture that values inclusivity and practical impact, potentially leading to broader societal benefits through improved innovation management practices. Originality/value This paper contributes to the innovation management field by proposing the CRPA, which integrates principles of Platform Thinking with Collaborative Inquiry. This novel approach is designed to improve the applicability and scope of innovation research, offering a robust framework that enhances engagement and utility across academic and business domains. It uses platforms as a theoretical lens to read a multi-stakeholder environment in the research domain

An Extreme Mountain Ultra-Marathon Decreases the Cost of Uphill Walking and Running

Purpose: To examine the effects of the world's most challenging mountain ultramarathon (MUM, 330 km, cumulative elevation gain of +24,000 m) on the energy cost and kinematics of different uphill gaits. Methods: Before (PRE) and immediately after (POST) the competition, 19 male athletes performed three submaximal 5-min treadmill exercise trials in a randomized order: walking at 5 km.h-1, +20%; running at 6 km.h-1, +15%; and running at 8 km.h-1, +10%. During the three trials, energy cost was assessed using an indirect calorimetry system and spatiotemporal gait parameters were acquired with a floor-level high-density photoelectric cells system. Results: The average time of the study participants to complete the MUM was 129 h 43 min 48 s (range: 107 h 29 min 24 s to 144 h 21 min 0 s). Energy costs in walking (-11.5 +/- 5.5%, P < 0.001), as well as in the first (-7.2 +/- 3.1%, P = 0.01) and second (-7.0 +/- 3.9%, P = 0.02) running condition decreased between PRE and POST, with a reduction both in the heart rate (-11.3, -10.0, and -9.3%, respectively) and oxygen uptake only for the walking condition (-6.5%). No consistent and significant changes in the kinematics variables were detected (P-values from 0.10 to 0.96). Conclusion: Though fatigued after completing the MUM, the subjects were still able to maintain their uphill locomotion patterns noted at PRE. The decrease (improvement) in the energy costs was likely due to the prolonged and repetitive walking/running, reflecting a generic improvement in the mechanical efficiency of locomotion after ~130 h of uphill locomotion rather than constraints imposed by the activity on the musculoskeletal structure and function

Radiological assessment of dementia: the Italian inter-society consensus for a practical and clinically oriented guide to image acquisition, evaluation, and reporting

Background: Radiological evaluation of dementia is expected to increase more and more in routine practice due to both the primary role of neuroimaging in the diagnostic pathway and the increasing incidence of the disease. Despite this, radiologists often do not follow a disease-oriented approach to image interpretation, for several reasons, leading to reports of limited value to clinicians. In our work, through an intersocietal consensus on the main mandatory knowledge about dementia, we proposed a disease-oriented protocol to optimize and standardize the acquisition/evaluation/interpretation and reporting of radiological images. Our main purpose is to provide a practical guideline for the radiologist to help increase the effectiveness of interdisciplinary dialogue and diagnostic accuracy in daily practice. Results: We defined key clinical and imaging features of the dementias (A), recommended MRI protocol (B), proposed a disease-oriented imaging evaluation and interpretation (C) and report (D) with a glimpse to future avenues (E). The proposed radiological practice is to systematically evaluate and score atrophy, white matter changes, microbleeds, small vessel disease, consider the use of quantitative measures using commercial software tools critically, and adopt a structured disease-oriented report. In the expanding field of cognitive disorders, the only effective assessment approach is the standardized disease-oriented one, which includes a multidisciplinary integration of the clinical picture, MRI, CSF and blood biomarkers and nuclear medicine

Flow Cytometric microsphere-based immunoassay as a novel non-radiometric method for the detection of glutamic acid decarboxylase autoantibodies in type 1 Diabetes Mellitus

The first measurable sign of arising autoimmunity in Type 1 Diabetes Mellitus is the detection of autoantibodies against beta-cell antigens, such as glutamic acid decarboxylase (GAD65). GAD65 autoantibodies (GADA) are usually measured by Radioligand Binding Assay (RBA). The aim of this work was to develop protocols of Flow Cytometric microsphere-based immunoassays (FloCMIA) which involved glutamic acid decarboxylase fused to thioredoxin (TrxGAD65) adsorbed on polystyrene microspheres. Detection of bound GADA was accomplished by the use of anti-human IgG-Alexa Fluor 488 (Protocol A), anti-human IgG-biotin and streptavidindichlorotriazinyl aminofluorescein (DTAF) (Protocol B) or TrxGAD65-biotin and streptavidin- DTAF (Protocol C). Serum samples obtained from 46 patients assayed for routine autoantibodies at Servicios Tecnológicos de Alto Nivel (STAN-CONICET) were analyzed by RBA, ELISA and three alternative FloCMIA designs. Protocol C exhibited the highest specificity (97.8%) and sensitivity (97.4%) and a wide dynamic range (1.00-134.40 SDs). Samples obtained from 40 new-onset diabetic patients were also analyzed to further evaluate the performance of protocol C. The latter protocol showed a sensitivity of 58.6% and a prevalence of 47.5%. Two patients resulted positive only by FloCMIA protocol C and its SDs were higher than RBA and ELISA, showing a significantly wide dynamic range. In conclusion, FloCMIA proved to be highly sensitive and specific, requiring a low sample volume; it is environmentally adequate, innovative and it represents a cost-effective alternative to traditional GADA determination by RBA and/or ELISA; making it applicable to most medium-complexity laboratories.Fil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Ureta, Daniela Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentin

Presenilin 1 Protein Directly Interacts with Bcl-2

Presenilin proteins are involved in familial Alzheimer's disease, a neurodegenerative disorder characterized by massive death of neurons. We describe a direct interaction between presenilin 1 (PS1) and Bcl-2, a key factor in the regulation of apoptosis, by yeast two-hybrid interaction system, by co-immunoprecipitation, and by cross-linking experiments. Our data show that PS1 and Bcl-2 assemble into a macromolecular complex, and that they are released from this complex in response to an apoptotic stimulus induced by staurosporine. The results support the idea of cross-talk between these two proteins during apoptosis

Gaia Focused Product Release: Radial velocity time series of long-period variables

Context. The third Gaia Data Release (DR3) provided photometric time series of more than 2 million long-period variable (LPV) candidates. Anticipating the publication of full radial-velocity data planned with Data Release 4, this Focused Product Release (FPR) provides radial-velocity time series for a selection of LPV candidates with high-quality observations. Aims. We describe the production and content of the Gaia catalog of LPV radial-velocity time series, and the methods used to compute the variability parameters published as part of the Gaia FPR. Methods. Starting from the DR3 catalog of LPV candidates, we applied several filters to construct a sample of sources with high-quality radial-velocity measurements. We modeled their radial-velocity and photometric time series to derive their periods and amplitudes, and further refined the sample by requiring compatibility between the radial-velocity period and at least one of the G, GBP, or GRP photometric periods. Results. The catalog includes radial-velocity time series and variability parameters for 9614 sources in the magnitude range 6 ≲ G/mag ≲ 14, including a flagged top-quality subsample of 6093 stars whose radial-velocity periods are fully compatible with the values derived from the G, GBP, and GRP photometric time series. The radial-velocity time series contain a mean of 24 measurements per source taken unevenly over a duration of about three years. We identify the great majority of the sources (88%) as genuine LPV candidates, with about half of them showing a pulsation period and the other half displaying a long secondary period. The remaining 12% of the catalog consists of candidate ellipsoidal binaries. Quality checks against radial velocities available in the literature show excellent agreement. We provide some illustrative examples and cautionary remarks. Conclusions. The publication of radial-velocity time series for almost ten thousand LPV candidates constitutes, by far, the largest such database available to date in the literature. The availability of simultaneous photometric measurements gives a unique added value to the Gaia catalog

A novel application of entropy analysis for assessing changes in movement variability during cumulative tackles in young elite rugby league players.

