Long-term time-lapse live imaging reveals extensive cell migration during annelid regeneration

Funding for Open Access provided by the UMD Libraries Open Access Publishing Fund.Background: Time-lapse imaging has proven highly valuable for studying development, yielding data of much finer resolution than traditional “still-shot” studies and allowing direct examination of tissue and cell dynamics. A major challenge for time-lapse imaging of animals is keeping specimens immobile yet healthy for extended periods of time. Although this is often feasible for embryos, the difficulty of immobilizing typically motile juvenile and adult stages remains a persistent obstacle to time-lapse imaging of post-embryonic development. Results: Here we describe a new method for long-duration time-lapse imaging of adults of the small freshwater annelid Pristina leidyi and use this method to investigate its regenerative processes. Specimens are immobilized with tetrodotoxin, resulting in irreversible paralysis yet apparently normal regeneration, and mounted in agarose surrounded by culture water or halocarbon oil, to prevent dehydration but allowing gas exchange. Using this method, worms can be imaged continuously and at high spatial-temporal resolution for up to 5 days, spanning the entire regeneration process. We performed a fine-scale analysis of regeneration growth rate and characterized cell migration dynamics during early regeneration. Our studies reveal the migration of several putative cell types, including one strongly resembling published descriptions of annelid neoblasts, a cell type suggested to be migratory based on “still-shot” studies and long hypothesized to be linked to regenerative success in annelids. Conclusions: Combining neurotoxin-based paralysis, live mounting techniques and a starvation-tolerant study system has allowed us to obtain the most extensive high-resolution longitudinal recordings of full anterior and posterior regeneration in an invertebrate, and to detect and characterize several cell types undergoing extensive migration during this process. We expect the tetrodotoxin paralysis and time-lapse imaging methods presented here to be broadly useful in studying other animals and of particular value for studying post-embryonic development.https://doi.org/10.1186/s12861-016-0104-

Change in Eosinophil Count in Patients with Heart Failure Treated with Anakinra

Background: Interleukin-1 blockade with anakinra leads to a transient increase in eosinophil blood count (eosinophils) in patients with acute myocardial infarction. We aimed to investigate the effect of anakinra on changes in eosinophils in patients with heart failure (HF) and their correlation with cardiorespiratory fitness (CRF). Methods: We measured eosinophils in 64 patients with HF (50% females), 55 (51-63) years of age, before and after treatment, and, in a subset of 41 patients, also after treatment cessation. We also evaluated CRF, measuring peak oxygen consumption (VO2) with a treadmill test. Results: Treatment with anakinra significantly and transiently increased eosinophils, from 0.2 [0.1-0.3] to 0.3 [0.1-0.4] x 10(3) cells/mu L (p < 0.001) and from 0.3 [0.2-0.5] to 0.2 [0.1-0.3] x 10(3) cells/mu L, with suspension (p < 0.001). Changes in eosinophils correlated with the changes in peak VO2 (Spearman's Rho = +0.228, p = 0.020). Eosinophils were higher in patients with injection site reactions (ISR) (n = 8, 13%; 0.5 [0.4-0.6] vs. 0.2 [0.1-0.4] x 10(3) cells/mu L, p = 0.023), who also showed a greater increase in peak VO2 (3.0 [0.9-4.3] vs. 0.3 [-0.6-1.8] mLO(2)center dot kg(-1)center dot min(-1), p = 0.015). Conclusion: Patients with HF treated with anakinra experience a transient increase in eosinophils, which is associated with ISR and a greater improvement in peak VO2

Obstructed Labor and Caesarean Delivery: The Cost and Benefit of Surgical Intervention

Background: Although advances in the reduction of maternal mortality have been made, up to 273,000 women will die this year from obstetric etiologies. Obstructed labor (OL), most commonly treated with Caesarean delivery, has been identified as a major contributor to global maternal morbidity and mortality. We used economic and epidemiological modeling to estimate the cost per disability-adjusted life-year (DALY) averted and benefit-cost ratio of treating OL with Caesarean delivery for 49 countries identified as providing an insufficient number of Caesarean deliveries to meet demand. Methods and Findings Using publicly available data and explicit economic assumptions, we estimated that the cost per DALY (3,0,0) averted for providing Caesarean delivery for OL ranged widely, from $251 per DALY averted in Madagascar to$3,462 in Oman. The median cost per DALY averted was $304. Benefit-cost ratios also varied, from 0.6 in Zimbabwe to 69.9 in Gabon. The median benefit-cost ratio calculated was 6.0. The main limitation of this study is an assumption that lack of surgical capacity is the main factor responsible for DALYs from OL. Conclusions: Using the World Health Organization's cost-effectiveness standards, investing in Caesarean delivery can be considered “highly cost-effective” for 48 of the 49 countries included in this study. Furthermore, in 46 of the 49 included countries, the benefit-cost ratio was greater than 1.0, implying that investment in Caesarean delivery is a viable economic proposition. While Caesarean delivery alone is not sufficient for combating OL, it is necessary, cost-effective by WHO standards, and ultimately economically favorable in the vast majority of countries included in this study

Electrophysiological evidence of enhanced performance monitoring in recently abstinent alcoholic men

RATIONALE: Chronic alcoholism is associated with mild to moderate cognitive impairment. Under certain conditions, impairment can be ameliorated by invoking compensatory processes. OBJECTIVE: To identify electrophysiological mechanisms of such compensation that would be required to resolve response conflict. METHODS: 14 abstinent alcoholic men and 14 similarly aged control men performed a variation of the Eriksen flanker task during an electroencephalography (EEG) recording to examine whether alcoholics could achieve and maintain control-level performance and whether EEG markers could identify evidence for the action of compensatory processes in the alcoholics. Monitoring processes engaged following a response were indexed by the correct related negativity (CRN) and error related negativity (ERN), two medial-frontal negative event-related potentials. RESULTS: The alcoholics were able to perform at control levels on accuracy and reaction time (RT). Alcoholics generated larger ERN amplitudes following incorrect responses and larger CRNs following correct responses than controls. Both groups showed evidence of post-error slowing. Larger CRN amplitudes in the alcoholics were related to longer RTs. Also observed in the alcoholics was an association between smaller CRN amplitudes and length of sobriety, suggesting a normalization of monitoring activity with extended abstinence. CONCLUSIONS: To the extent that greater amplitude of these electrophysiological markers of performance monitoring indexes greater resource allocation and performance compensation, the larger amplitudes observed in the alcoholic than control group support the view that elevated performance monitoring enables abstinent alcoholics to overcome response conflict, as was evident in their control-level performance

WE‐C‐WAB‐03: Correspondence Between FDG‐PET and Diffusion‐Weighted MRI After Deformable Registration in Locally‐Advanced Non‐Small Cell Lung Cancer

Purpose: To develop and evaluate a framework for aligning diffusion‐weighted MR images (DWI) to CT and PET/CT in locally‐advanced lung cancer, and to evaluate the correspondence of FDG‐PET and DWI prior to radiation therapy. Methods: Pretreatment FDG‐PET/CT, 4D fan beam planning CT, and MR were acquired in five locally‐advanced lung cancer patients. Deformable registration was used to align the b=0 s/m2 DWI to a high‐resolution morphological MRI to reduce spatial distortion and respiratory effects. The morphological MRI was then registered to planning CT to map DWI to the planning CT reference frame. Apparent diffusion coefficient (ADC) was computed from DWI. PET/CT was also registered to planning CT. 40% of maximum lesion SUV (SUVmax) threshold was used to delineate primary tumor on PET, and a physician delineated the lesion on DWI. Dice coefficient between PET and DWI primary tumor volumes was computed to assess whole lesion location. To establish correspondence of tumor subvolumes, the region of 70% SUVmax on PET (high SUV) was delineated, and the ADC distribution from the spatially‐registered DWI extracted in this region. This process was repeated for the 40%–50% SUVmax (low SUV) region. Results: All registrations were judged visually acceptable. The PET and DWI‐defined primary tumor Dice coefficient was 0.6 +/‐0.1 after registration. The mean ADC corresponding to the high SUV region was lower than the mean ADC in the low SUV region in 4/5 patients (mean difference of −130 m2/s). One patient had higher ADC in the high SUV region, with a difference of 94 m2/s between regions. This patient had a highly heterogeneous lesion with small hyperintense pockets on ADC images indicating necrosis. Conclusion: Deformable registration of thoracic MR appears feasible to reduce the effects of distortion and motion artifacts. High SUV generally corresponded with the most restricted diffusion signal from DWI