BMC Medicine最新文献

Background: The effect of milk on the risk of ischemic heart disease (IHD) and acute myocardial infarction (MI) is unclear. We aimed to examine the association between non-fermented and fermented milk consumption on these endpoints and investigate the relationship between milk intake and cardiometabolic-related proteins in plasma.

Methods: Our study is based on two Swedish prospective cohort studies that included 59,998 women and 40,777 men without IHD or cancer at baseline who provided repeated measures of diet and lifestyle factors and plasma proteomics data in two subcohorts. Through registry linkage, 17,896 cases with IHD were documented during up to 33 years of follow-up, including 10,714 with MI. We used time-updated multivariable Cox regression analysis to examine non-fermented or fermented milk intake with time to IHD or MI. Using high-throughput multiplex immunoassays, 276 cardiometabolic plasma proteins were measured in two subcohorts. We applied multivariable-adjusted regression models using a discovery-replication design to examine protein associations with increasing consumption of non-fermented or fermented milk.

Results: The results for non-fermented milk differed by sex (p-value for interaction = 0.01). In women, we found a pattern of successively greater risk of IHD and MI at non-fermented milk intake levels higher than 1.5 glasses/day. Compared with an intake of 0.5 glass/day (100 mL/day), non-fermented milk intake of 2 glasses/day in women conferred a multivariable-adjusted hazard ratio (HR) of 1.05 (95% CI 1.01-1.08) for IHD, an intake of 3 glasses/day an HR of 1.12 (95% CI 1.06-1.19), and an intake of 4 glasses/day an HR of 1.21 (95% CI 1.10-1.32). Findings were similar for whole, medium-fat, and low-fat milk. We did not detect higher risks of IHD with increasing milk intakes in men. Fermented milk intake was unrelated to the risk of IHD or MI in either sex. Increasing non-fermented milk intake in women was robustly associated with a higher concentration of plasma ACE2 and a lower concentration of FGF21.

Conclusions: We show a positive association between high amounts of non-fermented milk intake and IHD in women but not men. We suggest metabolic pathways related to ACE2 and FGF21 potentially underlie the association.

Despite the common belief that human papillomavirus (HPV) primarily affects women, it is imperative to recognize and address the impact of HPV on boys and men. Overlooking the health implications for males is a notable gap, as efforts have predominantly focused on preventing HPV-related infections in women. This commentary aims to emphasize the importance of HPV awareness and vaccination for boys and men by highlighting the prevalence and consequences of HPV infection, elaborating on the associated health risks, elucidating the benefits of vaccination, and urging readers to recognize the necessity of protecting males from HPV. In addition, the increase in HPV-related cancers in men underscores the urgent need for increased awareness and vaccination. Although specific testing for HPV in men is not available, the inclusion of men and boys in gender-neutral vaccination programs can help reduce the harmful effects of this virus in both genders.

Background: Global food systems are essential to sustain life; however, unhealthy diets are the leading cause of poor health and death worldwide. Natural food environments are a critical source of healthful food such as fresh fruit and vegetables, lean meat and aquatic foods, particularly in low- and middle-income countries (LMICs) and Indigenous food systems. Understanding and monitoring natural food environments is critical to protecting the supply of healthy food, and the land and water it comes from, for current and future generations.

Methods: A scoping review was applied to classify and summarise empirical methods and measures used for characterising natural food environments. The ways in which food environment characteristics are conceptualised and measured for natural (wild and cultivated) food environments were explored. Data were extracted from the included studies using the following fields: study country, aim/objective(s), type of natural food environment (wild vs. cultivated), method or measure used to measure the food environment, key food environment characteristic/s (up to four) measured and key findings in relation to the food environment measurement.

Results: One hundred forty seven studies were found to be relevant in this review. Most studies investigated food environments in LMICs, with almost two-thirds of all studies focussing on middle-income countries (n = 89, 61%). There was a strong focus on food security and home-based agriculture from studies that measured the cultivated food environment in LMICs, while the majority of studies on the cultivated food environment from high-income countries focussed on urban and community gardening. In addition to the most common survey-based methodological approaches, our review yielded a broad range of both qualitative and quantitative methods for measuring natural food environments, such as geospatial analysis; biochemical analysis of food, soil and water; citizen science; photovoice and food availability calendars.

Conclusions: Our review demonstrated that the concept and characteristics of the food environment are a promising conceptualization for measuring natural food environments, particularly in relation to food availability, healthiness and food security. Mapping the currently used methods and measures to assess natural food environments is important to help identify critical leverage points for strengthening policy interventions, and monitoring and evaluation of progress.

Background: Zaire Ebolavirus disease (EVD) outbreaks can be controlled using rVSV-ZEBOV vaccination and other public health measures. People in high-risk areas may have pre-existing antibodies from asymptomatic Ebolavirus exposure that might affect response to rVSV-ZEBOV. Therefore, we assessed the impact pre-existing immunity had on post-vaccination IgG titre, virus neutralisation, and reactogenicity following vaccination.

