Estimation of infant vaccination coverage at national and region level in Ethiopia: a cross-sectional study.

Introduction: an increasing trend of routine immunization performance has generally been observed over the past decade in Ethiopia. However, inconsistencies were observed over time and among different sources of data. This review analyzed systematically data from various sources and produced regional and national coverage estimates for antigens offered in the infant immunization program in Ethiopia. Methods: we collated data from administrative reports, population-based surveys and other sources to produce annual estimates of vaccination coverage. We obtained relevant data for each of the 9 Regional States and 2 city administrations, for the period 2007-2016. Region level estimates were produced based on survey results, interpolation between or extrapolation. We aggregated the resulting region level estimates, using a population-weighted approach, to give national estimates. Results: we found that the national Penta 3 coverage of Ethiopia increased from 59% in 2007 to 71% in 2016. For the 110 vaccination estimates produced at region level, 71 were based on interpolation or extrapolation from empirical anchor points; 18% were based on surveys and 17% were based on administrative data. Conclusion: while we recognize the critical importance of improving the quality of information on vaccination coverage from administrative reporting systems, we are also cognizant of the expected continued need for region level surveys and improved rapid-monitoring exercises.

Innovative approach for potential scale-up to jump-start simplified management of sick young infants with possible serious bacterial infection when a referral is not feasible: Findings from implementation research.

BACKGROUND: Neonatal bacterial infections are a common cause of death, which can be managed well with inpatient treatment. Unfortunately, many families in low resource settings do not accept referral to a hospital. The World Health Organization (WHO) developed a guideline for management of young infants up to 2 months of age with possible serious bacterial infection (PSBI) when referral is not feasible. Government of Ethiopia with WHO evaluated the feasibility of implementing this guideline to increase coverage of treatment. OBJECTIVE: The objective of this study was to implement a simplified antibiotic regimen (2 days gentamicin injection and 7 days oral amoxicillin) for management of sick young infants with PSBI in a programme setting when referral was not feasible to identify at least 80% of PSBI cases, achieve an overall adequate treatment coverage of at least 80% and document the challenges and opportunities for implementation at the community level in two districts in Tigray, Ethiopia. METHODS: Using implementation research, we applied the PSBI guideline in a programme setting from January 2016 to August 2017 in Raya Alamata and Raya Azebo Woredas (districts) in Southern Tigray, Ethiopia with a population of 260884. Policy dialogue was held with decision-makers, programme implementers and stakeholders at federal, regional and district levels, and a Technical Support Unit (TSU) was established. Health Extension Workers (HEWs) working at the health posts and supervisors working at the health centres were trained in WHO guideline to manage sick young infants when referral was not feasible. Communities were sensitized towards appropriate home care. RESULTS: We identified 854 young infants with any sign of PSBI in the study population of 7857 live births. The expected live births during the study period were 9821. Assuming 10% of neonates will have any sign of PSBI within the first 2 months of life (n = 982), the coverage of appropriate treatment of PSBI cases in our study area was 87% (854/982). Of the 854 sick young infants, 333 (39%) were taken directly to a hospital and 521 (61%) were identified by HEW at health posts. Of the 521 young infants, 27 (5.2%) had signs of critical illness, 181 (34.7%) had signs of clinical severe infection, whereas 313 (60.1%) young infants 7-59 days of age had only fast breathing pneumonia. All young infants with critical illness accepted referral to a hospital, while 117/181 (64.6%) infants with clinical severe infection accepted referral. Families of 64 (35.3%) infants with clinical severe infection refused referral and were treated at the health post with injectable gentamicin for 2 days plus oral amoxicillin for 7 days. All 64 completed recommended gentamicin doses and 63/64 (98%) completed recommended amoxicillin doses. Of 313 young infants, 7-59 days with pneumonia who were treated by the HEWs without referral with oral amoxicillin for 7 days, 310 (99%) received all 14 doses. No deaths were reported among those treated on an outpatient basis at health posts. But 35/477 (7%) deaths occurred among young infants treated at hospital. CONCLUSIONS: When referral is not feasible, young infants with PSBI can be managed appropriately at health posts by HEWs in the existing health system in Ethiopia with high coverage, low treatment failure and a low case fatality rate. Moreover, fast breathing pneumonia in infants 7-59 days of age can be successfully treated at the health post without referral. Relatively higher mortality in sick young infants at the referral level health facilities warrants further investigation.

Mitigating the mistreatment of childbearing women: evaluation of respectful maternity care intervention in Ethiopian hospitals.

OBJECTIVES: There is a lack of evidence on approaches to mitigating mistreatment during facility-based childbirth. This study compares the experiences of mistreatment reported by childbearing women before and after implementation of a respectful maternity care intervention. DESIGN: A pre-post study design was undertaken to quantify changes in women's experiences of mistreatment during facility-based childbirth before and after the respectful maternity care intervention. INTERVENTION: A respectful maternity care intervention was implemented in three hospitals in southern Ethiopia between December 2017 and September 2018 and it included training of service providers, placement of wall posters in labour rooms and post-training supportive visits for quality improvement. OUTCOME MEASURES: A 25-item questionnaire asking women about mistreatment experiences was administered to 388 women (198 in the pre-intervention, 190 in the post-intervention). The outcome variable was the number of mistreatment components experienced by women, expressed as a score out of 25. Multilevel mixed-effects Poisson modelling was used to assess the change in mistreatment score from pre-intervention to post-intervention periods. RESULTS: The number of mistreatment components experienced by women was reduced by 18% when the post-intervention group was compared with the pre-intervention group (adjusted regression coefficient (Aß)=0.82, 95% CI 0.74 to 0.91). Women who had a complication during pregnancy (Aß=1.17, 95% CI 1.01 to 1.34) and childbirth (Aß=1.16, 95% CI 1.03 to 1.32) experienced a greater number of mistreatment components. On the other hand, women who gave birth by caesarean birth after trial of vaginal birth (Aß=0.76, 95% CI 0.63 to 0.92) and caesarean birth without trial of vaginal birth (Aß=0.68, 95% CI 0.47 to 0.98) experienced a lesser number of mistreatment components compared with those who had vaginal birth. CONCLUSIONS: Women reported significantly fewer mistreatment experiences during childbirth following implementation of the intervention. Given the variety of factors that lead to mistreatment in health facilities, interventions designed to mitigate mistreatment need to involve structural changes.

Health system capacity for tuberculosis care in Ethiopia: evidence from national representative survey.

OBJECTIVE: The objective of this study was to evaluate the tuberculosis (TB) health system capacity and its variations by location and types of health facilities in Ethiopia. DESIGN: We used the Service Provision Assessment plus (SPA+) survey data that were collected in 2014 in all hospitals and randomly selected health centers and private facilities in all regions of Ethiopia. We assessed structural, process and overall health system capacity based on the Donabedian quality of care model. Multiple linear regression and spatial analysis were done to assess TB capacity score variation across regions. SETTING: The study included 873 public and private health facilities all over Ethiopia. PARTICIPANTS: None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULTS: A total of 873 health facilities were included in the analysis. The overall TB care capacity score was 76.7%, 55.9% and 37.8% in public hospitals, health centers and private facilities, respectively. The health system capacity score for TB was higher in the urban (60.4%) facilities compared to that of the rural (50.0%) facilities (ß = 8.0, 95% CI: 4.4, 11.6). Health centers (ß = -16.2, 95% CI: -20.0, -12.3) and private health facilities (ß = -38.3, 95% CI: -42.4, -35.1) had lower TB care capacity score than hospitals. Overall TB care capacity score were lower in Western and Southwestern Ethiopia and in Benishangul-Gumuz and Gambella regions. CONCLUSIONS: The health system capacity score for TB care in Ethiopia varied across regions. Health system capacity improvement interventions should focus on the private sectors and health facilities in the rural and remote areas to ensure equity and improve quality of care.

Quality of Kangaroo Mother Care services in Ethiopia: Implications for policy and practice.

