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Knowledge levels and attitudes of nursing trainees regarding sexuality in old age - An explorative quantitative survey Abstract. Background: In professional geriatric nursing, sexuality in old age is often tabooed - in spite of this demographic group having the desire to live their sexuality. Generally, the possibility to experience sexuality - for example in nursing homes - is limited. Aim: The main objective of this study is to portray the knowledge and attitudes of geriatric nursing trainees towards sexuality in old age in cross section, and to analyze possible differences between training years. Methods: A cross-sectional study was conducted with written standardized surveys of 420 trainees on three research questions: (1) sexuality in old age and its role during class, (2) subjective vs. objective sex education, and (3) sexual assistance and attitudes towards it. Differences between years of education and subgroups were analyzed statistically (Kruskal-Wallis- and chi-square tests). Results: Results showed that addressing sexuality in old age during lessons was perceived to increase with a higher training year. However, 15.1 % experienced it as being exclusively negative. Concerning objective sex education, 15.7 % misjudged frequent masturbation as being psychologically harmful or did not know better. Furthermore, 9.3 % believed homosexuality to be a disease. Differences between years of training could not be found in these variables. The knowledge about sexual assistance increased with higher training years. Conclusions: Regarding these results, we suggest that the subject of sexuality in old age should be intensified as part of the curriculum for geriatric nursing from an early stage on. The aim should be to reduce tabooing and to increase the level of knowledge.

Current therapies for Alzheimer's disease seek to correct for defective cholinergic transmission by preventing the breakdown of acetylcholine through inhibition of acetylcholinesterase, these however have limited clinical efficacy. An alternative approach is to directly activate cholinergic receptors responsible for learning and memory. The M1-muscarinic acetylcholine (M1) receptor is the target of choice but has been hampered by adverse effects. Here we aimed to design the drug properties needed for a well-tolerated M1-agonist with the potential to alleviate cognitive loss by taking a stepwise translational approach from atomic structure, cell/tissue-based assays, evaluation in preclinical species, clinical safety testing, and finally establishing activity in memory centers in humans. Through this approach, we rationally designed the optimal properties, including selectivity and partial agonism, into HTL9936-a potential candidate for the treatment of memory loss in Alzheimer's disease. More broadly, this demonstrates a strategy for targeting difficult GPCR targets from structure to clinic., Competing Interests: Declaration of interests T.T. and M.W. are shareholders and board members of Sosei Heptares. The authors A.J.H.B., G.A.B., K.A.B., J.B., J.E.C., M.S.C., R.M.C., J.C.E., E.H., A.J., C.J.L., J.L., F.H.M., P.J.N., K.O., G.O., J.C.P., M.P., N.R., P.R., B.G.T., R.T.S., C.d.G., G.M., and B.T. are or have been employees of Heptares Therapeutics and are shareholders of Sosei Heptares., (Copyright © 2021. Published by Elsevier Inc.)

N-(3,5-Dichloro-1-oxido-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 351591) has been identified as a potent (IC(50) = 58 nM) and highly selective type 4 phosphodiesterase (PDE4) inhibitor with oral bioactivity in several animal models of lung inflammation. N-(3,5-Dichloro-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 365351), the only significant in vivo metabolite, is also a potent and highly selective PDE4 inhibitor (IC(50) = 20 nM). Both SCH 351591 and SCH 365351 inhibited cytokine production in human blood mononuclear cell preparations. Oral SCH 351591 significantly attenuated allergen-induced eosinophilia and airway hyperreactivity in allergic guinea pigs at doses as low as 1 mg/kg. In this model, oral SCH 365351 showed similar potency. When SCH 351591 was administered orally to allergic cynomolgus monkeys at 3 mg/kg, Ascaris suum-induced lung eosinophilia was blocked. Hyperventilation-induced bronchospasm in nonallergic guinea pigs, a model for exercise-induced asthma, was also suppressed significantly by oral SCH 351591 at 0.3 mg/kg. Cilomilast (SB 207499; Ariflo), a PDE4 inhibitor currently being developed for asthma and chronic obstructive pulmonary disease (COPD), was 10- to 30-fold less potent than SCH 351591 at inhibiting guinea pig lung eosinophilia and hyperventilation-induced bronchospasm. In a ferret model of emesis, maximum nonemetic oral doses of SCH 351591 and cilomilast were 5 and 1 mg/kg, respectively. Comparison of plasma levels at these nonemetic doses in ferrets to those at doses inhibiting hyperventilation-induced bronchospasm in guinea pigs gave a therapeutic ratio of 16 for SCH 351591 and 4 for cilomilast. Thus, SCH 351591 exhibits a promising preclinical profile as a treatment for asthma and COPD.

The synthesis and pharmacological profile of a novel series of 7-methoxybenzofuran-4-carboxamides is described. Some of these compounds were found to be potent inhibitors of phosphodiesterase type 4 (PDE4).

1. Phosphodiesterase (PDE) 4 inhibitors have been shown to inhibit eosinophil PDE4 activity in vitro and accumulation of eosinophils in experimental airways inflammation. However, direct effects on eosinophil trafficking have not been studied in detail and it is not known if activity in vitro translates into efficacy in vivo. In the present study, we compared the activity of five PDE4 inhibitors in vitro and against trafficking of (111)In-eosinophils in cutaneous inflammation in the guinea-pig. 2. The rank order of potency for inhibition of PDE4 activity in guinea-pig eosinophil, neutrophil and macrophage, and human neutrophil lysates was RP73401 > SB207499 >CDP840 > rolipram > LAS31025. On TNFalpha production by human PBMC, all inhibitors with the exception of rolipram showed potency similar to their effect on neutrophil lysates. 3. In a brain cerebellum binding assay, the rank order of potency at displacing [3H]-rolipram was RP73401 > rolipram > SB207499 > CDP840 > LAS30125. 4. Trafficking of (111)In-eosinophils to skin sites injected with PAF, ZAP or antigen in sensitized sites was inhibited by oral administration of all PDE4 inhibitors. The rank order of potency was RP73401 = rolipram > LAS31025 > SB207499 > CDP840. 5. With the exception was RP73401, which was the most potent compound in all assays, there was no clear relationship between activity of PDE4 inhibitors in vitro and capacity to inhibit eosinophil trafficking in vivo. Thus, we conclude that in vitro activity of PDE4 inhibitors does not predict in vivo efficacy in an experimental model of eosinophil trafficking.

Novel xanthine analogues are described which are selective PDE4 inhibitors with improved therapeutic potential over theophylline.

The synthesis and pharmacological profile of a novel series of potent and selective phosphodiesterase type IV (PDE IV) inhibitors is described.

A series of novel selective phosphodiesterase 4 (PDE4) inhibitors has been developed which displays activity both in vitro and in vivo. These compounds possess good selectivity for the catalytic site of PDE4 over the high affinity Rolipram binding site. In vivo studies demonstrate a reduced propensity to display the emetic side effects which are commonly observed with PDE4 inhibitors.