How do predisposing factors differ between delirium motor subtypes? A systematic review and meta-analysis

BACKGROUND: Delirium is a common neurocognitive disorder in hospitalised older adults with vast negative consequences. The predominant method of subtyping delirium is by motor activity profile into hypoactive, hyperactive and mixed groups. OBJECTIVE: This systematic review and meta-analysis investigated how predisposing factors differ between delirium motor subtypes. METHODS: Databases (Medline, PsycINFO, Embase) were systematically searched for studies reporting predisposing factors (prior to delirium) for delirium motor subtypes. A total of 61 studies met inclusion criteria (N = 14,407, mean age 73.63 years). Random-effects meta-analyses synthesised differences between delirium motor subtypes relative to 22 factors. RESULTS: Hypoactive cases were older, had poorer cognition and higher physical risk scores than hyperactive cases and were more likely to be women, living in care homes, taking more medications, with worse functional performance and history of cerebrovascular disease than all remaining subtypes. Hyperactive cases were younger than hypoactive and mixed subtypes and were more likely to be men, with better cognition and lower physical risk scores than all other subtypes. Those with no motor subtype (unable to be classified) were more likely to be women and have better functional performance. Effect sizes were small. CONCLUSIONS: Important differences in those who develop motor subtypes of delirium were shown prior to delirium occurrence. We provide robust quantitative evidence for a common clinical assumption that indices of frailty (institutional living, cognitive and functional impairment) are seen more in hypoactive patients. Motor subtypes should be measured across delirium research. Motor subtyping has great potential to improve the clinical risk assessment and management of delirium

Adult autologous mesenchymal stem cells for the treatment of suspected non-infectious inflammatory diseases of the canine central nervous system: safety, feasibility and preliminary clinical findings

Non-infectious inflammatory diseases of the canine central nervous system (CNS) are common idiopathic disorders grouped under the term meningoencephalomyelitis of unknown origin (MUO). Ante mortem diagnosis is achieved via assessment of clinical signs, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis, but the definitive diagnosis needs histopathological examination. MUO are mostly considered as autoimmune CNS disorders, so that suppressing the immune reaction is the best management method for patients. Mesenchymal stem cells (MSCs) are under investigation to treat autoimmune and degenerative disorders due to their immunomodulatory and regenerative properties. This study aims to verify the safety, feasibility, and efficacy of MSCs treatment in canine idiopathic autoimmune inflammatory disorders of the CNS

The effects of computerised cognitive training on post-CABG delirium and cognitive change: A prospective randomised controlled trial

Background: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG). Improving cognition pre- and post-operatively using computerised cognitive training (CCT) may be an effective approach to improve cognitive outcomes in CABG patients. Objectives: Investigate the effect of remotely supervised CCT on cognitive outcomes, including delirium, in older adults undergoing CABG surgery. Methods: Thirty-six participants, were analysed in a single-blinded randomised controlled trial (CCT Intervention: n = 18, Control: n = 18). CCT was completed by the intervention group pre-operatively (every other day, 45–60-minute sessions until surgery) and post-operatively, beginning 1-month post-CABG (3 x 45–60-minute sessions/week for 12-weeks), while the control group maintained usual care plus weekly phone calls. Cognitive assessments were conducted pre- and post-operatively at multiple follow-ups (discharge, 4-months and 6-months). Post-operative delirium incidence was assessed daily until discharge. Cognitive change data were calculated at each follow-up for each cognitive test (Addenbrooke’s Cognitive Examination III and CANTAB; z-scored). Results: Adherence to the CCT intervention (completion of three pre-operative or 66% of post-operative sessions) was achieved in 68% of pre-CABG and 59% of post-CABG participants. There were no statistically significant effects of CCT on any cognitive outcome, including delirium incidence. Conclusion: Adherence to the CCT program was comparatively higher than previous feasibility studies, possibly due to the level of supervision and support provided (blend of face-to-face and home-based training, with support phone calls). Implementing CCT interventions both pre- and post-operatively is feasible in those undergoing CABG. No statistically significant benefits from the CCT interventions were identified for delirium or cognitive function post-CABG, likely due to the sample size available (study recruitment greatly impacted by COVID-19). It also may be the case that multimodal intervention would be more effective

Angiogenic and anti-inflammatory properties of micro-fragmented fat tissue and its derived mesenchymal stromal cells.

