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BMC Cancer Jun 2024Wilms tumor is the most prevalent embryonal kidney malignancy in children worldwide. Previous genome-wide association study (GWAS) identified that LIM domain only 1...
BACKGROUND
Wilms tumor is the most prevalent embryonal kidney malignancy in children worldwide. Previous genome-wide association study (GWAS) identified that LIM domain only 1 (LMO1) gene polymorphisms affected the susceptibility to develop certain tumor types. Apart from LMO1, the LMO gene family members also include LMO2-4, each of which has oncogenic potential.
METHODS
We conducted this five-center case‒control study to assess the correlations between single nucleotide polymorphisms in LMO family genes and Wilms tumor susceptibility. Odds ratios and 95% confidence intervals were calculated to evaluate the strength of the association.
RESULTS
We found LMO1 rs2168101 G > T and rs11603024 C > T as well as LMO2 rs7933499 G > A were significantly associated with Wilms tumor risk. Stratified analysis demonstrated a protective role of rs2168101 GT/TT genotypes against Wilms tumor in the subgroups of age ≤ 18 months, males and clinical stages I/II compared to the rs2168101 GG genotype. Nevertheless, carriers with the rs11603024 TT genotype were more likely to have an increased risk of Wilms tumor than those with rs11603024 CC/CT genotypes in age > 18 months. And the rs11603024 was identified as a protective polymorphism for reducing the risk of Wilms tumor in the sex- and gender- subgroup. Likewise, carriers with the rs7933499 GA/AA genotypes were at significantly elevated risk of Wilms tumor in age ≤ 18 months and clinical stages I/II.
CONCLUSION
Overall, our study identified the importance of LMO family gene polymorphisms on Wilms tumor susceptibility in Chinese children. Further investigations are needed to validate our conclusions.
Topics: Child; Child, Preschool; Female; Humans; Infant; Male; Adaptor Proteins, Signal Transducing; Case-Control Studies; China; DNA-Binding Proteins; East Asian People; Genetic Predisposition to Disease; Genotype; Kidney Neoplasms; LIM Domain Proteins; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins; Transcription Factors; Wilms Tumor; Multigene Family
PubMed: 38937681
DOI: 10.1186/s12885-024-12557-3 -
BMC Pediatrics Jun 2024Hypoxemia is a common complication of childhood respiratory tract infections and non-respiratory infections. Hypoxemic children have a five-fold increased risk of death...
Hypoxemia and its clinical predictors among children with respiratory distress admitted to the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.
INTRODUCTION
Hypoxemia is a common complication of childhood respiratory tract infections and non-respiratory infections. Hypoxemic children have a five-fold increased risk of death compared to children without hypoxemia. In addition, there is limited evidence about hypoxemia and clinical predictors in Ethiopia. Therefore, this study was conducted to assess the prevalence and clinical predictors of hypoxemia among children with respiratory distress admitted to the University of Gondar Comprehensive Specialized Hospital.
METHODS
An institutional-based cross-sectional study was conducted from December 2020 to May 2021 in northwest Ethiopia. A total of 399 study participants were selected using systematic random sampling. The oxygen saturation of the child was measured using Masimo rad-5 pulse oximetry. SPSS version 21 software was used for statistical analysis.
RESULT
In this study, the prevalence of hypoxemia among children with respiratory distress was 63.5%. The clinical signs and symptoms significantly associated with hypoxemia were: head-nodding (AOR: 4.1, 95% CI: 1.81-9.28) and chest indrawing (AOR: 3.08, 95% CI: 1.32-7.16) which were considered statistically the risk factors for hypoxemia while inability to feed (AOR: 0.13, 95% CI: 0.02-0.77) was the protective factor for hypoxemia. The most sensitive predictors of hypoxemia were fast breathing with sensitivity (98.4%), nasal flaring (100.0%), chest indrawing (83.6%), and intercostal retraction (93.1%). The best specific predictors of hypoxemia were breathing difficulty with specificity (79.4%), inability to feed (100.0%), wheezing (83.0%), cyanosis (98.6%), impaired consciousness (94.2%), head-nodding (88.7%), and supra-sternal retraction (96.5%).
CONCLUSION AND RECOMMENDATION
The prevalence of hypoxemia among children was high. The predictors of hypoxemia were the inability to feed, head nodding, and chest indrawing. It is recommended that the health care settings provide immediate care for the children with an inability to feed, head nodding, and chest indrawing. The policymakers better to focus on preventive strategies, particularly those with the most specific clinical predictors.
