Multisensory stimulation and its effect on breast milk volume production in mothers of premature infants.

Introduction: In a significant number of NICUs, mothers are unable to provide enough maternal milk to feed their premature babies, so healthcare workers rely on human milk banks. Unfortunately, this service is not available in many countries, such as Peru, where premature infants receive formula. The aim of this study was to determine the effectiveness of multisensory stimulation on mother's own milk production. Methods: Participants in this study were postpartum mothers of preterm infants 27-37 weeks gestational age. The participants were assigned to three groups: (1) audiovisual stimulation (SAV) (n = 17), (2) audiovisual and olfactory stimulation (SAVO) (n = 17), and (3) control (n = 16). A questionnaire was used to collect demographic and obstetric data, including a record of mother's own milk volume. Results: There was no significant difference between the SAV, SAVO and control groups regarding age, marital status, education level, occupation, number of children, mode of delivery, Apgar and birth weight. On the other hand, a significant difference was observed between the SAV and SAVO groups regarding the amount of milk produced, with higher production between the fourth and seventh day (Tukey p < 0.05). Similarly, milk volume was significantly greater in the SAVO group compared to the SAV and control groups (OR = 1.032, 95% CI = 1.0036-1.062, p < 0.027). Conclusion: Multisensory stimulation in postpartum mothers of preterm infants caused an increase in the volume of mother's own milk production. However, more research is needed to explain the findings presented in this study.

A Qualitative Analysis of Latina Migrant Farmworkers' Perception of Mental Health: Voices From Wisconsin.

INTRODUCTION: Despite evidence showing Latinos' high prevalence of mental health, little is known about Latina migrant farmworkers' mental health experiences, especially those working in Midwestern states. Considering the multiple vulnerabilities observed among Latina migrant farmworkers, it is necessary to gain insight from own accounts and perceptions of mental health and mental health-seeking experiences. METHOD: A qualitative descriptive approach, using in-depth semi-structured interviews with open-ended questions, served to retrieve data from 34 Latina migrant farmworkers. This study was informed by Chicana, postcolonial, and Black feminist epistemologies. RESULTS: Thematic analysis identified themes within the data. These findings pertained to the conceptualization of mental health within the contexts of family, capacities, stigma, denial, and faith. DISCUSSION: Our results demonstrate the need for health care providers to consider Latina migrant farmworkers' perceptions about mental health and apply those in designing and implementing culturally informed policy and practice.

Substance Misuse Themes Among Women Living in Transitional Housing: Effects on Children, Intimate Partner Relationships, and Social Relationships.

ABSTRACT: Traditional substance misuse treatments have not always taken women or marginalized populations into consideration. A holistic approach that addresses how drugs may be used to cope with trauma caused by violence, poverty, and neglect as well as employment of engagement strategies that connect populations with culturally relevant support systems are key, especially in treating African American women. As substance misuse rates rise among African American women, characterizing how this may influence or be influenced by relationships (such as with children, intimate partners, and social relations) is especially important in the context of effective treatment. The purpose of this qualitative study was to examine the themes surrounding substance misuse and close relationships among women previously enrolled in a transitional housing treatment program grounded in social support. Many women discussed how the program itself was an impetus in addressing not only their own substance use but also intergenerational substance use within their families. Women also noted how relationships with their children were vastly different pretreatment compared with during and after treatment, specifically emphasizing a positive improvement. Regarding intimate relationships, African American women learned to establish assertiveness and navigate healthier social relationships, all while sustaining drug abstinence. It is important to acknowledge the role of the healthcare professional in ensuring effective and culturally relevant treatment for African American women; nursing curricula should include evidence-based practice education and training on mental health and substance misuse specific to marginalized communities to more deeply understand the complex intersections of substance misuse, poverty, and social relationships in the lives of women.

Centering Our Voices: Experiences of Violence Among Homeless African American Women.

Women experiencing homelessness who are also survivors of violence require uniquely tailored programs to accommodate complex needs. To understand how violence shaped the lives of formerly homeless African American women, an instrumental case study design and community-based participatory research approach was utilized in this qualitative study. Focus group interviews with graduates (N = 40) from a long-term transitional housing program were conducted. Using thematic analysis, identified themes included: cycles of violence, violence in the community, relationships with children, and coping with violence. These themes illustrated survivors' growth through supportive programming and highlighted services dedicated to empowering women who have experienced violence.

Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis.

We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studies on plasma HC and 22 on MTHFR genotypes. Due to age-related HC differences, adult and paediatric SCD were separated: 879 adult SCD and 834 controls (CTR) yielded a neutral effect size; 427 paediatric SCD and 625 CTR favoured SCD (p = 0.001) with wide heterogeneity (I2 = 95.5%) and were sub-grouped by country: six studies (Dutch Antilles n = 1, USA n = 5) yielded a neutral effect size, four (India n = 1, Arab countries n = 3) favoured SCD (p < 0.0001). Moreover, 249 SCD in VOC and 419 out of VOC yielded a neutral effect size. The pooled prevalence of the MTHFR TT genotype in 267 SCD equalled that of 1199 CTR (4.26% vs. 2.86%, p = 0.45), and in 84 SCD with IS equalled that of 86 without IS (5.9% vs. 3.7%, p = 0.47); removal of one paediatric study yielded a significant effect size (p = 0.006). Plasma HC in paediatric SCD from Middle East and India was higher, possibly due to vitamin deficiencies. Despite its low prevalence in SCD, the MTHFR TT genotype relates to adult IS.

The health facility as a risk factor for multidrug-resistant gram-negative bacteria in critically ill patients with COVID-19.

BACKGROUND: The relationship between Multidrug Resistant-Gram Negative Bacteria (MDR-GNB) infection and colonization in critically ill COVID-19 patients has been observed, however, it is still poorly understood. This study evaluated the risk factors for acquiring MDR-GNB in patients with severe COVID-19 in Intensive Care Units (ICU). METHODS: This is a nested case-control study in a cohort of 400 adult patients (≥ 18 years old) with COVID-19, hospitalized in the ICU of 4 hospitals in the city of Curitiba, Brazil. Cases were critical COVID-19 patients with one or more MDR GNB from any surveillance and/or clinical cultures were taken during their ICU stay. Controls were patients from the same units with negative cultures for MDR-GNB. Bivariate and multivariate analyses were done. RESULTS: Sixty-seven cases and 143 controls were included. Independent risk factors for MDR bacteria were: male gender (OR = 2.6; 95% CI 1.28‒5.33; p = 0.008); the hospital of admission (OR = 3.24; 95% CI 1.39‒7.57; p = 0.006); mechanical ventilation (OR = 25.7; 95% CI 7.26‒91; p < 0.0001); and desaturation on admission (OR = 2.6; 95% CI 1.27‒5.74; p = 0.009). CONCLUSIONS: Male gender, desaturation, mechanical ventilation, and the hospital of admission were the independent factors associated with MDR-GNB in patients in the ICU with COVID-19. The only modifiable factor was the hospital of admission, where a newly opened hospital posed a higher risk. Therefore, coordinated actions toward a better quality of care for critically ill COVID-19 patients are essential.

High-Flow Nasal Cannula Therapy in Patients With COVID-19: Predictive Response Factors.

BACKGROUND: COVID-19 pneumonia has been responsible for many ICU patients' admissions with hypoxemic respiratory failure, and oxygen therapy is one of the pillars of its treatment. The current pandemic scenario has limited the availability of ICU beds and access to invasive ventilation equipment. High-flow nasal cannula (HFNC) can reduce the need for orotracheal intubation compared with conventional oxygen therapy, providing better results than noninvasive respiratory support. However, HFNC use has been controversial due to concerns about the benefits and risks of aerosol dispersion. In this context, we evaluated the performance of the HFNC therapy in patients with COVID-19 and investigated factors that can predict favorable responses. METHODS: A prospective observational study was conducted, which included hospitalized adult subjects with COVID-19 in the respiratory wards who needed oxygen therapy. Clinical and laboratory parameters were collected to compare HFNC therapy use and the outcomes. RESULTS: In 6 months, 128 subjects were included and the success rate of HFNC therapy was 53%. Logistic regression analysis showed that the Charlson comorbidity score, need for oxygen flow, [Formula: see text], and breathing frequency predicted therapy failure. The mortality rate increased among the non-responders versus the responders (47% vs 3%), 48% of failure occurred in the first 24 h of the HFNC therapy. A ROX (respiratory frequency - oxygenation) index > 4.98 in 6 h and > 4.53 in 24 h predicted success of the HFNC therapy with an area under the curve of 0.7, and a ROX index < 3.47 predicted failure with 88% of specificity. CONCLUSIONS: HFNC in the subjects with COVID-19 was associated with reduced mortality and improved oxygenation in the subjects with respiratory distress. Close monitoring of specific parameters defines eligible patients and rapidly identifies those in need of invasive ventilatory support.

