Vascular risk factors, white matter lesions and cognitive impairment in Parkinson’s disease: the PACOS longitudinal study

Background: Vascular risk factors (VRFs) may be associated with cognitive decline in early Parkinson’s disease (PD) but results are inconclusive. The identification of modifiable risk factors is relevant for prevention and treatment. Methods: Parkinson’s disease (PD) patients of the PACOS cohort who underwent a baseline and follow-up neuropsychological evaluation were enrolled in the study. PD with Mild Cognitive Impairment (MCI) and dementia (PDD) were diagnosed according to the MDS criteria. A Baseline 1.5 T brain MRI was used to calculate the white matter lesions (WMLs) burden using the Wahlund visual scale. Laboratory data, presence of hypertension, diabetes and use of anti-hypertensive drugs were collected and the Framingham Risk (FR) score was calculated. VRFs predicting PD-MCI and PDD were evaluated using Cox proportional hazard regression model. Results: Out of 139 enrolled patients, 84 (60.4%) were classified as normal cognition (NC) and 55 (39.6%) as MCI at baseline. At follow-up 28 (33.3%) PD-NC developed MCI and 4 (4.8%) PDD (follow-up time 23.5 ± 10.3 months). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD. At multivariate analysis among PD-NC a systolic blood pressure (SBP) > 140 mmHg was the stronger predictor of MCI (adjHR 4.04; 95% CI 1.41–11.3) while the presence of MCI at baseline (adj HR 7.55; 95% CI 1.76–32.3) and a severe WMLs burden (adj HR 2.80; 95% CI 0.86–9.04) were the strongest predictors of PDD, even if this latter association has a trend towards significance. Conclusion: Hypertension represents the most important modifiable risk factor for PD-MCI in the PACOS cohort, increasing the risk of about four times

Clinical aspects of short-chain acyl-CoA dehydrogenase deficiency

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation. SCADD is biochemically characterized by increased C4-carnitine in plasma and ethylmalonic acid in urine. The diagnosis of SCADD is confirmed by DNA analysis showing SCAD gene mutations and/or variants. SCAD gene variants are present in homozygous form in approximately 6% of the general population and considered to confer susceptibility to development of clinical disease. Clinically, SCADD generally appears to present early in life and to be most frequently associated with developmental delay, hypotonia, epilepsy, behavioral disorders, and hypoglycemia. However, these symptoms often ameliorate and even disappear spontaneously during follow-up and were found to be unrelated to the SCAD genotype. In addition, in some cases, symptoms initially attributed to SCADD could later be explained by other causes. Finally, SCADD relatives of SCADD patients as well as almost all SCADD individuals diagnosed by neonatal screening remained asymptomatic during follow-up. This potential lack of clinical consequences of SCADD has several implications. First, the diagnosis of SCADD should never preclude extension of the diagnostic workup for other potential causes of the observed symptoms. Second, patients and parents should be clearly informed about the potential lack of relevance of the disorder to avoid unfounded anxiety. Furthermore, to date, SCADD is not an optimal candidate for inclusion in newborn screening programs. More studies are needed to fully establish the relevance of SCADD and solve the question as to whether SCADD is involved in a multifactorial disease or represents a nondisease

Latitude does not influence cavity entrance orientation of South American avian excavators

In the Northern Hemisphere, several avian cavity excavators (e.g., woodpeckers) orient their cavities increasingly toward the equator as latitude increases (i.e., farther north), and it is proposed that they do so to take advantage of incident solar radiation at their nests. If latitude is a key driver of cavity orientations globally, this pattern should extend to the Southern Hemisphere. Here, we test the prediction that cavities are oriented increasingly northward at higher (i.e., colder) latitudes in the Southern Hemisphere and describe the preferred entrance direction(s) of 1501 cavities excavated by 25 avian species (n = 22 Picidae, 2 Trogonidae, 1 Furnariidae) across 12 terrestrial ecoregions (15°S ? 55°S) in South America. We used Bayesian projected normal mixed-effects models for circular data to examine the influence of latitude, and potential confounding factors, on cavity orientation. Also, a probability model selection procedure was used to simultaneously examine multiple orientation hypotheses in each ecoregion, to explore underlying cavity-orientation patterns. Contrary to predictions, and patterns from the Northern Hemisphere, birds did not orient their cavities more toward the equator with increasing latitude, suggesting that latitude may not be an important underlying selective force shaping excavation behavior in South America. Moreover, unimodal cavity-entrance orientations were not frequent among the ecoregions analyzed (infour ecoregions), whereas bimodal (in five ecoregions) or uniform (in three ecoregions) werealso common, although many of these patterns were not very sharp. Our results highlight the need to include data from under-studied biotas and regions to improve inferences at macroecology scales. Furthermore, we suggest a re-analysis of Northern Hemisphere cavity orientation patterns using a multimodel approach, and a more comprehensive assessment of the role of environmental factors as drivers of cavity orientation at different spatial scales in both hemispheres.Fil: Ojeda, Valeria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Schaaf, Alejandro Alberto. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Altamirano, Tatiana Edith. University of British Columbia; CanadáFil: Bonaparte, Eugenia Bianca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Bragagnolo, Laura Araceli. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Chazarreta, L.. Secretaría de Ambiente y Desarrallo Sustentable de la Nación; ArgentinaFil: Cockle, Kristina Louise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Dias, R.. Universidade do Brasília; BrasilFil: Di Sallo, Facundo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Ibarra, T.. Pontificia Universidad Católica de Chile; ChileFil: Ippi, Silvina Graciela. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jauregui, Adrian. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Área Zoología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jimenez, Jaime E.. Universidad de Magallanes; ChileFil: Lammertink, J. Martjan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Lopez, F.. Universidad Nacional de La Pampa; ArgentinaFil: Nuñez Montellano, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; ArgentinaFil: de la Peña, Martín. No especifíca;Fil: Rivera, Luis Osvaldo. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Vivanco, Constanza Guadalupe. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Santillán, Miguel. Museo de Historia Natural de La Pampa; ArgentinaFil: Soto, G.. Cornell University; Estados UnidosFil: Vergara, P.. Universidad de Santiago de Chile; ChileFil: Politi, Natalia. University of North Texas; Estados Unido