Topics: Humans; Ethiopia; Female; Hypoxia; Male; Cross-Sectional Studies; Child, Preschool; Prevalence; Infant; Risk Factors; Child; Hospitals, University; Respiratory Distress Syndrome; Hospitals, Special; Oximetry
PubMed: 38937669
DOI: 10.1186/s12887-024-04892-y -
Nature Reviews. Cardiology Jun 2024Autoimmune diseases are associated with a dramatically increased risk of atherosclerotic cardiovascular disease and its clinical manifestations. The increased risk is... (Review)
Review
Autoimmune diseases are associated with a dramatically increased risk of atherosclerotic cardiovascular disease and its clinical manifestations. The increased risk is consistent with the notion that atherogenesis is modulated by both protective and disease-promoting immune mechanisms. Notably, traditional cardiovascular risk factors such as dyslipidaemia and hypertension alone do not explain the increased risk of cardiovascular disease associated with autoimmune diseases. Several mechanisms have been implicated in mediating the autoimmunity-associated cardiovascular risk, either directly or by modulating the effect of other risk factors in a complex interplay. Aberrant leukocyte function and pro-inflammatory cytokines are central to both disease entities, resulting in vascular dysfunction, impaired resolution of inflammation and promotion of chronic inflammation. Similarly, loss of tolerance to self-antigens and the generation of autoantibodies are key features of autoimmunity but are also implicated in the maladaptive inflammatory response during atherosclerotic cardiovascular disease. Therefore, immunomodulatory therapies are potential efficacious interventions to directly reduce the risk of cardiovascular disease, and biomarkers of autoimmune disease activity could be relevant tools to stratify patients with autoimmunity according to their cardiovascular risk. In this Review, we discuss the pathophysiological aspects of the increased cardiovascular risk associated with autoimmunity and highlight the many open questions that need to be answered to develop novel therapies that specifically address this unmet clinical need.
PubMed: 38937626
DOI: 10.1038/s41569-024-01045-7 -
In Vivo (Athens, Greece) 2024Matrix metalloproteinase 13 (MMP13) has been reported to be involved in tumor development and progression, including of colorectal cancer (CRC). This study aimed at...
BACKGROUND/AIM
Matrix metalloproteinase 13 (MMP13) has been reported to be involved in tumor development and progression, including of colorectal cancer (CRC). This study aimed at evaluating whether the MMP13 rs2252070 gene polymorphism is associated with clinicopathological factors and its influence on long-term survival in Swedish patients with CRC.
PATIENTS AND METHODS
A total of 723 patients with CRC were genotyped using TaqMan single nucleotide polymorphism assays based on polymerase chain reaction.
RESULTS
Assessing clinicopathological factors, we demonstrated that having the G/G genotype for MMP13 rs2252070 was significantly associated with poor differentiation, higher serum level of carcinoembryonic antigen and higher lymph node status. Moreover, the presence of a G allele was significantly related to larger tumor size in rectal cancer but had a significantly protective role against mucinous cancer, perineural invasion and lymphovascular invasion. Kaplan-Meier analysis showed no difference between genotypes regarding cancer-specific survival.
CONCLUSION
Our findings highlight the potential of MMP13 rs2252070 polymorphism as a useful predictor of poor differentiation, serum level of carcinoembryonic antigen, lymph node status, tumor size, mucinous cancer, perineural invasion and lymphovascular invasion in patients with CRC.
Topics: Humans; Colorectal Neoplasms; Male; Female; Polymorphism, Single Nucleotide; Sweden; Matrix Metalloproteinase 13; Aged; Middle Aged; Genotype; Genetic Predisposition to Disease; Prognosis; Alleles; Kaplan-Meier Estimate; Aged, 80 and over; Adult; Carcinoembryonic Antigen; Neoplasm Staging; Biomarkers, Tumor; Genetic Association Studies
PubMed: 38936942
DOI: 10.21873/invivo.13628 -
In Vivo (Athens, Greece) 2024The up-regulation of matrix metalloproteinase-9 (MMP-9) expression is a characteristic feature observed across various malignancies, including nasopharyngeal carcinoma...
BACKGROUND/AIM
The up-regulation of matrix metalloproteinase-9 (MMP-9) expression is a characteristic feature observed across various malignancies, including nasopharyngeal carcinoma (NPC). Nevertheless, the influence of MMP-9 genotype in the context of NPC remains underexplored. This study examined the implications of MMP-9 promoter rs3918242 genotypes on the susceptibility to NPC in Taiwan.
MATERIALS AND METHODS
In a cohort comprising 208 NPC cases and 416 healthy controls, genotyping of MMP-9 rs3918242 was conducted utilizing polymerase chain reaction-restriction fragment length polymorphism methodology.
