Adult hippocampal neurogenesis is the process of generation and functional incorporation of new neurons, formed by adult neural stem cells in the dentate gyrus. Adult hippocampal neurogenesis is highly dependent upon the integration of dynamic external stimuli and is instrumental in the formation of new spatial memories. Adult hippocampal neurogenesis is therefore uniquely sensitive to the summation of neuronal circuit and neuroimmune environments that comprise the neurogenic niche, and has powerful implications in diseases of aging and neurological disorders. This sensitivity underlies the neurogenic niche alterations commonly observed in Alzheimer’s disease, the most common form of dementia. This review summarizes Alzheimer’s disease associated changes in neuronal network activity, neuroinflammatory processes, and adult neural stem cell fate choice that ultimately result in neurogenic niche dysfunction and impaired adult hippocampal neurogenesis. A more comprehensive understanding of the complex changes mediating neurogenic niche disturbances in Alzheimer’s disease will aid development of future therapies targeting adult neurogenesis.

Mathematical optimization can be used to place automated external defibrillators (AEDs) in locations that maximize coverage of out-of-hospital cardiac arrests (OHCAs). We sought to determine whether optimization can improve alignment between AED locations and OHCA counts across levels of socioeconomic deprivation.

All suspected OHCAs and registered AEDs in Scotland between Jan. 2011 and Sept. 2017 were included and mapped to a corresponding socioeconomic deprivation level using the Scottish Index of Multiple Deprivation (SIMD). We used mathematical optimization to determine optimal locations for placing 10%, 25%, 50%, and 100% additional AEDs, as well as locations for relocating existing AEDs. For each AED placement policy, we examined the impact on AED distribution and OHCA “coverage” (suspected OHCA occurring within 100m of AED) with respect to SIMD quintiles.

We identified 49,432 suspected OHCAs and 1532 AEDs. The distribution of existing AED locations across SIMD quintiles significantly differed from the distribution of suspected OHCAs (P<0.001). Optimization-guided AED placement increased coverage of suspected OHCAs compared to existing AED locations (all P<0.001). Optimization resulted in more AED placements and increased OHCA coverage in areas of greater socioeconomic deprivation, such that resulting distributions across SIMD quintiles matched the shape of the OHCA count distribution. Optimally relocating existing AEDs achieved similar OHCA coverage levels to that of doubling the number of total AEDs.

Mathematical optimization results in AED locations and suspected OHCA coverage that more closely resembles the suspected OHCA distribution and results in more equitable coverage across levels of socioeconomic deprivation.

Mathematical optimization results in AED locations and suspected OHCA coverage that more closely resembles the suspected OHCA distribution and results in more equitable coverage across levels of socioeconomic deprivation.

Targeted temperature management (TTM) following out-of-hospital cardiac arrest (OHCA) prolongs the QT-interval but our knowledge of different temperatures and risk of arrhythmia is incomplete.

To assess whether the QTc, QT-peak (QTp) and T-peak to T-end interval (TpTe) may be useful markers of ventricular arrhythmia in contemporary post cardiac arrest treatment.

An ECG-substudy of the TTM-trial (TTM at 33°C vs. 36°C) with serial ECGs from 680 (94%) patients. Bazett’s (B) and Fridericia’s (F) formula were used for heart rate correction of the QT, QTp and TpTe. Ventricular arrhythmia (VT/VF) were registered during the first three days of post cardiac arrest care.

The QT, QTc and QTp intervals were prolonged more at 33°C compared to 36°C and restored to similar and lower levels after rewarming. The TpTe-interval remained between 92-100ms throughout TTM in both groups. The QTc intervals were associated with ventricular arrhythmia, but not after adjustment for cardiac arrest characteristics. The QTp-interval was not associated with risk of ventricular arrhythmia. Heart rate corrected TpTe-intervals were associated with higher risk of arrhythmia (Odds ratio (OR) TpTe(B) 1.12 (1.02-1.23, p=0.01 TpTe(F) 1.12 (1.02-1.23, p=0.02) per 20ms). Further a prolonged TpTe-interval≥90ms was consistently associated with higher risk (OR

TpTe(B) 2.05 (1.25-3.37), p<0.01, TpTe(F) 2.14 (1.32-3.49), p<0.01).

TTM prolongs the QT-interval by prolongation of the QTp-interval without association to increased risk. The TpTe-interval is not significantly affected by core temperature, but heart rate corrected TpTe intervals are robustly associated with risk of ventricular arrhythmia.

The TTM-trial is registered and accessible at ClinicalTrials.gov (Identifier NCT01020916).

The TTM-trial is registered and accessible at ClinicalTrials.gov (Identifier NCT01020916).

Seismocardiography measures the vibrations produced by the beating heart using an accelerometer sensor placed on the chest. We evaluated the ability of smartphone seismocardiography to distinguish between the presence and absence of spontaneous circulation.

Seismocardiography signals were obtained using a smartphone placed on the sternum in a convenience sample of 60 adult patients (30 comatose patients with spontaneous circulation and 30 deceased patients). The maximum, minimum, and standard deviation (SD) of acceleration values for head-to-foot, right-to-left, and dorsoventral axes and the three axis-root mean square (RMS) of the acceleration signals were calculated. selleck inhibitor Blinded observers (n = 156) were each asked to determine the presence or absence of spontaneous circulation based on seismocardiography video clips for each of the 60 patients.

The seismocardiography revealed periodic large positive peaks in the patients with spontaneous circulation, which were absent in the patients without spontaneous circulation. For each of the four output measurements (three independent axes plus the three-axis RMS), the acceleration maxima and SD were significantly higher and the minima significantly lower in the patients with spontaneous circulation than in those without spontaneous circulation (all P < 0.001 except the minimum of three axis-RMS results [P = 0.009]). The observers accurately identified the seismocardiography signals from patients without spontaneous circulation, with a sensitivity of 97.6% (95% confidence interval, 97.0%-98.2%) and a specificity of 98.4% (95% confidence interval, 97.8%-99.0%).

In conclusion, blinded observers accurately distinguished between seismocardiography signals from patients with and without spontaneous circulation.

In conclusion, blinded observers accurately distinguished between seismocardiography signals from patients with and without spontaneous circulation.