Gait analysis in a <i>Mecp2</i> knockout mouse model of Rett syndrome reveals early-onset and progressive motor deficits

Rett syndrome (RTT) is a genetic disorder characterized by a range of features including cognitive impairment, gait abnormalities and a reduction in purposeful hand skills. Mice harbouring knockout mutations in the &lt;i&gt;Mecp2&lt;/i&gt; gene display many RTT-like characteristics and are central to efforts to find novel therapies for the disorder. As hand stereotypies and gait abnormalities constitute major diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes will be of importance in assessing preclinical therapeutic outcomes. We therefore aimed to assess gait properties over the prodromal phase in a functional knockout mouse model of RTT. In male &lt;i&gt;Mecp2&lt;/i&gt; knockout mice, we observed alterations in stride, coordination and balance parameters at 4 weeks of age, before the onset of other overt phenotypic changes as revealed by observational scoring. These data suggest that gait measures may be used as a robust and early marker of &lt;i&gt;Mecp2&lt;/i&gt;-dysfunction in future preclinical therapeutic studies

Incorporating image quality in multi-algorithm fingerprint verification

The final publication is available at Springer via http://dx.doi.org/10.1007/11608288_29Proceedings of International Conference, ICB 2006, Hong Kong (China)The effect of image quality on the performance of fingerprint verification is studied. In particular, we investigate the performance of two fingerprint matchers based on minutiae and ridge information as well as their score-level combination under varying fingerprint image quality. The ridge-based system is found to be more robust to image quality degradation than the minutiae-based system. We exploit this fact by introducing an adaptive score fusion scheme based on automatic quality estimation in the spatial frequency domain. The proposed scheme leads to enhanced performance over a wide range of fingerprint image quality.This work has been supported by Spanish MCYT TIC2003-08382-C05-01 and by European Commission IST-2002-507634 Biosecure NoE projects

Risk factors for delirium and cognitive decline following coronary artery bypass grafting surgery: a systematic review and meta-analysis

Background: Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery-related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. Methods and Results: We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer-reviewed, English publications reporting post-CABG delirium or cognitive decline data, for at least one risk factor. Random-effects meta-analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety-seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit; higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1–6 months) post-CABG cognitive decline. Conclusions: This meta-analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable.Danielle Greaves, Peter J. Psaltis, Daniel H.J. Davis, Tyler J. Ross, Erica S. Ghezzi, Amit Lampit, Ashleigh E. Smith, Hannah A.D. Keag

Gender and ethnicity differences in the prevalence of scleroderma-related autoantibodies

Autoantibodies to topoisomerase I (topo I), RNA polymerase III (RNAPIII), centromere, U3RNP/fibrillarin, Th, PM-Scl, and U1RNP found in scleroderma (SSc) are associated with unique clinical subsets. The effects of race and gender on autoantibody prevalence and clinical manifestations were examined. Autoantibodies in sera from 105 SSc (include 75 Caucasian, 24 African-American, 6 others; 89 females and 16 males) were analyzed by immunofluorescence and immunoprecipitation. Clinical information was from database. SSc-related autoantibodies seldom coexist except for anti-topo I and anti-U1RNP. Anti-topo I (35% vs 15%), anti-U3RNP (30% vs 3%, p 08= 080.0005), and anti-U1RNP (30% vs 13%) were more common in African-Americans vs Caucasians. Anti-centromere (17%) and anti-PM-Scl (only in 8% of female) were found only in Caucasians. In race/gender combination, all three African-American males had anti-topo I (p 08= 080.04). Anti-U3RNP (35% vs 3%, p 08= 080.0005) and anti-U1RNP were common in African-American females. In African-American, all nucleolar dominant staining sera had anti-U3RNP; nuclear pattern was topo I (50%), U1RNP (19%), and RNAPIII (13%). In Caucasian, nucleolar was anti-Th (43%) and PM-Scl (29%); nuclear pattern was RNAPIII (29%), topo I (24%), and U1RNP (18%). Anti-topo I, anti-RNAPIII, and anti-U3RNP were associated with diffuse SSc while anti-centromere, anti-Th, and anti-U1 with limited disease. Proximal scleroderma was less common in African-American with anti-topo I (38% vs 91% in Caucasian, p 08= 080.04). The production of SSc-related autoantibodies is gender and race dependent, and this can be highly relevant in understanding their clinical significance. \ua9 2011 Clinical Rheumatology

Exclusive expression of MeCP2 in the nervous system distinguishes between brain and peripheral Rett syndrome-like phenotypes

This is a pre-copyedited, author-produced version of an article accepted for publication in Human Molecular Genetics following peer review. The version of record Ross, P. D., et al. (2016). "Exclusive expression of MeCP2 in the nervous system distinguishes between brain and peripheral Rett syndrome-like phenotypes." Human Molecular Genetics 25(20): 4389-4404.] is available online at: https://doi.org/10.1093/hmg/ddw269Work in SC’s laboratory was supported by the Biotechnology and Biological Sciences Research Council (PhD studentship for PDR), a consortium grant from the Rett Syndrome Research Trust, the Chief Scientist Office (Scottish Executive Health Department) [grant ETM/334], RS Macdonald Charitable Trust, Rosetrees Trust [grant M530], and the Rett Syndrome Association Scotland. Work in AB’s laboratory was supported by a Consortium Grant from the Rett Syndrome Research Trust, by Wellcome Trust programme grant [091580] and by Wellcome Trust Centre Core Grant [092076]. Funding to pay the Open Access publication charges for this article was provided by the Scottish Executive Health Department

Avaliação da aterosclerose subclínica e de níveis plasmáticos de LDL minimamente modificada em pacientes com espondilite anquilosante e sua correlação com a atividade da doença

AbstractIntroductionAccelerated atherosclerosis has been shown in some autoimmune diseases, mainly in Systemic Lupus Erythematosus and Rheumatoid Arthritis. Although high preva- lence of corticosteroids use may be a confounding factor due to their detrimental effects on several risk factors, systemic inflammation per se is supposed to play an important role in atherogenesis in these patients.MethodsWe have evaluated sub-clinical atherosclerosis and plasma levels of circulating electronegative LDL, which represents the fraction of LDL that is minimally modified, in patients with ankylosing spondylitis (AS). Fourteen patients who fulfilled the modified New York criteria for AS were compared with 13 paired controls. Carotid intimal-media thick- ness (IMT) was assessed by ultrasonography bilaterally in common carotid artery, internal carotid artery and in the bifurcation. Groups were homogeneous regarding cardiovascular risk factors. Only a single patient in AS group was in use of corticosteroid.ResultsThe presence of active inflammation was demonstrated by elevated BASDAI and higher CRP levels and in patients versus controls (12.36 vs. 3.45mg/dl, P = 0.002). No dif- ference was found in carotid IMT between both groups, in any site of artery. Averaged IMT (6 measurements, at 3 pre-specified sites bilaterally) was 0.72 ± 0.28 in AS group and 0.70 ± 0.45mm in controls (P = 0.91). Minimally modified LDL did not differ significantly either between patients and controls (14.03 ± 17.40 vs. 13.21 ± 10.21; P = 0.88).ConclusionsPatients with AS did not show increased carotid IMT in comparison to con- trols. In the same way, circulating plasma levels of LDL (-), did not differ significantly in both groups

Outcome of COVID-19 infections in patients with adrenal insufficiency and excess

Background: Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. Methods: A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing's syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. Results: Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison's disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. Conclusion: This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules.Metabolic health: pathophysiological trajectories and therap