Successful substance use disorder recovery in transitional housing: Perspectives from African American women.

Through the lens of Black Feminist Thought, the intersectionality of poverty, racism, and sexism in the lives of urban dwelling African American women was explored. Reflections on recovery among women previously enrolled in a transitional housing treatment program were gathered via semistructured interviews, using an instrumental case study design. Four major themes surrounding the context of recovery were identified and analyzed: Knowledge and awareness of addiction, importance of social support and support groups, peace of mind that resulted from a new lifestyle, and women's desire to maintain their recovery status. Many women did not realize that their drug use constituted an addiction prior to their enrollment in the program. Social support and support groups such as AA, NA, and AODA helped the women to maintain their recovery, and this newfound recovery resulted in additional stress relief. Finally, many women felt empowered to maintain their recovery, not only for themselves but also their children. Paradigm shifts in treatment and recovery processes are needed to better serve minority populations, specifically focusing on women and African Americans. Recovery services must shift from previously male centered, hegemonic, pathology-oriented treatment modalities to serve populations more efficiently and equitably. Furthermore, to create effective social change in recovery, programs must address the social determinants of substance misuse, addictive behaviors, and underlying structural inequalities resulting from the intersection of racism, sexism, and classism. Deeper understandings of complex social issues must be disseminated, particularly for women battling substance misuse who are homeless, racially discriminated against and marginalized. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Application of Postcolonial Feminist Theory, Chicana Feminist Thought, and Black Feminist Thought in Analyzing the Mental Health Needs of Latina Migrant Farmworkers: A Shared Legacy.

The purpose of this theoretical article is to analyze the utility of postcolonial, Black, and Chicana feminist frameworks to inform nursing research and practice specific to mental health needs of Latina women migrant farmworkers. Twentieth-century Western feminist narratives overlooked the intersecting systems of oppression experienced by women of color, including Latina women. Feminist epistemologies are useful in understanding the complex sociopolitical contexts that have impacted women's health outcomes and well-being. This analysis is critical to shaping nursing care that meets the unique health needs of migrant farmworker women while considering their sociopolitical realities.

Adverse childhood experiences among previously homeless African American women.

OBJECTIVE: To learn how adverse childhood experiences (ACEs) impacted the life course trajectory of formerly homeless and at-risk African American women. DESIGN: Intersectionality and life course theory informed this qualitative pilot study, based on an instrumental case study design. SAMPLE: Forty previously homeless and at-risk African American women, who were graduates from a long-term transitional living facility in Milwaukee, Wisconsin. MEASUREMENTS: Focus group interviews and one individual interview provided data about participants' life experiences prior to, during, and following their time at the transitional living facility, which provided supportive wrap-around services. Interviews were audiotaped, transcribed, and line-by-line thematic analysis was conducted to identify themes. Fifteen focus group participants also completed ACE questionnaires. RESULTS: Participants reported a high prevalence of multiple ACEs, and three themes were identified: childhood experiences with family conflict, childhood experiences of abuse, and negative coping mechanisms. One-hundred percent of women had experienced at least one ACE, based on ACE questionnaire responses. CONCLUSIONS: ACEs affect various parts of patient's lives as adults. For nurses and other healthcare professionals, connecting with community resources provides the opportunity to strategically approach health improvement with wrap-around resources to improve health outcomes.

'I was broken in so many different ways': The intersection of complex factors impacting homeless and at-risk African American women's mental health and well-being.

