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Cancers Jun 2024Melanoma is the cancer with the highest risk of dissemination to the central nervous system (CNS), one of the leading causes of mortality from this cancer.
BACKGROUND
Melanoma is the cancer with the highest risk of dissemination to the central nervous system (CNS), one of the leading causes of mortality from this cancer.
OBJECTIVE
To identify patients at higher risk of developing CNS metastases and to evaluate associated prognostic factors.
METHODS
A cohort study (1998-2023) assessed patients who developed CNS melanoma metastases. Multivariate logistic regression was used to identify predictive factors at melanoma diagnosis for CNS metastasis. Cox regression analysis evaluated the CNS-independent metastasis-related variables impacting survival.
RESULTS
Out of 4718 patients, 380 (8.05%) developed CNS metastases. Multivariate logistic regression showed that a higher Breslow index, mitotic rate ≥ 1 mm, ulceration, and microscopic satellitosis were significant risk factors for CNS metastasis development. Higher patient age and the location of the primary tumor in the upper or lower extremities were protective factors. In survival analysis, post-CNS metastasis, symptomatic disease, prior non-CNS metastases, CNS debut with multiple metastases, elevated LDH levels, and leptomeningeal involvement correlated with poorer survival.
CONCLUSION
Predictive factors in the primary tumor independently associated with brain metastases include microscopic satellitosis, ulceration, higher Breslow index, and trunk location. Prognostic factors for lower survival in CNS disease include symptomatic disease, multiple CNS metastases, and previous metastases from different sites.
PubMed: 38927977
DOI: 10.3390/cancers16122272 -
Biomedicines Jun 2024Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in...
Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF-/- C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF-/-; MIF-/-+Bet; TAA group, which received TAA; TAA+Bet; MIF-/-+TAA; and MIF-/-+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver.
PubMed: 38927544
DOI: 10.3390/biomedicines12061337 -
Biomedicines May 2024Amyloid β-peptide (Aβ) synthesis and deposition are the primary factors underlying the pathophysiology of Alzheimer's disease (AD). Aβ oligomer (Aβo) exerts its...
Amyloid β-peptide (Aβ) synthesis and deposition are the primary factors underlying the pathophysiology of Alzheimer's disease (AD). Aβ oligomer (Aβo) exerts its neurotoxic effects by inducing oxidative stress and lesions by adhering to cellular membranes. Though several antidepressants have been investigated as neuroprotective agents in AD, a detailed comparison of their neuroprotection against Aβo-induced neurotoxicity is lacking. Here, we aimed to elucidate the neuroprotective effects of clinically prescribed selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants at the cellular level and establish the underlying mechanisms for their potential clinical applications. Therefore, we compared the neuroprotective effects of three antidepressants, fluoxetine (Flx), duloxetine (Dlx), and mirtazapine (Mir), by their ability to prevent oxidative stress-induced cell damage, using SH-SY5Y cells, by evaluating cell viability, generation of reactive oxygen species (ROS) and mitochondrial ROS, and peroxidation of cell membrane phospholipids. These antidepressants exhibited potent antioxidant activity (Dlx > Mir > Flx) and improved cell viability. Furthermore, pretreatment with a 5-hydroxytryptamine 1A (5-HT) antagonist suppressed their effects, suggesting that the 5-HT receptor is involved in the antioxidant mechanism of the antidepressants' neuroprotection. These findings suggest the beneficial effects of antidepressant treatment in AD through the prevention of Aβ-induced oxidative stress.
PubMed: 38927365
DOI: 10.3390/biomedicines12061158 -
BMC Public Health Jun 2024Global warming has led to an increase in the number and intensity of extreme heat events, posing a significant threat to the health and safety of workers, especially...
PURPOSE
Global warming has led to an increase in the number and intensity of extreme heat events, posing a significant threat to the health and safety of workers, especially those working outdoors, as they often have limited access to cooling strategies. The present systematic literature review (a) summarizes the current knowledge on the impacts of climate change on outdoor workers, (b) provides historical background on this issue, (c) explores factors that reduce and increase thermal stress resilience, (d) discusses the heat mitigation strategies, and (e) provides an overview of existing policy and legal frameworks on occupational heat exposure among outdoor workers.
MATERIALS AND METHODS
In this systematic review, we searched scientific databases including Scopus (N = 855), Web of Science (N = 828), and PubMed (N = 202). Additionally, we identified relevant studies on climate change and heat-stress control measures through Google Scholar (N = 116) using specific search terms. In total, we monitored 2001 articles pertaining to worker populations (men = 2921; women = 627) in various outdoor climate conditions across 14 countries. After full-text assessment, 55 studies were selected for inclusion, and finally, 29 eligible papers were included for data extraction.
RESULTS
Failure to implement effective control strategies for outdoor workers will result in decreased resilience to thermal stress. The findings underscore a lack of awareness regarding certain adaptation strategies and interventions aimed at preventing and enhancing resilience to the impact of climate change on heat stress prevalence among workers in outdoor tropical and subtropical environments. However, attractive alternative solutions from the aspects of economic and ecological sustainability in the overall assessment of heat stress resilience can be referred to acclimatization, shading, optimized clothing properties and planned breaks.
CONCLUSION
The integration of climate change adaptation strategies into occupational health programs can enhance occupational heat resilience among outdoor workers. Conducting cost-benefit evaluations of health and safety measures for thermal stress adaptation strategies among outdoor workers is crucial for professionals and policymakers in low- and middle-income tropical and subtropical countries. In this respect, complementary measures targeting hydration, work-rest regimes, ventilated garments, self-pacing, and mechanization can be adopted to protect outdoor workers. Risk management strategies, adaptive measures, heat risk awareness, practical interventions, training programs, and protective policies should be implemented in hot-dry and hot-humid climates to boost the tolerance and resilience of outdoor workers.
Topics: Humans; Climate Change; Heat Stress Disorders; Occupational Exposure; Hot Temperature; Female; Male
PubMed: 38926816
DOI: 10.1186/s12889-024-19212-3 -
Alzheimer's Research & Therapy Jun 2024Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive...
BACKGROUND
Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype.
METHODS
Participants from a large, prospective, population-based, Swedish study were included (n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions.
RESULTS
The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3-20.8) years. When examining independent effects, APOE ε4 genotype(p < 0.01), and higher HbA(p < 0.001), were associated with future low memory function. Higher BMI (p < 0.05), and HbA(p < 0.05), lower high-density lipoprotein cholesterol (HDL-C)(p < 0.05)and stroke(p < 0.001) were associated with future low attention/executive function. The strongest factors associated with both better memory and attention/executive functions were higher education and alcohol consumption. Further, significant interaction effects between predictors and APOE genotype were found. For memory function, the protective effects of education were greater among ɛ4-carriers(p < 0.05). For attention/executive function, the protective effects of alcohol were greater among ɛ2 or ɛ4-carriers(p < 0.05). Also, attention/executive function was lower among ɛ4-carriers with higher BMI(p < 0.05) and ɛ2-carriers with higher HbA1c-levels(p < 0.05).
CONCLUSIONS
Targeting cardiovascular risk factors in mid-life could have greater effect on future attention/executive functions rather than memory, whereas targeting diabetes could be beneficial for multiple cognitive domains. In addition, effects of different risk factors may vary depending on the APOE genotype. The varied cognitive profiles suggest that different mechanisms and brain regions are affected by the individual risk factors. Having detailed knowledge about the specific cognitive effects of different risk factors might be beneficial in preventive health counseling.
Topics: Humans; Female; Male; Middle Aged; Risk Factors; Follow-Up Studies; Prospective Studies; Sweden; Executive Function; Cognition; Attention; Body Mass Index; Memory; Glycated Hemoglobin; Aged; Alcohol Drinking; Genotype; Apolipoprotein E4; Neuropsychological Tests; Cognitive Dysfunction
PubMed: 38926747
DOI: 10.1186/s13195-024-01497-6 -
Laboratory Animal Research Jun 2024Necrotizing enterocolitis (NEC) is a severe inflammatory bowel disease in neonates. Our group has developed an experimental model of NEC, with an effectiveness of 73%....
BACKGROUND
Necrotizing enterocolitis (NEC) is a severe inflammatory bowel disease in neonates. Our group has developed an experimental model of NEC, with an effectiveness of 73%. Cannabidiol (CBD) is an innovative treatment for neonatal cerebral hypoxic-ischemic pathologies due to its neuroprotective effect, as a potent anti-inflammatory and reducing oxidative stress substance. Our aim was to evaluate the effect of CBD on intestinal lesions in an experimental model of NEC.
RESULTS
Mortality and intestinal histological damage was significantly lower in the CBD group compared to the rest (p<0.05), establishing CBD as a protective factor against the development of NEC (OR=0.0255; 95% CI=0.0015-0.4460). At IHQ level (TUNEL technique), a lower cell death rate was also observed in the CBD group compared to the VEH group (p<0.05).
CONCLUSIONS
In our experimental model, intraperitoneal CBD acts as a protective factor against NEC, resulting in less histological damage and a lower rate of intestinal cell death.
PubMed: 38926744
DOI: 10.1186/s42826-024-00211-9 -
BMC Musculoskeletal Disorders Jun 2024While risk factors for osteoarthritis (OA) are well known, it is not well understood why certain individuals maintain high mobility and joint health throughout their...
OBJECTIVE
While risk factors for osteoarthritis (OA) are well known, it is not well understood why certain individuals maintain high mobility and joint health throughout their life while others demonstrate OA at older ages. The purpose of this study was to assess which demographic, clinical and MRI quantitative and semi-quantitative factors are associated with preserving healthy knees in older individuals.
METHODS
This study analyzed data from the OA Initiative (OAI) cohort of individuals at the age of 65 years or above. Participants without OA at baseline (BL) (Kellgren-Lawrence (KL) ≤ 1) were followed and classified as incident cases (KL ≥ 2 during follow-up; n = 115) and as non-incident (KL ≤ 1 over 96-month; n = 391). Associations between the predictor-variables sex, age, BMI, race, clinical scoring systems, T relaxation times and Whole-Organ Magnetic Resonance Imaging-Score (WORMS) readings at BL and the preservation of healthy knees (KL ≤ 1) during a 96-month follow-up period were assessed using logistic regression models.
RESULTS
Obesity and presence of pain showed a significant inverse association with maintaining radiographically normal joints in patients aged 65 and above. T relaxation times of the lateral femur and tibia as well as the medial femur were also significantly associated with maintaining radiographically normal knee joints. Additionally, absence of lesions of the lateral meniscus and absence of cartilage lesions in the medial and patellofemoral compartments were significantly associated with maintaining healthy knee joints.
CONCLUSION
Overall, this study provides protective clinical parameters as well as quantitative and semi-quantitative MR-imaging parameters associated with maintaining radiographically normal knee joints in an older population over 8 years.
Topics: Humans; Male; Aged; Female; Magnetic Resonance Imaging; Knee Joint; Osteoarthritis, Knee; Follow-Up Studies; Risk Factors; Aged, 80 and over; Obesity
PubMed: 38926717
DOI: 10.1186/s12891-024-07590-z -
Scientific Reports Jun 2024This study aims to further understand the changes in physical activity level(PAL) and mental health among adolescents before and after the outbreak of COVID-19 and...
This study aims to further understand the changes in physical activity level(PAL) and mental health among adolescents before and after the outbreak of COVID-19 and explore the protective role of physical activity (PA) on the mental health of adolescents during major disasters. A convenient sampling method was used to conduct a cross-sectional survey. The cross-sectional data from 2838 Chinese middle school students (mean age = 14.91 ± 1.71 years, 49.54% female) were used, of which 1,471 and 1,367 were in 2021 and 2022, respectively. The PAL was collected using the Physical Activity Questionnaire for Children (PAQ-CN), mental health status was collected using the Mental Health Inventory of Middle School Students (MMHI-60), sociodemographic information was collected using a self-reported questionnaire. Before and after the outbreak of COVID-19, the PAL of adolescents was 2.36 ± 0.74 and 2.50 ± 0.66, respectively, with a significant difference (p < 0.01, 95% CI: 0.09, 0.19). The mental health scores were 1.71 ± 0.60 and 1.86 ± 0.73, respectively, with a significant difference (p < 0.01, 95% CI: - 0.20, - 0.10). The detection rates of mental health problems were 27.50% and 35.50%, respectively. The rates of achieving PAL standards were 30.20% and 18.00% among adolescents, while the rates of not achieving PAL standards were 39.60% and 18.00%. PA is a protective factor for the mental health of adolescents during major disasters.
Topics: Humans; COVID-19; Adolescent; Female; Male; Mental Health; Exercise; Students; Cross-Sectional Studies; Surveys and Questionnaires; SARS-CoV-2; China; Schools; Disease Outbreaks; Child
PubMed: 38926496
DOI: 10.1038/s41598-024-65599-9 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early...
OBJECTIVES
To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.
METHODS
A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.
RESULTS
A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (=3.370, 95%: 1.500-7.568, <0.05), and high gestational age at birth was a protective factor against BPD (<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (=5.017, 95%: 1.040-24.190, <0.05).
CONCLUSIONS
The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.
Topics: Humans; Bronchopulmonary Dysplasia; Risk Factors; Infant, Newborn; Female; Retrospective Studies; Male; Infant, Premature; Twins; Gestational Age; Birth Weight; Logistic Models
PubMed: 38926378
DOI: 10.7499/j.issn.1008-8830.2312005 -
British Journal of Sports Medicine Jun 2024To conduct a meta-analytic review of psychosocial predictors of doping intention, doping use and inadvertent doping in sport and exercise settings.
OBJECTIVE
To conduct a meta-analytic review of psychosocial predictors of doping intention, doping use and inadvertent doping in sport and exercise settings.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Scopus, Medline, Embase, PsychINFO, CINAHL Plus, ProQuest Dissertations/Theses and Open Grey.
ELIGIBILITY CRITERIA
Studies (of any design) that measured the outcome variables of doping intention, doping use and/or inadvertent doping at least one psychosocial determinant of those three variables.
RESULTS
We included studies from 25 experiments (N=13 586) and 186 observational samples (N=3 09 130). Experimental groups reported lower doping intentions (=-0.21, 95% CI (-0.31 to -0.12)) and doping use (=-0.08, 95% CI (-0.14 to -0.03), but not inadvertent doping (=-0.70, 95% CI (-1.95 to 0.55)), relative to comparators. For observational studies, protective factors were inversely associated with doping intentions (=-0.28, 95% CI -0.31 to -0.24), doping use (=-0.09, 95% CI -0.13 to to -0.05) and inadvertent doping (=-0.19, 95% CI -0.32 to -0.06). Risk factors were positively associated with doping intentions (=0.29, 95% CI 0.26 to 0.32) and use (=0.17, 95% CI 0.15 to 0.19), but not inadvertent doping (=0.08, 95% CI -0.06 to 0.22). Risk factors for both doping intentions and use included prodoping norms and attitudes, supplement use, body dissatisfaction and ill-being. Protective factors for both doping intentions and use included self-efficacy and positive morality.
CONCLUSION
This study identified several protective and risk factors for doping intention and use that may be viable intervention targets for antidoping programmes. Protective factors were negatively associated with inadvertent doping; however, the empirical volume is limited to draw firm conclusions.
PubMed: 38925889
DOI: 10.1136/bjsports-2023-107910