•Over 20% of E. coli O157 illnesses and over 5% of Salmonella illnesses are estimated to be attributable to beef consumption in the United States.•Irradiating ground beef is one possible method to ...reduce disease burden.•Simulation modeling suggests that irradiating 50% of the currently unirradiated ground beef supply could avert 3,285 E. coli O157 illnesses and 20,308 Salmonella illnesses.•Additional studies should assess whether targeted irradiation of higher-risk ground beef products could prevent similar numbers of illnesses with less total product irradiated.
Over 20% of E. coli O157 illnesses and over 5% of Salmonella illnesses are estimated to be attributable to beef consumption in the United States. Irradiating ground beef is one possible method to reduce disease burden. We simulated the effect of ground beef irradiation on illnesses, hospitalizations, deaths, and direct healthcare costs from ground beef-associated E. coli O157 and Salmonella illnesses in the United States. To estimate the fraction of illnesses, hospitalizations, deaths, and direct healthcare costs preventable by ground beef irradiation, we multiplied the disease burden attributable to ground beef; the estimated percentage of ground beef sold that is not currently irradiated; the percentage of unirradiated ground beef that would be irradiated; and the percentage reduction in risk of illness after irradiation. We multiplied this fraction by estimates of burden and direct healthcare costs to calculate the numbers or amounts averted. Model inputs were obtained from the literature and expert opinion. We used Monte Carlo simulation to incorporate uncertainty in inputs into model estimates. Simulation outcomes were summarized with means and 95% uncertainty intervals (UI). Irradiating 50% of the currently unirradiated ground beef supply would avert 3,285 (95% UI: 624–9,977) E. coli O157 illnesses, 135 (95% UI: 24–397) hospitalizations, 197 (95% UI: 34–631) hemolytic uremic syndrome cases, 2 (95% UI: 0–16) deaths, and $2,972,656 (95% UI: $254,708–$14,496,916) in direct healthcare costs annually. For Salmonella, irradiation would avert 20,308 (95% UI: 9,858–38,903) illnesses, 400 (95% UI: 158–834) hospitalizations, 6 (95% UI: 0–18) deaths, and $7,318,632 (95% UI: $1,436,141–$26,439,493) in direct healthcare costs. Increasing ground beef irradiation could reduce E. coli O157 and Salmonella burden in the United States. Additional studies should assess whether targeted irradiation of higher-risk ground beef products could prevent similar numbers of illnesses with less total product irradiated.
Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are neurodevelopmental and neurodegenerative disorders respectively, with devastating effects not only on the individual but also the ...society. Collectively, a number of factors contribute to the expression of ASD and AD. It is of utmost curiosity that these disorders express at different stages of life and there is an involvement of certain susceptible genes. This genetic basis makes the background of common associations like memory deficits, cognition changes, demyelination, oxidative stress and inflammation, an integral part of both disorders. Modern technology resulting in genetically modified crops and increase in gadgets emitting electromagnetic frequencies have resulted in enhanced risks for neurological dysfunctions and disorders like ASD and AD. Subsequent advances in the psychological, pharmacological, biochemical and nutritional aspects of the disorders have resulted in the development of newer therapeutic approaches. The common clinical features like language impairment, executive functions, and motor problems have been discussed along with the patho-physiological changes, role of DNA methylation, myelin development, and heavy metals in the expression of these disorders. Psychopharmacological and nutritional approaches towards the reduction and management of risk factors have gained attention from the researchers in recent years. Current major therapies either target the inflammatory pathways or reduce cellular oxidative stress. This contribution focuses on the commonalities of the two disorders.
Background
Up to 80% of breast cancers (BCa) are estrogen receptor positive and current treatments target the estrogen receptor (endocrine therapies) and/or CDK4/6 (CDK4/6 inhibitors).
CCND1
encodes ...the protein cyclin D1, responsible for regulation of G1 to S phase transition in the cell cycle.
CCND1
amplification is common in BCa and contributes to increased cyclin D1 expression. As there are signalling interactions between cyclin D1 and the estrogen receptor, understanding the impact of
CCND1
amplification on estrogen receptor positive patients’ disease outcomes, is vital. This review aims to evaluate
CCND1
amplification as a prognostic and predictive biomarker in BCa.
Materials and Methods
Publications were retrieved from the databases: PubMed, MEDLINE, Embase and Cochrane library. Exclusion criteria were duplication, publication type, non-English language,
in vitro
and animal studies, not BCa, male BCa, premenopausal BCa, cohort size <35,
CCND1
amplification not reported. Publications with cohort duplication, and inadequate recurrence free survival (RFS) and overall survival (OS) data, were also excluded. Included publications were assessed for Risk of Bias (RoB) using the Quality In Prognosis Studies tool. Statistical analyses (Inverse Variance and Mantel-Haenszel) were performed in Review Manager. The PROSPERO registration number is CRD42020208179.
Results
CCND1
amplification was significantly associated with positive estrogen receptor status (OR:1.70, 95% CI:1.19-2.43, p = 0.004) and cyclin D1 overexpression (OR: 5.64, 95% CI: 2.32-13.74, p=0.0001).
CCND1
amplification was significantly associated with shorter RFS (OR: 1.64, 95% CI: 1.13-2.38, p = 0.009), and OS (OR: 1.51, 95% CI: 1.19-1.92, p = 0.0008) after removal of studies with a high RoB. In endocrine therapy treated patients specifically,
CCND1
amplification predicted shorter RFS (HR: 2.59, 95% CI: 1.96-3.41, p < 0.00001) and OS (HR: 1.59, 95% CI: 1.00-2.49, p = 0.05) also after removal of studies with a high RoB.
Conclusion
While a lack of standardised approach for the detection of
CCND1
amplification is to be considered as a limitation,
CCND1
amplification was found to be prognostic of shorter RFS and OS in BCa.
CCND1
amplification is also predictive of reduced RFS and OS in endocrine therapy treated patients specifically. With standardised methods and cut offs for the detection of
CCND1
amplification,
CCND1
amplification would have potential as a predictive biomarker in breast cancer patients.
Systematic Review Registration
https://www.crd.york.ac.uk/prospero/
, identifier CRD42020208179.
Sickle cell disease is characterized by clinical complications resulting in vaso-occlusive crisis with prominent attributes of oxidative stress, inflammation, and pain. Inflammation is an integral ...part of this disease which further exacerbates the pain during a crisis. Omega-3 fatty acids are known to possess anti-inflammatory and anti-aggregatory properties and assist in diminishing the slow physiological inactivation.
A pilot nutritional interventional study was conducted wherein forty-three children with sickle cell disease aged 5-16 years were supplemented with omega-3 fatty acids for a period of six months. Analysis of oxidative stress, as well as inflammatory parameters, was done pre and post-supplementation.
Increased free oxygen radical transference values depicting free radical generation is enhanced in these patients along with a reduced antioxidant defense, as seen by decreased free oxygen radical defense values. Supplementation with omega-3 fatty acids for a period of six months significantly reduced the inflammatory marker homocysteine in all patients, whereas high sensitive C reactive protein was significantly reduced only in females of the age group 11-16years. Simultaneously a significant reduction in oxidative stress parameters with a concomitant increase of antioxidant defense was observed in all patients.
The authors’ findings suggest the regulatory effects of omega-3 fatty acids as cellular activators in alleviating the complications due to sickle cell disease. Omega-3 fatty acids hold promise as future therapeutic candidates in patients with sickle cell disease.
Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty ...liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. Majorly the thromboxanes, prostaglandins, leukotrienes, lipoxins, and so forth form the group of lipid mediators influencing inflammation. Of special mention are the omega-6 and omega-3 fatty acids that regulate inflammatory mediators of interest in hepatocytes and adipocytes via the cyclooxygenase and lipoxygenase pathways. They also exhibit profound effects on eicosanoid production. The inflammatory cyclooxygenase pathway arising from arachidonic acid is a critical step in the progression of inflammatory responses. New oxygenated products of omega-3 metabolism, namely, resolvins and protectins, behave as endogenous mediators exhibiting powerful anti-inflammatory and immune-regulatory actions via the peroxisome proliferator-activated receptors (PPARs) and G protein coupled receptors (GPCRs). In this review we attempt to discuss the complex pathways and links between obesity and inflammation particularly in relation to different lipid mediators.
Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vβ21.3+ T-cell subgroup. Here we apply muti-single cell ...omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children. Here we show that in Multi-Inflammatory Syndrome in Children (MIS-C), the natural killer cell and monocyte population demonstrate heightened CD95 (Fas) and Interleuking 18 receptor expression. Additionally, TCR Vβ21.3+ CD4+ T-cells exhibit skewed differentiation towards T helper 1, 17 and regulatory T cells, with increased expression of the co-stimulation receptors ICOS, CD28 and interleukin 18 receptor. We observe no functional evidence for NLRP3 inflammasome pathway overactivation, though MIS-C monocytes show elevated active caspase 8. This, coupled with raised IL18 mRNA expression in CD16- NK cells on single cell RNA sequencing analysis, suggests interleukin 18 and CD95 signalling may trigger activation of TCR Vβ21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.