Methods: In this prospective cohort study, 2115 consenting close contacts ("proches") of EVD survivors were recruited. Proches were vaccinated with rVSV-ZEBOV and followed up for 28 days for safety and immunogenicity. Anti-GP IgG titre at baseline and day 28 was assessed by ELISA. Samples from a representative subset were evaluated using live virus neutralisation.

Results: Ten percent were seropositive at baseline. At day 28, IgG in baseline seronegative (GMT 0.106 IU/ml, 95% CI: 0.100 to 0.113) and seropositive (GMT 0.237 IU/ml, 0.210 to 0.267) participants significantly increased from baseline (both p < 0.0001). There was strong correlation between antibody titres and virus neutralisation in day 28 samples (Spearman's rho 0.75). Vaccinees with baseline IgG antibodies against Zaire Ebolavirus had similar safety profiles to those without detectable antibodies (63.6% vs 66.1% adults experienced any adverse event; 49.1% vs 60.9% in children), with almost all adverse events graded as mild. No serious adverse events were attributed to vaccination. No EVD survivors tested positive for Ebolavirus by RT-PCR.

Conclusions: These data add further evidence of rVSV-ZEBOV safety and immunogenicity, including in people with pre-existing antibodies from suspected natural ZEBOV infection whose state does not blunt rVSV-ZEBOV immune response. Pre-vaccination serological screening is not required.

Background: Hepatitis B virus (HBV) is an enveloped DNA virus that causes chronic hepatitis B (CHB) infection. Annexin, a Ca²⁺-activated protein, is widely expressed in various organs and tissues and has potential utility in disease diagnosis and treatment. However, the relationship between the annexin family and CHB remains unclear.

Methods: Clinical samples from hepatitis patients and donors or healthy individuals were collected. Transcriptome sequencing in CHB liver tissues and HBV-infected cells were performed. HepG2.2.15 cells with the full-length HBV genome and HBV-infected HepG2-NTCP cell models were established. HBV-infected mouse model was constructed and adeno-associated virus was utilized.

Results: ANXA4 expression was elevated during CHB infection. ANXA4 knockdown promoted HBV replication and aggravated liver injury, while ANXA4 overexpression alleviated that. Mechanistically, autophagy pathway was activated by ANXA4 deficiency, promoting autophagic degradation of minichromosome maintenance complex component 2 (MCM2). MCM2 inhibition activated HBV replication, while MCM2 overexpression attenuated ANXA4 deficiency-induced HBV replication and liver injury. Clinically, the expression of hepatitis B viral protein was negatively correlated with the ANXA4 levels, and CHB patients with high ANXA4 levels (> 8 ng/ml) showed higher sensitivity to interferon therapy.

Conclusions: ANXA4 functions as a protective factor during HBV infection. ANXA4 expression is elevated under HBV attack to restrict HBV replication by inhibiting autophagic degradation of MCM2, thereby alleviating liver injury and suppressing the CHB infection process. ANXA4 also enhances the sensitivity of CHB patients to interferon therapy. Therefore, ANXA4 is expected to be a new target for CHB treatment and prognostic evaluation.

Background: Postoperative radiotherapy (PORT) is crucial for patients with thoracic locally advanced esophageal squamous cell carcinoma (LA-ESCC, pT3-4aN0-3M0) following esophagectomy. However, the appropriate radiation volume has not been well established. This study aimed to determine the optimal PORT volume for LA-ESCC patients.

Methods: LA-ESCC patients post-esophagectomy were randomly assigned to either the large-field irradiation (LFI, primary lesion and lymph node tumor bed plus elective nodal irradiation) group or the small-field irradiation (SFI, primary lesion and lymph node tumor bed alone) group. Stratification was based on T stage and the number of lymph node metastases. The primary endpoint was disease-free survival (DFS), while the secondary endpoints included overall survival (OS), adverse events, and patterns of initial failure.

Results: A total of 401 patients were randomly assigned to the intention-to-treat analysis(LFI group, n = 210; SFI group, n = 191). The median DFS of patients in the LFI group was 47.9 months and 48.1 months in the SFI group (HR = 0.87, 95%CI, 0.65 to 1.16; p = 0.32). The estimated one-year and three-year OS rates were 89.2% and 63.2% for patients in the LFI group, compared to 86.6% and 60.7% for the SFI group, respectively. The difference of OS between the two groups was not significant (HR = 0.86, 95%CI, 0.63 to 1.16; p = 0.35). Fewer patients in the LFI group experienced locoregional recurrence compared to the SFI group (12.9% vs 20.4%, p = 0.013). Additionally, locoregional recurrence-free survival of the LFI group was significantly longer than that of SFI group (HR = 0.54, 95%CI, 0.34-0.87; p = 0.01). The most common toxicity was grade 2 esophagitis, observed in 22.9% of the LFI group and 16.8% of the SFI group. Grade 3 adverse events occurred in 6.7% of the LFI group and 2.6% of the SFI group. No grade 4 or 5 toxicities were observed. Adverse events did not significantly differ between the two groups.

Conclusions: Postoperative radiotherapy, with the specified radiation volume shows encouraging survival outcomes that are comparable to those of neoadjuvant chemoradiotherapy in patients with thoracic LA-ESCC. Both postoperative irradiation fields were found to be feasible and safe.

Background: Predicting which children and young people (CYP) are at the highest risk of developing post-COVID-19 condition (PCC) could improve care pathways. We aim to develop and validate prediction models for persistent PCC up to 24 months post-infection in CYP.

Methods: CYP who were PCR-positive between September 2020 and March 2021, with follow-up data up to 24-months post-infection, were analysed. Persistent PCC was defined in two ways, as PCC at (a) 3, 6, 12 and 24 months post-infection (N = 943) or (b) 6, 12 and 24 months post-infection (N = 2373). Prediction models were developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping; the final model was adjusted for overfitting.

Results: While 24.7% (233/943) of CYP met the PCC definition 3 months post-infection, only 7.2% (68/943) continued to meet the PCC definition at all three subsequent timepoints, i.e. at 6, 12 and 24 months. The final models predicting risk of persistent PCC (at 3, 6, 12 and 24 months and at 6, 12 and 24 months) contained sex (female), history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems, with additional variables (e.g. older age at infection and region of residence) in the model predicting PCC at 6, 12 and 24 months. Internal validation showed minimal overfitting of models with good calibration and discrimination measures (optimism-adjusted calibration slope: 1.064-1.142; C-statistic: 0.724-0.755).

Conclusions: To our knowledge, these are the only prediction models estimating the risk of CYP persistently meeting the PCC definition up to 24 months post-infection. The models could be used to triage CYP after infection. CYP with factors predicting longer-term symptomology, may benefit from earlier support.

Background: Epidemiological studies show inconsistent links between hearing/vision impairment and dementia risk. Using multisource data, we investigated how single or combined sensory impairments relate to risks of all-cause and specific types of dementia.

Methods: We employed a triangulation approach combining three methodologies. We analyzed 90,893 UK Biobank (UKB) adults to explore single and joint effects of hearing and vision impairments on all-cause and Alzheimer's disease (AD), vascular dementia (VD) and non-AD non-VD (NAVD). A meta-analysis of prospective studies involving 937,908 participants provided stronger evidence. Finally, we conducted Mendelian randomization (MR) analysis using genome-wide association studies from UKB (361,194 participants) and FinnGen (412,181 participants) to validate relationships between sensory impairments and dementia occurrence.

Results: In the UKB cohort study, compared to participants with normal hearing, those in the mild and severe hearing impairment groups had progressively and significantly higher risk of all-cause dementia (mild: HR1.52, 95%CI 1.31-1.77; severe: HR1.80, 95%CI 1.36-2.38), AD (mild: HR1.63, 95%CI 1.30-2.04; severe: HR2.18, 95%CI 1.45-3.27), VD (mild: HR1.68, 95%CI 1.19-2.37; severe: HR1.47, 95%CI 1.22-1.78), and NAVD (mild: HR1.47, 95%CI 1.22-1.78; severe: HR1.98, 95%CI 1.43-2.75). Besides, vision impairment was associated with an increased risk of all-cause dementia (HR1.55, 95%CI 1.18-2.04) and NAVD (HR1.51, 95%CI 1.07-2.13). Furthermore, dual sensory impairment was associated with stepwise increased risks of all-cause and cause-specific dementia than single hearing or vision impairment. In the meta-analysis of 31 prospective cohort studies, risks of all-cause dementia and AD were elevated in participants with single hearing impairment (all-cause dementia: HR1.30, 95%CI 1.21-1.40; AD: HR1.30, 95%CI 1.21-1.40) and dual sensory impairment (all-cause dementia: HR1.63, 95%CI1.14-2.12; AD: HR 2.55, 95%CI 1.19-3.91), while single vision impairment only associated with higher risk of all-cause dementia (HR1.43, 95%CI 1.16-1.71) but not AD. Finally, the MR analysis revealed a significant association between hearing impairment and all-cause dementia (OR1.74, 95%CI 1.01-2.99), AD (OR1.56, 95%CI 1.09-2.23), and NAVD (OR1.14, 1.02-1.26), as well as vision impairment and NAVD (OR1.62, 95%CI 1.13-2.33).

Conclusions: Our findings showed significant associations between hearing and vision impairments and increased risks of all-cause and cause-specific dementia. Standardized hearing and vision assessment and intervention should be emphasized in dementia prevention strategies.