Sacral neuromodulation therapy of the lower urinary tract: A review of the literature and unanswered questions

Objective: To review the evidence surrounding Sacral Neuromodulation therapy and delineate areas that will need more research. Methods: An extensive search was performed on the available literature on SNM for lower urinary tract dysfunction. Based on the results of the search, the mechanisms of action, indications, technique, and patient characteristics of therapy failures and success are presented and discussed. Results: SNM is accepted by the FDA since 1997 for the treatment of lower urinary tract dysfunction. As it is a relatively new procedure, there are variations in the technique of lead placement, generator choice, testing interval, patient selection, time to explantation, and definitions of therapy failures and successes. Conclusions: SNM is a safe and therapeutic option for the treatment of urgencyfrequency syndrome, urge incontinence, and idiopathic urinary retention. However, there are multiple unanswered questions that require extensive research.

Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer disease

OBJECTIVE Alzheimer disease(AD)is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited.Over-activation of N-methyl-D-aspar⁃tate(NMDA)receptors,amyloidβ(Aβ)aggrega⁃tion,a decrease in cerebral blood flow(CBF),and downstream pathological events play impor⁃tant roles in the disease progression of AD.This study seeks to explore the efficacy and mecha⁃nism of action of MN-08,a novel memantine ni⁃trate,in established animal models of AD.METHODS MN-08′s effectiveness as a preventative and therapeutic agent was tested in 2-to 8-month-old APP/PS1 transgenic mice and 9-to 12-month-old 3×Tg-AD mice,respectively.The neuroprotective mechanism of MN-08 was tested in the glutamate cell model.The pharmacokinet⁃ics and safety of MN-08 in vivo were determined in normal rats and beagle dogs.For the behavioral test,Western blotting analysis,pathology,ELISA test and in vitro cell tests,investigators were blinded to the experimental grouping and drug treatment.RESULTS MN-08,a novel meman⁃tine nitrate,was found to inhibit Aβaccumulation,prevent neuronal and dendritic spine loss,and consequently attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice(for a 6-month preventative course)and in the 8-month-old triple-transgenic(3×Tg-AD)mice(for a 4-month therapeutic course).In vitro,MN-08 could bind to and antagonize NMDA receptors,inhibit the calcium influx,and reverse the dysregula⁃tions of ERK and PI3K/Akt/GSK3βpathway,sub⁃sequently preventing glutamate-induced neuro⁃nal loss.In addition,MN-08 had favorable phar⁃macokinetics,blood-brain barrier penetration,and safety profiles in rats and beagle dogs.CON⁃CLUSION The novel memantine nitrate MN-08 may be a useful therapeutic agent for AD.

Effects of key design parameters of tine furrow opener on soil seedbed properties

The structural parameters of tine furrow openers have significant effects on soil property of seed furrow in no-till planting,thereby affecting crop growth and yields.In order to analyze the effects of key parameters of tine furrow openers on soil properties(soil bulk density,soil water-stable aggregates(WSA),and soil disturbance)of the surface soil layer of 0-10 cm and surface straw disturbance,the tine furrow openers with different structural parameters,including cutting edge thickness,cutting edge curve,penetration clearance angle and rake angle,were designed and tested under no-till conditions.Orthogonal test and single factor test were performed to analyze the effects of different parameters.Results showed that the rake angle,cutting edge thickness and cutting edge curve had significant effects on cross-sectional area of furrow(Af)and disturbance of surface straw;the rake angle had a significant effect on soil bulk density.Soil types and operating depth had significant effects on soil disturbance caused by tine furrow openers.The concave type tine furrow opener produced the lowest soil disturbance and soil bulk density of seed furrow,the highest surface straw disturbance and the greatest content of WSA(>0.5 mm).With increasing rake angles of tine furrow opener,the width of seedbed(Wsb)and the Af decreased first and then increased,respectively,while the width of soil throw(Wst)and the height of ridge(Hr)increased.The Wsb and Af created by tine furrow opener with 60°rake angle were significantly lower than that with others,respectively.The tine furrow opener with rake angle ranged from 45°to 60°created the lowest soil bulk density.As the penetration clearance angle increased,the content of WSA(>0.5 mm)decreased,but the effect of penetration clearance angle on the content of WSA(<0.5 mm)was not significant.The cutting edge thickness(<2 mm)had no significant effects on soil properties of seedbed.This study could provide a reference for optimal design of the tine furrow opener to create more suitable seedbed environment,and promote the application of the light no-till planters.