Polycystin-1 regulates cardiomyocyte mitophagy.

Polycystin-1 (PC1) is a transmembrane protein found in different cell types, including cardiomyocytes. Alterations in PC1 expression have been linked to mitochondrial damage in renal tubule cells and in patients with autosomal dominant polycystic kidney disease. However, to date, the regulatory role of PC1 in cardiomyocyte mitochondria is not well understood. The analysis of mitochondrial morphology from cardiomyocytes of heterozygous PC1 mice (PDK1+/- ) using transmission electron microscopy showed that cardiomyocyte mitochondria were smaller with increased mitochondria density and circularity. These parameters were consistent with mitochondrial fission. We knocked-down PC1 in cultured rat cardiomyocytes and human-induced pluripotent stem cells (iPSC)-derived cardiomyocytes to evaluate mitochondrial function and morphology. The results showed that downregulation of PC1 expression results in reduced protein levels of sub-units of the OXPHOS complexes and less functional mitochondria (reduction of mitochondrial membrane potential, mitochondrial respiration, and ATP production). This mitochondrial dysfunction activates the elimination of defective mitochondria by mitophagy, assessed by an increase of autophagosome adapter protein LC3B and the recruitment of the Parkin protein to the mitochondria. siRNA-mediated PC1 knockdown leads to a loss of the connectivity of the mitochondrial network and a greater number of mitochondria per cell, but of smaller sizes, which characterizes mitochondrial fission. PC1 silencing also deregulates the AKT-FoxO1 signaling pathway, which is involved in the regulation of mitochondrial metabolism, mitochondrial morphology, and processes that are part of cell quality control, such as mitophagy. Together, these data provide new insights about the controls that PC1 exerts on mitochondrial morphology and function in cultured cardiomyocytes dependent on the AKT-FoxO1 signaling pathway.

Timing of Maternal Discharge after Cesarean Delivery and Risk of Maternal Readmission.

OBJECTIVE: Despite legislation and hospital policies (present in some institutions) mandating a minimum length of stay in an effort to decrease the frequency of hospital readmissions, the effectiveness of this approach remains uncertain.We hypothesized that following cesarean delivery (CD), the rates of maternal readmission or unscheduled health care visits are lower in patients discharged on postoperative day (POD) 3 or ≥4 as compared with those discharged earlier on POD 2. METHODS: This is a secondary analysis of a multicenter randomized trial comparing adjunctive azithromycin for unscheduled CD to prevent infection. Groups were compared based on the duration of hospitalization measured in days from delivery (POD 0) to day of discharge and categorized as POD 2, 3, and ≥4. The primary outcome was the composite of any maternal postpartum readmission, unscheduled clinic, or emergency room (ER) visit, within 6 weeks of delivery. Secondary outcomes included components of the primary outcome and neonatal readmissions. We excluded women with hypertensive disorders of pregnancy and infections diagnosed prior to POD 2. RESULTS: A total of 1,391 patients were included. The rate of the primary outcome of any readmission increased with POD at discharge: 5.9% for POD 2, 9.4% for POD 3, and 10.9% for POD ≥4 group (trend for p = 0.03). The primary outcome increased with later discharge (POD ≥4 when compared with POD 2). Among components of the composite, ER and unscheduled clinic visits, but not maternal readmissions, increased with the timing of discharge for patients discharged on POD ≥4 when compared with POD 2. Using logistic regression, discharge on POD 3 and on POD ≥4 was significantly associated with the composite (adjusted odds ratios [aOR] 2.6, 95% confidence interval [CI] [1.3-5.3]; aOR 2.9, 95% CI [1.3-6.4], respectively) compared with POD 2. CONCLUSION: The risk of maternal readmission composite following uncomplicated but unscheduled CD was not lower in patients discharged home on POD 3 or ≥4 compared with patients discharged earlier (POD 2). KEY POINTS: · Risk of maternal readmission is higher in patients discharged on POD 3 or 4 compared with POD 2.. · No significant differences by the timing of discharge were observed for any neonatal readmissions.. · Timing of discharge should include an individualized approach with the option of discharge by POD 2..

Sound variation by hypertrophy and atrophy sonic muscle in the male southern black drum (Pogonias courbina).

The male and female southern black drum possess highly specialized, bilateral, striated sonic muscles used in sound production during courtship by males and in the production of disturbance calls by both males and females. Androgen-driven hypertrophy of the sonic muscles in males during the late spring spawning period results in increased growth of sonic muscle mass followed by post-spawning atrophy of sonic muscles. We examined changes in sonic muscle morphology and in the sound characteristics of males and females underlying seasonal changes in sonic muscle mass and muscle contraction as measured by sound production. In males, the sound pressure level increased while sound pulse duration decreased with increasing sonic muscle mass, indicating that sonic muscle fibers contract with greater force and shorter duration during the spawning season. Interpulse interval and the total number of pulses varied seasonally with muscle mass, which suggests that the effects of steroids on male southern black drum sound characteristics are more pronounced peripherally than in the central nervous system. In females, no increase in sonic muscle mass was found, and therefore, a change was not observed in the acoustic variables analyzed. Seasonal sonic muscle hypertrophy in males likely functions as a secondary sexual characteristic that maximizes vocalization amplitude or loudness during the spawning period.

Time from neuraxial anesthesia placement to delivery is inversely proportional to umbilical arterial cord pH at scheduled cesarean delivery.

BACKGROUND: Neuraxial block-related hypotension and maternal obesity contribute to uterine hypoperfusion and decreased umbilical arterial pH at cesarean delivery. Between the time of anesthesia placement and delivery, the fetus may be exposed to a hypoperfused uterine environment without surgeon awareness of fetal compromise. OBJECTIVE: We sought to evaluate neonatal umbilical arterial pH according to predelivery time intervals at scheduled term cesarean. STUDY DESIGN: We performed a retrospective cohort study of cesarean deliveries between September 2014 and February 2017. Singleton gestations undergoing scheduled cesarean delivery under spinal anesthesia between 37 and 41 weeks with a reassuring preoperative nonstress test were included. Time intervals between operative room entry, spinal anesthesia placement, skin incision, uterine incision, and delivery were calculated. The primary outcome was umbilical arterial pH. Demographic data, maternal blood pressures, predelivery time intervals, and delivery outcomes were analyzed according to umbilical arterial pH intervals of <7.0, 7.01-7.10, 7.11-7.20, 7.21-7.30, and >7.30. Umbilical cord gas analytes and neonatal outcomes were analyzed by spinal to delivery time. Stepwise linear regression was performed to identify predictors of decreasing umbilical arterial pH. Receiver-operator characteristic curves were calculated for spinal to delivery time and umbilical arterial pH <7.0 and 7.1. RESULTS: Among 527 included participants, median umbilical arterial pH was 7.27 [interquartile range, 7.23-7.29] and body mass index was 35 kg/m2 [interquartile range, 30-41]. Both maternal body mass index and hypotensive episodes increased with decreasing umbilical arterial pH (P <.001, P ≤ .02). All predelivery time intervals (operative room to delivery, spinal to skin, spinal to delivery, and uterine incision to delivery) increased as umbilical arterial pH interval decreased (P < .05 for all). In a stepwise linear regression, maternal body mass index, noncephalic presentation, spinal start to delivery interval, uterine incision to delivery interval, and maximum reduction in blood pressure from baseline were predictive of decreasing umbilical arterial pH after controlling for confounding variables (F [5,442] = 17.7, P = .0001], adjusted R2 of 0.157. When evaluated by spinal to delivery time, both umbilical arterial and venous pH and partial pressure of carbon dioxide decreased (P < .001 for all), but base deficit and neonatal outcomes were similar (P ≥ .7 for all). There were 2 cases of hypoxic-ischemic encephalopathy (0.38%). A receiver-operating characteristic curve demonstrated that a spinal start to delivery time greater than 27 minutes was associated with an umbilical arterial pH <7.1 (area under the curve, 0.74, 100% sensitivity, 21% specificity), and an interval greater than 30 minutes was associated with an umbilical arterial pH <7.0 (area under the curve, 0.80, 100% sensitivity, 33% specificity). CONCLUSION: Longer spinal-to-delivery and uterine incision-to-delivery time intervals were associated with decreasing umbilical arterial pH at scheduled term cesarean delivery. Efforts to minimize predelivery time following spinal placement could reduce the frequency of unanticipated neonatal acidemia.

Implantation of subcutaneous defibrillator is feasible and safe with monitored anesthesia care.

BACKGROUND: The perioperative anesthesia care during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is still evolving. OBJECTIVE: To assess the feasibility and safety of S-ICD implantation with monitored anesthesia care (MAC) versus general anesthesia (GA) in a tertiary care center. METHODS: This is a single-center retrospective study of patients undergoing S-ICD implantation between October 2012 and May 2019. Patients were categorized into MAC and GA group based on the mode of anesthesia. Procedural success without escalation to GA was the primary endpoint of the study, whereas intraprocedural hemodynamics, need of pharmacological support for hypotension and bradycardia, length of the procedure, stay in the post-anesthesia care unit, and postoperative pain were assessed as secondary endpoints. RESULTS: The study comprises 287 patients with MAC in 111 and GA in 176 patients. Compared to MAC, patients in GA group were younger and had a higher body mass index. All patients had successful S-ICD implantation. Only one patient (0.9%) in the MAC group was converted to GA. Despite a similar baseline heart rate (HR) and mean arterial blood pressure (MAP) in both groups, patients with GA had significantly lower HR and MAP during the procedure and more frequently required pharmacological hemodynamic support. Length of the procedure, stay in the postanesthesia care unit, and postoperative pain was similar in both groups. CONCLUSION: This retrospective experience suggests that implantation of S-ICD is feasible and safe with MAC. Use of GA is associated with more frequent administration of hemodynamic drugs during S-ICD implantation.

The Trouble with Anesthetizing the Dead.

I reflect on the practical reality of anesthetizing organ donors who have been declared dead by neurologic criteria. I also treat some issues and questions that arise for the physician who is drafted into such cases.

The Effect of Trabeculae Carneae on Left Ventricular Diastolic Compliance: Improvement in Compliance With Trabecular Cutting.

The role of trabeculae carneae in modulating left ventricular (LV) diastolic compliance remains unclear. The objective of this study was to determine the contribution of trabeculae carneae to the LV diastolic compliance. LV pressure-volume compliance curves were measured in six human heart explants from patients with LV hypertrophy at baseline and following trabecular cutting. The effect of trabecular cutting was also analyzed with finite-element model (FEM) simulations. Our results demonstrated that LV compliance improved after trabecular cutting (p < 0.001). Finite-element simulations further demonstrated that stiffer trabeculae reduce LV compliance further, and that the presence of trabeculae reduced the wall stress in the apex. In conclusion, we demonstrate that integrity of the LV and trabeculae is important to maintain LV stiffness and loss in trabeculae leads to more LV compliance.

Oospore dimensions and morphology in North American Tolypella (Charophyceae, Charophyta).

Characteristics of the oospores have been used to delimit sections and, in some cases, species in the genus Tolypella A. Braun. To test the utility of oospore characters for identifying North American species of Tolypella, we investigated oospores from field-collected and herbarium specimens. Oospore dimensions (length, width, and length to width ratio) and morphology (color, ridge number and shape, wall ornamentation, and basal impression number) were measured. Oospore dimensions were statistically analyzed and oospore morphology was studied with light and scanning electron microscopy. Statistical analyses showed significant differences in length, width, and length to width ratios among most Tolypella species and populations but there was considerable overlap, which suggested that species identification based on oospore measurements alone is not wholly reliable. In addition, oospore morphology was not unique for every species.

Cerebral oxygenation and processed EEG response to clamping and shunting during carotid endarterectomy under general anesthesia.

Clamping and shunting during carotid endarterectomy (CEA) surgery causes changes in cerebral blood flow. The purpose of this study was to assess and compare, side by side, the cerebral oxygenation (rSO2) and processed electroencephalogram (EEG) response bilaterally to carotid artery clamping and shunting in patients undergoing CEA under general anesthesia. With institutional approval and written informed consent, patients undergoing CEA under general anesthesia and routine carotid artery shunting were recorded bilaterally, simultaneously and continuously with an rSO2 and processed EEG monitor. The response of the monitors during carotid artery clamping and shunting were assessed and compared between monitors and bilaterally within each monitor. Sixty-nine patients were included in the study. At clamping the surgical-side and contralateral-side rSO2 dropped significantly below the baseline incision value (-17.6 and -9.4% respectively). After shunting, the contralateral-side rSO2 returned to baseline while the surgical-side rSO2 remained significantly below baseline (-9.0%) until the shunt was removed following surgery. At clamping the surgical-side and contralateral-side processed EEG also dropped below baseline (-19.9 and -20.6% respectively). However, following shunt activation, the processed EEG returned bilaterally to baseline. During the course of this research, we found the rSO2 monitor to be clinically more robust (4.4% failure rate) than the processed EEG monitor (20.0% failure rate). There was no correlation between the rSO2 or processed EEG changes that occurred immediately after clamping and the degree of surgical side stenosis measured pre-operatively. Both rSO2 and processed EEG respond to clamping and shunting during CEA. Cerebral oximetry discriminates between the surgical and contralateral side during surgery. The rSO2 monitor is more reliable in the real-world clinical setting. Future studies should focus on developing algorithms based on these monitors that can predict clamping-induced cerebral ischemia during CEA in order to decide whether carotid artery shunting is worth the associated risks. From the practical point of view, the rSO2 monitor may be the better monitor for this purpose.

