Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
Add more filters

Publication year range
1.
Res Sq ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38826445

ABSTRACT

Background: Burnout is exhaustion caused by exposure to chronic stress. Prior to the COVID-19 pandemic, people with disabilities experienced high levels of burnout due to discrimination, barriers to accessing resources, and lack of accommodations. Caregivers have also experienced high levels of burnout during the COVID-19 pandemic. Background: While researchers have examined burnout among caregivers of disabled children, less research has focused on the experiences of disabled caregivers. We examined the association between caregiver disability and burnout during the pandemic. Methods: We distributed an online survey to caregivers of children enrolled in socially vulnerable elementary and middle schools in San Diego County, California between September and December, 2022. Our survey included demographic questions, questions about pandemic experiences, and a continuous burnout measure. We analyzed survey data to test our hypothesis that caregivers with a disability experienced higher levels of burnout than their non-disabled counterparts during the height of the COVID-19 pandemic. We used multivariable linear regression analysis adjusting for household income and caregiver education level. Results: Disabled caregivers self-reported higher levels of burnout than non-disabled caregivers (B = 0.72; p < 0.001) during the COVID-19 pandemic in bivariate and multivariable analyses. Caregivers with a higher household income (B = 0.04; p = 0.017) and more education (B = 0.13; p = 0.005) also reported higher levels of burnout. Conclusion: The COVID-19 pandemic exacerbated existing difficulties faced by disabled caregivers who often struggle to balance the demands of caregiving with their available resources. Targeted programs and policies are needed to support disabled caregivers during health emergencies that exacerbate existing inequities in access to resources.

2.
PLoS One ; 19(5): e0295618, 2024.
Article in English | MEDLINE | ID: mdl-38805443

ABSTRACT

BACKGROUND: Institutional mistrust has weakened COVID-19 mitigation efforts. Assessing to what extent institutional mistrust impacts parental decision making is important in formulating structural efforts for improving future pandemic response. We hypothesized that institutional mistrust is associated with lower parental endorsement for COVID-19 vaccination. METHODS: We distributed an online survey among parents from schools in areas with high levels of social vulnerability relative to the rest of San Diego County. We defined vaccination endorsement as having a child aged 5 years or older who received at least one COVID-19 vaccine dose or being very likely to vaccinate their child aged 6 months-4 years when eligible. Institutional mistrust reflected the level of confidence in institutions using an aggregate score from 11 to 44. We built a multivariable logistic regression model with potential confounding variables. FINDINGS: Out of 290 parents in our sample, most were female (87.6%), reported their child as Hispanic/Latino (73.4%), and expressed vaccination endorsement (52.1%). For every one-point increase in mistrust score, there was an 8% reduction in the likelihood of participants endorsing vaccination for their child. Other statistically significant correlates that were positively associated with vaccination endorsement included parent vaccination status, child age, parent age, and Hispanic/Latino ethnicity. CONCLUSION: Our study further demonstrates how institutional mistrust hinders public response during health emergencies. Our findings also highlight the importance of building confidence in institutions and its downstream effects on pandemic preparedness and public health. One way that institutions can improve their relationship with constituents is through building genuine partnerships with trusted community figures.


Subject(s)
COVID-19 Vaccines , COVID-19 , Parents , Schools , Trust , Vaccination , Humans , Female , Male , California , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19/psychology , Parents/psychology , COVID-19 Vaccines/administration & dosage , Child , Adult , Vaccination/psychology , Adolescent , Child, Preschool , SARS-CoV-2 , Surveys and Questionnaires , Middle Aged
3.
Article in English | MEDLINE | ID: mdl-37372747

ABSTRACT

This study focuses on smoking-cessation strategies for United States (US) Vietnamese individuals, a group with high smoking rates, particularly those with limited English proficiency (LEP). The researchers conducted 16 in-depth interviews with a diverse group of participants, including healthcare professionals, community leaders, and former tobacco users. Data were analyzed using the Phase-Based Model of smoking cessation, resulting in several helpful strategies across the four phases: Motivation, Preparation, Cessation, and Maintenance. Prominent advice for the Motivation Phase included having a strong determination to quit and a reason why, such as protecting loved ones. For the Preparation and Cessation Phases, participants recommended healthy coping mechanisms, avoiding triggers, changing habits, and gradually reducing the number of cigarettes smoked. In the Maintenance Phase, strategies included regular exercise and setting boundaries with other people who smoke. Participants also stressed the importance of social support throughout all four phases. These findings have implications for healthcare providers working with US Vietnamese who smoke, especially those with LEP. By understanding the unique challenges this group faces in accessing smoking-cessation resources, providers can offer tailored support and guidance. Ultimately, this study provides useful strategies for helping US Vietnamese quit smoking, improving their health outcomes and quality of life.


Subject(s)
Health Personnel , Smoking Cessation , Southeast Asian People , Humans , Health Personnel/psychology , Quality of Life , Smoking Cessation/ethnology , Smoking Cessation/methods , Smoking Cessation/psychology , Southeast Asian People/psychology , United States/epidemiology , Leadership , Residence Characteristics , Vietnam/ethnology
4.
Int J Hyg Environ Health ; 247: 114044, 2023 01.
Article in English | MEDLINE | ID: mdl-36395654

ABSTRACT

BACKGROUND: Safe drinking water is a fundamental human right, yet more than 785 million people do not have access to it. The burden of water management disproportionately falls on women and young girls, and they suffer the health, psychosocial, political, educational, and economic effects. While water conditions and disease outcomes have been widely studied, few studies have summarized the research on drinking water and implications for gender equity and empowerment (GEE). METHODS: A systematic review of primary literature published between 1980 and 2019 was conducted on drinking water exposures and management and the implications for GEE. Ten databases were utilized (EMBASE, PubMed, Web of Science, Cochrane, ProQuest, Campbell, the British Library for Development Studies, SSRN, 3ie International Initiative for Impact Evaluation, and clinicaltrials.gov). Drinking water studies with an all-female cohort or disaggregated findings according to gender were included. RESULTS: A total of 1280 studies were included. GEE outcomes were summarized in five areas: health, psychosocial stress, political power and decision-making, social-educational conditions, and economic and time-use conditions. Water quality exposures and implications for women's health dominated the literature reviewed. Women experienced higher rates of bladder cancer when exposed to arsenic, trihalomethanes, and chlorine in drinking water and higher rates of breast cancer due to arsenic, trichloroethylene, and disinfection byproducts in drinking water, compared to men. Women that were exposed to arsenic experienced higher incidence rates of anemia and adverse pregnancy outcomes compared to those that were not exposed. Water-related skin diseases were associated with increased levels of psychosocial stress and social ostracization among women. Women had fewer decision-making responsibilities, economic independence, and employment opportunities around water compared to men. CONCLUSION: This systematic review confirms the interconnected nature of gender and WaSH outcomes. With growing attention directed towards gender equity and empowerment within WaSH, this analysis provides key insights to inform future research and policy.


Subject(s)
Arsenic , Drinking Water , Waterborne Diseases , Male , Pregnancy , Female , Humans , Gender Equity , Trihalomethanes
5.
Transl Behav Med ; 13(2): 64-72, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36271869

ABSTRACT

Rapid identification and isolation/quarantine of COVID-19 cases or close contacts, respectively, is a vital tool to support safe, in-person learning. However, safe isolation or quarantine for a young child also necessitates home confinement for at least one adult caregiver, as well as rapid learning material development by the teacher to minimize learning loss. The purpose of this study is to better understand barriers and supports to student home confinement. We conducted a mixed-methods study using focus group discussions and a self-administered online survey with parents and staff members from 12 elementary schools and childcare sites across San Diego County serving low-income and socially vulnerable families. Focus group participants reported that mental distress and loneliness, learning loss, childcare, food, income loss, and overcrowded housing were major barriers related to home confinement. The experiences described by FGD participants were prevalent in a concurrent community survey: 25% of participants reported that isolation would be extremely difficult for a household member who tested positive or was exposed to COVID-19, and 20% were extremely concerned about learning loss while in isolation or quarantine. Our findings suggest that there are serious structural impediments to safely completing the entire recommended course of isolation or quarantine, and that the potential for isolation or quarantine may also lead to increased hesitancy to access diagnostic testing.


BACKGROUND: During the COVID-19 pandemic, home confinement (isolation and quarantine) are important public health tools to keep children learning in-person at schools. However, isolation or quarantine for young children also means that often their caregivers must also go into home confinement, as well as forcing teachers to adapt their lessons to online teaching. PURPOSE: The purpose of this study is to better understand what makes home confinement comfortable or difficult for students and their families. METHODS: We did focus group discussions and shared an online survey with parents and staff members from 12 elementary schools and childcare centers across San Diego County vulnerable families. RESULTS: Focus group participants said that mental distress and loneliness, learning loss, childcare, food, income loss, and overcrowded housing made home confinement hard to do. Also 25% of survey participants said that isolation would be difficult for a household member who tested positive or was exposed to COVID-19, and 20% were really concerned about their child's learning loss if the family had to isolate or do quarantine. CONCLUSIONS: Our study's results suggest that there are serious structural issues for school families to safely go into isolation or quarantine, and because of this may make families more hesitant to get tested for COVID-19.


Subject(s)
COVID-19 , Mental Disorders , Adult , Child , Humans , COVID-19/prevention & control , Quarantine , Schools , Poverty
6.
medRxiv ; 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-34704096

ABSTRACT

Background: Schools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown. Methods: The objective of this study was to determine the effectiveness and accuracy of community-based passive wastewater and surface (environmental) surveillance to detect SARS-CoV-2 infection in neighborhood schools compared to weekly diagnostic (PCR) testing. We implemented an environmental surveillance system in nine elementary schools with 1700 regularly present staff and students in southern California. The system was validated from November 2020 - March 2021. Findings: In 447 data collection days across the nine sites 89 individuals tested positive for COVID-19, and SARS-CoV-2 was detected in 374 surface samples and 133 wastewater samples. Ninety-three percent of identified cases were associated with an environmental sample (95% CI: 88% - 98%); 67% were associated with a positive wastewater sample (95% CI: 57% - 77%), and 40% were associated with a positive surface sample (95% CI: 29% - 52%). The techniques we utilized allowed for near-complete genomic sequencing of wastewater and surface samples. Interpretation: Passive environmental surveillance can detect the presence of COVID-19 cases in non-residential community school settings with a high degree of accuracy. Funding: County of San Diego, Health and Human Services Agency, National Institutes of Health, National Science Foundation, Centers for Disease Control.

7.
Lancet Reg Health Am ; 19: 100449, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36844610

ABSTRACT

Background: Schools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown. Methods: The objective of this study was to determine the effectiveness and accuracy of community-based passive wastewater and surface (environmental) surveillance to detect SARS-CoV-2 infection in neighborhood schools compared to weekly diagnostic (PCR) testing. We implemented an environmental surveillance system in nine elementary schools with 1700 regularly present staff and students in southern California. The system was validated from November 2020 to March 2021. Findings: In 447 data collection days across the nine sites 89 individuals tested positive for COVID-19, and SARS-CoV-2 was detected in 374 surface samples and 133 wastewater samples. Ninety-three percent of identified cases were associated with an environmental sample (95% CI: 88%-98%); 67% were associated with a positive wastewater sample (95% CI: 57%-77%), and 40% were associated with a positive surface sample (95% CI: 29%-52%). The techniques we utilized allowed for near-complete genomic sequencing of wastewater and surface samples. Interpretation: Passive environmental surveillance can detect the presence of COVID-19 cases in non-residential community school settings with a high degree of accuracy. Funding: County of San Diego, Health and Human Services Agency, National Institutes of Health, National Science Foundation, Centers for Disease Control.

8.
J Orthop Res ; 40(9): 2103-2112, 2022 09.
Article in English | MEDLINE | ID: mdl-34914129

ABSTRACT

Degeneration of articular cartilage is often triggered by a small tissue crack. As cartilage structure and composition change with age, the mechanics of cracked cartilage may depend on the tissue age, but this relationship is poorly understood. Here, we investigated cartilage mechanics and crack deformation in immature and mature cartilage exposed to a full-thickness tissue crack using indentation testing and histology, respectively. When a cut was introduced, tissue cracks opened wider in the mature cartilage compared to the immature cartilage. However, the opposite occurred upon mechanical indentation over the cracked region. Functionally, the immature-cracked cartilages stress-relaxed faster, experienced increased tissue strain, and had reduced instantaneous stiffness, compared to the mature-cracked cartilages. Taken together, mature cartilage appears to withstand surface cracks and maintains its mechanical properties better than immature cartilage and these superior properties can be explained by the structure of their collagen fibrous network.


Subject(s)
Cartilage, Articular , Stress, Mechanical , Cartilage, Articular/physiopathology , Humans
9.
Front Public Health ; 10: 921596, 2022.
Article in English | MEDLINE | ID: mdl-35942259

ABSTRACT

In 2020, Mexico reported the lowest tuberculosis (TB) incidence on record, and it is unclear to what extent COVID-19 has impacted TB surveillance, diagnosis, and treatment. It is important to understand COVID-19's impact in Baja California (BC), which has the highest TB burden in Mexico. With the increasing number of migrants and asylum seekers arriving in BC, limited resources and crowded living conditions increase the risk of TB transmission. The purpose of this study was to assess the impact of COVID-19 on TB diagnosis and treatment in BC. We were also interested in health disparities experienced by migrants in BC. We conducted a mixed methods analysis using quantitative surveillance data obtained from the Mexico National TB Program (NTP) and qualitative data collected through in-depth interviews and focus group discussions with TB program directors and personnel in BC's four provincial health jurisdictions. Compared to the year prior, surveillance data from March 2020 - February 2021 revealed that TB incidence in BC declined by 30.9% and favorable TB outcomes (TB cure or treatment completion) declined by 49.8%. Elucidating differences by migrant status was complicated by the lack of standardized collection of migrant status by the NTP. Qualitative analysis revealed that TB diagnostic and treatment supplies and services became limited and disproportionately accessible across jurisdictions since the pandemic began; however, favorable adaptations were also reported, such as increased telemedicine use and streamlined care referral processes. Participants shared that migrant status is susceptible to misclassification and that TB care is difficult due to the transitory nature of migrants. This study did not identify major differences in TB service delivery or access between migrants and non-migrants in BC; however, migrant status was frequently missing. COVID-19 has overwhelmed health systems worldwide, disrupting timely TB diagnostic and treatment services, and potentially caused underdiagnosis of TB in BC. TB programs in BC should quickly restore essential services that were disrupted by COVID-19 while identifying and preserving beneficial program adaptations, such as telemedicine and streamlined care referral processes. Improved methods for documenting migrant status of TB cases are also needed.


Subject(s)
COVID-19 , Refugees , Transients and Migrants , Tuberculosis , COVID-19/diagnosis , COVID-19/epidemiology , Humans , Mexico/epidemiology , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/therapy
10.
Aust Orthod J ; 27(2): 162-8, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22372273

ABSTRACT

AIMS: The aim of the present study was to compare diagnostic assessments of anterior tooth and bone status in a randomised cohort of pre-orthodontic patients using panoramic and periapical radiographs. METHOD: Four hundred and forty-four cases with matched periapical and panoramic radiographs were examined by three observers. Two were final-year postgraduate endodontic students and the other, a final-year Honours degree dental student. Multi-rater Kappa values were used to assess the reliability of the observers, with a value of 1 equating to complete agreement. RESULTS: With the exception of endodontic Class 1 and 2 palatal invaginations, reliability exceeded 0.95 for all three observers. An assessment of the graduate endodontic students revealed only a marginal increase in the kappa values. Statistical analysis (p < 0.05) determined that developmental anomalies or tooth/bone pathoses were more reliably detected by observers using periapical radiographs compared with panoramic films. This finding has relevance given the likelihood of anterior dental trauma among young children. CONCLUSION: While there have been considerable improvements in the quality of dental panoramic radiography, the present study indicated that a reliable pre-orthodontic or post-trauma diagnostic assessment should include both panoramic and intra-oral radiographs.


Subject(s)
Alveolar Process/diagnostic imaging , Cuspid/diagnostic imaging , Incisor/diagnostic imaging , Radiography, Bitewing/standards , Radiography, Panoramic/standards , Anodontia/diagnostic imaging , Cohort Studies , Cuspid/abnormalities , Dental Enamel/diagnostic imaging , Dental Pulp Calcification/diagnostic imaging , Humans , Incisor/abnormalities , Jaw Diseases/diagnosis , Observer Variation , Periapical Diseases/diagnostic imaging , Root Resorption/diagnostic imaging , Tooth Diseases/diagnostic imaging , Tooth Fractures/diagnostic imaging , Tooth Root/injuries , Tooth, Nonvital/diagnostic imaging , Tooth, Supernumerary/diagnostic imaging
11.
Saf Health Work ; 12(2): 184-191, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34178395

ABSTRACT

BACKGROUND: Hearing protection devices (HPDs) are often used in the workplace to prevent hearing damage caused by noise. However, a factor that can lead to hearing loss in the workplace is improper HPD fitting, and the previous literature has shown that instructing workers on how to properly insert their HPDs can make a significant difference in the degree of attenuation. METHODS: Two studies were completed on a total of 33 Hydro One workers. A FitCheck Solo field attenuation estimation system was used to measure the personal attenuation rating (PAR) before and after providing one-on-one fitting instructions. In addition, external ear canal diameters were measured, and a questionnaire with items related to frequency of use, confidence, and discomfort was administered. RESULTS: Training led to an improvement in HPD attenuation, particularly for participants with poorer PARs before training. The questionnaire results indicated that much HPD discomfort is caused by heat, humidity, and communication difficulties. External ear canal asymmetry did not appear to significantly influence the measured PAR. CONCLUSION: In accordance with the previous literature, our studies suggest that one-on-one instruction is an effective training method for HPD use. Addressing discomfort issues from heat, humidity, and communication issues could help to improve the use of HPDs in the workplace. Further research into the effects of canal asymmetry on the PAR is needed.

12.
J Invest Dermatol ; 126(8): 1792-803, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16628194

ABSTRACT

Atopic dermatitis (AD) is a common chronic skin inflammatory disease. Long-term use of topical corticosteroids in skin inflammation poses risks of systemic and local side effects. The NF-kappaB transcription factor family plays a central role in the progression and maintenance of AD. This study explores the possibility of using topical NF-kappaB Decoy as a novel therapeutic alternative for targeting Th1/Th2-driven skin inflammation in experimental AD. A high-affinity, topical NF-kappaB Decoy developed for human efficacy demonstrates: (i) efficient NF-kappaB Decoy penetration in pig skin, (ii) NF-kappaB Decoy nuclear localization in keratinocytes and key immune cells, and (iii) potent "steroid-like" efficacy in a chronic dust-mite antigen skin inflammation treatment model. NF-kappaB Decoy exerts its anti-inflammatory action through the effective inhibition of essential regulators of inflammation and by induction of apoptosis of key immune cells. Unlike betamethasone valerate (BMV), long-term NF-kappaB Decoy treatment does not induce skin atrophy. Moreover, topical NF-kappaB Decoy, in contrast to BMV, restores compromised stratum corneum integrity and barrier function. Steroid withdrawal causes rapid rebound of inflammation, while the NF-kappaB Decoy therapeutic benefit was maintained for weeks. Thus, topical NF-kappaB Decoy provides a novel mechanism of reducing chronic skin inflammation with improved skin homeostasis and minimal side effects.


Subject(s)
Dermatitis, Atopic/drug therapy , Immunosuppressive Agents/administration & dosage , Oligodeoxyribonucleotides/administration & dosage , Skin/drug effects , Administration, Topical , Animals , Apoptosis/drug effects , Apoptosis/immunology , Atrophy , Cell Division/drug effects , Cell Division/immunology , Dermatitis, Atopic/immunology , Dermatitis, Atopic/pathology , Ear, External , Edema/drug therapy , Edema/immunology , Male , Mice , Mice, Inbred Strains , Ointments , Permeability/drug effects , Skin/immunology , Skin/pathology
13.
Ann Anat ; 193(6): 486-93, 2011 Dec 20.
Article in English | MEDLINE | ID: mdl-22074679

ABSTRACT

Even now, sepsis remains a major problem in modern clinical medicine, leading to systemic inflammatory response including altered leukocyte subset distribution and increased cytokine release. As immune cells are known to express NPY receptors, we investigated the effects of a specific NPY Y(2) receptor agonist (NPY(13-36)) and/or the corresponding Y(2) receptor antagonist BIIE0246 treatment on blood (by FACS analyses) and tissue (by immunohistochemistry) leukocyte subsets as well as on levels of IL-4, IL-6, IL-10, TNF-α, INF-γ (by Cytometric Bead Array) in healthy and acutely endotoxemic rats. Results show a significant decrease in blood monocytes after LPS challenge in endotoxemic control animals (by 93%), in endotoxemic NPY(13-36) treated animals (by 83%) and in endotoxemic BIIE0246 treated animals (by 88%) as compared to the corresponding healthy controls. Endotoxemic control animals showed a significant increase of TNF-α (by 98%) as compared to the healthy control group. A treatment with NPY(13-36) significantly stabilized TNF-α level in endotoxemic animals. This study indicates distinct subset- and cytokine-specific in vivo effects induced by an NPY Y(2) receptor specific treatment after a short-term LPS challenge.


Subject(s)
Arginine/analogs & derivatives , Benzazepines/pharmacology , Cytokines/immunology , Endotoxemia/immunology , Leukocytes/immunology , Neuropeptide Y/pharmacology , Peptide Fragments/pharmacology , Receptors, Neuropeptide Y/antagonists & inhibitors , Animals , Arginine/pharmacology , Cells, Cultured , Leukocytes/drug effects , Male , Rats , Rats, Inbred Lew
14.
Anesthesiol Clin ; 28(2): 225-49, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20488392

ABSTRACT

Postoperative nausea and vomiting (PONV) continues to be one of the most common complaints following surgery, occurring in more than 30% of surgeries, or as high as 70% to 80% in certain high-risk populations without prophylaxis. The 5-hydroxytryptamine type 3 (5-HT(3)) receptor antagonists continue to be the mainstay of antiemetic therapy, but newer approaches, such as neurokinin-1 antagonists, a longer-acting serotonin receptor antagonist, multimodal management, and novel techniques for managing high-risk patients are gaining prominence. The related problem of postdischarge nausea and vomiting (PDNV) has received increasing attention from health care providers. The issues of PONV and PDNV are especially significant in the context of ambulatory surgeries, which comprise more than 60% of the combined 56.4 million ambulatory and inpatient surgery visits in the United States. Because of the relatively brief period that ambulatory patients spend in health care facilities, it is particularly important to prevent and treat PONV and PDNV swiftly and effectively.


Subject(s)
Ambulatory Surgical Procedures/adverse effects , Antiemetics/therapeutic use , Postoperative Nausea and Vomiting/drug therapy , Acupressure/methods , Acupuncture Therapy/methods , Benzamides/therapeutic use , Butyrophenones/therapeutic use , Combined Modality Therapy/methods , Glucocorticoids/therapeutic use , Humans , Neurotransmitter Agents/therapeutic use , Phenothiazines/therapeutic use , Postoperative Nausea and Vomiting/etiology , Propofol/therapeutic use , Risk Factors
15.
Gut ; 56(4): 524-33, 2007 Apr.
Article in English | MEDLINE | ID: mdl-16950831

ABSTRACT

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a key transcriptional regulator of inflammatory bowel disease (IBD). AIM: To investigate the therapeutic potential of a locally administered "non-viral" nuclear factor-kappaB decoy (NFkappaBD) in multiple experimental models of IBD. METHODS: A fully phosphorothioated decoy oligonucleotide with improved stability that specifically binds NF-kappaB and blocks inflammatory mediators regulated by this transcription factor without the help of viral envelope-assisted delivery was developed. The therapeutic effects of NFkappaBD were studied in the trinitrobenzene sulphonic acid, oxazolone and dextran sodium sulphate induced colitis models. RESULTS: Intracolonic administration of NFkappaBD results in the delivery of NFkappaBD to inflammatory cells and a reduction of NF-kappaB heterodimers. In the T helper cell 1-driven trinitrobenzene sulphonic acid-induced colitis model, mice receiving NFkappaBD treatment exhibit a dose-dependent reduction in disease severity and a more rapid recovery to normal body weight, similar to a clinically relevant dose of budesonide. Clinical efficacy was corroborated by considerable reductions in colitis pathology and tissue levels of several pro-inflammatory markers, including tumour necrosis factor alpha, interleukin 6, interleukin 1beta and monocyte chemotactic protein 1. NFkappaBD also mitigates disease activity in the T helper cell 2-like oxazolone colitis and epithelial injury-related acute dextran sodium sulphate colitis models. Interestingly, restoration of tissue homeostasis is observed in NFkappaBD-treated animals with the rapid re-emergence of functional goblet cells and a return to normal patterns of cell proliferation in the mucosal epithelium and smooth muscle cell layers. CONCLUSIONS: These data support the potential use of "naked" NFkappaBD as a cross-functional therapeutic in IBD, and show for the first time that it can facilitate the restoration of colon homeostasis and function.


Subject(s)
Genetic Therapy/methods , Inflammatory Bowel Diseases/therapy , Oligodeoxyribonucleotides/administration & dosage , Animals , Colon/metabolism , Dextran Sulfate , Disease Models, Animal , Female , Gene Transfer Techniques , Homeostasis/drug effects , Inflammation Mediators/metabolism , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Microscopy, Confocal , NF-kappa B/metabolism , Oligodeoxyribonucleotides/therapeutic use , Oxazolone , Trinitrobenzenesulfonic Acid
SELECTION OF CITATIONS
SEARCH DETAIL