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1.
J Biomed Phys Eng ; 14(5): 513-516, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39391274

RESUMO

The search for extraterrestrial intelligence is a fascinating and important endeavor, but it raises significant ethical and safety concerns. In the search for extraterrestrial intelligence, scientists use knowledge of physics to identify potential communication methods and signals that may be used by extraterrestrial civilizations. One of the most notable scientists to highlight these concerns was the late physicist Stephen Hawking, who cautioned that actively attempting to communicate with extraterrestrial civilizations could harm humanity. While it is true that we cannot predict the intentions of any potential extraterrestrial civilizations, some scientists argue that the potential advantages of seeking contact outweigh the potential risks. Deciding to initiate contact with extraterrestrial civilizations is a complex issue that requires balancing scientific curiosity with concerns for our own safety. The "Intelligence Trap" is a concept in psychology that suggests that highly intelligent people are more susceptible to cognitive biases and flawed thinking than less intelligent people. It can be argued that Hawking's warnings may be an example of the so-called intelligence trap, as some evidence from the field of physics suggests. Nonetheless, Hawking emphasized that it is crucial for scientists and policymakers to carefully weigh the potential risks and benefits of such efforts and proceed with caution.

2.
Cureus ; 16(9): e68561, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39364524

RESUMO

Background We defined the progression of atherosclerosis in patients by brachial-ankle pulse wave velocity (ba-PWV) and determined the relationship between ba-PWV and body composition factors, muscle strength, and patient characteristics. Methodology The arterial stiffness index, body composition, anthropometric parameters, blood test data, and background factors were evaluated in 109 patients with type 2 diabetes mellitus (T2DM). Statistical analysis was conducted using logistic regression analysis and analysis of covariance (p < 0.05). Results The mean age of the participants was 62.87 ± 12.11 years, body mass index (BMI) was 25.72 ± 4.35 kg/m², ba-PWV was 1653.08 ± 366.55 cm/s, systolic blood pressure was 138.87 ± 16.74 mmHg, the number of years of disease was 11.17 ± 9.51 years, and hemoglobin A1c value was 6.90 ± 0.74%. Binomial logistic regression analysis of ba-PWV divided into two groups by arterial stiffness index, ≥ (or <) 1,400 cm/s, showed systolic blood pressure (odds ratio = 1.11, 95% confidence interval = 1.05-1.18, p < 0.001), BMI, and number of years of disease were significant independent variables. The cut-off value for BMI was 26.28 kg/m². BMI was a significant explanatory factor for ba-PWV in the analysis of covariance (p < 0.001). Conclusion BMI was associated with the incidence of atherosclerosis in patients with T2DM. We proposed a cut-off value for BMI below which the atherosclerosis index increased, a result that may reflect the influence of the metabolic paradox.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39378011

RESUMO

Preterm birth rates among Black individuals continue to be inequitably high in the USA. Black immigrants appear to have a preterm birth advantage over US-born counterparts. This national cross-sectional study of singleton non-Hispanic Black individuals in the USA from 2011 to 2018 aimed to investigate if the Black immigrant preterm birth advantage varied geographically and how this advantage associated with county-level social drivers of health. Generalized linear mixed models explored the odds of preterm birth (< 37 weeks) by birthing person's nativity, defined as US- versus foreign-born. In county-level analyses, five measures were explored as possible sources of structural risk for or resilience against preterm birth: percent of residents in poverty, percent uninsured, percent with more than a high school education, percent foreign-born, and racial polarization. County-level immigrant advantage among foreign-born compared to US-born Black individuals was defined by a disparity rate ratio (RR); RR < 1 indicated a county-level immigrant preterm birth advantage. Linear regression models at the level of counties quantified associations between county-level factors and disparity RRs. Among 4,072,326 non-Hispanic Black birthing individuals, immigrants had 24% lower adjusted odds of preterm birth compared to US-born Black individuals (aOR 0.77, 95% CI 0.76-0.78). In county-level analyses, the immigrant advantage varied across counties; disparity RRs ranged from 0.13 to 2.82. County-level lack of health insurance and education greater than high school were both associated with immigrant preterm birth advantage. Future research should explore policies within counties that impact risk of preterm birth for both US-born and immigrant Black individuals.

4.
J Adolesc ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39263965

RESUMO

INTRODUCTION: Whether adolescents' life satisfaction varies with gender is unclear. In a recently published study, Brisson et al. found unadjusted mean scores of life satisfaction to be higher in boys than in girls in Luxembourg, a country ranking high in gender-equality indexes. However, gender was no longer predictive of life satisfaction when well-identified predictors of life satisfaction were included in the model. The present work aimed to replicate Brisson et al.'s study in Kazakhstan, a less gender-equal country than Luxembourg, and test the gender-equality-paradox hypothesis. METHODS: We used cross-sectional data from the Health-Behavior in School-aged Children study conducted in 2022 to mirror Brisson et al.'s study design. We relied on a nationally representative sample of 7369 school attendees in Kazakhstan (MAGE = 13.4; SDAGE = 1.7; 52.3% female). We performed general linear modeling analyses to achieve our research goals. RESULTS AND CONCLUSIONS: In keeping with Brisson et al.'s study, we found unadjusted mean scores of life satisfaction to be higher in boys than in girls. The magnitude of the gender gap was lower in Kazakhstan than in Luxembourg. In contrast to Brisson et al.'s study, controlling for well-identified predictors of life satisfaction did not annul the gap in question but changed its sign. This result suggests that, ceteris paribus, girls were more satisfied with their life than boys. Overall, our replication study supports the gender-equality-paradox hypothesis. Future studies may investigate whether this paradox stems from gendered criteria of life satisfaction assessment and/or sociobiological differences in health profiles.

5.
J Clin Med ; 13(17)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39274535

RESUMO

Background/Objectives: Overweight and obesity are generally considered risk factors for premature mortality. However, scientific evidence suggests that among older populations, mild conditions of overweight might be associated with reduced comorbidity and longer survival. This study investigates the potential association between anthropometric parameters and survival among a cohort of nonagenarians in Sardinia, Italy. Methods: This study included 200 subjects (50% females) aged 89 and older, enrolled in 2018 in the Sardinian Blue Zone-a population known for longevity-and followed for up to six years. Anthropometric variables such as body height, weight, age, sex, comorbidity, disability, and food group intake were collected using validated questionnaires and analyzed through multivariable analysis. Results: Out of 200 participants at baseline, 28 (14%) were still alive after six years of follow-up (females 10%, males 18%). Mean survival was 3.36 years (range 0.1-6.9 years) for males and 3.03 years (range 0.2-6.6 years) for females. Participants with a Body Mass Index (BMI) in the range of 25.0-27.0 kg/m2 among males and 25.0-27.2 kg/m2 among females had longer survival compared to those who were underweight (p = 0.002) or obese (p < 0.0001). The Cox proportional hazards regression model, adjusted for age, sex, and comorbidity, revealed a statistically significant association between the BMI and survival, demonstrating an inverted-U relationship. This indicates that mild overweight was associated with a survival advantage compared to both normal weight and obesity. Conclusions: Our study indicates that mild, but not severe, overweight in nonagenarians is associated with extended lifespan. Therefore, primary care physicians and geriatricians should exercise caution before recommending calorie-restricted diets for mildly overweight elderly patients.

6.
J Mol Evol ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39256250

RESUMO

This literature review is to present a new direction in developing better treatment or preventive measures. The larger the body of an organism, the more numerous the cells, which theoretically lead to a higher risk of cancer. However, observational studies suggest the lack of correlation between body size and cancer risk, which is known as Peto's paradox. The corollary of Peto's paradox is that large organisms must be cancer-resistant. Further investigation of the anti-cancer mechanisms in each species could be potentially rewarding, and how the anti-cancer mechanisms found in wild animals can help influence and develop more effective cancer treatment in humans is the main focus of this literature review. Due to a lack of research and understanding of the exact molecular mechanisms of the researched species, only a few (Elephants and rodents) that have been extensively researched have made substantive contributions to human oncology. A new research direction is to investigate the positively selective genes that are related to cancer resistance and see if homologous genes are presented in humans. Despite the great obstacle of applying anti-cancer mechanisms to the human body from phylogenetically distant species, this research direction of gaining insights through investigating cancer-resisting evolutionary adaptations in wild animals has great potential in human oncology research.

7.
J Sport Health Sci ; : 100987, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39277081

RESUMO

BACKGROUND: There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels. This study aimed to assess the association of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels. METHODS: This study utilized individual participant data from 21 cohort studies, comprising both published and unpublished data. Eligibility criteria included individual-level data on leisure-time and occupational physical activity (categorized as sedentary, low, moderate, and high) along with data on all-cause and/or cardiovascular mortality. A 2-stage individual participant data meta-analysis was conducted, with separate analysis of each study using Cox proportional hazards models (Stage 1). These results were combined using random-effects models (Stage 2). RESULTS: Higher leisure-time physical activity levels were associated with lower all-cause and cardiovascular mortality risk across most occupational physical activity levels, for both males and females. Among males with sedentary work, high compared to sedentary leisure-time physical activity was associated with lower all-cause (hazard ratios (HR) = 0.77, 95% Confidence interval(95%CI): 0.70-0.85) and cardiovascular mortality (HR = 0.76, 95%CI: 0.66-0.87) risk. Among males with high levels of occupational physical activity, high compared to sedentary leisure-time physical activity was associated with lower all-cause (HR = 0.84, 95%CI: 0.74-0.97) and cardiovascular mortality (HR = 0.79, 95%CI: 0.60-1.04) risk, while HRs for low and moderate levels of leisure-time physical activity ranged between 0.87 and 0.97 and were not statistically significant. Among females, most effects were similar but more imprecise, especially in the higher occupational physical activity levels. CONCLUSION: Higher levels of leisure-time physical activity were generally associated with lower mortality risks. However, results for workers with moderate and high occupational physical activity levels, especially women, were more imprecise. Our findings suggests that workers may benefit from engaging in high levels of leisure-time physical activity, irrespective of their level of occupational physical activity.

8.
Sci Rep ; 14(1): 22133, 2024 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333782

RESUMO

Patients with stage IIB/C (T4a-bN0) colon cancer often exhibit worse survival rates compared to those with stage IIIA (T1-2N1, T1N2a) colon cancer. This study re-evaluates the survival paradox using the latest Surveillance, Epidemiology, and End Results (SEER) data (released on April 17, 2024) to inform potential revisions to the staging criteria. Utilizing SEER data with 8th edition TNM staging criteria, 4692 colon cancer patients diagnosed between 2018 and 2021 were analyzed with chi-square test. Cox regression and Kaplan-Meier survival analysis were employed to assess factors associated with cancer-specific survival (CSS) and overall survival (OS). The 3-year CSS rates for stage IIB and IIC were 73.1% and 70.3%, respectively, whereas stage IIIA had a substantially higher CSS rate of 91% (P < 0.001). Similarly, the OS rates were 64.9% and 63.0% for stage IIB and IIC, respectively, compared to 83.1% for stage IIIA (P < 0.001). Multivariate analyses revealed stage IIIA patients had significantly lower risks of cancer-specific mortality (hazard ratio (HR) = 0.374, 95% CI: 0.296-0.473, P < 0.001) and overall mortality (HR = 0.575, 95% CI: 0.483-0.685, P < 0.001) compared to stage IIB patients. The upcoming 9th edition of the AJCC staging system should address this paradox by integrating advanced diagnostic markers and emphasizing the aggressive biology of T4 tumor, providing more accurate prognostic information and guiding more effective treatment strategies for colon cancer patients.


