Psychological impact amongst patients with COVID-19 in Perak state.

INTRODUCTION: Psychological distress had been documented since the beginning of the COVID-19 outbreak in 2019. The aim of the study is to describe the psychological impact among those who were hospitalized for COVID-19 infection within 6 months after being discharged from the hospital. The psychological impact in this study is defined as depression, anxiety, and stress. MATERIALS AND METHODS: This was a cross-sectional study conducted from July 2020 till August 2021 in a regional state hospital, north of Malaysia. All patients requiring hospitalization for COVID-19 were approached within the first 2 weeks after admission to administer the Depression, Anxiety and Stress Scale - 21 Items (DASS-21) scale. Follow-up phone calls were made within 3 months of discharged to enquire about the DASS-21 items as well as the Impact of Event Scale-Revised (IES-R) scale items. Participants above the age of 18 and technology savvy to answer an online questionnaire were recruited for the study. We excluded participants with a known history of psychotic disorder from the study. We utilised the DASS-21 to screen for depression, anxiety, and stress, as well as the IES-R to identify symptoms of post-traumatic stress disorder. Participants could answer the questionnaires in either English or Bahasa Malaysia. For comparison of two categorical data, a chi-square was applied. A univariate analysis was first conducted and all variables with a p ≤0.3 was then entered into the multivariate analysis for the final output. Other than the univariate analysis, all other p values <0.05 were considered to be statistically significant. All data collected were tabulated and analysed in the SPSS v21.0 system. RESULTS: A total of 306 out of 696 COVID-19 patients responded. The mean age for the participants was 31.69 (SD:11.19) years old. From the total, 54.2% were ladies, 78.8% were Malay, 50.7% were unmarried, 55.2% had higher education, and 67.6% were employed at the time of the survey. We found 20.5% of the participants were depressed, 38.9% had moderate anxiety, and 17.3% were stressed. From the total, 31.7% of the participants were deemed to have had some symptoms of post-traumatic stress disorder (PTSD) ranging from mild to severe. From the final multivariate analysis, it was found that depression (p=0.02) had a 2.78 times likeliness of having PTSD, anxiety (p<0.001) had a 3.35 times likeliness of having PTSD and stressed patients (p=0.02) 2.86 times likeliness of having PTSD when compared to those without PTSD. CONCLUSION: Patients reported to suffer from symptoms of PTSD and might benefit from psychological interventions to mitigate the impact in the long run.

Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly.

The p21-activated kinase PAK is targeted to focal complexes (FCs) through interactions with the SH3 domains of the PAK-interacting exchange factor PIX and Nck. PIX is a Rac GTP exchange factor that also binds the G-protein-coupled receptor kinase-interacting protein known as GIT1. Overexpression of GIT1 in fibroblasts or epithelial cells causes a loss of paxillin from FCs and stimulates cell motility. This is due to the direct interaction of a C-terminal 125-residue domain of GIT1 with paxillin, under the regulation of PIX. In its activated state, GIT1 can promote FC disassembly independent of actin-myosin contractile events. Additionally, GIT directly couples to a key component of FCs, focal adhesion kinase (FAK), via a conserved Spa2 homology domain. We propose that GIT1 and FAK cooperate to promote motility both by directly regulating focal complex dynamics and by the activation of Rac.

PAK kinases are directly coupled to the PIX family of nucleotide exchange factors.

The PAK family of kinases are regulated through interaction with the small GTPases Cdc42 and Rac1, but little is known of the signaling components immediately upstream or downstream of these proteins. We have purified and cloned a new class of Rho-p21 guanine nucleotide exchange factor binding tightly through its N-terminal SH3 domain to a conserved proline-rich PAK sequence with a Kd of 24 nM. This PAK-interacting exchange factor (PIX), which is widely expressed and enriched in Cdc42- and Rac1-driven focal complexes, is required for PAK recruitment to these sites. PIX can induce membrane ruffling, with an associated activation of Rac1. Our results suggest a role for PIX in Cdc42-to-Rac1 signaling, involving the PIX/PAK complex.

Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes.

The family of p21-activated protein kinases (PAKs) appear to be present in all organisms that have Cdc42-like GTPases. In mammalian cells, PAKs have been implicated in the activation of mitogen-activated protein kinase cascades, but there are no reported effects of these kinases on the cytoskeleton. Recently we have shown that a Drosophila PAK is enriched in the leading edge of embryonic epithelial cells undergoing dorsal closure (N. Harden, J. Lee, H.-Y. Loh, Y.-M. Ong, I. Tan, T. Leung, E. Manser, and L. Lim, Mol. Cell. Biol. 16:1896-1908, 1996), where it colocalizes with structures resembling focal complexes. We show here by transfection that in epithelial HeLa cells alpha-PAK is recruited from the cytoplasm to distinct focal complexes by both Cdc42(G12V) and Rac1(G12V), which themselves colocalize to these sites. By deletion analysis, the N terminus of PAK is shown to contain targeting sequences for focal adhesions which indicate that these complexes are the site of kinase function in vivo. Cdc42 and Rac1 cause alpha-PAK autophosphorylation and kinase activation. Mapping alpha-PAK autophosphorylation sites has allowed generation of a constitutively active kinase mutant. By fusing regions of Cdc42 to the C terminus of PAK, activated chimeras were also obtained. Plasmids encoding these different constitutively active alpha-PAKs caused loss of stress fibers when introduced into both HeLa cells and fibroblasts, which was similar to the effect of introducing Cdc42(G12V) or Rac1(G12V). Significantly dramatic losses of focal adhesions were also observed. These combined effects resulted in retraction of the cell periphery after plasmid microinjection. These data support our previous suggestions of a role for PAK downstream of both Cdc42 and Rac1 and indicate that PAK functions include the dissolution of stress fibers and reorganization of focal complexes.