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Previous studies indicated an association between impaired cerebral perfusion and post-procedural neurological disorders. We investigated whether intra-procedural hypoxaemia or hypocapnia are associated with delirium after surgery.Inpatients ≥60 yr of age undergoing anaesthesia for surgical or interventional procedures between 2009 and 2020 at an academic healthcare network in the USA (Massachusetts) were included in this hospital registry study. The primary exposure was intra-procedural hypoxaemia, defined as peripheral oxygen saturation90% for2 cohering min. The co-primary exposure was hypocapnia during general anaesthesia, defined as end-tidal carbon dioxide pressure ≤25 mm Hg for5 cohering min. The primary outcome was delirium within 7 days after surgery.Of 71 717 included patients, 1702 (2.4%) developed postoperative delirium, and hypoxaemia was detected in 2532 (3.5%). Of 42 894 patients undergoing general anaesthesia, 532 (1.2%) experienced hypocapnia. The occurrence of either hypoxaemia (adjusted odds ratio [ORIntra-procedural hypoxaemia and hypocapnia were dose-dependently associated with a higher risk of postoperative delirium. These findings support maintaining normal gas exchange to avoid postoperative neurological disorders.

Contains fulltext : 252733.pdf (Publisher’s version ) (Open Access) Objective: To overcome memory decrements in healthy aging, compensation strategies and mnemonics have been found to be promising. The effects of musical mnemonics in aging have been scarcely studied. Methods: The present study examined the effects of musical presentation of digits (pitch sequences, rhythms, and their combinations) on working memory performance in young and older adults, as compared to spoken presentation. Results: A facilitating effect of rhythm was found in both groups, whereas pitch and melodic cues affected performance negatively in older adults only. Musical training did not moderate the effect of musical mnemonics. Discussion: To investigate whether persons with working memory impairment also benefit from musical mnemonics, follow-up research in older persons with, for instance, mild cognitive impairment or Alzheimer's dementia is recommended. 14 p.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

R-spondin 4 (RSPO4) is a suggestive risk gene of stage III-IV, grade C periodontitis and upregulated in gingiva of mice resistant to bacteria-induced alveolar bone loss. We aimed to replicate the association, identify and characterize the putative causal variant(s) and molecular effects, and understand the downstream effects of RSPO4 upregulation.We performed a two-step association study for RSPO4 with imputed genotypes of a German-Dutch (896 stage III-IV, grade C periodontitis cases, 7104 controls) and Spanish sample (441 cases and 1141 controls). We analysed the allelic effects on transcription factor binding sites with reporter gene and antibody electrophoretic mobility shift assays. We used CRISPR/dCas9 activation and RNA sequencing to pinpoint RSPO4 as the target gene and to analyse downstream effects.RSPO4 was associated with periodontitis (rs6056178, pRSPO4 is a potential periodontitis risk gene and modifies host defence and barrier integrity.

While cross-clamp site is a known risk factor for postoperative acute and chronic renal dysfunction following open abdominal aortic aneurysm surgery (AAA), the additive impact of patient demographic and clinical factors is lacking. In this study, we investigated the impact of body mass index (BMI), surgical duration and aneurysm diameter on the association between proximal cross-clamp location and postoperative renal dysfunction.In this study, we conducted a retrospective analysis of 4,197 patients undergoing open AAA surgery between 2011 and 2018 using data housed in the American College of Surgeons National Safety Quality Improvement Program (ACS-NSQIP) database. The primary outcome was renal dysfunction, which was defined as patients requiring dialysis within 30 days or patients with ≥2 mg/dL rise in creatinine from baseline. We assessed the incidence of renal dysfunction with regard to clamp location and subsequently used multivariable logistic regression to assess clinical and demographic factors associated with renal dysfunction. We used a regression model to plot the association of BMI, surgical duration, and aneurysm diameter with an adjusted probability of postoperative acute and chronic renal dysfunction for individual cross-clamp locations.Of the 4,197 patients analyzed, 405 patients (9.6%) developed renal dysfunction within 30 days with 287 patients requiring dialysis. Patients with supraceliac clamp location had the highest incidence of renal dysfunction (20.4%). Our data showed a significant association of renal dysfunction with higher BMI patients [OR 1.04 (1.02, 1.07), P = 0.001], longer operative times [OR1.01 (1.01, 1.02), P 0.001], clamp location between the superior mesenteric artery (SMA) and renal artery [OR 1.80 (1.17, 2.78), P = 0.007] and supraceliac clamp location [OR 2.47 (1.62, 3.76), P 0.001].The incidence of renal dysfunction increases with suprarenal clamps. Patients with higher BMI, longer operative times, and increasing aneurysm diameter, and a suprarenal clamp have a significantly increased risk of renal dysfunction compared to those who also had a suprarenal clamp but lower BMI, shorter operative times and smaller aneurysm diameter.

Driving pressure (ΔP) and mechanical power (MP) may be important mediators of lung injury in acute respiratory distress syndrome (ARDS) however there is little evidence for strategies directed at lowering these parameters. We applied predictive modeling to estimate the effects of modifying ventilator parameters on ΔP and MP.2,622 ARDS patients (Berlin criteria) from the Medical Information Mart for Intensive Care IV database (MIMIC-IV version1.0) admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center between 2008 and 2019 were included. Flexible confounding-adjusted regression models for time varying data were fit to estimate the effects of adjusting PEEP and tidal volume (VReduction in VThis novel conditional modeling confirmed expected response patterns for ΔP, with the response to adjustments depending on patients' lung mechanics. Furthermore a V

Background Previous studies linked a high intensity of ventilation, measured as mechanical power, to mortality in patients suffering from “classic” ARDS. By contrast, mechanically ventilated patients with a diagnosis of COVID-19 may present with intact pulmonary mechanics while undergoing mechanical ventilation for longer periods of time. We investigated whether an association between higher mechanical power and mortality is modified by a diagnosis of COVID-19. Methods This retrospective study included critically ill, adult patients who were mechanically ventilated for at least 24 h between March 2020 and December 2021 at a tertiary healthcare facility in Boston, Massachusetts. The primary exposure was median mechanical power during the first 24 h of mechanical ventilation, calculated using a previously validated formula. The primary outcome was 30-day mortality. As co-primary analysis, we investigated whether a diagnosis of COVID-19 modified the primary association. We further investigated the association between mechanical power and days being alive and ventilator free and effect modification of this by a diagnosis of COVID-19. Multivariable logistic regression, effect modification and negative binomial regression analyses adjusted for baseline patient characteristics, severity of disease and in-hospital factors, were applied. Results 1,737 mechanically ventilated patients were included, 411 (23.7%) suffered from COVID-19. 509 (29.3%) died within 30 days. The median mechanical power during the first 24 h of ventilation was 19.3 [14.6–24.0] J/min in patients with and 13.2 [10.2–18.0] J/min in patients without COVID-19. A higher mechanical power was associated with 30-day mortality (ORadj 1.26 per 1-SD, 7.1J/min increase; 95% CI 1.09–1.46; p = 0.002). Effect modification and interaction analysis did not support that this association was modified by a diagnosis of COVID-19 (95% CI, 0.81–1.38; p-for-interaction = 0.68). A higher mechanical power was associated with a lower number of days alive and ventilator free until day 28 (IRRadj 0.83 per 7.1 J/min increase; 95% CI 0.75–0.91; p Conclusion A higher mechanical power is associated with elevated 30-day mortality. While patients with COVID-19 received mechanical ventilation with higher mechanical power, this association was independent of a concomitant diagnosis of COVID-19.

Background Combining oxygen facemask with apnoeic oxygenation using high-flow-nasal-oxygen (HFNO) for preoxygenation in the operating room has not been studied against standard oxygen facemask alone. We hypothesized that facemask-alone would be associated with lower levels of lowest end-tidal oxygen (EtO2) within 2 min after intubation in comparison with facemask combined with HFNO. Methods In an international prospective before–after multicentre study, we included adult patients intubated in the operating room from September 2022 to December 2022. In the before period, preoxygenation was performed with facemask-alone, which was removed during laryngoscopy. In the after period, facemask combined with HFNO was used for preoxygenation and HFNO for apnoeic oxygenation during laryngoscopy. HFNO was maintained throughout intubation. The primary outcome was the lowest EtO2 within 2 min after intubation. The secondary outcome was SpO2 ≤ 95% within 2 min after intubation. Subgroup analyses were performed in patients without and with obesity. This study was registered 10 August 2022 with ClinicalTrials.gov, number NCT05495841. Results A total of 450 intubations were evaluated, 233 with facemask-alone and 217 with facemask combined with HFNO. In all patients, the lowest EtO2 within 2 min after intubation was significantly lower with facemask-alone than with facemask combined with HFNO, 89 (85–92)% vs 91 (88–93)%, respectively (mean difference − 2.20(− 3.21 to − 1.18), p p = 0.004]; as in patients without obesity [90(86–92)% vs 91(89–93)%, p = 0.001)]. SpO2 ≤ 95% was more frequent with facemask-alone (14/232, 6%) than with facemask combined with HFNO (2/215, 1%, p = 0.004). No severe adverse events were recorded. Conclusions Combining facemask with HFNO for preoxygenation and apnoeic oxygenation was associated with increased levels of lowest EtO2 within 2 min after intubation and less desaturation.

The Energy Cloud (EC) is an emerging theme that has emerged as an option to the issues of managing energy supply and demand, since it makes use of tools that streamline this process, such as cloud computing, data processing, and smart devices. Efforts need to be focused on the regulation of this energy management model and understanding what affects or delays this process which is essential for the diffusion of EC. Thus, the objective of this paper is to present and discuss, through a systematic literature review, the factors that interfere in the energy regulatory process with emphasis on EC. This research resulted in 29 Critical Success Factors (CSF), which, according to similar characteristics, were grouped into 7 Fundamental Points of View (FPV): economic, personal or socio-cultural, availability, institutional and market, regulatory infrastructure, external and information factors, and ideology. The CSFs and FPVs were cited 183 times in the selected articles. The analysis of these factors contributed to the identification of barriers that affect the energy regulatory process, delaying the development towards an EC environment, and discussed the main regulatory challenges and opportunities in this area.

This paper presents a before and after analysis of the impact of posted speed limit (PSL) changes on passenger car (FHWA class 2 vehicle) speeds in Portland, Oregon. The study focuses on urban roads, comparing sites that underwent a PSL 5-mph reduction (treatment sites) and sites where the PSL did not change (control sites). Sites with a high percentage of and priority for cyclists (neighborhood greenways) and sites with a more standard traffic composition were compared. Differences in speed characteristics such as mean and 85th percentile speeds, the speed variance, and the proportion of vehicles exceeding a speed threshold (relative to the PSL) were evaluated on aggregate and individual scales. A series of statistical hypothesis tests were employed to assess changes in the speed characteristics among individual data set pairs. The results suggest distinct differences between the treatment and control groups and neighborhood greenway and non-greenway sites. Although there is a high degree of variability, the treatment group experienced more decreases in the speed characteristics, and by a greater amount than the control group, on average. Within the treatment group, sites with a priority for cyclists were even more likely to experience a larger reduction in operating speeds. These results could be interpreted as link-level data providing indirect yet supporting evidence for the safety in numbers hypothesis and changes in motorists’ behavior on neighborhood greenways.

Contains fulltext : 291980.pdf (Publisher’s version ) (Open Access) Based on the idea that music acts as a mnemonic aid, musical mnemonics (i.e., sung presentation of information, also referred to as 'music as a structural prompt'), are being used in educational and therapeutic settings. However, evidence in general and patient populations is still scarce. We investigated whether musical mnemonics affect working and episodic memory performance in cognitively unimpaired individuals and persons with Alzheimer's dementia (AD). Furthermore, we examined the possible contribution of musical expertise. We comprehensively searched the PubMed and PsycINFO databases for studies published between 1970 and 2022. Also, reference lists of all identified papers were manually extracted to identify additional articles. Of 1,126 records identified, 37 were eligible and included. Beneficial effects of musical mnemonics on some aspect of memory performance were reported in 28 of 37 studies, including nine on AD. Nine studies found no beneficial effect. Familiarity contributed positively to this beneficial effect in cognitively unimpaired adults, but require more extensive investigation in AD. Musical expertise generally did not lead to additional benefits for cognitively unimpaired participants, but may benefit people with AD. Musical mnemonics may help to learn and remember verbal information in cognitively unimpaired individuals and individuals with memory impairment. Here, we provide a theoretical model of the possible underlying mechanisms of musical mnemonics, building on previous frameworks. We also discuss the implications for designing music-based mnemonics 14 april 2023 23 p.

Encapsulation of rocuronium or vecuronium with sugammadex can reverse neuromuscular block faster than neostigmine reversal. This pharmacodynamic profile might facilitate patient discharge after ambulatory surgery.We included patients who underwent ambulatory surgery with general anaesthesia and neuromuscular block between 2016 and 2021 from hospital registries at two large academic healthcare networks in the USA. The primary outcome was postoperative length of stay in the ambulatory care facility (PLOS-ACF). We examined post hoc whether the type of reversal affects postoperative nausea and vomiting and direct hospital costs.Among the 29 316 patients included, 8945 (30.5%) received sugammadex and 20 371 (69.5%) received neostigmine for reversal. PLOS-ACF and costs were lower in patients who received sugammadex vs neostigmine (adjusted difference in PLOS-ACF: -9.5 min; 95% confidence interval [95% CI], -10.5 to -8.5 min; adjusted difference in direct hospital costs: -US$77; 95% CI, -$88 to -$66; respectively; P0.001). The association was magnified in patients over age 65 yr, with ASA physical status2 undergoing short procedures (2 h) (adjusted difference in PLOS-ACF: -18.2 min; 95% CI, -23.8 to -12.4 min; adjusted difference in direct hospital costs: -$176; 95% CI, -$220 to -$128; P0.001). Sugammadex use was associated with reduced postoperative nausea and vomiting (17.2% vs 19.6%, P0.001), which mediated its effects on length of stay.Reversal with sugammadex compared with neostigmine was associated with a small decrease in postoperative length of stay in the ambulatory care unit. The effect was magnified in older and high-risk patients, and can be explained by reduced postoperative nausea and vomiting. Sugammadex reversal in ambulatory surgery may also help reduce cost of care.

Periodontitis is a common complex inflammatory disease of the oral cavity. It is characterized by inflammation of gingival tissues and alveolar bone loss. Recently, a genome-wide association study and 2 genome-wide association study meta-analyses found 2 associated regions (haplotype blocks) at the inhibitory immune receptor gene SIGLEC5 to increase the risk for periodontitis. The aims of the current study were the identification of the putative causal variants underlying these associations, characterization of their molecular biological effects, and validation of SIGLEC5 as the target gene. We mapped the associated single-nucleotide polymorphisms to DNA elements with predictive features of regulatory functions and screened the associated alleles for transcription factor (TF) binding sites. Antibody electrophoretic mobility shift assays (EMSAs) with allele-specific probes were used to identify TF binding and to quantify allele-specific effects on binding affinities. Luciferase reporter assays were used to quantify the effect directions and allele-specific strength of the associated regulatory elements. We used CRISPR-dCas9 gene activation to validate SIGLEC5 as a target of the association. EMSA in peripheral blood mononuclear cells showed that E-26 transformation–specific TF-related gene (ERG) binds at rs11084095, with almost complete loss of binding at the minor A-allele. Allele-specific reporter genes showed enhancer function of the DNA sequence at rs11084095, which was abrogated in the background of the A-allele. EMSA in B lymphocytes showed that TF MAF bZIP (MAFB) binds at the common G-allele of rs4284742, whereas the minor A-allele reduced TF binding by 69%, corresponding to 9-fold reduction of luciferase reporter gene activity by the A-allele. Using CRISPR-dCas9, we showed that the enhancer at rs4284742 strongly activated SIGLEC5 expression, validating this gene as the target gene of the association. We conclude that rs11084095 and rs4284742 are putatively causal for the genome-wide significant associations with periodontitis at SIGLEC5 that impair ERG and MAFB binding, respectively.

The eukaryotic protozoanEntamoeba gingivalis(E.g.) is strongly associated with inflamed periodontal pockets. Unlike other obligate anaerobicEntamoebaspecies, it is considered to not have a life cycle of actively dividing trophozoites and dormant cysts. Accordingly, it has been regarded as non-infectious. To investigate ifE.gis capable of encystation in response to adverse environmental conditions, we cultivated clinical isolates ofE.g. collected from inflamed periodontal pockets in antibiotics for 8 days. The cytomorphological and ultrastructure forms of the amoeba were investigated by transmission and scanning electron microscopy to reveal cyst formation. We observed exocysts and the encapsulated trophozoids separated by an intra-cystic space, a dense poorly vesiculated cytoplasma and polygonal surface areas of cysts. The cysts walls were composed of chitin. Cysts were conspicuously smaller compared to trophozoids and lacked pseudo- and filipodia. We did not observe multi-nucleated trophozoids after antibiotic induces encystation. Cyst formation inE.gmay explain why established treatment approaches often do not stop periodontal tissue destruction during periodontitis and periimplantitis.