Assuntos
Neoplasias do Colo , Estadiamento de Neoplasias , Programa de SEER , Humanos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Taxa de Sobrevida , Estimativa de Kaplan-Meier , Prognóstico , Adulto , Modelos de Riscos Proporcionais , Idoso de 80 Anos ou mais
9.
Appetite ; : 107692, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39332532

RESUMO

Most people eat meat, yet report valuing the environment, animal life, and their health which contradicts this dietary behaviour. The psychological discomfort aroused by this value-behaviour inconsistency, and the strategies meat eaters use to resolve this unpleasant state, is termed the 'meat paradox'. Vegetarians eschew meat consumption, but the negative implications of dairy are comparable to meat. We investigated the 'dairy paradox' in a sample of vegetarians (N = 378) using an experimental design. Specifically, we tested whether vegetarians experienced cognitive dissonance after reading about the environmental, animal welfare, and health impacts of dairy consumption when compared to a control group not exposed to this information. Then, we examined to what extent perceiving dairy consumption as Natural, Necessary, Normal, Nice, or Neglectable, and denial of cows' mental states (Experience or Agency) predicted reduced cognitive dissonance. Vegetarians in the dissonance-induction condition reported experiencing significantly greater dissonance, though they more strongly rejected the justification strategies. Instead, they reported greater intentions to reduce their dairy consumption than vegetarians in the control condition. Rather than replicating findings from the meat paradox literature, these results suggest that vegetarians respond to uncomfortable feelings about their value-behaviour conflict with a greater intention to abandon the incongruent behaviour, rather than endorsing the cognitions that justify it. This research provides evidence that vegetarians experience a dairy paradox. Given the success of our study in shifting participants away from behavioural justification and toward behavioural change intentions, our findings can help guide the design of interventions seeking to reduce dairy consumption.

10.
ESC Heart Fail ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39308333

RESUMO

AIMS: Mitral transcatheter edge-to-edge repair (M-TEER) is a valid treatment option for severe mitral regurgitation (MR), necessitating accurate risk stratification of M-TEER candidates for effective patient selection, optimal periprocedural care and improved long-term outcomes. The body mass index (BMI) is a simple and practical prognostic index, and the obesity paradox has been widely reported. METHODS AND RESULTS: Between April 2018 and June 2021, 2149 patients undergoing M-TEER were registered in the prospective multicentre registry and classified into three groups: underweight (BMI < 18.5 kg/m2), normal weight (18.5 â‰¦ BMI < 25 kg/m2) and overweight and obese (25 kg/m2 â‰¦ BMI). The impact of underweight on the all-cause, cardiovascular and non-cardiovascular mortality following M-TEER was evaluated [follow-up duration: 436 (363-733) days]. The participants (median BMI: 21.1 kg/m2) were categorized as underweight (n = 450, 20.9%), normal weight (n = 1409, 65.6%) and overweight and obese (n = 290, 13.5%). Compared with the other two groups, the underweight group exhibited several negative prognostic factors, including older age, frailty, no dyslipidaemia, hypoalbuminaemia, residual MR and non-home discharge. Underweight patients had the highest rate of all-cause, cardiovascular and non-cardiovascular mortality, whereas those in the other two groups were similar. As per the multivariate analysis, underweight itself was associated with all-cause mortality (hazard ratio: 1.52, 95% confidence interval: 1.17-1.97, P = 0.009) and cardiovascular mortality (hazard ratio: 1.45, 95% confidence interval: 1.04-2.01, P = 0.028). CONCLUSIONS: Underweight patients had the highest mortality rate after M-TEER. Comorbidities, residual MR, discharge disposition and underweight status were correlated with postprocedural outcome.

11.
Biol Lett ; 20(9): 20240284, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39319668

RESUMO

The degree to which within-population variation in sexual trait expression relates to resource heterogeneity remains poorly explored. This is particularly true in lek-mating species, where genetic explanations for male phenotypic variance and mating success are dominant. Here, we demonstrate a link between fine-scale fruit resource availability and indices of male mating success in the white-bearded manakin (Manacus manacus), a lek-mating frugivorous bird that produces energetically costly courtship displays. We used motion-activated camera traps to monitor male display behaviour and female visitation at male courts while concurrently conducting twice-monthly fruit surveys around courts. We observed significant variability in ripe fruit biomass among display courts and leks, and mean fruit biomass at courts significantly predicted male display rates. In turn, male display rate was the strongest predictor of female visitation to courts. Causal modelling supported the hypothesis that hyper-local fruit availability indirectly affects female visitation via its direct effects on male display rate. The demonstration that resource availability at fine spatial scales predicts display rate in a lekking organism-for which resource-related variables are typically not considered to play important roles in shaping male reproductive variance-has implications for the expression, honesty and maintenance of sexually selected traits under fluctuating ecological conditions.


Assuntos
Frutas , Animais , Masculino , Feminino , Passeriformes/fisiologia , Preferência de Acasalamento Animal , Seleção Sexual , Comportamento Sexual Animal/fisiologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-39243214
13.
Adv Exp Med Biol ; 1460: 1-25, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39287847

RESUMO

Increase in the prevalence of obesity has become a major worldwide health problem in adults as well as among children and adolescents. In the last four decades, studies have revealed that the significant increase in the prevalence of obesity has become a pandemic. Obesity is the result of complex interactions between biological, genetic, environmental, and behavioral factors. Indeed, almost all of the children suffering from obesity in early childhood face with being overweight or obese in adolescence. Different phenotypes have different risk factors in the clinical evaluation of obesity. Individuals suffering from metabolically unhealthy obesity (MUO) are at an excess risk of developing cardiovascular diseases (CVDs), several cancer types, and metabolic syndrome (MetS), whereas the metabolically healthy obesity (MHO) phenotype has a high risk of all-cause mortality and cardiometabolic events but not MetS. While most obese individuals have the MUO phenotype, the frequency of the MHO phenotype is at most 10-20%. Over time, approximately three-quarters of obese individuals transform from MHO to MUO. Total adiposity and truncal subcutaneous fat accumulation during adolescence are positively and independently associated with atherosclerosis in adulthood. Obesity, in general, causes a large reduction in life expectancy. However, the mortality rate of morbid obesity is greater among younger than older adults. Insulin resistance (IR) develops with the central accumulation of body fat. MHO patients are insulin-sensitive like healthy normal-weight individuals and have lower visceral fat content and cardiovascular consequences than do the majority of MUO patients. MetS includes clustering of abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. The average incidence of MetS is 3%, with a 1.5-fold increase in the risk of death from all causes in these patients. If lifestyle modifications, dietary habits, and pharmacotherapy do not provide any benefit, then bariatric surgery is recommended to reduce weight and improve comorbid diseases. However, obesity treatment should be continuous in obese patients by monitoring the accompanying diseases and their consequences. In addition to sodium-glucose co-transporter-2 (SGLT2) inhibitors, the long-acting glucagon-like peptide-1 (GLP-1) receptor agonist reduces the mean body weight. However, caloric restriction provides more favorable improvement in body composition than does treatment with the GLP-1 receptor (GLP1R) agonist alone. Combination therapy with orlistat and phentermine are the US Food and Drug Administration (FDA)-approved anti-obesity drugs. Recombinant leptin and synthetic melanocortin-4-receptor agonists are used in rarely occurring, monogenic obesity, which is due to loss of function in the leptin-melanocortin pathway.


Assuntos
Síndrome Metabólica , Obesidade , Fenótipo , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Prevalência , Obesidade/epidemiologia , Obesidade/metabolismo , Fatores de Risco , Adolescente , Criança , Resistência à Insulina
14.
Adv Exp Med Biol ; 1460: 167-198, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39287852

RESUMO

Obesity-related co-morbidities decrease life quality, reduce working ability, and lead to early death. In the adult population, eating addiction manifests with excessive food consumption and the unrestrained overeating behavior, which is associated with increased risk of morbidity and mortality and defined as the binge eating disorder (BED). This hedonic intake is correlated with fat preference and the total amount of dietary fat consumption is the most potent risk factor for weight gain. Long-term BED leads to greater sensitivity to the rewarding effects of palatable foods and results in obesity fatefully. Increased plasma concentrations of non-esterified free fatty acids and lipid-overloaded hypertrophic adipocytes may cause insulin resistance. In addition to dietary intake of high-fat diet, sedentary lifestyle leads to increased storage of triglycerides not only in adipose tissue but also ectopically in other tissues. Lipid-induced apoptosis, ceramide accumulation, reactive oxygen species overproduction, endoplasmic reticulum stress, and mitochondrial dysfunction play role in the pathogenesis of lipotoxicity. Food addiction and BED originate from complex action of dopaminergic, opioid, and cannabinoid systems. BED may also be associated with both obesity and major depressive disorder. For preventing morbidity and mortality, as well as decreasing the impact of obesity-related comorbidities in appropriately selected patients, opiate receptor antagonists and antidepressant combination are recommended. Pharmacotherapy alongside behavioral management improves quality of life and reduces the obesity risk; however, the number of licensed drugs is very few. Thus, stereotactic treatment is recommended to break down the refractory obesity and binge eating in obese patient. As recent applications in the field of non-invasive neuromodulation, transcranial magnetic stimulation and transcranial direct current stimulation are thought to be important in image-guided deep brain stimulation in humans. Chronic overnutrition most likely provides repetitive and persistent signals that up-regulate inhibitor of nuclear factor kappa B (NF-κB) kinase beta subunit/NF-κB (IKKß/NF-κB) in the hypothalamus before the onset of obesity. However, how the mechanisms of high-fat diet-induced peripheral signals affect the hypothalamic arcuate nucleus remain largely unknown.


Assuntos
Hiperfagia , Obesidade , Humanos , Hiperfagia/fisiopatologia , Hiperfagia/psicologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Transtorno da Compulsão Alimentar/terapia , Transtorno da Compulsão Alimentar/psicologia , Transtorno da Compulsão Alimentar/fisiopatologia , Animais , Comportamento Alimentar/fisiologia
15.
Phys Life Rev ; 51: 33-59, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39288541

RESUMO

Parrondo's paradox refers to the paradoxical phenomenon of combining two losing strategies in a certain manner to obtain a winning outcome. It has been applied to uncover unexpected outcomes across various disciplines, particularly at different spatiotemporal scales within ecosystems. In this article, we provide a comprehensive review of recent developments in Parrondo's paradox within the interdisciplinary realm of the physics of life, focusing on its significant applications across biology and the broader life sciences. Specifically, we examine its relevance from genetic pathways and phenotypic regulation, to intercellular interaction within multicellular organisms, and finally to the competition between populations and species in ecosystems. This phenomenon, spanning multiple biological domains and scales, enhances our understanding of the unified characteristics of life and reveals that adaptability in a drastically changing environment, rather than the inherent excellence of a trait, underpins survival in the process of evolution. We conclude by summarizing our findings and discussing future research directions that hold promise for advancing the field.

16.
Int J Law Psychiatry ; 97: 102017, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293323

RESUMO

This conceptual article examines the organisational crisis in England's National Health Service in light of the recently launched model of policing called Right Care Right Person introduced to reduce police hours spent dealing with mental health crisis calls. It is a move that has come with concerns for health services because these newly created gaps alongside the existing ones pose challenges around funding and timescales in implementing the new model. It is a curious case of organisational paradox that diverting mentally ill persons into health services and 'decriminalising' those whose health conditions bring them to the attention of the justice system, has raised concerns in the health sector about access to adequate mental health services unless an arm of the justice system is involved. Given the similarities in health and legal systems in the Anglo-Western world, this English model has international implications about organisational paradoxes in health systems.

17.
Nitric Oxide ; 152: 31-47, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299646

RESUMO

The biochemical interplay between antioxidants and pro-oxidants maintains the redox homeostatic balance of the cell, which, when perturbed to moderate or high extents, has been implicated in the onset and/or progression of chronic diseases such as diabetes mellitus, cancer, and neurodegenerative diseases. Thioredoxin, glutaredoxin, and lipoic acid-like thiol oxidoreductase systems constitute a unique ensemble of robust cellular antioxidant defenses, owing to their indispensable roles as S-denitrosylases, S-deglutathionylases, and disulfide reductants in maintaining a reduced free thiol state with biological relevance. Thus, in cells subjected to nitrosative stress, cellular antioxidants will S-denitrosylate their cognate S-nitrosoprotein substrates, rather than participate in trans-S-nitrosylation via protein-protein interactions. Researchers have been at the forefront of vaguely establishing the concept of 'transnitrosylation' and its influence on pathophysiology with experimental evidence from in vitro studies that lack proper biochemical logic. The suggestive and reiterative use of antioxidants as transnitrosylases in the scientific literature leaves us on a cliffhanger with several open-ended questions that prompted us to 'hunt' for scientific logic behind the trans-S-nitrosylation chemistry. Given the gravity of the situation and to look at the bigger picture of 'trans-S-nitrosylation', we aim to present a novel attempt at justifying the hesitance in accepting antioxidants as capable of transnitrosylating their cognate protein partners and reflecting on the need to resolve the controversy that would be crucial from the perspective of understanding therapeutic outcomes involving such cellular antioxidants in disease pathogenesis. Further characterization is required to identify the regulatory mechanisms or conditions where an antioxidant like Trx, Grx, or DJ-1 can act as a cellular transnitrosylase.