African American women are at higher risk of poor mental ill health compared with other racial and ethnic groups in the United States. For low-income and homeless African American populations, the risk of poor mental ill health is even higher. The purpose of our study was to learn what programmes at a long-term transitional living centre helped at-risk and homeless African American mothers to succeed on their own, in accordance with self-identified goals. We conducted ten focus group interviews with 39 graduates of a long-term transitional living centre located in a Midwestern city, and an individual interview with the founder of that centre (N = 40). Our study was informed by Black Feminist Thought, Life Course Theory, and an instrumental case study design. Thematic analysis was used to identify patterns in the qualitative data collected. Findings pertaining to mental health included impacts of adverse childhood experiences, lack of social networks, child placement in foster care, and implications on self-esteem and self-worth. Our findings demonstrate the need for healthcare providers to take into account the intersecting factors facing African American women experiencing homelessness undergirded by systemic racism, which impacts their mental health and well-being.

The health facility as a risk factor for multidrug-resistant gram-negative bacteria in critically ill patients with COVID-19

Abstract Background The relationship between Multidrug Resistant-Gram Negative Bacteria (MDR-GNB) infection and colonization in critically ill COVID-19 patients has been observed, however, it is still poorly understood. This study evaluated the risk factors for acquiring MDR-GNB in patients with severe COVID-19 in Intensive Care Units (ICU). Methods This is a nested case-control study in a cohort of 400 adult patients (≥ 18 years old) with COVID-19, hospitalized in the ICU of 4 hospitals in the city of Curitiba, Brazil. Cases were critical COVID-19 patients with one or more MDR GNB from any surveillance and/or clinical cultures were taken during their ICU stay. Controls were patients from the same units with negative cultures for MDR-GNB. Bivariate and multivariate analyses were done. Results Sixty-seven cases and 143 controls were included. Independent risk factors for MDR bacteria were: male gender (OR = 2.6; 95% CI 1.28‒5.33; p = 0.008); the hospital of admission (OR = 3.24; 95% CI 1.39‒7.57; p = 0.006); mechanical ventilation (OR = 25.7; 95% CI 7.26‒91; p < 0.0001); and desaturation on admission (OR = 2.6; 95% CI 1.27‒5.74; p = 0.009). Conclusions Male gender, desaturation, mechanical ventilation, and the hospital of admission were the independent factors associated with MDR-GNB in patients in the ICU with COVID-19. The only modifiable factor was the hospital of admission, where a newly opened hospital posed a higher risk. Therefore, coordinated actions toward a better quality of care for critically ill COVID-19 patients are essential.

Rapid Serological Tests for SARS-CoV-2: Diagnostic Performance of 4 Commercial Assays.

OBJECTIVE: To assess the diagnostic performance of lateral flow immunochromatographic assays (LFAs) of 4 different manufacturers to identify SARS-CoV-2 antibodies (IgM, IgG, or total), comparing them with the nucleic acid amplification test (NAAT) or the clinical defined test (definite or probable SARS-CoV-2 infection, respectively). METHODS: One hundred nineteen serum samples were randomly selected by convenience and distributed in the following groups: (1) group with SARS-CoV-2 infection (n = 82; RT-qPCR positive [definite, n = 70] and probable [n = 12]); (2) other diseases (n = 27; other viruses identified [n = 8] and SARS of other etiologies [n = 19]); and (3) healthy control group (n = 10). LFAs of 4 manufacturers were compared: MedTest Coronavirus (COVID-19) IgG/IgM (MedLevensohn, Brazil); COVID-19 IgG/IgM ECO Test (Ecodiagnóstica, Brazil); Camtech COVID-19 IgM/IgG Rapid Test Kit (Camtech Diagnostics Pte Ltd, Singapore); and 1-Step COVID-19 Test for total antibodies (Guangzhou Wondfo Biotech Co., China). RESULTS: The 4 tests studied showed high diagnostic performance characteristics for the diagnoses of definite or probable SARS-CoV-2 infection. The best measures were for the Wondfo test: sensitivity (86.59%; 95% CI: 77.26-93.11%), specificity (100%; 90.51-100%), DOR (257; 60-1,008), LR+ (33.43; 4.82-231.85), LR- (0.13; 0.08-0.23), accuracy (90.76%; 84.06-95.29%), and Matthews correlation coefficient (MCC) 0.82. Although considering only the probable SARS-CoV-2 infection (PCR-) cases, all the kits studied showed limited values. CONCLUSION: Our data demonstrate the excellent performance of LFA for the diagnoses of definite or probable SARS-CoV-2 infection. There was substantial heterogeneity in sensitivities of IgM and IgG antibodies among the different kits. LFA tests cannot replace molecular diagnostics but should be used as an additional screening tool.

Antiphospholipid Antibodies in Sickle Cell Disease: A Systematic Review and Exploratory Meta-Analysis.

The relationship between antiphospholipid antibodies (aPL) and sickle cell disease (SCD) has never been systematically addressed. Our aim was to evaluate potential links between SCD and aPL in all age groups. EMBASE/PubMed was screened from inception to May 2020 and Peto odds ratios for rare events were calculated. The pooled prevalence (PP) of IgG anticardiolipin antibodies (aCL) was higher in individuals with SCD than in controls (27.9% vs 8.7%, P < 0.0001), that of IgM aCL was similar in the two groups (2.9% vs 2.7%); only individuals with SCD were positive for lupus anticoagulant (LA) (7.7% vs 0%, P < 0.0001). The PP of leg ulcers was similar between aPL positive and negative individuals (44% vs 53%) and between patients in acute crisis and stable patients (5.6% vs 7.3%). Reporting of aPL as a binary outcome and not as a titer precluded further interpretation. The results indicate that a prospective case-control study with serial measurements of a panel of aPL in SCD patients might be warranted, in order to understand further the possible pathogenic role of aPL in SCD.

Autoimmune haemolytic anaemia and antiphospholipid antibodies in paediatrics: a systematic review and meta-analysis.

INTRODUCTION/OBJECTIVE: The relationship between autoimmune haemolytic anaemia (AIHA) and antiphospholipid antibodies (aPL) has never been addressed via a meta-analysis in the paediatric age group. We evaluated the link between AIHA and aPL in childhood systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). METHODS: EMBASE and PubMed were screened from inception to May 2020 and Peto's odds ratio for rare events was employed for the between group comparisons. RESULTS: The meta-analysis included 11 articles for a total of 575 children: the pooled prevalence of AIHA was greater in (1) IgG aCL-positive than IgG aCL-negative children (39.7% vs 20.9%, p = 0.005); (2) in APS-positive than APS-negative SLE children (36.8% vs 13.2%, p = 0.01); and (3) in SLE-related APS than in primary APS children (53% vs 16.2%, p = 0.008). CONCLUSIONS: The pooled prevalence of AIHA is greatest in SLE with aPL/APS, low-moderate in SLE without aPL/APS, and lowest in primary APS. Key Points • Antiphospholipid antibodies strongly relate to autoimmune haemolytic anaemia. • Autoimmune haemolytic anaemia is more common in systemic lupus erythematosus with antiphospholipid antibodies.

The Role of Nurses as Allies Against Racism and Discrimination: An Analysis of Key Resistance Movements of Our Time.

The remnants of colonialism manifesting as structural violence, racism, and oppression continue to plague our society as evidenced by the persistence of health inequities, particularly for minority populations in the United States. As a profession bound by moral and ethical mandates, nursing must resist and deconstruct oppression in all its forms. Nurses, informed by critical race theory, intersectionality, and historical trauma, can become formidable allies with marginalized populations in the fight for social justice and health equity.

Lipid Peroxidation-Derived Aldehydes, 4-Hydroxynonenal and Malondialdehyde in Aging-Related Disorders.

