-
JAMA Psychiatry Jun 2024Recurrent copy number variants (rCNVs) have been associated with increased risk of psychiatric disorders in case-control studies, but their population-level impact is...
IMPORTANCE
Recurrent copy number variants (rCNVs) have been associated with increased risk of psychiatric disorders in case-control studies, but their population-level impact is unknown.
OBJECTIVE
To provide unbiased population-based estimates of prevalence and risk associated with psychiatric disorders for rCNVs and to compare risks across outcomes, rCNV dosage type (deletions or duplications), and locus features.
DESIGN, SETTING, AND PARTICIPANTS
This genetic association study is an analysis of data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) case-cohort sample of individuals born in Denmark in 1981-2008 and followed up until 2015, including (1) all individuals (n = 92 531) with a hospital discharge diagnosis of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder, major depressive disorder (MDD), or schizophrenia spectrum disorder (SSD) and (2) a subcohort (n = 50 625) randomly drawn from the source population. Data were analyzed from January 2021 to August 2023.
EXPOSURES
Carrier status of deletions and duplications at 27 autosomal rCNV loci was determined from neonatal blood samples genotyped on single-nucleotide variant microarrays.
MAIN OUTCOMES AND MEASURES
Population-based rCNV prevalence was estimated with a survey model using finite population correction to account for oversampling of cases. Hazard ratio (HR) estimates and 95% CIs for psychiatric disorders were derived using weighted Cox proportional hazard models. Risks were compared across outcomes, dosage type, and locus features using generalized estimating equation models.
RESULTS
A total of 3547 rCNVs were identified in 64 735 individuals assigned male at birth (53.8%) and 55 512 individuals assigned female at birth (46.2%) whose age at the end of follow-up ranged from 7.0 to 34.7 years (mean, 21.8 years). Most observed increases in rCNV-associated risk for ADHD, ASD, or SSD were moderate, and risk estimates were highly correlated across these disorders. Notable exceptions included high ASD-associated risk observed for Prader-Willi/Angelman syndrome duplications (HR, 20.8; 95% CI, 7.9-55). No rCNV was associated with increased MDD risk. Also, rCNV-associated risk was positively correlated with locus size and gene constraint but not with dosage type. Comparison with published case-control and community-based studies revealed a higher prevalence of deletions and lower associated increase in risk for several rCNVs in iPSYCH2015.
CONCLUSIONS AND RELEVANCE
This study found that several rCNVs were more prevalent and conferred less risk of psychiatric disorders than estimated previously. Most case-control studies overestimate rCNV-associated risk of psychiatric disorders, likely because of selection bias. In an era where genetics is increasingly being clinically applied, these results highlight the importance of population-based risk estimates for genetics-based predictions.
PubMed: 38922630
DOI: 10.1001/jamapsychiatry.2024.1453 -
Journal of Toxicology and Environmental... Jun 2024Although the last pandemic created an urgency for development of vaccines, there was a continuous and concerted effort to search for therapeutic medications among...
Although the last pandemic created an urgency for development of vaccines, there was a continuous and concerted effort to search for therapeutic medications among existing drugs with different indications. One of the medications of interest that underwent this change was infliximab (IFM). This drug is used as an anti-inflammatory, predominantly in patients with Crohn 's disease, colitis ulcerative, and rheumatoid arthritis. In addition to these patients, individuals infected with Coronavirus Disease (COVID-19) were administered this chimeric monoclonal antibody (IMF) to act as an immunomodulator for patients in the absence of comprehensive research. Consequently, the present study aimed to examine the genotoxic effects attributed to IFM treatment employing different assays using mouse . Therefore, IFM was found to induce genotoxic effects as evidenced by the comet assay but did not demonstrate genotoxic potential utilizing mouse bone marrow MN test. The results of evaluating the expression of the P53 and BCL-2 genes using RT-qPCR showed stimulation of expression of these genes at 24 hr followed by a decline at 48 hr. Although the comet assay provided positive results, it is noteworthy that based upon negative findings in the micronucleus test, the data did not demonstrate significant changes in the genetic material that might affect the therapeutic use of IFM. The stimulation of expression of P53 and BCL-2 genes at 24 hr followed by a decline at 48 hr suggest a transient, if any, effect on genetic material. However, there is still a need for more research to more comprehensively understand the genotoxic profile of this medication.