BACKGROUND: Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for advanced cell-based therapies. They are routinely obtained enzymatically from fat lipoaspirate (LP) as SVF, and may undergo prolonged ex vivo expansion, with significant senescence and decline in multipotency. Besides, these techniques have complex regulatory issues, thus incurring in the compelling requirements of GMP guidelines. Hence, availability of a minimally manipulated, autologous adipose tissue would have remarkable biomedical and clinical relevance. For this reason, a new device, named Lipogems® (LG), has been developed. This ready-to-use adipose tissue cell derivate has been shown to have in vivo efficacy upon transplantation for ischemic and inflammatory diseases. To broaden our knowledge, we here investigated the angiogenic and anti-inflammatory properties of LG and its derived MSC (LG-MSCs) population. METHODS: Human LG samples and their LG-MSCs were analyzed by immunohistochemistry for pericyte, endothelial and mesenchymal stromal cell marker expression. Angiogenesis was investigated testing the conditioned media (CM) of LG (LG-CM) and LG-MSCs (LG-MSCs-CM) on cultured endothelial cells (HUVECs), evaluating proliferation, cord formation, and the expression of the adhesion molecules (AM) VCAM-1 and ICAM-1. The macrophage cell line U937 was used to evaluate the anti-inflammatory properties, such as migration, adhesion on HUVECs, and release of RANTES and MCP-1. RESULTS: Our results indicate that LG contained a very high number of mesenchymal cells expressing NG2 and CD146 (both pericyte markers) together with an abundant microvascular endothelial cell (mEC) population. Substantially, both LG-CM and LG-MSC-CM increased cord formation, inhibited endothelial ICAM-1 and VCAM-1 expression following TNFα stimulation, and slightly improved HUVEC proliferation. The addition of LG-CM and LG-MSC-CM strongly inhibited U937 migration upon stimulation with the chemokine MCP-1, reduced their adhesion on HUVECs and significantly suppressed the release of RANTES and MCP-1. CONCLUSIONS: Our data indicate that LG micro-fragmented adipose tissue retains either per se, or in its embedded MSCs content, the capacity to induce vascular stabilization and to inhibit several macrophage functions involved in inflammation

Factors associated with cognitive decline and delirium after transcatheter aortic valve implantation: Preliminary evidence

Background: Transcatheter aortic valve implantation (TAVI) has become the standard for treating severe symptomatic aortic stenosis in those with prohibitive surgical risk. Cognitive complications, including delirium and cognitive decline are common following TAVI, yet an understanding of pre-procedural factors associated with these outcomes is lacking. This prospective observational study set out to identify geriatric pre-procedural factors associated with post-procedural delirium and cognitive decline in patients undergoing TAVI. / Methods: Cognitive outcomes of TAVI patients aged ≥60 years (N=32) were measured over one-year post-TAVI. Pre-procedural measures included frailty, gait, visual symptoms, voice pitch, dysphagia, blink rate, mood, and sleep. Primary outcomes were post-procedural delirium and cognitive decline. / Results: Delirium was present in 25% of patients over two days following TAVI and 26% experienced cognitive decline in the year post-TAVI. Daily physical activity was a protective factor against cognitive decline, and worse baseline visual memory was associated with delirium. While non-significant and with very large confidence intervals, moderate to large effect sizes were found for associations between slowed gait speed, pre-existing atrial fibrillation, and dysphagia for delirium, and slower gait speed, higher blink rate, pre-existing atrial fibrillation for cognitive decline. / Conclusion: Though underpowered, measures of considerable effect size were identified (although non-significant and with large variability). In larger studies, these novel geriatric factors could further be explored for predicting cognitive complications following TAVI. Improvement of risk prediction for cognitive decline and delirium following TAVI could assist with early identification of those at risk, informing clinical decision-making and allowing for targeted intervention to reduce post-procedural incidence of these complications

Organic electronics allows the photo-electric excitation and inhibition of neuronal activity in primary neuronal cultures and acute retinal explants

