Tracking and Assessing Oil Spill Toxicity to Aquatic Organisms: A Novel Approach.

An in situ exposure and effects bioassay system was developed for assessing the toxicity of oil spills to aquatic organisms. The assessment tool combines components of 2 previously developed systems, the sediment ecotoxicity assessment ring (SEA Ring) and the drifting particle simulator. The integrated drifting exposure and effects assessment ring (DEEAR) is comprised of a Global Positioning System (GPS) float, a drifter drogue, the SEA Ring, and the Cyclops-7 fluorescent sensor. Polyethylene passive sampling devices (PED) were mounted for an additional means to characterize water quality conditions and exposures. The DEEAR is optimized for evaluating oil exposure and toxicity in the shallow surface mixing layer of marine waters. A short-term preliminary test was conducted in San Diego, California, USA, to verify the operation of the GPS tracking, the iridium communications, and the integrated SEA Ring exposure system. Further, a proof-of-concept demonstration was conducted offshore in the Santa Barbara Channel, where natural oil seeps produce surface slicks and sheens. Two DEEAR units were deployed for 24 h-one within the oil slick and one in an area outside observable slicks. An aerial drone provided tracking of the surface oil and optimal sites for deployment. The DEEAR proof-of-concept demonstrated integrated real-time tracking and characterization of oil exposures by grab samples, PED, and fluorescent sensors. Oil exposures were directly linked to toxic responses in fish and mysids. This novel integrated system shows promise for use in a variety of aquatic sites to more accurately determine in situ oil exposure and toxicity. Environ Toxicol Chem 2021;40:1452-1462. © 2021 SETAC.

Public Response to Suicide News Reports as Reflected in Computerized Text Analysis of Online Reader Comments.

Previous research has documented the rise in rates of suicidal behaviors following media reports of celebrity suicide. Whereas most research has focused on documenting and analyzing suicide rates, little is known about more subtle psychological effects of celebrity suicide on the public, such as despair and feelings of abandonment. The Internet has revolutionized the responses to news reports, enabling immediate and anonymous responses potentially reflecting these psychological processes. Thus, the current study explored the unique psychological impact of a celebrity suicide on the public by analyzing the big data of readers' comments to suicide news reports, using computational linguistics methods. Readers' comments (N = 14,506) to suicide news reports were retrieved from 4 leading online news sites. The comments were posted in response to 1 of 1 types of reports: a celebrity suicide (Robin Williams), a non-celebrity suicide, and general reports of suicide as a social phenomenon. LIWC software for computerized linguistic analysis was used to calculate the frequency of the various types of words used. Comparison of the responses to the 3 types of suicide reports revealed higher frequency of first-person pronouns and for emotionally charged words on comments to a celebrity suicide, compared with comments to the other types of suicide reports. The findings suggest that celebrity suicide news reports evoke the expression of positive emotions, possibly related to the venerated celebrity, alongside negative, internalized emotions, and feelings of social isolation. Theoretical, practical, and methodological implications are discussed.

Evaluating the efficacy of DGT to quantify copper in stormwater at end-of-pipe.

In many cases, stormwater compliance monitoring is labor intensive, expensive, and largely unsuccessful in providing the data needed to support stormwater management goals. To help address these issues, diffusive gradients in thin film (DGTs), time-integrative passive samplers for metals, were evaluated to monitor copper in stormwater runoff. DGTs were co-located with traditional autosamplers within the stormwater conveyance systems at Naval Base San Diego (NBSD) to provide a direct comparison with composite sampling. DGTs were exposed in the laboratory to flow-averaged composite samples from NBSD stormwater conveyance systems. These experiments showed increasing uptake over time (range = 1.5-24 h) for copper, with positive, linear correlations (r2 > 0.980) between exposure duration and copper mass accumulated. However, it appears that the corresponding calculations of the DGT-labile fraction (CDGT) relative to the dissolved fraction fluctuated across the different exposure durations. In general, trends observed for CDGT measurements from the field were consistent with trends in the lab DGT exposures and traditional dissolved metal measurements from composite samples. Finally, time-weighted average copper concentrations from DGTs deployed for the first and second phases of storm events were within 30% of measurements from DGTs that were deployed for the entire storm event in the same stormwater vault. Cumulatively, these results show promise for continuous monitoring with DGTs as an approach that produces data more representative of exposure to the receiving environment during episodic events than data from traditional grab or composite chemistry sampling, and can represent significant cost savings.

