Impact of oral health on cognitive functioning, decline and impairment among older adults in England

Several studies have assessed the association between oral health and cognition in the elderly, although very few studies have investigated the longitudinal association in England. Different theories have been reported in the literature explaining the potential pathways between oral health and cognitive impairment, including inflammatory and nutritional factors. Additionally, social factors are a significant risk factor for cognitive impairment and are also highly correlated with oral health. This thesis aimed to examine the association between various oral health measures with cognitive functioning, change of cognitive functioning over time, and cognitive impairment in a nationally representative sample of older English adults. Additionally, the inflammatory, nutritional and social pathways were assessed. Secondary data from wave 3 (2006-07) to wave 8 (2016-17) of the English Longitudinal Study of Ageing (ELSA) were analysed. Three oral health measures were examined at baseline (wave 3) including self-reported oral health, oral impacts and edentulism. Cognitive functioning outcomes examined were memory using the word recall test and executive function using the animal naming test. Cognitive impairment was assessed at the follow-up wave 8 using the modified Telephone Interview for Cognitive Status (mTICS). Linear regression was used to assess the association with cognitive functioning cross-sectionally and longitudinally, linear mixed-effects models were used to assess the association with the change of cognitive functioning over time, and time-lag logistic regression models were used to assess the association with the subsequent cognitive impairment. Finally, several Structural Equation Models (SEM) were used to analyse the potential pathways of the association between oral health and cognitive impairment. This thesis showed that edentulism significantly predicted lower memory and executive function; while self-reported oral health predicted lower memory only in the edentate sample. The thesis also showed weak evidence of oral impacts predicting memory decline, although the association was marginally non-significant in the full model. Edentulism and oral impacts were strong predictors of subsequent cognitive impairment, independent of many covariates. The association between edentulism and cognitive impairment was significantly mediated by social isolation and preceded by inflammation. The overall findings of this thesis highlights the importance of oral and cognitive health in a national sample of older people. The results highlight the opportunity for future research to examine the potential effect of oral health in preventing or slowing the onset of dementia

Experimental Evaluation of the Critical Flutter Speed on Wings of Different Aspect Ratio

In this work, wind tunnel experiments were conducted to evaluate the critical flutter speed of wings for three pertinent flight parameters (i) the aspect ratio (AR), (ii) the angle of attack (AoA), and (iii) the aircraft propeller excitation. Six symmetrical wings (NACA0012 design), of fixed chord length of 80 mm and varied AR from 8.75 to 15, were used for this purpose. These wings were mounted horizontally in the wind tunnel as fixed-free condition. The airflow speed is increased slowly until the wing flutters. The results show that the critical flutter speed decreases when the AR increases. For higher AR, the effect of the AoA on the flutter speed is minimal. However, for low AR, the AoA is vital in delaying the flutter instability of the wing. This critical speed spans low to moderate Reynolds numbers based on the wing chord length (Rec =7×104-2×105) which corresponds to the speed range of High Altitude and Long Endurance (HALE) aircraft. In contrast, for a propeller excitation outside the resonance region of the wing, its effect of the on flutter characteristics is not noticeable

A spectroscopic, thermodynamic and molecular docking study of the binding mechanism of dapoxetine with calf thymus DNA

Dapoxetine is a selective serotonin reuptake inhibitor, used to treat premature ejaculation in men. Dapoxetine may interact with theDNAand hence this study investigated dapoxetine and calf thymusDNA(ctDNA) binding interaction. The interaction study of ligands to DNA is of importance in the development of molecular probes and therapeutic agents. Spectroscopic techniques including spectrofluorometry and spectrophotometry were employed to study this interaction. Fluorescence studies indicated a static quenching mechanism between dapoxetine and ctDNA. Groove binding was suggested as the mode of interaction between dapoxetine and ctDNA based onUVabsorption, circular dichroism (CD) spectroscopy, iodide quenching and molecular docking studies. The studies conducted at three different temperatures 298, 303 and 310 K indicated a strong binding interaction at higher temperatures. Thermodynamic studies conducted indicated involvement of hydrophobic interaction between ctDNA and dapoxetine and were entropy-driven. Ethidium bromide probe study suggested that dapoxetine does not bind to ctDNA in an intercalative fashion. Iodide quenching studies further proved the non-intercalative binding of ctDNA with dapoxetine. Ionic strength studies conducted ruled out the electrostatic binding mechanism between ctDNA and dapoxetine. Molecular docking analysis performed for the dapoxetine with calf thymus DNA (ctDNA) interaction and confirmed minor groove binding of dapoxetine to ctDNA. The study helped to reveal the binding interaction mechanism between dapoxetine and ctDNA

Patient and healthcare provider experience and perceptions of a preoperative rehabilitation class for lumbar discectomy: A qualitative study