Among the various mechanisms involved in aging, it was proposed long ago that a prominent role is played by oxidative stress. A major way by which the latter can provoke structural damage to biological macromolecules, such as DNA, lipids, and proteins, is by fueling the peroxidation of membrane lipids, leading to the production of several reactive aldehydes. Lipid peroxidation-derived aldehydes can not only modify biological macromolecules, by forming covalent electrophilic addition products with them, but also act as second messengers of oxidative stress, having relatively extended lifespans. Their effects might be further enhanced with aging, as their concentrations in cells and biological fluids increase with age. Since the involvement and the role of lipid peroxidation-derived aldehydes, particularly of 4-hydroxynonenal (HNE), in neurodegenerations, inflammation, and cancer, has been discussed in several excellent recent reviews, in the present one we focus on the involvement of reactive aldehydes in other age-related disorders: osteopenia, sarcopenia, immunosenescence and myelodysplastic syndromes. In these aging-related disorders, characterized by increases of oxidative stress, both HNE and malondialdehyde (MDA) play important pathogenic roles. These aldehydes, and HNE in particular, can form adducts with circulating or cellular proteins of critical functional importance, such as the proteins involved in apoptosis in muscle cells, thus leading to their functional decay and acceleration of their molecular turnover and functionality. We suggest that a major fraction of the toxic effects observed in age-related disorders could depend on the formation of aldehyde-protein adducts. New redox proteomic approaches, pinpointing the modifications of distinct cell proteins by the aldehydes generated in the course of oxidative stress, should be extended to these age-associated disorders, to pave the way to targeted therapeutic strategies, aiming to alleviate the burden of morbidity and mortality associated with these disturbances.

Clinical effectiveness of platelets in additive solution treated with two commercial pathogen-reduction technologies.

BACKGROUND: Two noninferiority, randomized, controlled trials were conducted in parallel comparing the safety and efficacy of platelets treated with Intercept or Mirasol pathogen-reduction technologies versus standard platelets. STUDY DESIGN AND METHODS: The primary endpoint was the percentage of hematology patients who developed World Health Organization Grade 2 or greater bleeding. A noninferiority margin of 11% was chosen based on expected Grade 2 or greater bleeding in 20% of controls. The study was closed for financial restrictions before reaching the planned sample size of 828 patients, and an intention-to-treat analysis was conducted on 424 evaluable patients. RESULTS: In the Intercept trial (113 treated vs. 115 control patients), the absolute risk difference in Grade 2 or greater bleeding was 6.1%, with an upper one-sided 97.5% confidence limit of 19.2%. The absolute risk difference in the Mirasol trial (99 treated vs. 97 control patients) was 4.1%, and the upper one-sided 97.5% confidence limit was 18.4%. Neither absolute risk difference was statistically significant. In both trials, posttransfusion platelet count increments were significantly lower in treated versus control patients. Mean blood component use in treated patients versus controls was 54% higher (95% confidence interval, 36%-74%; Intercept) and 34% higher (95% confidence interval, 16%-54%; Mirasol) for platelets and 23% higher (95% confidence interval, 8%-39%; Intercept) and 32% higher (95% confidence interval, 10%-57%; Mirasol) for red blood cells. Unexpected reactions and adverse events were not reported. Mortality did not differ significantly between treated and control patients. CONCLUSION: Although conclusions on noninferiority could not be drawn due to low statistical power, the study provides additional information on the safety and efficacy of pathogen-reduced platelets treated with two commercial pathogen-reduction technologies.

Risk factors for mortality in patients with ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae

Abstract Background: The ideal therapeutic option for ventilator associated pneumonia caused by carbapenem-resistant Enterobacteriaceae is not defined. The aim of this study was to assess mortality-associated risk factors in patients with VAP by CRE and determine the outcome of several treatment options. Methods: This was a retrospective study performed in two tertiary hospitals involving patients with VAP caused by CRE between January 2010 and August 2014. The outcomes were mortality within 30 days of VAP diagnosis and overall mortality during hospital admission. Risk factors for mortality were assessed by comparing variables of survivors and non-survivors. Results: One hundred and twelve patients with CRE-VAP were included, 73 (65%) male, median age 56 years. The 30-day mortality was 57.1% and the overall hospital mortality was 67%. In the binary logistic regression analysis, only age >50 years was independently associated to increased mortality. Polymyxin was the most used drug (47.5%), followed by tigecycline (29.2%) and aminoglycosides (2.4%). Combined therapy with two active drugs was used by 17 patients (20.8%). No therapeutic option was independently associated to survival. However, combined therapy with two active drugs was superior to the therapy with a single active drug when inappropriate therapy was the comparator (p = 0.044). The addition of carbapenem was not associated with increased survival. Conclusion: The best therapeutic option for VAP by CRE is still not completely defined, but the therapy with at least two active drugs was superior in this study.

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity.

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity.