The p53 protein is a central tumour suppressor regulating numerous genes involved in cell cycle control, DNA repair, and apoptosis. Mutations in p53 occur in over half of all cancers, disrupting these regulatory pathways and enhancing tumour progression. Many cell lines, including MCF-7 breast cancer cells, exhibit oscillatory p53 and MDM2 activity, a phenomenon linked to radiosensitivity and the cellular response to ionizing radiation.

We investigated the dose-dependent dynamics of p53 activation in MCF-7 cells exposed to γ-radiation in the dose range of 0.1 to 8 Gy. Using western blot analysis and real-time quantitative PCR, we examined dynamics of the expression of p53 and its downstream targets, including CDKN1A, GADD45A, and MDM2 genes. Our findings reveal that while oscillations in p53 and its downstream targets are prominent at high radiation doses, transient peak expression persists even at doses as low as 0.1 Gy, though with delayed onset and diminished amplitude.

The results extend the knowledge on p53 dynamics down to 0.1 Gy. They challenge the previous models that predicted the absence of oscillations at low radiation doses.

CSN3 (κ-casein) is essential for casein micelle formation and cellular differentiation, and dysregulated CSN3 has been linked to tumorigenesis. However, its role in colorectal cancer (CRC) remains unclear.

CSN3 expression in CRC was evaluated using GEO and TCGA datasets, immunohistochemistry, and qRT-PCR. Its biological functions were investigated using gain- and loss-of-function approaches combined with CCK-8, apoptosis, wound-healing, and Transwell assays. Transcriptomic analysis of the GEO dataset GSE21510 was used to identify CSN3-associated signaling pathways, which were further investigated by western blotting, RT-qPCR, co-immunoprecipitation (Co-IP), AKT inhibition, and CSN1S1 knockdown rescue experiments. CSN3 was significantly upregulated in CRC tissues and was associated with lymph node metastasis, advanced TNM stage, and poor prognosis. Functionally, CSN3 overexpression promoted CRC cell proliferation, migration, and invasion while suppressing apoptosis, whereas CSN3 knockdown produced the opposite effects. CSN3 also promoted epithelial-mesenchymal transition (EMT). Mechanistically, enrichment analysis and western blotting demonstrated that CSN3 activated the PI3K/AKT/mTOR signaling pathway, accompanied by increased phosphorylation of PI3K, AKT, mTOR, p70S6K, and 4EBP1. MK-2206 attenuated CSN3-induced proliferation, migration, invasion, and EMT, partially restored apoptosis, and reduced AKT phosphorylation. STRING and Co-IP supported an association between CSN3 and CSN1S1. CSN1S1 knockdown attenuated CSN3-induced proliferation, migration, invasion, EMT, and AKT activation.

CSN3 promotes malignant CRC cell phenotypes partly through AKT signaling, with CSN1S1 contributing to CSN3-mediated AKT activation and tumor-promoting effects, suggesting potential prognostic relevance in CRC.

The impact of breast cancer and its treatments on musculoskeletal health is a critical aspect of survivorship care. This article highlights common complications such as pain, weakness, reduced mobility, and decreased bone health, which can significantly affect quality of life. The article provides an overview of evidence-based strategies for prevention, assessment, and management of these issues. By addressing musculoskeletal health proactively, clinicians can support improved function and long-term outcomes for patients with breast cancer.

Central nervous system cancer, encompassing both primary and metastatic brain and spinal cord lesions, presents unique rehabilitation challenges due to their inherent characteristics, presentation, and cancer treatments. Rehabilitation impairments in this population necessitate an interdisciplinary rehabilitation approach focused on quality of life and functional independence. This article provides an overview of the epidemiology, treatments, and associated sequelae of primary and metastatic brain and spine tumors. Rehabilitation clinicians should be familiar with current treatments, unique challenges, and expectations throughout the rehabilitation continuum.

Older refugees, exposed to a cluster of biological and social vulnerabilities, are more susceptible to infectious disease outbreaks and their complications. This study developed a predictive model estimating self-reported COVID-19 infection risk among older Syrian refugees in Lebanon using social determinants of health. Additionally, it described the barriers to diagnostic testing among those who reported having had COVID-19 infection at least once.

This prediction modeling analysis uses data from a longitudinal study conducted between September 2020 and March 2022. Syrian refugees aged 50 years or older living in households that received assistance from a humanitarian organization were interviewed by phone. Self-reported occurrence at least one COVID-19 infection was the outcome of interest. The predictors were identified using adaptive lasso regression. The apparent model performance and discrimination were presented using the calibration slope and the Area Under the Curve (AUC).

Of 2,886 participants (median [IQR] age: 56 [52 -62]; 52.9% males), 283 individuals (9.8%) reported a COVID-19 infection at least once. Six predictors of at least one COVID-19 infection were identified: living outside informal tented settlements, having elementary and preparatory education or above, having chronic conditions, not receiving cash assistance, being water insecure and having unmet waste management needs. The apparent model had modest discrimination (AUC = 0.621 [95%CI: 0.587 to 0.655]) and good calibration (c-Slope = 1.004 [95%CI: 0.704 to 1.304]). Nearly half of the cases were diagnosed through testing. The main reasons for not testing were perception that the tests were unnecessary (n = 91 [63.6%]) or inability to afford them (n = 46 [32.2%]).

The identified predictors provide insight into characteristics associated with higher predicted risk of COVID-19 infection among Syrian refugees. However, given the model's modest predictive performance and reliance on lasso tuning, further validation and refinement in other populations and settings are needed before implementation. Awareness campaigns, screening measures, and cash assistance may be associated with reduced risk of infection in future pandemics.

Disease now-casting increasingly relies on non-traditional data, such as online activity, which offer fast, inexpensive insights but are often noisy, unstructured, and influenced by behavioral confounders. Models using search engine data have frequently suffered from overfitting and unstable performance. However, pandemics may help distinguish true disease signals from behavioral noise, as both tend to surge during outbreaks. We propose a hybrid approach to improve prediction that combines model evaluation with behavioral insight. We apply simple supervised and unsupervised methods to different flu and COVID-19 datasets, using the 2009 H1N1 and 2020 COVID-19 pandemics as training periods. In both cases, selecting a curated subset of search terms improved model performance, reduced overfitting, and increased stability, consistently outperforming models that used search terms indiscriminately. These results suggest that feature curation informed by behavioral insights can enhance now-casting beyond purely statistical approaches. Our method offers a scalable and adaptable framework for integrating digital epidemiology into public health surveillance.

The COVID-19 pandemic posed significant challenges, including rehospitalization of patients due to SARS-CoV-2 reinfection, particularly in the context of variants of concern and Brazil's COVID-19 vaccination campaign. This study aimed to estimate the rate of rehospitalizations due to reinfection in the municipality of Rio de Janeiro (2020-2022), assess the impact of individual vaccination status, and identify factors associated with this outcome. Cohort study including individuals aged 18 years or older who were hospitalized with Severe Acute Respiratory Illness (SARI) resulting from SARS-CoV-2 infection in Rio de Janeiro. Data from four administrative databases (SIPNI, e-SUS Notifica, SIVEP-Gripe, and SIM) were integrated through record linkage. Rehospitalizations due to reinfection were defined as those occurring ≥90 days after the initial hospitalization. Annual rehospitalization rates were calculated per 100 person-years. The analysis included demographics, hospital discharge disposition, and vaccination-related variables. Cox proportional hazards models with deaths considered as competing risks were used. Of the 59,001 individuals included, 1,957 (3.3%) experienced rehospitalization. The main finding was that a complete vaccination regimen with a booster (≥3 doses) was associated with a 39% reduction in the risk of rehospitalization (sHR: 0.61; 95% CI: 0.52-0.73), while older age, multimorbidity, and Black race/skin color emerged as significant risk factors. Full vaccination with booster doses offered protection against COVID-19-related rehospitalization; however, racial inequities, advanced age, and comorbidities remain important risk factors. Public health policies that expand periodic booster vaccination, strengthen health education, and address social vulnerabilities are urgently needed as a fundamental strategy for preventing future pandemics.

Transient tachypnea of the newborn (TTN) commonly affects near- and full-term infants and often requires respiratory support. The use of nebulized salbutamol to improve respiratory outcomes has been of interest, though its clinical efficacy remains controversial. This systematic review and meta-analysis aimed to evaluate whether nebulized salbutamol improves clinical outcomes in affected infants. We searched PubMed, Scopus, Embase, and the Cochrane Library for randomized controlled trials (RCTs) evaluating the efficacy of nebulized salbutamol in infants with TTN. We used a random-effects model to calculate mean differences (MDs) with 95% confidence intervals (CIs). Twenty-five studies were included in the systematic review, comprising seventeen RCTs for meta-analysis involving 1,317 infants. The analysis showed that salbutamol significantly decreased the duration of respiratory support (MD: -14.85 hours; 95% CI [-25.05, -4.65]; p = 0.004), duration of continuous positive airway pressure (MD: -18.19 hours; 95% CI [-30.03, -6.35]; p = 0.003), duration of oxygen requirement (MD: -24.57 hours; 95% CI [-35.03, -14.10]; p < 0.001), and length of hospitalization (MD: -1.17 days; 95% CI [-1.69, -0.65]; p < 0.001). However, there was no significant decrease in duration of tachypnea (MD: -9.93 hours; 95% CI [-25.42, 5.56]; p = 0.21) or duration of neonatal intensive care unit stay (MD: -0.84 days; 95% CI [-2.62, 0.94]; p = 0.36). Subgroup analysis for respiratory support duration showed no significant effect in infants with clinical score of TTN < 5 (MD: -10.88 hours; 95% CI [-24.48, 2.73]; p = 0.12), while the certainty of evidence for all outcomes was low to very low. Nebulized salbutamol may improve clinical outcomes relevant to the evolution of the disease in TTN infants, with potential benefits in certain subgroups such as those with greater disease severity, though the available evidence is of low to very low certainty. Therefore, our confidence in its efficacy in treating TTN remains limited.

Smoking cessation is the most effective intervention for modifying the clinical course of chronic obstructive pulmonary disease (COPD), yet many patients continue to smoke after diagnosis. We evaluated the characteristics associated with cessation at one year among smokers with COPD in a multicentre randomised cessation trial.

This prespecified subgroup analysis included patients with COPD randomised to immediate referral to a smoking cessation clinic or to usual care. Smoking status one year later was determined through a structured telephone interview, and patients who had quit were contacted and their cessation was verified by exhaled carbon monoxide measurement; 48 of the 220 patients (21.8%) were lost to follow-up, leaving 172 patients for analysis. A prespecified six-variable logistic regression model was fitted; Firth penalised regression and an analysis classifying patients lost to follow-up as continuing smokers were prespecified sensitivity analyses.

Of 172 patients, 32 (18.6%) had quit at one year: 24 of 93 (25.8%) allocated to immediate referral versus 8 of 79 (10.1%) allocated to usual care (p = 0.010). Quitters were older and had a lower baseline FEV1 in unadjusted comparisons. In the multivariable model, usual care was associated with lower odds of cessation (OR, 0.25; 95% CI, 0.09-0.64), whereas absence of comorbidity (OR, 2.64; 95% CI, 1.06-6.60) and more than 1 exacerbation-related hospitalisation (OR, 9.32; 95% CI, 1.97-44.06) were associated with higher odds; the latter estimate rests on 10 patients and is imprecise. Baseline FEV1 and Fagerström score were not independently associated with cessation.

Immediate referral to a cessation clinic was the factor most strongly associated with one-year abstinence, together with absence of comorbidity and, tentatively, repeated hospitalisation; greater disease severity was associated with quitting only in unadjusted comparisons. These exploratory findings support structured cessation pathways in routine COPD care.

This review article prepares emergency physicians to recognize and manage critical illness in postpartum patients, a population at heightened risk of preventable morbidity and mortality in North America amid persistent racial/geographic disparities and shrinking obstetric access. It highlights key physiologic changes after delivery that complicate patient management. The article focuses on 3 immediate postpartum emergencies (postpartum hemorrhage, postpartum preeclampsia, and amniotic fluid embolism) and 3 subacute (pulmonary embolism, peripartum cardiomyopathy, and spontaneous coronary artery dissection). It concludes with system-level strategies to improve safety and outcomes.