Calcium Channels in the Heart: Disease States and Drugs.

Calcium ions are the major signaling ions in the cells. They regulate muscle contraction, neurotransmitter secretion, cell growth and migration, and the activity of several proteins including enzymes and ion channels and transporters. They participate in various signal transduction pathways, thereby regulating major physiological functions. Calcium ion entry into the cells is regulated by specific calcium channels and transporters. There are mainly six types of calcium channels, of which only two are prominent in the heart. In cardiac tissues, the two types of calcium channels are the L type and the T type. L-type channels are found in all cardiac cells and T-type are expressed in Purkinje cells, pacemaker and atrial cells. Both these types of channels contribute to atrioventricular conduction as well as pacemaker activity. Given the crucial role of calcium channels in the cardiac conduction system, mutations and dysfunctions of these channels are known to cause several diseases and disorders. Drugs targeting calcium channels hence are used in a wide variety of cardiac disorders including but not limited to hypertension, angina, and arrhythmias. This review summarizes the type of cardiac calcium channels, their function, and disorders caused by their mutations and dysfunctions. Finally, this review also focuses on the types of calcium channel blockers and their use in a variety of cardiac disorders.

Child maltreatment and cognitive and academic functioning in two generations.

BACKGROUND: Childhood maltreatment has been associated with deficits in cognitive functioning and poor academic performance. Not known is whether these characteristics are the direct consequence of the childhood maltreatment (that is, maltreatment plays a causal role) or whether other factors explain the relationship. OBJECTIVES: To examine whether childhood maltreatment predicts cognitive and academic functioning and whether these relationships are explained by other factors (parent cognitive and academic functioning, family social class, or parent maltreatment). PARTICIPANTS: Data are from a longitudinal study of previously maltreated children, matched controls, and a subset of their offspring (697 parent-offspring dyads) interviewed in 2009-2010. METHOD: Cognitive and academic functioning were assessed in both parents and offspring with the same measures. Maltreatment was determined through official records. Hierarchical linear regressions were conducted to examine predictors of offspring cognitive and academic functioning. RESULTS: Childhood maltreatment was associated with poorer cognitive functioning and worse academic performance in both generations. Controlling for age, sex, race, and whether the parent had more than one child in the study, offspring maltreatment predicted offspring cognitive functioning when it was the only predictor in the model. In a final model with all variables, only parent cognitive functioning predicted offspring cognitive functioning and parent academic functioning and parent history of maltreatment predicted offspring academic functioning. CONCLUSION: These results challenge assumptions that childhood maltreatment directly causes deficits in cognitive and academic functioning. Policy makers and practitioners may need to rethink the design of interventions to improve the cognitive and academic functioning of maltreated children.

Randomized Trial of Academic Training and Medication Decision-Making for Adolescents with ADHD in Usual Care.

Objective: This study tested two family-based interventions designed for delivery in usual care: Changing Academic Support in the Home for Adolescents with ADHD (CASH-AA), containing motivational interventions, homework management and schoolwork organization training, and family-school partnership building; and Medication Integration Protocol (MIP), containing ADHD psychoeducation, medication decision-making, and integrated medication management.Method: This study used a cluster randomized design to test CASH-AA + MIP versus CASH-AA Only for adolescents with ADHD in five sites. Therapists (N = 49) were site clinicians randomized to condition. Clients (N = 145) included 72% males; 42% White Non-Hispanic, 37% Hispanic American, 15% African American, and 6% more than one race; average age was 14.8 years. Fidelity data confirmed protocol adherence and between-condition differentiation.Results: One-year improvements were observed across conditions in several outcomes. Overall, CASH-AA + MIP produced greater declines in adolescent-report inattentive symptoms and delinquent acts. Similarly, among non-substance users, CASH-AA + MIP clients attended more treatment sessions. In contrast, among substance users, CASH-AA Only clients showed greater declines in caregiver-report hyperactive symptoms and externalizing.Conclusions: This study provides initial experimental support for family-based ADHD medication decision-making when coupled with academic training in usual care. The treatment protocols, CASH-AA and MIP, showed positive effects in addressing not only ADHD symptoms but also common co-occurring problems, and youth with substance use problems benefitted along with non-using peers.

Improving Substance Use Services for Juvenile Justice-Involved Youth: Complexity of Process Improvement Plans in a Large Scale Multi-site Study.

Despite the high prevalence of substance use disorders among juvenile offenders, most do not receive services. System-level process improvement plans to address unmet service needs can be optimized by combining data-driven decisions and facilitated meetings with behavioral health stakeholders. This paper operationalizes and analyzes the level of specified complexity among process improvement plans evident within 36 juvenile probation and drug courts across 7 states. To inform more effective implementation strategies, this analysis identifies and prioritizes promising courses of agency enhancement toward addressing unmet substance use needs.

A Prospective, Longitudinal Examination of the Influence of Childhood Home and School Contexts on Psychopathic Characteristics in Adolescence.

Much of the existing research examining etiological contributors to psychopathic characteristics considers only biological and physiological deficits, with little consideration given to contextual factors that may play a role in their development. This prospective, longitudinal study examined the influence of childhood home and school environments on adolescent psychopathic characteristics among 390 youth (50.5% female; 46.2% Black/African American, 44.9% Hispanic/Latino, 6.9% Asian or Native American/Alaska Native, and 2.1% Non-Hispanic White). Specifically, this study examined (1) the effect of home chaos and poor parental monitoring on adolescent primary and secondary psychopathy and callous-unemotional traits through the lens of multiple reporters, and (2) whether classroom climate quality across three years of childhood moderated these relationships. The results indicated that delinquency and home chaos in childhood were related to primary psychopathy in adolescence and that exposure to higher quality classroom climates across childhood acted as a buffer by mitigating the negative relationship between parental monitoring in childhood and secondary psychopathy in adolescence. These findings have implications for designing interventions to mitigate the manifestation of youth psychopathy.

Using Goal Achievement Training in juvenile justice settings to improve substance use services for youth on community supervision.

BACKGROUND: The link between substance use and involvement in the juvenile justice system has been well established. Justice-involved youth tend to have higher rates of drug use than their non-offending peers. At the same time, continued use can contribute to an elevated risk of recidivism, which leads to further, and oftentimes more serious, involvement with the juvenile justice system. Because of these high rates of use, the juvenile justice system is well positioned to help identify youth with substance use problems and connect them to treatment. However, research has found that only about 60% of juvenile probation agencies screen all youth for substance involvement, and even fewer provide comprehensive assessment or help youth enroll in substance use treatment. METHOD: This paper describes an integrated training curriculum that was developed to help juvenile justice agencies improve their continuum of care for youth probationers with substance use problems. Goal Achievement Training (GAT) provides a platform for continuous quality improvement via two sessions delivered onsite to small groups of staff from juvenile justice and behavioral health agencies. In the first session, participants are taught to identify goals and goal steps for addressing identified areas of unmet need (i.e., screening, assessment, and linkage to treatment services). In the second session, participants learn principles and strategies of data-driven decision-making for achieving these goals. This paper highlights GAT as a model for the effective implementation of cost-efficient training strategies designed to increase self-directed quality improvement activities that can be applied to any performance domain within juvenile justice settings. Efforts to monitor implementation fidelity of GAT within the specific context of the juvenile justice settings are highlighted. DISCUSSION: Challenges to setting the stage for process improvement generally, as well as specific hurdles within juvenile justice settings are discussed, as are next steps in disseminating findings regarding the fidelity to and effectiveness of GAT in this unique context. TRIAL REGISTRATION: Clinical Trials Registration number - NCT02672150 .

A model for rigorously applying the Exploration, Preparation, Implementation, Sustainment (EPIS) framework in the design and measurement of a large scale collaborative multi-site study.

BACKGROUND: This paper describes the means by which a United States National Institute on Drug Abuse (NIDA)-funded cooperative, Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), utilized an established implementation science framework in conducting a multi-site, multi-research center implementation intervention initiative. The initiative aimed to bolster the ability of juvenile justice agencies to address unmet client needs related to substance use while enhancing inter-organizational relationships between juvenile justice and local behavioral health partners. METHODS: The EPIS (Exploration, Preparation, Implementation, Sustainment) framework was selected and utilized as the guiding model from inception through project completion; including the mapping of implementation strategies to EPIS stages, articulation of research questions, and selection, content, and timing of measurement protocols. Among other key developments, the project led to a reconceptualization of its governing implementation science framework into cyclical form as the EPIS Wheel. The EPIS Wheel is more consistent with rapid-cycle testing principles and permits researchers to track both progressive and recursive movement through EPIS. Moreover, because this randomized controlled trial was predicated on a bundled strategy method, JJ-TRIALS was designed to rigorously test progress through the EPIS stages as promoted by facilitation of data-driven decision making principles. The project extended EPIS by (1) elucidating the role and nature of recursive activity in promoting change (yielding the circular EPIS Wheel), (2) by expanding the applicability of the EPIS framework beyond a single evidence-based practice (EBP) to address varying process improvement efforts (representing varying EBPs), and (3) by disentangling outcome measures of progression through EPIS stages from the a priori established study timeline. DISCUSSION: The utilization of EPIS in JJ-TRIALS provides a model for practical and applied use of implementation frameworks in real-world settings that span outer service system and inner organizational contexts in improving care for vulnerable populations. TRIAL REGISTRATION: NCT02672150 . Retrospectively registered on 22 January 2016.

Perceived Need for Treatment and Engagement in Mental Health Services Among Community-Referred Racial/Ethnic Minority Adolescents.

This study examines clinical and family predictors of perceived need for treatment and engagement in mental health treatment services among community-referred racial/ethnic minority adolescents and their primary caregivers. Findings indicated that the majority of families perceived a need for treatment, but that perceived need was not associated with treatment engagement. Family factors (i.e., low cohesion and high conflict within the family) predicted perceived need for treatment among adolescents, whereas clinical factors (i.e., adolescent internalizing and externalizing symptomatology) predicted caregiver perceived need for adolescent treatment. Neither clinical nor family factors predicted treatment engagement.

The Benefits of Community and Juvenile Justice Involvement in Organizational Research.

The Juvenile Justice (JJ) system has a number of local behavioral health service community linkages for substance abuse, mental health, and HIV services. However, there have only been a few systemic studies that examine and seek to improve these community behavioral health linkages for justice-involved youth. Implementation research is a way of identifying, testing, and understanding effective strategies for translating evidence-based treatment and prevention approaches into service delivery. This article explores benefits and challenges of participatory research within the context of the National Institute on Drug Abuse (NIDA)'s Juvenile Justice Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS) implementation behavioral health study. The JJ-TRIALS study has involved JJ partners (representatives from state-level JJ agencies) throughout the study development, design, and implementation. Proponents of participatory research argue that such participation strengthens relations between the community and academia; ensures the relevancy of research questions; increases the capacity of data collection; and enhances program recruitment, sustainability, and extension. The extent of the impact that JJ partners have had on the JJ-TRIALS study will be discussed, as well as the benefits local JJ agencies can derive from both short- and long-term participation. Issues associated with the site selection, participation, and implementation of evidence-based practices also will be discussed.

Congenic Strains Confirm the Pleiotropic Effect of Chromosome 4 QTL on Mouse Femoral Geometry and Biomechanical Performance.

A pleiotropic quantitative trait locus (QTL) for bone geometry and mechanical performance in mice was mapped to distal chromosome 4 via an intercross of recombinant congenic mice HcB-8 and HcB-23. To study the QTL in isolation, we have generated C3H.B10-(rs6355453-rs13478087) (C.B.4.3) and C3H.B10-(rs6369860-D4Mit170) (C.B.4.2) congenic strains that harbor ~20 Mb and ~3 Mb, respectively, of chromosome 4 overlapping segments from C57BL/10ScSnA (B10) within the locus on a C3H/DiSnA (C3H) background. Using 3-point bend testing and standard beam equations, we phenotyped these mice for femoral mid-diaphyseal geometry and biomechanical performance. We analyzed the results via 2-way ANOVA, using sex and genotype as factors. In the C.B.4.3 strain, we found that homozygous B10/B10 male mice had smaller cross sectional area (CSA) and reduced total displacement than homozygous C3H/C3H mice. Sex by genotype interaction was also observed for maximum load and stiffness for C3H/C3H and B10/B10 mice, respectively. In C.B.4.2 strain, we found that homozygous B10/B10 mice had lower total displacement, post-yield displacement (PYD), stiffness, yield load and maximum load than mice harboring C3H allele. Sex by genotype interaction was observed in B10/B10 mice for perimeter, outer minor axis (OMA) and CSA. There were no significant differences in tissue level mechanical performance, which suggest that the QTL acts primarily on circumferential bone size. These data confirm the prior QTL mapping data and support other work demonstrating the importance of chromosome 4 QTL on bone modeling and bone responses to mechanical loading.

Sensitive electrochemical immunosensor for matrix metalloproteinase-3 based on single-wall carbon nanotubes.

A novel electrochemical immunosensor for the detection of matrix metalloproteinase-3 (MMP-3), a cancer biomarker protein, based on vertically aligned single-wall carbon nanotube (SWCNT) arrays is presented. Detection was based on a sandwich immunoassay consisting of horseradish peroxidase (14-16 labels) conjugated to a secondary antibody and/or a polymer bead loaded with multi-enzyme labels. Performance was optimized by effective minimization of non-specific binding (NSB) events using Bovine serum albumin (BSA), Tween-20 and optimization of the primary antibody and secondary antibody concentrations. Results provided a detection limit of 0.4 ng mL(-1) (7.7 pM) for the 14-16 label sensor protocol and 4 pg mL(-1) (77 fM) using a multiply enzyme labeled polymeric bead amplification strategy in 10 microL of calf serum. This immunosensor based on SWCNT arrays offers great promise for a rapid, simple, cost-effective method for clinical screening of cancer biomarkers for point-of-care diagnosis.

Analyzing the contribution of community change to population health outcomes in an adolescent pregnancy prevention initiative.

Few evaluations of community initiatives have established a link between intermediate outcomes, such as community or systems change, and more distant population-level health outcomes (e.g., estimated rates of employment or adolescent pregnancy). This article describes an analysis of the contribution of community changes facilitated by a community health initiative to prevent adolescent pregnancy to the population-level outcome of birth rates for teens. The authors examine a hypothesis that this link might be expected when community changes are of greater amount, intensity, duration, and exposure. The results showed reductions in birth rates in Target Area A, where there was a greater concentration of community changes and a slight increase where there were far fewer changes. This report provides a method for describing empirically the contribution of environmental change to more distant population-level outcomes.