Diabetes mellitus and hard braking events in older adult drivers.

BACKGROUND: Diabetes mellitus (DM) can impair driving safety due to hypoglycemia, hyperglycemia, diabetic peripheral neuropathy, and diabetic eye diseases. However, few studies have examined the association between DM and driving safety in older adults based on naturalistic driving data. METHODS: Data for this study came from a multisite naturalistic driving study of drivers aged 65-79 years at baseline. Driving data for the study participants were recorded by in-vehicle recording devices for up to 44 months. We used multivariable negative binomial modeling to estimate adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (HBEs, defined as maneuvers with deceleration rates ≥ 0.4 g) associated with DM. RESULTS: Of the 2856 study participants eligible for this analysis, 482 (16.9%) reported having DM at baseline, including 354 (12.4%) insulin non-users and 128 (4.5%) insulin users. The incidence rates of HBEs per 1000 miles were 1.13 for drivers without DM, 1.15 for drivers with DM not using insulin, and 1.77 for drivers with DM using insulin. Compared to drivers without DM, the risk of HBEs was 48% higher for drivers with DM using insulin (aIRR 1.48; 95% CI: 1.43, 1.53). CONCLUSION: Older adult drivers with DM using insulin appear to be at increased proneness to vehicular crashes. Driving safety should be taken into consideration in DM care and management.

Association between polypharmacy and hard braking events in older adult drivers.

BACKGROUND: Polypharmacy (i.e., simultaneous use of two or more medications) poses a serious safety concern for older drivers. This study assesses the association between polypharmacy and hard braking events in older adult drivers. METHODS: Data for this study came from a naturalistic driving study of 2990 older adults. Information about medications was collected through the "brown-bag review" method. Primary vehicles of the study participants were instrumented with data recording devices for up to 44 months. Multivariable negative binomial model was used to estimate the adjusted incidence rate ratios (aIRRs) and 95 % confidence intervals (CIs) of hard-braking events (i.e., maneuvers with linear deceleration rates ≥0.4 g) associated with polypharmacy. RESULTS: Of the 2990 participants, 2872 (96.1 %) were eligible for this analysis. At the time of enrollment, 157 (5.5 %) drivers were taking fewer than two medications, 904 (31.5 %) were taking 2-5 medications, 895 (31.2 %) were taking 6-9 medications, 571 (19.9 %) were taking 10-13 medications, and 345 (12.0 %) were taking 14 or more medications. Compared to drivers using fewer than two medications, the risk of hard-braking events increased 8 % (aIRR 1.08, 95 % CI 1.04, 1.13) for users of 2-5 medications, 12 % (aIRR 1.12, 95 % CI 1.08, 1.16) for users of 6-9 medications, 19 % (aIRR 1.19, 95 % CI 1.15, 1.24) for users of 10-13 medications, and 34 % (aIRR 1.34, 95 % CI 1.29, 1.40) for users of 14 or more medications. CONCLUSIONS: Polypharmacy in older adult drivers is associated with significantly increased incidence of hard-braking events in a dose-response fashion. Effective interventions to reduce polypharmacy use may help improve driving safety in older adults.

Effects of Storage Time and Thawing Method on Selected Nutrients in Whole Fish for Zoo Animal Nutrition.

Piscivores in human care receive whole fish that were frozen, stored and thawed before feeding. Nutrient losses have been documented, but exact changes during storage and with different thawing methods are unknown. Primarily, it was hypothesized that frozen fish lose different vitamins and trace minerals during a storage period of six months. Secondly, that different thawing methods have a significant influence on the degree of vitamin loss. Three fish species, herring (Clupeus harengus), mackerel (Scomber scombrus) and capelin (Mallotus villosus) were analyzed at four time points within a storage period of 6 months at -20 °C. At each time point, three thawing methods were applied: thawing in a refrigerator (R), thawing at room temperature (RT), and thawing under running water (RW). The following nutrients were analyzed: vitamin A, B1, D3 and E, iron (Fe), copper (Cu), zinc (Zn) and selenium (Se). The statistical method used was a linear mixed effect model. Cu was below detection limits in all analyzed samples, vitamin B1 in most analyzed herring (44/48 samples) and capelin (in 25/36 samples), respectively. In addition, the vitamin D3 concentration was also below detection limits in half of the capelin samples (18/36). No concentration changes of Fe (p = 0.616), Zn (p = 0.686) or Se (p = 0.148) were observed during a storage period of six months, in contrast to a significant decrease in vitamin A (p = 0.019), D3 (p = 0.034) and E (p = 0.003) concentrations. Thawing fish with different thawing methods did not result in concentration changes of Fe (p = 0.821), Zn (p = 0.549) or Se (p = 0.633), but in a significant concentration change of vitamin A (p = 0.002). It is essential to supplement vitamins B1 and E in diets containing whole fish to avoid deficiencies in piscivorous species, and care should be taken not to store fish longer than six months, due to the depletion of vitamins A, D3 and E.

"They just did what they usually do": Mistreatment, abuse, and neglect in nursing homes from the perspective of Ministry of Health auditing teams.

The aim of this article was to examine how Ministry of Health auditing teams experience quality of care, mistreatment, abuse, and neglect in nursing homes in Israel. The research included four in-depth focus groups consisting of 19 multidisciplinary auditors. The qualitative analysis was encoded in stages with repeated comparisons between individual participants and within groups and led to three main themes: (1) Failure in addressing basic, personal, and social needs of residents in nursing homes; (2) Mistreatment manifested in violation of residents' privacy and human dignity, neglect, and physical harm; (3) Abuse, including psychological, financial, and physical abuse. The findings can be explained by the characteristics of nursing homes as total institutions, as well as perceptions of ageism and de-humanization of the residents. In addition, the findings highlight the importance of the auditing role in monitoring the nursing homes' quality of care and the safety of the residents.

Occupational Conditions Associated With Negative Mental Health Outcomes in New York State Health Professionals During the COVID-19 Pandemic.

OBJECTIVE: The aim of this study was to assess occupational circumstances associated with adverse mental health among health care workers during the COVID-19 pandemic. METHODS: A cross-sectional study examined responses to an on-line survey conducted among 2076 licensed health care workers during the first pandemic peak. Mental health (depression, anxiety, stress, and anger) was examined as a multivariate outcome for association with COVID-related occupational experiences. RESULTS: Odds of negative mental health were increased among those who worked directly with patients while sick themselves (adjusted odds ratio, 2.29; 95% confidence interval, 1.71-3.08) and were independently associated with working more hours than usual in the past 2 weeks, having family/friends who died due to COVID-19, having COVID-19 symptoms, and facing insufficiencies in personal protective equipment/other shortages. CONCLUSIONS: Occupational circumstances were associated with adverse mental health outcomes among health care workers during the COVID-19 pandemic, and some are potentially modifiable.

Hopelessness in New York State Physicians During the First Wave of the COVID-19 Outbreak.

BACKGROUND: In the United States, New York State's health care system experienced unprecedented stress as an early epicenter of the coronavirus disease 2019 (COVID-19) pandemic. This study aims to assess the level of hopelessness in New York State physicians working on the frontlines during the first wave of the COVID-19 outbreak. METHODS: A confidential online survey sent to New York State health care workers by the state health commissioner's office was used to gather demographic and hopelessness data as captured by a brief Hopelessness Scale. Adjusted linear regression models were used to assess the associations of physician age, sex, and number of triage decisions made, with level of hopelessness. RESULTS: In total, 1330 physicians were included, of whom 684 were male (51.4%). Their average age was 52.4 years (SD=12.7), with the majority of respondents aged 50 years and older (55.2%). Almost half of the physician respondents (46.3%) worked directly with COVID-19 patients, and 163 (12.3%) were involved in COVID-19-related triage decisions. On adjusted analysis, physicians aged 40 to 49 years had significantly higher levels of hopelessness compared with those aged 50 years or more (µ=0.441, SD=0.152, P=0.004). Those involved in 1 to 5 COVID-19-related triage decisions had a significantly lower mean hopelessness score (µ=-0.572, SD=0.208, P=0.006) compared with physicians involved in none of these decisions. CONCLUSION: Self-reported hopelessness was significantly higher among physicians aged 40 to 49 years and those who had not yet been involved in a life or death triage decision. Further work is needed to identify strategies to support physicians at high risk for adverse mental health outcomes during public health emergencies such as the COVID-19 pandemic.

Factors Related to Self-Reported Distress Experienced by Physicians During Their First COVID-19 Triage Decisions.

OBJECTIVE: The aim of this study was to identify factors associated with distress experienced by physicians during their first coronavirus disease 2019 (COVID-19) triage decisions. METHODS: An online survey was administered to physicians licensed in New York State. RESULTS: Of the 164 physicians studied, 20.7% experienced severe distress during their first COVID-19 triage decisions. The mean distress score was not significantly different between physicians who received just-in-time training and those who did not (6.0 ± 2.7 vs 6.2 ± 2.8; P = 0.550) and between physicians who received clinical guidelines and those who did not (6.0 ± 2.9 vs 6.2 ± 2.7; P = 0.820). Substantially increased odds of severe distress were found in physicians who reported that their first COVID-19 triage decisions were inconsistent with their core values (adjusted odds ratio, 6.33; 95% confidence interval, 2.03-19.76) and who reported having insufficient skills and expertise (adjusted odds ratio 2.99, 95% confidence interval 0.91-9.87). CONCLUSION: Approximately 1 in 5 physicians in New York experienced severe distress during their first COVID-19 triage decisions. Physicians with insufficient skills and expertise, and core values misaligned to triage decisions are at heightened risk of experiencing severe distress. Just-in-time training and clinical guidelines do not appear to alleviate distress experienced by physicians during their first COVID-19 triage decisions.

Using Naturalistic Driving Data to Predict Mild Cognitive Impairment and Dementia: Preliminary Findings from the Longitudinal Research on Aging Drivers (LongROAD) Study.

Emerging evidence suggests that atypical changes in driving behaviors may be early signals of mild cognitive impairment (MCI) and dementia. This study aims to assess the utility of naturalistic driving data and machine learning techniques in predicting incident MCI and dementia in older adults. Monthly driving data captured by in-vehicle recording devices for up to 45 months from 2977 participants of the Longitudinal Research on Aging Drivers study were processed to generate 29 variables measuring driving behaviors, space and performance. Incident MCI and dementia cases (n = 64) were ascertained from medical record reviews and annual interviews. Random forests were used to classify the participant MCI/dementia status during the follow-up. The F1 score of random forests in discriminating MCI/dementia status was 29% based on demographic characteristics (age, sex, race/ethnicity and education) only, 66% based on driving variables only, and 88% based on demographic characteristics and driving variables. Feature importance analysis revealed that age was most predictive of MCI and dementia, followed by the percentage of trips traveled within 15 miles of home, race/ethnicity, minutes per trip chain (i.e., length of trips starting and ending at home), minutes per trip, and number of hard braking events with deceleration rates ≥ 0.35 g. If validated, the algorithms developed in this study could provide a novel tool for early detection and management of MCI and dementia in older drivers.

Potentially Inappropriate Medication Use and Hard Braking Events in Older Drivers.

Potentially inappropriate medications (PIMs) identified by the American Geriatrics Society should generally be avoided by older adults because of ineffectiveness or excess risk of adverse effects. Few studies have examined the effects of PIMs on driving safety measured by prospectively and objectively collected driving data. Data for this study came from the Longitudinal Research on Aging Drivers study, a multisite naturalistic driving study of older adults. Multivariable negative binominal modeling was used to estimate incidence rate ratios and 95% confidence intervals of hard braking events (proxies for unsafe driving behavior defined as events with a deceleration rate ≥0.4 g) associated with PIM use among older drivers. The study sample consisted of 2932 drivers aged 65-79 years at baseline, including 542 (18.5%) who used at least one PIM. These drivers were followed through an in-vehicle recording device for up to 44 months. The overall incidence of hard braking events was 1.16 per 1000 miles. Use of PIMs was associated with a 10% increased risk of hard braking events. Compared to drivers who were not using PIMs, the risk of hard braking events increased 6% for those using one PIM, and 24% for those using two or more PIMs. Use of PIMs by older adult drivers is associated in a dose-response fashion with elevated risks of hard braking events. Reducing PIM use in older adults might help improve driving safety as well as health outcomes.

Prevalence of Potentially Inappropriate Medication use in older drivers.