Background: Lumbar disc disease is a leading cause of low back pain. Lumbar discectomy (LD) may be indicated if symptoms are not managed conservatively. Rehabilitation has traditionally been delivered postoperatively; however, there is increasing delivery preoperatively. There are few data concerning perceptions and experiences of preoperative rehabilitation. Exploring experiences of preoperative rehabilitation may help in the development and delivery of effective care for patients. Objectives: To develop an understanding of patient and healthcare provider (HCP) experiences, perspectives and preferences of preoperative LD rehabilitation, including why patients do not attend. Design: A qualitative interpretive approach using focus groups and individual interviews. Methods: Data were collected from; a) patients listed for surgery and attended the preoperative rehabilitation (October 2019 to March 2020), b) patients listed for surgery but did not attend rehabilitation, and c) HCPs involved in the delivery of rehabilitation. Data were transcribed verbatim and analysed using thematic analysis. Results/findings: Twenty participants were included, twelve patients and eight HCPs. The preoperative class was a valuable service for both patients and HCPs. It provided a solution to staffing and time pressures. It provided the required education and exercise content helping the patients along their surgery pathway. Travel distance, transportation links, parking difficulty and cost, lack of knowledge about the class aims, and previous negative experiences were barriers to patient attendance. Conclusions: For most patients and HCPs, the preoperative class was valuable. Addressing the challenges and barriers could improve attendance. Future research should focus on management of patient expectations and preferences preoperatively

The recurrent missense mutation p.(Arg367Trp) in YARS1 causes a distinct neurodevelopmental phenotype

Abstract: Pathogenic variants in aminoacyl-tRNA synthetases (ARS1) cause a diverse spectrum of autosomal recessive disorders. Tyrosyl tRNA synthetase (TyrRS) is encoded by YARS1 (cytosolic, OMIM*603,623) and is responsible of coupling tyrosine to its specific tRNA. Next to the enzymatic domain, TyrRS has two additional functional domains (N-Terminal TyrRSMini and C-terminal EMAP-II-like domain) which confer cytokine-like functions. Mutations in YARS1 have been associated with autosomal-dominant Charcot-Marie-Tooth (CMT) neuropathy type C and a heterogenous group of autosomal recessive, multisystem diseases. We identified 12 individuals from 6 families with the recurrent homozygous missense variant c.1099C > T;p.(Arg367Trp) (NM_003680.3) in YARS1. This variant causes a multisystem disorder with developmental delay, microcephaly, failure to thrive, short stature, muscular hypotonia, ataxia, brain anomalies, microcytic anemia, hepatomegaly, and hypothyroidism. In silico analyses show that the p.(Arg367Trp) does not affect the catalytic domain responsible of enzymatic coupling, but destabilizes the cytokine-like C-terminal domain. The phenotype associated with p.(Arg367Trp) is distinct from the other biallelic pathogenic variants that reside in different functional domains of TyrRS which all show some common, but also divergent clinical signs [(e.g., p.(Phe269Ser)—retinal anomalies, p.(Pro213Leu)/p.(Gly525Arg)—mild ID, p.(Pro167Thr)—high fatality)]. The diverse clinical spectrum of ARS1-associated disorders is related to mutations affecting the various non-canonical domains of ARS1, and impaired protein translation is likely not the exclusive disease-causing mechanism of YARS1- and ARS1-associated neurodevelopmental disorders. Key messages: The missense variant p.(Arg367Trp) in YARS1 causes a distinct multisystem disorder.p.(Arg367Trp) affects a non-canonical domain with cytokine-like functions.Phenotypic heterogeneity associates with the different affected YARS1 domains.Impaired protein translation is likely not the exclusive mechanism of ARS1-associated disorders

High-performance field effect transistors using electronic inks of 2D molybdenum oxide nanoflakes

Planar 2D materials are possibly the ideal channel candidates for future field effect transistors (FETs), due to their unique electronic properties. However, the performance of FETs based on 2D materials is yet to exceed those of conventional silicon based devices. Here, a 2D channel thin film made from liquid phase exfoliated molybdenum oxide nanoflake inks with highly controllable substoichiometric levels is presented. The ability to induce oxygen vacancies by solar light irradiation in an aqueous environment allows the tuning of electronic properties in 2D substoichiometric molybdenum oxides (MoO3-x). The highest mobility is found to be approximate to 600 cm(2) V-1 s(-1) with an estimated free electron concentration of approximate to 1.6 x 10(21) cm(-3) and an optimal I-On/I-Off ratio of >10(5) for the FETs made of 2D flakes irradiated for 30 min (x = 0.042). These values are significant and represent a real opportunity to realize the next generation of tunable electronic devices using electronic inks

Teleworking Survey in Saudi Arabia: Reliability and Validity of Arabic Version of the Questionnaire

