Markers of Futile Resuscitation in Traumatic Hemorrhage: A Review of the Evidence and a Proposal for Futility Time-Outs during Massive Transfusion.

The reduction in the blood supply following the 2019 coronavirus pandemic has been exacerbated by the increased use of balanced resuscitation with blood components including whole blood in urban trauma centers. This reduction of the blood supply has diminished the ability of blood banks to maintain a constant supply to meet the demands associated with periodic surges of urban trauma resuscitation. This scarcity has highlighted the need for increased vigilance through blood product stewardship, particularly among severely bleeding trauma patients (SBTPs). This stewardship can be enhanced by the identification of reliable clinical and laboratory parameters which accurately indicate when massive transfusion is futile. Consequently, there has been a recent attempt to develop scoring systems in the prehospital and emergency department settings which include clinical, laboratory, and physiologic parameters and blood products per hour transfused as predictors of futile resuscitation. Defining futility in SBTPs, however, remains unclear, and there is only nascent literature which defines those criteria which reliably predict futility in SBTPs. The purpose of this review is to provide a focused examination of the literature in order to define reliable parameters of futility in SBTPs. The knowledge of these reliable parameters of futility may help define a foundation for drawing conclusions which will provide a clear roadmap for traumatologists when confronted with SBTPs who are candidates for the declaration of futility. Therefore, we systematically reviewed the literature regarding the definition of futile resuscitation for patients with trauma-induced hemorrhagic shock, and we propose a concise roadmap for clinicians to help them use well-defined clinical, laboratory, and viscoelastic parameters which can define futility.

Traumatic Brain Injury as an Independent Predictor of Futility in the Early Resuscitation of Patients in Hemorrhagic Shock.

This review explores the concept of futility timeouts and the use of traumatic brain injury (TBI) as an independent predictor of the futility of resuscitation efforts in severely bleeding trauma patients. The national blood supply shortage has been exacerbated by the lingering influence of the COVID-19 pandemic on the number of blood donors available, as well as by the adoption of balanced hemostatic resuscitation protocols (such as the increasing use of 1:1:1 packed red blood cells, plasma, and platelets) with and without early whole blood resuscitation. This has underscored the urgent need for reliable predictors of futile resuscitation (FR). As a result, clinical, radiologic, and laboratory bedside markers have emerged which can accurately predict FR in patients with severe trauma-induced hemorrhage, such as the Suspension of Transfusion and Other Procedures (STOP) criteria. However, the STOP criteria do not include markers for TBI severity or transfusion cut points despite these patients requiring large quantities of blood components in the STOP criteria validation cohort. Yet, guidelines for neuroprognosticating patients with TBI can require up to 72 h, which makes them less useful in the minutes and hours following initial presentation. We examine the impact of TBI on bleeding trauma patients, with a focus on those with coagulopathies associated with TBI. This review categorizes TBI into isolated TBI (iTBI), hemorrhagic isolated TBI (hiTBI), and polytraumatic TBI (ptTBI). Through an analysis of bedside parameters (such as the proposed STOP criteria), coagulation assays, markers for TBI severity, and transfusion cut points as markers of futilty, we suggest amendments to current guidelines and the development of more precise algorithms that incorporate prognostic indicators of severe TBI as an independent parameter for the early prediction of FR so as to optimize blood product allocation.

Observations of substance use treatment engagement during the period of community re-entry following residential treatment.

BACKGROUND: The period of community re-entry following residential substance use treatment is associated with elevated risk for return to substance use. Although continuity of care is best practice, many individuals do not engage in follow-up treatment, struggle to engage in follow-up treatment, or continue to use substances while participating in follow-up treatment. There is a need to both characterize treatment engagement during community re-entry following residential substance use treatment as well as understand how treatment impacts substance use during this high-risk period. METHOD: This observational study used retrospective self-report to examine treatment engagement and substance use among individuals who had exited residential substance use treatment. Participants completed a Timeline Follow-back interview reporting substance use and treatment engagement in the 30 days following residential treatment. RESULTS: Most participants (83.1 %) reported engaging in substance use treatment following discharge. The most common treatments were Alcoholics Anonymous/Narcotics Anonymous (61.1 %), medication for addiction treatment (40 %), and outpatient therapy (29.2 %). Participants were less likely to use substances on a day in which they engaged in outpatient therapy (OR = 0.32, 95 % CI [0.12, 0.90], p = 0.030) and more likely on days they engaged in medication treatment (OR = 21.49, 95 % CI [1.46, 316.74], p = 0.025). CONCLUSION: Findings characterize engagement in substance use treatment in the month following residential treatment. Treatment engagement was common during community re-entry; however, only outpatient therapy was found to reduce substance use during this high-risk period. Findings may inform intervention efforts during the high-risk period of community re-entry.

Racial Microaggressions Mediate the Association Between Posttraumatic Stress and Alcohol Use Among Women of Color Experiencing Intimate Partner Violence.

Objective: Women of Color (WoC) experiencing intimate partner violence (IPV) have elevated rates of posttraumatic stress disorder (PTSD) and alcohol use and related harm (e.g., increased alcohol use and negative consequences). This secondary data analysis assessed the role of racial microaggressions in the association between PTSD and alcohol use and related harm among WoC experiencing IPV. Methods: Participants were 103 WoC currently experiencing IPV and using substances (Mage=40.39, 51.5% Black) who were recruited from the community and completed assessments of PTSD, racial microaggressions, and alcohol use and related harm. Results: Assumptions of Inferiority (e.g., intelligence; B = 1.44, SE = 0.90, 95% CI [0.10, 3.54]) and Environmental Microaggressions (e.g., portrayal in media; B = 1.88, SE = 1.03, 95% CI [0.28, 4.30]) explained the association between PTSD and alcohol use and related harm. Conclusions: Findings underscore the influence of specific microaggressions in the relation between PTSD and alcohol use and related harm among WoC experiencing IPV.

Experimentally Induced Reductions in Alcohol Consumption and Brain, Cognitive, and Clinical Outcomes in Older Persons With and Those Without HIV Infection (30-Day Challenge Study): Protocol for a Nonrandomized Clinical Trial.

BACKGROUND: Both alcohol consumption and HIV infection are associated with worse brain, cognitive, and clinical outcomes in older adults. However, the extent to which brain and cognitive dysfunction is reversible with reduction or cessation of drinking is unknown. OBJECTIVE: The 30-Day Challenge study was designed to determine whether reduction or cessation of drinking would be associated with improvements in cognition, reduction of systemic and brain inflammation, and improvement in HIV-related outcomes in adults with heavy drinking. METHODS: The study design was a mechanistic experimental trial, in which all participants received an alcohol reduction intervention followed by repeated assessments of behavioral and clinical outcomes. Persons were eligible if they were 45 years of age or older, had weekly alcohol consumption of 21 or more drinks (men) or 14 or more drinks (women), and were not at high risk of alcohol withdrawal. After a baseline assessment, participants received an intervention consisting of contingency management (money for nondrinking days) for at least 30 days followed by a brief motivational interview. After this, participants could either resume drinking or not. Study questionnaires, neurocognitive assessments, neuroimaging, and blood, urine, and stool samples were collected at baseline, 30 days, 90 days, and 1 year after enrollment. RESULTS: We enrolled 57 persons with heavy drinking who initiated the contingency management protocol (mean age 56 years, SD 4.6 years; 63%, n=36 male, 77%, n=44 Black, and 58%, n=33 people with HIV) of whom 50 completed 30-day follow-up and 43 the 90-day follow-up. The planned study procedures were interrupted and modified due to the COVID-19 pandemic of 2020-2021. CONCLUSIONS: This was the first study seeking to assess changes in brain (neuroimaging) and cognition after alcohol intervention in nontreatment-seeking people with HIV together with people without HIV as controls. Study design strengths, limitations, and lessons for future study design considerations are discussed. Planned analyses are in progress, after which deidentified study data will be available for sharing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03353701; https://clinicaltrials.gov/study/NCT03353701. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53684.

An investigation of laboratory-based positive and negative emotional suppression in relation to posttraumatic stress disorder symptom clusters.

BACKGROUND: Emotional suppression is a clinically significant aspect of emotion regulation with robust associations to psychopathology, including posttraumatic stress disorder (PTSD). Despite the fast-growing body of literature highlighting the role of positive emotion regulation difficulties in the development and maintenance of PTSD, extant work on emotional suppression and PTSD has almost exclusively focused on the role of negative emotions. OBJECTIVE: The present study aimed to advance this literature by examining the associations between PTSD symptom clusters and participants' use of state emotional suppression during a laboratory task designed to elicit negative or positive emotions. METHOD: Participants were 108 community women (Mage = 39.55; 33% Black/African American) currently experiencing intimate partner violence (IPV) by a male partner and using substances. Participants were interviewed using a structured diagnostic assessment for PTSD and reported on state emotional intensity and emotional suppression following idiographic negative or positive emotion inductions. RESULTS: Results of the moderation analyses showed that, when controlling for state emotional intensity, women experiencing clinical levels of PTSD symptom Clusters B (intrusive recollections), D (negative alterations in cognitions and mood), and E (alterations in arousal and reactivity) were significantly more likely to utilize emotional suppression, but only in the context of positive-not negative-emotions. CONCLUSIONS: Findings provide evidence for a link between PTSD and positive emotional suppression among women currently experiencing IPV by a male partner and using substances, highlighting positive emotional suppression as a potential target in PTSD treatment for IPV populations with comorbid substance use concerns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Experimental Investigation of the Influence of Positive Emotion Dysregulation on Risky Behavior Following Idiographic Emotion Inductions.

An experimental paradigm with subjective and objective assessments was used to further explicate the role of positive emotion dysregulation on risky behavior. Participants were 151 community women currently experiencing intimate partner violence and using substances (Mage = 40.81, 43.0% white). Participants were randomly assigned to positive, negative, and neutral idiographic emotion inductions. Subjective (state self-report) and objective (high frequency heart rate variability [hfHRV], skin conductance response, and salivary cortisol) markers of emotion dysregulation were assessed, following which participants completed subjective (state urges for substances) and objective (Balloon Analogue Risk Task) measures of risky behavior. Results showed (a) greater self-reported state emotion dysregulation and lower hfHRV predicted more urges for substances in the positive (versus negative and neutral) emotion induction conditions; and (b) lower hfHRV predicted more behavioral risk-taking propensity in the positive (versus neutral) emotion induction condition. Findings provide additional support for the influence of positive emotion dysregulation on risky behavior.

Ecological investigation of the co-occurrence of posttraumatic stress disorder symptoms and cannabis use among community women experiencing intimate partner violence.

BACKGROUND: Women experiencing intimate partner violence (IPV) are at increased risk for developing hazardous patterns of cannabis use. Research suggests that women experiencing IPV use cannabis to cope with posttraumatic stress disorder (PTSD) symptoms. To advance research, we used experience sampling methods to explicate the within-day concurrent and proximal relations between PTSD symptom clusters and cannabis use among women experiencing IPV. METHOD: Participants were 145 community women (M age = 40.66, 41.6% white, 31.4% Black, 10.9% Hispanic or Latina, 8% American Indian/Alaska Native, 5.8% Bi-/multi-racial) experiencing IPV and using substances who completed three surveys a day for 30 days. RESULTS: Externalizing behavior (OR = 1.37, 95% CI [1.15, 1.65], p < 0.001) and dysphoric arousal (OR = 1.27, 95% CI [1.09, 1.49], p = 0.002) PTSD symptom clusters were associated with cannabis use reported in the same survey period. Results from the lagged models found no proximal associations between PTSD symptom clusters and cannabis use. CONCLUSIONS: Results highlight the acute effects of externalizing behavior and dysphoric arousal PTSD symptoms on cannabis use among women experiencing IPV. These findings may inform prevention and intervention efforts for cannabis use in this population.

Acrylic-based culture plate format perfusion device to establish liver endothelial-epithelial interface.

Microphysiological Systems (MPSs) or organs-on-chips, are microfluidic devices used to model human physiology in vitro. Polydimethylsiloxane (PDMS) is the most widely used material for organs-on-chips due to its established fabrication methods and biocompatibility properties. However, non-specific binding of small molecules limits PDMS for drug screening applications. Here, we designed a novel acrylic-based MPS to capture the physiological architecture that is observed universally in tissues across the body: the endothelial-epithelial interface (EEI). To reconstruct the EEI biology, we designed a membrane-based chip that features endothelial cells on the underside of the membrane exposed to mechanical shear from the path of media flow, and epithelial cells on the opposite side of the membrane protected from flow, as they are in vivo. We used a liver model with a hepatic progenitor cell line and human umbilical vein endothelial cells to assess the biological efficacy of the MPS. We computationally modeled the physics that govern the function of perfusion through the MPS. Empirically, efficacy was measured by comparing differentiation of the hepatic progenitor cells between the MPS and 2D culture conditions. We demonstrated that the MPS significantly improved hepatocyte differentiation, increased extracellular protein transport, and raised hepatocyte sensitivity to drug treatment. Our results strongly suggest that physiological perfusion has a profound effect on proper hepatocyte function, and the modular chip design motivates opportunities for future study of multi-organ interactions.

Shorter Duration Hepatitis C Virus Treatment is Associated with Better Persistence to Prescription Refills in People Who Inject Drugs: A Real-World Study.

INTRODUCTION: Direct-acting antiviral (DAA) therapy is highly effective in curing hepatitis C virus (HCV) infection in people who inject drugs (PWID). Previous studies showed declining persistence to DAA therapy over the course of treatment. This study compares real-world medication persistence to prescription refills for 8- versus 12-week DAA in treatment-naïve PWID with chronic HCV with compensated cirrhosis or without cirrhosis. METHODS: Symphony Health's claims database was used to collect data from patients with chronic HCV aged ≥ 12 years who were prescribed 8- or 12-week DAA therapy between August 2017 and November 2020 and had a diagnosis of addicted drug use within 6 months prior to index date. Eligible patients had medical/pharmacy claims in the 6 months before and 3 months after the first index medication fill date (i.e., index date). Patients completing all refills (8-week = 1 refill, 12-week = 2 refills) were deemed persistent. The percentage of persistent patients in each group, and at each refill step, was determined; outcomes were also assessed in a subgroup of Medicaid-insured patients. RESULTS: This study assessed 7203 PWID with chronic HCV (8-week, 4002; 12-week, 3201). Patients prescribed 8-week DAA treatment were younger (42.9 ± 12.4 vs 47.5 ± 13.2, P < 0.001) and had fewer comorbidities (P < 0.001). Patients receiving 8- versus 12-week DAA had greater refill persistence (87.9% vs 64.4%, P < 0.001). Similar percentages of patients missed their first refill (8-week, 12.1% vs 12-week, 10.8%); nearly 25% of patients receiving 12-week DAA missed their second refill. After baseline characteristics were controlled, patients prescribed 8- versus 12-week DAA were more likely to be persistent (odds ratio [95% confidence interval] 4.3 [3.8, 5.0]). Findings in the Medicaid-insured subgroup were consistent. CONCLUSION: Patients prescribed 8- vs 12-week DAA therapy had significantly greater prescription refill persistence. Most nonpersistence was due to missed second refills, highlighting the potential benefit of shorter treatment durations in this population.

Combined Use of RT-qPCR and NGS for Identification and Surveillance of SARS-CoV-2 Variants of Concern in Residual Clinical Laboratory Samples in Miami-Dade County, Florida.

Over the course of the COVID-19 pandemic, SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and immune escape capabilities, such as Delta and Omicron, have triggered waves of new COVID-19 infections worldwide, and Omicron subvariants continue to represent a global health concern. Tracking the prevalence and dynamics of VOCs has clinical and epidemiological significance and is essential for modeling the progression and evolution of the COVID-19 pandemic. Next generation sequencing (NGS) is recognized as the gold standard for genomic characterization of SARS-CoV-2 variants, but it is labor and cost intensive and not amenable to rapid lineage identification. Here we describe a two-pronged approach for rapid, cost-effective surveillance of SARS-CoV-2 VOCs by combining reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) and periodic NGS with the ARTIC sequencing method. Variant surveillance by RT-qPCR included the commercially available TaqPath COVID-19 Combo Kit to track S-gene target failure (SGTF) associated with the spike protein deletion H69-V70, as well as two internally designed and validated RT-qPCR assays targeting two N-terminal-domain (NTD) spike gene deletions, NTD156-7 and NTD25-7. The NTD156-7 RT-qPCR assay facilitated tracking of the Delta variant, while the NTD25-7 RT-qPCR assay was used for tracking Omicron variants, including the BA.2, BA.4, and BA.5 lineages. In silico validation of the NTD156-7 and NTD25-7 primers and probes compared with publicly available SARS-CoV-2 genome databases showed low variability in regions corresponding to oligonucleotide binding sites. Similarly, in vitro validation with NGS-confirmed samples showed excellent correlation. RT-qPCR assays allow for near-real-time monitoring of circulating and emerging variants allowing for ongoing surveillance of variant dynamics in a local population. By performing periodic sequencing of variant surveillance by RT-qPCR methods, we were able to provide ongoing validation of the results obtained by RT-qPCR screening. Rapid SARS-CoV-2 variant identification and surveillance by this combined approach served to inform clinical decisions in a timely manner and permitted better utilization of sequencing resources.

Religiosity and hazardous substance use: The moderating role of trauma-related shame.

BACKGROUND AND OBJECTIVES: Hazardous substance use is a major public health concern among individuals with a history of sexual victimization. Although increased religiosity has been known to serve as a protective factor against hazardous substance use, religious individuals with a history of sexual victimization may be at a greater risk for hazardous substance use due to difficulties reconciling sexual victimization with their religious beliefs. Individuals with greater trauma-related shame may engage in hazardous substance use as a means of coping with the traumatic event. METHOD: The present study consisted of 614 participants (Mage = 34.57, 50% women). RESULTS: Results suggested that organizational, nonorganizational, and intrinsic religiosity were positively associated with hazardous alcohol use at higher, but not lower, levels of trauma-related shame. Organizational and intrinsic religiosity were positively associated with hazardous drug use at higher, but not lower, levels of trauma-related shame. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This is the first study to examine the role of trauma-related shame in the relationship between religiosity and hazardous substance use. The findings underline the importance of targeting trauma-related shame in religious individuals with a history of sexual victimization.

Physiomimetic In Vitro Human Models for Viral Infection in the Liver.

Viral hepatitis is a leading cause of liver morbidity and mortality globally. The mechanisms underlying acute infection and clearance, versus the development of chronic infection, are poorly understood. In vitro models of viral hepatitis circumvent the high costs and ethical considerations of animal models, which also translate poorly to studying the human-specific hepatitis viruses. However, significant challenges are associated with modeling long-term infection in vitro. Differentiated hepatocytes are best able to sustain chronic viral hepatitis infection, but standard two-dimensional models are limited because they fail to mimic the architecture and cellular microenvironment of the liver, and cannot maintain a differentiated hepatocyte phenotype over extended periods. Alternatively, physiomimetic models facilitate important interactions between hepatocytes and their microenvironment by incorporating liver-specific environmental factors such as three-dimensional ECM interactions and co-culture with non-parenchymal cells. These physiologically relevant interactions help maintain a functional hepatocyte phenotype that is critical for sustaining viral hepatitis infection. In this review, we provide an overview of distinct, novel, and innovative in vitro liver models and discuss their functionality and relevance in modeling viral hepatitis. These platforms may provide novel insight into mechanisms that regulate viral clearance versus progression to chronic infections that can drive subsequent liver disease.

Downregulation of SOCS1 increases interferon-induced ISGylation during differentiation of induced-pluripotent stem cells to hepatocytes.

Background & Aims: Increased expression of IFN-stimulated gene 15 (ISG15) and subsequently increased ISGylation are key factors in the host response to viral infection. In this study, we sought to characterize the expression of ISG15, ISGylation, and associated enzymes at each stage of differentiation from induced pluripotent stem cells (iPSCs) to hepatocytes. Methods: To study the regulation of ISGylation, we utilized patient samples and in vitro cell culture models including iPSCs, hepatocytes-like cells, immortalized cell lines, and primary human hepatocytes. Protein/mRNA expression were measured following treatment with poly(I:C), IFNα and HCV infection. Results: When compared to HLCs, we observed several novel aspects of the ISGylation pathway in iPSCs. These include a lower baseline expression of the ISGylation-activating enzyme, UBE1L, a lack of IFN-induced expression of the ISGylation-conjugation enzyme UBE2L6, an attenuated activation of the transcription factor STAT1 and constitutive expression of SOCS1. ISGylation was observed in iPSCs following downregulation of SOCS1, which facilitated STAT1 activation and subsequently increased expression of UBE2L6. Intriguingly, HCV permissive transformed hepatoma cell lines demonstrated higher intrinsic expression of SOCS1 and weaker ISGylation following IFN treatment. SOCS1 downregulation in HCV-infected Huh 7.5.1 cells led to increased ISGylation. Conclusions: Herein, we show that high basal levels of SOCS1 inhibit STAT1 activation and subsequently IFN-induced UBE2L6 and ISGylation in iPSCs. Furthermore, as iPSCs differentiate into hepatocytes, epigenetic mechanisms regulate ISGylation by modifying UBE1L and SOCS1 expression levels. Overall, this study demonstrates that the development of cell-intrinsic innate immunity during the differentiation of iPSCs to hepatocytes provides insight into cell type-specific regulation of host defense responses and related oncogenic processes. Impact and implications: To elucidate the mechanism underlying regulation of ISGylation, a key process in the innate immune response, we studied changes in ISGylation-associated genes at the different stages of differentiation from iPSCs to hepatocytes. We found that high basal levels of SOCS1 inhibit STAT1 activation and subsequently IFN-induced UBE2L6 and ISGylation in iPSCs. Importantly, epigenetic regulation of SOCS1 and subsequently ISGylation may be important factors in the development of cell type-specific host defense responses in hepatocytes that should be considered when studying chronic infections and oncogenic processes in the liver.

Physiologically relevant microsystems to study viral infection in the human liver.

Viral hepatitis is a leading cause of liver disease and mortality. Infection can occur acutely or chronically, but the mechanisms that govern the clearance of virus or lack thereof are poorly understood and merit further investigation. Though cures for viral hepatitis have been developed, they are expensive, not readily accessible in vulnerable populations and some patients may remain at an increased risk of developing hepatocellular carcinoma (HCC) even after viral clearance. To sustain infection in vitro, hepatocytes must be fully mature and remain in a differentiated state. However, primary hepatocytes rapidly dedifferentiate in conventional 2D in vitro platforms. Physiologically relevant or physiomimetic microsystems, are increasingly popular alternatives to traditional two-dimensional (2D) monocultures for in vitro studies. Physiomimetic systems reconstruct and incorporate elements of the native cellular microenvironment to improve biologic functionality in vitro. Multiple elements contribute to these models including ancillary tissue architecture, cell co-cultures, matrix proteins, chemical gradients and mechanical forces that contribute to increased viability, longevity and physiologic function for the tissue of interest. These microsystems are used in a wide variety of applications to study biological phenomena. Here, we explore the use of physiomimetic microsystems as tools for studying viral hepatitis infection in the liver and how the design of these platforms is tailored for enhanced investigation of the viral lifecycle when compared to conventional 2D cell culture models. Although liver-based physiomimetic microsystems are typically applied in the context of drug studies, the platforms developed for drug discovery purposes offer a solid foundation to support studies on viral hepatitis. Physiomimetic platforms may help prolong hepatocyte functionality in order to sustain chronic viral hepatitis infection in vitro for studying virus-host interactions for prolonged periods.

Modeling reciprocal relations between emotion dysregulation and alcohol use using dynamic structural equation modeling: A micro-longitudinal study.

BACKGROUND: Research examining emotion dysregulation and alcohol use has increased exponentially over the past decade. However, these studies have been limited by their use of cross-sectional designs and narrow definitions of emotion dysregulation. To address these significant gaps in the extant literature, this study utilized state-of-the-art methodology (i.e., experience sampling) and statistics (i.e., dynamic structural equation modeling) to examine potential reciprocal associations between negative and positive emotion dysregulation and alcohol use at the momentary level. METHODS: Participants were 145 community women (mean age = 40.56, 40.3% white) experiencing intimate partner violence (IPV) and using substances. Surveys assessing negative and positive emotion dysregulation and alcohol use (i.e., number of standard drinks) were administered three times a day for 30 days using phone-based interactive voice recording. RESULTS: Significant contemporaneous effects indicated that negative and positive emotion dysregulation both co-occurred with alcohol use. However, levels of negative and positive emotion dysregulation did not predict later alcohol use, nor did alcohol use predict later levels of negative or positive emotion dysregulation. There was significant variability among participants in cross-lagged effects. CONCLUSIONS: Findings showed that negative and positive emotion dysregulation co-occurred with alcohol use and that there was significant interindividual variability in the cross-lagged associations between negative and positive emotion dysregulation and alcohol use. Research using idiographic approaches may identify women experiencing IPV for whom negative and positive emotion dysregulation drive alcohol use and alcohol use drives negative and positive emotion dysregulation.

RT-LAMP-Based Molecular Diagnostic Set-Up for Rapid Hepatitis C Virus Testing.

Hepatitis C virus (HCV) infections occur in approximately 3% of the world population. The development of an enhanced and extensive-scale screening is required to accomplish the World Health Organization's (WHO) goal of eliminating HCV as a public health problem by 2030. However, standard testing methods are time-consuming, expensive, and challenging to deploy in remote and underdeveloped areas. Therefore, a cost-effective, rapid, and accurate point-of-care (POC) diagnostic test is needed to properly manage the disease and reduce the economic burden caused by high case numbers. Herein, we present a fully automated reverse-transcription loop-mediated isothermal amplification (RT-LAMP)-based molecular diagnostic set-up for rapid HCV detection. The set-up consists of an automated disposable microfluidic chip, a small surface heater, and a reusable magnetic actuation platform. The microfluidic chip contains multiple chambers in which the plasma sample is processed. The system utilizes SYBR green dye to detect the amplification product with the naked eye. The efficiency of the microfluidic chip was tested with human plasma samples spiked with HCV virions, and the limit of detection observed was 500 virions/mL within 45 min. The entire virus detection process was executed inside a uniquely designed, inexpensive, disposable, and self-driven microfluidic chip with high sensitivity and specificity.

Depression and alcohol use in American Indian adolescents: The influence of family factors.

BACKGROUND: Rates of both depression and alcohol use are disproportionately higher among American Indian (AI) adolescents than adolescents in the general population. The co-occurrence of depression and alcohol use is common and clinically relevant given their reciprocal negative influences on outcomes. Family factors may be especially relevant because they could have a buffering effect on this relationship due to the importance of kinship and community in AI communities. The current study examines the roles of family warmth and parental monitoring in the association between depressive symptoms and alcohol use in a large, nationally representative sample of AI adolescents. METHODS: Data were collected from 3498 AI 7th to 12th graders (47.8% female) residing on or near a reservation during the period 2009 to 2013. Participants reported on their depressive symptoms, family factors, and alcohol use. RESULTS: There was a small, but statistically significant positive association between depressive symptoms and alcohol use (r = 0.11, p < 0.001). Greater depressive symptoms were associated with significantly less perceived family warmth (ß = -0.09, 95% CI [-0.13, -0.06]), which was associated with significantly greater alcohol use (ß = -0.39, 95% CI [-0.55, -0.23]). Family warmth significantly accounted for the association between depressive symptoms and alcohol use at high (ß = 0.04, SE = 0.02, 95% CI [0.004, 0.09]), but not low, levels of parental monitoring (ß = 0.02, SE = 0.02, 95% CI [-0.002, 0.06]). CONCLUSIONS: Results of the present study suggest that developing culturally sensitive prevention and treatment approaches focusing on increasing both family warmth and parental monitoring are important to address the co-occurrence of depression and alcohol misuse among AI adolescents.