Significant global variation exists in the incidence of lower extremity amputation. Ethnicity and social deprivation play a significant role but it is the role of diabetes and its complications that is most profound. Lower extremity amputation reporting methods demonstrate significant variation with no single standard upon which to benchmark care. Effective standardized reporting methods of major, minor and at-risk populations are needed in order to quantify and monitor the growing multidisciplinary team effect on lower extremity amputation rates globally.

The forebrain cholinergic system promotes higher brain function in part by signaling through the M1 muscarinic acetylcholine receptor (mAChR). During Alzheimer's disease (AD), these cholinergic neurons degenerate, therefore selectively activating M1 receptors could improve cognitive function in these patients while avoiding unwanted peripheral responses associated with non-selective muscarinic agonists. We describe here benzyl quinolone carboxylic acid (BQCA), a highly selective allosteric potentiator of the M1 mAChR. BQCA reduces the concentration of ACh required to activate M1 up to 129-fold with an inflection point value of 845 nM. No potentiation, agonism, or antagonism activity on other mAChRs is observed up to 100 μM. Furthermore studies in M1−/− mice demonstrates that BQCA requires M1 to promote inositol phosphate turnover in primary neurons and to increase c-fos and arc RNA expression and ERK phosphorylation in the brain. Radioligand-binding assays, molecular modeling, and site-directed mutagenesis experiments indicate that BQCA acts at an allosteric site involving residues Y179 and W400. BQCA reverses scopolamine-induced memory deficits in contextual fear conditioning, increases blood flow to the cerebral cortex, and increases wakefulness while reducing delta sleep. In contrast to M1 allosteric agonists, which do not improve memory in scopolamine-challenged mice in contextual fear conditioning, BQCA induces β-arrestin recruitment to M1, suggesting a role for this signal transduction mechanism in the cholinergic modulation of memory. In summary, BQCA exploits an allosteric potentiation mechanism to provide selectivity for the M1 receptor and represents a promising therapeutic strategy for cognitive disorders.

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Until recently, phytopathogenic bacteria have not been considered potential biological weed control candidates because they lack the ability to penetrate intact plants. This deficiency can be overcome by providing entry wounds or using surfactants. Spray application ofPseudomonas syringaepv.tagetis(5 × 108cells/ml) in aqueous buffer with a surfactant produced severe disease in Canada thistle, common ragweed, Jerusalem artichoke, sunflower, and certain other members of the Compositae under field conditions. Spray application of the bacterium without surfactant was ineffective on all reported hosts.Xanthomonas campestrispv.poannuacontrolled annual bluegrass in bermudagrass golf greens when applied by spray during mowing. The bacterium entered through mowing injuries, causing lethal, systemic wilt. Application of the bacterium to annual bluegrass in the absence of fresh mowing injuries failed to produce symptoms. Under field conditions, this previously unknown pathovar's host range was limited to a single subspecies of annual bluegrass, but inundative application to freshly mowed turf resulted in infection of diverse annual bluegrass biotypes. In field trials, six monthly applications resulted in greater than 70% control. The preceding examples are among the first attempts to use foliar phytopathogenic bacteria for biological weed control. Efficacy of these bacterial bioherbicides and of future biocontrol strategies employing bacteria is dependent on facilitated host penetration.

E-learning supplemented with a podcast results in greater knowledge acquisition when compared with a traditional lecture, without a loss of satisfaction with teaching. Using augmented Web-based educational tools reduces demands on teaching time with no decrease in quality for selected parts of the curriculum.