BACKGROUND: Providing high-quality kangaroo mother care (KMC) is a strategy proven to improve outcomes in premature babies. However, whether KMC is consistently and appropriately provided in Ethiopia is unclear. This study assesses the quality of KMC services in Ethiopia and the factors associated with its appropriate initiation among low birth weight neonates. METHODS: We used data from the 2016 national Emergency Obstetric and Newborn Care (EmONC) assessment which contains data on all health facilities providing delivery care services in Ethiopia (N = 3,804). We described the quality of KMC services provided to low-birth weight (LBW) babies in terms of infrastructure, processes and outcomes (survival status at discharge). We also explored the factors associated with appropriate KMC initiation using multivariable logistic regression models. RESULTS: The quality of KMC services in Ethiopia was poor. The facilities included scored only 59.0% on average on a basic index of service readiness. KMC was initiated for only 46.4% of all LBW babies included in the sample. Among those who received KMC, 66.7% survived, 13.3% died and 20.4% had no data on survival status at discharge. LBW babies born in health centers were twice more likely to receive KMC compared to those born in hospitals (AOR = 2.0, 95% CI: 1.3-3.0). Public facilities, those with a staff rotation policy in place for newborn care, and those with separate newborn corners were also more likely to initiate KMC for LBW babies. CONCLUSIONS: We found low levels of appropriate KMC initiation, inadequate infrastructure and staffing, and poor survival among LBW babies in Ethiopia. Efforts must be made to improve the adoption of this life saving technique, particularly in hospitals and in the private sector where KMC remains underutilized. Facilities should also dedicate specific spaces for newborn care that enables mothers to provide KMC. In addition, improving record keeping and data quality for routine health data is a priority.

Low effective coverage of family planning and antenatal care services in Ethiopia.

OBJECTIVE: To assess the quality and effective coverage (EC) of family planning (FP) and antenatal care (ANC) services in Ethiopia. DESIGN: Secondary analyses of the 2014 Ethiopia Service Provision Assessment Plus Survey and 2016 Ethiopia Demographic and Health Survey data. SETTING AND PARTICIPANTS: Women using FP and ANC. MAIN OUTCOME MEASURES: Quality indices are created as a proportion of recommended clinical actions done in observations of ANC and FP visits. We adjust the crude coverage of ANC and of FP by the quality to estimate EC for both services. RESULTS: The crude coverage of FP was 61% and 62% for ANC in Ethiopia in 2016. On average, quality was 35.8% during FP visits and 86% of women received <50% of the recommended clinical actions. When adjusting the crude coverage to account for the quality of service, Ethiopia's FP services EC was 22%. On average, ANC quality was 34% and 81% received <50% of the recommended ANC clinical actions. When adjusting the crude coverage by the service quality, the mean EC of ANC services was 22% in Ethiopia. CONCLUSIONS: The quality of both FP and ANC services is low in Ethiopia, with women obtaining only a fraction of the standard clinical actions during their visits. In addition, there is considerable variation in EC across Ethiopia's regions, with variation driven largely by variations in crude coverage. To improve EC, actions are needed to improve the quality of ANC and FP care.

Capacity of health facilities for diagnosis and treatment of HIV/AIDS in Ethiopia.

BACKGROUND: There are dearth of literature on the capacity of the health system to diagnose and treat HIV/AIDS in Ethiopia. In this study we evaluated the capacity of health facilities for HIV/AIDS care, its spatial distribution and variations by regions and zones in Ethiopia. METHODS: We analyzed the Service Provision Assessment plus (SPA+) survey data that were collected in 2014 in all regions of Ethiopia. We assessed structural, process and overall capacity of the health system based on the Donabedian quality of care model. We included 5 structural and 8 process indicators and overall capacity score was constructed by taking the average of all indicators. Multiple linear regression was done using STATA 14 to assess the association of the location and types of health facilities with overall capacity score. Maps displaying the average capacity score at Zonal level were produced using ArcGIS Desktop v10.3 (Environmental Systems Research Institute Inc., Redlands CA, USA). RESULTS: A total of 873 health facilities were included in the analysis. Less than 5% of the private facilities provided antiretroviral therapy (ART); had national ART guideline, baseline CD4 count or viral load and tuberculosis screening mechanisms. Nearly one-third of the health centers (34.9%) provided ART. Public hospitals have better capacity score (77.1%) than health centers (45.9%) and private health facilities (24.8%). The overall capacity score for urban facilities (57.1%) was higher than that of the rural (38.2%) health facilities (ß = 15.4, 95% CI: 11.7, 19.2). Health centers (ß = - 21.4, 95% CI: -25.4, - 17.4) and private health facilities (ß = - 50.9, 95% CI: -54.8, - 47.1) had lower overall capacity score than hospitals. Facilities in Somali (ß = - 13.8, 95% CI: -20.6, - 7.0) and SNNPR (ß = - 5.0, 95% CI: -9.8, - 0.1) regions had lower overall capacity score than facilities in the Oromia region. Zones located in emerging regions such as Gambella and Benishangul Gumz and in remote areas of Oromia and SNNPR had lower capacity score in terms of process indicators. CONCLUSIONS: There is a significant geographical heterogeneity on the capacity of health facilities for HIV/AIDS care and treatment in Ethiopia. Targeted capacity improvement initiatives are recommended with focus on health centers and private health facilities, and emerging Regions and the rural and remote areas.

Effects of polio eradication activities on routine immunization: lessons from the 2013 outbreak response in Somali region of Ethiopia.

INTRODUCTION: Ethiopia experienced several WPV importations with a total of 10 WPV1 cases confirmed during the 2013 outbreak alone before it is closed in 2015. We evaluated supplemental immunization activities (SIAs), including lessons learned for their effect on the routine immunization program during the 2013 polio outbreak in Somali regional state. METHODS: We used descriptive study to review documents and analyse routine health information system reports from the polio outbreak affected Somali regional state. RESULTS: All data and technical reports of the 15 rounds of polio SIAs from June 2013 through June 2015 and routine immunization coverages for DPT-Hib-HepB 3 and measles were observed. More than 93% of the SIAs were having administrative coverage above 95%. The trend of routine immunization for the two antigens, over the five years (2011 through 2015) did not show a consistent pattern against the number of SIAs. Documentations showed qualitative positive impacts of the SIAs strengthening the routine immunization during all courses of the campaigns. CONCLUSION: The quantitative impact of polio SIAs on routine immunization remained not so impressive in this study. Clear planning, data consistencies and completeness issues need to be cleared for the impact assessment in quantitative terms, in polio legacy planning as well as for the introduction of injectable polio vaccine through the routine immunization.

Acquiring snapshots of the orientation of trans-membrane protein domains using a hybrid FRET pair.

One challenge in studying the function of membrane-embedded proteins is determining the orientation of key domains in the context of the changing and dynamic membrane environment. We describe a confocal microscopy setup that utilizes external electric field pulses to direct dipicrylamine (DPA) to a membrane leaflet. The detection of FRET between DPA and a fluorescent probe attributes it to the inner or outer leaflet of a membrane. By utilizing short acquisition times and confocal imaging, this attribution could be made even in changing membrane environments. Our setup adds versatility to the study of the biological activity of membrane-embedded proteins.

Single color FRET based measurements of conformational changes of proteins resulting from translocation inside cells.

Translocation of proteins to different parts of the cell is necessary for many cellular mechanisms as a means for regulation and a variety of other functions. Identifying how these proteins undergo conformational changes or interact with various partners during these events is critical to understanding how these mechanisms are executed. A protocol is presented that identifies conformational changes in a protein that occur during translocation while overcoming challenges in extracting distance information in very different environments of a living cell. Only two samples are required to be prepared and are observed with one optical setup. Live-cell FRET imaging has been applied to identify conformational changes between two native cysteines in Bax, a member of the Bcl-2 family of proteins that regulates apoptosis. Bax exists in the cytosol and translocates to the mitochondria outer membrane upon apoptosis induction. The distance, r, between the two native cysteines in the cytosolic structure of Bax necessitates the use of a FRET donor-accepter pair with R0~r as the most sensitive probe for identifying structural changes at these positions. Alexa Fluor 546 and Dabcyl, a dark acceptor, were used as FRET pairs - resulting in single color intensity variations of Alexa-546 as a measure of FRET efficiency. An internal reference, conjugated to Bax, was employed to normalize changes in fluorescence intensity of Alexa Fluor 546 due to inherent inhomogeneities in the living cell. This correction allowed the true FRET effects to be measured with increased precision during translocation. Normalization of intensities to the internal reference identified a FRET efficiency of 0.45±0.14 in the cytosol and 0.11±0.20 in the mitochondria. The procedure for the conjugation of the internal reference and FRET probes as well as the data analysis is presented.

PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding.

Genetic studies indicate that the mitochondrial kinase PINK1 and the RING-between-RING E3 ubiquitin ligase Parkin function in the same pathway. In concurrence, mechanistic studies show that PINK1 can recruit Parkin from the cytosol to the mitochondria, increase the ubiquitination activity of Parkin, and induce Parkin-mediated mitophagy. Here, we used a cell-free assay to recapitulate PINK1-dependent activation of Parkin ubiquitination of a validated mitochondrial substrate, mitofusin 1. We show that PINK1 activated the formation of a Parkin-ubiquitin thioester intermediate, a hallmark of HECT E3 ligases, both in vitro and in vivo. Parkin HECT-like ubiquitin ligase activity was essential for PINK1-mediated Parkin translocation to mitochondria and mitophagy. Using an inactive Parkin mutant, we found that PINK1 stimulated Parkin self-association and complex formation upstream of mitochondrial translocation. Self-association occurred independent of ubiquitination activity through the RING-between-RING domain, providing mechanistic insight into how PINK1 activates Parkin.

FAT10 modifies p53 and upregulates its transcriptional activity.

FAT10, also known as diubiquitin, has been implicated in the regulation of diverse cellular processes, including mitosis, immune response, and apoptosis. We seek to identify FAT10-targeted proteins, an essential step in elucidating the physiological function of FAT10. To this end, human FAT10 or its non-conjugatable derivative, FAT10ΔGG, was overexpressed in HEK293 cells. We observed a number of high molecular weight FAT10 conjugates in cells expressing wild-type FAT10, but not in FAT10ΔGG. The FAT10 conjugates are inducible by TNF-α and accumulated significantly when cells were treated with proteasome inhibitor, MG132. Among them, tumor suppressor p53 was found to be FATylated. The p53 transcriptional activity was found to be substantially enhanced in FAT10-overexpressing cells. In addition, overexpressing FAT10 in HEK293 cells also reduced the population of p53 which cross reacted with monoclonal anti-p53 antibody, PAB240, known to recognize only the transcriptionally inactive p53. FAT10 in the nucleus was found co-localized with p53 and altered its subcellular compartmentalization. Furthermore, overexpressing FAT10 led to a reduction in the size of promyelocytic leukemia nuclear bodies (PML-NBs) and altered their distribution in the nucleus. Based on these observations, a potential mechanism which correlates FATylation of p53 to its translocation and transcriptional activation is discussed.

Expression of SUMO-2/3 induced senescence through p53- and pRB-mediated pathways.

Three highly homologous small ubiquitin-related modifier (SUMO) proteins have been identified in mammals. Modifications of proteins by SUMO-1 have been shown to regulate transcription, nucleocytoplasmic transport, protein stability, and protein-protein interactions. Relative to SUMO-1, little is known about the functions of SUMO-2 or SUMO-3 (referred to as SUMO-2/3). Here, stable cell lines overexpressing processed forms of SUMO-2/3 (SUMO-2/3GG) as well as their non-conjugatable derivatives, SUMO-2/3DeltaGG, were established. Cells overexpressing SUMO-2/3GG showed a premature senescence phenotype as revealed by cellular morphology and senescence-associated galactosidase activity. The senescence pathway protein p21 was up-regulated in cells overexpressing SUMO-2/3GG. In contrast, cells overexpressing non-conjugatable forms of SUMO-2/3DeltaGG showed neither an apparent senescent phenotype nor elevated p21. Both p53 and pRB were found to be modified by SUMO-2/3. Site-directed mutagenesis studies showed that Lys-386 of p53, the SUMO-1 modification site, is also the modification site for SUMO-2/3. In addition, H2O2 treatment of untransfected cells caused an increase in p53 sumoylation by SUMO-2/3, whereas that by SUMO-1 remained unchanged. Moreover, knocking down tumor suppressor proteins p53 or pRB using small interfering RNA significantly alleviated the premature senescence phenotypes in SUMO-2/3GG overexpressing cells. Together, our results reveal that p53 and pRB can be sumoylated by SUMO-2/3 in vivo, and such modification of p53 and pRB may play roles in premature senescence and stress response.

A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers.