PubMed: 38922576
DOI: 10.1080/15287394.2024.2368619 -
Drug Delivery and Translational Research Jun 2024The resistance of malignant tumors to multiple drugs is a significant obstacle in cancer treatment and prognosis. Accordingly, we synthesized a celastrol (Cel) prodrug...
The resistance of malignant tumors to multiple drugs is a significant obstacle in cancer treatment and prognosis. Accordingly, we synthesized a celastrol (Cel) prodrug (Cel-CSO) by conjugating chitosan oligosaccharides (CSO) to Cel for reversing Taxol resistance in chemotherapy, followed by self-assembly with Taxol into a novel nanoplatform of Cel-CSO/Taxol nanoparticles (termed NPs). NPs showed a suitable size (about 153 nm), excellent stability and prolonged release of Cel and Taxol in a manner that depended on both pH and time. NPs effectively inhibited the overexpression of multidrug resistance-related protein P-gp, hypoxia inducible factor-1α (HIF-1α), and triggered the MCF-7/Taxol cell apoptosis through inhibiting the PI3K/AKT/NF-κB/HIF-1α pathway. In tumor-bearing mice, NPs exhibited significant curative effects in inducing apoptosis of MCF-7/Taxol tumors which showed a low expression level of P-gp, microtubule-related proteins TUBB3 and Tau. The results indicated that NPs may be a promising strategy to overcome drug resistance caused by P-gp, which improve the antitumor effects in drug-resistant breast cancer.
PubMed: 38922561
DOI: 10.1007/s13346-024-01653-3 -
Brazilian Journal of Microbiology :... Jun 2024Foodborne diseases remain a worldwide concern, despite the advances made in sanitation, pathogen surveillance and food safety management systems. The methods routinely... (Review)
Review
Foodborne diseases remain a worldwide concern, despite the advances made in sanitation, pathogen surveillance and food safety management systems. The methods routinely applied for detecting pathogens in foods are time consuming, labor intensive and usually require trained and qualified individuals. The objective of this review was to highlight the use of biosensors, with a focus on the electrochemical devices, as promising alternatives for detecting foodborne pathogens. These biosensors present high speed for obtaining results, with the possibility of evaluating foods in real time, at low cost, ease of use, in addition to being compact and portable. These aspects are considered advantageous and suitable for use in food safety management systems. This work also shows some limitations for the application of biosensors, and we present perspectives with the development and use of nanomaterials.
PubMed: 38922532
DOI: 10.1007/s42770-024-01427-6 -
Cell Biology and Toxicology Jun 2024The primary objective of this investigation is to delve into the involvement of the long noncoding RNA (lncRNA) SPACA6P-AS in breast cancer (BC) development, focusing on...
OBJECTIVE
The primary objective of this investigation is to delve into the involvement of the long noncoding RNA (lncRNA) SPACA6P-AS in breast cancer (BC) development, focusing on its expression pattern, association with clinical-pathological features, impact on prognosis, as well as its molecular and immunological implications.
METHODS
Bioinformatics analysis was conducted utilizing RNA sequencing data of 1083 BC patients from the TCGA database. Functional exploration of SPACA6P-AS was carried out through the construction of survival curves, GO and KEGG enrichment analysis, and single-sample gene set enrichment analysis (ssGSEA). Furthermore, its functionality was validated through in vitro cell experiments and in vivo nude mouse model experiments.
RESULTS
SPACA6P-AS showed a remarkable increase in expression levels in BC tissues (p < 0.001) and demonstrated a close relationship to poor prognosis (overall survival HR = 1.616, progression-free interval HR = 1.40, disease-specific survival HR = 1.54). Enrichment analysis revealed that SPACA6P-AS could impact biological functions such as protease regulation, endopeptidase inhibitor activity, taste receptor activity, taste transduction, and maturity-onset diabetes of the young pathway. ssGSEA analysis indicated a negative correlation between SPACA6P-AS expression and immune cell infiltration like dendritic cells and neutrophils, while a positive correlation was observed with central memory T cells and T helper 2 cells. Results from in vitro and in vivo experiments illustrated that silencing SPACA6P-AS significantly inhibited the proliferation, migration, and invasion capabilities of BC cells. In vitro experiments also highlighted that dendritic cells with silenced SPACA6P-AS exhibited enhanced capabilities in promoting the proliferation of autologous CD3 + T cells and cytokine secretion. These discoveries elucidate the potential multifaceted roles of SPACA6P-AS in BC, including its potential involvement in modulating immune cell infiltration in the tumor microenvironment.
CONCLUSION
The high expression of lncRNA SPACA6P-AS in BC is closely linked to poor prognosis and may facilitate tumor progression by influencing specific biological processes, signaling pathways, and the immune microenvironment. The regulatory role of SPACA6P-AS positions it as a prospective biomarker and target for therapeutic approaches for BC diagnosis and intervention.
Topics: Humans; Breast Neoplasms; Animals; RNA, Long Noncoding; Female; Gene Expression Regulation, Neoplastic; Mice, Nude; Mice; Cell Line, Tumor; Prognosis; Cell Proliferation; Mice, Inbred BALB C; Middle Aged; Cell Movement; Computational Biology
PubMed: 38922500
DOI: 10.1007/s10565-024-09870-9 -
GeroScience Jun 2024Oncobiosis has emerged as a key contributor to the development, and modulator of the treatment efficacy of cancer. Hereby, we review the modalities through which the...
Oncobiosis has emerged as a key contributor to the development, and modulator of the treatment efficacy of cancer. Hereby, we review the modalities through which the oncobiome can support the progression of tumors, and the emerging therapeutic opportunities they present. The review highlights the inherent challenges and limitations faced in sampling and accurately characterizing oncobiome. Additionally, the review underscores the critical need for the standardization of microbial analysis techniques and the consistent reporting of microbiome data. We provide a suggested metadata set that should accompany microbiome datasets from oncological settings so that studies remain comparable and decipherable.
PubMed: 38922379
DOI: 10.1007/s11357-024-01255-4 -
Medical & Biological Engineering &... Jun 2024The exponential growth in data volume has necessitated the adoption of alternative storage solutions, and DNA storage stands out as the most promising solution. However,... (Review)
Review
The exponential growth in data volume has necessitated the adoption of alternative storage solutions, and DNA storage stands out as the most promising solution. However, the exorbitant costs associated with synthesis and sequencing impeded its development. Pre-compressing the data is recognized as one of the most effective approaches for reducing storage costs. However, different compression methods yield varying compression ratios for the same file, and compressing a large number of files with a single method may not achieve the maximum compression ratio. This study proposes a multi-file dynamic compression method based on machine learning classification algorithms that selects the appropriate compression method for each file to minimize the amount of data stored into DNA as much as possible. Firstly, four different compression methods are applied to the collected files. Subsequently, the optimal compression method is selected as a label, as well as the file type and size are used as features, which are put into seven machine learning classification algorithms for training. The results demonstrate that k-nearest neighbor outperforms other machine learning algorithms on the validation set and test set most of the time, achieving an accuracy rate of over 85% and showing less volatility. Additionally, the compression rate of 30.85% can be achieved according to k-nearest neighbor model, more than 4.5% compared to the traditional single compression method, resulting in significant cost savings for DNA storage in the range of $0.48 to 3 billion/TB. In comparison to the traditional compression method, the multi-file dynamic compression method demonstrates a more significant compression effect when compressing multiple files. Therefore, it can considerably decrease the cost of DNA storage and facilitate the widespread implementation of DNA storage technology.
PubMed: 38922373
DOI: 10.1007/s11517-024-03156-2 -
Eating Disorders Jun 2024Transgender and gender-expansive (TGE) individuals suffer from eating disorders (EDs) at disproportionate rates relative to their gender-conforming counterparts. While...
Transgender and gender-expansive (TGE) individuals suffer from eating disorders (EDs) at disproportionate rates relative to their gender-conforming counterparts. While literature on EDs in TGE populations is growing and evolving, best practice guidelines are scant. A framework for providing gender-affirming care (GAC) in an ED treatment setting was developed by integrating findings from a focused literature review and insights from leading experts. Following synchronous and asynchronous training, the protocol was implemented in a virtual ED treatment setting with a national reach serving patients ages 6-24 years. This paper offers a summary of best practices and approaches for providing GAC in ED treatment settings. The use of GAC practices has the potential to address underlying issues and inequities in treatment delivery and outcomes. We encourage ED treatment providers to consider the adoption/adaptation of GAC best practices to more effectively meet the needs of TGE patients. More research is needed to better understand the influence of individual and collective GAC practices on specific ED treatment outcomes.
PubMed: 38922313
DOI: 10.1080/10640266.2024.2371250 -
Minerva Anestesiologica Jun 2024Children with autism spectrum disorder (ASD) often require multiple interventions receiving general anesthesia during their lifetimes. However, a single negative...
Behavioral training and mirroring techniques to prepare for elective anesthesia in children with autism spectrum disorder: a prospective evaluation of implemented program.
BACKGROUND
Children with autism spectrum disorder (ASD) often require multiple interventions receiving general anesthesia during their lifetimes. However, a single negative experience may trigger and/or aggravate anxiety and subsequent development of unwanted behavior. This monocentric study assessed the compliance with mask induction of children with ASD who followed a preoperative preparation using behavioral training with positive reinforcement technique and use of mirroring technique.
METHODS
Prospective observational study including all children with ASD scheduled for day case treatment receiving general anesthesia, from November 2019 to August 2022. The primary outcome was Induction Compliance Checklist (ICC) score. The secondary outcomes were child's anxiety in the operating room assessed by the modified Yale Anxiety Scale (mYPAS), the comportment of the child in the recovery room, parental satisfaction about perioperative management (0 to 10 numerical scale) and the satisfaction of the caregivers about anesthetic management (0 to 10 numerical scale). Behavioral changes were assessed one month after the procedure when possible.
RESULTS
In total, 43 children from 1 to 17 years old were included. Median ICC score was 3 [1-6]. Induction Compliance was considered as excellent in 18.6% of patients, good in 39.5%, fair in 14.0% and poor in 27.9%. Seven patients (16.3%) needed restraint during induction.
CONCLUSIONS
The use of behavioral and mirroring techniques implemented as a preparation program for children with ASD could facilitate mask induction of anesthesia. Such a preparation achieves good to excellent compliance in almost 60% of patients.
PubMed: 38922283
DOI: 10.23736/S0375-9393.24.18021-2 -
Comparative Analysis of Maize Physico-Chemical Parameters and Mycotoxin Levels in Dual Environments.Toxins Jun 2024Maize ( L.) stands as a vital staple food globally, holding significant nutritional and economic value. However, its susceptibility to mycotoxin contamination under... (Comparative Study)
Comparative Study
Maize ( L.) stands as a vital staple food globally, holding significant nutritional and economic value. However, its susceptibility to mycotoxin contamination under stressful environmental conditions poses a considerable concern. This study aimed to assess the quality and pasting characteristics of maize varieties across two distinct regions and examine the occurrence of mycotoxins influenced by climatic factors. Five maize varieties were cultivated in triplicate in the Golegã and Coruche regions. The nutritional composition (protein, fat, fiber, ash, starch, and lutein), pasting properties, and mycotoxin levels were evaluated. A statistical analysis revealed notable differences in the nutritional profiles of the maize varieties between the two regions, particularly in the protein and lutein content. The peak viscosity ranged from 6430 to 8599 cP and from 4548 to 8178 cP in the maize varieties from the Coruche and Golegã regions, respectively. Additionally, a significant correlation was observed between the climatic conditions and the grain nutritional quality components ( < 0.05). The M variety showed the highest ash content, protein content, final viscosity, and setback viscosity and the lowest peak viscosity. The Y variety revealed the lowest fat, fiber, and lutein content and the maximum peak viscosity. The incidence of mycotoxins was notably higher in the varieties from Coruche, which was potentially attributable to higher temperatures and lower precipitation levels leading to more frequent drought conditions. Fumonisin B1 was detected in 58% of the varieties from Coruche and 33% of the samples from Golegã, while deoxynivalenol was found in 87% and 80% of the varieties from Coruche and Golegã, respectively. The H variety, which was harvested in Coruche, exhibited the highest number of fumonisins and higher amounts of protein, lutein, and fat, while fumonisins were not detected in the Golegã region, which was potentially influenced by the precipitation levels. The K variety revealed higher protein and lutein contents, a lower amount of fat, excellent pasting properties (a higher peak viscosity and holding strength and a lower peak time), and no fumonisins B1 or B2. This variety may be considered well adapted to higher temperatures and drier conditions, as verified in the Coruche region. In conclusion, our study underscored the profound impact of environmental factors on the quality and occurrence of mycotoxins in maize varieties.
Topics: Zea mays; Mycotoxins; Food Contamination; Nutritive Value; Viscosity
PubMed: 38922169
DOI: 10.3390/toxins16060275