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737 result(s) for "You Are Not Alone"
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CONFIDENTIAL CHAT
Dear A Circle Of Love--A month ago. I clipped your letter and, I guess, laid it aside. It hit close to home, but I wasn't able to deal with it. Now I've brought it back out and am ready to respond.
Individual and intimate-partner factors associated with cervical cancer screening in Central Uganda
Intimate-partner factors have a significant effect on the uptake of services that affect maternal reproductive health outcomes. There is limited research on intimate-partner factors associated with cervical cancer screening. Therefore, this article examines the intimate-partner correlates of cervical cancer screening among married women in Central Uganda. We conducted a cross-sectional survey in Wakiso and Nakasongola districts in Central Uganda. A total of 656 married women aged 25–49 participated in the study. Frequency distributions for descriptive statistics and Pearson chi-squared tests were done to identify the association of selected individual explanatory variables and intimate-partner factors with cervical cancer screening. Finally, multivariable complementary log-log regressions were used to estimate intimate-partner factors associated with women’s cervical cancer screening uptake in Central Uganda. About 2 in 10 (20%) of the participants had been screened for cervical cancer. The following characteristics when examined separately in relation to the uptake of cervical cancer screening service and were significant: woman’s age, education attainment, occupation, wealth index, parity, male partner’s age, and male partner’s emotional support. After adjusting for independent factors, cervical cancer screening was significantly associated with women who had; attained secondary (AOR = 2.19; CI 1.18–4.06) compared to none/ primary education, and received partner’s emotional support (AOR = 30.06; CI 13.44–67.20) compared to those who did not receive partner’s emotional support. In Central Uganda, cervical cancer screening among married women was significantly associated with women’s education, and partner’s emotional support. These factors point to the importance of intimate-partner factors. Therefore, more effort should be directed at encouraging men’s participation. This should be supplemented with empowering women through education to increase uptake of screening services.
Individual and intimate-partner factors associated with cervical cancer screening in Central Uganda
Intimate-partner factors have a significant effect on the uptake of services that affect maternal reproductive health outcomes. There is limited research on intimate-partner factors associated with cervical cancer screening. Therefore, this article examines the intimate-partner correlates of cervical cancer screening among married women in Central Uganda. We conducted a cross-sectional survey in Wakiso and Nakasongola districts in Central Uganda. A total of 656 married women aged 25–49 participated in the study. Frequency distributions for descriptive statistics and Pearson chi-squared tests were done to identify the association of selected individual explanatory variables and intimate-partner factors with cervical cancer screening. Finally, multivariable complementary log-log regressions were used to estimate intimate-partner factors associated with women’s cervical cancer screening uptake in Central Uganda. About 2 in 10 (20%) of the participants had been screened for cervical cancer. The following characteristics when examined separately in relation to the uptake of cervical cancer screening service and were significant: woman’s age, education attainment, occupation, wealth index, parity, male partner’s age, and male partner’s emotional support. After adjusting for independent factors, cervical cancer screening was significantly associated with women who had; attained secondary (AOR = 2.19; CI 1.18–4.06) compared to none/ primary education, and received partner’s emotional support (AOR = 30.06; CI 13.44–67.20) compared to those who did not receive partner’s emotional support. In Central Uganda, cervical cancer screening among married women was significantly associated with women’s education, and partner’s emotional support. These factors point to the importance of intimate-partner factors. Therefore, more effort should be directed at encouraging men’s participation. This should be supplemented with empowering women through education to increase uptake of screening services.
Triad of homocysteine, ROCK2 and vimentin as a convergent biomarker signature in pseudoexfoliation
Background Pseudoexfoliation (PEX) is a complex age-related disorder traditionally considered ocular in origin but increasingly recognized as a systemic condition involving extracellular matrix (ECM) dysregulation, oxidative stress, and cytoskeletal alterations. The disease typically presents as pseudoexfoliation syndrome (PEXS), with a subset of patients progressing to pseudoexfoliation glaucoma (PEXG), characterized by elevated intraocular pressure and optic nerve damage. While genetic susceptibility has been explored, dynamic molecular markers that reflect disease activity and progression remain underdeveloped. Objective This study investigates the plasma levels of three candidate biomolecules, homocysteine (Hcy), Rho-associated coiled-coil containing protein kinase 2 (ROCK2), and vimentin (VIM), in individuals with PEXS, PEXG, and age-matched controls, to evaluate their potential as systemic indicators of disease presence and progression. Methods A total of 72 participants (24 controls, 24 PEXS, 24 PEXG) were recruited from a single Indian cohort. Plasma Hcy was measured via fluorometric assay, and ROCK2/VIM by ELISA. Analyses included ANOVA, effect size estimation, logistic regression, LASSO modelling, ROC analysis, and unsupervised clustering. Marker interactions and stage associations were assessed through correlation and distribution analyses. Functional validation involved HLE-B3 cells treated with Hcy, followed by immunoblotting for ROCK2 and VIM. Bioinformatics (pathway enrichment, STITCH, TF prediction) identified upstream regulators and pathways. Results All three biomarkers were significantly elevated in PEXS and PEXG compared to controls ( p  < 0.001), with large effect sizes. Hcy and VIM levels progressively increased from PEXS to PEXG, while ROCK2 peaked in PEXS. The three-marker model combining Hcy, ROCK2, and VIM demonstrated a robust diagnostic profile, achieving a high sensitivity of 0.94 and specificity of 0.88, indicating a more balanced classification performance compared to individual or two-marker combinations. Clustering analyses revealed three molecular subgroups with moderate alignment to clinical staging (ARI = 0.32). Correlation and distribution analyses suggested stage-specific marker interactions. Bioinformatic findings present SP1 as a shared upstream regulator linking Hcy to ROCK2 and VIM expression, supported by in vitro findings. Conclusion Homocysteine, ROCK2, and vimentin form a clinically relevant biomarker panel with strong diagnostic and staging utility. The findings suggest a mechanistic axis driven by Hcy, possibly through SP1-mediated regulation, contributing to cytoskeletal and fibrotic alterations. This integrated pathway highlights potential molecular targets for pharmacological intervention and offers a foundation for future risk-based screening for pseudoexfoliation.
Altered proteome in translation initiation fidelity defective eIF5G31R mutant causes oxidative stress and DNA damage
The recognition of the AUG start codon and selection of an open reading frame (ORF) is fundamental to protein biosynthesis. Defect in the fidelity of start codon selection adversely affect proteome and have a pleiotropic effect on cellular function. Using proteomic techniques, we identified differential protein abundance in the translation initiation fidelity defective eIF5 G31R mutant that initiates translation using UUG codon in addition to the AUG start codon. Consistently, the eIF5 G31R mutant altered proteome involved in protein catabolism, nucleotide biosynthesis, lipid biosynthesis, carbohydrate metabolism, oxidation–reduction pathway, autophagy and re-programs the cellular pathways. The utilization of the upstream UUG codons by the eIF5 G31R mutation caused downregulation of uridylate kinase expression, sensitivity to hydroxyurea, and DNA damage. The eIF5 G31R mutant cells showed lower glutathione levels, high ROS activity, and sensitivity to H 2 O 2 .
eIF2β zinc-binding domain interacts with the eIF2γ subunit through the guanine nucleotide binding interface to promote Met-tRNAiMet binding
The heterotrimeric eIF2 complex consists of a core eIF2γ subunit to which binds eIF2α and eIF2β subunits and plays an important role in delivering the Met-tRNAiMet to the 40S ribosome and start codon selection. The intricacies of eIF2β-γ interaction in promoting Met-tRNAiMet binding are not clearly understood. Previously, the zinc-binding domain (ZBD) eIF2βS264Y mutation was reported to cause Met-tRNAiMet binding defect due to the intrinsic GTPase activity. We showed that the eIF2βS264Y mutation has eIF2β-γ interaction defect. Consistently, the eIF2βT238A intragenic suppressor mutation restored the eIF2β-γ and Met-tRNAiMet binding. The eIF2β-ZBD residues Asn252Asp and Arg253Ala mutation caused Met-tRNAiMet binding defect that was partially rescued by the eIF2βT238A mutation, suggesting the eIF2β-ZBD modulates Met-tRNAiMet binding. The suppressor mutation rescued the translation initiation fidelity defect of the eIF2γN135D SW-I mutation and eIF2βF217A/Q221A double mutation in the HTH domain. The eIF2βT238A suppressor mutation could not rescue the eIF2β binding defect of the eIF2γV281K mutation; however, combining the eIF2βS264Y mutation with the eIF2γV281K mutation was lethal. In addition to the previously known interaction of eIF2β with the eIF2γ subunit via its α1-helix, the eIF2β-ZBD also interacts with the eIF2γ subunit via guanine nucleotide-binding interface; thus, the eIF2β-γ interacts via two distinct binding sites.