An Insertion Within SIRPß1 Shows a Dual Effect Over Alzheimer's Disease Cognitive Decline Altering the Microglial Response.

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPß1, a surface receptor that triggers amyloid-ß(Aß) phagocytosis via TYROBP. Objective: To analyze the impact of this copy-number variant in SIRPß1 expression and how it affects AD molecular etiology. Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPß1 isoform-specific phagocytosis assays were performed in HEK393T cells. Results: The insertion alters the SIRPß1 protein isoform landscape compromising its ability to bind oligomeric Aß and its affinity for TYROBP. SIRPß1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aß ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPß1 duplication allele correlates with higher TREM2 expression and an increased microglial activation. Conclusions: The SIRPß1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aß. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPß1 structural variant might be considered as a potential modulator of this causative pathway.

Effect of Nordic Sensi® Chair on Behavioral and Psychological Symptoms of Dementia in Nursing Homes Residents: A Randomized Controlled Trial.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are present in most people with dementia (PwD), including Alzheimer's disease. There is consensus that non-pharmacological therapies represent the first line of treatment to address BPSD. OBJECTIVE: We explore the efficacy of the use of a rocking chair (Nordic Sensi® Chair, NSC) in the treatment of BPSD in nursing home residents with moderate and severe dementia. METHODS: We carried out a 16-week randomized, single-blind, controlled, clinical trial with PwD admitted to nursing homes. Participants were assigned to a treatment group (n = 40) that received three times a week one session per day of 20 minutes in the NSC and a control group (n = 37). The Neuropsychiatric Inventory-Nursing Home (NPI-NH) was used as primary efficacy outcome. Occupational distress for the staff was evaluated using the NPI-NH Occupational Disruptiveness subscale (NPI-NH-OD). Statistical analyses were conducted by means of a Mixed Effects Model Analysis. RESULTS: Treatment with the NSC was associated with a beneficial effect in most of BPSD, as reflected by differences between the treatment and control group on the NPI-NH total score (mean change score -18.87±5.56 versus -1.74±0.67, p = 0.004), agitation (mean change score -2.32±2.02 versus -0.78±1.44, p = 0.003) and irritability (mean change score -3.35±2.93 versus -1.42±1.31, p = 0.004). The NPI-NH-OD total score also improved the most in the treatment group (mean change score -9.67±7.67 versus -7.66±6.08, p = 0.003). CONCLUSIONS: The reduction in overall BPSD along with decreased caregiver occupational disruptiveness represent encouraging findings, adding to the potential of nonpharmacological interventions for nursing home residents living with dementia.

The Genetic Research in Alzheimer Disease (GERALD) Initiative Finds rs9320913 as a Neural eQTL of lincRNA AL589740.1.

Alzheimer's disease is the most common cause of dementia worldwide, and longitudinal studies are crucial to find the factors affecting disease development. Here, we describe a novel initiative from southern Spain designed to contribute in the identification of the genetic component of the cognitive decline of Alzheimer's disease patients. The germline variant rs9320913 is a C>A substitution mapping within a gene desert. Although it has been previously associated to a higher educational achievement and increased fluid intelligence, its role on Alzheimer's disease risk and progression remains elusive. A total of 407 subjects were included in the study, comprising 153 Alzheimer disease patients and 254 healthy controls. We have explored the rs9320913 contribution to both Alzheimer disease risk and progression according to the Mini-Mental State Exams. We found that rs9320913 maps within a central nervous system lincRNA AL589740.1. eQTL results show that rs9320913 correlated with the brain-frontal cortex (beta = -0.15, p value = 0.057) and brain-spinal cord (beta of -0.23, p value = 0.037). We did not find rs9320913 to be associated to AD risk, although AA patients seemed to exhibit a less pronounced Mini-Mental State Exam score decline.

Ventajas del abordaje externo para la artroplastia de rodilla por genu valgo severo / Advantages of the lateral approach in severe genu valgus knee arthroplasty

Introducción: El tratamiento del valgo severo es complejo. El abordaje externo descrito por Keblish es ventajoso para tratar estas deformidades. Evaluamos nuestros resultados utilizando un abordaje externo en artroplastias de rodilla con genu valgo severo. Materiales y Métodos: De 795 artroplastias primarias realizadas entre enero de 2012 y marzo de 2020, analizamos 40 que tenían un abordaje externo. Todos los pacientes tenían una deformidad en valgo >20° y un ligamento colateral medial suficiente. Se incluyó a 33 mujeres (3 bilaterales) y 4 hombres, el promedio de edad era de 71 años. La causa fue fundamentalmente osteoartrosis (82%). La deformidad prequirúrgica era de 27°. Las mediciones preoperatorias eran: KSS 15 (rango 5-42) y KFS 17 (rango 0-40). El tiempo promedio de cirugía fue de 91 minutos y el seguimiento, de 37 meses. Resultados: El ángulo femorotibial posoperatorio fue de 6,2° (rango 4-40), el KSS posoperatorio fue de 79 (rango 46-95) y el KFS, de 82 (rango 60-100). Hubo tres complicaciones (7%): una infección, un mal posicionamiento de componentes y uno de neuropraxia peronea. Conclusiones: En la artroplastia de rodilla por genu valgo, este abordaje permite restituir el eje femorotibial, lograr una adecuada estabilidad de la prótesis, aun con implantes sin mayor grado de constreñimiento, con una tasa de complicaciones equiparable a la de otras técnicas. Nivel de Evidencia: IV

Introduction: The treatment of severe valgus is complex. The lateral approach described by Keblish is advantageous for the treatment of these deformities. We decided to evaluate our outcomes using a lateral approach in severe genu valgus knee arthroplasty. Materials and Methods: Of 795 primary arthroplasties from January 2012 to March 2020, we analyzed 40 performed by lateral approach. All had a valgus deformity greater than 20° and a sufficient medial collateral ligament. 33 women (3 bilateral) and 4 men were included. Average age was 71 years (59-79). The main cause was osteoarthrosis (82%). The presurgical deformity was 27° (21-39). The preoperative measurements were: Knee Society Score (KSS) 15 (5 to 42). Preoperative functional score (KFS): 17 (0 to 40). Average surgical time: 91 minutes. The average postoperative follow-up was 37 months. Results: Postoperative femorotibial angle 6.2° (range 4° to 10°). Postoperative KSS 79 (46-95). KFS 82 (60-100). Complications: 3 cases (7%), one infection, one case with poor positioning of components, and one case of peroneal neuropraxia. Conclusion: In knee arthroplasty due to genu valgus, this approach allows restoring the femoro-tibial axis and achieving adequate prosthetic stability, even with implants without a greater degree of constraint, with a complication rate comparable to other techniques. Level of Evidence: IV

Improving the Pass-Band Return Loss in Liquid Crystal Dual-Mode Bandpass Filters by Microstrip Patch Reshaping.

In this paper, the design and experimental characterization of a tunable microstrip bandpass filter based on liquid crystal technology are presented. A reshaped microstrip dual-mode filter structure has been used in order to improve the device performance. Specifically, the aim is to increase the pass-band return loss of the filter by narrowing the filter bandwidth. Simulations confirm the improvement of using this new structure, achieving a pass-band return loss increase of 1.5 dB at least. Because of the anisotropic properties of LC molecules, a filter central frequency shift from 4.688 GHz to 5.045 GHz, which means a relative tuning range of 7.3%, is measured when an external AC voltage from 0 Vrms to 15 Vrms is applied to the device.