Palliative CT-Guided Cordotomy for Medically Intractable Pain in Patients with Cancer.

Palliative cervical cordotomy can be performed via percutaneous radiofrequency ablation of the lateral C1-2 spinothalamic tract. This rare procedure can be safe, effective, and advantageous in mitigating medically intractable unilateral extremity pain for selected patients with end-stage cancer. This report reviews the indications, techniques, risks, and potential benefits of cordotomy. We describe our recent experience treating 3 patients with CT-guided C1-2 cordotomy and provide the first characterization of spinal cord diffusion MR imaging changes associated with successful cordotomy.

Engineering Human Microbiota: Influencing Cellular and Community Dynamics for Therapeutic Applications.

The complex relationship between microbiota, human physiology, and environmental perturbations has become a major research focus, particularly with the arrival of culture-free and high-throughput approaches for studying the microbiome. Early enthusiasm has come from results that are largely correlative, but the correlative phase of microbiome research has assisted in defining the key questions of how these microbiota interact with their host. An emerging repertoire for engineering the microbiome places current research on a more experimentally grounded footing. We present a detailed look at the interplay between microbiota and host and how these interactions can be exploited. A particular emphasis is placed on unstable microbial communities, or dysbiosis, and strategies to reestablish stability in these microbial ecosystems. These include manipulation of intermicrobial communication, development of designer probiotics, fecal microbiota transplantation, and synthetic biology.

Response to anti-PD1 therapy with nivolumab in metastatic sarcomas.

BACKGROUND: Manipulation of immune checkpoints such as CTLA4 or PD-1 with targeted antibodies has recently emerged as an effective anticancer strategy in multiple malignancies. Sarcomas are a heterogeneous group of diseases in need of more effective treatments. Different subtypes of soft tissue and bone sarcomas have been shown to express PD-1 ligand. METHODS: We retrospectively analyzed a cohort of patients (pts) with relapsed metastatic/unresectable sarcomas, who were treated with nivolumab provided under a patient assistance program from the manufacturer. Pts underwent CT or PET/CT imaging at baseline and after at least four doses of nivolumab; RECIST 1.1 criteria were used for response assessment. RESULTS: Twenty-eight pts with soft tissue (STS, N = 24) or bone sarcoma (N = 4), received IV nivolumab 3 mg/kg every 2 weeks from July 2015. Median age was 57 (24-78), male:female ratio was 14:14; the median number of nivolumab cycles was eight. Eighteen pts concomitantly received pazopanib at 400-800 mg daily. The most common side effect was grade 1-2 LFT elevations; grade 3-4 toxicity occurred in five patients (colitis, LFT elevations, pneumonitis). Twenty-four pts received at least four cycles. We observed three partial responses: one dedifferentiated chondrosarcoma, one epithelioid sarcoma and one maxillary osteosarcoma (last two patients on pazopanib); nine patients had stable disease including three leiomyosarcomas; 12 patients had progression of disease including 4 leiomyosarcoma. Clinical benefit (response + stability) was observed in 50% of the evaluable patients. CONCLUSIONS: These data provide a rationale for further exploring the efficacy of nivolumab and other checkpoint inhibitors in soft tissue and bone sarcoma.

Progress in the treatment of Ewing sarcoma: are the rumors of the demise of cytotoxic chemotherapy premature?

In this issue, Bollling et. al. review the development of treatment of Ewing sarcoma as it evolved over the past 30 years of clinical trials in Europe, largely under the leadership of Heribert Jurgens to whom this review is dedicated. The 44 authors were teachers, colleagues, students and co-investigators of Jurgens. The authors attribute the ability to make progress in the treatment of Ewing sarcoma through the establishment of larger and still larger cooperative studies in order to demonstrate statistically significant advances in the treatment of this rare disease.

Improving blood transfusion practice by educational emphasis of the Blood Utilization Committee: experience of one hospital.

AIM: The aim of this study was to reduce crossmatch to transfusion ratio through development of a new Blood Utilization Committee. BACKGROUND: Blood utilization hinges on the cooperation between transfusion services, medical staff, nursing and administration. Transfusion committees have attempted to bring about better oversight and bridge the gap between departments but in our institution this did not work until we had a catalyst to drive the effort. The unabashed desire and enthusiasm of one of our cardiac surgeons for self-improvement led to the formation of a new Blood Utilization Committee in October of 2012. STUDY DESIGN AND METHODS: Crossmatch and transfusion data were gathered from our blood bank information system starting with the 4th quarter of 2011 through the 1st quarter of 2013. The crossmatch to transfusion ratio (C:T) was calculated and comparisons were made between the results from before and after the initiation of the committee. RESULTS: At the commencement of the committee the initial C:T for the cardiac team was 2.48. We calculated a decrease of the C:T to 1.5 four months after the November 2012 formation of the new committee. The P-value calculated (P<0.0005) proved that the decrease was statistically significant. CONCLUSION: The initial impulse generated by the cardiothoracic surgery team is now spreading to other DRG groups in our hospital and we are seeing a drop in their C:T as well. Better blood utilization is attainable when the physicians who perform most transfusions lead the charge.

Nickel and Copper Toxicity to Embryos of the Long-Spined Sea Urchin, Diadema savignyi.

The sensitivity of long-spined sea urchins (Diadema savignyi) collected from Guam (Northern Marianas Islands), USA, to nickel and copper in seawater was explored using 48-h embryo-larval development toxicity tests. The median effective concentrations (EC50) averaged 94 µg L(-1) for nickel, and 19 µg L(-1) from a single exposure to copper, and suggest relatively high sensitivity of this species to nickel compared with other sea urchin genera, but similar sensitivity to copper. Ambient nickel and copper concentrations concurrently sampled from 16 near-shore locations around Guam were one to two orders of magnitude lower than those that would be expected to result in adverse effects to D. savignyi embryos. Although nationally recommended chronic ambient water quality criteria, currently 8.2 and 3.1 µg L(-1) for nickel and copper, respectively, were not exceeded, recently derived qualifying toxicity data should be considered for updating these criteria to ensure protectiveness of sensitive tropical species.

In vitro toxicity in long-term cell culture of MR contrast agents targeted to cartilage evaluation.

OBJECTIVE: Contrast-enhanced magnetic resonance (MR) imaging methods have been proposed for non-invasive evaluation of osteoarthritis (OA). We measured cell toxicities of cartilage-targeted low-generation dendrimer-linked nitroxide MR contrast agents and gadopentetate dimeglumine (Gd-DTPA) on cultured chondrocytes. DESIGN: A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48-h to different salts (citrate, maleate, tartrate) and concentrations of generation one or two diaminobutyl-linked nitroxides (DAB4-DLN or DAB8-DLN), Gd-DTPA, or staurosporine (positive control). Impact on microscopic cell appearance, MTT spectrophotometric assays of metabolic activity, and quantitative PicoGreen assays of DNA content (cell proliferation) were measured and compared to untreated cultures. RESULTS: Chondrocyte cultures treated with up to 7.5 mM Gd-DTPA for 48-h had no statistical differences in DNA content or MTT reaction compared to untreated cultures. At all doses, DAB4-DLN citrate treated cultures had results similar to untreated and Gd-DTPA-treated cultures. At doses >1 mM, DAB4-DLN citrate treated cultures showed statistically greater DNA and MTT reaction than maleate and tartrate DAB4-DLN salts. Cultures exposed to 5 mM or 7.5 mM DAB8-DLN citrate exhibited rounded cells, poor cell proliferation, and barely detectable MTT reaction. Treatment with 0.1 µM staurosporine caused chondrocyte death. CONCLUSION: Long-term exposure, greater than clinically expected, to either DAB4-DLN citrate or Gd-DTPA had no detectable toxicity with results equivalent to untreated cultures. DAB4-DLN citrate was more biocompatible than either the maleate or tartrate salts. Cells exposed for 48-h to 5 mM or 7.5 mM DAB8-DLN salts demonstrated significant cell toxicity. Further evaluation of DAB8-DLN with clinically appropriate exposure times is required to determine the maximum useful concentration.

Spaceflight and hind limb unloading induce similar changes in electrical impedance characteristics of mouse gastrocnemius muscle.

OBJECTIVE: To assess the potential of electrical impedance myography (EIM) to serve as a marker of muscle fiber atrophy and secondarily as an indicator of bone deterioration by assessing the effects of spaceflight or hind limb unloading. METHODS: In the first experiment, 6 mice were flown aboard the space shuttle (STS-135) for 13 days and 8 earthbound mice served as controls. In the second experiment, 14 mice underwent hind limb unloading (HLU) for 13 days; 13 additional mice served as controls. EIM measurements were made on ex vivo gastrocnemius muscle. Quantitative microscopy and areal bone mineral density (aBMD) measurements of the hindlimb were also performed. RESULTS: Reductions in the multifrequency phase-slope parameter were observed for both the space flight and HLU cohorts compared to their respective controls. For ground control and spaceflight groups, the values were 24.7±1.3°/MHz and 14.1±1.6°/MHz, respectively (p=0.0013); for control and HLU groups, the values were 23.9±1.6°/MHz and 19.0±1.0°/MHz, respectively (p=0.014). This parameter also correlated with muscle fiber size (ρ=0.65, p=0.011) for spaceflight and hind limb aBMD (ρ=0.65, p=0.0063) for both groups. CONCLUSIONS: These data support the concept that EIM may serve as a useful tool for assessment of muscle disuse secondary to immobilization or microgravity.

An in vivo method for measuring the adsorption of plasma proteins to titanium in humans.

A novel method of collecting in vivo plasma proteins of humans from osteotomies prepared during insertion of an oral implant is described. A rod containing a collecting portion with a predetermined surface is introduced into the osteomy, removed, and transferred for enzyme-linked immunosorbent assay analysis. Two experiments were used to examine the feasibility of the method. In the first, titanium (Ti) rods with different roughness were exposed for 10 min to the blood. Blasted and acid-etched surfaces adsorbed four times more and acid-etched surfaces adosorbed two times more plasma proteins as compared to machined surfaces. In the second experiment, blasted and acid-etched rods were wetted for 10 s prior to the insertion. The adsorption for fibronectin, albumin, fibrinogen, and IgG was enhanced significantly compared with nonwetted rods. These results are discussed in the light of previous methods used in studies on adsorption. Thus, use of the collecting instrument enables aspects of human plasma-implant interface to be studied in a more realistic manner.

Embryonic disruption of the candidate dyslexia susceptibility gene homolog Kiaa0319-like results in neuronal migration disorders.

Developmental dyslexia, the most common childhood learning disorder, is highly heritable, and recent studies have identified KIAA0319-Like (KIAA0319L) as a candidate dyslexia susceptibility gene at the 1p36-34 (DYX8) locus. In this experiment, we investigated the anatomical effects of knocking down this gene during rat corticogenesis. Cortical progenitor cells were transfected using in utero electroporation on embryonic day (E) 15.5 with plasmids encoding either: (1) Kiaa0319l small hairpin RNA (shRNA), (2) an expression construct for human KIAA0319L, (3) Kiaa0319l shRNA+KIAA0319L expression construct (rescue), or (4) controls (scrambled Kiaa0319l shRNA or empty expression vector). Mothers were injected with 5-bromo-2-deoxyuridine (BrdU) at either E13.5, E15.5, or E17.5. Disruption of Kiaa0319l function (by knockdown, overexpression, or rescue) resulted in the formation of large nodular periventricular heterotopia in approximately 25% of the rats, which can be seen as early as postnatal day 1. Only a small subset of heterotopic neurons had been transfected, indicating non-cell autonomous effects of the transfection. Most heterotopic neurons were generated in mid- to late-gestation, and laminar markers suggest that they were destined for upper cortical laminae. Finally, we found that transfected neurons in the cerebral cortex were located in their expected laminae. These results indicate that KIAA0319L is the fourth of four candidate dyslexia susceptibility genes that is involved in neuronal migration, which supports the association of abnormal neuronal migration with developmental dyslexia.

Electrical impedance alterations in the rat hind limb with unloading.

OBJECTIVES: Methods are needed for quantifying muscle deconditioning due to immobilization, aging, or spaceflight. Electrical impedance myography (EIM) is one technique that may offer easy-to-follow metrics. Here, we evaluate the time course and character of the change in single- and multi-frequency EIM parameters in the hind-limb suspension model of muscle deconditioning in rats. METHODS: Sixty-two rats were studied with EIM during a two-week period of hind limb unloading followed by a two-week recovery period. Random subsets of animals were sacrificed at one-week time intervals to measure muscle fiber size. RESULTS: Significant alterations were observed in nearly all impedance parameters. The 50 kHz phase and multi-frequency phase-slope, created by taking the slope of a line fitted to the impedance values between 100-500 kHz, appeared most sensitive to disuse atrophy, the latter decreasing by over 33.0±6.6% (p<0.001), a change similar to the maximum reduction in muscle fiber size. Impedance alterations, however, lagged changes in muscle fiber size. CONCLUSIONS: EIM is sensitive to disuse change in the rat, albeit with a delay relative to alterations in muscle fiber size. Given the rapidity and simplicity of EIM measurements, the technique could prove useful in providing a non-invasive approach to measuring disuse change in animal models and human subjects.

Bilateral subcortical heterotopia with partial callosal agenesis in a mouse mutant.

Cognition and behavior depend on the precise placement and interconnection of complex ensembles of neurons in cerebral cortex. Mutations that disrupt migration of immature neurons from the ventricular zone to the cortical plate have provided major insight into mechanisms of brain development and disease. We have discovered a new and highly penetrant spontaneous mutation that leads to large nodular bilateral subcortical heterotopias with partial callosal agenesis. The mutant phenotype was first detected in a colony of fully inbred BXD29 mice already known to harbor a mutation in Tlr4. Neurons confined to the heterotopias are mainly born in midgestation to late gestation and would normally have migrated into layers 2-4 of overlying neocortex. Callosal cross-sectional area and fiber number are reduced up to 50% compared with coisogenic wildtype BXD29 substrain controls. Mutants have a pronounced and highly selective defect in rapid auditory processing. The segregation pattern of the mutant phenotype is most consistent with a two-locus autosomal recessive model, and selective genotyping definitively rules out the Tlr4 mutation as a cause. The discovery of a novel mutation with strong pleiotropic anatomical and behavioral effects provides an important new resource for dissecting molecular mechanisms and functional consequences of errors of neuronal migration.

Self-hypnosis for coping with labour pain: a randomised controlled trial.

OBJECTIVE: To estimate the use of epidural analgesia and experienced pain during childbirth after a short antenatal training course in self-hypnosis to ease childbirth. DESIGN: Randomised, controlled, single-blinded trial using a three-arm design. SETTING: Aarhus University Hospital Skejby in Denmark during the period July 2009 until August 2011. POPULATION: A total of 1222 healthy nulliparous women. METHOD: Use of epidural analgesia and self-reported pain during delivery was compared in three groups: a hypnosis group receiving three 1-hour lessons in self-hypnosis with additional audiorecordings to ease childbirth, a relaxation group receiving three 1-hour lessons in various relaxation methods and mindfulness with audiorecordings for additional training, and a usual care group receiving ordinary antenatal care only. PRIMARY OUTCOME: Use of epidural analgesia. Secondary outcomes included self-reported pain. RESULTS: There were no between-group differences in use of epidural analgesia-31.2% (95% confidence interval [95% CI] 27.1-35.3) in the hypnosis group, 29.8% (95% CI 25.7-33.8) in the relaxation group and 30.0% (95% CI 24.0-36.0) in the control group. No statistically significant differences between the three groups were observed for any of the self-reported pain measures. CONCLUSION: In this large randomised controlled trial of a brief course in self-hypnosis to ease childbirth, no differences in use of epidural analgesia or pain experience were found across study groups. Before turning down self-hypnosis as a method for pain relief, further studies are warranted with focus on specific subgroups.

Dcdc2 knockout mice display exacerbated developmental disruptions following knockdown of doublecortin.

The dyslexia-associated gene DCDC2 is a member of the DCX family of genes known to play roles in neurogenesis, neuronal migration, and differentiation. Here we report the first phenotypic analysis of a Dcdc2 knockout mouse. Comparisons between Dcdc2 knockout mice and wild-type (wt) littermates revealed no significant differences in neuronal migration, neocortical lamination, neuronal cilliogenesis or dendritic differentiation. Considering previous studies showing genetic interactions and potential functional redundancy among members of the DCX family, we tested whether decreasing Dcx expression by RNAi would differentially impair neurodevelopment in Dcdc2 knockouts and wild-type mice. Consistent with this hypothesis, we found that deficits in neuronal migration, and dendritic growth caused by RNAi of Dcx were more severe in Dcdc2 knockouts than in wild-type mice with the same transfection. These results indicate that Dcdc2 is not required for neurogenesis, neuronal migration or differentiation in mice, but may have partial functional redundancy with Dcx.

Persistent spatial working memory deficits in rats following in utero RNAi of Dyx1c1.

Disruptions in the development of the neocortex are associated with cognitive deficits in humans and other mammals. Several genes contribute to neocortical development, and research into the behavioral phenotype associated with specific gene manipulations is advancing rapidly. Findings include evidence that variants in the human gene DYX1C1 may be associated with an increased risk of developmental dyslexia. Concurrent research has shown that the rat homolog for this gene modulates critical parameters of early cortical development, including neuronal migration. Moreover, recent studies have shown auditory processing and spatial learning deficits in rats following in utero transfection of an RNA interference (RNAi) vector of the rat homolog Dyx1c1 gene. The current study examined the effects of in utero RNAi of Dyx1c1 on working memory performance in Sprague-Dawley rats. This task was chosen based on the evidence of short-term memory deficits in dyslexic populations, as well as more recent evidence of an association between memory deficits and DYX1C1 anomalies in humans. Working memory performance was assessed using a novel match-to-place radial water maze task that allows the evaluation of memory for a single brief (∼4-10 seconds) swim to a new goal location each day. A 10-min retention interval was used, followed by a test trial. Histology revealed migrational abnormalities and laminar disruption in Dyx1c1 RNAi-treated rats. Dyx1c1 RNAi-treated rats exhibited a subtle, but significant and persistent impairment in working memory as compared to Shams. These results provide further support for the role of Dyx1c1 in neuronal migration and working memory.

The association between the embolic load and atrial size in acute pulmonary embolism.

BACKGROUND: Early identification by computed tomography pulmonary angiography (CTPA) of patients with acute pulmonary embolism (PE) who have signs associated with a high embolic burden would be highly desirable. OBJECTIVES: To investigate whether an increased obstruction of the pulmonary vasculature is associated with reduced left atrial (LA) and increased right atrial (RA) areas. METHODS: We retrospectively analyzed a consecutive series of CTPA studies of 137 patients with acute PE and 38 controls without PE between October 2004 and March 2006. Left and right atrial areas and longitudinal and short axis diameters were measured and correlated with the pulmonary arterial obstruction index (PAOI) divided into tertiles (obstruction of < 12.5%, 12.5%-42.5% and ≥ 42.5%). RESULTS: There was a significant negative age- and gender-adjusted correlation between the PAOI and LA measurements, particularly the LA area (r = -0.259) and the LA short axis diameter (r = -0.331). All RA measurements had positive correlations (RA area, r = 0.279; RA short axis diameter, r = 0.313). The LA/RA area ratio correlated negatively with the PAOI (r = -0.447). All above-mentioned correlations had P < 0.002. All the LA measurements were the largest in the controls and gradually decreased with higher PAOIs. A receiver operating characteristic curve analysis demonstrated that the RV/LV diameter, LA/RA area and LA/RA short axis diameter ratios had comparable discriminative ability for higher PAOI tertiles. CONCLUSIONS: The higher the clot load in the pulmonary arteries, the smaller the LA area and the larger the RA area. Atrial area measurements by CTPA may serve as a real-time parameter in assessing the severity of PE upon diagnosis.

The effects of embryonic knockdown of the candidate dyslexia susceptibility gene homologue Dyx1c1 on the distribution of GABAergic neurons in the cerebral cortex.

Developmental dyslexia is a language-based learning disability, and a number of candidate dyslexia susceptibility genes have been identified, including DYX1C1, KIAA0319, and DCDC2. Knockdown of function by embryonic transfection of small hairpin RNA (shRNA) of rat homologues of these genes dramatically disrupts neuronal migration to the cerebral cortex by both cell autonomous and non-cell autonomous effects. Here we sought to investigate the extent of non-cell autonomous effects following in utero disruption of the candidate dyslexia susceptibility gene homolog Dyx1c1 by assessing the effects of this disruption on GABAergic neurons. We transfected the ventricular zone of embryonic day (E) 15.5 rat pups with either Dyx1c1 shRNA, DYX1C1 expression construct, both Dyx1c1 shRNA and DYX1C1 expression construct, or a scrambled version of Dyx1c1 shRNA, and sacrificed them at postnatal day 21. The mothers of these rats were injected with BrdU at either E13.5, E15.5, or E17.5. Neurons transfected with Dyx1c1 shRNA were bi-modally distributed in the cerebral cortex with one population in heterotopic locations at the white matter border and another migrating beyond their expected location in the cerebral cortex. In contrast, there was no disruption of migration following transfection with the DYX1C1 expression construct. We found untransfected GABAergic neurons (parvalbumin, calretinin, and neuropeptide Y) in the heterotopic collections of neurons in Dyx1c1 shRNA treated animals, supporting the hypothesis of non-cell autonomous effects. In contrast, we found no evidence that the position of the GABAergic neurons that made it to the cerebral cortex was disrupted by the embryonic transfection with any of the constructs. Taken together, these results support the notion that neurons within heterotopias caused by transfection with Dyx1c1 shRNA result from both cell autonomous and non-cell autonomous effects, but there is no evidence to support non-cell autonomous disruption of neuronal position in the cerebral cortex itself.