February 23, 2024

“identify a feature of your product or service that is unique or so uncommon that it can’t be obtained elsewhere at the same price or at all”

2:59 PM

“scarcity applies not only to the count of items but also to the traits or elements of the items”

2:59 PM

“The wording change I proposed began by assigning to her clients *possession* of something they wanted, “We have a deal,” which they would *lose* if they failed to compromise”

3:54 PM

“when a desirable item is rare or unavailable, consumers no longer base its fair price on perceived quality; instead, they base it on the item’s scarcity”

3:54 PM

“Ongoing neurovascular dysfunction contributes to type 2 diabetes mellitus (T2DM)-induced cognitive deficits.”

8:13 AM

“early post onset of T2DM interventions may reduce evolving neurovascular dysfunction and thereby lead to diminution of T2DM-induced cognitive deficits”

8:14 AM

“neurovascular changes in T2DM rats treated with exosomes derived from cerebral endothelial cells (CEC-Exos)”

8:16 AM

“CEC-Exos twice weekly or saline for 4 consecutive weeks”

9:29 AM

“T2DM induces neurovascular dysfunction and is a risk factor for cognitive deficits ([2](javascript:;)), and neurovascular dysfunction in midlife is highly related to the development of Alzheimer disease and dementia later in life”

9:30 AM

“exosomes derived from mesenchymal stromal cells improve neurological outcome in rodent models of stroke and traumatic brain injury”

9:31 AM

“The parent cells determine the exosome cargo profile, which affects recipient cell biological function”

9:32 AM

“Microvascular endothelial dysfunction has recently emerged as a significant risk factor for the development of [cognitive impairment](https://www.sciencedirect.com/topics/medicine-and-dentistry/cognitive-defect)”

7:43 AM

“obesity-related hyperinsulinemia/insulin resistance, systemic inflammation, and gut [dysbiosis](https://www.sciencedirect.com/topics/medicine-and-dentistry/dysbiosis) lead to cognitive impairment through induction of endothelial dysfunction and disruption of the blood brain barrier.”

7:43 AM

“[Endothelial dysfunction](https://www.sciencedirect.com/topics/medicine-and-dentistry/endothelial-dysfunction) disrupts blood flow, reduces vascular tone, and impairs the blood brain barrier (BBB)”

7:45 AM

“Endothelial cells are responsible for maintaining [vascular tone](https://www.sciencedirect.com/topics/medicine-and-dentistry/blood-vessel-tone), regulating blood flow, modulating the inflammatory response, and the trafficking of molecules between the periphery and the brain”

7:45 AM

“This is mediated in part by disruption in specialized receptors on endothelial cells that transduce mechanical and chemical stimuli to facilitate the release of signaling molecules such as [nitric oxide](https://www.sciencedirect.com/topics/medicine-and-dentistry/nitric-oxide) (NO), [endothelin](https://www.sciencedirect.com/topics/medicine-and-dentistry/endothelin), and [prostanoids](https://www.sciencedirect.com/topics/medicine-and-dentistry/prostanoid).”

7:45 AM

“Insulin resistance is characterized by reductions in phosphoinositide 3-kinase (PI3K) signaling and increased mitogen-activated protein [kinase signaling](https://www.sciencedirect.com/topics/medicine-and-dentistry/kinase-signaling), which leads to decreased NO production, a characteristic of endothelial dysfunction”

7:48 AM

“Obesity induced disruption of NO has been linked to impaired neurovascular coupling in preclinical models”

7:51 AM

“this impairment in neurovascular coupling has been associated with cognitive impairment and [neurodegeneration](https://www.sciencedirect.com/topics/medicine-and-dentistry/neurodegeneration)”

7:51 AM

“Vascular contributions to cognitive impairment has been increasingly recognized in both preclinical and clinical studies”

7:56 AM

“BBB breakdown precedes and activates [neuroinflammation](https://www.sciencedirect.com/topics/medicine-and-dentistry/neuroinflammation) and [neurodegeneration](https://www.sciencedirect.com/topics/medicine-and-dentistry/neurodegeneration).”

7:56 AM

“aged mice fed a HFD for 24 months had decreased hippocampal microvascular density accompanied by impairments in hippocampal-dependent cognitive function”

7:57 AM

“infiltration of serum-derived substances into the hippocampal space allows for microglial activation and subsequent reductions in endothelial cell tight junction protein expression in obesity”

7:58 AM

“obesity-induced systemic inflammation is associated with poorer cognitive outcomes”

8:00 AM

“The incidence of diabetes-associated cognitive dysfunction (DACD) among diabetic individuals is currently 13.5%, which seriously impacts self-glycemic management and may lead to life-threatening complications, including hypoglycemia, hyperglycemic hyperosmotic coma, and ketoacidosis.”

1:44 AM

“The worldwide prevalence of diabetes is predicted to exceed 640 million by 2040. [1](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext#bib1) GBD 2017 Disease and Injury Incidence and Prevalence Collaborators Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. *Lancet.* 2018; 392: 1789-1858 • [Summary](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_1_2&dbid=4&doi=10.1016/j.ebiom.2023.104653&key=10.1016%2FS0140-6736%2818%2932279-7&cf=abstract&site=lancet-site) • [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_1_2&dbid=4&doi=10.1016/j.ebiom.2023.104653&key=10.1016%2FS0140-6736%2818%2932279-7&cf=fulltext&site=lancet-site) • [Full Text PDF](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_1_2&dbid=4&doi=10.1016/j.ebiom.2023.104653&key=10.1016%2FS0140-6736%2818%2932279-7&cf=pdf&site=lancet-site) • [PubMed](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_1_2&dbid=8&doi=10.1016/j.ebiom.2023.104653&key=30496104&cf=) • [Scopus (8024)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_1_2&dbid=137438953472&doi=10.1016/j.ebiom.2023.104653&key=2-s2.0-85056201393&cf=) • [Google Scholar](http://scholar.google.com/scholar_lookup?hl=en&volume=392&publication_year=2018&pages=1789-1858&journal=Lancet&author=GBD+2017+Disease+and+Injury+Incidence+and+Prevalence+Collaborators&title=Global%2C+regional%2C+and+national+incidence%2C+prevalence%2C+and+years+lived+with+disability+for+354+diseases+and+injuries+for+195+countries+and+territories%2C+1990-2017%3A+a+systematic+analysis+for+the%C2%A0Global+Burden+of+Disease+Study+2017) [](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext/#) , [2](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext#bib2) • Zilliox L.A. • Chadrasekaran K. • Kwan J.Y. • Russell J.W. Diabetes and cognitive impairment. *Curr Diab Rep.* 2016; 16: 87 • [Crossref](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=16&doi=10.1016/j.ebiom.2023.104653&key=10.1007%2Fs11892-016-0775-x&cf=) • [PubMed](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=8&doi=10.1016/j.ebiom.2023.104653&key=27491830&cf=) • [Scopus (284)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=137438953472&doi=10.1016/j.ebiom.2023.104653&key=2-s2.0-84982845400&cf=) • [Google Scholar](http://scholar.google.com/scholar_lookup?hl=en&volume=16&publication_year=2016&pages=87&journal=Curr+Diab+Rep&author=Zilliox+L.A.&author=Chadrasekaran+K.&author=Kwan+J.Y.&author=Russell+J.W.&title=Diabetes+and+cognitive+impairment) [](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext/#) Furthermore, the incidence of diabetes-associated cognitive dysfunction (DACD) among diabetic individuals is currently 13.5% [3](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext#bib3) • Gao Y. • Xiao Y. • Miao R. • et al. The prevalence of mild cognitive impairment with type 2 diabetes mellitus among elderly people in China: a cross-sectional study. *Arch Gerontol Geriatr.* 2016; 62: 138-142 • [Crossref](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=16&doi=10.1016/j.ebiom.2023.104653&key=10.1016%2Fj.archger.2015.09.003&cf=) • [PubMed](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=8&doi=10.1016/j.ebiom.2023.104653&key=26381432&cf=) • [Scopus (64)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016/j.ebiom.2023.104653&key=2-s2.0-84952987053&cf=) • [Google Scholar](http://scholar.google.com/scholar_lookup?hl=en&volume=62&publication_year=2016&pages=138-142&journal=Arch+Gerontol+Geriatr&author=Gao+Y.&author=Xiao+Y.&author=Miao+R.&title=The+prevalence+of+mild+cognitive+impairment+with+type+2+diabetes+mellitus+among+elderly+people+in+China%3A+a+cross-sectional+study) [](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext/#) and may is over 24.2% in those above 75 years old. [4](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext#bib4) • Biessels G.J. • Whitmer R.A. Cognitive dysfunction in diabetes: how to implement emerging guidelines. *Diabetologia.* 2020; 63: 3-9 • [Crossref](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=16&doi=10.1016/j.ebiom.2023.104653&key=10.1007%2Fs00125-019-04977-9&cf=) • [PubMed](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=8&doi=10.1016/j.ebiom.2023.104653&key=31420699&cf=) • [Scopus (109)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=137438953472&doi=10.1016/j.ebiom.2023.104653&key=2-s2.0-85071048858&cf=) • [Google Scholar](http://scholar.google.com/scholar_lookup?hl=en&volume=63&publication_year=2020&pages=3-9&journal=Diabetologia&author=Biessels+G.J.&author=Whitmer+R.A.&title=Cognitive+dysfunction+in+diabetes%3A+how+to+implement+emerging+guidelines) [](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext/#) DACD is mainly characterized by diabetes-associated cognitive decrement, mild cognitive impairment, and dementia. [5](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext#bib5) • Biessels G.J. • Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. *Nat Rev Endocrinol.* 2018; 14: 591-604 • [Crossref](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_5_2&dbid=16&doi=10.1016/j.ebiom.2023.104653&key=10.1038%2Fs41574-018-0048-7&cf=) • [PubMed](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_5_2&dbid=8&doi=10.1016/j.ebiom.2023.104653&key=30022099&cf=) • [Scopus (637)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_5_2&dbid=137438953472&doi=10.1016/j.ebiom.2023.104653&key=2-s2.0-85050161551&cf=) • [Google Scholar](http://scholar.google.com/scholar_lookup?hl=en&volume=14&publication_year=2018&pages=591-604&journal=Nat+Rev+Endocrinol&author=Biessels+G.J.&author=Despa+F.&title=Cognitive+decline+and+dementia+in+diabetes+mellitus%3A+mechanisms+and+clinical+implications) [](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext/#) These symptoms seriously impact self-glycemic management and may lead to critical complications, including hypoglycemia, hyperglycemic hyperosmotic coma, and ketoacidosis. As the most serious stage of DACD, dementia is the second leading cause of death among individuals with diabetes. [6](https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00218-9/fulltext#bib6) • Pearson-Stuttard J. • Bennett J. • Cheng Y.J. • et al. Trends in predominant causes of death in individuals with and without diabetes in England from 2001 to 2018: an epidemiological analysis of linked primary care records. *Lancet Diabetes Endocrinol.* 2021; 9: 165-173 • [Summary](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016/j.ebiom.2023.104653&key=10.1016%2FS2213-8587%2820%2930431-9&cf=abstract&site=lancet-site) • [Full Text](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016/j.ebiom.2023.104653&key=10.1016%2FS2213-8587%2820%2930431-9&cf=fulltext&site=lancet-site) • [Full Text PDF](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=4&doi=10.1016/j.ebiom.2023.104653&key=10.1016%2FS2213-8587%2820%2930431-9&cf=pdf&site=lancet-site) • [PubMed](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=8&doi=10.1016/j.ebiom.2023.104653&key=33549162&cf=) • [Scopus (147)](https://www.thelancet.com/servlet/linkout?suffix=e_1_5_1_2_6_2&dbid=137438953472&doi=10.1016/j.ebiom.2023.104653&key=2-s2.0-85101052396&cf=) • [Google Scholar](http://scholar.google.com/scholar_lookup?hl=en&volume=9&publication_year=2021&pages=165-173&journal=Lancet+Diabetes+Endocrinol&author=”

1:46 AM