© 2021 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.Aims: Various studies have reported that young European women are more likely to develop early-onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype-by-sex (G × S) interactions contribute to the increased prevalence and severity. Materials and methods: Using the case-only design, we tested for differences in genetic effects between men and women in 896 North-West European early-onset cases, using imputed genotypes from the OmniExpress genotyping array. Population-representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population. Results: In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S-associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome-wide-associated with heel bone mineral density (CPEB4, MECOM), waist-to-hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13). Conclusions: Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter-sex phenotypic variation in early-onset periodontitis.

BACKGROUND: It is unclear whether intraoperative arterial hypotension is associated with postoperative delirium. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with increased odds of delirium after surgery. METHODS: Adult noncardiac surgical patients undergoing general anesthesia at 2 academic medical centers between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as the cumulative duration of an intraoperative mean arterial pressure (MAP) = 15 minutes; median [IQR], 21 [17-31] minutes) durations of intraoperative hypotension. The primary outcome was a new diagnosis of delirium within 30 days after surgery. In secondary analyses, we assessed the association between a MAP decrease of >30% from baseline and postoperative delirium. Multivariable logistic regression adjusted for patient- and procedure-related factors, including demographics, comorbidities, and markers of procedural severity, was used. RESULTS: Among 316,717 included surgical patients, 2183 (0.7%) were diagnosed with delirium within 30 days after surgery; 41.7% and 2.6% of patients had a MAP 30% from baseline was not associated with postoperative delirium compared to no hypotension, also when additionally adjusted for the cumulative duration of a MAP 30%: ORadj, 1.13; 95% CI, 0.91-1.40; P = .262 and prolonged duration of MAP decrease >30%: ORadj, 1.19; 95% CI, 0.95-1.49; P = .141). CONCLUSIONS: In patients undergoing noncardiac surgery, a MAP

Background Acute right ventricular (RV) failure is a well-described, yet not completely understood, complication of durable left ventricular assist device (LVAD) implantation. Although temporary percutaneous LVAD may have a similar hemodynamic impact on the RV, evidence in this setting is minimal. Purpose This study aims to assess the acute adaptation of the RV to isolated left side support with the Impella device in cardiogenic shock (CS). Methods Consecutive patients assisted with an Impella device and monitored with a pulmonary artery catheter in two tertiary centres between September 2018 and November 2021 were included. Clinical and hemodynamic data were retrospectively recorded at the baseline and up to 72 hours after the implantation of the pLVAD and analysed. Two subgroups analysis were performed to test the chance of a different trend on the basis of baseline RV hemodynamics and of the cause of CS. Results Forty-eight consecutive patients were included; median age was 61 (51.5–70.5) years, 83.3% were male. 54.2% presented with SCAI (Society for Cardiovascular Angiography and Interventions) stage D cardiogenic shock [1], mostly due to myocardial infarction (AMI-CS 56.3%). Impella support was associated with a relevant improvement of the systemic perfusion and left ventricular (LV) loading condition (Table 1). At 24 hours, cardiac output improved from 3.4 (2.6–4.2) to 4.0 (3.0–5.5) L/min, p When stratifying patients by RV hemodynamic parameters at baseline [2], a significantly more pronounced improvement of RAP, RAP/pulmonary capillary wedge pressure (PCWP) and PAPi in the first 24 and 48 hours was seen in those who had poor RV hemodynamics at the baseline (Table 2). Thus, at 24 and 48-hours no differences were detectable anymore in RV hemodynamic parameters between the subgroup with and without RV dysfunction at the baseline evaluation. When stratifying patients by CS aetiology, those with a non-ischemic cause of CS showed a trend toward progressively better parameters of RV function than patients with AMI-CS [median PAPi at 48 hours 1.55 (0.85–2.89) versus 1 (0.73–1.47) in AMI-CS, p=0.1; median RAP/PCWP at 48 hours 0.68 (0.55–0.81) versus 0.89 (0.77–0.92) in AMI-CS, p=0.01]. Conclusion In this cohort of patients with cardiogenic shock undergoing isolated LV support a significant improvement of systemic perfusion and LV loading condition was followed by a tendency towards an improvement of right ventricular function, even in patients with compromised RV hemodynamic profiles at baseline. Funding Acknowledgement Type of funding sources: None.

Metagenomic techniques have facilitated the discovery of thousands of viruses, yet because samples are often highly biodiverse, fundamental data on the specific cellular hosts are usually missing. Numerous gastrointestinal viruses linked to human or animal diseases are affected by this, preventing research into their medical or veterinary importance. Here, we developed a computational workflow for the prediction of viral hosts from complex metagenomic datasets. We applied it to seven lineages of gastrointestinal cressdnaviruses using 1,124 metagenomic datasets, predicting hosts of four lineages. The Redondoviridae, strongly associated to human gum disease (periodontitis), were predicted to infect Entamoeba gingivalis, an oral pathogen itself involved in periodontitis. The Kirkoviridae, originally linked to fatal equine disease, were predicted to infect a variety of parabasalid protists, including Dientamoeba fragilis in humans. Two viral lineages observed in human diarrhoeal disease (CRESSV1 and CRESSV19, i.e. pecoviruses and hudisaviruses) were predicted to infect Blastocystis spp. and Endolimax nana respectively, protists responsible for millions of annual human infections. Our prediction approach is adaptable to any virus lineage and requires neither training datasets nor host genome assemblies. Two host predictions (for the Kirkoviridae and CRESSV1 lineages) could be independently confirmed as virus–host relationships using endogenous viral elements identified inside host genomes, while a further prediction (for the Redondoviridae) was strongly supported as a virus–host relationship using a case–control screening experiment of human oral plaques.

Music is increasingly used in a wide array of settings, from clinical recovery to sports or well-being interventions. Motivation related to music is often considered as a possible working mechanism for music to facilitate these processes, however this has not previously been systematically evaluated. In the current systematic review, studies were considered that involved music (therapy) interventions, together with measures such as wanting to practice, liking the musical activities, or patient adherence to an intervention. The objective of this review was to examine whether music increases motivation in task performance and/or rehabilitation settings, and whether this is commonly related to better clinical or training outcomes. Seventy-nine studies met the inclusion criteria, the majority of which (85%) indicated an increased level of motivation with music as compared to without. Moreover, in those studies where motivation was increased, clinical or other outcomes were improved in most cases (90%). These results support the notion of motivation as an underlying mechanism of music-based interventions, but more robust evidence is needed to ascertain which mechanisms are crucial in increasing motivation from a behavioural, cognitive, and neurobiological point of view, as well as how motivational mechanisms relate to other factors of effectiveness in music-based paradigms.

To assess whether intraoperative use of nitrous oxide (N2O) as an adjunct to general anesthesia is associated with a shorter length of stay in the postanesthesia care unit (PACU). We analyzed data from adult patients who underwent non-cardiothoracic surgery under general anesthesia between May 2008 and December 2018. We assessed the association between intraoperative low- and high-dose N2O and PACU length of stay. A total of 148,284 patients were included in the primary analysis. After adjusting for a priori defined confounders, a high dose of N2O significantly decreased PACU length of stay, with a calculated difference of −9.1 min (95% confidence interval [CI], −10.5 to −7.7; P 30 min difference) in patients who underwent complex surgical procedures and received intraoperative antiemetic therapy.

Transit goals have typically focused on commuter trips but facilitating urban last mile freight logistics is a potential strategy to increase transit ridership and mitigate the demands of parcel distribution on the transportation network. Presently, most parcel lockers operate out of private businesses, but consumer surveys have found that transit users may be interested in locker facilities at transit facilities. The implementation of an unmanned, secure, common carrier parcel locker system could have benefits for non-transit users as well. This research presents a multiple-criteria approach for analyzing the potential of public transportation facilities as hosts for a common carrier locker system. Several accessibility and equity metrics, including ridership, mode of transportation, spatial distribution, and sociodemographic profiles of coverage areas are utilized. A case study utilizing real-word data from the Portland, OR region and its transit facilities is used to illustrate accessibility and equity tradeoffs. The results demonstrate that multiple facility types have the potential to host a locker system but there are complex accessibility and equity tradeoffs to be considered by stakeholders and policy makers when prioritizing locations.

Objective Behcet's disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behcet's disease in a diverse multiethnic population. Methods A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray-24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. Results We identified 2 novel genetic susceptibility loci for Behcet's disease, including a risk locus in IFNGR1 (rs4896243) (odds ratio [OR] 1.25; P = 2.42 x 10(-9)) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 x 10(-8)). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide-stimulated monocytes. In addition, our results replicated the association (P < 5 x 10(-8)) of 6 previously identified susceptibility loci in Behcet's disease: IL10, IL23R, IL12A-AS1, CCR3, ADO, and LACC1, reinforcing the notion that these loci are strong genetic factors in Behcet's disease shared across ancestries. We also identified >30 genetic susceptibility loci with a suggestive level of association (P < 5 x 10(-5)), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behcet's disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated. Conclusion We performed the largest genetic association study in Behcet's disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [R01AR070148]; NIH [U54GM104938, U19AI082714, UM1AI144292, P30AR053483, P30AR073750], Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) grant number R01AR070148 to Dr. Sawalha. Recruitment and genotyping of the EuropeanAmerican controls was supported by NIH grants number U54GM104938, U19AI082714, UM1AI144292, P30AR053483, and P30AR073750 to Drs. Guthridge and James. This work was supported by the use of study data downloaded from the dbGaP web site, under dbGaP accession phs000272. v1.p1.

Genome-wide association studies identified various loci associated with periodontal diseases, but assigning causal alleles remains difficult. Likewise, the generation of biological meaning underlying a statistical association has been challenging. Here, we characterized the genetic association at the gene ST8SIA1 that increases the risk for severe periodontitis in smokers. We used CRISPR/dCas9 activation and RNA-sequencing to identify genetic interaction partners of ST8SIA1 and to determine its function in the cell. We used reporter gene assays to identify regulatory elements at the associated single-nucleotide polymorphisms (SNPs) and to determine effect directions and allele-specific changes of enhancer activity. Antibody electrophoretic mobility shift assays proved allele-specific transcription factor binding at the putative causal SNPs. We found the reported periodontitis risk gene ABCA1 as the top upregulated gene following ST8SIA1 activation. Gene set enrichment analysis showed highest effects on integrin cell surface interactions (area under the curve [AUC] = 0.85; q = 4.9 × 10−6) and cell cycle regulation (AUC = 0.89; q = 1.6 × 10−5). We identified 2 associated repressor elements in the introns of ST8SIA1 that bind the transcriptional repressor BACH1. The putative causative variant rs2012722 decreased BACH1 binding by 40%. We also pinpointed ST8SIA1 as the target gene of the association. ST8SIA1 inhibits cell adhesion with extracellular matrix proteins, integrins, and cell cycle, as well as enhances apoptosis. Likewise, tobacco smoke reportedly results in an inhibition of cell adhesion and a decrease in integrin-positive cells and cell growth. We conclude that impaired ST8SIA1 repression, independently caused by reduced BACH1 binding at the effect T allele, as well as by tobacco smoke, contributes to higher ST8SIA1 levels, and in smokers who carry the effect T allele, both factors would be additive with damaging effects on the gingival barrier integrity. The activity of ST8SIA1 is also linked with the periodontitis risk gene ABCA1.

Objective: We aimed to identify a microRNA (miRNA) that is significantly upregulated in blood and in cells of the oral mucosa upon exposure to the periodontitis main risk factors oral inflammation and tobacco smoke, to subsequently identify its target gene and to describe the molecular mechanism of gene regulation. Background: miRNAs are associated with many disorders. Array-based miRNA expression studies indicated a number of differentially expressed miRNAs in the pathology of oral diseases. However, these miRNAs mostly lacked replication, and their target genes have remained unknown. Methods: 863 miRNAs were analyzed in blood from 18 PD cases and 70 controls (Geniom Biochip). Selected miRNAs were analyzed for upregulation in the inflamed oral mucosa of PD patients using published miRNA expression profiling studies from gingival cells. hsa-miR-374b-5p mimic was overexpressed in primary gingival fibroblasts (pGFs) from 3 donors, and genome-wide mRNA expression was quantified (Clarion Array). Gene-specific regulation was validated by qRT-PCR and Luciferase activity in HeLa cells. Results: hsa-miR-374b-5p showed >twofold change (FC) in 3 independent studies performed in blood, gingival tissues, and cells. After hsa-miR-374b-5p overexpression, genome-wide expression analysis showed UHMK1 as top 1 downregulated gene in pGFs (p = 2.5 × 10-04 , fold change = -1.8). Reporter genes demonstrated that hsa-miR-374b-5p downregulates mRNA levels (p = .02; FC = -1.5), leading to reduction in protein activity (p = .013, FC = -1.3). Conclusions: hsa-miR-374b-5p is upregulated in blood and ginvial cells exposed to oral inflammation and tobacco smoke and regulates UHMK1, which has a role in osteoclast differentiation.