Objectives: This study aimed to adapt the survey questionnaire designed by Moens et al. (2021) and determine the validity and reliability of the Arabic version of the survey in a sample of the Saudi population experiencing teleworking. Methods: The questionnaire includes 2 sections. The first consists of 13 items measuring the impact of extended telework during the coronavirus disease 2019 (COVID-19) crisis. The second section includes 6 items measuring the impact of the COVID-19 crisis on self-view of telework and digital meetings. The survey instrument was translated based on the guidelines for the cultural adaptation of self-administrated measures. Results: The reliability of the questionnaire responses was measured by Cronbach’s alpha. The construct validity was checked through exploratory factor analysis followed by confirmatory factor analysis (CFA) to further assess the factor structure. CFA revealed that the model had excellent fit (root mean square error of approximation, 0.00; comparative fit index, 1.0; Tucker-Lewis index, 1; standardized root mean squared residual, 0.0). Conclusions: The Arabic version of the teleworking questionnaire had high reliability and good validity in assessing experiences and perceptions toward teleworking. While the validated survey examined perceptions and experiences during COVID-19, its use can be extended to capture experiences and perceptions during different crises

Physical, structural, and gamma ray shielding studies on novel (35+x) PbO-5TeO2-20Bi2O3-(20-x) MgO-20B2O3 glasses

The primary aim of this investigation is to synthesize a novel glass system with a composition (35+x) PbO-5TeO2-20Bi2O3-(20-x) MgO-20B2O3 (where x=0, 5, 10, 15, and 20 mol%) by melt quenching method. The confirmation of the amorphous behavior and the presence of the various vibration modes and stretching modes have been analyzed using the XRD and FTIR techniques, respectively. The radiation shielding parameters of these glasses were reported using MCNP5 simulation. The effects of PbO on the MCNP5 parameters were investigated in detail. The mass attenuation coefficient (MAC) was simulated via MCNP5 code, and it was found that the MAC values from MCNP5 all follow the same trend as the XCOM data. The similarity means that the two simulations strongly agree with each other. The linear attenuation coefficient (LAC) was calculated for all the glasses. The glass sample with 55 mol% of the PbO has the greatest LAC at any energy, such as 0.317 at 10 MeV, the lowest investigated energy. From the LAC values, other parameters such as transmission factor (TF), lead equivalent thickness (dlead), and half-value layer (HVL) were reported. The results for the TF of the glasses revealed that the glass systems become more effective as their thickness increases. Glass sample with 35 mol % of the PbO recorded the highest TF at all energies due to its lack of PbO content, such as 15.533% for a thickness of 1 cm and 6.122% for 1.5-cm thickness at 0.3 MeV. The radiation protection efficiency (RPE) was also determined, and we found that the glasses with the greater PbO content and least MgO content have the highest RPE. Therefore, based on the RPE values, glasses with the greater PbO are the most effective radiation shield from the investigated glasses. © 2021, Australian Ceramic Society.This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-Track Research Funding Program

Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features

Major Facilitator Superfamily Domain containing 2a (MFSD2A) is an essential endothelial lipid transporter at the blood-brain barrier. Biallelic variants affecting function in MFSD2A cause autosomal recessive primary microcephaly 15 (MCPH15, OMIM# 616486). We sought to expand our knowledge of the phenotypic spectrum of MCPH15 and demonstrate the underlying mechanism of inactivation of the MFSD2A transporter. We carried out detailed analysis of the clinical and neuroradiological features of a series of 27 MCPH15 cases, including eight new individuals from seven unrelated families. Genetic investigation was performed through exome sequencing (ES). Structural insights on the human Mfsd2a model and in-vitro biochemical assays were used to investigate the functional impact of the identified variants. All patients had primary microcephaly and severe developmental delay. Brain MRI showed variable degrees of white matter reduction, ventricular enlargement, callosal hypodysgenesis, and pontine and vermian hypoplasia. ES led to the identification of six novel biallelic MFSD2A variants (NG_053084.1, NM_032793.5: c.556+1G>A, c.748G>T; p.(Val250Phe), c.750_753del; p.(Cys251SerfsTer3), c.977G>A; p.(Arg326His), c.1386_1435del; p.(Gln462HisfsTer17), and c.1478C>T; p.(Pro493Leu)) and two recurrent variants (NM_032793.5: c.593C>T; p.(Thr198Met) and c.476C>T; p.(Thr159Met)). All these variants and the previously reported NM_032793.5: c.490C>A; p.(Pro164Thr) resulted in either reduced MFSD2A expression and/or transport activity. Our study further delineates the phenotypic spectrum of MCPH15, refining its clinical and neuroradiological characterization and supporting that MFSD2A deficiency causes early prenatal brain developmental disruption. We also show that poor MFSD2A expression despite normal transporter activity is a relevant pathomechanism in MCPH15

Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy