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The objective of this paper was to examine the school-related experiences of youth during the COVID-19 pandemic. Participants represented both clinical and community youth aged 14 to 28 who were sampled as part of a larger study. Feedback from youth attending school during the pandemic was qualitatively examined and youth who planned to attend school prior to the pandemic and did (n = 246) and youth who planned to attend but did not (n = 28) were compared quantitatively. Youth appreciated the flexibility of online learning and some also reported experiencing a lack of support from their school and the need for instructor training on how to deliver virtual classes effectively. Future studies should examine what factors influence student engagement with virtual learning, what strategies could improve supports for student in their long-term career development, and the longitudinal experiences of youth who may have chosen not to go back to school due to the pandemic. This survey was conducted in Ontario, Canada. A more diverse sample collected outside of Ontario would improve generalizability. Qualitative data were based on survey responses and not interviews. Thus we were unable to discern the reasons youth decided to attend school, or not, during the COVID-19 pandemic.

Objective: Integrated youth services (IYS) are an emerging model of care offering a broad range of mental health and social services for youth in one location. This study aimed to determine the IYS service characteristics most important to youth, as well as to determine whether different classes of youth have different service preferences, and if so, what defines these classes. Methods: Ontario youth aged 14–29 years with mental health challenges were recruited to participate in a discrete choice experiment (DCE) survey. The DCE contained 12 attributes, each represented by 4 levels representing core characteristics of IYS models. To supplement the DCE questions, demographic information was collected and a mental health screener was administered. Preferences were examined, latent class analyses were conducted, and latent classes were compared. Results: As a whole, participants endorsed the IYS model of service delivery. Among 274 youth, there were three latent classes: 1) the Focused Service (37.6%) latent class prioritized efficient delivery of mental health services. 2) The Holistic Services (30.3%) latent class prioritized a diverse array of mental health and social services delivered in a timely fashion. 3) The Responsive Services (32.1%) latent class prioritized services that matched the individual needs of the youth being served. Differences between classes were observed based on sociodemographic and clinical variables. Conclusions: IYS is an acceptable model of care, in that it prioritizes components that reflect youth preferences. The differences in preference profiles of different groups of youth point to the need for flexible models of service delivery. Service design initiatives should take these preferences into account, designing services that meet the needs and preferences of a broad range of youth. Working locally to co-design services with the youth in the target population who wish to be engaged will help meet the needs of youth. [ABSTRACT FROM AUTHOR]

Aim: To examine mental health in conjunction with physical health during the COVID‐19 pandemic among youth with physical health conditions compared to those without. Methods: A cross‐sectional survey of 622 youth aged 14 to 28 was conducted. Analyses were conducted to understand the changes in mental and physical health among youth in four groups: (a) participants with a friend or family member diagnosed with COVID‐19, (b) participants with symptoms associated with COVID‐19, (c) participants with atopic conditions (asthma and allergies), and (d) participants with other preexisting physical health conditions. Results: Many participants with physical health concerns met screening criteria for an internalizing disorder, which was significantly higher than the rate found among participants without physical health conditions. Significantly greater declines in self‐reported mental health were observed during the COVID‐19 period compared to 3 months earlier among youth reporting physical health concerns compared to those without physical health concerns. Substance use does not appear to have been affected. Conclusions: Mental health concerns are highly prevalent among youth with physical health concerns, and also appear to be exacerbated by the COVID‐19 pandemic. Physical health concerns appear to constitute risk factors for heightened mental health responses to the pandemic situation. System planners striving to adapt mental health services to meet social/physical distancing recommendations are urged to consider youth with physical health conditions and ensure that adequate integrated mental health and physical health supports are available to them. [ABSTRACT FROM AUTHOR]

Aim: The issue of youth who are not engaged in education, employment or training has been a focus of policymakers for decades. Although interventions exist for these youth, they often measure success in ways that fail to capture what youth seek to gain. The project aims to address this gap by assessing youth‐oriented outcomes for interventions targeting upcoming youth. Acknowledging the stigma attached to the deficit‐based notion of not engaged in education, employment or training, hereafter we refer to 'upcoming youth', a term coined by youth partners on the project. This study asks what youth want to achieve by participating in an intervention for upcoming youth, with a view to guiding service and research design. Methods: A mixed‐methods discrete choice experiment will be conducted with youth engaged as partners. A qualitative (focus group) stage will be conducted to design discrete‐choice experiment attributes and levels. The experiment will be piloted and administered online to approx. 500 youth (aged 14‐29) across Canada to identify the outcomes that youth prioritize for interventions. Latent class analyses will then be conducted to explore clusters of outcomes that different groups of youth prioritize. Conclusions: From a strengths‐based recovery‐oriented framework, hearing the voices of the target population is important in designing and evaluating services. This youth‐oriented research project will identify the intervention outcomes that are the highest priority for upcoming youth. Findings will inform the development, implementation and testing of interventions targeting relevant outcomes for youth who are not engaged in education, employment or training. [ABSTRACT FROM AUTHOR]

Purpose: Foam cell macrophage (FCM) formation is an early event in atherosclerosis that could contribute to fibrous cap development, although it has also been strongly implicated in cap rupture and thrombus formation. To understand this apparent paradox we compared the transcriptome of FCM and non-foamy macrophages (NFM) produced in vivo using Illumina bead chips.Methods: Sponges were implanted into fat-fed ApoE null or chow-fed C57Bl6 mice to produce FCM or NFM, respectively. Cells were purified based on their buoyant density and/or differential adherence. Gene expression was examined using Ingenuity Pathway Analysis, GO annotation and clustering (DAVID Bioinformatics Resources). Data was confirmed using q-PCR and IHC.Results: The functions enriched/upregulated in FCM included connective tissue development, function and disorders as well as immune response, cell signalling. The primary canonical pathway upregulated in the FCM was liver X receptor/retinoid X receptor (LXR/RXR) activation, consistent with a recent study using peritoneal FCM from LDLr knockout mice (Spann et al Cell 2012;151:138). We confirmed that FCM had more mRNA for LXR, RXR and target genes using qRT-PCR, and used IHC to identify LXRα containing FCM in the sponges. GO identified hepatic fibrosis pathways as highly upregulated in the FCM and Ingenuity suggested a role for transforming growth factor β1 (TGFβ1). For example, there was an increase in mRNA for many extracellular matrix proteins (including collagens 1, 4, 6, 8, biglycan and decorin), connective tissue growth factor (CTGF), BMP-1 and Fos/FosB/Jun/JunB. FCM also had more mRNA for matrix proteases (including cathepsins C and E and matrix metalloproteinases 2 and 23), without a corresponding difference in their inhibitors. Using IHC we established that many cells within the sponges and brachiocephalic arteries from fat-fed ApoE mice contained CTGF. As TGFβ1-induced CTGF expression is known to be regulated via SMADs, we examined these tissues for the presence of phosphoSMAD2 (pSMAD2) by IHC and found that it was present in the cytoplasm and nucleus of sponge FCM and plaque cells.Conclusions: Our data confirm the paradox introduced by Spann and colleagues showing that FCMs are anti-inflammatory via LXR activation. We have extended this by showing that FCM can contribute to fibrosis and matrix deposition, possibly due to exposure to TGFβ1. Clearly additional factors, including mediators of innate and acquired immunity, must be responsible for converting FCM from an anti-inflammatory/pro-fibrotic phenotype into cells capable of mediating plaque rupture. [ABSTRACT FROM PUBLISHER]

Establishing preclinical models of Alzheimer's disease that predict clinical outcomes remains a critically important, yet to date not fully realized, goal. Models derived from human cells offer considerable advantages over non-human models, including the potential to reflect some of the inter-individual differences that are apparent in patients. Here we report an approach using induced pluripotent stem cell-derived cortical neurons from people with early symptomatic Alzheimer's disease where we sought a match between individual disease characteristics in the cells with analogous characteristics in the people from whom they were derived. We show that the response to amyloid-β burden in life, as measured by cognitive decline and brain activity levels, varies between individuals and this vulnerability rating correlates with the individual cellular vulnerability to extrinsic amyloid-β in vitro as measured by synapse loss and function. Our findings indicate that patient-induced pluripotent stem cell-derived cortical neurons not only present key aspects of Alzheimer's disease pathology but also reflect key aspects of the clinical phenotypes of the same patients. Cellular models that reflect an individual's in-life clinical vulnerability thus represent a tractable method of Alzheimer's disease modelling using clinical data in combination with cellular phenotypes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The Clinical Institute Withdrawal Assessment-Alcohol, Revised (CIWA-Ar) is an assessment tool used to quantify alcohol withdrawal syndrome (AWS) severity and inform benzodiazepine treatment for alcohol withdrawal., Objectives: To evaluate the prescribing patterns and appropriate use of the CIWA-Ar protocol in a general hospital setting, as determined by the presence or absence of documented AWS risk factors, patients' ability to communicate, and provider awareness of the CIWA-Ar order., Methods: This retrospective chart review included 118 encounters of hospitalized patients placed on a CIWA-Ar protocol during one year. The following data were collected for each encounter: patient demographics, admitting diagnosis, ability to communicate, and admission blood alcohol level; and medical specialty of the clinician ordering CIWA-Ar, documentation of the presence or absence of established AWS risk factors, specific parameters of the protocol ordered, service admitted to, provider documentation of awareness of the active protocol within 48 h of initial order, total benzodiazepine dose equivalents administered and associated adverse events., Results: 57% of patients who started on a CIWA-Ar protocol had either zero or one documented risk factor for AWS (19% and 38% respectively). 20% had no documentation of recent alcohol use. 14% were unable to communicate. 19% of medical records lacked documentation of provider awareness of the ordered protocol. Benzodiazepine associated adverse events were documented in 15% of encounters., Conclusions: The judicious use of CIWA-Ar protocols in general hospitals requires mechanisms to ensure assessment of validated alcohol withdrawal risk factors, exclusion of patients who cannot communicate, and continuity of care during transitions.

Safety-net patients' socioeconomic barriers interact with limited digital and health literacies to produce a "knowledge gap" that impacts the delivery of healthcare via telehealth technologies. Six focus groups (2 African- American and 4 Latino) were conducted with patients who received teleretinal screening in a U.S. urban safety-net setting. Focus groups were analyzed using a modified grounded theory methodology. Findings indicate that patients' knowledge gap is primarily produced at three points during the delivery of care: (1) exacerbation of patients' pre-existing personal barriers in the clinical setting; (2) encounters with technology during screening; and (3) lack of follow up after the visit. This knowledge gap produces confusion, potentially limiting patients' perceptions of care and their ability to manage their own care. It may be ameliorated through delivery of patient education focused on both disease pathology and specific role of telehealth technologies in disease management.

Background: Thelper1 (Th1) lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1) macrophage activation or production of matrix degrading metalloproteinases (MMPs) and their tissue inhibitors, TIMPs., Methods & Results: We studied the effect of T-bet deletion in apolipoproteinE (ApoE) knockout mice fed a high fat diet (HFD) or normal chow diet (ND). Transcript levels of M1/M2 macrophage polarization markers, selected MMPs and TIMPs were measured by RT-qPCR in macrophages isolated from subcutaneous granulomas or in whole aortae. Immunohistochemistry of aortic sinus (AS) and brachiocephalic artery (BCA) plaques was conducted to quantify protein expression of the same factors. Deletion of T-bet decreased mRNA for the M1 marker NOS-2 in granuloma macrophages but levels of M2 markers (CD206, arginase-1 and Ym-1), MMPs-2, -9, -12, -13, -14 and -19 or TIMPs-1 to -3 were unchanged. No mRNA differences were observed in aortic extracts from mice fed a HFD for 12 weeks. Moreover, AS and BCA plaques were similarly sized between genotypes, and had similar areas stained for NOS-2, COX-2, MMP-12 and MMP-14 proteins. T-bet deletion increased MMP-13, MMP-14 and arginase-1 in AS plaques. After 35 weeks of ND, T-bet deletion reduced the size of AS and BCA plaques but there were no differences in the percentage areas stained for M1 or M2 markers, MMPs-12, -13, -14, or TIMP-3., Conclusions: Absence of Th1 lymphocytes is associated with reduced plaque size in ApoE knockout mice fed a normal but not high fat diet. In either case, M1 macrophage polarization and expression of several MMPs related to plaque instability are either maintained or increased.

Background: Rupture of advanced atherosclerotic plaques accounts for most life-threatening myocardial infarctions. Classical (M1) and alternative (M2) macrophage activation could promote atherosclerotic plaque progression and rupture by increasing production of proteases, including matrix metalloproteinases (MMPs). Lymphocyte-derived cytokines may be essential for generating M1 and M2 phenotypes in plaques, although this has not been rigorously tested until now., Methods and Results: We validated the expression of M1 markers (iNOS and COX-2) and M2 markers (arginase-1, Ym-1, and CD206) and then measured MMP mRNA levels in mouse macrophages during classical and alternative activation in vitro. We then compared mRNA expression of these genes ex vivo in foam cells from subcutaneous granulomas in fat-fed immune-competent ApoE knockout (KO) and immune-compromised ApoE/Rag-1 double-KO mice, which lack all T and B cells. Furthermore, we performed immunohistochemistry in subcutaneous granulomas and in aortic root and brachiocephalic artery atherosclerotic plaques to measure the extent of M1/M2 marker and MMP protein expression in vivo. Classical activation of mouse macrophages with bacterial lipopolysaccharide in vitro increased MMPs-13, -14, and -25 but decreased MMP-19 and TIMP-2 mRNA expressions. Alternative activation with IL-4 increased MMP-19 expression. Foam cells in subcutaneous granulomas expressed all M1/M2 markers and MMPs at ex vivo mRNA and in vivo protein levels, irrespective of Rag-1 genotype. There were also similar percentages of foam cell macrophages (FCMs) carrying M1/M2 markers and MMPs in atherosclerotic plaques from ApoE KO and ApoE/Rag-1 double-KO mice., Conclusion: Classical and alternative activation leads to distinct MMP expression patterns in mouse macrophages in vitro. M1 and M2 polarization in vivo occurs in the absence of T and B lymphocytes in either granuloma or plaque FCMs.

The authors present the case of a 43-year-old gentleman who was admitted for an elective surgical removal of an eroded gastric band. The patient reported no medical concerns and other than a mild anaemia of haemoglobin of 10.6, his preoperative assessment was non-significant. Postoperatively, the patient spiked temperatures on multiple occasions. When a travel history was subsequently taken, the patient revealed he had returned from Nigeria the night before his elective surgery. The patient tested positive for Plasmodium falciparum malaria for which he was successfully managed with oral quinine and doxycycline, and recuperated well both from malaria and the surgery. P falciparum malaria is a medical emergency and increases the morbidity and mortality of anaesthesia and surgery. Travel histories are not currently routinely taken as part of the preoperative assessment for elective surgical admissions; the authors argue that it should become a mandatory part.

Most acute coronary events occur in the upstream region of stenotic atherosclerotic plaques that experience laminar shear stress (LSS) elevated above normal physiological levels. Many studies have described the atheroprotective effect on endothelial behavior of normal physiological LSS (approximately 15 dynes/cm(2)) compared to static or oscillatory shear stress (OSS), but it is unknown whether the levels of elevated shear stress imposed by a stenotic plaque would preserve, enhance or reverse this effect. Therefore we used transcriptomics and related functional analyses to compare human endothelial cells exposed to laminar shear stress of 15 (LSS15-normal) or 75 dynes/cm(2) (LSS75-elevated). LSS75 upregulated expression of 145 and downregulated expression of 158 genes more than twofold relative to LSS15. Modulation of the metallothioneins (MT1-G, -M, -X) and NADPH oxidase subunits (NOX2, NOX4, NOX5, and p67phox) accompanied suppression of reactive oxygen species production at LSS75. Shear induced changes in dual specificity phosphatases (DUSPs 1, 5, 8, and 16 increasing and DUSPs 6 and 23 decreasing) were observed as well as reduced ERK1/2 but increased p38 MAP kinase phosphorylation. Amongst vasoactive substances, endothelin-1 expression decreased whereas vasoactive intestinal peptide (VIP) and prostacyclin expression increased, despite which intracellular cAMP levels were reduced. Promoter analysis by rVISTA identified a significant over representation of ATF and Nrf2 transcription factor binding sites in genes upregulated by LSS75 compared to LSS15. In summary, LSS75 induced a specific change in behavior, modifying gene expression, reducing ROS levels, altering MAP kinase signaling and reducing cAMP levels, opening multiple avenues for future study., (Copyright © 2011 Wiley-Liss, Inc.)

The results of a successful demonstration of the selection module of an optoelectronic parallel-processing database filter is presented. The module utilizes 4 x 4 arrays of AND and XOR logic gates that respectively perform the functions of reducing the data fields and determining a match between the input data and a selection argument. The logic arrays were fabricated with InGaP/GaAs heterojunction phototransistors that drive vertical-cavity surface-emitting lasers (VCSEL's). The VCSEL's provide the free-space optical interconnection between stages. The design of the system and the optical power budget are discussed.

Parenteral hyperalimentation is an important means of nutritional support for critically ill patients. Calculating the amount of additives necessary for the appropriate compounding of hyperalimentations is a tedious process with many opportunities for error. A new computer program written in Pascal has been created to reduce pharmacy processing time. Menus and single-keystroke entry are implemented wherever practicable. A hard-copy printout and an individualized label are generated on command. Program testing has resulted in an 88% reduction of processing time.