Several advances in recent decades in digital imaging, artificial intelligence, and multiplex modalities have improved our ability to automatically analyze and interpret imaging data. Imaging technologies such as optical coherence tomography, optical projection tomography, and quantitative phase microscopy allow analysis of tissues and cells in 3-dimensions and with subcellular granularity. Improvements in computer vision and machine learning have made algorithms more successful in automatically identifying important features to diagnose disease. Many new automated multiplex modalities such as antibody barcoding with cleavable DNA (ABCD), single cell analysis for tumor phenotyping (SCANT), fast analytical screening technique fine needle aspiration (FAST-FNA), and portable fluorescence-based image cytometry analyzer (CytoPAN) are under investigation. These have shown great promise in their ability to automatically analyze several biomarkers concurrently with high sensitivity, even in paucicellular samples, lending themselves well as tools in FNA. Not yet widely adopted for clinical use, many have successfully been applied to human samples. Once clinically validated, some of these technologies are poised to change the routine practice of cytopathology. With advancements in computer vision and machine learning, artificial intelligence (AI) and deep learning algorithms have made huge strides in their ability to analyze and interpret imaging data. Cytology was the first setting in which AI was implemented in the pathology laboratories, in the form of computer-assisted Pap test screening. Initially developed with the intention of diagnosing rather than screening, there was significant debate about their broad application to clinical samples. These early systems used morphometric differences to distinguish normal from abnormal cell populations, but due to morphometric overlap between cell populations, and artifact from conventional cytology specimen preparation such as air drying and obscuring blood, the frequently encountered inaccuracies made these tools better suited for screening tests . Since tAn oft-cited challenge in cytology image processing is the three-dimensional 3D) nature of a cytology specimen compared to a histology slide, and early inaccuracies in Pap test computer-assisted screening were partially attributed to the cellular overlap in conventional cervical cytology smears . HoweverD nature in situ imaging than in anatomic pathology. Inasmuch as it pertains to the field of gynecologic pathology and by proxy, cervical cytopathology, a study reported an 88% sensitivity and 69% specificity in detecting high-grade squamous epithelial lesions in loop electrosurgical excision procedure specimens  technology uses light and measurement of back-reflected light, conceptually similar to ultrasound, to examine tissues at the subcellular level. Studies have shown the ability of OCT technology to distinguish normal from neoplastic tissue, though it has been adopted more widely in clinical fields for pecimens . Other cpecimens , 6.Novel imaging techniques also exist that allow 3D imaging of cells in suspension. The Cell-CT instrument employs optical projection tomography and uses a scanning objective lens that can assess single cells and bare nuclei suspended in a microcapillary tube. Similar to a computed tomography (CT) scan, the instrument takes 500 two-dimensional (2D) images of individual cells, and a 3D reconstructed image is produced, with reported resolution close to 1 micrometer, allowing for analysis of sub-cellular features that might not be apparent in routine 2D analysis . With thAnother novel microscopy technique is quantitative phase microscopy that relies on light interference effect to identify cellular features at a resolution near 1 nanometer. The refractive index of cell nuclei as measured by quantitative phase microscopy has been shown to be a sensitive measure of malignancy or premalignancy, and can identify subtle aberrations that were not identified by routine histopathologic examination in breast cancer specimens . Since tThese novel microscopy and image capturing techniques have shown promise in their ability to analyze diseased samples at the cellular and subcellular level. Further studies will undoubtedly show their use in more routine clinical practice. Their development and adoption may diminish many of the unique obstacles that have heretofore favored the application of image analysis and computational pathology to histopathology over cytopathology.Concurrent with the advances in image capture technology has been an increased demand for image analysis. In recent years, the interest in developing computational methods to screen, diagnose, and streamline pathology workflow has increased dramatically. Advances in AI, image analysis, and deep learning are augmenting the myriad ways that computational pathology can be applied to cytopathology.Machine learning is the branch of AI that pertains to the ability of computer algorithms to improve and perform tasks without explicit instruction. It is the use of algorithms to analyze data, automatically learn, and then apply that to new data to make intelligent decisions. Conventional machine learning requires significant engineering and manual input. Based on linear techniques, it has limited ability to process raw data, and this can only be performed with a predetermined set of instructions. With the historical use of conventional machine learning, these algorithms were much less effective when encountering new variables that had not been programmed. Deep machine learning is a more novel subfield of machine learning that employs artificial neural networks (ANN). Inspired by the nervous system, these ANN are complex models with interconnected “neurons” structured into a hierarchy of multiple layers. It is inherently non-linear and too complex to be programmed manually, eliminating the need for manual input of labels to handle large sets of data. With deep machine learning, feature extraction is an inherent part of the computer program rather than determined by human input , 10. In One of the earliest successes of deep learning was image classification, or the ability to give a meaningful label to an image. Initially trained through large labeled image libraries, image classification programs are an example of supervised learning wherein the end goal is to classify something as “x” or “not x.” Different features or explanatory variables are then weighted based on the data gathered from the training set. Through the use of deep learning to extract feature vectors, image classification models have become even more granular in their ability to identify differentiating features in cell morphology , 14. FurThe current era of medicine can seem full of contradictions. With advances in molecular diagnostics and targeted therapy, more and more predictive and prognostic ancillary tests are being performed. Simultaneously, ever-burgeoning healthcare costs have highlighted the need for proper resource utilization . It is iPrecision medicine, guided by predictive biomarkers of individual patients' tumors, has increased overall survival as well as reduced treatment-associated toxicity . Assessmin situ visualization of multiple markers, and thus cell types, in the same slide or specimen. This ability to concurrently examine different populations of cells in situ adds a level of refinement that opens up doors to explore the tumor microenvironment.Multiplex immunohistochemistry/immunofluorescence (M-IHC/IF) allows in situ, in single cells. When used as an adjunct to conventional cytomorphology, it can increase the specificity and sensitivity of tumor detection  is a technology that can assess hundreds of proteins in small cellular samples, such as FNA  technology has also been successfully applied to clinical samples  fixes samples with barcoded antibodies in a cyclic fashion that are then imaged with an automated image cytometer  is another exciting technology at the intersection of multiplex biomarker analysis and computational pathology  approval is not required to use digital pathology systems in a clinical setting. Instead, they are designed, manufactured, and validated in individual laboratories as laboratory developed tests, and the College of American Pathologists (CAP) recommends explicit documentation of this in the pathology report. CAP and Clinical Laboratory Improvement Amendments (CLIA) also require a similar validation process for the use of AI-based technologies on patient samples . The devCulturally, there may also exist reluctance to adopt these new technologies. A valid criticism of AI is that deep machine learning, relying on deep neural networks with multiple, non-linear, abstract layers, is inherently a “black box.” There can be a tendency in these algorithms for bias and/or discrimination, and the lack of transparency can make adjustments difficult. This underscores the need for explainable and transparent systems, ones in which developers can interrogate the algorithms and identify which features are weighted in decision making processes –52. The Ultimately, with continued improvement in these modalities to accurately diagnose disease, further validation through studies with human subjects, approval by regulatory boards, and growing trust between stakeholders and these systems, these advances are poised to change the practice of cytopathology.RL reviewed and synthesized the relevant information and was the primary author of the review article. TK reviewed and synthesized the relevant information and contributed figures and discussion of the review article. JR made substantial contributions to the conception, drafting, and revision of the article. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Pregnancy complications such as gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP) are frequent and influence not only fetal outcomes but also the maternal cardiac function. GDM and HDP may act as a proxy for increased metabolic and cardiovascular risk later in life. Speckle tracking echocardiography (STE) is a relatively new imaging technique that provides more sensitive assessment than conventional echocardiography of the maternal cardiac function. Recent research suggests that STE can be used during pregnancy and postpartum as a useful method of early detection of subclinical maternal cardiac changes related to pregnancy complications, such as GDM and HDP, and as an indicator for future maternal cardiovascular disorders. The aim of this review was to underline the current value of STE in the follow-up protocol of high-risk pregnant women, as a mean for pre- and postpartum monitoring. A review of the literature was conducted in the PubMed database to select relevant articles regarding the association of STE changes and HDP or GDM in the prenatal and postpartum maternal evaluations. Both GDM and HDP are associated with subtle myocardial changes in shape, size and function; these preclinical cardiac changes, often missed by conventional evaluation, can be detected using STE. Left ventricular global circumferential strain might be an important predictor of maternal cardiovascular disorders and might help to define a high-risk group that requires regular monitoring later in life and timely intervention. Echocardiography is a consecrated diagnostic and follow-up method for the adult population with cardiovascular (CV) risk factors and cardiac disease. In pregnancy, maternal echocardiography is reserved for selected cases, with previous cardiac pathologies or onset of symptoms suggesting heart failure either when assessed by the cardiologist or for research purposes, as observed in the recent literature ,2 A new The aim of this review is to underline the value of newer echocardiography techniques in the follow-up protocol of high-risk pregnancies, as a mean for pre- and post-partum monitoring. Pregnancy complications, such as gestational diabetes (GDM) or hypertensive disorders of pregnancy (HDP), can foreshadow subsequent cardiovascular and metabolic disease in future life . TherefoSpecific and standardized assessment of the cardiac function has been the subject of broad and permanent interest ,6. The aHowever, echocardiography is a widely available, non-invasive, not irradiating technique, suitable for maternal heart monitoring in pregnancy and postpartum. Its main disadvantages are related to image acquisition, which is operator- and acoustic-window dependent and to that the assessment of ventricular function is related to geometric assumptions of the normal heart, with less reliability in some cases .M-Mode echocardiography, a method that measures the mid-left ventricle diameters in the short axis and volumes obtained by cubing the diameters, estimates left ventricular fractional shortening and ejection fraction  Figure . A more Global myocardial performance has been assessed by other echocardiographic methods, derived from Doppler analysis, such as myocardial performance index (Tei index) and tissue Doppler mitral annular systolic velocity . These mAnother approach to assess left cardiac function is three-dimensional echocardiography that eliminates the geometric assumptions and operator dependent measurements . A relatively new tool for assessing left ventricular function through myocardial strain with a high temporal and spatial resolution is speckle-tracking imaging . This meCurrently, speckle tracking echocardiography is the most applicable method in the context of pregnancy related complications and has shown the most promising results in detection of subclinical myocardial dysfunction. Two-dimensional speckle-tracking echocardiography is proposed as a novel technique for objective and quantitative evaluation of global and regional myocardial function. The myocardial deformation strains are obtained by frame-by-frame automatic measurement of the distance between two points of each LV segment during the cardiac cycle. The ST allows quantification of myocardial or more correct endocardial deformation. This technique enables us to calculate the segmental, as well as the global longitudinal, strain and strain rate. It measures myocardial velocities and deformation parameters and has evolved to be the imaging modality of choice to detect subclinical cardiac dysfunction .Subclinical cardiac dysfunction precedes the development of heart failure and other cardiovascular diseases, but often goes undiagnosed by conventional echocardiography. Recognition of subclinical myocardial dysfunction offers clinicians an opportunity for early intervention and prevention of symptomatic cardiovascular disease and novel imaging method, such as STE, might be a useful screening strategy. For example, subclinical LV systolic dysfunction in the general population with diabetes mellitus, detected using LV global longitudinal strain, is associated with an increased incidence of cardiovascular events, defined as a composite of acute coronary syndrome, cerebrovascular stroke, cardiovascular death and hospitalization for heart failure ,23.Speckle tracking echocardiography is an advanced, non-invasive imaging technique that provides fast and accurate assessment of cardiac function, global and regional function of both atrial and ventricular chambers, in-plane translation motion and independently from the angle of insonation . The infIt has been demonstrated over the last 10 years that speckle tracking echocardiography is a reliable method in predicting heart failure. Studies in non-pregnant population showed that there is a specific pattern of changes when using speckle tracking, not only in arterial hypertension, but also following diabetes mellitus . Early sIn comparison with other methods of assessing heart function, the main benefit of SPE is represented by the capacity to evaluate the two-dimensional displacement of cardiac muscle spots during the cardiac cycle and to calculate, in an angle-independent way, heart deformation through the distance variation between the speckles in the analysed segment . TherefoMyocardial deformation during cardiac cycle, contraction and relaxation, is defined by the term strain . It reprThe adult myocardium possesses a complex structure, based on right-handed helical fibers at endocardial layer and left-handed helical fibers in epicardial layer . HarmoniDefined by a positive curve, radial strain shows the radial myocardial deformation corresponding to systolic thickening. This parameter is assessing left ventricular dyssynchrony and, hence, has proved to be one of the most accurate methods to identify potential responders to cardiac resynchronization therapy in patients with end-stage heart failure . CircumfThe rotation degrees of the intermediate myocardial planes gradually change from base to apex and the rotation is null at papillary muscles level. A parasternal short-axis section at basal and apical planes can assess left ventricular twisting value .Gestational diabetes affects one out of seven pregnancies and is associated with adverse perinatal outcomes for both the mother and the fetus. Women whose pregnancies were complicated with GDM have a seven-fold higher incidence of type 2 diabetes later in life and a two-fold higher risk of cardiovascular events during the first 10 years postpartum  MoreoverWe did a search on PubMed with no time restriction for words such as “echocardiography” and “pregnancy” and “gestational diabetes”. We retrieved 354 results out of which only 19 were related to maternal cardiac echocardiography in relation to diabetes. After reading the studies, we found eight studies that used STE and reported subtle differences between cardiac function in pregnant women with and without diabetes. .Increased post-partum cardiovascular risk after GDM might be explained by subclinical cardiac changes which appear during pregnancy in women exposed to high glycemic levels and insulin resistance. Most of the studies reported early changes at STE; the main finding when comparing the pregnancies complicated by GDM to normal population is reduced left ventricular global longitudinal strain (LV-GLS).A recent large prospective longitudinal study  enrolledp < 0.001 for both) and lower left ventricular ejection fraction. Early subclinical systolic functional impairment is easily proven by speckle tracking in fetuses with gestational diabetic mothers; functional changes were more evident in the right ventricle [Gestational diabetes also has an impact on the offspring cardiac function, manifesting early signs of subclinical cardiac dysfunction since intrauterine life. A recent study illustrated that fetuses of mothers with gestational diabetes mellitus possessed more globular hearts with higher right and left ventricular sphericity index  was extensively studied in the context of hypertensive disorders of pregnancy. Left ventricular-GLS represents LV myocardial shortening in the longitudinal axis and is an important index of global LV function. It is an early marker of subclinical alterations of subendocardial longitudinal fibers, which are the first to be affected in ischemic injuries and arterial hypertension . AlthougA recent systematic review regarding STE findings in pregnancies complicated by hypertensive disorders analyzed 16 relevant studies and reported that LV-GLS was decreased in women with any form of hypertensive complication. Additionally, women with early onset or severe form of preeclampsia showed other deformation changes, such as decreased left ventricular global radial and circumferential strain . These pReduced sensitivity of conventional echocardiography in detecting subclinical cardiac changes is supported by the results of a systematic review on women with a history of preeclampsia assessed by conventional echocardiography, which failed to show any difference in left ventricular ejection fraction, isovolumetric relaxation time, or deceleration time. The results suggest that cardiac morbidity associated with preeclampsia is a result of an increased incidence of the cardiovascular risk factors within the population group , rather than the preeclampsia alone. In terms of measurement of global myocardial deformation, speckle tracking imaging is a useful tool to assess maternal cardiac function, showing reduced strain in preeclampsia as compared to normotensive pregnancies .A prospective observational study  includinAnother study published in 2020 by Vasapollo et al.  reportedAssessing both preeclampsia and fetal growth restriction in fetal cardiac remodeling, Youssef et al.  demonstrDuring pregnancies affected by preeclampsia, mild diastolic dysfunction can be detected with standard echocardiographic techniques, but STE can also identify systolic dysfunction . A recenFurthermore, the subtle systolic and diastolic dysfunction observed in late pregnancy, when complicated by gestational diabetes, also persist for at least six months post-partum . Long-teAll these data support the coordinated use of speckle tracking by teams of maternal fetal specialists and cardiologists in patients with pregnancy complications, both pre and postpartum. The desired outcome would be to design tailored monitoring protocols for every clinical situation, in order to foresee possible long-term effects temporarily unmasked during pregnancy .It may well be that speckle tracking is for hypertensive diseases of pregnancy what the oral glucose tolerance test is for gestational diabetes mellitus, both for pregnancy and for the long-term follow-up. The current literature is limited concerning the use of speckle tracking in patients with pregnancy complications such as maternal gestational diabetes, preeclampsia and fetal growth restriction and comparative studies. Focus on a larger number of cases with a continuous postnatal monitoring is needed, especially for complications such as preeclampsia, in order to improve early prediction of frequent maternal complications.


Even though lifestyle changes are the mainstay approach to address obesity, Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most effective and durable treatments facing this pandemic and its associated metabolic conditions. The traditional classifications of bariatric surgeries labeled them as “restrictive,” “malabsorptive,” or “mixed” types of procedures depending on the anatomical rearrangement of each one of them. This conventional categorization of bariatric surgeries assumed that the “restrictive” procedures induce their weight loss and metabolic effects by reducing gastric content and therefore having a smaller reservoir. Similarly, the “malabsorptive” procedures were thought to induce their main energy homeostatic effects from fecal calorie loss due to intestinal malabsorption. Observational data from human subjects and several studies from rodent models of bariatric surgery showed that neither of those concepts is completely true, at least in explaining the multiple metabolic changes and the alteration in energy balance that those two surgeries induce. Rather, neuro-hormonal mechanisms have been postulated to underly the physiologic effects of those two most performed bariatric procedures. In this review, we go over the role the autonomic nervous system plays- through its parasympathetic and sympathetic branches- in regulating weight balance and glucose homeostasis after SG and RYGB. Obesity is associated with several co-morbidities that carry a significant burden on the healthcare system and quality of life of all affected subjects around the world. As of 2014, 13% of adults worldwide were obese, with the most affected region being the American continent, for the prevalence of obesity among adults in the United States increased from 33.7% in 2007–2008 to 42.4% in 2017–2018 . PredictThe traditional theory which attributes “restriction” of gastric pouch to reduced caloric consumption and small intestinal bypass to decreased caloric absorption has been repetitively evaluated. It was shown that gastric pouch or sleeve size did not affect meal size or food intake reduction post-bariatric surgery . AdditioBoth arms of the autonomic nervous system have been postulated to play a metabolic regulatory role in bariatric surgery. This review will review go over each system (sympathetic and parasympathetic) in regulating variable metabolic effects of RYGB and SG.The autonomic neurons of the sympathetic and parasympathetic nervous system innervate multiple organs and regulate their many of their homeostatic functions. The autonomic nervous system often works in a closed-loop feedback mechanism where sensing of variable biological factors is transmitted via afferent neurons to the brain or brain stem. Subsequently, homeostatic centers or nuclei within the central nervous system process these signals and transmit response orders via efferent/motor neurons to target body organs. Both sympathetic and parasympathetic nervous systems maintain whole-body homeostasis  in the face of both endogenous and exogenous perturbations .An earlier hypothesis postulated that weight gain in obesity is partially due to sympathetic nervous underactivity causing reduction in thermogenesis . HoweverThe peripheral nervous system is also involved in direct and indirect regulation of food intake. Vagal afferent neurons in the duodenum and stomach are shown to respond to mechanical stretch by luminal nutrients while also integrating other visceral sensory information along with metabolic, signals, through neuronal projection into brain stem centers. After vagotomy, neuroendocrine signaling pathways from gut hormones, such as ghrelin, are disrupted. Although, celiac branch vagotomy performed concomitantly with RYGB in rat model resulted in a slightly lesser degrees of weight reduction compared to RYGB without vagotomy, this effect seemed to be transient . Weight Roux-en-Y gastric bypass, traditionally considered as the gold standard weight loss procedure, has become the second most performed bariatric procedure since 2013. Laparoscopic sleeve gastrectomy (LSG) has become the most performed bariatric procedure worldwide, because of its efficacy in achieving weight loss results and improvements in obesity-associated comorbidities that are comparable to those of RYGB with lower operative and post-operative complications . In compBariatric surgery, including RYGB and LSG, markedly ameliorate glycemic control and may reverse or prevent T2DM in individuals with obesity . The metComparing the early weight loss-independent and later weight loss-dependent (after 1 year) glycemic controls of these surgeries, LSG and RYGB showed similar changes on glycemic control, despite lower concentrations of GLP-1 and slightly less BMI reduction following LSG . This isThe increased profile of GLP-1 after bariatric surgeries is thought to be explained by the hind-gut theory, in which stimulation of the distal intestine resulted from rapid nutrient entry further down the gastrointestinal tract such as ileum, where most of L-cells are found . In addiPeptide YY (PYY), an anorexigenic peptide secreted by L-cells mostly located in the ileum and colon, reduces appetite, decreases the contraction of gallbladder, slows gastric emptying, suppresses gastric and pancreatic secretion, and increases nutrient absorption in the ileum. It was demonstrated that reduced PYY secretion in obese patients significantly increases after LSG, comparable to those observed after RYGB .Bariatric surgery improves metabolic abnormalities in morbidly obese individuals. Hyperlipidemia, hypertension, T2DM, and obstructive sleep apnea are improved substantially following the surgery. Although improved blood pressure following RYGB has been attributed to weight-loss, lower blood pressure can occur before the reduction of body weight . TherefoIt is recognized that obesity is characterized by sympathetic nervous activation which contributes to hypertension associated with obesity. The time course of this change as well as the underlying mechanisms are not completely understood . In addiUsing microneurography to directly measure sympathetic activity, it was demonstrated that human subjects who had undergone RYGB experience a reduced systemic sympathetic tone, specifically a muscular sympathetic nerve activity contributing (MSNA) to total energy expenditure .in vivo studies with mice suggested that RYGB but not LSG increases splanchnic nerve activity, which induces thermogenesis of visceral fat and enhances resting metabolic rate . RYGB has shown to decrease systemic sympathetic nerve activity (SNA) and likely to increase splanchnic sympathetic nerve activity, selectively, to activate thermogenesis and lipolysis of visceral white adipose tissue.In vivo studies showed that RYGB causes a significant reduction in the weight of rats with T2DM, augmented the concentrations of serum insulin and GLP-1. These metabolic effects following RYGB partially depend on hepatic branch of the vagus nerve, as selective vagotomy of this nerve is associated with weight regain and the relative lower levels of serum GLP-1 and insulin  . ∼70% of insulin .Mc4r mutations and mice with Mc4r-deficiency (Melanocortin-4 receptors (MC4R) are expressed in the hypothalamus and hindbrain as well as in autonomic neurons including parasympathetic vagal sensory neurons and preganglionic cholinergic motor neurons (parasympathetic and sympathetic). They play an important role in regulation food intake and energy expenditure in response to peripheral energy signals such as micro-nutrients or gut hormones. In line with these observations, severe obesity was found in humans with naturally occurring ficiency . Moreoveficiency .in vitro, as well as improved early diabetes resolution following surgery that is weight-independent than non-carriers. They suggested that MC4Rs mediated autonomic efferent signaling is key to induce metabolic effects following RYGB, including these weight-independent benefits such as improved glucose profile , Oleoylethanolamide (OEA), is produced by enterocytes of the upper small intestine. It was shown that OEA can activate PPAR-α receptors via vagal sensory output to suppress fat intake through striatal  and hypoPrevious studies have shown a beneficial effect of weight loss primarily on measures of parasympathetic activity after RYGB . Other sIn summary, there is convincing evidence that the parasympathetic nervous system activity – represented mainly by the vagus nerve- is modulated after RYGB. This alteration in vagal tone has been tightly connected to changes in several gut hormones and early improvement in glucose metabolism post-RYGB.Reduced vagal function and increased sympathetic activity were observed in obese subjects. The improvement in parasympathetic tone following LSG was evidenced by enhanced heart rate variability in women with obesity, as early as the first month after surgery . LSG hasad libitum and pair feeding), which were associated with a body weight-independent reduction in hypothalamic PERK-mediated ER stress, inflammation of hypothalamus and sympathetic nervous system tone.Using high-fat diet induced obese mice underwent sham or LSG surgery and implantation of radio telemeters, The sympathetic nerve system is a key regulator in the production of leptin by white fat. Leptin production is extremely reduced in mice exposed to a cold environment, when sympathetic stimulation of white fat was enhanced. This can also occur after administration of norepinephrine and isoproterenol. Thus sympathetic nerve excitement inhibits the synthesis of leptin . In contLaparoscopic sleeve gastrectomy surgery reduces stomach capacity and removes the fundus by excising the larger curvature of the stomach, thereby reducing the level of circulating ghrelin, which is predominantly secreted from the fundus and upper gastric body. As the level of ghrelin is reduced, people are prone to feeling full and reducing food intake, thereby reducing caloric intake . It can Sympathetic neuron-associated macrophages (SAMs) are subset of macrophages recently characterized and identified within the white adipose tissue and long the sympathetic fibers innervating fat cells. They express SLC6A2 transporter which is responsible for noradrenaline degradation and consequently decreasing SNS- mediated thermogenesis. SAMs have been observed to be elevated in state of obesity and eliminating them or their degradation enzyme (SCLC6A2) results in activated thermogenesis. We do not know yet, the effect of either RYGB or SG on SAMs level or activity within WAT .In summary, LSG seems to have an early systemic neuro-inhibitory sympathetic effect that might be responsible for the blood pressure, and leptin reduction effects. There is limited proof that LSG (like RYGB) can induce activation of selective autonomic sympathetic nerves or tracts (such as the splanchnic) or augment sympathetic-mediated thermogenesis.Bariatric surgery might also change taste acuity an/or olfaction, and potentially influence food preference and caloric consumption, which in turn leads to weight loss. Heightened sensitivity to sweetness could also be altered by the increase in GLP-1, P-YY and changes in other regulators hormones  that occur post RYGB and LSG. Several gut hormones and their receptors are expressed within the taste buds themselves, suggesting a possible role in palatability in addition to their known metabolic functions .Variable gastrointestinal signaling inputs are thought to be involved in ingestion of food, which can directly- or indirectly- activate vagal afferent nerve endings in a predominantly paracrine fashion to induce gastric relaxation, and pancreatic exocrine secretion. Circulating neurohormones such as CCK and GLP-1 act directly at the brainstem to modulate vagal afferent and efferent activity in addition to their potential actions as neurotransmitters within these neurocircuits . One of Weight loss and improved glycemic profile following LSG have been attributed to a theory denominating the “gastric hypothesis,” which asserts that alterations in the secretion/action of gut hormones such as GLP-1, GIP, leptin, and PYY triggered by direct stomach manipulation are responsible for the rapid restoration of insulin secretion and sensitivity . GhrelinIn summary, glucose regulation after LSG seems to be partially medicated by the changes in gut hormones post-surgery and partially by the weight loss itself. The role of parasympathetic nervous system in regulating glucose homeostasis post-sleeve gastrectomy is less defined or data is lacking at least. It is more likely; however, that the parasympathetic nervous system is more involved (directly or indirectly) in changes in food intake behavior after LSG.Bariatric surgery achieves sustainable improvements in treating metabolic dysfunction related to obesity and improves overall health. The underlying mechanisms by which these procedures cause weight loss and metabolic improvement appear to be diverse and are not yet fully identified. Current evidence suggests that the autonomic parasympathetic nervous system (mainly through its vagus arm) contributes to food intake reduction and improvements in glucose homeostasis following bariatric surgeries. The sympathetic nervous system is also altered after bariatric surgery, with human models showing decrease in systemic tone to the that might correlates with improvement in blood pressure and other homeostatic patterns. Rodent models of RYGB suggest a selective increase in the splanchnic sympathetic nerve activity of the gut, innervating the visceral fat and leading to augmented sympathetic-mediated thermogenesis. Future studies that further unfold details about the underlying molecular mechanisms communicating new energy signals from the gut to the brain along a neuro-hormonal pathway is essential to help us understand how this procedure induces its powerful metabolic effects. Development of effective and less-invasive therapies for weight-management  would highly benefit from this information.MM conceptualized the idea and design of the review and critically revised the manuscript. ZA and HW wrote the first draft of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


There is an astonishing diversity of ways in which people benefit from coral reefs. They provide recreation, resource extraction, inspirational, and educational opportunities, among many others as well as being valued just for their existence. As the condition of coral reef ecosystems decline, so do their ability to provide these benefits. Prudent management of coral reefs and the benefits they provide are important as some predict most coral reefs globally will be lost by the mid-21st century. Meanwhile, coral reef managers have limited tools and relevant data to design and implement effective environmental management practices that will enable coral reefs to provide benefits demanded by society. We demonstrate an approach to identify and measure environmental components of coral reefs that directly benefit human well-being. The approach views ecosystems through the lens of a specific set of beneficiaries and the biophysical features directly relevant to each. We call these biophysical features Final Ecosystem Goods and Services (FEGS). In our demonstration, we (1) identify a range of beneficiaries of coral reefs; (2) identify metrics of FEGS for those beneficiaries; and (3) describe how data quantifying those biophysical metrics might be used to facilitate greater economic and social understanding. Human well-being is reliant upon ecosystems goods and services (EGS) that sustain our society, human health, and economy, and they are often assumed to be available for free . The chaIncreasingly, greater emphasis is placed on integrating the full set of benefits when considering decisions that can impact EGS with a growing awareness about the complexity and diversity of connections between natural and human systems. Ecosystems provide goods or tangible biophysical components of nature that provide services to humans . These EEcological products and processes directly experienced by human beneficiaries are final ecosystem goods and services (FEGS) . BeneficAlthough the Millennium Ecosystem Assessment  was pivoThe FEGS framework is distinguished from other ecosystem service definitions  by takinFinal ecosystem goods and services serve as the linking metrics to clarify the benefits experienced by people in the specific ways in which they directly interact with ecosystems. Final ecosystem goods and services are contrasted with the broader set of essential intermediate ecosystem goods and services (IEGS) that are required to support or regulate FEGS ; Fig. 1.Coral reefs were chosen as one of seven ecosystems examined as part of a larger U.S. national effort developing FEGS metrics using a similar structured process and shared expertise on metric development across these ecosystems . Coral rProtection of ecosystem benefits is important for coral reef managers; a priority heightened by the presence of rapidly increasing coastal human populations increased sea temperatures and ocean acidification  increasePrevious studies addressing coral reef EGS have primarily focused on identifying ecological characteristics that contribute to the resistance, recovery, and conservation of ecosystem services based on key ecological traits, life history strategies, and functional ecology of coral reefs . This woOur objective was to demonstrate how to apply the FEGS conceptual framework to link people’s well-being to coral reef ecosystems by adopting a user-centric perspective. Coral reefs were chosen as one of seven ecosystems examined as part of a larger U.S. national effort developing FEGS metrics using a similar structured process and shared expertise on metric development across these ecosystems . The metAcknowledgments) who were biophysical scientists familiar with the principles of biophysical metric development and selection  and a social scientist with a specialty in decision science and EGS (L. Sharpe). The metrics team worked to select the beneficiaries, attributes, and FEGS biophysical metrics that related to elements of human well-being . MetricsStep 1: Delineate ecosystem boundaries;Step 2: Specify beneficiaries and begin to define the final good or service for each beneficiary by asking “What directly matters to that beneficiary?”;Step 3: Select attributes guided by the questions from a standardized list of ecosystem attributes directly used, appreciated, or enjoyed by each beneficiary. Refine ecosystem attributes at the level necessary to support the specification of metrics of the FEGS for each beneficiary; andStep 4: Specify metrics for each beneficiary to develop the FEGS and FEGS metrics using these steps:Define the ideal metric;Define the available biophysical measures closely related to that ideal metric;Use the metrics team expertise to evaluate the ideal metric to determine if the metric(s) proposed sufficiently translate the FEGS into the desired information most easily understood by the beneficiary; andMetrics team validate metrics and metrics vetted by FEGS team, review, revise, and repeat until consensus among both groups.Key to the FEGS approach is designating the beneficiaries, then identifying relevant biophysical attributes and how to measure them . The folCoral reef ecosystems were categorized employing the Final Ecosystem Goods and Services Classification System (FEGS-CS) environment classification . FEGS-CSThe metrics teams attempted to identify all likely beneficiary groups to evaluate the utility of this approach across a diverse spectrum of uses. We included beneficiaries from direct use, indirect use, optional use, and the least tangible non-use value necessary for a total economic benefits analysis . We did https://www.census.gov/naics/ last accessed May 2021; We chose beneficiaries using the National Ecosystem Services Classification System (NESCS) Plus  that conThe metrics team identified which ecosystem attributes provide a final good or service for each beneficiary and their defined use by answering “What matters to this beneficiary?” as a heuristic question . GeneralIn NESCS Plus, Tier 1 attributes for FEGS are basic components of all ecosystems classified as Water, Air, Weather, Soil and Substrate, Natural Materials, Flora, Fungi, Fauna, and Extreme Events , Composite , all Tier 1 attributes are mutually exclusive except for the last one. Final ecosystem goods and services Tier 2 attributes divided each Tier 1 attribute into multiple and more specific attributes . For exaEach attribute was considered by the metrics team and appraised how well and to what degree the FEGS attribute was appreciated by the beneficiary. We defined how each beneficiary directly interacted with the coral reef by considering all the ways that the beneficiary  used, apFirst, the metrics defined the desired information that lead to a biophysical measurement for each sub-attribute of the ecosystem to identify an ideal metric that was most meaningful to that beneficiary. The metrics team identified metrics that reflected the sub-attributes to embody biophysical aspects of nature that ecologists could measure and monitor directly, often those used for environmental assessment programs. Many potential metrics were scrutinized to select subsets of metrics that were most meaningful to the beneficiaries’ interests. The metrics team considered whether the biophysical metric chosen represented the most apparent, tangible, and intuitive features that resonated with the specific beneficiary. The metrics team described this information so that it would be easily understood by each beneficiary group and ensured the metric was not too technical. Best professional judgment and review of the ecological literature guided the development and identification of the best biophysical measures of reef condition contributing to FEGS .Frequently more than one metric was suggested for most beneficiaries as they might directly and simultaneously experience or perceive multiple metrics of an ecosystem at the same time. For example, coral reef viewers enjoy the seascape that encompass the sub-attributes of reef type, color, shape, rarity, diversity, richness, and abundance that directly contribute to their appreciation, enjoyment, and usage of the coral reef. The technical metrics and units for each one of these sub-attributes would not have much meaning to a lay beneficiary, rather an indicator of overall pleasure for viewing a coral reef seascape might integrate all or a combination of those sub-attribute metrics to develop a categorical metric or indicator. A rating of excellent, good, fair, or poor seascape viewing experience of coral reefs for beneficiaries might be more meaningful and easier to communicate to a nontechnical user . Final eThe proposed FEGS metrics were evaluated by assessing face validity, common sense, and qualitative research . Drafts The results for a single beneficiary were incorporated into a table designed to guide selection of appropriate metrics for additional FEGS-based assessments that could be conducted for specific decision contexts or locations beyond those identified as exemplified in the U.S. Environmental Protection Agency (U.S. EPA) national effort for FEGS development for seven different ecosystems . The tabA diverse spectrum of ecosystems services provided by coral reefs was identified and translated using the FEGS structured framework into related metrics to better facilitate economic and social evaluations for environmental management and policy decisions. The FEGS analysis results for 10 coral reef beneficiaries are in separate tables , cultural, spiritual, and ceremonial perspectives. Finally, Non-use beneficiaries cared about the existence of coral reef ecosystems in the present and future. Other beneficiaries analyzed were Ornamental Extractors using live reef organisms for display in aquariums or dead for jewelry or decorative products; Commercial or Industrial users focusing on Pharmaceutical Extractors using organisms for medical, cosmetic, and beauty products; and Aquaculturists rearing juvenile or adult corals for multiple purposes such as aquaria trade and reef restoration.Tier 1 attributes assigned for coral reefs were Water, Soil and Substrate, Flora, Fauna, and Extreme Events, Composite; Tier 2 attributes and sub-attributes developed for coral reef beneficiaries are bolded text in For this step, we detail the development FEGS metrics for two beneficiary classes to illustrate the application of the FEGS approach: recreational SCUBA divers and snorkelers, and anglers who catch fish on coral reefs. Results for the other eight beneficiaries are found in The metric team limited analysis of SCUBA divers and snorkelers (now referred to as divers) to those who were primarily interested in recreational diving or snorkeling . Their interests posited as questions were “Will my dive be enjoyable and safe?” and “Is the environment appealing?” , Step 2 Fourteen FEGS and metrics were developed for divers , after bThe presence of chemicals and contaminants in the seawater was identified as a critical sub-attribute to determine “Is the water quality high enough to be safe for diving?” . RecreatFish and coral community metrics reflecting what was most desired by divers were overall abundance; presence of rare species; biodiversity; species richness; size; color and unique behaviors and morphologies, most of which are surrogate metrics. A multimetric index expressed as a simple categorical indicator would be easier for divers to decide whether their dive would be enjoyable. Literature identifies the amount of live coral cover as the second most common coral community metric associated with making dives pleasurable  with corThe angler beneficiary merged three angler types: recreational catch and release and catch and eat, and subsistence anglers. We assumed anglers fished from boats and had minimal contact with the seawater, posing no health concerns from contaminated seawater exposure. Anglers were interested whether “Is this a good place to go fishing?” and “Will the boat be enjoyable and safe to fish from?” .The angler subclasses overlapped in their interest in Fauna , Step 3,There were many FEGS metrics which crosscut the spectrum of 12 coral reef beneficiaries as each angler subclass was considered individually for this exercise. Both wave intensity and current strength metrics were identified for 10 of the 12 (83%) beneficiaries for coral reefs . The mosThe suite of FEGS metrics identified for beneficiaries exemplify the wide diversity of ways stakeholders use and benefit from coral reefs –S8. We dWe developed our FEGS metrics using the hierarchical NESCS Plus classification to exemplify selection of the beneficiaries, attributes, FEGS, and biophysical metrics after defining the context using general and specific questions. It is likely that our selected elements may differ considerably, be less familiar, or of less importance for others with different management responsibilities. In those cases, there might not be consistent criteria to propose or select FEGS metrics on a comprehensive basis, so surrogate metrics can be substituted. In other cases, direct measurement of some attributes might be difficult or expensive, justifying the use of surrogate metrics that best approximate valued attributes while acknowledging inherent limitations of using surrogates.Coral reef managers desire tools and approaches to assist them in problem definition and finding solutions, because many have very limited resources, time, and expertise to make important decisions. Ecosystem-based management aims to guide local and regional experts to organize and streamline the level of information required to formulate the desired results and identify trade-offs and uncertainty in predicting ecosystem outcomes while weighing socioeconomic concerns against ecosystem condition . Final eThose identifying our current time as the Anthropocene Era have proposed that the trajectory of change imparted by humans is irreversible, and scientists must acknowledge that the forces of human impacts and intervention are rapidly changing the structure and function of reefs . ReportsThe FEGS framework can be adapted to many different applications, additional beneficiaries, and scaled up or down both spatially and temporally as required by decision needs of the environmental manager or communities. The identification of beneficiaries and FEGS linking metrics can be tailored to the local scale for a specific ecosystem and period of time. Examples include streams  or seasoA primary advantage of the FEGS framework is the ability to be very flexible for operationalizing EGS from a beneficiary perspective, particularly when paired with standardized and hierarchal classification systems  that canThe conceptual framework for ecosystem goods and services continues to be expanded and incorporated into decision-making by governmental, national, and international organizations as these entities better define their values. Supplement1


Classically, ROS have most often been considered harmful as they are common determinants of many cell death pathways including apoptosis, necrosis/necroptosis, ferroptosis, pyroptosis and autophagic cell death  result from the partial reduction of oxygen, and encompass both radical [superoxide anion (Oll death –8. This ll death  or macroll death . Howeverll death –14. Morefication –17 and afication –26. H2O2nslation –29. Beca2O2) to give rise to aggressive hydroxyl radicals that can damage any biomolecule, including DNA. Therefore, ROS are essential for pathogens killing by phagocytic cells as illustrated by chronic granulomatous disease (CGD), an inherited disorder of the NADPH oxidase characterized by recurrent and severe bacterial and fungal infections -mediated dephosphorylation regulates TTP to activate its mRNA-degrading function. Interfering with TTP expression or agonist of PP2A modulate monosodium urate (MSU) crystal-induced the expression of inflammation-related genes and NLRP3 inflammasome activation in a mitochondrial ROS-dependent manner suggesting that targeting TTP expression or function may provide a potential therapeutic strategy for inflammation caused by MSU crystals.ROS have also been proposed to be the common determinant of the inflammasome activation critical in the inflammatory process which is the determinant for an efficient immune response –38. The Canton et al. in the context of macrophages. Moreover, ROS are also required for full activation of lymphocytes as well as for the regulation of autoimmunity. Indeed, Bassoy et al. highlight the contribution of ROS in lymphocyte biology and stress their contribution in adaptive immunity with direct impact on the outcome of the antitumoral immune response as a consequence of the redox state in the tumor microenvironment (TME). Cali et al. showed the detrimental tolerogenic role of tumor-infiltrating myeloid cells (TIMs) actively dismantling effective immunity against cancer. TIMs inhibit T cell functions and promote tumor progression by multiple mechanism including the potentiation of the oxidative/nitrosative stress within the TME. They demonstrated that nitrosylation of granulocyte monocyte stimulating factor (GM-CSF) nourishes the expansion of this highly immunosuppressive myeloid subsets in tumor-bearing hosts.These studies demonstrate that ROS exert highly pleotropic functions in immunity. Therefore, it is essential to identify the specific intracellular sources of ROS and how they influence cellular processes in both physiological and pathological means, and how they impact on metabolic processes and inflammatory signaling as discussed by Mortimer et al. who focus on the emerging role of NOX2-derived ROS in the development and maintenance of adaptive immunity and the effects of excess ROS in systemic disease. To this regard, Chávez and Tse discussed the impact of mitochondrial-derived ROS and immunometabolism reprogramming in autoreactive T cell differentiation. Dysfunctional mitochondria have been involved in oxidative stress associated with many T cell-mediated autoimmune diseases. This agrees with the ability of mitochondrial-derived ROS to also contributed to T cell fate and function. Therefore, targeted manipulation of glycolysis and mitochondrial derived ROS could contribute to the elimination of autoreactive T cells while promoting immunosuppressive CD4 T regulatory (Treg). This targeted manipulation would have the advantage of avoiding global immunosuppression and preserving physiological immune response.The contribution of the ROS in adaptive immunity was further developed by Dumas and Knaus discuss essential consideration for effective Redox medicinal approaches.Finally, given the essential role of ROS for basic physiological functions as well as their contribution to pathophysiological situation, their therapeutic manipulation becomes an attractive strategy, although a non-trivial one. This special Research Topic covers the extremely wide span of ROS function in immune defense and regulation and, with that, also the urgent need for further study to exploit these pleotropic molecules for therapy approaches. ROS are not only essential for antimicrobial defense but also exert a variety of crucial regulatory functions, reaching from the modulation of transcriptional programs to mediating differentiation fate. On the other hand, oxidative stress can contribute to various pathologies, including neuronal degenerative diseases, autoimmunity as well as cancer. Therefore, the potential therapeutic intervention in ROS biology will need extensive temporal and spatial fine tuning.DM and MW wrote the manuscript. All authors contributed to the article and approved the submitted version.Work from Martinvalet’s lab was supported by grants from UNIPD SID 2018 and ERC starting grant ERC-2010-StG_20091118. Work from the Walch’s lab was supported by the Swiss National Science Foundation (SNSF grant # 310030_169928), the Novartis Foundation for Medical-Biological Research and the Vontobel-Foundation .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Suicide is a leading cause of death among youth and a prominent concern for school mental health providers. Indeed, schools play a key role in suicide prevention, including participating in risk assessments with students expressing suicidal ideation. In the context of the COVID-19 pandemic, many schools now need to offer mental health services, including suicide risk assessment, via eHealth platforms. Post pandemic, the use of eHealth risk assessments will support more accessible services for youth living in rural and remote areas. However, as the remote environment is a new context for many schools, guidance is needed on best practices for eHealth suicide risk assessment among youth.This study aims to conduct a rapid, systematic scoping review to explore promising practices for conducting school-based suicide risk assessment among youth via eHealth .This review included peer-reviewed articles and gray literature published in English between 2000 and 2020. Although we did not find studies that specifically explored promising practices for school-based suicide risk assessment among youth via eHealth platforms, we found 12 peer-reviewed articles and 23 gray literature documents that contained relevant information addressing our broader study purpose; thus, these 35 sources were included in this review.accessibility theme to a broader theme termed youth engagement, which included information on accessibility and building rapport, establishing a therapeutic space, and helping youth prepare for remote sessions. Finally, a new theme was identified in the gray literature findings, specifically concerning school mental health professional boundaries. A second key difference between the gray and peer-reviewed literature was the former’s focus on issues of equity and access and how technology can reinforce existing inequalities.We identified five key recommendation themes for school-based suicide risk assessment among youth via eHealth platforms in the 12 peer-reviewed studies. These included accessibility, consent procedures, session logistics, safety planning, and internet privacy. Specific recommendation themes from the 23 gray literature documents substantially overlapped with and enhanced three of the themes identified in the peer-reviewed literature—consent procedures, session logistics, and safety planning. In addition, based on findings from the gray literature, we expanded the For school mental health providers in need of guidance, we believe that these six recommendation themes  represent the most promising directions for school-based suicide risk assessment among youth using eHealth tools. However, suicide risk assessment among youth via eHealth platforms in school settings represents a critical research gap. On the basis of the findings of this review, we provide specific recommendations for future research, including the need to focus on the needs of diverse youth. Suicide is a leading cause of death among youth in the United States and Canada -3. BeyonIn the context of the COVID-19 pandemic, suicide risk for some youth may be elevated because of social isolation and the associated mental health impacts of the pandemic -9. In adSchools are a key suicide prevention and intervention site because of their frequent access to many youths. In the usual, non–COVID-19 context, school personnel are in regular contact with most students and thus have multiple opportunities to intervene -14. FurtGiven nationwide school closures that occurred because of the COVID-19 pandemic in March 2020 , schools across the United States and Canada are now providing school mental health services, including suicide risk assessment, through eHealth platforms. In our context, partner school divisions shared that they are still attempting to implement standardized suicide risk assessment protocols remotely but do not know optimal practices for delivery , leading to concerns about the safety and effectiveness of this process for students expressing suicide risk in these challenging times. Given the increased mental health distress some youth may experience during and following situations causing widespread loss or turmoil -24—incluThis study aims to address the following research question: What are promising practices for providing school-based suicide risk assessment to youth using eHealth? The overall objective of this review is to summarize current evidence on key recommendations for the remote implementation of suicide risk assessment protocols and apply these recommendations to the school context. To address this question and objective, we used a systematic scoping review methodology -28, follThe search protocol for this study was developed by the research team and reviewed by a medical research librarian and suicide prevention nonprofit organization before searches were conducted. To find relevant peer-reviewed literature for this scoping review, we searched six databases  on May 28, 2020. The first author conducted all the searches. The search terms were as follows: (youth OR adolescen* OR teen* OR child*) AND (risk OR suicid* OR safety OR self-harm OR self-injury OR “self-injur* behavio*”) AND (assessment* OR screen*) AND . We searched the first three search strings  as individual subject headings and as title or abstract search strings in each database. We searched the final search string (the technology terms) as a title search string only to increase the relevancy of returns.eHealth indicated that the first full-text articles on this topic primarily began to appear after the year 2000. Searches were not restricted by geographic region or methodology to be broadly inclusive. To be included, articles needed to provide information relevant to completing suicide risk assessments in an eHealth  environment. Studies were excluded if they did not make relevant recommendations, did not focus on risk assessment, risk assessments were not completed remotely within the study, the full text was not available, or the study was a duplicate . We made this restriction as we hypothesized that most eHealth articles would be relatively recent. Indeed, a special issue on eHealth ethics was published in 2000 , and a GThe screening of the retrieved studies was completed using Covidence by a team of 5 research assistants . Research assistants reviewed the titles and abstracts of each of the 2114 potential articles in pairs . Each meData from the 12 articles included were extracted using a standardized data charting template created for this study, based on the recommendations of Tricco et al  and LevaTo organize information extracted using the standardized data charting template into overall recommendation themes, the first author inductively applied codes to extract data using Dedoose, a web-based mixed methods data analysis software. Codes were then reviewed and revised by the second author, and the 2 authors met to arrive at a consensus on any discrepancies. From this coding, five recommendation themes emerged from 12 peer-reviewed articles.To supplement our peer-reviewed article search, we also included key websites  as a gray literature source. We chose to focus on websites in this part of the search as we felt these would have the most up-to-date information on remote suicide risk assessment among youth in the context of the COVID-19 pandemic. Websites for inclusion were identified by the research team and a suicide prevention nonprofit organization. These websites are not geographically restricted. Between May 28 and June 19, 2020, we reviewed 17 websites for information relevant to eHealth suicide risk assessment among youth .Treating Suicidal Patients During COVID-19: Best Practices and Telehealth [Each website was thoroughly reviewed by a research assistant, and potentially relevant documents or information were saved to a shared folder. These potentially relevant documents or information were then reviewed by a separate pair of research assistants  to determine if they met the study inclusion criteria. From these 17 websites, we identified 23 gray literature documents that met inclusion criteria. We note that we found three different offerings of similar webinar content about suicide risk assessment via eHealth during this search. In addition to the Suicide Prevention Resource Center webinar titled lehealth , this colehealth  and as plehealth . Therefolehealth  webinar lehealth -43,46-67Results section for more information).Once the 23 relevant documents were found, the pair of research assistants then abstracted information using the same procedure employed for peer-reviewed articles. The standardized data charting template for gray literature included the title of the relevant page on the website and a summary of relevant information about remote suicide risk assessment among youth. The abstracted information was then reviewed and themed by the first and second authors using the same procedure as for peer-reviewed articles (see above). Finally, themes from the peer-reviewed literature were compared, contrasted, and integrated with themes from the gray literature by the first and second authors. From this process, we ended up with six total recommendations . However, we found 12 articles that provided information relevant to the overall study purpose and that we felt could inform future research and practice on school-based suicide risk assessment with youth via eHealth within the parameters of a scoping review . The incAlthough youth, in general, experience an elevated risk of suicide , youth wBy coding abstracted data, we identified five overall recommendation themes in the 12 peer-reviewed articles: (1) accessibility, (2) consent procedures, (3) session logistics, (4) safety planning, and (5) internet privacy. A summary of recommendation themes is provided in Promising practice and relevant recommendationsYouth engagement: accessibility, building rapport, establishing a therapeutic space, and helping youth prepare for remote sessions (recommendation from peer-reviewed and gray literature)Choose a mode of technology that meets the youth’s needs or preferences Test technology before sessions and ensure devices are fully chargedBrainstorm ways to increase youth’s sense of privacy Discuss what virtual sessions will look like and ask youth what they need from the virtual relationship Make sure youth can see and hear you clearly the entire time and that they know you are the only one in your roomSet up the session to promote comfort and minimize distractions Use your facial expressions to convey warmth and enthusiasm, and give youth space to speakKeep youth engaged through various methods Consider providing youth with session transcripts to help them remember information and strategies to use in daily lifeSchool mental health professional boundaries (recommendation from gray literature only)Make sure youth and caregivers know when you are and are not available and who to contact when you are not availableUse an institutional  device, and have a clear schedule for when you meet with youthConsent procedures (recommendation from peer-reviewed and gray literature)Describe what the youth should expect to happen during sessions, what technology will be used , and the risks and benefits of eHealthObtain contact information for multiple caregivers (if possible) in case one is not available when you attempt to reach themProvide information on who the youth or caregiver should contact in an emergencyDescribe what will happen if the youth is determined to be at an immediate safety riskDetail the plan for what happens if the connection is lost during a session Obtain caregiver consent and youth assentSession logistics (recommendation from peer-reviewed and gray literature)Have a plan for what to do if you get disconnected or need to get immediate support to the youth Practice using the technology before the call starts, and make sure you are competent with the platformMake sure the technology meets relevant privacy requirementsVerify the youth’s identity at the start of the session (if you have not met them before or if you cannot see them) and confirm the youth’s physical locationMonitor how the youth is feeling throughout the sessionDocument when the assessment started and ended, what platform you used, if you had any technical difficulties, specific topics covered, and any other notesEnd the session by asking what could be improved for next timeIf a youth misses the session, check in to see how they are and what you can do to make the sessions easier or more comfortable for them to attendSafety planning (recommendation from peer-reviewed and gray literature)Follow the same basic steps as in-person risk assessments If the risk is not immediate, develop a safety plan and send it to the youth and their caregiver  and include contact information for 24-hour resourcesConsider using ongoing screening data to continually monitor risk , and provide youth with feedback on risk indicatorsInform caregivers if suicide risk issues arise and provide clear guidelines on how to manage risk and seek appropriate helpInternet privacy (recommendation from peer-reviewed literature only)Send virtual session invitations via a secure and encrypted emailGive each youth a unique, nonidentifiable username and passwordStore youth information  in an encrypted computer system and use encrypted point-to-point technologies when videoconferencingEnsure the virtual session hosting platform is compliant with relevant health privacy laws in your area Two articles discussed recommendations relevant to the accessibility of eMental health services, which also seemed potentially relevant for using eHealth for youth suicide risk assessment within school settings. Both articles were original empirical studies. One original study from Indonesia was conducted with youth whose mean age was 24.5 years , and theTwo articles discussed recommendations relevant to consent procedures in the eHealth environment. One of these articles was an original empirical study from the United Kingdom conducted with individuals aged between 16 and 30 years , and thbefore beginning the risk assessment process to ensure the youth’s immediate safety . If it is not safe to contact the caregiver, and the need is urgent, emergency services may need to be called to bring the youth to a setting for the assessment where there is supervision. Given these differences in the school  environment, the existing literature on consent for eHealth suicide risk assessment does not completely align with school-based needs. Thus, research specific to conducting eHealth suicide risk assessment with youth in the school environment is critically needed.However, one of our expert reviewers (a school psychologist) noted that the consent procedures described by these studies did not fully apply to the school context . In a typical face-to-face school setting, providers are able to conduct a suicide risk assessment without caregiver consent because there are adults in the school who will monitor the youth for safety throughout the process . At the end of the risk assessment process, the school provider then contacts the youth’s caregiver so that the caregiver can continue supervision as part of the safety plan . HoweverFive studies discussed recommendations relevant to eHealth session logistics. Four of these papers were original empirical studies from the United States, Indonesia, and Australia ,35,39,40Nine studies discussed recommendations relevant to eHealth safety planning. Six of these papers were original empirical studies from Australia, the United Kingdom, the United States, and Indonesia ,39,41,42Four studies discussed recommendations relevant to internet privacy when providing eMental health services. Three of these papers were original empirical studies from the United States and Indonesia ,35,42, aOverall, there was more specific and detailed information in the gray literature  on using eMental health with youth, both generally and for conducting suicide risk assessments. From the 17 websites , we extraccessibility theme to a broader theme termed youth engagement, which included information on accessibility, building rapport, establishing a therapeutic space, and helping youth prepare for remote sessions  youth engagement , (2) school mental health professional boundaries, (3) consent procedures, (4) session logistics, (5) safety planning, and (6) internet privacy. We believe these recommendation themes  with youth via eHealth. Thus, this represents a major gap in the literature. Although suicide risk assessments have been developed for use with youth in medical settings ,19, to oAlthough we found very limited peer-reviewed literature, we found many gray literature documents that provided specific information on conducting remote suicide risk assessments with youth. Many of the resulting recommendations overlapped and expanded upon the limited information available in the peer-reviewed literature. Thus, although more research on promising practices for conducting suicide risk assessment with youth via eHealth in the school setting is required, as school mental health providers are in need of immediate guidance in the face of the COVID-19 pandemic, we feel the key recommendation themes extracted from peer-reviewed and gray literature sources in this review represent a set of six promising practices for current implementation. However, research evidence is needed for these recommendations before widespread adoption and to support the development of effective school-based suicide risk assessments for youth.The lack of peer-reviewed studies in this review reflects the state of the e-suicide prevention literature more broadly. Specifically, in their systematic review of mobile or web-based suicide prevention literature published between 2000 and 2015, Perry et al  found onIn addition, although we did locate a number of studies that examined eMental health interventions generally for youth, almost none of them described their risk assessment procedures for participants experiencing suicidal ideation; thus, these articles were excluded from this review. As such, we recommend that future eMental health intervention research be explicit about describing procedures for how youth suicide risk can be assessed remotely.In the context of the COVID-19 pandemic, new research is emerging rapidly, including on the topic of suicide prevention. For example, a recent article by Szlyk, Berk, Peralta, and Miranda  . These complex algorithms can be implemented with machine learning, a type of artificial intelligence that learns patterns from data and then applies that knowledge automatically to improve risk prediction. Researchers have recently used this technique to analyze thousands of complex health records to predict which patients are at risk of attempting suicide, leading to a more clinically accurate risk prediction ,81. As tOur study has several limitations. First, many of the specific recommendations made in From this rapid, systematic scoping review, we conclude that promising practices for conducting suicide risk assessments with youth via eHealth in school settings represents a critical research gap. Future research with diverse groups of youth is required to address this gap. However, for school mental health providers searching for immediate guidance, we feel the recommendations in this review represent the most current promising practices for suicide risk assessment with youth via eHealth until additional research is available.


We examined daily fluctuations in future time perspective within the daily stress and awareness of aging processes. Awareness of age-related change (AARC) focuses on everyday experiences that highlight changes in behavior and functioning as a result of growing older. We integrated individual differences in control beliefs because those with higher control tend to be more resilient to stressors. We conducted a daily diary study of 112 older adults (aged 60-90) who completed measures of control beliefs at baseline and then daily measures of stressor exposure, appraisal , and AARC for eight consecutive days. Increases in threats to future plans were associated with increases in AARC losses, and those with low control were especially vulnerable to increases in threats to future plans. With a constricted future time perspective, any threats to future plans may be especially harmful for older adults who are low in control beliefs.