Previous research has shown that in vivo on-demand optogenetic stimulation of inhibitory interneurons expressing parvalbumin (PV) is sufficient to suppress seizures in a mouse model of temporal lobe epilepsy (TLE; Krook-Magnuson et al., 2013). Surprisingly, this intervention was capable of suppressing seizures when PV-expressing interneurons were stimulated ipsilateral or contralateral to the presumed seizure focus, raising the possibility of commissural inhibition in TLE. There are mixed reports regarding commissural PV interneuron projections in the healthy hippocampus, and it was previously unknown whether these connections would be maintained or modified following the network reorganization associated with TLE. Using retrograde labeling and viral vector technology in both sexes and the intrahippocampal kainate mouse model of TLE, we therefore examined these issues. Our results reveal that healthy controls possess a population of commissurally projecting hippocampal PV interneurons. Two weeks post-kainate injection, we see a slight, but not statistically significant decrease in retrogradely labeled PV interneurons in the hippocampus contralateral to kainate and tracer injection. By 6 months post-kainate, however, there is a significant increase in retrogradely labeled PV interneurons, suggesting commissural inhibitory axonal sprouting. Using viral GFP expression selectively in PV neurons, we demonstrate sprouting of commissural PV projections in the dentate gyrus of the kainate-injected hippocampus 6 months post-kainate. These findings indicate that PV interneurons supply direct inhibition to the contralateral hippocampus, and undergo sprouting in a mouse model of TLE.
PURPOSE Cancer is a growing problem in Africa, and delays in receiving timely cancer care often results in poorer outcomes. The purpose of this study was to identify the patient and health-system factors associated with delayed cancer care in adults living in the Northern Zone of Tanzania. PATIENTS AND METHODS Between July 2018 and July 2019, we surveyed adult patients presenting to an oncology clinic in Northern Tanzania. Delayed presentation was defined as 12 weeks or longer from initial symptoms to presentation for cancer care. Multivariate logistic regression and adjusted relative risk (aRR) were used to identify factors predicting delayed presentation. RESULTS Among 244 adult patients with cancer who completed the survey, 78% (n = 191) had delayed presentation. Patient-related factors associated with delayed presentation included lower educational attainment ( P = .03), increased travel time ( P = .05), lack of cancer knowledge ( P < .05), and fear of cancer and cancer treatments ( P < .05) on multivariate analysis. On analysis of aRR, patients without private car and those with health insurance had higher risk of delayed presentation (aRR: 1.27; 95% CI, 1.02 to 1.32 and aRR: 1.15; 95% CI, 1.01 to 1.32). There was a strong association with increased number of visits before presentation at the cancer center and delayed presentation ( P = .0009). CONCLUSION Cancer awareness and prevention efforts targeting patients and community-level health care workers are key to reduce delays in cancer care in Northern Tanzania.
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