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Unlike normal cells, cancer cells express high levels of phosphatidylserine on the extracellular leaflet of their cell membrane. Exploiting this characteristic, our lab developed a therapeutic agent that consists of the fusogenic protein, saposin C (SapC) which is embedded in dioleoylphosphatidylserine (DOPS) vesicles. These nanovesicles selectively target cancer cells and induce apoptosis. Here we review the data supporting use of SapC-DOPS to locate tumors for surgical resection or for treatment. In addition, there is important evidence suggesting that SapC-DOPS may also prove to be an effective novel cancer therapeutic reagent. Given that SapC-DOPS is easily labeled with lipophilic dyes, it has been combined with the far-red fluorescent dye, CellVue Maroon (CVM), for tumor targeting studies. We also have used contrast agents incorporated in the SapC-DOPS nanovesicles for computed tomography and magnetic resonance imaging, and review that data here. Administered intravenously, the fluorescently labeled SapC-DOPS traversed the blood–brain tumor barrier enabling identification of brain tumors. SapC-DOPS-CVM also detected a variety of other mouse tumors in vivo, rendering them observable by optical imaging using IVIS and multi-angle rotational optical imaging. Dye is detected within 30 min and remains within tumor for at least 7 days, whereas non-tumor tissues were unstained (some dye observed in the liver was transient, likely representing degradation products). Additionally, labeled SapC-DOPS ex vivo delineated tumors in human histological specimens. SapC-DOPS can also be labeled with contrast reagents for computed tomography or magnetic resonance imaging. In conclusion, labeled SapC-DOPS provides a convenient, specific, and nontoxic method for detecting tumors while concurrently offering a therapeutic benefit.

SUMMARYThe neurobiology of psychological concepts like schema, and psychotherapeutic strategies of cognitive behavioral therapy (CBT) is poorly understood, partly because learning to process information confounds, and is rarely distinguished from acquiring content-specific memory. Learning to learn changes one’s overall information-processing ability, whereas neurobiological investigations typically focus on memory for content from particular experiences. We investigated entorhinal cortex-to-dentate gyrus neural circuit changes while mice learn to learn during cognitive control training (CCT) to judiciously use and ignore information. CCT changes synaptic circuit function by persistently modifying an excitatory-inhibitory interneuron subcircuit lasting weeks. CCT increases dentate gyrus expression of PKMζ that maintains long-term potentiation, particularly in somatostatin-expressing inhibitory interneurons that mediate both widespread inhibition, and through disinhibition, also local excitation of dentate gyrus. These findings that CCT modifies excitation-inhibition circuit coordination provide direct neurobiological evidence for a CBT-neuroplasticity hypothesis that, beyond particular item/event associations, learning to learn persistently changes neural circuit function.

Background: The complications of chronic kidney disease (CKD) significantly contribute to morbidity and mortality, therefore clinical practice guidelines have been developed to facilitate early detection and treatment. However, given the high prevalence of CKD, many patients with early CKD are seen by non-nephrologists, who need to be aware of CKD complications, screening methods and treatments goals in order to initiate timely therapy and referral.Methods: This was a cross-sectional study conducted at three campuses of the Ziauddin University Hospital, Karachi, Pakistan in 2016. A questionnaire based survey was conducted to assess the knowledge and practices of doctors from various specialties regarding CKD.Results: We performed a questionnaire based survey to assess knowledge and practice patterns in CKD care among 156 doctors. There were 63 male and 50 female respondents. There were 24 attending doctors, 73 post-graduate trainees and 25 house-officers. Our data showed that although CKD risk factors are generally recognized, there is a paucity of knowledge regarding CKD management guidelines and staging of CKD. There is an awareness regarding timely referral to nephrology, but many would still not refer at the appropriate stage. Many also do not use standard equations to calculate Glomerular Filtration rate (GFR) and Creatinine Clearance]. Most do screen for diabetic nephropathy, know about ACE-I/ARBs and provide dietary counseling to CKD patients. The majority do not read medical journals to keep their knowledge up-to-date. Junior doctors (post-graduate trainees and house-officers) fared better than attending doctors in the knowledge and practice parameters.

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