Phylogeny of North American Tolypella (Charophyceae, Charophyta) based on plastid DNA sequences with a description of Tolypella ramosissima sp. nov.

Characeae (Charophyceae, Charophyta) contains two tribes with six genera: tribe Chareae with four genera and tribe Nitelleae, which includes Tolypella and Nitella. This paper uses molecular and morphological data to elucidate the phylogeny of Tolypella species in North America. In the most comprehensive taxonomic treatment of Characeae, 16 Tolypella species worldwide were subsumed into two species, T. intricata and T. nidifica, in two sections, Rothia and Tolypella respectively. It was further suggested that Tolypella might be a derived group within Nitella. In this investigation into species diversity and relationships in North American Tolypella, sequence data from the plastid genes atpB, psbC, and rbcL were assembled for a broad range of charophycean and land plant taxa. Molecular data were used in conjunction with morphology to test monophyly of the genus and species within it. Phylogenetic analyses of the sequence data showed that Characeae is monophyletic but that Nitelleae is paraphyletic with Tolypella sister to a monophyletic Nitella + Chareae. The results also supported the monophyly of Tolypella and the sections Rothia and Tolypella. Morphologically defined species were supported as clades with little or no DNA sequence differences. In addition, molecular data revealed several lineages and a new species (T. ramosissima sp. nov.), which suggests greater species diversity in Tolypella than previously recognized.

Changes in Immune Response during Pig Gestation with a Focus on Cytokines.

Pigs have the highest percentage of embryonic death not associated with specific diseases of all livestock species, at 20-45%. During gestation processes, a series of complex alterations can arise, including embryonic migration and elongation, maternal immunological recognition of pregnancy, and embryonic competition for implantation sites and subsequent nutrition requirements and development. Immune cells and cytokines act as mediators between other molecules in highly complex interactions between various cell types. However, other non-immune cells, such as trophoblast cells, are important in immune pregnancy regulation. Numerous studies have shed light on the crucial roles of several cytokines that regulate the inflammatory processes that characterize the interface between the fetus and the mother throughout normal porcine gestation, but most of these reports are limited to the implantational and peri-implantational periods. Increase in some proinflammatory cytokines have been found in other gestational periods, such as placental remodeling. Porcine immune changes during delivery have not been studied as deeply as in other species. This review details some of the immune system cells actively involved in the fetomaternal interface during porcine gestation, as well as the principal cells, cytokines, and molecules, such as antibodies, that play crucial roles in sow pregnancy, both in early and mid-to-late gestation.

Folate as a potential treatment for lethal ventricular arrhythmias in TANGO2-deficiency disorder.

TANGO2-deficiency disorder (TDD) is an autosomal-recessive genetic disease caused by biallelic loss-of-function variants in the TANGO2 gene. TDD-associated cardiac arrhythmias are recalcitrant to standard antiarrhythmic medications and constitute the leading cause of death. Disease modeling for TDD has been primarily carried out using human dermal fibroblast and, more recently, in Drosophila by multiple research groups. No human cardiomyocyte system has been reported, which greatly hinders the investigation and understanding of TDD-associated arrhythmias. Here, we established potentially novel patient-derived induced pluripotent stem cell differentiated cardiomyocyte (iPSC-CM) models that recapitulate key electrophysiological abnormalities in TDD. These electrophysiological abnormalities were rescued in iPSC-CMs with either adenoviral expression of WT-TANGO2 or correction of the pathogenic variant using CRISPR editing. Our natural history study in patients with TDD suggests that the intake of multivitamin/B complex greatly diminished the risk of cardiac crises in patients with TDD. In agreement with the clinical findings, we demonstrated that high-dose folate (vitamin B9) virtually abolishes arrhythmias in TDD iPSC-CMs and that folate's effect was blocked by the dihydrofolate reductase inhibitor methotrexate, supporting the need for intracellular folate to mediate antiarrhythmic effects. In summary, data from TDD iPSC-CM models together with clinical observations support the use of B vitamins to mitigate cardiac crises in patients with TDD, providing potentially life-saving treatment strategies during life-threatening events.

Topographic anatomy and vascularization of the glandula thyroidea in rats.

Topographical anatomy and detailed measurements of the glandula thyroidea (thyroid gland) and the glandula parathyroidea (parathyroid gland) were determined in rats, with significant differences identified between the sexes. In the rats (N = 10 male, 10 female), the glandula thyroidea were positioned at the level of the C1 and C2 vertebrae. One glandula parathyroidea was present in each glandula thyroidea lobe, localized in the cranial part of the lateral lobes in 60% of the animals. There was no glandula thyroidea left lobe in one female and no isthmus in two females. Both the A. thyroidea cranialis and the A. pharyngea ascendens originated from the A. carotis externa, which acted as a common trunk. On the left, the A. thyroidea caudalis originated from the truncus brachiocephalicus in all rats and on the right side was found to originate from both the truncus costocervicalis and the A. subclavia dextra in three females, and only from the truncus costocervicalis in seven females. The V. thyroidea cranialis opened into the V. jugularis interna in the neck region and at the level of the apertura thoracis cranialis, and the V. jugularis interna united with the V. thyroidea caudalis. In addition, on the right, the V. thyroidea cranialis joined the V. jugularis interna, at the level of the A. subclavia. The veins on both sides opened into the V. cava cranialis. Significant differences were observed between the sexes and detailed anatomical analysis of the glandula thyroidea and the glandula parathyroidea, and related vasculature and innervation, have been described in this paper.

Bridging the Translational Gap in Heart Failure Research: Using Human iPSC-derived Cardiomyocytes to Accelerate Therapeutic Insights.

Heart failure (HF) remains a leading cause of death worldwide, with increasing prevalence and burden. Despite extensive research, a cure for HF remains elusive. Traditionally, the study of HF's pathogenesis and therapies has relied heavily on animal experimentation. However, these models have limitations in recapitulating the full spectrum of human HF, resulting in challenges for clinical translation. To address this translational gap, research employing human cells, especially cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs), offers a promising solution. These cells facilitate the study of human genetic and molecular mechanisms driving cardiomyocyte dysfunction and pave the way for research tailored to individual patients. Further, engineered heart tissues combine hiPSC-CMs, other cell types, and scaffold-based approaches to improve cardiomyocyte maturation. Their tridimensional architecture, complemented with mechanical, chemical, and electrical cues, offers a more physiologically relevant environment. This review explores the advantages and limitations of conventional and innovative methods used to study HF pathogenesis, with a primary focus on ischemic HF due to its relative ease of modeling and clinical relevance. We emphasize the importance of a collaborative approach that integrates insights obtained in animal and hiPSC-CMs-based models, along with rigorous clinical research, to dissect the mechanistic underpinnings of human HF. Such an approach could improve our understanding of this disease and lead to more effective treatments.

Relating relational networks: An initial experimental analysis.

Studying relating of relational networks is a complex and challenging task. The main objective of the present study was to demonstrate relating within and across relational networks based on same/opposite and bigger/smaller contextual cues and establish antecedent control. After nonarbitrary pretraining of the contextual cues, two nonsense stimulus classes were established based on comparative relations. Participants were trained to select stimuli from an array of options based on a symbolic rule that established a relation between two stimuli: one of Network 1 and one of Network 2. Training involved relating Network 1 to Network 2, and testing assessed relating Network 2 to Network 1. Seven of eight participants reached the mastery criterion in training and responded accordingly in test. In a final stage, reinforcing and punishing consequences were varied systematically in the presence of two novel stimuli and antecedent control was observed for all 7 participants. Experiment 2 replicated the results of Experiment 1 but using contextual cues taken from natural language, and Experiment 3 sought to understand the effects of pretraining relational responding using natural language. The mastery criteria were reached by four of seven participants in Experiment 2 and by all eight participants in Experiment 3. Future studies could develop and refine the methods employed here in analyzing the relating of relational networks, thus allowing for an increasingly sophisticated behavior-analytic account of human language and cognition.

Using videos in active learning: An experience in veterinary anatomy.