BACKGROUND: Potentially Inappropriate Medication (PIM) use has been studied in a variety of older adult populations across the world. We sought to examine the prevalence and correlates of PIM use in older drivers. METHODS: We applied the American Geriatrics Society 2015 Beers Criteria to baseline data collected from the "brown-bag" review of medications for participants of the Longitudinal Research on Aging Drivers (LongROAD) study to examine the prevalence and correlates of PIM use in a geographically diverse, community-dwelling sample of older drivers (n = 2949). Proportions of participants who used one or more PIMs according to the American Geriatrics Society 2015 Beers Criteria, and estimated odds ratios (ORs) and 95% confidence intervals (CIs) of PIM use associated with participant characteristics were calculated. RESULTS: Overall, 18.5% of the older drivers studied used one or more PIM. The most commonly used therapeutic category of PIM was benzodiazepines (accounting for 16.6% of the total PIMs identified), followed by nonbenzodiazepine hypnotics (15.2%), antidepressants (15.2%), and first-generation antihistamines (10.5%). Compared to older drivers on four or fewer medications, the adjusted ORs of PIM use were 2.43 (95% CI 1.68-3.51) for those on 5-7 medications, 4.19 (95% CI 2.95-5.93) for those on 8-11 medications, and 8.01 (95% CI 5.71-11.23) for those on ≥12 medications. Older drivers who were female, white, or living in urban areas were at significantly heightened risk of PIM use. CONCLUSION: About one in five older drivers uses PIMs. Commonly used PIMs are medications known to impair driving ability and increase crash risk. Implementation of evidence-based interventions to reduce PIM use in older drivers may confer both health and safety benefits. TRIAL REGISTRATION: Not applicable.

ADCC can improve graft vs leukemia effect after T- and B-cell depleted haploidentical stem cell transplantation in pediatric B-lineage ALL.

Posttransplant relapsed B-cell precursor ALL can be cured by 2nd hematopoietic stem cell transplantation (HSCT) in 20% of patients. The major cause of death after second HSCT is leukemic relapse. One reliable predictor for survival after 2nd-HSCT are posttransplant MRD levels. Patients with detectable or increase of MRD are likely to relapse. Patients in complete molecular remission show the best leukemia-free survival and lowest cumulative incidence (CI) of relapse. As patients who undergo second or subsequent HSCT are high-risk patients, we evaluated the prophylactic use of the chimeric Fc-optimized CD19-4G7SDIE-mAb. Posttransplant relapsed CD19+ BCP-ALL patients, who underwent a second or subsequent haplo-HSCT from a T- and B-cell depleted graft received posttransplant prophylactic CD19-4G7SDIE-mAb treatment on compassionate use in complete molecular remission, to increase the antileukemic activity of the new reconstituting immune system by recruiting Fc-expressing effector cells. NK cells recovered early and robust. The 3 year overall survival in 15 evaluable patients was 56%, the 3 year event-free survival was 55% and the CI of relapse 38%. Compared to a historical control group, the CI of relapse was markedly lower and consecutively the EFS higher. Posttransplant-targeted therapy may overcome the need for unspecific GvL effect of undesired GvHD, that can cause severe morbidity and mortality. Due to a low adverse event profile the CD19-4G7SDIE-mAb may be suitable for broad administration to consolidate posttransplant MRD negativity.

Metastatic Thymoma in a Scarlet Macaw ( Ara macao ).

A 49-year-old female scarlet macaw ( Ara macao ) was presented with a mass in the cervical region. The bird showed no evidence of pain or discomfort, it swallowed food normally, and its breathing pattern was unremarkable. Results of contrast radiographic imaging revealed a well-demarcated mass in the right cervical region not related to the crop. After surgical resection and histopathologic evaluation, a malignant nodular stage of an epithelioid cortical-type thymoma was diagnosed. One year later, metastasis of the thymoma to the lung was diagnosed and confirmed at postmortem examination. The final diagnosis was corrected to malignant nodular stage of an epithelioid cortical-type thymoma with metastasis to the lung. This is the first report in an avian species of a malignant thymoma with metastasis to the lung after complete resection of the initial cervical thymoma and a survival time of 1 year.

Focal bacterial meningitis following ascending bite wound infection leading to paraparesis in a captive California sea lion (Zalophus californianus).

Magnetic resonance imaging was performed on a 15-yr-old captive female California sea lion (Zalophus californianus) with a 2-wk history of progressive paraparesis and a 9-mo history of exudative skin lesion on the left thoracic wall. Magnetic resonance images showed a well-defined muscle infiltrating lesion ventrolateral to the seventh cervical to the third thoracic vertebra on the left side, which extended through the left intervertebral foramina C7 to T3 into the vertebral canal, causing spinal cord compression and displacement as well as inflammation of the spinal cord and nerves. This lesion surprisingly caused no forelimb deficits. Differential diagnoses included abscess formation or neoplasia. Pathologic examination revealed chronic focal purulent meningitis associated with widespread paraspinal fistulous inflammation originating from a chronic dermal ulcer. Mainly Escherichia coli var. haemolytica and Clostridium perfringens were identified as the underlying agents.

Accuracy of malignant hyperthermia diagnoses in hospital discharge records.

BACKGROUND: In 1997, the International Classification of Diseases (ICD), 9th Revision Clinical Modification (ICD-9) coding system introduced the code for malignant hyperthermia (MH) (995.86). The aim of this study was to estimate the accuracy of coding for MH in hospital discharge records. METHODS: An expert panel of anesthesiologists reviewed medical records for patients with a discharge diagnosis of MH based on ICD-9 or ICD-10 codes from January 1, 2006 to December 31, 2008 at six tertiary care medical centers in North America. All cases were categorized as possible, probable, or fulminant MH, history of MH (family or personal) or other. RESULTS: A total of 47 medical records with MH diagnoses were reviewed; 68.1% had a documented surgical procedure and general anesthesia, and 23.4% (95% CI, 12.3-38.0%) had a possible, probable, or fulminant MH event. Dantrolene was given in 81% of the MH events. All patients judged to have an incident MH event survived to discharge. Family and personal history of MH accounted for 46.8% of cases. High fever without evidence of MH during admission accounted for 23.4%, and the reason for MH coding was unclear in 6.4% of cases. CONCLUSIONS: Approximately one quarter of ICD-9 or ICD-10 coded MH diagnoses in hospital discharge records refer to incident MH episodes and an additional 47% to MH susceptibility (including personal history or family history). Information such as surgical procedure, anesthesia billing data, and dantrolene administration may aid in identifying incident MH cases among those with an ICD-9 or ICD-10 coded MH diagnosis in their hospital discharge records.

Validation of climate model-inferred regional temperature change for late-glacial Europe.

Comparisons of climate model hindcasts with independent proxy data are essential for assessing model performance in non-analogue situations. However, standardized palaeoclimate data sets for assessing the spatial pattern of past climatic change across continents are lacking for some of the most dynamic episodes of Earth's recent past. Here we present a new chironomid-based palaeotemperature dataset designed to assess climate model hindcasts of regional summer temperature change in Europe during the late-glacial and early Holocene. Latitudinal and longitudinal patterns of inferred temperature change are in excellent agreement with simulations by the ECHAM-4 model, implying that atmospheric general circulation models like ECHAM-4 can successfully predict regionally diverging temperature trends in Europe, even when conditions differ significantly from present. However, ECHAM-4 infers larger amplitudes of change and higher temperatures during warm phases than our palaeotemperature estimates, suggesting that this and similar models may overestimate past and potentially also future summer temperature changes in Europe.

Cost-effectiveness analysis of stocking dantrolene in ambulatory surgery centers for the treatment of malignant hyperthermia.

BACKGROUND: Malignant hyperthermia (MH) is a rare hypermetabolic syndrome of the skeletal muscle and a potentially fatal complication of general anesthesia. Dantrolene is currently the only specific treatment for MH. The Malignant Hyperthermia Association of the United States has issued guidelines recommending that 36 vials (20 mg per vial) of dantrolene remain in stock at every surgery center. However, the cost of stocking dantrolene in ambulatory surgery centers has been a concern. The purpose of this analysis is to assess the cost-effectiveness of stocking dantrolene in ambulatory surgery centers as recommended by the Malignant Hyperthermia Association of the United States. METHODS: A decision tree model was used to compare treatment with dantrolene to a supportive care-only strategy. Model assumptions include the incidence of MH, MH case fatality with dantrolene treatment and with supportive care-only. Sensitivity analyses were performed to assess the robustness of the estimated cost-effectiveness. RESULTS: The estimated annual number of MH events in ambulatory surgery centers in the United States was 47. The incremental effectiveness of dantrolene compared with supportive care was 33 more lives saved per year. The incremental cost-effectiveness ratio was $196,320 (in 2010 dollars) per life saved compared with a supportive care strategy. Sensitivity analysis showed that the results were robust for the plausible range of all variables and assumptions tested. CONCLUSION: The results of this analysis suggest that stocking dantrolene for the treatment of MH in ambulatory surgery centers as recommended by the Malignant Hyperthermia Association of the United States is cost-effective when compared with the estimated values of statistical life used by U.S. regulatory agencies.

Prescription drug monitoring and dispensing of prescription opioids.

OBJECTIVE: In the United States, per-capita opioid dispensing has increased concurrently with analgesic-related mortality and morbidity since the 1990s. To deter diversion and abuse of controlled substances, most states have implemented electronic prescription drug monitoring programs (PDMPs). We evaluated the impact of state PDMPs on opioid dispensing. METHODS: We acquired data on opioids dispensed in a given quarter of the year for each state and the District of Columbia from 1999 to 2008 from the Automation of Reports and Consolidated Orders System and converted them to morphine milligram equivalents (MMEs). We used multivariable linear regression modeling with generalized estimating equations to assess the effect of state PDMPs on per-capita dispensing of MMEs. RESULTS: The annual MMEs dispensed per capita increased progressively until 2007 before stabilizing. Adjusting for temporal trends and demographic characteristics, implementation of state PDMPs was associated with a 3% decrease in MMEs dispensed per capita (p=0.68). The impact of PDMPs on MMEs dispensed per capita varied markedly by state, from a 66% decrease in Colorado to a 61% increase in Connecticut. CONCLUSIONS: Implementation of state PDMPs up to 2008 did not show a significant impact on per-capita opioids dispensed. To control the diversion and abuse of prescription drugs, state PDMPs may need to improve their usability, implement requirements for committee oversight of the PDMP, and increase data sharing with neighboring states.

Prescription drug monitoring and drug overdose mortality.

BACKGROUND: Abuse of prescription drugs, particularly opioid analgesics, has become a major source of injury mortality and morbidity in the United States. To prevent the diversion and misuse of controlled substances, many states have implemented prescription drug monitoring programs (PDMPs). This study assessed the impact of state PDMPs on drug overdose mortality. METHODS: We analyzed demographic and drug overdose mortality data for state-quarters with and without PDMPs in 50 states and the District of Columbia during 1999-2008, and estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) of drug overdose mortality associated with the implementation of state PDMPs through multivariable negative bionomial regression modeling. RESULTS: During the study period, annual national death rates from drug overdose increased by 96%, from 5.7 deaths per 100,000 population in 1999 to 11.2 in 2008. The impact of PDMPs on drug overdose mortality varied greatly across states, ranging from a 35% decrease in Michigan (aRR = 0.65; 95% CI = 0.54-0.77) to a more than 3-fold increase in Nevada (aRR = 3.37; 95% CI = 2.48-4.59). Overall, implementation of PDMPs was associated with an 11% increase in drug overdose mortality (aRR = 1.11; 95% CI = 1.02-1.21). CONCLUSIONS: Implementation of PDMPs did not reduce drug overdose mortality in most states through 2008. Program enhancement that facilitates the access and use of prescription drug monitoring data systems by healthcare practitioners is needed.

Potent inhibition of aldehyde dehydrogenase-2 by diphenyleneiodonium: focus on nitroglycerin bioactivation.

Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN) to yield nitric oxide (NO) or a related species that activates soluble guanylate cyclase (sGC), resulting in cGMP-mediated vasodilation. Accordingly, established ALDH2 inhibitors attenuate GTN-induced vasorelaxation in vitro and in vivo. However, the ALDH2 hypothesis has not been reconciled with early studies demonstrating potent inhibition of the GTN response by diphenyleneiodonium (DPI), a widely used inhibitor of flavoproteins, in particular NADPH oxidases. We addressed this issue and investigated the effects of DPI on GTN-induced relaxation of rat aortic rings and the function of purified ALDH2. DPI (0.3 µM) inhibited the high affinity component of aortic relaxation to GTN without affecting the response to NO, indicating that the drug interfered with GTN bioactivation. Denitration and bioactivation of 1-2 µM GTN, assayed as 1,2-glycerol dinitrate formation and activation of purified sGC, respectively, were inhibited by DPI with a half-maximally active concentration of about 0.2 µM in a GTN-competitive manner. Molecular modeling indicated that DPI binds to the catalytic site of ALDH2, and this was confirmed by experiments showing substrate-competitive inhibition of the dehydrogenase and esterase activities of the enzyme. Our data identify ALDH2 as highly sensitive target of DPI and explain inhibition of GTN-induced relaxation by this drug observed previously. In addition, the data provide new evidence for the essential role of ALDH2 in GTN bioactivation and may have implications to other fields of ALDH2 research, such as hepatic ethanol metabolism and cardiac ischemia/reperfusion injury.