Stellar metallicity from optical and UV spectral indices: Test case for WEAVE-StePS

Context. The upcoming generation of optical spectrographs on four meter-class telescopes, with their huge multiplexing capabilities, excellent spectral resolution, and unprecedented wavelength coverage, will provide high-quality spectra for thousands of galaxies. These data will allow us to examine of the stellar population properties at intermediate redshift, an epoch that remains unexplored by large and deep surveys. Aims. We assess our capability to retrieve the mean stellar metallicity in galaxies at different redshifts and signal-to-noise ratios (S/N), while simultaneously exploiting the ultraviolet (UV) and optical rest-frame wavelength coverage. Methods. The work is based on a comprehensive library of spectral templates of stellar populations, covering a wide range of age and metallicity values and built assuming various star formation histories, to cover an observable parameter space with diverse chemical enrichment histories and dust attenuation. We took into account possible observational errors, simulating realistic observations of a large sample of galaxies carried out with WEAVE at the William Herschel Telescope at different redshifts and S/N values. We measured all the available and reliable indices on the simulated spectra and on the comparison library. We then adopted a Bayesian approach to compare the two sets of measurements in order to obtain the probability distribution of stellar metallicity with an accurate estimate of the uncertainties. Results. The analysis of the spectral indices has shown how some mid-UV indices, such as BL3580 and Fe3619, can provide reliable constraints on stellar metallicity, along with optical indicators. The analysis of the mock observations has shown that even at S/N = 10, the metallicity can be derived within 0.3 dex, in particular, for stellar populations older than 2 Gyr. The S/N value plays a crucial role in the uncertainty of the estimated metallicity and so, the differences between S/N = 10 and S/N = 30 are quite large, with uncertainties of ~0.15 dex in the latter case. On the contrary, moving from S/N = 30 to S/N = 50, the improvement on the uncertainty of the metallicity measurements is almost negligible. Our results are in good agreement with other theoretical and observational works in the literature and show how the UV indicators, coupled with classic optical ones, can be advantageous in constraining metallicities. Conclusions. We demonstrate that a good accuracy can be reached on the spectroscopic measurements of the stellar metallicity of galaxies at intermediate redshift, even at low S/N, when a large number of indices can be employed, including some UV indices. This is very promising for the upcoming surveys carried out with new, highly multiplexed, large-field spectrographs, such as StePS at the WEAVE and 4MOST, which will provide spectra of thousands of galaxies covering large spectral ranges (between 3600 and 9000 Å in the observed frame) at relatively high S/N (>10 Å -1)F.R.D., A.I., M.L, S.Z., A.G., F.L.B. acknowledge financial support from grant 1.05.01.86.16 – Mainstream 2020. A.F.M. acknowledges support from RYC2021-031099-I and PID2021-123313NAI00 of MICIN/AEI/10.13039/501100011033/FEDER,UE. L.C. acknowledges financial support from Comunidad de Madrid under Atraccion de Talento grant 2018-T2/TIC-11612 and Spanish Ministerio de Ciencia e Innovacion MCIN/AEI/10.13039/501100011033 through grant PGC2018-093499-BI00. R.G.B. acknowledges financial support from the grants CEX2021-001131-S funded by MCIN/AEI/10.13039/501100011033 and to PID2019-109067-GB100. A.V. acknowledges support from grant PID2019-107427GB-C32 and PID2021-123313NA-I00 from the Spanish Ministry of Science, Innovation and Universities MCIU. This work has also been supported through the IAC project TRACES, which is partially supported through the state budget and the regional budget of the Consejería de Economía, Industria, Comercio y Conocimiento of the Canary Islands Autonomous Community. A.V. also acknowledges support from the ACIISI, Consejería de Economía, Conocimiento y Empleo del Gobierno de Canarias and the European Regional Development Fund (ERDF) under grant with reference ProID202101007

A systematic review on 'Foveal Crowding' in visually impaired children and perceptual learning as a method to reduce Crowding

Contains fulltext : 102577.pdf (publisher's version ) (Open Access)Background - This systematic review gives an overview of foveal crowding (the inability to recognize objects due to surrounding nearby contours in foveal vision) and possible interventions. Foveal crowding can have a major effect on reading rate and deciphering small pieces of information from busy visual scenes. Three specific groups experience more foveal crowding than adults with normal vision (NV): 1) children with NV, 2) visually impaired (VI ) children and adults and 3) children with cerebral visual impairment (CVI). The extent and magnitude of foveal crowding as well as interventions aimed at reducing crowding were investigated in this review. The twofold goal of this review is : [A] to compare foveal crowding in children with NV, VI children and adults and CVI children and [B] to compare interventions to reduce crowding. Methods - Three electronic databases were used to conduct the literature search: PubMed, PsycINFO (Ovid), and Cochrane. Additional studies were identified by contacting experts. Search terms included visual perception, contour interaction, crowding, crowded, and contour interactions. Results - Children with normal vision show an extent of contour interaction over an area 1.5-3x as large as that seen in adults NV. The magnitude of contour interaction normally ranges between 1-2 lines on an acuity chart and this magnitude is even larger when stimuli are arranged in a circular configuration. Adults with congenital nystagmus (CN) show interaction areas that are 2x larger than those seen adults with NV. The magnitude of the crowding effect is also 2x as large in individuals with CN as in individuals with NV. Finally, children with CVI experience a magnitude of the crowding effect that is 3x the size of that experienced by adults with NV. Conclusions - The methodological heterogeneity, the diversity in paradigms used to measure crowding, made it impossible to conduct a meta-analysis. This is the first systematic review to compare crowding ratios and it shows that charts with 50% interoptotype spacing were most sensitive to capture crowding effects. The groups that showed the largest crowding effects were individuals with CN, VI adults with central scotomas and children with CVI. Perceptual Learning seems to be a promising technique to reduce excessive foveal crowding effects.14 p

Joint contractures in the absence of inflammation may indicate mucopolysaccharidosis

<p>Abstract</p> <p>Background</p> <p>Undiagnosed patients with the attenuated form of mucopolysaccharidosis (MPS) type I often have joint symptoms in childhood that prompt referral to a rheumatologist. A survey conducted by Genzyme Corporation of 60 European and Canadian rheumatologists and pediatric rheumatologists demonstrated that < 20% recognized signs and symptoms of MPS I or could identify appropriate diagnosis tests. These results prompted formation of an international working group of rheumatologists, pediatric rheumatologists, and experts on MPS I to formulate a rheumatology-based diagnostic algorithm. The resulting algorithm applies to all MPS disorders with musculoskeletal manifestations.</p> <p>Bone and joint manifestations are prominent among most patients with MPS disorders. These life-threatening lysosomal storage diseases are caused by deficient activity of specific enzymes involved in the degradation of glycosaminoglycans. Patients with attenuated MPS disease often experience diagnostic delays. Enzyme replacement therapy is now commercially available for MPS I (laronidase), MPS II (idursulfase), and MPS VI (galsulfase).</p> <p>Presentation of the hypothesis</p> <p>Evolving joint pain and joint contractures in the absence of inflammation should always raise the suspicion of an MPS disorder. All such patients should undergo urinary glycosaminoglycan (uGAG) analysis (not spot tests for screening) in a reputable laboratory. Elevated uGAG levels and/or an abnormal uGAG pattern confirms an MPS disorder and specific enzyme testing will determine the MPS type. If uGAG analysis is unavailable and the patient exhibits any other common sign or symptom of an MPS disorder, such as corneal clouding, history of hernia surgery, frequent respiratory and/or ear, nose and throat infections; carpal tunnel syndrome, or heart murmur, proceed directly to enzymatic testing. Refer patients with confirmed MPS to a geneticist or metabolic specialist for further evaluation and treatment.</p> <p>Testing of the hypothesis</p> <p>We propose that rheumatologists, pediatric rheumatologists, and orthopedists consider our diagnostic algorithm when evaluating patients with joint pain and joint contractures.</p> <p>Implications of the hypothesis</p> <p>Children and young adults can suffer for years and sometimes even decades with unrecognized MPS. Rheumatologists may facilitate early diagnosis of MPS based on the presenting signs and symptoms, followed by appropriate testing. Early diagnosis helps ensure prompt and appropriate treatment for these progressive and debilitating diseases.</p

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts