Incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease in patients with multiple sclerosis initiating disease-modifying therapies: Retrospective cohort study using a frequentist model averaging statistical framework.

Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies-which was statistically significant for the comparison with teriflunomide-this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis.

Assessment of Efficacy and Safety of Zagotenemab: Results From PERISCOPE-ALZ, a Phase 2 Study in Early Symptomatic Alzheimer Disease.

BACKGROUND AND OBJECTIVES: Zagotenemab (LY3303560), a monoclonal antibody that preferentially targets misfolded, extracellular, aggregated tau, was assessed in the PERISCOPE-ALZ phase 2 study to determine its ability to slow cognitive and functional decline relative to placebo in early symptomatic Alzheimer disease (AD). METHODS: Participants were enrolled across 56 sites in North America and Japan. Key eligibility criteria included age of 60-85 years, Mini-Mental State Examination score of 20-28, and intermediate levels of brain tau on PET imaging. In this double-blind study, participants were equally randomized to 1,400 mg or 5,600 mg of zagotenemab, or placebo (IV infusion every 4 weeks for 100 weeks). The primary outcome was change on the Integrated AD Rating Scale (iADRS) assessed by a Bayesian Disease Progression model. Secondary measures include mixed model repeated measures analysis of additional cognitive and functional endpoints as well as biomarkers of AD pathology. RESULTS: A total of 360 participants (mean age = 75.4 years; female = 52.8%) were randomized, and 218 completed the treatment period. Demographics and baseline characteristics were reasonably balanced among arms. The mean disease progression ratio (proportional decline in the treated vs placebo group) with 95% credible intervals for the iADRS was 1.10 (0.959-1.265) for the zagotenemab low-dose group and 1.05 (0.907-1.209) for the high-dose, where a ratio less than 1 favors the treatment group. Secondary clinical endpoint measures failed to show a drug-placebo difference in favor of zagotenemab. No treatment effect was demonstrated by flortaucipir PET, volumetric MRI, or neurofilament light chain (NfL) analyses. A dose-related increase in plasma phosphorylated tau181 and total tau was demonstrated. Zagotenemab treatment groups reported a higher incidence of adverse events (AEs) (85.1%) compared with the placebo group (74.6%). This difference was not attributable to any specific AE or category of AEs. DISCUSSION: In participants with early symptomatic AD, zagotenemab failed to achieve significant slowing of clinical disease progression compared with placebo. Imaging biomarker and plasma NfL findings did not show evidence of pharmacodynamic activity or disease modification. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03518073. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with early symptomatic AD, zagotenemab does not slow clinical disease progression.

Unsettled adoptive identity: Understanding relationship challenges in adopted adolescents' identity narratives.

Adopted adolescents create identity narratives conceptualizing their connections to their families of adoption and birth. Previous work with a sample of adoptive adolescents identified a sub-group who reported negative experiences regarding adoption as part of their navigating of adoptive identity processes (the "Unsettled" group). The current study examined interviews with adolescents in the "Unsettled" group to elucidate these negative experiences, specifically through identifying the relationship challenges linked to adoption. Participants included 30 adopted adolescents (18 females, 12 males) from a longitudinal study of adoptive families. All the adolescents (M age = 15.2 years) were domestically adopted in infancy by heterosexual couples who were the same race as the adolescents (29 White, 1 Mexican American). Thematic analysis revealed six themes reflecting adolescents' relationship challenges as related to adoption, both in terms of interpersonal interactions and how relational experiences influenced adolescents' thoughts and feelings of past, present, and future selves: (a) Negative experiences in relationships with adoptive family members, (b) Negative experiences in relationships with birth family members, (c) Difficulties in the adoptive kinship network, (d) Negative thoughts and feelings toward the self as an adopted person, (e) Negative views toward adoption as a form of building a family, and (f) Negative connections between adoption and future relationships. Multiple subthemes were also identified that built upon topics within the adoption and family systems literature, such as communication among family members, navigation of birth family contact, and adopted adolescents' perceptions of loss. Also identified were four profiles across themes. Implications for mental health providers and adoption professionals are discussed.

Safety, Tolerability, and Pharmacokinetics of Zagotenemab in Participants with Symptomatic Alzheimer's Disease: A Phase I Clinical Trial.

Background: Zagotenemab (LY3303560), a monoclonal antibody, preferentially binds to extracellular, misfolded, aggregated tau that has been implicated in Alzheimer's disease (AD). Objective: The goal of this study was to assess the safety and pharmacokinetics of multiple doses of zagotenemab in participants with AD. Methods: This was a Phase Ib, multi-site, participant- and investigator-blind, placebo-controlled, parallel-group study in participants with mild cognitive impairment due to AD or mild to moderate AD. After screening, participants were randomized to zagotenemab 70 mg, 210 mg, or placebo every 4 weeks for up to 49 weeks and were followed up for 16 weeks. Results: A total of 13 males and 9 females, aged 59 to 84 years, were dosed. No deaths occurred during this study. A total of 4 serious adverse events occurred in 2 participants who then discontinued the study. The most commonly reported (3 or more participants) treatment-emergent adverse events were sinus bradycardia, headache, fall, and bronchitis. The pharmacokinetics profile showed generally linear exposures across the dose range studied with a clearance of ~8 mL/h. The half-life of zagotenemab in serum was ~20 days. A dose-dependent increase in plasma tau was observed. No other significant pharmacodynamic differences were observed due to low dose levels and limited treatment duration. Conclusions: No dose-limiting adverse events were observed with zagotenemab treatment. Pharmacokinetics of zagotenemab were typical for a monoclonal antibody. Meaningful pharmacodynamic differences were not observed.Clinicaltrials.gov: NCT03019536.

Birth Family Contact from Childhood to Adulthood: Adjustment and Adoption Outcomes in Adopted Young Adults.

Experiences of contact between adopted persons and birth family members have implications for psychological adjustment of adopted persons. The current study utilizes four contact trajectory groups, spanning from middle childhood to young adulthood and encompassing three aspects of birth family contact, in predicting psychological adjustment and adoption-related outcomes in adopted young adults. Data come from a longitudinal study of adoptive families in which adopted persons were domestically adopted in infancy by same-race parents in the United States. Adopted young adults in the group characterized by sustained high levels of contact and satisfaction with contact over time ('Extended Contact') displayed lower levels of psychological distress and higher levels of psychological well-being than adopted persons in the group characterized by contact that increased over time but remained limited ('Limited Contact'). Generally, adopted persons within the group characterized by consistent lack of contact ('No Contact') and the group characterized by contact that was initially present but ended ('Stopped Contact') did not differ in distress and well-being from those in the 'Extended Contact' group. No group differences were found on adoption dynamics and identity, however young adults in the 'Extended Contact' group generally reported more positive relationships with their birth mothers than those in the other groups. Findings are discussed in the context of heterogeneity in contact experiences and implications for policy and practice.

Parents' adaptation from conflict: Bicultural socialization beliefs and acculturative family conflict in Chinese American families.

Many Chinese American parents desire for their children to take on both Chinese heritage and mainstream American values and behaviors, referred to as their bicultural socialization beliefs. Parents' development of such beliefs appears linked with parent-adolescent conflict concerning cultural values, yet the direction and temporal ordering of this relation is unclear. The present study aimed to resolve discrepancies in the literature through examining the bidirectional relations between Chinese American parents' bicultural socialization beliefs and the acculturative family conflict they experience with their children. Relations were examined across two developmental periods of the children: adolescence and emerging adulthood. Data came from a longitudinal study of 444 Chinese American families from the west coast of the United States. Mothers and fathers reported on their own bicultural socialization beliefs for their children. Mothers, fathers, and adolescents/emerging adults each reported on levels of acculturative family conflict within mother-adolescent and father-adolescent dyads. Higher levels of family conflict in adolescence consistently predicted greater increases in parents' desires for their children to be bicultural in emerging adulthood. Results have implications for interventions with Chinese American families and demonstrate Chinese American parents as capable of adapting and growing from challenging, culturally based interactions with their children. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effect of Backward and Forward Walking on Lower Limb Strength, Balance, and Gait in Multiple Sclerosis: A Randomized Feasibility Trial.

BACKGROUND: Backward walking (BW) interventions have improved gait and balance in persons with stroke, cerebral palsy, and Parkinson disease but have not been studied in persons with multiple sclerosis (MS). We examined the feasibility of a BW intervention and how it affected strength, balance, and gait vs forward walking (FW) in persons with MS. METHODS: Sixteen persons with MS with a Patient-Determined Disease Steps (PDDS) scale score of 3 to 5 (gait impairment-late cane) were randomized to the FW (n = 8) or BW (n = 8) group. Participants did 30 minutes of FW or BW on a treadmill 3 times per week for 8 weeks (24 visits). Enrollment, adherence rate, and safety were tracked. The Timed Up and Go test, Six-Spot Step Test, single-leg stance, and abbreviated Activities-specific Balance Confidence scale were used to measure balance. Hip and knee flexion and extension strength (isometric peak torque), gait speed, and spatiotemporal gait parameters were measured. A 2×2 factorial multivariate analysis of covariance was used to examine changes in strength, balance, and gait, with the PDDS scale score as the covariate. RESULTS: Treatment adherence rate was 99.7%, with no safety concerns. After controlling for baseline differences in disability (PDDS scale score; P = .041), the BW group improved dominant hip flexion strength preintervention to postintervention compared with the FW group (F 1,13 = 9.03; P = .010). No other significant differences were seen between groups. CONCLUSIONS: This was the first study to look at BW as an intervention in persons with MS. Based on its feasibility, safety, and significant finding, BW should be studied in a larger, definitive trial in the future.

Establishing the Test-Retest Reliability and Minimal Detectable Change of the Multiple Sclerosis Resiliency Scale.

BACKGROUND: The Multiple Sclerosis Resiliency Scale (MSRS) was designed to assess factors connected to resilience when facing MS-related challenges. Although the MSRS has demonstrated good internal consistency and construct validity, its test-retest reliability has yet to be established. Identifying the minimal detectable change (MDC) of the scale will also improve its utility as an outcome measure for resilience-based interventions. This study aimed to determine the test-retest reliability and MDC of the MSRS. METHODS: Participants were 62 persons with MS who completed the MSRS twice, with a mean ± SD of 16.60 ± 3.97 days (range, 14-30 days) between assessments. Test-retest reliability was evaluated using a 2-way, random-effects, single-measurement intraclass correlation coefficient (ICC), with agreement between time 1 and time 2 visualized with a Bland-Altman plot. The MDC was calculated using the standard error of measurement with a 95% CI. RESULTS: At time 1, the mean ± SD MSRS score was 77.19 ± 11.97 (range, 45.83-97.00); at time 2, the mean ± SD score was 76.38 ± 12.75 (range, 46-98). The MSRS total score had good test-retest reliability (ICC = 0.88), with the subscale ICCs ranging from 0.77 (MS Peer Support) to 0.93 (Spirituality). The MDC for the total score was 11.95. CONCLUSIONS: These findings suggest that the MSRS has good test-retest reliability and that persons with MS with a difference of 12 points or more between assessments have experienced a reliable change. The results support the utility of the MSRS as a potential outcome measure for MS-related resilience.

Quantification of upper limb dysfunction in the activities of the daily living in persons with multiple sclerosis.

BACKGROUND: Dysfunction in upper limb (UL) function has been reported as an important indicator for disease progression in persons with multiple sclerosis (PwMS), thus a relevant outcome in clinical trials. However, standard assessment of UL function is limited to Nine-Hole Peg Test (NHPT) which assesses fine dexterity. This study aimed to deeply endophenotype UL involvement in PwMS and identify the most accurate set of measures needed to capture the complexity of UL dysfunction in the activities of daily living (ADL). METHODS: 257 PwMS underwent an extensive UL assessment using standardized measures of grip strength and endurance, coordination, vibratory and tactile sensation, dexterity, capacity and functionality. Limitation in ADL was defined from an objective perspective using a timed test (Test d'Evaluation de la performance des Membres Supérieurs des Personnes Âgées: TEMPA) and from a subjective perspective using a questionnaire (Disabilities of the Arm, Shoulder and Hand: DASH). Disease severity subgroups were compared utilizing the Kruskal-Wallis test and frequencies determined the prevalence of abnormal UL for each measure. The Jonckheere-Terpstra test compared tested variables with disease severity. Then Receiver operating characteristic (ROC) curve analysis was used to test the accuracy of each tested variable in defining abnormality in the TEMPA and DASH. Cut-off scores were calculated using the Youden index. The predictive value of various tests over TEMPA and DASH were tested using a linear regression analysis. RESULTS: UL dysfunction was highly prevalent in all the modalities tested, even in participants with no/mild disability. Box and Block Test (BBT), finger-nose test (FNT), and NHPT were independently selected with ROC analyses as the most accurate measures in detecting abnormalities in TEMPA and DASH. In multivariate regression models, BBT and FNT, and NHPT all contributed to predicting TEMPA (adj. R2 0.795, P < 0.001), while only BBT and FNT predicted DASH. CONCLUSIONS: UL dysfunction is highly prevalent in PwMS, even when global disability is mild. BBT and FNT are time-efficient and cost-effective measures that complement the NHPT for more precise monitoring of PwMS at all disease stages.

Robust Pharmacodynamic Effect of LY3202626, a Central Nervous System Penetrant, Low Dose BACE1 Inhibitor, in Humans and Nonclinical Species.

BACKGROUND: The development of beta-site amyloid-beta precursor protein cleaving enzyme (BACE) 1 inhibitors for the treatment of Alzheimer's disease requires optimization of inhibitor potency, selectivity, and brain penetration. Moreover, there is a need for low-dose compounds since liver toxicity was found with some BACE inhibitors. OBJECTIVE: To determine whether the high in vitro potency and robust pharmacodynamic effect of the BACE inhibitor LY3202626 observed in nonclinical species translated to humans. METHODS: The effect of LY3202626 versus vehicle on amyloid-ß (Aß) levels was evaluated in a series of in vitro assays, as well as in in vivo and multi-part clinical pharmacology studies. Aß levels were measured using analytical biochemistry assays in brain, plasma, and cerebrospinal fluid (CSF) of mice, dogs and humans. Nonclinical data were analyzed using an ANOVA followed by Tukey's post hoc test and clinical data used summary statistics. RESULTS: LY3202626 exhibited significant human BACE1 inhibition, with an IC50 of 0.615±0.101 nM in a fluorescence resonance energy transfer assay and an EC50 of 0.275±0.176 nM for lowering Aß1-40 and 0.228±0.244 nM for Aß1-42 in PDAPP neuronal cultures. In dogs, CSF Aß1hboxx concentrations were significantly reduced by ∼80% at 9 hours following a 1.5 mg/kg dose. In humans, CSF Aß1-42 was reduced by 73.1±7.96 % following administration of 6 mg QD. LY3202626 was found to freely cross the blood-brain barrier in dogs and humans. CONCLUSION: LY3202626 is a potent BACE1 inhibitor with high blood-brain barrier permeability. The favorable safety and pharmacokinetic/pharmacodynamic profile of LY3202626 supports further clinical development.

Mobile health (mHealth) usage, barriers, and technological considerations in persons with multiple sclerosis: a literature review.

OBJECTIVES: Persons with multiple sclerosis (MS) can face a number of potential healthcare-related barriers, for which mobile health (mHealth) technology can be potentially beneficial. This review aimed to understand the frequency, current uses, and potential barriers with mHealth usage among persons with MS. METHODS: A query string was used to identify articles on PubMed, MEDLINE, CINAHL, and IEEE Xplore that were published in English between January 2010 and December 2019. Abstracts were reviewed and selected based on a priori inclusion and exclusion criteria. Fifty-nine peer-reviewed research studies related to the study questions are summarized. RESULTS: The majority of persons with MS were reported as using smartphones, although rates of mHealth utilization varied widely. mHealth usage was grouped into 3 broad categories: (1) disability and symptom measurement; (2) interventions and symptom management; and (3) tracking and promoting adherence. While there have been an increasing number of mHealth options, certain limitations associated with MS (eg, poor dexterity, memory problems) may affect usage, although including persons with MS in the design process can address some of these issues. DISCUSSION: Given the increased attention to mHealth in this population and the current need for telehealth and at home devices, it is important that persons with MS and healthcare providers are involved in the development of new mHealth tools to ensure that the end product meets their needs. Considerations for addressing the potential mHealth use barriers in persons with MS are discussed.

Phase II (NAVIGATE-AD study) Results of LY3202626 Effects on Patients with Mild Alzheimer's Disease Dementia.

BACKGROUND: LY3202626 is a small molecule inhibitor of ß-site amyloid precursor protein cleaving enzyme (BACE)1 shown to reduce amyloid-ß (Aß)1-40 and Aß1-42 concentrations in plasma and cerebrospinal fluid developed for the treatment of Alzheimer's disease (AD). OBJECTIVE: To assess the change from baseline in flortaucipir positron emission tomography (PET) after treatment with LY3202626 compared with placebo in patients with mild AD dementia. METHODS: Patients received daily 3 mg or 12 mg doses of LY3202626 or placebo for 52 weeks. The primary outcome was assessment of cerebral neurofibrillary tangle load by flortaucipir PET. The study was terminated early following an interim analysis due to a low probability of identifying a statistically significant slowing of cognitive and/or functional decline. RESULTS: A total of 316 patients were randomized and 47 completed the study. There was no statistically significant difference between placebo and either dose of LY3202626 from baseline to 52 weeks, or in annualized change for flortaucipir PET. There was no clinically meaningful difference between placebo and LY3202626 doses on efficacy measures of cognition and function. No deaths or serious adverse events considered related to LY3202626 were reported. A statistically significant increase in treatment-emergent adverse events in the psychiatric disorders system organ class was reported for both LY3202626 doses compared to placebo. CONCLUSION: LY3202626 tested at doses generating 70-90% BACE inhibition was generally well tolerated in this study. LY3202626 treatment did not result in a clinically significant change in cerebral tau burden as measured by flortaucipir nor in change of functional or cognitive decline compared to placebo.

