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Targeting synaptic dysfunction in Alzheimer's disease therapy.
Nistic?, Robert,Pignatelli, Marco,Piccinin, Sonia,Mercuri, Nicola B,Collingridge, Graham Humana Press 2012 Molecular neurobiology Vol.46 No.3
<P>In the past years, major efforts have been made to understand the genetics and molecular pathogenesis of Alzheimer's disease (AD), which has been translated into extensive experimental approaches aimed at slowing down or halting disease progression. Advances in transgenic (Tg) technologies allowed the engineering of different mouse models of AD recapitulating a range of AD-like features. These Tg models provided excellent opportunities to analyze the bases for the temporal evolution of the disease. Several lines of evidence point to synaptic dysfunction as a cause of AD and that synapse loss is a pathological correlate associated with cognitive decline. Therefore, the phenotypic characterization of these animals has included electrophysiological studies to analyze hippocampal synaptic transmission and long-term potentiation, a widely recognized cellular model for learning and memory. Transgenic mice, along with non-Tg models derived mainly from exogenous application of Aβ, have also been useful experimental tools to test the various therapeutic approaches. As a result, numerous pharmacological interventions have been reported to attenuate synaptic dysfunction and improve behavior in the different AD models. To date, however, very few of these findings have resulted in target validation or successful translation into disease-modifying compounds in humans. Here, we will briefly review the synaptic alterations across the different animal models and we will recapitulate the pharmacological strategies aimed at rescuing hippocampal plasticity phenotypes. Finally, we will highlight intrinsic limitations in the use of experimental systems and related challenges in translating preclinical studies into human clinical trials.</P>
Luo Jessica,Willis Rhett N.,Ohlsen Suzanna M.,Piccinin Meghan,Moores Neal,Kwok Alvin C.,Agarwal Jayant P. 대한성형외과학회 2022 Archives of Plastic Surgery Vol.49 No.1
The introduction of acellular dermal matrix (ADM) to breast reconstruction has allowed surgeons to reexplore the prepectoral implant placement technique in postmastectomy breast reconstruction. Our institution adopted a novel approach using meshed ADM to lessen the financial burden of increased ADM utilization with the prepectoral breast reconstruction. This is a retrospective, single-center review of two-stage prepectoral breast reconstruction using meshed human-derived ADM for anterior prosthesis coverage. Patient demographics, oncologic data, perioperative characteristics, and complications were examined and reported as means with standard deviations. Cost-saving with the meshed technique was evaluated. Forty-eight patients (72 breasts) with a mean age of 48.5 ± 15.0 years (range 26–70 years) were included in the study. The mean follow-up time was 13.2 ± 4.4 months (range 4.1–25.8 months). Nineteen breasts (24.6%) experienced complications, with seromas being the most common complication (12.5%, n = 9). Expander removal and reoperation occurred at a rate of 8.3 and 9.7%, respectively. The average time to drain removal was 18.8 ± 6.6 days (range 8–32 days). Meshed ADM provided an average cost savings of $6,601 for unilateral and $13,202 for bilateral reconstructions. Our study found that human-derived meshed ADM can be safely used in two-staged prepectoral tissue expander-based breast reconstruction and can result in significant cost savings.
Luo Jessica,Willis Rhett N.,Ohlsen Suzanna M.,Piccinin Meghan,Moores Neal,Kwok Alvin C.,Agarwal Jayant P. 대한성형외과학회 2022 Archives of Plastic Surgery Vol.49 No.2
The introduction of acellular dermal matrix (ADM) to breast reconstruction has allowed surgeons to reexplore the prepectoral implant placement technique in postmastectomy breast reconstruction. Our institution adopted a novel approach using meshed ADM to lessen the financial burden of increased ADM utilization with the prepectoral breast reconstruction. This is a retrospective, single-center review of two-stage prepectoral breast reconstruction using meshed human-derived ADM for anterior prosthesis coverage. Patient demographics, oncologic data, perioperative characteristics, and complications were examined and reported as means with standard deviations. Cost-saving with the meshed technique was evaluated. Forty-eight patients (72 breasts) with a mean age of 48.5 ± 15.0 years (range 26–70 years) were included in the study. The mean follow-up time was 13.2 ± 4.4 months (range 4.1–25.8 months). Nineteen breasts (24.6%) experienced complications, with seromas being the most common complication (12.5%, n = 9). Expander removal and reoperation occurred at a rate of 8.3 and 9.7%, respectively. The average time to drain removal was 18.8 ± 6.6 days (range 8–32 days). Meshed ADM provided an average cost savings of $6,601 for unilateral and $13,202 for bilateral reconstructions. Our study found that human-derived meshed ADM can be safely used in two-staged prepectoral tissue expander-based breast reconstruction and can result in significant cost savings.