18.
Cancers (Basel) ; 16(17)2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39272808

RESUMO

BACKGROUND: Prior studies are inconclusive regarding the effect of obesity on mortality in persons with colorectal cancer (CRC). We sought to determine the association of pre-diagnosis body mass index (BMI) trajectories on mortality after CRC diagnosis. METHODS: Utilizing the Multiethnic Cohort, we included adults aged 18-75 between 1 January 1993 and 1 January 2019 with a diagnosis of CRC and at least three available BMIs. The primary exposure, BMI, was subjected to group-based trajectory modeling (GBTM). We evaluated all-cause and CRC-specific mortality, using Cox proportional hazard (PH) models. RESULTS: Of 924 persons, the median age was 60 years, and 54% were female. There was no statistically significant association between pre-cancer BMI trajectory and either all-cause or cancer-specific mortality. In competing risk analysis, the risk of CRC-specific mortality was higher for African Americans (HR = 1.56, 95% CI [1.00-2.43], p = 0.048) and smokers (HR = 1.59, 95% CI [1.10-2.32], p = 0.015). Risk of all-cause mortality was higher for Hawaiian persons (HR = 2.85, 95% CI [1.31-6.21], p = 0.009) and persons with diabetes (HR = 1.83, 95% CI [1.08-3.10], p = 0.026). CONCLUSIONS: Pre-diagnosis BMI trajectories were not associated with mortality after CRC diagnosis, whereas race/ethnicity, diabetes, and smoking were associated with an increased risk of death. Our findings suggest the obesity paradox alone does not account for mortality after CRC diagnosis.

19.
Artigo em Inglês | MEDLINE | ID: mdl-39248344

RESUMO

BACKGROUND: Recent studies have demonstrated an obesity paradox, where obese patients with cardiovascular disease have a better outcome compared to those with normal weight. However, the effect of obesity and body mass index (BMI) on the outcome of patients with cardiac resynchronization therapy (CRT) devices remains unclear. The current study aims to investigate this relationship using all available published data. METHODS: We systematically reviewed studies from Medline and EMBASE databases from inception to January 2024. Eligible studies must investigate the association between BMI status and all-cause mortality in individuals with CRT devices. Relative risk (RR) or hazard ratio (HR) and 95% CIs were retrieved from each study and combined using the generic inverse variance method. RESULTS: A total of 12 cohort studies were included in the meta-analysis. Pooled analysis showed that overweight and obesity patients had lower all-cause mortality compared to those with normal body weight with the pooled risk ratios (RR) for overweight of 0.77 (95% CI 0.69-0.87, I2 47%) and for obesity of 0.81 (95% CI 0.67-0.97, I2 59%). Conversely, the underweight exhibited higher all-cause mortality than the group with normal weight, with a pooled RR of 1.37 (95% CI 1.14-1.64, I2 0%). Additionally, higher BMI as continuous data was associated with decreased all-cause mortality, with a pooled HR of 0.94 (95% CI 0.89-0.98, I2 72%). CONCLUSIONS: The pooled analyses observed an obesity paradox in patients with CRT, where overweight and obesity were associated with reduced all-cause mortality, while underweight individuals exhibited higher all-cause mortality. Further research is necessary to investigate the underlying mechanisms and their implications for clinical practice.

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