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The mouse intranasal test (MINT) was developed to assess the immunogenic potential of detergent enzymes. The BDF1 mouse (H-2b/d), a cross of C57Bl/6 (H-2b) × DBA/2 (H-2d) has been used for most of the development work. Preliminary data in the CB6F1(H-2d/b), a cross of Balb/c (H-2d) × C57Bl/6 showed that this strain was similar to the BDF1 in its response to enzymes. These data also showed that the parental strains responded differently to the enzymes. To understand better the influence the major histocompatibility complex (MHC) background has on immune responses to enzymes, 3 different enzymes were tested in 4 inbred strains (C57Bl/6, DBA/2, Balb/c, and C57Bl/10), 2 hybrid strains (BDF1 and CB6F1), and 2 congenic strains (Balb.B10 and B10.D2). BDF1 mice rank enzymes the same as the guinea pig, which in turn correlates with sensitization in occupationally exposed humans. The ranking is based upon the dose of enzyme needed to give one-half maximal IgG1 antibody response (ED50) where Termamyl is more potent than Alcalase, which is equipotent to Savinase. The H-2d strains ranked the enzymes the same as the BDF1 but generated ED50s for the proteases that were one order of magnitude greater than the BDF1 ED50s. The response to Termamyl was the same in the two F1 strains and the H-2d strains. The H-2b strains did not rank the enzymes the same as BDF1 but the ED50s for the proteases were similar to the ED50s in the F1 strains. The response to Termamyl in the H-2b strains was lower than the response in the F1 and H-2d strains. Initial data show that the inbred strains will make enzyme-specific IgE antibody to high doses of enzyme with DBA/2 > Balb/c > C57Bl/6 in terms of the robustness of the response. The IgG1 responses in the congenic strains were similar to the responses in the H-2 matched strains. In addition, the antibody response to enzymes was consistent regardless of the source of BDF1 mice. The responses to these enzymes are clearly MHC linked with a role for Class II I-E molecules indicated. The current data strongly support the use of the F1 hybrid as an appropriate strain for evaluating allergic responses to enzymes. [ABSTRACT FROM PUBLISHER]

An intranasal (i.n.) dosing model was developed in mice as a potential alternative to more difficult, time-consuming, and costly guinea pig intratracheal (GPIT) or mouse intratracheal models for assessment of the respiratory immunogenicity of detergent enzymes. Using a benchmark enzyme, Alcalase (protease subtilisin Carlsberg), studies were conducted to standardize the model in terms of mouse strain, dosing and serum harvest regimen, and the primary immunoglobulin endpoint to use. The primary assay endpoint selected was the enzyme-specific IgG1 titer determined by an Alcalase-specific ELISA. This is not the primary allergenic antibody in mice (IgE is); however, IgG1 is coregulated with IgE via the IL-4/TH2 pathway and may have a role in mediating allergic-type responses. BDF1 mice (C57B1/6 × DBA/2) were selected as representative of high responder strains, with high response associated with the H-2b (C57B1/6) parent. The dosing regimen used for most studies incorporated three i.n. exposures (Days 1, 3, and 10) and bleeding of the animals on Day 15. The animals were anesthetized and then immunized by allowing them to inhale 5-μl aliquots of dosing solution into each nostril at each immunization. Positioning of the animals with their heads down (vs up) may have allowed more of the dosing solution to remain in the nasal region for a slightly longer period of time, but did not change the eventual GI tract migration and excretion of each dose. The presence of a detergent matrix in the enzyme dosing solution enhanced the IgG1 response. Immunizing with enzyme plus detergent gave highly consistent dose-response curves for Alcalase when evaluated over many studies. An enzyme-specific allergic antibody (IgE) response was weak and inconsistent under the dosing regimen used to generate the IgG1 response, but was stronger with longer-term dosing, consistent with the delay in IgE vs IgG1 responses seen in some other studies. Using IgG1 as a surrogate for allergic sensitization, we have preliminary data showing similar differential potencies between Alcalase and other test enzymes as detected in previous GPIT tests. On the basis of these data, we believe the i.n. immunization/IgG1 response model is a robust technique that may be useful in determining the relative immunogenicities of detergent enzymes and other proteins. [ABSTRACT FROM PUBLISHER]

The primary objective of this study was to examine the feasibility of using a mouse model to evaluate the immunogenicity of proteins as a potential method to determine occupational exposure guidelines. Mice were intratracheally administered a benchmark protein allergen, subtilisin Carlsberg (Alcalase) in detergent matrix once a week for 4 to 6 weeks and specific IgE and IgG1 levels were determined. In all experiments, specific IgE levels were determined by using a rat basophilic leukemia cell (RBL) release assay, while specific IgG1 was measured by an ELISA. A good correlation was observed between IgE titers determined by the RBL assay and rat passive cutaneous anaphylaxis assay. Intratracheal administration of protease with detergent matrix was found to result in significant IgE and IgG1 responses that were dose related. Detergent matrix was found to enhance the Alcalase-specific IgE and IgG1 response when administered by the intratracheal route. The IgG1 response was much more robust, easier to measure, and found to follow the IgE response. These results suggest that a mouse intratracheal model is a feasible approach to examining the immunogenic potency of enzymes using specific IgE or IgG1 as the end points. Additional development and validation of the mouse model with other types of proteins will be pursued. [ABSTRACT FROM AUTHOR]

Simple Summary: In Brazil, we have a considerable population of children living with HIV (CLWH), who are at a high risk of cancer development due to HIV infection (especially lymphomas), despite treatment with combined antiretroviral therapy (cART). This study aimed to learn how we might prevent these malignancies. We found a higher incidence of AIDS-defining malignancies (ADM) compared to non-AIDS-defining ones (NADM). In addition, ADM incidence rate decreased through widespread cART use. This study demonstrates the incidence of lymphoma in CLWH in Rio de Janeiro (RJ), Brazil, as well as the benefit of cART in reducing ADM and death occurrences in the Post-cART Era. The incidence of cancer in children living with HIV (CLWH) is high and lymphomas are the most common type of cancer in this population. The combined antiretroviral therapy (cART) changed the natural history of HIV infection. To determine the incidence and profile of these CLWH malignancies in Rio de Janeiro (RJ), Brazil, we conducted a retrospective and observational study of vertically infected CLWH, ranging from 0–20 incomplete years, from 1995 to 2018, at five reference centers. The study period was divided into three eras in accordance with the widespread use of cART in Brazil. 1306 patients were included. Of the 25 lymphomas found, 19 were AIDS-defining malignancies (ADM); 6 were non-AIDS-defining malignancies (NADM). The incidence rate (IR) of lymphoma developing was 1.70 per 1000 children-year (95% CI 1.09–2.50). ADM development IR decreased from 2.09–1.75–0.19 per 1000 children-year (p < 0.001) through cART eras. Cumulative Nelson–Aalen hazards of developing ADM over a 20-year period were 3.73% in the Early-cART era, 3.07% in the Mid-cART era, and 0.32% in the Late-cART era (p = 0.013). This study demonstrates the IR of lymphoma in CLWH in RJ, Brazil, as well as the benefit of cART in reducing ADM and death occurrence in the Post-cART era. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study involves a reanalysis of data from a randomized controlled trial to examine whether child–parent psychotherapy (CPP), an empirically based treatment focusing on the parent–child relationship as the vehicle for child improvement, is efficacious for children who experienced multiple traumatic and stressful life events (TSEs). Methods: Participants comprised 75 preschool-aged children and their mothers referred to treatment following the child''s exposure to domestic violence. Dyads were randomly assigned to CPP or to a comparison group that received monthly case management plus referrals to community services and were assessed at intake, posttest, and 6-month follow-up. Treatment effectiveness was examined by level of child TSE risk exposure (<4 risks versus 4+ TSEs). Results: For children in the 4+ risk group, those who received CPP showed significantly greater improvements in PTSD and depression symptoms, PTSD diagnosis, number of co-occurring diagnoses, and behavior problems compared to those in the comparison group. CPP children with <4 risks showed greater improvements in symptoms of PTSD than those in the comparison group. Mothers of children with 4+ TSEs in the CPP group showed greater reductions in symptoms of PTSD and depression than those randomized to the comparison condition. Analyses of 6-month follow-up data suggest improvements were maintained for the high risk group. Conclusions: The data provide evidence that CPP is effective in improving outcomes for children who experienced four or more TSEs and had positive effects for their mothers as well. Practice implications: Numerous studies show that exposure to childhood trauma and adversity has negative consequences for later physical and mental health, but few interventions have been specifically evaluated to determine their effectiveness for children who experienced multiple TSEs. The findings suggest that including the parent as an integral participant in the child''s treatment may be particularly effective in the treatment of young children exposed to multiple risks. [Copyright &y& Elsevier]

Objective: To examine the durability of improvement in child and maternal symptoms 6 months after termination of child-parent psychotherapy (CPP).Method: Seventy-five multiethnic preschool-age child-mother dyads from diverse socioeconomic backgrounds were randomly assigned to (1) CPP or (2) case management plus community referral for individual treatment. Children were 3 to 5 years old. Follow-up assessments were conducted 6 months after the end of a 1-year treatment period. Mothers completed the Child Behavior Checklist and the Symptom Checklist Revised to assess child's and mother's symptoms.Results: For treatment completers, general linear model (GLM) repeated-measures analyses support the durability of CPP with significant group x time interactions for children's total behavior problems and mothers' general distress. Intent-to-treat analyses revealed similar findings for children's behavior problems but were not significant for maternal symptoms.Conclusions: The findings provide additional evidence of the efficacy and durability of CPP with this population and highlight the importance of a relationship focus in the treatment of traumatized preschoolers. [ABSTRACT FROM AUTHOR]

The article discusses on the results of the clinical trials conducted on 75 multiethnic preschool-age child-mother pairs from diverse socioeconomic backgrounds to determine the durability of improvement in child and maternal symptoms six months after the termination of child-parent psychotherapy (CPP) in the U.S. The study revealed that general linear model repeated-measures analyses support durability of CPP with significant group based on time interaction for children's behavior problems.

Fraiberg and her colleagues (1975) introduced the metaphor “ghosts in the nursery” to describe the ways in which parents, by reenacting with their small children scenes from the parents' own unremembered early relational experiences of helplessness and fear, transmit child maltreatment from one generation to the next. In this article we propose that angels in the nursery—care-receiving experiences characterized by intense shared affect between parent and child in which the child feels nearly perfectly understood, accepted, and loved—provide the child with a core sense of security and self-worth that can be drawn upon when the child becomes a parent to interrupt the cycle of maltreatment. We argue that uncovering angels as growth-promoting forces in the lives of traumatized parents is as vital to the work of psychotherapy as is the interpretation and exorcizing of ghosts. Using clinical case material, we demonstrate the ways in which early benevolent experiences with caregivers can protect against even overwhelming trauma, and examine the reemergence of these benevolent figures in consciousness as an instrument of therapeutic change. Finally, we examine implications of the concept of “angels in the nursery” for research and clinical intervention. [ABSTRACT FROM AUTHOR]

Clinical psychology training for research-oriented scientist-practitioners tends to have a gap in research training during the predoctoral internship year. In 1982, the Clinical Psychology Training Program (CPTP) at the University of California, San Francisco (UCSF) began a 2-year clinical and clinical research training program combining an American Psychology Association (APA)-accredited internship and a postdoctoral fellowship. The goal of the program is to prepare graduates for leadership roles as principal investigators who are licensed clinicians able to function as independent practitioners. This article conveys the philosophy behind the program, its structure, and the results of the program over the last 31 years. The CPTP accepted 142 trainees, of whom 46 (32%) were minorities and 78 (55%) were women. CPTP fellows have published over 250 articles, chapters, and books with their mentors and have contributed to submitting research grants with them. The vast majority continued research and academic activities after graduation. The most recent self-study for APA accreditation reported that of 43 trainees admitted in the 10 years between 1999 and 2008, 41 (95%) went on to academic positions, research, or clinical positions in academic settings or research positions in other settings; 1 obtained a clinical position; and 1 provided no information. The program serves as a model for clinical psychology nationally, allowing for uninterrupted clinical research training during the internship and postdoctoral years, nurturing clinical psychologists committed to clinical research careers, and contributing substantially to the clinical research productivity of the host department. [ABSTRACT FROM AUTHOR]

This pilot study examined the potential impact of a perinatal adaptation to Child-Parent Psychotherapy (CPP), an evidence-based treatment for traumatized mother-child dyads, on maternal functioning 6 months post-partum among women with history of complex trauma and current intimate partner abuse. Pregnant women ( n = 64) enrolled during the third trimester of their pregnancy (Mean gestational age = 27.48 weeks, range of 12 to 42) and participated in weekly perinatal CPP sessions until their infant was 6 months old. Women completed measures of trauma history, depression, posttraumatic stress symptoms (PTSS), and child-rearing attitudes at pre- and post-treatment. Results showed decreases in depression and PTSS from pre- to post-treatment assessments, as well as an increase in positive child-rearing attitudes. As hypothesized, women with low maternal-fetal attachment demonstrated the greatest improvement in depression, PTSS, and child-rearing attitudes compared to women with high maternal-fetal attachment. The current study provides promising results indicating that a perinatal adaptation of CPP may lead to improved maternal mental health and parenting attitudes at a time of increased vulnerability in a high-risk population. [ABSTRACT FROM AUTHOR]

Objective: This study examined the influence of medical injury severity, perceived loss of physical functioning (conceptualized as physical resource loss), and global meaning making on psychological well-being among 79 veterans living with a spinal cord injury. Measures: Structured interviews were completed to assess perceived loss of physical abilities using the Conservation of Resources--Evaluation and SF-36 Health Survey, global meaning making (Purpose in Life scale), and psychological well-being (Sense of Well-Being Inventory). Medical injury severity was calculated from medical records. Results: Medical injury severity was not related to psychological well-being, whereas perceived loss of physical functioning was inversely associated. Global meaning making was significantly related to and accounted for a large portion of the variance in psychological well-being. Results suggest that global meaning making partially mediates perceived loss of physical resources and psychological well- being. Conclusion: The perceived loss of physical abilities and the generation of meaning and purpose in life are important variables that relate to positive adaptation following spinal cord injury. Treatment implications related to factors that increase quality of life following spinal cord injury are discussed. [ABSTRACT FROM AUTHOR]