The aim of this study was to identify between-position (forwards vs. backs) differences in movement variability in cumulative tackle events training during both attacking and defensive roles. Eleven elite adolescent male rugby league players volunteered to participate in this study (mean ± SD, age; 18.5 ± 0.5 years, height; 179.5 ± 5.0 cm, body mass; 88.3 ± 13.0 kg). Participants performed a drill encompassing four blocks of six tackling (i.e. tackling an opponent) and six tackled (i.e. being tackled by an opponent while carrying a ball) events (i.e. 48 total tackles) while wearing a micro-technological inertial measurement unit (WIMU, Realtrack Systems, Spain). The acceleration data were used to calculate sample entropy (SampEn) to analyse the movement variability during tackles performance. In tackling actions SampEn showed significant between-position differences in block 1 (p = 0.0001) and block 2 (p = 0.0003). Significant between-block differences were observed in backs (block 1 vs 3, p = 0,0021; and block 1 vs 4, p = 0,0001) but not in forwards. When being tackled, SampEn showed significant between-position differences in block 1 (p = 0.0007) and block 3 (p = 0.0118). Significant between-block differences were only observed for backs in block 1 vs 4 (p = 0,0025). Movement variability shows a progressive reduction with cumulative tackle events, especially in backs and when in the defensive role (tackling). Forwards present lower movement variability values in all blocks, particularly in the first block, both in the attacking and defensive role. Entropy measures can be used by practitioners as an alternative tool to analyse the temporal structure of variability of tackle actions and quantify the load of these actions according to playing position

Surface Plasmon Resonance Reveals a Different Pattern of Proinsulin Autoantibodies Concentration and Affinity in Diabetic Patients

Type 1 diabetes mellitus (DM) is characterized by autoimmune aggression against pancreatic beta cells resulting in absolute deficiency of insulin secretion. The first detectable sign of emerging autoimmunity during the preclinical asymptomatic period is the appearance of diabetes-related autoantibodies. In children at risk for type 1 DM, high-affinity Insulin autoantibodies reactive to proinsulin, are associated with diabetes risk. Autoantibodies are usually measured by radioligand binding assay (RBA) that provides quasi-quantitative values reflecting potency (product between concentration and affinity) of specific autoantibodies. Aiming to improve the characterization of the specific humoral immune response, we selected surface plasmon resonance (SPR) as an alternative method to measure proinsulin autoantibodies (PAA). This novel technology has allowed real time detection of antibodies interaction and kinetic analysis. Herein, we have employed SPR to characterize the PAA present in sera from 28 childhood-onset (mean age 8.31±4.20) and 23 adult-onset diabetic patients (≥65 years old, BMI<30) in terms of concentration and affinity. When evaluating comparatively samples from both groups, childhood-onset diabetic patients presented lower PAA concentrations and higher affinities (median 67.12×10−9 M and 3.50×107 M−1, respectively) than the adults (median 167.4×10−9 M and 0.84×107 M−1, respectively). These results are consistent with those from the reference method RBA (Standard Deviation score median 9.49 for childhood-onset group and 5.04 for adult-onset group) where the binding can be directly related to the intrinsic affinity of the antibody, suggesting that there is a different etiopathogenic pathway between both types of clinical presentation of the disease. This technology has shown to be a useful tool for the characterization of PAAs parameters as an alternative to radioimmunoassay, with high versatility and reproducibility associated to low occupational and environmental risk. However, this technology is not eligible for routine marker screening, but this is a powerful technique for a fine description of the thermodynamic parameters of antigen-antibody interaction

PHAT XX. AGB Stars and Other Cool Giants in M31 Star Clusters

The presence of asymptotic giant branch (AGB) stars in clusters provides key constraints for stellar models, as has been demonstrated with historical data from the Magellanic Clouds. In this work, we look for candidate AGB stars in M31 star clusters from the Panchromatic Hubble Andromeda Treasury survey. Our photometric criteria selects stars brighter than the tip of the red giant branch, which includes the bulk of the thermally pulsing AGB stars as well as early-AGB stars and other luminous cool giants expected in young stellar populations (e.g., massive red supergiants, and intermediate-mass red helium-burning stars). The AGB stars can be differentiated, a posteriori, using the ages already estimated for our cluster sample. 937 candidates are found within the cluster aperture radii, half ( 3c450) of which are very likely cluster members. Cross-matching with additional databases reveals two carbon stars and 10 secure variables among them. The field-corrected age distribution reveals the presence of young supergiants peaking at ages smaller than 108 yr, followed by a long tail of AGB stars extending up to the oldest possible ages. This long tail reveals the general decrease in the numbers of AGB stars from initial values of 3c 50 7 10-6 M 99-1 at 108 yr down to 3c 5 7 10-6 M 99-1 at 1010 yr. Theoretical models of near-solar metallicity reproduce this general trend, although with localized discrepancies over some age intervals, whose origin is not yet identified. The entire catalog is released together with finding charts to facilitate follow-up studies