Incidence and influencing factors of acute gastrointestinal injury after cardiac surgery.

BACKGROUND: To investigate the incidence and influencing factors of acute gastrointestinal injury (AGI) after cardiac surgery. METHODS: A total of 346 cases receiving treatment in the Intensive Care Unit (ICU) of the Department of Cardiovascular Surgery in our hospital from January 2021 to December 2021 were enrolled and their basic information was collected, including age, gender, height, weight, past medical history, Nutrition Risk Screening 2002, Body Mass Index (BMI), total operation duration, stay in ICU, preoperative blood routine examination results, complete biochemical examination, diamine oxidase (DAO) on Day 1, D-lactic acid index, a postoperative gastrointestinal condition, other postoperative complications and death during hospitalization. Moreover, logistic regression analysis was performed to identify the independent risk factors influencing the incidence of AGI after cardiac surgery. RESULTS: The incidence and mortality of AGI after cardiac surgery were 10.40% (36/346) and 25% (9/36), respectively. A dichotomous logistic regression multivariate analysis revealed that DAO on Day 1 (odd ratio = 1.062, p = 0.006) and stay in ICU (odd ratio = 1.192, p < 0.001) were independent risk factors of AGI after cardiac surgery, and total protein is a protective factor (odd ratio = 0.914, p = 0.012). CONCLUSIONS: Factors influencing AGI after cardiac surgery have been determined in this study. Our data suggest that patients with AGI after cardiac surgery have a decreased preoperative total protein, and elevated DAO on Day 1. Total protein and DAO on Day 1 were found to be correlated with AGI.

Glatiramer Acetate Complexed with CpG as Intratumoral Immunotherapy in Combination with Anti-PD-1.

CpG oligodeoxynucleotides are toll-like receptor 9 agonists capable of inducing potent pro-inflammatory immune responses. Although CpG oligodeoxynucleotides have shown promising antitumor effects, their systemic activity can trigger immune-related toxicity, limiting therapeutic application. We previously identified glatiramer acetate (GA), a cationic polypeptide approved for the treatment of relapsing-remitting multiple sclerosis, as an intratumoral delivery agent capable of complexing with CpG, thereby pinning it to the injection site and limiting systemic exposure. Here, we investigated whether the combination of CpG or GA-CpG polyplexes and intraperitoneal anti-PD-1 therapy would result in synergistic efficacy in AT84 and CT26 murine syngeneic models of head and neck and colon cancers, respectively. In both AT84 and CT26 tumor models, intratumoral CpG or GA-CpG treatment similarly suppressed tumor growth, but the efficacy was not amplified with anti-PD-1. Nevertheless, combination treatment increased cytotoxic T cell, helper T cell, and natural killer cell infiltration into AT84 tumors. Surprisingly, the combination of intratumoral GA and intraperitoneal anti-PD-1 treatment resulted in elevated systemic GM-CSF and IL-2 cytokine levels and demonstrated synergistic antitumor effects in the CT26 mouse tumor model. Moreover, tumors that responded most significantly to anti-PD-1 plus GA treatment showed increased markers of infiltration of CD4+ T cells and natural killer cells. Combinations of intratumoral GA or GA-CpG polyplexes with anti-PD-1 treatment warrant further investigation as combination cancer immunotherapy strategies.

Hopelessness and shame in relation to suicide attempts by Cuban adolescents.

Youth suicide rates in Cuba are very high compared with most other countries, despite considerable improvement in recent years. The purpose of our study was to determine whether hopelessness and shame distinguish adolescent suicide attempters from non-attempters, over and above the effects of depression and suicidal ideation. Participants were 844 Cuban adolescents from the province of Holguin in Eastern Cuba. The attempter groups included 38 participants being treated for suicide attempts in a day hospital and 82 participants in the community who self-reported a previous suicide attempt. The other participants were non-attempter controls. All participants were asked to complete measures of depression, hopelessness, shame and suicidal ideation. As expected, attempters scored higher than non-attempters on the control variables of depression and suicidal ideation. In addition, attempters self-reported greater shame, especially behavioral and characterological shame, than non-attempters. Contrary to our hypothesis, there was no significant difference in hopelessness between attempters and non-attempters. The results are inconsistent with the considerable narrative lore about hopelessness as a reason for suicide in Cuba and other socialist countries. However, some collective socialization practices may lead to shame.

Intratumoral Cancer Chemotherapy with a Carrier-Based Immunogenic Cell-Death Eliciting Platinum (IV) Agent.

A carrier-based, immunogenic cell death (ICD)-eliciting platinum(IV) chemotherapeutic agent was synthesized via complexation between an axially derivatized Pt(IV)-tocopherol and hyaluronan (HA)-tocopherol nanocarrier. The resultant HA-Pt(IV) complex demonstrated antiproliferative activity and induced calreticulin translocation, an indicator of ICD, in murine and human head and neck cancer (HNC) cells. The intratumorally administered HA-Pt(IV) treatments were tolerable and efficacious in both immunocompetent and immunodeficient mice with HNC, partially because of the direct cytotoxicity. Superior efficacy and survival were observed in the immunocompetent group, suggesting a possible Pt(IV)-induced immunological response, which would only manifest in animals with an intact immune system. Subsequent imaging of tumor tissues demonstrated increased macrophage infiltration in the HA-Pt(IV)-treated tumors compared to the nontreated controls and the cisplatin-treated tumors, suggesting favorable inflammatory activation. RNA sequencing of HA-Pt(IV)-treated tumors indicated that carbohydrate and vitamin metabolisms were the most important Kyoto Encyclopedia of Genes and Genomes pathways, and molecular function, biological process, and cellular component were highly enriched gene ontology categories.

Human intratumoral therapy: Linking drug properties and tumor transport of drugs in clinical trials.

Cancer therapies aim to kill tumor cells directly or engage the immune system to fight malignancy. Checkpoint inhibitors, oncolytic viruses, cell-based immunotherapies, cytokines, and adjuvants have been applied to prompt the immune system to recognize and attack cancer cells. However, systemic exposure of cancer therapies can induce unwanted adverse events. Intratumoral administration of potent therapies utilizes small amounts of drugs, in an effort to minimize systemic exposure and off-target toxicities. Here, we discuss the properties of the tumor microenvironment and transport considerations for intratumoral drug delivery. Specifically, we consider various tumor tissue factors and physicochemical factors that can affect tumor retention after intratumoral injection. We also review approved and clinical-stage intratumoral therapies and consider how the molecular and biophysical properties (e.g. size and charge) of these therapies influences intratumoral transport (e.g. tumor retention and cellular uptake). Finally, we offer a critical review and highlight several emerging approaches to promote tumor retention and limit systemic exposure of potent intratumoral therapies.

The Peer Victimization in College Survey: Construction and validation.

Colleges and universities are increasingly concerned about respect for diversity and tolerance of individual differences on their campuses. Nevertheless, no comprehensive measure of peer victimization has been developed and validated for use with college student populations. The Peer Victimization in College Survey (PVIC) is the first such measure. Study 1 (N = 733) reports how PVIC items were empirically derived to ensure construct coverage. Study 2 (N = 100) reports how intuitive PVIC subscales were established to distinguish between subtypes of college peer victimization. Study 3 (N = 520) provides evidence of convergent, discriminant, and construct validity for the PVIC, including its relations to risk factors and to outcomes such as depressive symptoms, anxiety, stress, and college sense of belonging. Study 4 (N = 633) validates several PVIC scaling methods and provides evidence of incremental validity of the measure over current (unvalidated) measures. The PVIC can assess subtypes of peer victimization on college campuses, evaluate the effectiveness of campus intervention efforts, and test hypotheses about the causes and effects of peer victimization. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Emotional and cognitive reactivity: Validating a multilevel modeling approach to daily diary data.

An increasing number of studies are applying multilevel modeling (MLM) to daily diary assessments of emotional and cognitive reactivity (ER and CR). Despite their generation of promising results, these methods have yet to be validated. The current study, consisting of 449 participants from over 90 different colleges and universities, had 2 goals: (a) to assess the convergent validity of these methods in relation to more conventional measures, and (b) to assess the construct validity of these methods in relation to depressive symptoms. Results support the extraction of within- versus between-person aspects of both constructs from daily diary data. Evidence of convergent validity derives from the association of MLM-based estimates of ER and CR with established self-report questionnaire methods. Evidence of construct validity derives from the relation of these estimates to symptoms of depression. The value of distinguishing within- from between-person aspects of ER and CR is discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Dynamic measures of emotional and cognitive reactivity in college students.

Questionnaire and mood-induction measures of emotional and cognitive reactivity (ER and CR) have noteworthy strengths as well as potential liabilities (as do virtually all measures of psychological constructs). Toward a solution to the fallible measurement problem, methodologists have long advocated utilizing qualitatively diverse assessment methods to converge upon the constructs of interests. The current article introduces and provides initial validation of the Behind Your Back measure that (unlike any other measure) simultaneously assesses both ER and CR in college students via methods that avoid some of the problems associated with conventional measures. For both ER and CR, 3 dimensions are hypothesized, representing (a) person-driven, (b) event-driven, and (c) person/event-driven aspects of ER and CR. Results support this tripartite structure and provide evidence of convergent and construct validity of the method, including significant relations to self-reported symptoms of depression. Implications of these BYB-derived dimensions for theory and enhancing practice are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Formulation and preclinical evaluation of a toll-like receptor 7/8 agonist as an anti-tumoral immunomodulator.

The toll-like receptor 7 and 8 (TLR7/8) agonist Resiquimod (R848) has been recognized as a promising immunostimulator for the treatment of cutaneous cancers in multiple clinical trials. However, systemic administration of R848 often results in strong immune-related toxicities while having limited therapeutic effects to the tumor. In the present study, a prodrug-based nanocarrier delivery system was developed that exhibited high therapeutic efficiency. R848 was conjugated to α-tocopherol to constitute an R848-Toco prodrug, followed by formulating with a tocopherol-modified hyaluronic acid (HA-Toco) as a polymeric nano-suspension. In vitro evaluation showed that the delivery system prolonged the release kinetics while maintaining TLR agonist activities. When administered subcutaneously, the nano-suspension formed a depot at the injection site, inducing localized immune responses without systemic expansion. This formulation also suppressed tumor growth and recruited immune cells to the tumor in a murine model of head and neck cancer. In a preclinical canine study of spontaneous mast cell tumors, the treatment led to a 67% response rate (three partial remissions and one complete remission).