Measurement of Urinary Gc-Globulin by a Fluorescence ELISA Technique: Method Validation and Clinical Evaluation in Septic Patients-A Pilot Study.

A major complication of sepsis is the development of acute kidney injury (AKI). In case of acute tubular damage, Gc-globulin, a known serum sepsis marker is increasingly filtrated into the urine therefore, urinary Gc-globulin (u-Gc) levels may predict septic AKI. We developed and validated a competitive fluorescence ELISA method for u-Gc measurement. Serum and urine samples from septic patients were collected in three consecutive days (T1, T2, T3) and data were compared to controls. Intra- and interassay imprecisions were CV < 14% and CV < 20%, respectively, with a recovery close to 100%. Controls and septic patients differed (p < 0.001) in their u-Gc/u-creatinine levels at admission (T1, median: 0.51 vs. 79.1 µg/mmol), T2 (median: 0.51 vs. 57.8 µg/mmol) and T3 (median: 0.51 vs. 55.6 µg/mmol). Septic patients with AKI expressed higher u-Gc/u-creatinine values than those without AKI at T1 (median: 23.6 vs. 136.5 µg/mmol, p < 0.01) and T3 (median: 34.4 vs. 75.8 µg/mmol, p < 0.05). AKI-2 stage patients exhibited more increased u-Gc/u-creatinine levels at T1 (median: 207.1 vs. 53.3 µg/mmol, p < 0.05) than AKI-1 stage individuals. Moderate correlations (p < 0.001) were observed between u-Gc/u-creatinine and se-urea, se-creatinine, se-hsCRP, WBC, u-total protein, u-albumin, u-orosomucoid/u-creatinine, and u-Cystatin C/u-creatinine levels. U-Gc testing may have a predictive value for AKI in septic patients.

Serum Total Antioxidant Capacity (TAC) and TAC/Lymphocyte Ratio as Promising Predictive Markers in COVID-19.

SARS-CoV-2 infection might cause a critical disease, and patients' follow-up is based on multiple parameters. Oxidative stress is one of the key factors in the pathogenesis of COVID-19 suggesting that its level could be a prognostic marker. Therefore, we elucidated the predictive value of the serum non-enzymatic total antioxidant capacity (TAC) and that of the newly introduced TAC/lymphocyte ratio in COVID-19. We included 61 COVID-19 (n = 27 ward, n = 34 intensive care unit, ICU) patients and 29 controls in our study. Serum TAC on admission was measured by an enhanced chemiluminescence (ECL) microplate assay previously validated by our research group. TAC levels were higher (p < 0.01) in ICU (median: 407.88 µmol/L) than in ward patients (315.44 µmol/L) and controls (296.60 µmol/L). Besides the classical parameters, both the TAC/lymphocyte ratio and TAC had significant predictive values regarding the severity (AUC-ROC for the TAC/lymphocyte ratio: 0.811; for TAC: 0.728) and acute kidney injury (AUC-ROC for the TAC/lymphocyte ratio: 0.747; for TAC: 0.733) in COVID-19. Moreover, the TAC/lymphocyte ratio had significant predictive value regarding mortality (AUC-ROC: 0.752). Serum TAC and the TAC/lymphocyte ratio might offer valuable information regarding the severity of COVID-19. TAC measured by our ECL microplate assay serves as a promising marker for the prediction of systemic inflammatory diseases.

Presepsin: gelsolin ratio, as a promising marker of sepsis-related organ dysfunction: a prospective observational study.

Introduction: We aimed to facilitate the diagnosis and prognosis of sepsis-related organ dysfunction through analyzing presepsin (PSEP) and gelsolin (GSN) levels along with a novel marker, the presepsin:gelsolin (PSEP:GSN) ratio. Methods: Blood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12 h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. PSEP was measured by a chemiluminescence-based POCT method while GSN was determined by an automated immune turbidimetric assay. Data were compared with routine lab and clinical parameters. Patients were categorized by the Sepsis-3 definitions. PSEP:GSN ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic instability, respiratory insufficiency and acute kidney injury (AKI). Results: In our single center prospective observational study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). In contrast to controls, significantly elevated (p < 0.001) admission PSEP:GSN ratios were found in non-septic and septic patients. Regarding 10-day mortality prediction, PSEP:GSN ratios were lower (p < 0.05) in survivors than in non-survivors during follow-up, while the prognostic performance of PSEP:GSN ratio was similar to widely used clinical scores (APACHE II, SAPS II, SOFA). PSEP:GSN ratios were also higher (p < 0.001) in patients with sepsis-related AKI than septic non-AKI patients during follow-up, especially in sepsis-related AKI patients needing renal replacement therapy. Furthermore, increasing PSEP:GSN ratios were in good agreement (p < 0.001) with the dosage and the duration of vasopressor requirement in septic patients. Moreover, PSEP:GSN ratios were markedly greater (p < 0.001) in patients with septic shock than in septic patients without shock. Compared to septic patients requiring oxygen supplementation, substantially elevated (p < 0.001) PSEP:GSN ratios were observed in septic patients with demand for mechanical ventilation, while higher PSEP:GSN ratios (p < 0.001) were also associated with extended periods of mechanical ventilation requirement in septic patients. Conclusion: PSEP:GSN ratio could be a useful complementary marker besides the routinely used SOFA score regarding the diagnosis and short term mortality prediction of sepsis. Furthermore, the significant increase of this biomarker may also indicate the need for prolonged vasopressor or mechanical ventilation requirement of septic patients. PSEP:GSN ratio could yield valuable information regarding the extent of inflammation and the simultaneous depletion of the patient's scavenger capacity during sepsis. Clinical trail registration: NIH U.S. National Library of Medicine, ClinicalTrails.gov. Trial identifier: NCT05060679, (https://clinicaltrials.gov/ct2/show/NCT05060679) 23.03.2022, Retrospectively registered.

Novel Damage Biomarkers of Sepsis-Related Acute Kidney Injury.

Sepsis-related acute kidney injury (AKI) is one of the most common complications of sepsis at the intensive care unit (ICU) with more adverse mortality rates. The early diagnosis and reliable monitoring of sepsis-related AKI are essential in achieving a favorable outcome. Novel serum and urinary biomarkers could yield valuable information during this process. Regarding the widely used Kidney Disease Improving Global Outcomes (KDIGO) classifications, the diagnosis of AKI is still based on the increase of serum creatinine levels and the decrease of urine output; however, these parameters have limitations in reflecting the extent of kidney damage, therefore more sensitive and specific laboratory biomarkers are needed for the early diagnosis and prognosis of sepsis-related AKI. Regarding this, several serum parameters are discussed in this review including presepsin and the most important actin scavenger proteins (gelsolin, Gc-globulin) while other urinary markers are also examined including cell cycle arrest biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), Cystatin C and actin. Novel biomarkers of sepsis-related AKI could facilitate the early diagnosis and monitoring of sepsis-related AKI.

Similarity of friends versus nonfriends in adolescence: Developmental patterns and ecological influences.

This study examines developmental change across adolescence in the similarity of friends versus nonfriends. This differential in similarity is a key aspect of the organization of the peer context of development: The stronger the correlation between friends for an attribute, the more the attribute delineates clustering and divisions of friendships. We investigated change in the correlation between friends across 12 attributes covering demographics, orientations to key institutions (family, school, religion), and problem behavior, and we expected that the link between similarity and friendship would increase during adolescence for most attributes other than gender. We also predicted that the social ecological factors of school size and attribute variability would be associated with stronger correlations between friends and partially mediate developmental change. Data are from two grade cohorts of 27 small school districts, followed from sixth through 11th grades (N = 454 time-specific networks and over 65,000 person/waves of data; 84.2% White, 6.8% Hispanic/Latino, 3.2% African American, 1.3% Asian, .5% Native American, 3.9% other or multiple). The data analysis takes the form of a three-level random effects meta-analysis of network level correlations between friends (Moran's I). As expected, declining dominance of gender was offset by the emergence of moderate correlations across a broader profile of attributes. The ecological opportunity factors of grade cohort size and attribute variability significantly mediated these increases in correlations between friends, accounting for 23 to 73% of age-related change for 10 of the 11 attributes other than gender. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Arrested Friendships? Justice Involvement and Interpersonal Exclusion among Rural Youth.

Objectives: We examine the impacts of adolescent arrest on friendship networks. In particular, we extend labeling theory by testing hypotheses for three potential mechanisms of interpersonal exclusion related to the stigma of arrest: rejection, withdrawal, and homophily. Method: We use longitudinal data on 48 peer networks from PROSPER, a study of rural youth followed through middle and high school. We test our hypotheses using stochastic actor-based models. Results: Our findings suggest that arrested youth are less likely to receive friendship ties from school peers, and are also less likely to extend them. Moreover, these negative associations are attenuated by higher levels of risky behaviors among peers, suggesting that results are driven by exclusion from normative rather than non-normative friendships. We find evidence of homophily on arrest but it appears to be driven by other selection mechanisms rather than a direct preference for similarity on arrest. Conclusions: Overall, our findings speak to how arrest may foster social exclusion in rural schools, thereby limiting social capital for already disadvantaged youth.

Urinary actin, as a potential marker of sepsis-related acute kidney injury: A pilot study.

INTRODUCTION: A major complication of sepsis is the development of acute kidney injury (AKI). Recently, it was shown that intracellular actin released from damaged tissues appears in the urine of patients with multiple organ dysfunction syndrome. Our aims were to measure urinary actin (u-actin) concentrations of septic and control patients and to test if u-actin levels could predict AKI and mortality. METHODS: Blood and urine samples were collected from septic and sepsis-related AKI patients at three time points (T1-3): T1: within 24 hours after admission; T2: second day morning; T3: third day morning of follow-up. Patients with malignancies needing palliative care, end-stage renal disease or kidney transplantation were excluded. Serum and u-actin levels were determined by quantitative Western blot. Patients were categorized by the Sepsis-3 and KDIGO AKI classifications. RESULTS: In our study, 17 septic, 43 sepsis-induced AKI and 24 control patients were enrolled. U-actin levels were higher in septic patients compared with controls during follow-up (p<0.001). At T1, the septic and sepsis-related AKI groups also showed differences (p<0.001), yet this increase was not statistically significant at T2 and T3. We also detected significantly elevated u-actin concentrations in AKI-2 and AKI-3 septic patients compared with AKI-1 septic patients (p<0.05) at T1 and T3, along with a significant increase in AKI-2 septic patients compared with AKI-1 septic patients at T2 (p<0.01). This tendency remained the same when referring u-actin to urine creatinine. Parameters of first-day septic patient samples could discriminate AKI from non-AKI state (AUC ROC, p<0.001): u-actin: 0.876; se-creatinine: 0.875. Derived cut-off value for u-actin was 2.63 µg/L (sensitivity: 86.0%, specificity: 82.4%). CONCLUSION: U-actin may be a complementary diagnostic biomarker to se-creatinine in sepsis-related AKI while higher u-actin levels also seem to reflect the severity of AKI. Further investigations may elucidate the importance of u-actin release in sepsis-related AKI.

Moderators of Friend Selection and Influence in Relation to Adolescent Alcohol Use.

Friendships form an important context in which adolescents initiate and establish alcohol use patterns, but not all adolescents may be equally affected by this context. Therefore, this study tests whether parenting practices (i.e., parental discipline, parental knowledge, unsupervised time with peers) and individual beliefs (i.e., alcohol descriptive norms, positive social expectations, moral approval of alcohol use) moderate friend selection and influence around alcohol use. Stochastic actor-based models were used to analyze longitudinal social network and survey data from 12,335 adolescents (aged 11 to 17, 51.3% female) who were participating in the PROSPER project. A separate model was estimated for each moderating variable. Adolescents who reported consistent parental discipline, less unsupervised time with peers, higher descriptive alcohol use norms, and less positive social expectations about alcohol use were less likely to select alcohol-using friends. Those who reported consistent parental discipline, better parental knowledge, lower descriptive alcohol use norms, and less positive social expectations were more influenced by their friends' level of alcohol use. Thus, adolescents with these characteristics whose friends frequently use alcohol are at greater risk whereas those whose friends do not use alcohol are at lower risk of using alcohol. The findings show that, although selection and influence processes are connected, they may function in different ways for different groups of adolescents. For some adolescents, it is particularly important to prevent them from selecting alcohol-using friends, because they are more susceptible to influence from such friends. These peer network dynamics might explain how proximal outcomes targeted by many prevention programs (i.e., parenting practices and individual beliefs) translate into changes in alcohol use.

Social Ties Cut Both Ways: Self-Harm and Adolescent Peer Networks.

Peers play an important role in adolescence, a time when self-harm arises as a major health risk, but little is known about the social networks of adolescents who cut. Peer network positions can affect mental distress related to cutting or provide direct social motivations for self-harm. This study uses PROSPER survey data from U.S. high school students (n = 11,160, 48% male, grades 11 and 12), finding that social networks predict self-cutting net of demographics and depressive symptoms. In final models, bridging peers predicts higher self-cutting, while claiming more friends predicts lower cutting for boys. The findings suggest that researchers and practitioners should consider peer networks both a beneficial resource and source of risk associated with cutting for teens and recognize the sociostructural contexts of self-harm for adolescents more broadly.

New Students' Peer Integration and Exposure to Deviant Peers: Spurious Effects of School Moves?

School moves during adolescence predict lower peer integration and higher exposure to delinquent peers. Yet mobility and peer problems have several common correlates, so differences in movers' and non-movers' social adjustment may be due to selection rather than to causal effects of school moves. Drawing on survey and social network data from a sample of 7th and 8th graders, this study compared the structure and behavioral content of new students' friendship networks to those of not only non-movers, but also of students about to move schools; the latter should resemble new students in both observed and unobserved ways. The results suggest that the association between school moves and friends' delinquency is due to selection, but the association between school moves and peer integration may not be entirely due to selection.

WHEN ONSET MEETS DESISTANCE: COGNITIVE TRANSFORMATION AND ADOLESCENT MARIJUANA EXPERIMENTATION.

PURPOSE: Desistance scholars primarily focus on changing social roles, cognitive transformations, and shifting identities to understand the cessation of serious crime and illicit drug use in adulthood. In the current study, we move the spotlight away from adulthood and toward adolescence, the developmental stage when the prevalence of offending and substance use peak and desistance from most of these behaviors begins. Our primary hypothesis is that changes in perceived psychic rewards surrounding initial forays into marijuana use strongly predict adolescents' decisions to cease or persist that behavior. In addition, based on social learning expectations, we hypothesize that peer perceptions and behaviors provide mechanisms for perceptual change. METHODS: We test these hypotheses using longitudinal data of marijuana use, perceptions, and peer networks from the PROmoting School-community-university Partnerships to Enhance Resilience (PROSPER) study. We estimate hazard models of marijuana initiation and within-person models of perceptual updating for youth from grades 6 to 12 (n=6,154). RESULTS: We find that changes in marijuana's perceived psychic rewards surrounding initiation differentiated experimenters from persisters. Experimenters had significantly lower updated perceptions of marijuana as a fun behavior compared to persisters and these perceptions dropped after the initiation wave. In contrast, persisters updated their perceptions in upward directions and maintained more positive perceptions over time. Inconsistent with social learning expectations, initiators' updated perceptions of marijuana as a fun activity were not explained by peer-reported behaviors or attitudes.

Peer beliefs and smoking in adolescence: a longitudinal social network analysis.

BACKGROUND: Peer smoking is one of the strongest predictors of adolescent cigarette use, but less is known about whether other peer characteristics also contribute to this behavior. OBJECTIVES: This study examined the links between adolescent cigarette use and peer beliefs about smoking. It tested whether peer beliefs about smoking are associated with changes in cigarette use, whether this association is a result of changes in individual beliefs about smoking, and how beliefs inform friendship choices. METHODS: Analyses drew on data collected from 29 school-based networks, each measured at five occasions as students moved from 6th through 9th grade, as part of the study of the PROSPER partnership model. Longitudinal social network models provided estimates of friendship selection and behavior for an average of 6,200 students at each measurement point and more than 9,000 students overall. RESULTS: Peer beliefs about smoking influenced cigarette use both directly and through their impact on individual beliefs. Respondents tended to name friends whose beliefs about smoking were similar to their own, and the likelihood of being named as a friend was higher for those who reported more positive beliefs about smoking. CONCLUSION: The results from this study suggest that peer beliefs about smoking, in addition to peer cigarette use itself, are associated with adolescent smoking through several mechanisms. Because beliefs favorable to cigarette use are present before adolescents actually smoke, these results underscore the importance of implementing smoking prevention programs in early adolescence.

Social Networks and the Diffusion of Adolescent Problem Behavior: Reliable Estimates of Selection and Influence from Sixth Through Ninth Grades.

Seeking to reduce problematic peer influence is a prominent theme of programs to prevent adolescent problem behavior. To support the refinement of this aspect of prevention programming, we examined peer influence and selection processes for three problem behaviors (delinquency, alcohol use, and smoking). We assessed not only the overall strengths of these peer processes, but also their consistency versus variability across settings. We used dynamic stochastic actor-based models to analyze five waves of friendship network data across sixth through ninth grades for a large sample of U.S. adolescents. Our sample included two successive grade cohorts of youth in 26 school districts participating in the PROSPER study, yielding 51 longitudinal social networks based on respondents' friendship nominations. For all three self-reported antisocial behaviors, we found evidence of both peer influence and selection processes tied to antisocial behavior. There was little reliable variance in these processes across the networks, suggesting that the statistical imprecision of the peer influence and selection estimates in previous studies likely accounts for inconsistencies in results. Adolescent friendship networks play a strong role in shaping problem behavior, but problem behaviors also inform friendship choices. In addition to preferring friends with similar levels of problem behavior, adolescents tend to choose friends who engage in problem behaviors, thus creating broader diffusion.

Revisiting "What They Think": Adolescent Drinking and the Importance of Peer Beliefs.

The association between delinquent peers and delinquent behavior is among the most consistent findings in the criminological literature, and a number of recent studies have raised the standards for determining the nature and extent of peer influence. Despite these advances, however, key questions about how deviant behavior is socially transmitted remain unresolved. In particular, much of the research examining peer influence is limited to peer behavior, despite a rich literature supporting the salience of beliefs, such as expectations and moral approval, in shaping behaviors. The current study takes advantage of advances in the modeling of peer influence and selection processes to re-examine the contributions of peer beliefs and behaviors to adolescent drinking. I employ longitudinal social network analysis to examine how peers contribute to the complex interplay between deviant beliefs and behaviors. I find evidence that beliefs related to peer drinking have both a direct and indirect impact on behavior and also play an important role in the friendship selection process. These results highlight the importance of understanding how peers influence deviant behavior and suggest that peer beliefs are an important part of this relationship.

Friends as a Bridge to Parental Influence: Implications for Adolescent Alcohol Use.

The current study investigates the possibility that friendship networks connect adolescents to influence from a broader group of adults beyond their own families. In doing so, we combine two rich traditions of research on adult influence on children and adolescents. Family research has suggested a number of ways in which effective parenting can reduce deviant behavior among adolescents. In addition, research on neighborhoods has advanced the idea that adults outside of the immediate family can exert social control that may reduce deviance. We employ longitudinal social network analysis to examine data drawn from the PROSPER Peers Project, a longitudinal study of adolescents following over 12,000 students in 27 non-metropolitan communities as they moved from 6th through 9th grade. We find evidence that the behavior of friends' parents is linked, both directly and indirectly, to adolescent alcohol use. Findings suggest that much of the influence from friends' parents is mediated through peer behavior, but that parental knowledge reported by friends continues to be associated with alcohol use even when controlling for competing mechanisms. Furthermore, adolescents tend to choose friends who report similar levels of parenting as themselves. Our results provide support for the position that friendships in adolescence connect youth to a broader network of adults and illustrate how adults outside of the family contribute to the social control of adolescents.

Peers and the Emergence of Alcohol Use: Influence and Selection Processes in Adolescent Friendship Networks.

This study addresses not only influence and selection of friends as sources of similarity in alcohol use, but also peer processes leading drinkers to be chosen as friends more often than non-drinkers, which increases the number of adolescents subject to their influence. Analyses apply a stochastic actor-based model to friendship networks assessed five times from 6th through 9th grades for 50 grade cohort networks in Iowa and Pennsylvania, which include 13,214 individuals. Results show definite influence and selection for similarity in alcohol use, as well as reciprocal influences between drinking and frequently being chosen as a friend. These findings suggest that adolescents view alcohol use as an attractive, high status activity and that friendships expose adolescents to opportunities for drinking.

Effects of PROSPER on the influence potential of prosocial versus antisocial youth in adolescent friendship networks.

OBJECTIVES: We test the hypothesis that an evidence-based preventive intervention will change adolescent friendship networks to reduce the potential for peer influence toward antisocial behavior. Altering adolescents' friendship networks in this way is a promising avenue for achieving setting-level prevention benefits such as expanding the reach and durability of program effects. METHODS: Beginning in 2002, the Promoting School-University Partnerships to Enhance Resilience (PROSPER) randomized control trial assigned two entire sixth-grade cohorts of 14 rural and small town school districts in Iowa and Pennsylvania to receive the intervention and of 14 to control. A family-based intervention was offered in sixth grade and a school-based intervention was provided in seventh grade. More than 11,000 respondents provided five waves of data on friendship networks, attitudes, and behavior in sixth through ninth grade. Antisocial influence potential was measured by the association between network centrality and problem behavior for each of 256 networks (time, grade cohort, and school specific). RESULTS: The intervention had a beneficial impact on antisocial influence potential of adolescents' friendship networks, with p < .05 for both of the primary composite measures. CONCLUSIONS: Current evidence-based preventive interventions can alter adolescents' friendship networks in ways that reduce the potential for peer influence toward antisocial behavior.