The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2 0 -deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.

ObjectivesAscertain the extent of differences between men and women in dispensed drugs since there is a lack of comprehensive overviews on sex differences in the use of prescription drugs.DesignCross-sectional population database analysis.MethodsData on all dispensed drugs in 2010 to the entire Swedish population (9.3 million inhabitants) were obtained from the Swedish Prescribed Drug Register. All pharmacological groups with ambulatory care prescribing accounting for >75% of the total volume in Defined Daily Doses and a prevalence of >1% were included in the analysis. Crude and age-adjusted differences in prevalence and incidence were calculated as risk ratios (RRs) of women/men.ResultsIn all, 2.8 million men (59%) and 3.6 million women (76%) were dispensed at least one prescribed drug during 2010. Women were dispensed more drugs in all age groups except among children under the age of 10. The largest sex difference in prevalence in absolute numbers was found for antibiotics that were more common in women, 265.5 patients (PAT)/1000 women and 191.3 PAT/1000 men, respectively. This was followed by thyroid therapy (65.7 PAT/1000 women and 13.1 PAT/1000 men) and antidepressants (106.6 PAT/1000 women and 55.4 PAT/1000 men). Age-adjusted relative sex differences in prevalence were found in 48 of the 50 identified pharmacological groups. The pharmacological groups with the largest relative differences of dispensed drugs were systemic antimycotics (RR 6.6 CI 6.4 to 6.7), drugs for osteoporosis (RR 4.9 CI 4.9 to 5.0) and thyroid therapy (RR 4.5 CI 4.4 to 4.5), which were dispensed to women to a higher degree. Antigout agents (RR 0.4 CI 0.4 to 0.4), psychostimulants (RR 0.6 CI 0.6 to 0.6) and ACE inhibitors (RR 0.7 CI 0.7 to 0.7) were dispensed to men to a larger proportion.ConclusionsSubstantial differences in the prevalence and incidence of dispensed drugs were found between men and women. Some differences may be rational and desirable and related to differences between the sexes in the incidence or prevalence of disease or by biological differences. Other differences are more difficult to explain on medical grounds and may indicate unequal treatment.

IMPORTANCETo our knowledge, it is unknown whether a prehospital stroke triage system combining symptom severity and teleconsultation could accurately select patients for primary stroke center bypass and hasten delivery of endovascular thrombectomy (EVT) without delaying intravenous thrombolysis (IVT). OBJECTIVE To evaluate the predictive performance of the newly implemented Stockholm Stroke Triage System (SSTS) for large-artery occlusion (LAO) stroke and EVT initiation. Secondary objectives included evaluating whether the Stockholm Stroke Triage System shortened onset-to-puncture time for EVT and onset-to-needle time (ONT) for IVT. DESIGN, SETTING, AND PARTICIPANTS This population-based prospective cohort study conducted from October 2017 to October 2018 across the Stockholm region (Sweden) included patients transported by first-priority ("code stroke") ambulance to the hospital for acute stroke suspected by an ambulance nurse and historical controls (October 2016-October 2017). Exclusion criteria were in-hospital stroke and helicopter or private transport. Of 2909 eligible patients, 4 (0.14%) declined participation. EXPOSURES Patients were assessed by ambulance nurses with positive the face-armspeech-time test or other stroke suspicion and were evaluated for moderate-to-severe hemiparesis (Ն2 National Institutes of Health stroke scale points each on the ipsilateral arm and leg [A2L2 test]). If present, the comprehensive stroke center (CSC) stroke physician was teleconsulted by phone for confirmation of stroke suspicion, assessment of EVT eligibility, and direction to CSC or the nearest primary stroke center. If absent, the nearest hospital was prenotified.MAIN OUTCOMES AND MEASURES Primary outcome: LAO stroke. Secondary outcomes: EVT initiation, onset-to-puncture time, and ONT. Predictive performance measures included sensitivity, specificity, positive and negative predictive values, the overall accuracy for LAO stroke, and EVT initiation. RESULTSWe recorded 2905 patients with code-stroke transports (1420 women [49%]), and of these, 323 (11%) had A2L2+ teleconsultation positive results and were triaged for direct transport to CSC (median age, 73 years [interquartile range (IQR), 64-82 years]; 55 women [48%]). Accuracy for LAO stroke was 87% (positive predictive value, 41%; negative predictive value, 93%) and 91% for EVT initiation (positive predictive value, 26%; negative predictive value, 99%). Endovascular thrombectomy was performed for 84 of 323 patients (26%) with triage-positive results and 35 of 2582 patients (1.4%) with triage-negative results. In EVT cases with a known onset time (77 [3%]), the median OPT was 137 minutes (IQR, previous year, 206 minutes [IQR,; n = 75) (P < .001). The regional median ONT (337 [12%]) was unchanged at 115 minutes (IQR, previous year, 115 minutes [IQR,; n = 360) (P = .79). The median CSC IVT door-to-needle time was 13 minutes (IQR,(10)(11)(12)(13)(14)(15)(16)(17)(18) 116 [4%]) (previous year, 31 minutes [IQR,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35...