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Background: Most individuals affected by cancer who are treated with certain chemotherapies suffer of CIPN. Therefore, there is a high patient and provider interest in complementary non-pharmacological therapies, but its evidence base has not yet been clearly pointed out in the context of CIPN. Methods: The results of a scoping review overviewing the published clinical evidence on the application of complementary therapies for improving the complex CIPN symptomatology are synthesized with the recommendations of an expert consensus process aiming to draw attention to supportive strategies for CIPN. The scoping review, registered at PROSPERO 2020 (CRD 42020165851), followed the PRISMA-ScR and JBI guidelines. Relevant studies published in Pubmed/MEDLINE, PsycINFO, PEDro, Cochrane CENTRAL, and CINAHL between 2000 and 2021 were included. CASP was used to evaluate the methodologic quality of the studies. Results: Seventy-five studies with mixed study quality met the inclusion criteria. Manipulative therapies (including massage, reflexology, therapeutic touch), rhythmical embrocations, movement and mind–body therapies, acupuncture/acupressure, and TENS/Scrambler therapy were the most frequently analyzed in research and may be effective treatment options for CIPN. The expert panel approved 17 supportive interventions, most of them were phytotherapeutic interventions including external applications and cryotherapy, hydrotherapy, and tactile stimulation. More than two-thirds of the consented interventions were rated with moderate to high perceived clinical effectiveness in therapeutic use. Conclusions: The evidence of both the review and the expert panel supports a variety of complementary procedures regarding the supportive treatment of CIPN; however, the application on patients should be individually weighed in each case. Based on this meta-synthesis, interprofessional healthcare teams may open up a dialogue with patients interested in non-pharmacological treatment options to tailor complementary counselling and treatments to their needs.

A range of novel carboxamide fungicides, inhibitors of the succinate dehydrogenase enzyme (SDH, EC 1.3.5.1) is currently being introduced to the crop protection market. The aim of this study was to explore the impact of structurally distinct carboxamides on target site resistance development and to assess possible impact on fitness. We used a UV mutagenesis approach in Mycosphaerella graminicola, a key pathogen of wheat to compare the nature, frequencies and impact of target mutations towards five subclasses of carboxamides. From this screen we identified 27 amino acid substitutions occurring at 18 different positions on the 3 subunits constituting the ubiquinone binding (Qp) site of the enzyme. The nature of substitutions and cross resistance profiles indicated significant differences in the binding interaction to the enzyme across the different inhibitors. Pharmacophore elucidation followed by docking studies in a tridimensional SDH model allowed us to propose rational hypotheses explaining some of the differential behaviors for the first time. Interestingly all the characterized substitutions had a negative impact on enzyme efficiency, however very low levels of enzyme activity appeared to be sufficient for cell survival. In order to explore the impact of mutations on pathogen fitness in vivo and in planta, homologous recombinants were generated for a selection of mutation types. In vivo, in contrast to previous studies performed in yeast and other organisms, SDH mutations did not result in a major increase of reactive oxygen species levels and did not display any significant fitness penalty. However, a number of Qp site mutations affecting enzyme efficiency were shown to have a biological impact in planta.Using the combined approaches described here, we have significantly improved our understanding of possible resistance mechanisms to carboxamides and performed preliminary fitness penalty assessment in an economically important plant pathogen years ahead of possible resistance development in the field.