医学最新文献

Therapeutic immunization against tumor neoantigens has the potential to induce potent and highly selective CD8⁺ T-cell-mediated antitumor immunity. Consequently, immunization strategies that generate robust neoantigen-specific T-cell responses are needed. Here, we tested homologous and heterologous DNA- and peptide-based immunization strategies using a neoantigen model. We observed that priming with DNA followed by peptide boost immunization elicited the strongest CD8⁺ T-cell responses, which exhibited effector and memory precursor phenotypes and led to the formation of circulating and skin-resident memory T cells. In prophylactic settings, this immunization regimen delayed the growth of B16F10 melanoma and rejected EL4 lymphoma cells expressing a self-antigen. In a therapeutic setting, a DNA prime-peptide boost eliminated EL4 tumors expressing the neo-epitope model in most mice. Consistently, DNA prime-peptide boost targeting two bona fide neoepitopes of MC38 tumor model elicited neoepitope-specific CD8⁺ T-cell responses and a marked therapeutic effect, which may be enhanced by combining with anti-PD-1 antibody. These results highlight the potential of DNA prime-peptide boost as a promising strategy for therapeutic neoantigen immunization that elicits strong CD8⁺ T-cell responses and potent antitumor effects.

Background: Rates of hypertensive disorders affecting pregnancy are increasing, and bipolar disorder is more common in pregnancy than previously thought.

Objective: The authors investigated differences in the incidence of hypertensive disorders of pregnancy between those with and without bipolar disorder (BPD) and between those receiving and not receiving pharmacotherapy for BPD. Differences in the incidence of hypertensive disorders of pregnancy in those with BPD between those on prophylactic aspirin (ASA) and not, were also examined.

Methods: EPIC COSMOS was used to examine records from 2019 to 2023.

Results: The authors found a meaningful difference in proportions between those with and without BPD when observing development of hypertensive disorders of pregnancy across years. Slightly increased odds of hypertensive disorders were found among those reporting BPD pharmacotherapy compared to those not. Slightly increased odds of hypertensive disorders occurred in those with BPD reporting ASA.

Conclusions: The increased odds among those reporting BPD pharmacotherapy could be due to sequelae of disease, medication used, or comorbidities. These findings further corroborate prior evidence of the increasing prevalence of both maternal health complications and mental health disorders int eh United States.

Regular exercise training can significantly improve the gut environment and influence the metabolic activity of the gut microbiota. These changes promote the production of beneficial metabolites, which may modulate blood pressure regulation through multiple mechanisms. The beneficial microbial species including Faecalibacterium prausnitzii, Bifidobacterium spp., Lactobacillus spp., Roseburia spp.,and Bacteroides spp. These beneficial microbes produce various metabolites during metabolism, including short-chain fatty acids, vitamins, lactic acid, bileacids, and gamma-aminobutyric acid. These metabolites are not only essential for maintaining gut health but also positively influence hypertension by modulating the nervous system, immune system, and improving metabolic function. This review aims to elucidate the complex interactions among exercise training, gut microbiota, and hypertension.

There has been a considerable controversy about vaccination practices of children with special health-care needs (CSHCNs) in China. We aim to describe current vaccination recommendations, immunization status, and vaccination safety of CSHCNs in Wuxi. We conducted a cross-sectional study of CSHCNs aged <18 y visiting the vaccination consultation clinic (VCC) at Wuxi Children's Hospital in 2020-2023. Demographic information was collected from Electronic Medical Records, vaccination data was obtained from Vaccination Integrated Service Management Information System of Jiangsu Province, China. Safety monitoring data was acquired from China National Adverse Events Following Immunization Information System (CNAEFIS). Descriptive data were presented as percentages, and Poisson test was used to compare the cumulative incidence of AEFIs between groups. Four thousand one hundred and twenty-two participants were included and the majority (73.0%) were under 12 months. The top three diseases consulted were those relating to the certain conditions originating in the perinatal period, developmental anomalies, and diseases of the blood or blood-forming organs. Only 6.1% had previously received all age-eligible vaccine doses before seeking evaluation. According to the vaccination guidance issued by the VCC, 59.9% were recommended to continue vaccine normally, partial vaccination was recommended for 37.2%, and 4.1% were advised to delay. A total of 3927 CSHCNs received 62,744 vaccine doses after consultation. None had serious adverse events and the cumulative incidence of AEFIs was higher than the general population of children. Specialist consultation is helpful to improve the vaccine uptake. Further research on strategies to improve the vaccination coverage of CSHCNs is warranted.

Background: Phenylcapsaicin (PC) may enhance high-intensity exercise performance by reducing perceived exertion, increasing mechanical output, and limiting muscle damage, making it potentially beneficial for CrossFit^® (CF) athletes.

Objective: To examine the acute effects of PC supplementation on performance, recovery, and metabolic responses during a CF session.

Methods: This study had a randomized, triple-blind, placebo-controlled crossover design. Fifty CF-trained athletes (50% women) ingested either 2.5 mg of PC or a placebo (PLA) 45 minutes before a standardized CF session, including a warm-up, weightlifting block, and WOD. Delayed-onset muscle soreness (DOMS) was assessed 24- and 48-hours post-session. Countermovement jump (CMJ) was evaluated pre- and post-session, while a deep squat at 70% 1RM was performed post-session. Throughout the session, heart rate, capillary lactate, rating of perceived exertion (RPE), and perceived recovery status (PRS) were monitored.

Results: Compared to PLA, PC improved squat performance at 70% 1RM in both load and repetitions (P ≤ 0.035), attenuated the decline in CMJ (P < 0.001), and maintained weightlifting performance over time (P interaction = 0.011), with significantly higher load in round 9 (P = 0.030). No differences were observed during the WOD (P interaction ≥ 0.826). DOMS was significantly lower in the PC group at both 24 h and 48 h (P = 0.030), while no group differences were found for lactate, RPE, PRS, or heart rate (P interaction ≥ 0.340). Analysis stratified by sex showed that PC reduced CMJ loss in men (P = 0.043) and increased squat load in women (P = 0.021).

Conclusion: In conclusion, acute PC supplementation enhances performance and recovery in CF athletes.

Purpose: Cystic fibrosis (CF) is a genetic disease primarily affecting the lungs and digestive system. Individuals with advanced CF lung disease may require transplantation to survive. Family members often take on significant caregiving roles, facing both emotional and practical challenges throughout the transplantation process. This study explores the experiences of such family members to inform and improve supportive care practices.

Method: Employing a naturalistic, exploratory design, this qualitative study used purposive sampling to recruit 19 family members of lung transplant recipients with CF. Data were collected through semi-structured interviews and analysed using reflexive thematic analysis.

Results: The analysis identified three main themes and eight subthemes: (I) balancing hope and despair on the waiting list, (II) navigating challenges and finding relief after the transplantation, and (III) unmet support and informational needs before and after transplantation.

Conclusion: This study highlights the emotional burden and caregiving responsibilities shouldered by family members of individuals with CF who have undergone lung transplantation. The findings emphasise the importance of person- and family-centred interventions, including support for palliative care discussions. A more structured and inclusive framework is essential to address the often-overlooked needs of families throughout the transplantation process.

In May 2022, a global outbreak of mpox (formerly known as monkeypox) was declared an international public health emergency. During this time, healthcare workers scrambled to respond to the outbreak amidst a lack of resources, knowledge gaps and pressures related to COVID-19. This period posed a risk of heightened moral distress, defined as distress arising from a situation in which a healthcare worker knows the right thing to do but is externally constrained from doing so. An international survey of healthcare workers was developed to understand their experiences of responding to mpox, including open-text questions regarding moral distress. Drawing on thematic analysis of these open text responses, this paper conceptualises the forms of distress experienced by health workers as 'outbreak distress'-an emotional and psychological response to the synergistic effects that arise from stressed systems, uncertainty and stigma that characterise many, and especially new, infectious disease outbreaks. In the context of pandemic preparedness, outbreak distress represents a novel concept for understanding additional pressures on healthcare systems in future unknown and re-emerging outbreaks.

Background: Tuberculosis screening is recommended for people living with HIV. The QuantiFERON-TB test measures the cell-mediated response against M. Tuberculosis. The Gold-In-Tube measures the response of CD4+ T-cells, often leading to indeterminate results. The new Gold-Plus (QFT-GP) also measures CD8+ T-cells response, thus reducing uncertainties. However, studies on people living with HIV, that would benefit from a test independent from CD4+ T-cells, are scarce.

Objective: This study addresses this gap by evaluating the performance of QFT-GP specifically in a large cohort of people living with HIV in a low TB-endemic setting.

Methods: We retrospectively evaluated the frequency of indeterminate QFT-GP tests in a cohort of people living with HIV with at least one test. We collected demographic data, CD4+ and CD8+ T-cell count at nadir and at the time of testing, and history of prior TB infection or treatment. We correlated the QFT-GP results to the CD4+ T-cell count.

Results: Six hundred and ninety five patients were included (males/females 72.5/27.5%), median age was 51 ± 14 years. Only 1,2% of tests were indeterminate, and there was no association with the CD4+ or CD8+ T-cell count at the moment of the test or at the nadir.

Conclusions: QFT-GP has few indeterminate results, even in patients with a low CD4+ T-cell count.

Background: Oral food challenges are indicated when food allergies cannot be confirmed by clinical history or investigations, such as blood or skin-prick tests. However, few studies have examined adults' experiences of oral food challenges.

Methods: Semi-structured, individual interviews were conducted with 18 adults who had undergone an oral food challenge at a UK hospital.

Results: Three main themes were identified using thematic analysis, describing experiences before, during, and after testing: "A limited and scared life," "facing fear and uncertainty in a safe environment," and "living with revised boundaries." Prior to the test, participants described a life characterized by fear of reactions, hypervigilance, planning and restrictive diets, limiting social participation. During testing, participants experienced an emotional rollercoaster, confronting something previously avoided, which could potentially cause a severe reaction. After testing, participants reported reduced fear and uncertainty following clarification of their allergies, leading to greater freedom, and for those who tested negative, a return to viewing food as a source of pleasure, rather than fear.

Conclusions: Oral food challenges reduce fear and uncertainty surrounding allergies, providing clarity about which foods trigger reactions. Greater availability of oral food challenges would enable adults with suspected allergies to live less restricted and more enjoyable lives.