A Sensitive Homecage-Based Novel Object Recognition Task for Rodents

The recognition of novel objects is a common cognitive test for rodents, but current paradigms have limitations, such as low sensitivity, possible odor confounds and stress due to being performed outside of the homecage. We have developed a paradigm that takes place in the homecage and utilizes four stimuli per trial, to increase sensitivity. Odor confounds are eliminated because stimuli consist of inexpensive, machined wooden beads purchased in bulk, so each experimental animal has its own set of stimuli. This paradigm consists of three steps. In Step 1, the sampling phase, animals freely explore familiar objects (FO). Novel Objects (NO1 and NO2) are soiled with bedding from the homecage, to acquire odor cues identical to those of the FO. Steps 2 and 3 are test phases. Herein we report results of this paradigm from neurologically intact adult rats and mice of both sexes. Identical procedures were used for both species, except that the stimuli used for the mice were smaller. As expected in Step 2 (NO1 test phase), male and female rats and mice explored NO1 significantly more than FO. In Step 3 (NO2 test phase), rats of both sexes demonstrated a preference for NO2, while this was seen only in female mice. These results indicate robust novelty recognition during Steps 2 and 3 in rats. In mice, this was reliably seen only in Step 2, indicating that Step 3 was difficult for them under the given parameters. This paradigm provides flexibility in that length of the sampling phase, and the delay between test and sampling phases can be adjusted, to tailor task difficulty to the model being tested. In sum, this novel object recognition test is simple to perform, requires no expensive supplies or equipment, is conducted in the homecage (reducing stress), eliminates odor confounds, utilizes 4 stimuli to increase sensitivity, can be performed in both rats and mice, and is highly flexible, as sampling phase and the delay between steps can be adjusted to tailor task difficulty. Collectively, these results indicate that this paradigm can be used to quantify novel object recognition across sex and species

Evaluation of a Technology-Based Survivor Care Plan for Breast Cancer Survivors: Pre-Post Pilot Study.

BACKGROUND: As of 2016, almost 16 million individuals were cancer survivors, including over 3.5 million survivors of breast cancer. Because cancer survivors are living longer and have unique health care needs, the Institute of Medicine proposed a survivor care plan as a way to alleviate the many medical, emotional, and care coordination problems of survivors. OBJECTIVE: This pilot study for breast cancer survivors was undertaken to: (1) examine self-reported changes in knowledge, confidence, and activation from before receipt to after receipt of a survivor care plan; and (2) describe survivor preferences for, and satisfaction with, a technology-based survivor care plan. METHODS: A single group pretest-posttest design was used to study breast cancer survivors in an academic cancer center and a community cancer center during their medical visit after they completed chemotherapy. The intervention was a technology-based survivor care plan. Measures were taken before, immediately after, and 1 month after receipt of the survivor care plan. RESULTS: A total of 38 breast cancer survivors agreed to participate in the study. Compared to baseline levels before receipt of the survivor care plan, participants reported increased knowledge both immediately after its receipt at the academic center (P\u3c.001) and the community center (P\u3c.001) as well as one month later at the academic center (P=.002) and the community center (P\u3c.001). Participants also reported increased confidence immediately following receipt of the survivor care plan at the academic center (P=.63) and the community center (P=.003) and one month later at both the academic center (P=.63) and the community center (P\u3c.001). Activation was increased from baseline to post-survivor care plan at both the academic center (P=.05) and community center (P\u3c.001) as well as from baseline to 1-month follow-up at the academic center (P=.56) and the community center (P\u3c.001). Overall, community center participants had lower knowledge, confidence, and activation at baseline compared with academic center participants. Overall, 22/38 (58%) participants chose the fully functional electronic survivor care plan. However, 12/23 (52%) in the community center group chose the paper version compared to 4/15 (27%) in the academic center group. Satisfaction with the format (38/38 participants) and the content (37/38 participants) of the survivor care plan was high for both groups. CONCLUSIONS: This study provides evidence that knowledge, confidence, and activation of survivors were associated with implementation of the survivor care plan. This research agrees with previous research showing that cancer survivors found the technology-based survivor care plan to be acceptable. More research is needed to determine the optimal approach to survivor care planning to ensure that all cancer survivors can benefit from it

Reply Brief of Appellant on Motion for Leave to Appeal and Appeal as of Right

Reply Brief of Appellant on Motion for Leave to Appeal and Appeal as of Righ

Reply Brief of Appellant on Motion for Leave to Appeal and Appeal as of Right

Reply Brief of Appellant on Motion for Leave to Appeal and Appeal as of Righ

Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing.

Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching and development of Ancylostoma caninum hookworms and kill Schistosoma mansoni flatworms, three widely divergent parasitic helminth species. C. elegans mutants with resistance to known anthelmintic drugs such as ivermectin are equally or more susceptible to these three drugs, suggesting that they may act on novel targets to kill worms. Sertraline, paroxetine, and chlorpromazine have long histories of use clinically as antidepressant or antipsychotic medicines. They may represent new classes of anthelmintic drug that could be used in combination with existing front-line drugs to boost effectiveness of anti-parasite treatment as well as offset the development of parasite drug resistance

Olfactory Memory Impairment Differs by Sex in a Rodent Model of Pediatric Radiotherapy

Although an effective treatment for pediatric brain tumors, cranial radiation therapy (CRT) damages surrounding healthy tissue, thereby disrupting brain development. Animal models of pediatric CRT have primarily relied on visual tasks to assess cognitive impairment. Moreover, there has been a lack of sex comparisons as most research on the cognitive effects of pediatric CRT does not include females. Therefore, we utilized olfaction, an ethologically relevant sensory modality, to assess cognitive impairment in an animal model of CRT that included both male and female mice. Specifically, we used the novel odor recognition (NOdorR) task with social odors to test recognition memory, a cognitive parameter that has been associated with olfactory neurogenesis, a form of cellular plasticity damaged by CRT. In addition to odor recognition memory, olfactory ability or discrimination of non-social and social odors were assessed both acutely and 3 months after CRT. Magnetic resonance imaging (MRI) and histology were performed after behavioral testing to assess long-term damage by CRT. Long-term but not acute radiation-induced impairment in odor recognition memory was observed, consistent with delayed onset of cognitive impairment in human patients. Males showed greater exploration of social odors than females, but general exploration was not affected by irradiation. However, irradiated males had impaired odor recognition memory in adulthood, compared to non-irradiated males (or simply male controls). Female olfactory recognition memory, in contrast, was dependent on estrus stage. CRT damage was demonstrated by (1) histological evaluation of olfactory neurogenesis, which suggested a reduction in CRT versus control, and (2) imaging analyses which showed that the majority of brain regions were reduced in volume by CRT. Specifically, two regions involved in social odor processing (amygdala and piriform cortex) were damaged by cranial irradiation in males but not females, paralleling olfactory recognition findings