4-Methylamphetamine (4-MA) is an emerging drug of abuse that acts as a substrate at plasma membrane transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT), thereby causing non-exocytotic release of monoamine transmitters via reverse transport. Prior studies by us showed that increasing the N-alkyl chain length of N-substituted 4-MA analogs converts 4-MA from a transportable substrate (i.e., releaser) at DAT and NET to a non-transported blocker at these sites. Here we studied the effects of the individual optical isomers of N-methyl-, N-ethyl-, and N-n-propyl 4-MA on monoamine transporters and abuse-related behavior in rats because action/function might be related to stereochemistry. Uptake inhibition and release assays were conducted in rat brain synaptosomes whereas electrophysiological assessments of drug-transporter interactions were examined using cell-based biosensors. Intracranial-self stimulation (ICSS) in rats was employed to assess abuse potential in vivo. The experimental evidence demonstrates that S(+)N-methyl 4-MA is a potent and efficacious releaser at DAT, NET, and SERT with the highest abuse potential among the test drugs whereas R(−)N-methyl 4-MA, is a less potent releaser with reduced abuse potential. The S(+)ethyl analog displays decreased efficacy as a releaser at DAT but retains full release activity at NET and SERT with a reduction in abuse-related effects; the R(−)ethyl analog has a similar profile but is less potent. S(+)N-Propyl 4-MA is a non-transported blocker at DAT and NET, but an efficacious releaser at SERT, whereas the R enantiomer is almost inactive. In conclusion, the S enantiomers of the N-alkyl 4-MA analogs are most potent. Lengthening the N-alkyl chain converts compounds from potent non-selective releasers showing abuse-related effects, to more selective SERT releasers with no apparent abuse potential.
Barrier islands are at the forefront of storms and sea-level rise. High disturbance regimes and sediment mobility make these systems sensitive and dynamic. Island foredunes are protective structures against storm-induced overwash that are integrally tied to dune grasses via biogeomorphic feedbacks. Shifts in dune grass dominance could influence dune morphology and susceptibility to overwash, altering island stability. In a glasshouse study, two dune grasses, Ammophila breviligulata and Uniola paniculata, were planted together and subjected to a 20 cm burial to quantify morphological and physiological responses. Burial had positive effects on both plants as indicated by increased electron transport rate and total biomass. Ammophila breviligulata performance declined when planted with U. paniculata. Uniola paniculata was not affected when planted with A. breviligulata but did have higher water use efficiency and nitrogen use efficiency. Planted in mixture, differential reallocation of biomass occurred between species potentially altering resource acquisition further. As U. paniculata migrates into A. breviligulata dominated habitat and A. breviligulata performance diminishes, biotic interactions between these and other species may affect dune formation and community structure. Our study emphasizes the importance of studying biotic interactions alongside naturally occurring abiotic drivers.
For many years, public health in Kentucky has measured the number of clinical visits and other LPHA services but failed to determine specific characteristics and variables that influence community health status. This study suggests that LPHAs in Kentucky can advance public health practice by having well-educated directors, giving annual incremental raises, and utilizing the agency reserve funds to meet budget shortfalls in the short run. Furthermore, LPHAs with an associated home health agency may need to reassess their impact and need in their community, considering the negative effect it may have on county health status.
This study evaluated the two-year clinical outcomes of 3.1 mm diameter dental implants, immediately provisionalized and later restored using same-day dentistry, in 10 patients receiving 11 narrow-diameter (3.1 mm) single implants. Each implant was placed and immediately restored with a provisional crown after placement. At least 2 months after placement, the implant was restored with a prefabricated titanium abutment and an all-ceramic crown using a same-day dentistry protocol. Clinical outcomes, including apical bone loss, probing depths, gingival index, and surgical and prosthetic complications, were documented. There was no implant failure over the course of two years. No surgical complications were reported. Two cases lost provisional crowns. One crown needed to be remade due to esthetic concern. The cumulative two-year survival rate of the implants was 100%. Implant bone loss after two years of functional loading was −0.56 ± 0.54 mm and −0.32 ± 0.68 mm for mesial and distal crestal bone, respectively. Two prosthetic complications included recementation of a crown and remaking of a crown. This exploratory study suggests that immediate provisionalization and a same-day restorative dentistry digital workflow protocol for narrow-diameter implants appear to be predictable clinical procedures with no reported surgical complications and minimal prosthetic complications.
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