4-Hydroxynonenal regulates mitochondrial function in human small airway epithelial cells

Prolonged exposure to oxidative stress causes Acute Lung Injury (ALI) and significantly impairs pulmonary function. Previously we have demonstrated that mitochondrial dysfunction is a key pathological factor in hyperoxic ALI. While it is known that hyperoxia induces the production of stable, but toxic 4-hydroxynonenal (4-HNE) molecule, it is unknown how the reactive aldehyde disrupts mitochondrial function. Our previous in vivo study indicated that exposure to hyperoxia significantly increases 4-HNE-Protein adducts, as well as levels of MDA in total lung homogenates. Based on the in vivo studies, we explored the effects of 4-HNE in human small airway epithelial cells (SAECs). Human SAECs treated with 25 μM of 4-HNE showed a significant decrease in cellular viability and increased caspase-3 activity. Moreover, 4-HNE treated SAECs showed impaired mitochondrial function and energy production indicated by reduced ATP levels, mitochondrial membrane potential, and aconitase activity. This was followed by a significant decrease in mitochondrial oxygen consumption and depletion of the reserve capacity. The direct effect of 4-HNE on the mitochondrial respiratory chain was confirmed using Rotenone. Furthermore, SAECs treated with 25 μM 4-HNE showed a time-dependent depletion of total Thioredoxin (Trx) proteins and Trx activity. Taken together, our results indicate that 4-HNE induces cellular and mitochondrial dysfunction in human SAECs, leading to an impaired endogenous antioxidant response.     

A Human Rights-Based Approach to Farmworker Health: An Overarching Framework to Address the Social Determinants of Health

Migrant and seasonal workers have a right to the highest attainable standard of health. Unfortunately, these farmworkers face a multitude of challenges. They are employed in one of the most dangerous industries and face serious occupational health risks, while positioned at the bottom of the social hierarchy. They often lack formal education and training, English language proficiency, legal status, access to information, and equitable opportunities to health and healthcare. This article will explore the international human rights conventions that support farmworkers’ right to health and healthcare in the United States. International human rights may provide a valuable legal framework that could be used to advocate on behalf of farmworkers and address the social determinants of health. Therefore, a Human Rights-Based Approach to Farmworker health will be presented along with recommendations for how to advance health and access to healthcare among this population. Fostering the health and well-being of migrant and seasonal farmworkers is critical to advancing equity, social justice, and maintaining the workforce required to meet production needs and safeguard the economic competitiveness of the industry.     

The effect of a selective cyclooxygenase-2 inhibitor (celecoxib) on chronic periodontitis

BACKGROUND: Non-steroidal anti-inflammatory agents inhibit the production of cyclooxygenase (COX) products and can attenuate bone loss. In this double-masked, placebo-controlled, randomized clinical trial, the efficacy of celecoxib (COX-2 inhibitor) was evaluated in conjunction with scaling and root planing (SRP) in subjects with chronic periodontitis (CP). METHODS: A total of 131 subjects were randomized to receive SRP and either celecoxib (200 mg) or placebo every day for 6 months. Clinical outcomes were assessed every 3 months for 12 months as mean changes from baseline. Primary efficacy parameters included clinical attachment level (CAL) and probing depth (PD). Secondary outcomes included percentages of tooth sites with CAL loss or gain > or =2 mm, changes in bleeding on probing (BOP), plaque index, and mobility. Prior to analysis, tooth sites were grouped based on baseline PD as shallow (1 to 3 mm), moderate (4 to 6 mm), or deep (> or =7 mm). RESULTS: Mean PD reduction and CAL gain were greater in the celecoxib group, primarily in moderate and deep sites, throughout the study (PD: 3.84 mm versus 2.06 mm, P <0.001; CAL: 3.74 mm versus 1.43 mm, P <0.0001 for deep sites at 12 months). The celecoxib group also exhibited a greater percentage of sites with > or =2 mm CAL gain and fewer sites with > or =2 mm CAL loss. Both groups showed improved plaque control and BOP scores. Demographic, social, and behavioral factors did not affect treatment outcomes. CONCLUSIONS: Celecoxib can be an effective adjunctive treatment to SRP to reduce progressive attachment loss in subjects with CP. Its beneficiary effect persisted even at 6 months postadministration. However, given the increased cardiovascular risks associated with the use of this drug, close patient supervision and strict adherence to dosage and administration guidelines established by the Unites States Food and Drug Administration are of paramount importance.     

Examiner training and reliability in two randomized clinical trials of adult dental caries

Objectives: This report describes the training of dental examiners participating in two dental caries clinical trials and reports the inter‐ and intra‐examiner reliability scores from the initial standardization sessions. Methods: Study examiners were trained to use a modified International Caries Detection and Assessment System II system to detect the visual signs of non‐cavitated and cavitated dental caries in adult subjects. Dental caries was classified as no caries (S), non‐cavitated caries (D1), enamel caries (D2), and dentine caries (D3). Three standardization sessions involving 60 subjects and 3,604 tooth surface calls were used to calculate several measures of examiner reliability. Results: The prevalence of dental caries observed in the standardization sessions ranged from 1.4 percent to 13.5 percent of the coronal tooth surfaces examined. Overall agreement between pairs of examiners ranged from 0.88 to 0.99. An intra‐class coefficient threshold of 0.60 was surpassed for all but one examiner. Inter‐examiner unweighted kappa values were low (0.23‐0.35), but weighted kappas and the ratio of observed to maximum kappas were more encouraging (0.42‐0.83). The highest kappa values occurred for the S/D1 versus D2/D3 two‐level classification of dental caries, for which seven of the eight examiners achieved observed to maximum kappa values over 0.90. Intra‐examiner reliability was notably higher than inter‐examiner reliability for all measures and dental caries classifications employed. Conclusion: The methods and results for the initial examiner training and standardization sessions for two large clinical trials are reported. Recommendations for others planning examiner training and standardization sessions are offered.     

Novel Approach to Inpatient Glucometric Monitoring and Variability in a Community Hospital Setting

Background:

Hyperglycemia and glucose variability in the hospital environment are associated with higher rates of complications, longer lengths of stay, and mortality. Standardized metrics are needed to assess the efficacy and safety of glucose management interventions.

Methods:

Glucometric data were collected from 2024 inpatients in a San Diego hospital between 2009 and 2011. As a complementary measure of glucose control, individual patient excursion rates were calculated using counts of distinct excursions from normal to critical glucose ranges >180 or <70 mg/dL. Prediction models for excursion rates were devised, based on patient demographic and clinical characteristics.

Results:

Patients were predominantly male (51.2%), Caucasian (86.0%), and elderly (median age 72 years). Obesity was prevalent: 32% were overweight and 33% were obese. Median length of hospitalization was 5.0 days (range, 0.8-139.4 days). Unadjusted rate of excursions >180 mg/dL was 0.456 per 24 hours. The proportion of zero excursions decreased as severity of illness decreased, but was unrelated to age. Excursion rates were slightly smaller for major and extreme severity of illness compared to mild or moderate illness severity. Excursion rates did not vary in a monotone fashion with age, although the general pattern reflected a reduction in excursion rates from the first age quartile (19 to 59) through the last age quartile (83 to 100). Using the Akaike information criterion, zero-inflated negative binomial models were identified as appropriate for analyzing glucose excursion rates.

Conclusions:

Systematic approaches to glucose reporting and management in the hospital environment offer “windows of opportunity” to improve diabetes care.