A New Genotype of Trichophyton quinckeanum with Point Mutations in Erg11A Encoding Sterol 14-α Demethylase Exhibits Increased Itraconazole Resistance.

Trichophyton quinckeanum, the causative agent of mouse favus, has been responsible for several infections of animal owners in recent years and showed an infection peak around 2020 in Jena, Thuringia. The isolated T. quinckeanum strains from Thuringia differ in some positions of the ITS region compared to strains from the IHEM collection as well as to Trichophyton schoenleinii. All T. quinckeanum strains of the new genotype show up to a 100-fold increased itraconazole resistance as measured by microplate laser nephelometry (MLN) assays. Analysis of genes involved in Trichophyton indotineae azole resistance, such as Erg1, which encodes squalene epoxidase, and Erg11B, one of two copies of the sterol 14-α demethylase gene, show a 100% identity between the two T. quinckeanum genotypes. In contrast, Erg11A fragments differ in 15-nucleotide positions between both T. quinckeanum genotypes, resulting in the unique amino acid substitution Ala256Ser in resistant strains. The new T. quinckeanum genotype may have evolved through interspecies mating. Mating type analysis showed a nearly 100% identity of the minus type MAT1-1-1 fragment for all T. quinckeanum isolates. The closely related Trichophyton schoenleinii belongs to the plus mating type and has 100% identical fragments of Erg1 and Erg11B. Erg11A protein sequences of T. schoenleinii and T. quinckeanum showed increased diversity.

Augmented antibody-based anticancer therapeutics boost neutrophil cytotoxicity.

Most clinically used anticancer mAbs are of the IgG isotype, which can eliminate tumor cells through NK cell-mediated antibody-dependent cellular cytotoxicity and macrophage-mediated antibody-dependent phagocytosis. IgG, however, ineffectively recruits neutrophils as effector cells. IgA mAbs induce migration and activation of neutrophils through the IgA Fc receptor (FcαRI) but are unable to activate NK cells and have poorer half-life. Here, we combined the agonistic activity of IgG mAbs and FcαRI targeting in a therapeutic bispecific antibody format. The resulting TrisomAb molecules recruited NK cells, macrophages, and neutrophils as effector cells for eradication of tumor cells in vitro and in vivo. Moreover, TrisomAb had long in vivo half-life and strongly decreased B16F10gp75 tumor outgrowth in mice. Importantly, neutrophils of colorectal cancer patients effectively eliminated tumor cells in the presence of anti-EGFR TrisomAb but were less efficient in mediating killing in the presence of IgG anti-EGFR mAb (cetuximab). The clinical application of TrisomAb may provide potential alternatives for cancer patients who do not benefit from current IgG mAb therapy.

Relatives' burden of caring for people screened positive for dementia in primary care : Results of the DelpHi study.

BACKGROUND: There is a lack of data describing caregiver burden in primary care where most (informal) caregiving is provided. OBJECTIVE: The aims of the paper are to describe the burden of people caring for persons with dementia (PWD) in primary care in multiple dimensions and to analyze factors associated with specific dimensions of caregiver burden. MATERIAL AND METHODS: Analyses are based on cross-sectional data of the general physician-based, cluster-randomized, controlled intervention trial DelpHi-MV (Dementia: life and person-centered help). A sample of n = 310 community dwelling PWD screened positive for dementia (DemTect < 9) and their caregivers provided sociodemographic and disease-related data, caregiver burden was assessed in 20 dimensions using the Berlin inventory on relatives' burden in dementia (Berliner Inventar zur Angehörigenbelastung - Demenz, BIZA-D). RESULTS: Depending on the dimension of objective burden due to caring, between 71.3 % and 92.3 % of the caregivers reported an objective burden. The average burden ranged from 3.68 to 9.81 (scale range 0-16). The subjective burden due to caring ranged from 0.1 to 1.1 (scale range 0-4). Between 22.6 and 51.6 % of our sample indicated burdens due to perceived conflicts. Logistic regression models associating caregiver burden with specifics of PWD and caregivers reached statistical significance for nearly all dimensions of the BIZA-D. Functional and cognitive impairment were statistically significant factors in 12 out of 20 and 5 out of 20 dimensions, respectively. CONCLUSION: This is first quantitative in-depth analysis of burden for caregiver of people screened positive for dementia in primary care in Germany. In general, caregiver burden was perceived as being low to moderate by caregivers and lower than reported from other settings.