Examination failure rate is high in veterinary anatomy in Brazilian universities. We report here our active learning experience in which students recorded video reports on veterinary anatomical specimens of locomotor apparatus to support classic learning. Eighteen students were divided into 2 groups, case group (V3) and control (E). Case group students individually recorded video reports of prosected specimens weekly. Acceptance and efficacy of the strategy were assessed with a Likert scale anonymous questionnaire and students' scores in theoretical exams. The method was highly accepted and the performance test proved that recording videos is an effective strategy for active learning in anatomy.

Tolerance of polysomnography in children with neurodevelopmental disorders compared to neurotypical peers.

STUDY OBJECTIVES: Diagnostic polysomnography (PSG) is the gold standard test to evaluate sleep-disordered breathing in children. Little is known about how children with neurodevelopmental disorders (NDD) tolerate electrodes and sensors in PSG compared to neurotypical children. METHODS: In this retrospective cohort study of children > 12 months of age who underwent diagnostic PSG at our center from 01/01/2021-30/06/2021, we used sleep technician and physician reports to determine how PSG was tolerated in children with NDD compared to neurotypical children. Subanalyses included tolerance of individual electrodes and sensors and subgroups of NDD (eg, Trisomy 21). RESULTS: A total of 132 children with a NDD and 139 neurotypical children underwent diagnostic PSG. The median age of all children was 8 years, 39% were female, and 50% had a sleep disorder identified on PSG, with no significant differences between NDD and neurotypical groups. The most poorly tolerated sensors for all children were the nasal prongs (poorly tolerated in 30% of all children), followed by thermistor (14%) and electroencephalography electrodes (6%). Children with NDD were > 3 times more likely (odds ratio 3.1, 95% confidence interval 1.8-5.3) to experience problems tolerating any study leads than neurotypical children. Subgroup analysis revealed children with Trisomy 21 had the greatest difficulty tolerating PSG set-up and leads. CONCLUSIONS: This retrospective study demonstrates that children with neurodevelopmental disorders are less likely to tolerate PSG monitoring than neurotypical children and highlights the need to develop alternative measures for evaluation of sleep disorders in this population. CITATION: Lanzlinger D, Kevat A, Collaro A, Poh SH, Pérez WP, Chawla J. Tolerance of polysomnography in children with neurodevelopmental disorders compared to neurotypical peers. J Clin Sleep Med. 2023;19(9):1625-1631.

Grappling with the Complexity of Behavioral Processes in Human Psychological Suffering: Some Potential Insights from Relational Frame Theory.

Relational frame theory (RFT) has historically been considered the basic explanatory science behind acceptance and commitment therapy (ACT). However, some have argued that there has been an increasing separation between the two in recent years. The primary aim of the current article is to explore the extent to which RFT concepts, particularly those that have been proposed recently in the context of "up-dating" the theory, may be used to build stronger links between basic and applied behavior analyses in which there is a shared language of relatively precise technical terms. As an example of this strategy, we outline RFT process-based experimental and conceptual analyses of the impact of one of the most widely used sets of interventions employed in the ACT literature, defusion. In addition, we suggest a potential experimental methodology for analyzing the basic behavioral processes involved. Overall, the current article should be seen as part of a broader research agenda that aims to explore how RFT may be used to provide a functional-analytic abstractive treatment of the behavioral processes involved in human psychological suffering.

Generalized contextual control based on nonarbitrary and arbitrary transfer of stimulus functions.

Two experiments with human adults investigated the extent to which the transfer of function in accordance with nonarbitrary versus arbitrary stimulus relations may be brought under contextual control. Experiment 1 comprised four phases. Phase 1 consisted of multiple-exemplar training to establish discriminative functions for solid, dashed, or dotted lines. Phase 2 trained and tested two equivalence classes, each containing a 3D picture, a solid, a dashed, and a dotted form. During Phase 3, a discriminative function was established for each 3D picture. Phase 4 presented the solid, dashed, and dotted stimuli in two different frames, black or gray. The black frame cued function transfer based on nonarbitrary stimulus relations (Frame Physical); the gray frame cued function transfer based on equivalence relations (Frame Arbitrary). Testing and training with the frames was continued until contextual control was established; subsequently contextual control was demonstrated with novel equivalence classes with stimuli composed of the same forms. Experiment 2 replicated and extended Experiment 1 by demonstrating that such contextual control generalized to novel equivalence classes comprising novel forms and responses. The potential implications of the findings for developing increasingly precise experimental analyses of clinically relevant phenomena are considered (e.g., defusion).