Interfacing organic electronics and biology offers new possibilities in biotechnology, due to the unique properties exhibited by organic conducting polymers (e.g. biological affinity, mechanical flexibility, ease of functionalization and cost effectiveness). Organic conducting polymers have been exploited as materials for cellular interfaces in several fashions as: (i) passive electrode coatings or culturing substrates, (ii) organic biosensors or (iii) actuators for neurotransmitter release and electrodes for controlled cell seeding, growth and activity detection. Very recently, an organic photovoltaic donor-acceptor blend has been exploited for neuron stimulation by a photo-electric process. With respect to previous examples with inorganic semiconductors, this system has several advantages including flexibility, no power requirement and biocompatibility. Here, we report the novel use of a single component semiconductor organic polymer for the direct control of neuronal activity. This interface, that is more efficient than the classical bulk hetero-junction interface, has the remarkable capability to evoke excitation of neuronal firing in response to illumination. We demonstrate that the polymer layer has the ability to induce action potential firing up to 20 Hz in cultured hippocampal neurons. Moreover, this interface has been exploited to restore visual response in retinal explants obtained from animal models of retinal degeneration (light-blinded albino SD rats). By recording local field potentials in the RGC layer, we demonstrated the ability of the organic conductive polymer to mimic the function of photoreceptors and induce retinal activation of retinal ganglion cells after light illumination. These results paved the way to the development of a new and disruptive technology for interfacing artificial devices with neuronal networks, with applications in neuroprosthesis and brain machine interface research

Organic electronics allows the photo-electric excitation of neuronal activity in primary neuronal cultures and acute retinal explants

Interfacing organic electronics and biology offers new possibilities in biotechnology, due to the unique properties exhibited by organic conducting polymers (e.g. biological affinity, mechanical flexibility, ease of functionalization and cost effectiveness). Organic conducting polymers have been exploited as materials for cellular interfaces in several fashions as: (i) passive electrode coatings or culturing substrates, (ii) organic biosensors or (iii) actuators for neurotransmitter release and electrodes for controlled cell seeding, growth and activity detection. Very recently, an organic photovoltaic donor-acceptor blend has been exploited for neuron stimulation by a photo-electric process. With respect to previous examples with inorganic semiconductors, this system has several advantages including flexibility, no power requirement and biocompatibility. Here, we report the novel use of a single component semiconductor organic polymer for the direct control of neuronal activity. This interface, that is more efficient than the classical bulk hetero-junction interface, has the remarkable capability to evoke neuronal firing in response to illumination. We demonstrate that the polymer layer has the ability to induce action potential firing up to 20 Hz in cultured hippocampal neurons. Moreover, this interface has been exploited to restore visual response in retinal explants obtained from animal models of retinal degeneration (light-blinded albino SD rats). By recording local field potentials in the RGC layer, we demonstrated the ability of the organic conductive polymer to mimic the function of photoreceptors and induce retinal activation of retinal ganglion cells after light illumination. These results paved the way to the development of a new and disruptive technology for interfacing artificial devices with neuronal networks, with applications in neuroprosthesis and brain machine interface research

The effects of anticholinergic medications on cognition in children: a systematic review and meta-analysis

Cognitive side effects of anticholinergic medications in older adults are well documented. Whether these poor cognitive outcomes are observed in children has not been systematically investigated. We aimed to conduct a systematic review and meta-analysis on the associations between anticholinergic medication use and cognitive performance in children. Systematic review was conducted using Medline, PsychInfo, and Embase, identifying studies testing cognitive performance relative to the presence versus absence of anticholinergic medication(s) in children. We assessed effects overall, as well as relative to drug class, potency (low and high), cognitive domain, and duration of administration. The systematic search identified 46 articles suitable for meta-analysis. For the most part, random effects meta-analyses did not identify statistically significant associations between anticholinergic exposure and cognitive performance in children; the one exception was a small effect of anticholinergic anti-depressants being associated with better cognitive function (Hedges’ g = 0.24, 95% CI 0.06–0.42, p = 0.01). Anticholinergic medications do not appear to be associated with poor cognitive outcomes in children, as they do in older adults. The discrepancy in findings with older adults may be due to shorter durations of exposure in children, differences in study design (predominantly experimental studies in children rather than predominantly epidemiological in older adults), biological ageing (e.g. blood brain barrier integrity), along with less residual confounding due to minimal polypharmacy and comorbidity in children

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis