Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, we report the discovery of a series of tetrahydropyrimidopyrimidinone derivatives. Starting with hit compound 1a, medicinal chemistry optimization led to compound 31. This molecule displays potent activity, an exquisite selectivity for Vps34 with excellent properties. The X-ray crystal structure of compound 31 in human Vps34 illustrates how the unique molecular features of the morpholine synthon bestows selectivity against class I PI3Ks. This molecule exhibits suitable in vivo mouse PK parameters and induces a sustained inhibition of Vps34 upon acute administration. Compound 31 constitutes an optimized Vps34 inhibitor that could be used to investigate human cancer biology.

Background: Emotional memory is an adaptive process that improves the memorization of emotional events or stimuli. In Post-Traumatic Stress Disorder (PTSD), emotional memory may be altered, which in turn may affect symptoms. Having a clearer view of the processes of interaction between memory and emotional stimuli in PTSD may improve our knowledge of this disorder, and could create new therapeutic management tools. Thus, we performed a systematic review of the evidence of specific emotional memory in PTSD patients.Method: Following PRISMA guidelines, a systematic review of MEDLINE, PsycInfo, and ScienceDirect was undertaken to identify controlled studies on emotional memory that used cognitive tasks on PTSD patients. The initial research was conducted from June 2017 to July 2017, and search terms included: Post-Traumatic Stress Disorder; PTSD; emotional memory; emotion; emotional; memory; and episodic memory.Results: Eighteen studies reporting on 387 PTSD patients met the eligibility criteria. Among the studies selected, 11 observed specific memory processing in PTSD patients, such as a greater memorization of negative information, or a trend to false recognition of negative information. In addition, attentional and inhibition processing seem to play an important role in emotional memory in PTSD sufferers. Furthermore, other studies that did not find behavioral differences between PTSD and control groups nevertheless showed differences in both specific cerebral activities and neurohormone levels during emotional memory tasks.Conclusion: This review has several limitations, including a limited number of controlled studies, small sample sizes, different tasks and methods. Nevertheless, the results of this systematic review provide interesting information on emotional memory for clinicians and researchers, as they seem to highlight facilitated memory processing for negative information in PTSD patients. This topic needs further controlled studies with sensitive behavioral tasks. Also, future studies may evaluate emotional memory after symptom amelioration.

Background: Emotional memory is an adaptive process that improves the memorization of emotional events or stimuli. In Post-Traumatic Stress Disorder (PTSD), emotional memory may be altered, which in turn may affect symptoms. Having a clearer view of the processes of interaction between memory and emotional stimuli in PTSD may improve our knowledge of this disorder, and could create new therapeutic management tools. Thus, we performed a systematic review of the evidence of specific emotional memory in PTSD patients.Method: Following PRISMA guidelines, a systematic review of MEDLINE, PsycInfo, and ScienceDirect was undertaken to identify controlled studies on emotional memory that used cognitive tasks on PTSD patients. The initial research was conducted from June 2017 to July 2017, and search terms included: Post-Traumatic Stress Disorder; PTSD; emotional memory; emotion; emotional; memory; and episodic memory.Results: Eighteen studies reporting on 387 PTSD patients met the eligibility criteria. Among the studies selected, 11 observed specific memory processing in PTSD patients, such as a greater memorization of negative information, or a trend to false recognition of negative information. In addition, attentional and inhibition processing seem to play an important role in emotional memory in PTSD sufferers. Furthermore, other studies that did not find behavioral differences between PTSD and control groups nevertheless showed differences in both specific cerebral activities and neurohormone levels during emotional memory tasks. Conclusion:This review has several limitations, including a limited number of controlled studies, small sample sizes, different tasks and methods. Nevertheless, the results of this systematic review provide interesting information on emotional memory for clinicians and researchers, as they seem to highlight facilitated memory processing for negative information in PTSD patients. This topic needs further controlled studies with sensitive behavioral tasks. Also, future studies may evaluate emotional memory after symptom amelioration.

Background: Mild Cognitive Impairment [MCI] is a transition stage between normal aging and dementia. It seems to be useful to treat MCI before the onset of early dementia, though no pharmacological treatment is recommended [1]. These case studies aimed to assess the efficacy of long-term repetitive Transcranial Magnetic Stimulation [rTMS] treatment on cognition, and clinical changes, in elderly MCI patients. Methods: Three patients with MCI were treated by rTMS with different parameters of stimulation, targeting the Dorsolateral Prefrontal Cortex for three, six or twelve months. Cognition, depressive symptoms and overall clinical change were assessed before and after rTMS. Results: After treatment, all three MCI patients improved their cognition and overall clinical state. The three patients had no significant depressive symptoms at any time. Conclusions: Our results highlight the cognitive and clinical benefits of long-term rTMS treatment in MCI patients, without side effects. This cognitive improvement is regardless of