Ubiquitin-like modifiers (UBLs) contain ubiquitin homology domains and can covalently modify target proteins in a manner similar to ubiquitylation. In this study, we revealed a general proteomic approach to elucidate the enzymatic pathways and identify target proteins for three UBLs: SUMO-2, SUMO-3, and NEDD8. Expression plasmids containing the cDNAs of Myc/6xHis doubly-tagged processed or non-conjugatable forms of these UBLs were constructed. The constructed vectors were then used to transfect HEK 293 Tet-On cells, and stable cell lines expressing these UBLs and their mutants were established. The epitope-tagged proteins were purified by immunoprecipitation under native conditions or by affinity chromatography on nickel resin under denaturing conditions. Purified proteins were analyzed using liquid chromatography coupled with mass spectrometry (LC-MS/MS). Most of the E1-like activating enzymes, E2-like conjugating enzymes and the majorities of the known target as well as some previously unreported proteins for SUMO-2, SUMO-3, and NEDD8 pathways were identified.

Selective field effects on intracellular vacuoles and vesicle membranes with nanosecond electric pulses.

Electric pulses across intact vesicles and cells can lead to transient increase in permeability of their membranes. We studied the integrity of these membranes in response to external electric pulses of high amplitude and submicrosecond duration with a primary aim of achieving selective permeabilization. These effects were examined in two separate model systems comprising of 1), a mixed population of 1,2-di-oleoyl-sn-glycero-3-phosphocholine phospholipid vesicles and in 2), single COS-7 cells, in which large endosomal membrane vacuoles were induced by stimulated endocytosis. It has been shown that large and rapidly varying external electric fields, with pulses shorter than the charging time of the outer-cell membrane, could substantially increase intracellular fields to achieve selective manipulations of intracellular organelles. The underlying principle of this earlier work is further developed and applied to the systems studied here. Under appropriate conditions, we show preferential permeabilization of one vesicle population in a mixed preparation of vesicles of similar size distribution. It is further shown that large endocytosed vacuoles in COS-7 cells can be selectively permeabilized with little effect on the integrity of outer cell membrane.

Sumoylation of heterogeneous nuclear ribonucleoproteins, zinc finger proteins, and nuclear pore complex proteins: a proteomic analysis.

SUMO, a small ubiquitin-related modifier, is known to covalently attach to a number of nuclear regulatory proteins such as p53, IkappaB, promyelocytic leukemia protein and c-Jun. The sumoylation reaction is catalyzed by the SUMO protease, which exposes the C-terminal active glycine residue of the nascent SUMO, the heterodimeric SUMO activating enzyme, the SUMO conjugating enzyme, Ubc9, and SUMO protein ligases, in a manner similar to ubiquitinylation. Identification of SUMO-regulated proteins is hampered by the fact that many sumoylated proteins are present at a level below normal detection limit. This limitation was overcome by either in vivo overexpression of Myc-SUMO or in vitro sumoylation with excess biotin-SUMO and Ubc9. Sumoylated proteins so obtained were affinity purified or isolated by immunoprecipitation. The isolated sumoylated proteins were identified by sequence analysis using mass spectrometric methods. Results reveal that several heterogeneous nuclear ribonucleoproteins (hnRNPs), zinc finger proteins, and nuclear pore complex proteins were sumoylated. The sumoylation of hnRNP A1, hnRNP F, and hnRNP K were confirmed in vivo by coimmunoprecipitation. In view of the facts that hnRNPs have been implicated in RNA splicing, transport, stability, and translation, our findings suggest that sumoylation could play an important role in regulating mRNA metabolism.

Stable and controllable RNA interference: Investigating the physiological function of glutathionylated actin.

RNA interference is an effective method to silence specific gene expression. Its application to mammalian cells, however, has been hampered by various shortcomings. Recently, it was reported that introduction of 22-bp double-stranded RNAs (dsRNAs) would specifically suppress expression of endogenous and heterogeneous genes in various mammalian cell lines. However, using this method, we failed to knock out proteins of interest effectively. Here we report the development of a stable and controllable method for generating dsRNA intracellularly. Tetracycline-responsive transactivator-containing cells were transfected with a vector capable of tetracycline-induced bidirectionally overexpressing sense and antisense RNA to form dsRNA in vivo. With this method, glutaredoxin, monitored by Western blot, was knocked out by overexpressing 290-base sense and antisense RNA in NIH 3T3 cells controlled by tetracycline or doxycycline. By using these glutaredoxin knocked-out cells, we have demonstrated that actin deglutathionylation plays a key role in growth factor-mediated actin polymerization, translocalization, and reorganization near the cell periphery.