Donanemab in Early Alzheimer's Disease.

BACKGROUND: A hallmark of Alzheimer's disease is the accumulation of amyloid-ß (Aß) peptide. Donanemab, an antibody that targets a modified form of deposited Aß, is being investigated for the treatment of early Alzheimer's disease. METHODS: We conducted a phase 2 trial of donanemab in patients with early symptomatic Alzheimer's disease who had tau and amyloid deposition on positron-emission tomography (PET). Patients were randomly assigned in a 1:1 ratio to receive donanemab (700 mg for the first three doses and 1400 mg thereafter) or placebo intravenously every 4 weeks for up to 72 weeks. The primary outcome was the change from baseline in the score on the Integrated Alzheimer's Disease Rating Scale (iADRS; range, 0 to 144, with lower scores indicating greater cognitive and functional impairment) at 76 weeks. Secondary outcomes included the change in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), the 13-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog13), the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL), and the Mini-Mental State Examination (MMSE), as well as the change in the amyloid and tau burden on PET. RESULTS: A total of 257 patients were enrolled; 131 were assigned to receive donanemab and 126 to receive placebo. The baseline iADRS score was 106 in both groups. The change from baseline in the iADRS score at 76 weeks was -6.86 with donanemab and -10.06 with placebo (difference, 3.20; 95% confidence interval, 0.12 to 6.27; P = 0.04). The results for most secondary outcomes showed no substantial difference. At 76 weeks, the reductions in the amyloid plaque level and the global tau load were 85.06 centiloids and 0.01 greater, respectively, with donanemab than with placebo. Amyloid-related cerebral edema or effusions (mostly asymptomatic) occurred with donanemab. CONCLUSIONS: In patients with early Alzheimer's disease, donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed. Longer and larger trials are necessary to study the efficacy and safety of donanemab in Alzheimer's disease. (Funded by Eli Lilly; TRAILBLAZER-ALZ ClinicalTrials.gov number, NCT03367403.).

Cognitive Behavioral Therapy for the Management of Multiple Sclerosis-Related Pain: A Randomized Clinical Trial.

BACKGROUND: Pain is a common and often debilitating symptom in persons with multiple sclerosis (MS). Besides interfering with daily functioning, pain in MS is associated with higher levels of depression and anxiety. Although cognitive behavioral therapy (CBT) for pain has been found to be an effective treatment in other populations, there has been a dearth of research in persons with MS. METHODS: Persons with MS with at least moderate pain severity (N = 20) were randomly assigned to one of two groups: CBT plus standard care or MS-related education plus standard care, each of which met for 12 sessions. Changes in pain severity, pain interference, and depressive symptom severity from baseline to 15-week follow-up were assessed using a 2×2 factorial design. Participants also rated their satisfaction with their treatment and accomplishment of personally meaningful behavioral goals. RESULTS: Both treatment groups rated their treatment satisfaction as very high and their behavioral goals as largely met, although only the CBT plus standard care group's mean goal accomplishment ratings represented significant improvement. Although there were no significant differences between groups after treatment on the three primary outcomes, there was an overall improvement over time for pain severity, pain interference, and depressive symptom severity. CONCLUSIONS: Cognitive behavioral therapy or education-based programs may be helpful adjunctive treatments for persons with MS experiencing pain.

Adoptive Parenting Cognitions: Acknowledgement of Differences as a Predictor of Adolescents' Attachment to Parents.

OBJECTIVE: Adoptive parents' acknowledgement of differences is defined as the propensity to think that adoptive and nonadoptive families are different in important ways. Few studies have examined the implications of such cognitions for the parent-child bond. DESIGN: Structural equation modeling was utilized to examine the relation between adoptive parents' acknowledgement of differences and adolescents' later attachment to their parents in a sample of within-race domestic infant adoptions. Data from 189 adoptive families were drawn from two waves (middle childhood, adolescence) of the Minnesota/Texas Adoption Research Project, a longitudinal study of openness in adoption. RESULTS: Levels of acknowledgement of differences displayed by the adoptive mother and adoptive father during middle childhood positively predicted adopted adolescents' feelings of attachment towards the respective parent 8 years later. This relation depended on adopted adolescents' attitude toward adoption-related communication during middle childhood as well as the adoptive family's level of openness during middle childhood. CONCLUSIONS: Acknowledgement of differences in adoptive families has positive implications for the parent-child bond.

Author Correction: Targeting cardiac fibrosis with engineered T cells.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ethical Considerations in Adoption Research: Navigating Confidentiality and Privacy Across the Adoption Kinship Network.

Adoption research often includes multiple members of the adoption network, each of whom has distinctive perspectives. Participants may include adopted individuals and their siblings as well as adoptive parents, birth parents, and adoption professionals. Due to these multiple informants and the sensitivity of the topics explored in adoption research, researchers encounter several unique ethical concerns when working with populations impacted by adoption. The current paper addresses confidentiality and privacy issues that arise when conducting adoption research. Examples from a longitudinal study on openness in adoption are provided to highlight strategies that can be used to address these issues.

CRISPR-mediated live imaging of genome editing and transcription.

We report a robust, versatile approach called CRISPR live-cell fluorescent in situ hybridization (LiveFISH) using fluorescent oligonucleotides for genome tracking in a broad range of cell types, including primary cells. An intrinsic stability switch of CRISPR guide RNAs enables LiveFISH to accurately detect chromosomal disorders such as Patau syndrome in prenatal amniotic fluid cells and track multiple loci in human T lymphocytes. In addition, LiveFISH tracks the real-time movement of DNA double-strand breaks induced by CRISPR-Cas9-mediated editing and consequent chromosome translocations. Finally, by combining Cas9 and Cas13 systems, LiveFISH allows for simultaneous visualization of genomic DNA and RNA transcripts in living cells. The LiveFISH approach enables real-time live imaging of DNA and RNA during genome editing, transcription, and rearrangements in single cells.

Targeting cardiac fibrosis with engineered T cells.

Fibrosis is observed in nearly every form of myocardial disease1. Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess extracellular matrix, resulting in increased stiffness and reduced compliance of the tissue. Excessive cardiac fibrosis is an important factor in the progression of various forms of cardiac disease and heart failure2. However, clinical interventions and therapies that target fibrosis remain limited3. Here we demonstrate the efficacy of redirected T cell immunotherapy to specifically target pathological cardiac fibrosis in mice. We find that cardiac fibroblasts that express a xenogeneic antigen can be effectively targeted and ablated by adoptive transfer of antigen-specific CD8+ T cells. Through expression analysis of the gene signatures of cardiac fibroblasts obtained from healthy and diseased human hearts, we identify an endogenous target of cardiac fibroblasts-fibroblast activation protein. Adoptive transfer of T cells that express a chimeric antigen receptor against fibroblast activation protein results in a significant reduction in cardiac fibrosis and restoration of function after injury in mice. These results provide proof-of-principle for the development of immunotherapeutic drugs for the treatment of cardiac disease.

Trajectories of birth family contact in domestic adoptions.

Emotional distance regulation theory (Broderick, 1993; Grotevant, 2009) guided this examination of the changes in family structure and process in adoptive kinship networks experiencing different arrangements of contact between birth and adoptive family members. Group-based trajectory modeling was used to reveal four trajectories of postadoption contact experienced between adoptive and birth family members in adoptive kinship networks of same-race, domestic infant adoptions. Data were drawn from the Minnesota Texas Adoption Research Project, a study of 190 adoptive families and 169 birth mothers followed across four longitudinal waves (middle childhood, adolescence, emerging adulthood, young adulthood). Three aspects of the birth family adoptive family relationship measured at four times were used to create the groups: frequency of contact between the adopted person and birth mother, satisfaction of the adopted person with the openness arrangements, and number of adoptive and birth family members involved in the contact. Four trajectory groups emerged: no contact (41.6% of sample), stopped contact (13.7%), limited contact (26.3%), and extended contact (18.4%). Group membership was validated by coders who matched interview transcripts with group descriptions at levels significantly above chance. Knowledge of trajectories will assist professionals providing postadoption services. (PsycINFO Database Record (c) 2019 APA, all rights reserved).