Inflammation plays an integral role in the complications of sickle cell disease (SCD), which can lead to vaso-occlusive crisis and extreme pain. SCD is accompanied by numerous complications, ...including cardiovascular disease, cognitive decline and endothelial dysfunction, contributing to mortality. As disease severity increases with age, the present study aimed to assess if age is also correlated with a definite pattern of progression of the two inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and total homocysteine (tHCY). The findings of the present study could lead to an improved understanding of the threshold levels of these inflammatory markers and timely interventions to delay complications. In an observational study, levels of hsCRP and tHCY were analyzed in 70 patients (35 male and 35 female patients) with SCD aged between 5 and 16 years. hsCRP levels were in the high-risk range in 64.29% (n=45) of all male and female patients. A sex-wise distribution showed that, of the 35 male patients, 74.28% (n=26) were in the high-risk range, and of the 35 female patients, 54.28% (n=19) were in the high-risk range. An age-wise distribution showed that of the 41 patients in the 5-10-years age group, 70.73% (n=29), were in the high-risk range. In comparison, of the 29 patients in the 11-16-years age group, 55.17% (n=16) were in the high-risk range. tHCY levels were observed to be in the normal range in 98.57% (n=69) of all children, as compared with 1.43% (n=1) in the high-risk range. Furthermore, a sex-wise distribution showed that female patients in the high-risk group of hsCRP had higher concentrations of tHCY as compared with the male patients in that risk group. An age-wise distribution of hsCRP concentration also showed that the risk of CVD in patients in the 11-16-years age group was higher with increased concentrations of tHCY. A weak negative correlation was observed between age and hsCRP concentrations (r-value=-0.280; P=0.026) and a weak positive correlation was detected between tHCY and age (r-value=0.259; P=0.036). In conclusion, the results of the present study indicated that higher levels of hsCRP could be a useful marker in children with SCD, and levels of tHCY may be an adjunct marker as the disease progresses with age.
This paper introduces Matrix-Valued Neural Coordinated Federated Deep Extreme Machine Learning, a novel approach for enhancing health prediction and intrusion detection on the Internet of Healthcare ...Things (IoHT). By leveraging Machine Learning (ML), blockchain, and Intrusion Detection Systems (IDS), this technique ensures the security of medical data while enabling predictive health analytics. The IoHT, characterized by its vast network of interconnected devices, poses significant challenges in security and confidentiality. However, the integration of proposed technique empowers healthcare systems to proactively address these concerns while enhancing patient outcomes and reducing healthcare costs. Smart healthcare, enabled by ML and blockchain, is revolutionizing healthcare 5.0. Healthcare systems may employ IoHTs' intelligent and interactive characteristics using proposed approach. Despite its benefits, medical data aggregation poses security, ownership, and regulatory compliance challenges. Federated Learning (FL) is a key technique for distributed learning that protects data. The proposed architecture has several unique benefits like 1) it provides a thorough examination of the incorporation of blockchain technology with FL for healthcare 5.0; 2) it takes the lead in creating a robust healthcare monitoring system that utilizes blockchain technology and IDS to identify and prevent harmful actions; 3) the development of crucial blockchain elements by means of mutual neuronal synchronization of Artificial Neural Networks (ANNs) showcases pioneering progress in safeguarding medical data; and 4) the framework underwent a thorough empirical assessment and outperformed existing methods in accurately predicting intrusion detection and disease prediction, achieving an impressive efficiency rate of 97.75% and 98% respectively. This development represents a major step forward in improving security and predictive abilities within the IoHT ecosystem, offering the potential for revolutionary advancements in healthcare delivery and patient care.
Health consciousness has increased the desire of people around the world to consume functional foods. Omega-3 essential fatty acids are one among these beneficial and important health supplements ...without which a general predisposition to degenerative and stress related disorders can occur. Saudi Arabia has shown an alarming increase in obesity (Al-Nozha et al., 2005), diabetes (Alqurashi et al., 2011), and cardiovascular disease (Al-Nozha et al., 2004) in the last few decades mainly due to nutritional transitions and lifestyle alterations (Amuna and Zotor, 2008). Lack of nutrient dense foods and the prevailing food related disorder of obesity (Popkin, 2001; Prentice, 2014) especially render egg as a choice food to be value-added for attaining nutritional security in Saudi Arabia and in effect reverse the increasing incidences of lifestyle diseases. Nutritional intervention through a commonly consumed food product would be an important step in improving the health of the people, and reducing health care costs. As eggs are a frequently consumed food item in Saudi Arabia, enriching them with omega-3 fatty acids would be an excellent way to alleviate the existing problems. A significant deposition of omega-3 fatty acids in the eggs was observed when the diet of hens was supplemented with omega-3 fatty acids from either flaxseed or fish oil source. Inadequacy of omega-3 fatty acids could thus be rectified by producing omega-3 enriched eggs from hens supplemented with flaxseed or fish oil source, and thus contribute toward better health choice of the consumer.
The aim of this study is to investigate the heat and mass transfer characteristics of Burgers nanofluid in the presence of thermo-diffusion effects. The analysis considers higher-order slip effects ...to study the transport phenomena. Additionally, the study examines the impact of thermal radiation and chemical reactions on the flow. Variable thermal conductivity assumptions are made for heat transfer analysis. The Cattaneo–Christov model, an extension of Fourier heat and mass theories, is employed for the analysis. Heat transfer evaluation is conducted using convective thermal constraints, and numerical computations are carried out using the Runge–Kutta method. The study visually represents the impact of flow parameters through graphical analysis. It is suggested that heat transfer can be significantly improved through the interaction of slip effects, and the concentration phenomenon is enhanced by the Soret number.
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