Response of Polish Psychiatric Patients to the Russian Invasion of Ukraine in February 2022―Predictive Role of Risk Perception and Temperamental Traits

This study examined the impact of the Russian invasion of Ukraine in February 2022 on Polish patients with depression and schizophrenia. It has been hypothesized that possible changes in symptoms may be predicted by the subjective risk perception related with the Russo-Ukraine War (RUW) as well as by temperamental traits. The study was conducted with 80 patients with schizophrenia or depression. A questionnaire measuring sociodemographic characteristics, perception of risk, temperamental characteristics, and symptoms of depression and schizophrenia were used as research tools. Symptom intensity was compared with the average symptom intensity calculated on the basis of archival symptom measurements from the three consecutive months preceding the outbreak of the RUW. Predictors of change in symptoms were also analyzed, taking into account sociodemographic variables, the level of risk perception, and temperamental traits. The results indicate the specific patterns of reactions to war danger for patients with different types of psychiatric diagnosis. Depressed patients reacted with an increase in seven symptoms related to unworthiness and/or guilt, lack of interest, and/or pleasure and pessimism. The response of schizophrenic patients was related only with an increase in positive symptoms. This study highlights the need to provide more support to psychiatric patients in acute emergencies

AFM Imaging Reveals Topographic Diversity of Wild Type and Z Variant Polymers of Human α1-Proteinase Inhibitor.

α1-Proteinase inhibitor (antitrypsin) is a canonical example of the serpin family member that binds and inhibits serine proteases. The natural metastability of serpins is crucial to carry out structural rearrangements necessary for biological activity. However, the enhanced metastability of the mutant Z variant of antitrypsin, in addition to folding defect, may substantially contribute to its polymerization, a process leading to incurable serpinopathy. The metastability also impedes structural studies on the polymers. There are no crystal structures of Z monomer or any kind of polymers larger than engineered wild type (WT) trimer. Our understanding of polymerization mechanisms is based on biochemical data using in vitro generated WT oligomers and molecular simulations. Here we applied atomic force microscopy (AFM) to compare topography of monomers, in vitro formed WT oligomers, and Z type polymers isolated from transgenic mouse liver. We found the AFM images of monomers closely resembled an antitrypsin outer shell modeled after the crystal structure. We confirmed that the Z variant demonstrated higher spontaneous propensity to dimerize than WT monomers. We also detected an unexpectedly broad range of different types of polymers with periodicity and topography depending on the applied method of polymerization. Short linear oligomers of unit arrangement similar to the Z polymers were especially abundant in heat-treated WT preparations. Long linear polymers were a prominent and unique component of liver extracts. However, the liver preparations contained also multiple types of oligomers of topographies undistinguishable from those found in WT samples polymerized with heat, low pH or guanidine hydrochloride treatments. In conclusion, we established that AFM is an excellent technique to assess morphological diversity of antitrypsin polymers, which is important for etiology of serpinopathies. These data also support previous, but controversial models of in vivo polymerization showing a surprising diversity of polymer topography

AFM Imaging Reveals Topographic Diversity of Wild Type and Z Variant Polymers of Human α₁-Proteinase Inhibitor - Fig 4

<p><b>Volume distributions of WT α</b>_<b>1</b><b>-PI (A) and Z variant (B) particles.</b> The distributions revealed a prevailing content of objects, which size was consistent with monomers. Surprisingly, the presence of larger molecules was also detected. Among the larger objects, particles with volume approximately twice as big as monomers were the most abundant. The content of dimers and bigger particles was more pronounced in the Z variant (B) than in the wild type (A). The volume of particles was calculated with the grain analysis of SPIP software. Relative count of particles is shown. Total of 847 and 639 particles were analyzed for the WT and Z variant, respectively. Histogram bin size was 5 nm. Fitted normal distribution curves are shown in green for monomers and in blue for dimers, whereas total frequency distribution is represented by red traces (OriginPro).</p

AFM height images of human Z mutant α₁-PI preparations obtained from a PiZ mouse liver.

<p>(A) Images of two representative fragments of fields with α₁-PI particles. The presence of long, linear, often tangled strands of polymers is striking. Arrows in the top image point at the types of particles presented in zoomed-in B to E panels on the right. The examples are marked b to e, respectively. (B)–(E) galleries of zoomed-in images of diverse polymer and oligomer types. In particular: (B) fragments of long polymer fibers with straight, smooth and compact arrangement of units; (C) fragments of long polymer fibers with grainy appearance and loose arrangement of well discernible units; (D) linear, short and thin oligomers with compact arrangement of units; (E) oligomers built from large globular units arranged as “large packed beads”.</p