RESULTS
Individuals harbouring the variant CT or TT genotype of MMP-9 rs3918242 did not demonstrate a discernible alteration in NPC risk when compared to wild-type CC carriers [odds ratio (OR)=0.83 and 0.79, with 95% confidence intervals (95%CI)=0.56-1.24 and 0.27-2.29; p=0.4205 and 0.8675, respectively]. Moreover, the presence of the variant T allele did not confer a modified risk of NPC (OR=0.84, 95%CI=0.60-1.19, p=0.3761). Intriguingly, a protective effect associated with the MMP-9 rs3918242 CT genotype against NPC risk was discerned among individuals abstaining from betel quid chewing behaviour (OR=0.51, 95%CI=0.30-0.87, p=0.0166). Notably, no significant association was established between the MMP-9 rs3918242 CT or TT genotype and NPC risk among individuals with or without smoking or alcohol consumption habits.
CONCLUSION
Presence of the variant CT or TT genotype at MMP-9 rs3918242 did not appear to substantially contribute to an elevated risk of NPC. Notably, a protective effect against NPC risk was observed in individuals carrying the CT genotype, particularly in those abstaining from betel quid chewing.
Topics: Humans; Matrix Metalloproteinase 9; Male; Female; Genetic Predisposition to Disease; Nasopharyngeal Carcinoma; Middle Aged; Genotype; Polymorphism, Single Nucleotide; Adult; Nasopharyngeal Neoplasms; Risk Factors; Case-Control Studies; Alleles; Promoter Regions, Genetic; Genetic Association Studies; Odds Ratio; Taiwan; Gene Frequency; Aged
PubMed: 38936920
DOI: 10.21873/invivo.13623 -
The Journal of School Health Jun 2024Despite historical and contemporary trauma, American Indian and Alaska Native (AIAN; Indigenous) communities responded with resilience to the COVID-19 pandemic. However,...
BACKGROUND
Despite historical and contemporary trauma, American Indian and Alaska Native (AIAN; Indigenous) communities responded with resilience to the COVID-19 pandemic. However, AIANs experienced disproportionate rates of infection, hospitalization, death, and reduced life expectancy. School closures exacerbated disparities, leading to learning loss, economic instability, and mental health challenges among AIAN youth.
METHODS
The Project SafeSchools cohort study employed a comprehensive longitudinal convergent mixed-methods approach, integrating community-based participatory research principles. The study enrolled Navajo Nation caregivers whose children were eligible to attend local reservation-based schools. We conducted an analysis of caregiver self-report baseline data collected between August 2021 and May 2022.
RESULTS
A total of 242 caregivers completed at least part of the baseline assessment and were included in data analysis. Caregivers were primarily female (88.7%), non-Hispanic (97%), and Indigenous (97%). Most caregivers were in their late 30s (mean age 38), with varying educational backgrounds and employment statuses. Children were evenly split between males and females and distributed across different age groups. Most children attended school at baseline in various formats, including in-person, hybrid, and online-only settings. Caregivers reported a range of psychosocial and behavioral risks, including general mental distress, depressive symptoms, and anxiety for themselves and their children. Furthermore, caregivers and children exhibited various protective factors, such as strong cultural identity, resilience, and academic self-efficacy.
CONCLUSIONS
This study highlights the higher rates of mental health distress among participating caregivers and children compared to national averages. Despite these challenges, cultural protective factors remained strong and should guide future crisis response efforts.
PubMed: 38936839
DOI: 10.1111/josh.13487 -
Loss of Gcn2 exacerbates gossypol induced oxidative stress, apoptosis and inflammation in zebrafish.Fish & Shellfish Immunology Jun 2024Gossypol, a naturally occurring compound found in cottonseed meal, shows promising therapeutic potential for human diseases. However, within the aquaculture industry, it...
Gossypol, a naturally occurring compound found in cottonseed meal, shows promising therapeutic potential for human diseases. However, within the aquaculture industry, it is considered an antinutritional factor. The incorporation of cottonseed meal into fish feed introduces gossypol, which induces intracellular stresses and hinders overall health of farmed fish. The aim of this study is to determine the role of General control nonderepressible 2 (gcn2), a sensor for intracellular stresses in gossypol-induced stress responses in fish. In the present study, we established two gcn2 knockout zebrafish lines. A feeding trial was conducted to assess the growth-inhibitory effect of gossypol in both wild type and gcn2 knockout zebrafish. The results showed that in the absence of gcn2, zebrafish exhibited increased oxidative stress and apoptosis when exposed to gossypol, resulting in higher mortality rates. In feeding trial, dietary gossypol intensified liver inflammation in gcn2 zebrafish, diminishing their growth and feed conversion. Remarkably, administering the antioxidant N-acetylcysteine (NAC) was effective in reversing the gossypol induced oxidative stress and apoptosis, thereby increasing the gossypol tolerance of gcn2 zebrafish. Exposure to gossypol induces more severe mitochondrial stress in gcn2 zebrafish, thereby inducing metabolic disorders. These results reveal that gcn2 plays a protective role in reducing gossypol-induced oxidative stress and apoptosis, attenuating inflammation responses, and enhancing the survivability of zebrafish in gossypol-challenged conditions. Therefore, maintaining appropriate activation of Gcn2 may be beneficial for fish fed diets containing gossypol.
PubMed: 38936520
DOI: 10.1016/j.fsi.2024.109727 -
European Journal of Pharmacology Jun 2024Given estrogen's recognized regulatory influence on diverse metabolic and immune functions, this study sought to explore its potential impact on fibrosis and elucidate...
AIM
Given estrogen's recognized regulatory influence on diverse metabolic and immune functions, this study sought to explore its potential impact on fibrosis and elucidate the underlying metabolic regulations.
METHODS
Female mice underwent ovary removal surgery, followed by carbon tetrachloride (CCl) administration to induce liver injury. Biochemical index analysis and histopathological examination were then conducted. The expression levels of alpha-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and collagen type 1 alpha 1 chain (COL1A1) were assessed using western blotting to further elucidate the extent of liver injury. Finally, metabolite extraction and metabolomic analysis were performed to evaluate metabolic changes.
RESULTS
Ovary removal exacerbated CCl-induced liver damage, while estrogen supplementation provided protection against hepatic changes resulting from OVX. Furthermore, estrogen mitigated liver injury induced by CCl treatment in vivo. Estrogen supplementation significantly restored liver damage induced by OVX and CCl. Comparative analysis revealed significant alterations in pathways including aminoacyl-tRNA biosynthesis, glycine, serine, and threonine metabolism, lysine degradation, and taurine and hypotaurine metabolism in estrogen treatment.
CONCLUSION
Estrogen supplementation alleviates liver injury induced by OVX and CCl, highlighting its protective effects against fibrosis and associated metabolic alterations.
PubMed: 38936452
DOI: 10.1016/j.ejphar.2024.176774 -
General Hospital Psychiatry Jun 2024Caregiving burden is set to increase with the rising incidence of cancer globally. The meta-analysis seeks to investigate the prevalence of suicide, suicidal ideation... (Review)
Review
OBJECTIVE
Caregiving burden is set to increase with the rising incidence of cancer globally. The meta-analysis seeks to investigate the prevalence of suicide, suicidal ideation and self-harm among the caregivers of patients with cancer (CPCs).
METHODS
This PRISMA-adherent systematic review involved a systematic search of PubMed, Embase, Cochrane and PsycINFO for all studies that evaluated the prevalence of suicide, suicidal ideation and self-harm in CPCs. Random effects meta-analyses were used for primary analysis.
RESULTS
Eleven studies were included. Meta-analyses indicated that the prevalence of suicidal ideation in CPCs was 11% (95%CI:6-18), suicide prevalence was 6% (95%CI:3-12), and self-harm prevalence was 15% (95%CI:8-26). Subgroup analyses revealed that CPCs above the age of 50 experienced a greater prevalence of suicidal ideation (17%, 95%CI:10-28) as compared to CPCs below 50 (6%, 95%CI:3-12). Family caregivers particularly spouses were also found to have a higher prevalence of suicidal ideation (17%, 95%CI:13-23), as compared to children (5%, 95%CI:2-10) or mothers (3%, 95%CI:1-8). Systematic review found that having a pre-existing mental health condition and lower socioeconomic status increased likelihood of suicidality.
CONCLUSION
We highlight the need for more support of CPCs at risk of suicidality. Additional research is warranted to identify other risk and protective factors.
PubMed: 38936297
DOI: 10.1016/j.genhosppsych.2024.06.011 -
International Emergency Nursing Jun 2024Workplace wellbeing encompasses all aspects of working life. Peak health organisations recognise that poor workplace wellbeing is costly, both to individuals and to the...
Workplace wellbeing encompasses all aspects of working life. Peak health organisations recognise that poor workplace wellbeing is costly, both to individuals and to the organisation, and the value in promoting healthy workplaces. Workplace wellbeing improves when its barriers are acknowledged and addressed, and protective factors are promoted. The Emergency Department (ED) is a place of intense and challenging activity, exacerbated by high workloads and overcrowding. This impacts negatively on patient care, staff safety and wellbeing. We held focus groups across four EDs to discuss barriers and enablers to wellbeing and found four core themes: Workplace Satisfaction; Barriers to Wellbeing; Organisational Culture that Prioritises Staff Wellbeing; Self-care and Self Compassion. From this, and existing literature, we collaboratively developed a contextualised staff wellbeing framework titled: 'Staff Wellbeing Good Practice Framework: From Surviving to Thriving, How to Protect your Wellbeing in the Emergency Department' that emphasises their values of Competence, Connection and Control.
PubMed: 38936273
DOI: 10.1016/j.ienj.2024.101487