Impact of anxiety and depression on disease activity and quality of life in patients with lupus nephritis.

Background of the Study: Lupus is an autoimmune disease that affects multiple body systems and requires long-term treatment. The multisystem effect of this disease and long treatment may cause anxiety and depression in patients with lupus nephritis (LN) and ultimately deteriorate their quality of life and also affects the activity of the disease. Aim of the Study: This study aims to assess anxiety, depression, and quality of life in patients with LN and their relationship with disease activity. Material and Methods: A descriptive cross-sectional study was conducted to assess anxiety, depression, and quality of life among patients with LN. A total enumerative technique was used for the recruitment of 100 patients and data collected using standardized tools were analyzed. Results: The results of the study showed that the majority of patients (60.0%) with LN had moderate anxiety and most of them (61.0%) had moderate depression that affected their quality of life and impacted the disease activity index in lupus. Conclusion: LN patients experience significant levels of anxiety and depression, which deteriorates their quality of life and negatively impacts disease activity. Active surveillance for these conditions and early diagnosis might help in the improvement of health-related outcomes in such patients.

Doubly Constrained C-terminal of Roc (COR) Domain-Derived Peptides Inhibit Leucine-Rich Repeat Kinase 2 (LRRK2) Dimerization.

Missense mutations along the leucine-rich repeat kinase 2 (LRRK2) protein are a major contributor to Parkinson's Disease (PD), the second most commonly occurring neurodegenerative disorder worldwide. We recently reported the development of allosteric constrained peptide inhibitors that target and downregulate LRRK2 activity through disruption of LRRK2 dimerization. In this study, we designed doubly constrained peptides with the objective of inhibiting C-terminal of Roc (COR)-COR mediated dimerization at the LRRK2 dimer interface. We show that the doubly constrained peptides are cell-permeant, bind wild-type and pathogenic LRRK2, inhibit LRRK2 dimerization and kinase activity, and inhibit LRRK2-mediated neuronal apoptosis, and in contrast to ATP-competitive LRRK2 kinase inhibitors, they do not induce the mislocalization of LRRK2 to skein-like structures in cells. This work highlights the significance of COR-mediated dimerization in LRRK2 activity while also highlighting the use of doubly constrained peptides to stabilize discrete secondary structural folds within a peptide sequence.

Combined FCS and PCH Analysis to Quantify Protein Dimerization in Living Cells.

Protein dimerization plays a crucial role in the regulation of numerous biological processes. However, detecting protein dimers in a cellular environment is still a challenge. Here we present a methodology to measure the extent of dimerization of GFP-tagged proteins in living cells, using a combination of fluorescence correlation spectroscopy (FCS) and photon counting histogram (PCH) analysis of single-color fluorescence fluctuation data. We named this analysis method brightness and diffusion global analysis (BDGA) and adapted it for biological purposes. Using cell lysates containing different ratios of GFP and tandem-dimer GFP (diGFP), we show that the average brightness per particle is proportional to the fraction of dimer present. We further adapted this methodology for its application in living cells, and we were able to distinguish GFP, diGFP, as well as ligand-induced dimerization of FKBP12 (FK506 binding protein 12)-GFP. While other analysis methods have only sporadically been used to study dimerization in living cells and may be prone to errors, this paper provides a robust approach for the investigation of any cytosolic protein using single-color fluorescence fluctuation spectroscopy.

The tale of proteolysis targeting chimeras (PROTACs) for Leucine-Rich Repeat Kinase 2 (LRRK2).

Here we present the rational design and synthetic methodologies towards proteolysis-targeting chimeras (PROTACs) for the recently-emerged target leucine-rich repeat kinase 2 (LRRK2). Two highly potent, selective, brain-penetrating kinase inhibitors were selected, and their structure was appropriately modified to assemble a cereblon-targeting PROTAC. Biological data show strong kinase inhibition and the ability of the synthesized compounds to enter the cells. However, data regarding the degradation of the target protein are inconclusive. The reasons for the inefficient degradation of the target are further discussed.

Vaccine related reactogenicity for primary immunization: a randomized controlled trial of 23(wider) vs. 25(narrower) gauge needles with same lengths.

OBJECTIVES: To compare vaccine related reactogenicity during primary immunization in healthy infants using 23 vs. 25 gauge needles. METHODS: This randomized controlled trial was conducted in Vaccination Room of the Advanced Pediatrics Center. 155 participants for primary immunization were assigned to two intervention groups (23 vs. 25 gauge). Parent-reported local and systemic reactions were recorded daily for three days after the immunization. RESULTS: Swelling (24%) and tenderness (21%) were the two most common parent-reported local symptoms followed by restriction of movements (18%) and redness (10%) on day 1. Any local reaction on day 1 was statistically similar in 25 gauge vs. 23 gauge group (RR 0.77; 95% CI: 0.32 to 1.82) (P = 0.54), but fever (day 1) showed higher trend in 23 gauge needle group (RR 2.24; 95% CI: 0.92-5.47) (P = 0.07). Furthermore, on analysis of serially reported local and systemic reactions for 3 consecutive days by generalized estimating equations, odds of redness, swelling, tenderness, restricted movement and fever were statistically similar between two needle groups. On the other hand, median (± SE) crying time (in seconds) was significantly prolonged in the 25 gauge needle (39 ± 2) as compared to 23 gauge group (30 ± 1.3) (log rank test, P = 0.001). CONCLUSIONS: The use of same length needles with narrower (25) or wider (23) gauge did not show significant differences in local reactogenicity during primary immunization. Fever, however, was reduced marginally in 25 gauge group whereas crying duration was significantly shorter with 23 gauge needle. Finally, larger studies are needed to further evaluate objectively the outcome of reactogenicity.