Expression and sub-cellular localization of the CCAAT/enhancer binding protein alpha in relation to postnatal development and malignancy of the prostate

BACKGROUND: C/EBPalpha is a critical mediator of terminal differentiation and a tumor suppressor through its strong antiproliferative actions on cell cycle regulatory proteins. C/EBPalpha also appears to regulate androgen receptor (AR) AR signaling. There, is a paucity of information on the expression and sub-cellular localization of C/EBPalpha in normal mouse and human prostate and in prostate cancer. METHODS: Immunohistochemistry of tissues including tissue arrays, quantitative polymerase chain reaction and mRNA expression database mining. RESULTS: In the mouse prostate epithelium, C/EBPalpha was present at 1 week postnatal localized in the cytosol, began to show nuclear localization at 8 weeks and continued to show prominent nuclear expression at 10 weeks and beyond; C/EBPalpha mRNA was expressed at all ages. In humans, C/EBPalpha showed prominent nuclear localization from peripubescence up to middle age but was sequestered in the cytosol in older individuals; the mRNA level for C/EBPalpha remained essentially unchanged. Most prostate adenocarcinomas expressed a range of levels of C/EBPalpha mRNA and protein that were relatively high in metastatic tumors in a manner that correlated with AR expression; however, most cells showed C/EBPalpha sequestered in the cytosol. CONCLUSIONS: Temporal changes in sub-cellular localization of C/EBPalpha are consistent with a role in prostate differentiation and as a prostate tumor suppressor; the cytoplasmic sequestration of C/EBPalpha, unique to older human prostates, is arguably a permissive condition for the greater frequency of proliferative disorders of the prostate. In malignant prostate C/EBPalpha may be available to regulate AR signaling through transient changes in its sub-cellular localization.     

Frequency of electrode migration after cochlear implantation in the early postoperative period. What are associated risk factors?

Objectives

To estimate the prevalence of, and risk factors associated with electrode migration (EM) in cochlear implant (CI) recipients.

Design

Historical cohort study of all CIs performed between 1 January 2018 and 1 August 2021 in a single tertiary adult and paediatric CI centre in the UK.

Main Outcome Measures

The primary aim is to determine the prevalence of electrode migration, comparing intraoperative surgeon report and examination of a routine plain radiograph performed 2 weeks after surgery. EM is defined as the detection of movement of two or more electrodes out of the cochlea from the time of surgery. Multivariate analysis was performed to investigate preoperative and intraoperative risk factors that might predispose to migration.

Results

Four hundred and sixty-five patients, having 516 distinct surgeries, with 628 implants were analysed. EM occurred following 11.5% of implant operations. Pre-existing cochlear abnormality was an independent associated risk factor for EM (OR: 3.40 ⟨1.20–9.62⟩ p = .021). Demographics, surgical technique, usage of a precurved electrode, CSF leak, surgeon seniority and intraoperative telemetry did not influence risk of migration. There were 5 implants (0.8%) which migrated later than 2 weeks, with a median date of imaging diagnosis (x-ray or CT scan) of 263 days ⟨IQR:198⟩, for which head injury was a common precipitating factor. There were differences in the risk of migration between different lateral wall electrodes.

Conclusion

EM in the early postoperative period is a common occurrence and is more likely in implant recipients with obstructed or malformed cochleae.     

Individual,household, and community level risk factors of stunting in children younger than 5 years: Findings from a national surveillance system in Nepal

Despite substantial reductions in recent years in Nepal, stunting prevalence in children younger than 5 years remains high and represents a leading public health concern. To identify factors contributing to the stunting burden, we report multilevel risk factors associated with stunting in 4,853 children aged 6–59 months in a nationally and agroecologically representative random sample from the first year of the Policy and Science for Health, Agriculture, and Nutrition Community Studies, a community‐based observational, mixed‐panel study. Mixed effects logistic regressions controlling for multilevel clustering in the study design were used to examine the association of individual‐, household‐, and community‐level factors associated with stunting. Stunting prevalence was 38% in our sample. After adjustment for potential confounding variables, maternal factors, including maternal height and education, were generally the strongest individual‐level risk factors for stunting, adjusted odds ratio (AOR) = 2.52, 95% CI [1.96, 3.25], short (<145 cm) versus not short mothers; AOR = 2.09, 95% CI [1.48, 2.96], uneducated mothers versus secondary school graduates. Among the household‐ and community‐level factors, household expenditure and community infrastructure (presence of paved roads, markets, or hospitals) were strongly, inversely associated with increased stunting risk, AOR = 1.68, 95% CI [1.27, 2.24], lowest versus highest household expenditure quintile; AOR = 2.38, 95% CI [1.36, 4.14], less developed (lacking paved roads, markets, or hospitals) versus more developed communities. Although most factors associated with stunting are not rapidly modifiable, areas for future research and possible interventions emerged.     

Impact of Dietary Trajectories on Obesity and Dental Caries in Preschool Children: Findings from the Healthy Smiles Healthy Kids Study

This study examines the impact of longitudinal dietary trajectories on obesity and early childhood caries (ECC) in preschool children in Australia. Mother–infant dyads from the Healthy Smiles Healthy Kids study were interviewed at 4 and 8 months, and 1, 2, and 3 years of age. Children underwent anthropometric and oral health assessments between 3 and 4 years of age. Multivariable logistic regression and negative binomial regression analysis were performed for the prevalence of overweight and obesity, and the number of tooth surfaces with dental caries, respectively. The intake of core, discretionary, and sugary foods showed distinct quadratic (n = 3) trajectories with age. The prevalence of overweight or obesity was 10% (n = 72) and that of early childhood caries (ECC) was 33% (mean decayed, missing, and filled tooth surfaces (dmfs) score: 1.96). Children with the highest trajectories of discretionary foods intake were more likely to be overweight or obese (adjusted OR: 2.51, 95 %CI: 1.16–5.42). Continued breastfeeding beyond 12 months was associated with higher dmfs scores (adjusted IRR: 2.17, 95 %CI: 1.27–3.73). Highest socioeconomic disadvantage was the most significant determinant for overweight or obesity (adjusted OR: 2.86, 95 %CI: 1.11–7.34) and ECC (adjusted IRR: 2.71, 95 %CI: 1.48–4.97). Targeted health promotion interventions should be designed to prevent the incidence of two highly prevalent conditions in preschool children.