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Journal of Applied Microbiology Dec 2022Betalains are nitrogen-containing plant pigments that can be red-violet (betacyanins) or yellow-orange (betaxanthins), currently employed as natural colourants in the... (Review)
Review
Betalains are nitrogen-containing plant pigments that can be red-violet (betacyanins) or yellow-orange (betaxanthins), currently employed as natural colourants in the food and cosmetic sectors. Betalains exhibit antimicrobial activity against a broad spectrum of microbes including multidrug-resistant bacteria, as well as single-species and dual-species biofilm-producing bacteria, which is highly significant given the current antimicrobial resistance issue reported by The World Health Organization. Research demonstrating antiviral activity against dengue virus, in silico studies including SARS-CoV-2, and anti-fungal effects of betalains highlight the diversity of their antimicrobial properties. Though limited in vivo studies have been conducted, antimalarial and anti-infective activities of betacyanin have been observed in living infection models. Cellular mechanisms of antimicrobial activity of betalains are yet unknown; however existing research has laid the framework for a potentially novel antimicrobial agent. This review covers an overview of betalains as antimicrobial agents and discussions to fully exploit their potential as therapeutic agents to treat infectious diseases.
Topics: Humans; Betalains; SARS-CoV-2; Betacyanins; Anti-Infective Agents; COVID-19 Drug Treatment
PubMed: 36036373
DOI: 10.1111/jam.15798 -
JAMA Network Open Jun 2023To date, limited data exist regarding the association between Agent Orange and bladder cancer, and the Institute of Medicine concluded that the association between...
IMPORTANCE
To date, limited data exist regarding the association between Agent Orange and bladder cancer, and the Institute of Medicine concluded that the association between exposure to Agent Orange and bladder cancer outcomes is an area of needed research.
OBJECTIVE
To examine the association between bladder cancer risk and exposure to Agent Orange among male Vietnam veterans.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide Veterans Affairs (VA) retrospective cohort study assesses the association between exposure to Agent Orange and bladder cancer risk among 2 517 926 male Vietnam veterans treated in the VA Health System nationwide from January 1, 2001, to December 31, 2019. Statistical analysis was performed from December 14, 2021, to May 3, 2023.
EXPOSURE
Agent Orange.
MAIN OUTCOMES AND MEASURES
Veterans exposed to Agent Orange were matched in a 1:3 ratio to unexposed veterans on age, race and ethnicity, military branch, and year of service entry. Risk of bladder cancer was measured by incidence. Aggressiveness of bladder cancer was measured by muscle-invasion status using natural language processing.
RESULTS
Among the 2 517 926 male veterans (median age at VA entry, 60.0 years [IQR, 56.0-64.0 years]) who met inclusion criteria, there were 629 907 veterans (25.0%) with Agent Orange exposure and 1 888 019 matched veterans (75.0%) without Agent Orange exposure. Agent Orange exposure was associated with a significantly increased risk of bladder cancer, although the association was very slight (hazard ratio [HR], 1.04; 95% CI, 1.02-1.06). When stratified by median age at VA entry, Agent Orange was not associated with bladder cancer risk among veterans older than the median age but was associated with increased bladder cancer risk among veterans younger than the median age (HR, 1.07; 95% CI, 1.04-1.10). Among veterans with a diagnosis of bladder cancer, Agent Orange was associated with lower odds of muscle-invasive bladder cancer (odds ratio [OR], 0.91; 95% CI, 0.85-0.98).
CONCLUSIONS AND RELEVANCE
In this cohort study among male Vietnam veterans, there was a modestly increased risk of bladder cancer-but not aggressiveness of bladder cancer-among those exposed to Agent Orange. These findings suggest an association between Agent Orange exposure and bladder cancer, although the clinical relevance of this was unclear.
Topics: Male; Humans; Middle Aged; Agent Orange; Veterans; 2,4-Dichlorophenoxyacetic Acid; Retrospective Studies; Cohort Studies; 2,4,5-Trichlorophenoxyacetic Acid; Polychlorinated Dibenzodioxins; Urinary Bladder Neoplasms
PubMed: 37368398
DOI: 10.1001/jamanetworkopen.2023.20593 -
Journal of Military and Veterans' Health Apr 2022Agent Orange, a dioxin-containing toxin, was used as an herbicide during the Vietnam War. Exposures to Agent Orange were initially linked to birth defects among...
Agent Orange, a dioxin-containing toxin, was used as an herbicide during the Vietnam War. Exposures to Agent Orange were initially linked to birth defects among Vietnamese civilians residing near aerially sprayed regions. Years later, returning South Korean and U.S. Veterans exposed to Agent Orange exhibited increased rates of malignancy, cardiovascular disease, diabetes and birth defects in their offspring. Growing evidence that herbicides and pesticides contribute to chronic diseases including neurodegeneration raises concern that Agent Orange exposures may have increased the risk for later development of peripheral or central nervous system (CNS) degeneration. This article reviews published data on the main systemic effects and the prevalence rates, relative risks, characteristics and correlates of Agent Orange-associated peripheral neuropathy and CNS dementia-associated diseases. The critical findings were that relatively high levels of Agent Orange exposure increased risk of developing peripheral neuropathy either alone or as a co-factor complication of diabetes mellitus and likely contributed to the pathogenesis of CNS degenerative diseases, including Alzheimer's, Parkinson's and vascular dementias. Given the protracted intervals between the Agent Orange exposures and disease emergence, additional research is needed to identify mechanistic correlates of the related neurological disorders, including lifestyle co-factors.
PubMed: 36785586
DOI: No ID Found -
American Journal of Respiratory and... Sep 2022There is limited literature exploring the relationship between military exposures and idiopathic pulmonary fibrosis (IPF). To evaluate whether exposure to Agent Orange...
There is limited literature exploring the relationship between military exposures and idiopathic pulmonary fibrosis (IPF). To evaluate whether exposure to Agent Orange is associated with an increased risk of IPF among veterans. We used Veterans Health Administration data to identify patients diagnosed with IPF between 2010 and 2019. We restricted the cohort to male Vietnam veterans and performed multivariate logistic regression to examine the association between presumptive Agent Orange exposure and IPF. We conducted sensitivity analyses restricting the cohort to army veterans (highest theoretical burden of exposure, surrogate for dose response) and a more specific case definition of IPF. Fine-Gray competing risk models were used to evaluate age to IPF diagnosis. Among 3.6 million male Vietnam veterans, 948,103 (26%) had presumptive Agent Orange exposure. IPF occurred in 2.2% of veterans with Agent Orange exposure versus 1.9% without exposure (odds ratio, 1.14; 95% confidence interval [CI], 1.12-1.16; < 0.001). The relationship persisted after adjusting for known IPF risk factors (odds ratio, 1.08; 95% CI, 1.06-1.10; < 0.001). The attributable risk among exposed veterans was 7% (95% CI, 5.3-8.7%; < 0.001). Numerically greater risk was observed when restricting the cohort to ) Vietnam veterans who served in the army and ) a more specific definition of IPF. After accounting for the competing risk of death, veterans with Agent Orange exposure were still more likely to develop IPF. Presumptive Agent Orange exposure is associated with greater risk of IPF. Future research should validate this association and investigate the biological mechanisms involved.
Topics: 2,4,5-Trichlorophenoxyacetic Acid; 2,4-Dichlorophenoxyacetic Acid; Agent Orange; Humans; Idiopathic Pulmonary Fibrosis; Male; Polychlorinated Dibenzodioxins; Veterans
PubMed: 35559726
DOI: 10.1164/rccm.202112-2724OC -
JAMA Neurology Apr 2021Agent Orange is a powerful herbicide that contains dioxin and was used during the Vietnam War. Although prior studies have found that Agent Orange exposure is associated...
IMPORTANCE
Agent Orange is a powerful herbicide that contains dioxin and was used during the Vietnam War. Although prior studies have found that Agent Orange exposure is associated with increased risk of a wide range of conditions, including neurologic disorders (eg, Parkinson disease), metabolic disorders (eg, type 2 diabetes), and systemic amyloidosis, the association between Agent Orange and dementia remains unclear.
OBJECTIVE
To examine the association between Agent Orange exposure and incident dementia diagnosis in US veterans of the Vietnam era.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included Veterans Health Administration data from October 1, 2001, and September 30, 2015, with up to 14 years of follow-up. Analyses were performed from July 2018 to October 2020. A 2% random sample of US veterans of the Vietnam era who received inpatient or outpatient Veterans Health Administration care, excluding those with dementia at baseline, those without follow-up visits, and those with unclear Agent Orange exposure status.
EXPOSURES
Presumed Agent Orange exposure documented in electronic health record.
MAIN OUTCOMES AND MEASURES
Fine-Gray competing risk models were used to compare the time to dementia diagnosis (with age as the time scale) for veterans with vs without presumed Agent Orange exposure (as per medical records), adjusting for demographic variables and medical and psychiatric comorbidities.
RESULTS
The total sample was 511 189 individuals; after exclusions, 316 351 were included in analyses. Veterans were mostly male (n = 309 889 [98.0%]) and had a mean (SD) age of 62 (6.6) years; 38 121 (12.1%) had presumed Agent Orange exposure. Prevalence of most conditions, including Parkinson disease, diabetes, and amyloidosis, was similar at baseline among veterans with and without Agent Orange exposure. After adjusting for demographic variables and comorbidities, veterans exposed to Agent Orange were nearly twice as likely as those not exposed to receive a dementia diagnosis over a mean (SD) of 5.5 (3.8) years of follow-up (1918 of 38 121 [5.0%] vs 6886 of 278 230 [2.5%]; adjusted hazard ratio: 1.68 [95% CI, 1.59-1.77]). Veterans with Agent Orange exposure developed dementia at a mean of 1.25 years earlier (at a mean [SD] age of 67.5 [7.0] vs 68.8 [8.0] years).
CONCLUSIONS AND RELEVANCE
Veterans with Agent Orange exposure were nearly twice as likely to be diagnosed with dementia, even after adjusting for the competing risk of death, demographic variables, and medical and psychiatric comorbidities. Additional studies are needed to examine potential mechanisms underlying the association between Agent Orange exposure and dementia.
Topics: Aged; Agent Orange; Cohort Studies; Defoliants, Chemical; Dementia; Electronic Health Records; Environmental Exposure; Female; Follow-Up Studies; Humans; Male; Middle Aged; Veterans; Veterans Health Services; Vietnam Conflict
PubMed: 33492338
DOI: 10.1001/jamaneurol.2020.5011 -
JAMA Network Open Dec 2023Hepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are...
IMPORTANCE
Hepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers.
OBJECTIVE
To assess the association of AO exposure and HCC in a national cohort of Vietnam veterans.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included Vietnam veterans who served between 1966 and 1975, were male, were older than 18 years at the time of deployment, and had established follow-up in the Veterans Affairs (VA) between 2000 and 2019. Veterans with AO exposure were identified in the disability data via validated clinical surveys. Relevant clinical risk factors for cirrhosis and HCC were collected. Patients were stratified based on cirrhosis status, as defined by consecutive diagnosis found by documented International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision scores or calculated Fibrosis-4 scores. Data were collected from January 1, 2019, to December 31, 2020, and analyzed from December 2020 to October 2023.
MAIN OUTCOME AND MEASURES
Incident HCC was the primary outcome. AO and HCC association was estimated using a multivariable Cox regression analysis, with death and liver transplant as competing events.
RESULTS
Of the 296 505 eligible veterans (222 545 [75.1%] White individuals and 44 342 [15.0%] Black individuals), 170 090 (57%) had AO exposure (mean [SD] age, 21.62 [3.49] years; 131 552 White individuals [83.2%] and 22 767 Black individuals [14.4%]) and 35 877 (12.1%) had cirrhosis. Veterans who were not exposed to AO were more likely to smoke (109 689 of 126 413 [86.8%] vs 146 061 of 170 090 [85.9%]); use alcohol (54 147 of 126 413 [42.8%] vs 71 951 of 170 090 [42.3%]) and have viral hepatitis (47 722 of 126 413 [37.8%] vs 58 942 of 170 090 [34.7%]). In a multivariable competing risk model, AO exposure was not associated with HCC. Among veterans with cirrhosis, self-identification as Hispanic individuals (aHR, 1.51; 95% CI, 1.30-1.75; P <.001) or Black individuals (aHR, 1.18; 95% CI, 1.05-1.32; P = .004), and having a diagnosis of viral hepatitis (aHR, 3.71; 95% CI, 3.26-4.24; P <.001), alcohol-associated liver disease (aHR, 1.32; 95% CI, 1.19-1.46; P <.001), and nonalcoholic fatty liver disease (NAFLD) (aHR, 1.92; 95% CI, 1.72-2.15; P <.001) were associated with HCC. Among veterans without cirrhosis, hypertension (aHR, 1.63; 95% CI, 1.23-2.15; P <.001) and diabetes (aHR, 1.52; 95% CI, 1.13-2.05; P = .005) were also associated with HCC. Early smoking and alcohol use were significant risk factors for HCC.
CONCLUSIONS AND RELEVANCE
In this large nationwide cohort study of Vietnam veterans, AO exposure was not associated with HCC. Smoking, alcohol, viral hepatitis, and NAFLD were the most important clinical risk factors for HCC.
Topics: Humans; Male; Young Adult; Adult; Female; Military Personnel; Carcinoma, Hepatocellular; Agent Orange; Non-alcoholic Fatty Liver Disease; Cohort Studies; Retrospective Studies; Liver Neoplasms; Liver Cirrhosis; Ethanol; Hepatitis, Viral, Human
PubMed: 38048128
DOI: 10.1001/jamanetworkopen.2023.46380