Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization.

BACKGROUND: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception. METHODS: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period. FINDINGS: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood. INTERPRETATION: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality. FUNDING: WHO.

Identification and genetic characterization of a recently identified enterovirus C116 in China.

Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection.

Serological investigation and isolation of Salmonella abortus equi in horses in Xinjiang.

BACKGROUND: Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is one of the main pathogens that causes abortion in pregnant horses and donkeys, which was highly infectious and greatly restricts the healthy development of the horse industry. OBJECTIVES: In order to investigate the prevalence and biological characteristics of S. abortus equi in different regions and breeds of horses in Xinjiang. METHODS: This study conducted ELISA detection of S. abortus equi antibodies on serum samples of 971 horses collected from three large-scale horse farms and five free-range horse farms in Yili Prefecture and Bayingol Mongolian Autonomous Prefecture of Xinjiang from 2020 to 2023. On this basis, bacterial isolation, culture, identification, and drug sensitivity tests were conducted on 42 samples of aborted foal tissues and 23 mare vaginal swabs. RESULTS: The results showed that the positive rate of S. abortus equi antibody was as high as 20.91% in 971 horse serum samples. Among them, the positive rate in the Ili region (29.09%) was significantly higher than that in the Bayingole region (11.24%), and the positive rate in mares (22.45%) was higher than that in stallions (14.05%). In terms of horse breeds, the positive rates of self-propagating thoroughbred horses, half-bred horses, Ili horses and Yanqi horses were 43.22%, 28.81%, 14.72% and 11.24% respectively. In addition, S. abortus equi was more susceptible to juvenile and elderly horses, with positive rates of 70.00%and 41.86%, respectively, both of which were significantly higher than young (10.97%) and adult (19.79%) horses. Further, 9 strains of S. abortus equi were obtained through bacterial isolation, culture and identification, which were resistant to five antibiotics (Clarithromycin, Clindamycin, penicillin, Sulfamethoxazole and Rifampicin), and sensitive to 13 antimicrobial agents (Amoxicillin, Ciprofloxacin and Gentamicin, et al.). CONCLUSION: There was a high infection rate of S. abortus equi in Ili Prefecture and self-propagating thoroughbred horses, and juvenile or old mares were more susceptible, which will provide scientific basis for the prevention of S. abortus equi infection in different regions and breeds of horses in Xinjiang.

A qualitative study on the willingness and influencing factors of master of geriatric nursing specialist postgraduates to volunteer for home respite care for disabled elderly families.

BACKGROUND: As China's population ages, the demand for care for the disabled elderly is increasing, and family caregivers find it challenging to meet the comprehensive care needs of the disabled elderly. Through home respite services, families of the disabled elderly can receive help and support from specialized nursing professionals to ease the burden on family caregivers and provide high-quality services. This study explores the willingness and influencing factors of Master of Geriatric Nursing Specialist postgraduates in China to volunteer to provide home respite services for disabled elderly individuals. METHODS: A qualitative study based on Grounded Theory used Strauss and Corbin's programmatic version. A purposive sampling method was employed to conduct semi-structured interviews with 12 Master of Geriatric Nursing Specialist postgraduates from a tertiary hospital in Changsha, Hunan Province, China. RESULTS: The willingness of Master of Geriatric Nursing Specialist postgraduates to volunteer to provide home respite services for the disabled elderly was established as a core category, which was influenced by three main categories: personal factors, service object factors, and social factors, and nine categories formed from 39 initial concepts were included under the main category. CONCLUSIONS: Influenced by China's traditional cultural background, Master of Geriatric Nursing Specialist postgraduates in China have shown high motivation in volunteering to provide home respite services for the families of the disabled elderly but have been challenged by several challenges from China's healthcare environment and education system. Relevant departments need to adopt a series of policies and measures to increase volunteers' willingness to participate in respite care and promote its development.

High-dimensional variable selection for ordinal outcomes with error control.

Many high-throughput genomic applications involve a large set of potential covariates and a response which is frequently measured on an ordinal scale, and it is crucial to identify which variables are truly associated with the response. Effectively controlling the false discovery rate (FDR) without sacrificing power has been a major challenge in variable selection research. This study reviews two existing variable selection frameworks, model-X knockoffs and a modified version of reference distribution variable selection (RDVS), both of which utilize artificial variables as benchmarks for decision making. Model-X knockoffs constructs a 'knockoff' variable for each covariate to mimic the covariance structure, while RDVS generates only one null variable and forms a reference distribution by performing multiple runs of model fitting. Herein, we describe how different importance measures for ordinal responses can be constructed that fit into these two selection frameworks, using either penalized regression or machine learning techniques. We compared these measures in terms of the FDR and power using simulated data. Moreover, we applied these two frameworks to high-throughput methylation data for identifying features associated with the progression from normal liver tissue to hepatocellular carcinoma to further compare and contrast their performances.

MiR-122 knockdown regulates vascular smooth muscle cells phenotypic switching through enhanced FOXO3 expression.

Vascular smooth muscle cells (VSMCs) phenotypic switching is identified as enhanced dedifferentiation, proliferation, and migration ability of VSMCs, in which microRNAs have been identified as important regulators of the process. The present study is aimed to explore the pathophysiological effect of miR-122 on VSMC phenotypic modulation. Here, the result showed that the decreased miR-122 expression was found in VSMCs subjected to platelet-derived growth factor-BB (PDGF-BB) treatment. Next, we investigated the response of miR-122 knockdown in VSMCs with PDGF-BB stimulation. MiR-122 silencing showed increased proliferation and migration capability, whereas attenuated the differentiation markers expression. The above results were reversed by miR-122 overexpression. Finally, we further demonstrated that FOXO3 was an important target for miR-122. Collectively, we demonstrated that miR-122 silencing promoted VSMC phenotypic modulation partially through upregulated FOXO3 expression that indicated miR-122 may be a novel therapeutic target for neointimal formation.

Cystathionine-ß-synthase (CBS)/H2S system promotes lymph node metastasis of esophageal squamous cell carcinoma (ESCC) by activating SIRT1.

Lymph node metastasis is a key factor of death and prognosis in patients with esophageal squamous cell carcinoma (ESCC). Previous studies have demonstrated that Cystathionine-ß-synthase (CBS)/H2S system plays important roles in progression of various cancer. However, the function and mechanism of CBS/H2S system in lymph node metastasis of ESCC remains unclear. Here, we found that CBS was highly expressed in human ESCC tissues and closely associated with lymph node metastasis in ESCC patients. Functional studies demonstrated that CBS could significantly promote lymph node metastasis of ESCC tumor cells. In vitro, CBS knockdown inhibited tumor cell proliferation, migration and invasion, whereas CBS overexpression produced the opposite results. In vivo, downregulation of CBS distinctly inhibited ESCC tumor growth and lymphatic metastasis, as evidenced by the decreased size and weight of tumor and popliteal lymph node. Meanwhile, we also found high expression of CBS-induced ESCC angiogenesis and lymphangiogenesis in vitro and in vivo by upregulating VEGF, VEGF-C, and VEGF-D. Mechanistically, CBS up-regulated the expression of SIRT1 and thus interrupted the Notch1/Hes1 axis, which plays a crucial role in lymph node metastasis of ESCC. Moreover, it was demonstrated that H2S derived from CBS-activated SIRT1 via increasing the NAD+/NADH ratio and promoting the phosphorylation of SIRT1. In addition, H2S derived from CBS also enhanced SIRT1 protein stability. Taken together, these data show that the high expression of CBS/H2S system promotes ESCC lymph node metastasis via activating SIRT1 signaling pathway and CBS could serve as a potential therapeutic target for clinical intervention in ESCC.

Tandem gene amplification restores photosystem II accumulation in cytochrome b559 mutants of cyanobacteria.

Cytochrome (Cyt) b559 is a key component of the photosystem II complex (PSII) that is essential for its proper functioning and assembly. Site-directed mutants of the model cyanobacterium Synechocystis sp. PCC6803 with mutated heme axial ligands of Cyt b559 have little PSII and are therefore unable to grow photoautotrophically. Here we describe two types of Synechocystis autotrophic transformants that retained the same mutations in Cyt b559 but are able to accumulate PSII and grow photoautotrophically. Whole-genome sequencing revealed that all of these autotrophic transformants carried a variable number of tandem repeats (from 5 to 15) of chromosomal segments containing the psbEFLJ operon. RNA-seq analysis showed greatly increased transcript levels of the psbEFLJ operon in these autotrophic transformants. Multiple copies of the psbEFLJ operon in these transformants were only maintained during autotrophic growth, while its copy numbers gradually decreased under photoheterotrophic conditions. Two-dimensional PAGE analysis of membrane proteins revealed a strong deficiency in PSII complexes in the Cyt b559 mutants that was reversed in the autotrophic transformants. These results illustrate how tandem gene amplification restores PSII accumulation and photoautotrophic growth in Cyt b559 mutants of cyanobacteria, and may serve as an important adaptive mechanism for cyanobacterial survival.

The availability of neither D2 nor CP43 limits the biogenesis of photosystem II in tobacco.

The pathway of photosystem II (PSII) assembly is well understood, and multiple auxiliary proteins supporting it have been identified, but little is known about rate-limiting steps controlling PSII biogenesis. In the cyanobacterium Synechocystis PCC6803 and the green alga Chlamydomonas reinhardtii, indications exist that the biosynthesis of the chloroplast-encoded D2 reaction center subunit (PsbD) limits PSII accumulation. To determine the importance of D2 synthesis for PSII accumulation in vascular plants and elucidate the contributions of transcriptional and translational regulation, we modified the 5'-untranslated region of psbD via chloroplast transformation in tobacco (Nicotiana tabacum). A drastic reduction in psbD mRNA abundance resulted in a strong decrease in PSII content, impaired photosynthetic electron transport, and retarded growth under autotrophic conditions. Overexpression of the psbD mRNA also increased transcript abundance of psbC (the CP43 inner antenna protein), which is co-transcribed with psbD. Because translation efficiency remained unaltered, translation output of pbsD and psbC increased with mRNA abundance. However, this did not result in increased PSII accumulation. The introduction of point mutations into the Shine-Dalgarno-like sequence or start codon of psbD decreased translation efficiency without causing pronounced effects on PSII accumulation and function. These data show that neither transcription nor translation of psbD and psbC are rate-limiting for PSII biogenesis in vascular plants and that PSII assembly and accumulation in tobacco are controlled by different mechanisms than in cyanobacteria or in C. reinhardtii.

Identification of multiple nonphotochemical quenching processes in the extremophilic red alga Cyanidioschyzon merolae.

Nonphotochemical quenching acts as a frontline response to prevent excitation energy from reaching the photochemical reaction center of photosystem II before photodamage occurs. Strong fluorescence quenching after merely one multi-turnover saturating light pulse characterizes a unique feature of nonphotochemical quenching in red algae. Several mechanisms underlying red algal nonphotochemical quenching have been proposed, yet which process(es) dominantly account for the strong fluorescence quenching is still under discussion. Here we assessed multiple nonphotochemical quenching processes in the extremophilic red alga Cyanidioschyzon merolae under light pulse and continuous illumination conditions. To assess the nonphotochemical quenching processes that might display different kinetics, fluorescence emission spectra at 77 K were measured after different periods of light treatments, and external fluorophores were added for normalization of the fluorescence level. The phycobilisome- and photosystem II-related nonphotochemical quenching processes were distinguished by light preferentially absorbed by phycobilisomes and photosystems, respectively. Multiple nonphotochemical quenching processes, including the energetic decoupling of phycobilisomes from photosystem II, the energy spillover from phycobilisomes to photosystem I and from photosystem II to photosystem I, were identified along with the previously identified intrinsic quenching within photosystem II. The ability to use multiple nonphotochemical quenching processes appears to maximize the light harvesting efficiency for photochemistry and to provide the flexibility of the energy redistribution between photosystem II and photosystem I. The effect of the various ionophores on the nonphotochemical quenching level suggests that nonphotochemical quenching is modulated by transmembrane gradients of protons and other cations.

γδ T cells exhibit multifunctional and protective memory in intestinal tissues.

The study of T cell memory and the target of vaccine design have focused on memory subsumed by T cells bearing the αß T cell receptor. Alternatively, γδ T cells are thought to provide rapid immunity, particularly at mucosal borders. Here, we have shown that a distinct subset of mucosal γδ T cells mounts an immune response to oral Listeria monocytogenes (Lm) infection and leads to the development of multifunctional memory T cells capable of simultaneously producing interferon-γ and interleukin-17A in the murine intestinal mucosa. Challenge infection with oral Lm, but not oral Salmonella or intravenous Lm, induced rapid expansion of memory γδ T cells, suggesting contextual specificity to the priming pathogen. Importantly, memory γδ T cells were able to provide enhanced protection against infection. These findings illustrate that γδ T cells play a role with hallmarks of adaptive immunity in the intestinal mucosa.

Controlled variable selection in Weibull mixture cure models for high-dimensional data.

Medical breakthroughs in recent years have led to cures for many diseases. The mixture cure model (MCM) is a type of survival model that is often used when a cured fraction exists. Many have sought to identify genomic features associated with a time-to-event outcome which requires variable selection strategies for high-dimensional spaces. Unfortunately, currently few variable selection methods exist for MCMs especially when there are more predictors than samples. This study develops high-dimensional penalized Weibull MCMs, which allow for identification of prognostic factors associated with both cure status and/or survival. We demonstrated how such models may be estimated using two different iterative algorithms. The model-X knockoffs method was combined with these algorithms to control the false discovery rate (FDR) in variable selection. Through extensive simulation studies, our penalized MCMs have been shown to outperform alternative methods on multiple metrics and achieve high statistical power with FDR being controlled. In an acute myeloid leukemia (AML) application with gene expression data, our proposed approach identified 14 genes associated with potential cure and 12 genes with time-to-relapse, which may help inform treatment decisions for AML patients.

Analysis and Design of Single-Ended Resonant Converter for Wireless Power Transfer Systems.

Single-ended resonant converters such as Class-E inverters have been widely considered as a potential topology for small- and medium-power wireless power transfer (WPT) applications, which feature compact circuits, low switching losses, and cost benefits, as they only use a low-side switch with a simple gate driver. However, there remains a practical challenge in the design of voltage stress, efficiency, and power density. In this paper, a single-ended resonant converter with a primary parallel resonant-matching network is investigated to absorb the bulky input-choke inductors of the Class-E inverters into the coil inductance. The analytical expressions for all the converter parameters are derived based on time-domain resonant waveforms, including: (1) analysis of critical zero-voltage switching (ZVS) conditions and (2) power transfer capabilities under the given maximum switch voltage stress. Furthermore, this paper elaborates on the design methodology of the proposed single-ended resonant converters, and an optimal operating point is chosen to ensure soft-switching operation and rated power. Finally, the accuracy of the proposed model is verified by simulation and experimental results.

Effects of moisture content on the enolization products formation in glucose-proline Maillard reaction models.

BACKGROUND: 2,3-Dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP) and 5-hydroxymethylfurfural (HMF) are two main enolization products in the Maillard reaction and found in some foodstuffs. For many years, whether they are functional or noxious to human health has been a matter of debate. Thus, insight into their formation pathways is important to manage Maillard reaction products. In this study, DDMP and HMF were quantified and compared with regard to their formation and degradation in the d-glucose and l-proline Maillard reaction models using different moisture contents (0, 0.1, 0.5, 1.0, and 4.0 mL) at 150 °C for various heating times. RESULTS: DDMP was predominantly generated in dry or low water-content heating models along with n increased 1-deoxyglucosone (1-DG) generation via 2,3-enolization. However, increasing moisture content resulted in a decay of reaction intensity, 1-DG, and DDMP due to a change in the reaction mechanism from 2,3-enolization to 1,2-enolization, which facilitated 3-deoxyglucosone (3-DG) and HMF formation. CONCLUSION: Increased moisture content in glucose-proline models reduced reaction intensity and also inhibited DDMP and facilitated HMF formation by promoting the pathway change from 2,3-enolization to 1,2-enolization to generate more 3-DG. A water content of 1.0 mL was identified as a critical value, from which the 1,2-enolization became a primary pathway occurring in the Maillard reaction. © 2022 Society of Chemical Industry.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Setting-specific Transmission Rates: A Systematic Review and Meta-analysis.

BACKGROUND: Understanding the drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is crucial for control policies, but evidence of transmission rates in different settings remains limited. METHODS: We conducted a systematic review to estimate secondary attack rates (SARs) and observed reproduction numbers (Robs) in different settings exploring differences by age, symptom status, and duration of exposure. To account for additional study heterogeneity, we employed a beta-binomial model to pool SARs across studies and a negative-binomial model to estimate Robs. RESULTS: Households showed the highest transmission rates, with a pooled SAR of 21.1% (95% confidence interval [CI]:17.4-24.8). SARs were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of ≤5 days. SARs related to contacts at social events with family and friends were higher than those for low-risk casual contacts (5.9% vs 1.2%). Estimates of SARs and Robs for asymptomatic index cases were approximately one-seventh, and for presymptomatic two-thirds of those for symptomatic index cases. We found some evidence for reduced transmission potential both from and to individuals younger than 20 years of age in the household context, which is more limited when examining all settings. CONCLUSIONS: Our results suggest that exposure in settings with familiar contacts increases SARS-CoV-2 transmission potential. Additionally, the differences observed in transmissibility by index case symptom status and duration of exposure have important implications for control strategies, such as contact tracing, testing, and rapid isolation of cases. There were limited data to explore transmission patterns in workplaces, schools, and care homes, highlighting the need for further research in such settings.

Effect of evidence updates on key determinants of measles vaccination impact: a DynaMICE modelling study in ten high-burden countries.

BACKGROUND: Model-based estimates of measles burden and the impact of measles-containing vaccine (MCV) are crucial for global health priority setting. Recently, evidence from systematic reviews and database analyses have improved our understanding of key determinants of MCV impact. We explore how representations of these determinants affect model-based estimation of vaccination impact in ten countries with the highest measles burden. METHODS: Using Dynamic Measles Immunisation Calculation Engine (DynaMICE), we modelled the effect of evidence updates for five determinants of MCV impact: case-fatality risk, contact patterns, age-dependent vaccine efficacy, the delivery of supplementary immunisation activities (SIAs) to zero-dose children, and the basic reproduction number. We assessed the incremental vaccination impact of the first (MCV1) and second (MCV2) doses of routine immunisation and SIAs, using metrics of total vaccine-averted cases, deaths, and disability-adjusted life years (DALYs) over 2000-2050. We also conducted a scenario capturing the effect of COVID-19 related disruptions on measles burden and vaccination impact. RESULTS: Incorporated with the updated data sources, DynaMICE projected 253 million measles cases, 3.8 million deaths and 233 million DALYs incurred over 2000-2050 in the ten high-burden countries when MCV1, MCV2, and SIA doses were implemented. Compared to no vaccination, MCV1 contributed to 66% reduction in cumulative measles cases, while MCV2 and SIAs reduced this further to 90%. Among the updated determinants, shifting from fixed to linearly-varying vaccine efficacy by age and from static to time-varying case-fatality risks had the biggest effect on MCV impact. While varying the basic reproduction number showed a limited effect, updates on the other four determinants together resulted in an overall reduction of vaccination impact by 0.58%, 26.2%, and 26.7% for cases, deaths, and DALYs averted, respectively. COVID-19 related disruptions to measles vaccination are not likely to change the influence of these determinants on MCV impact, but may lead to a 3% increase in cases over 2000-2050. CONCLUSIONS: Incorporating updated evidence particularly on vaccine efficacy and case-fatality risk reduces estimates of vaccination impact moderately, but its overall impact remains considerable. High MCV coverage through both routine immunisation and SIAs remains essential for achieving and maintaining low incidence in high measles burden settings.

Clinical metagenomics assessments improve diagnosis and outcomes in community-acquired pneumonia.

BACKGROUND: Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease's complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques. RESULTS: We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes. CONCLUSIONS: Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP. TRIAL REGISTRATION: Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628 .

Trimetazidine can prevent the occurrence of contrast-induced nephropathy after percutaneous coronary intervention in elderly patients with renal insufficiency.

BACKGROUND: Contrast-induced nephropathy (CIN) has become a common cause of hospital-acquired acute kidney injury in elderly patients. Trimetazidine (TMZ) is a type of anti-ischemic drug developed in recent years, which can reduce the incidence of CIN. This study aimed to evaluate the efficacy of TMZ in the prevention of contrast-induced nephropathy in elderly patients with renal insufficiency undergoing percutaneous coronary intervention (PCI) and to explore the mechanism of action. METHODS: A total of 310 elderly patients with renal insufficiency undergoing elective PCI were enrolled and randomly assigned to a control group (n = 155, hydration only) and a TMZ group (n = 155, 20 mg thrice daily orally 24 hours before and 72 hours after PCI). The primary endpoint of the study was the incidence of CIN, which was defined as an increase of 25% or more, or an absolute increase of 0.5 mg/dL or more in serum creatinine from baseline value, at 48 to 72 hours following the exposure to contrast media (CM). RESULTS: The incidence of CIN was significantly lower in the TMZ group than that in the control group (3.2% vs. 9.7%, p = 0.021). There was no difference regarding the incidence of major adverse events during hospitalization between the TMZ group and control group (1.9% vs. 2.6%, p = 1.000). Binary logistic regression results showed that TMZ was protective factors of CIN (OR = 0.274; 95% CI: 0.089-0.847; p = 0.025). CONCLUSION: Therefore, we came to the conclusion that prophylactic administration of TMZ can prevent the occurrence of CIN in elderly patients with renal insufficiency undergoing PCI and has a certain protective effect on the renal function of patients. According to the experimental results and the mechanism of TMZ on cardiomyocytes, we speculate that TMZ increases kidney glucose metabolism, reduces fatty acid oxidation, and also has a protective effect on kidney free radical damage and ischemia-reperfusion injury.

Organic Nanoplatforms for Iodinated Contrast Media in CT Imaging.

X-ray computed tomography (CT) imaging can produce three-dimensional and high-resolution anatomical images without invasion, which is extremely useful for disease diagnosis in the clinic. However, its applications are still severely limited by the intrinsic drawbacks of contrast media (mainly iodinated water-soluble molecules), such as rapid clearance, serious toxicity, inefficient targetability and poor sensitivity. Due to their high biocompatibility, flexibility in preparation and modification and simplicity for drug loading, organic nanoparticles (NPs), including liposomes, nanoemulsions, micelles, polymersomes, dendrimers, polymer conjugates and polymeric particles, have demonstrated tremendous potential for use in the efficient delivery of iodinated contrast media (ICMs). Herein, we comprehensively summarized the strategies and applications of organic NPs, especially polymer-based NPs, for the delivery of ICMs in CT imaging. We mainly focused on the use of polymeric nanoplatforms to prolong circulation time, reduce toxicity and enhance the targetability of ICMs. The emergence of some new technologies, such as theragnostic NPs and multimodal imaging and their clinical translations, are also discussed.

Telomere lengths in women treated for breast cancer show associations with chemotherapy, pain symptoms, and cognitive domain measures: a longitudinal study.

BACKGROUND: Survival rates for breast cancer (BC) have improved, but quality of life post-diagnosis/treatment can be adversely affected, with survivors reporting a constellation of psychoneurological symptoms (PNS) including stress, anxiety, depression, pain, fatigue, sleep disturbance, and cognitive dysfunction. METHODS: To assess a potential relationship between telomere length (TL) and the development/persistence of PNS, we longitudinally studied 70 women (ages 23-71) with early stage BC (I-IIIA) at 5 time-points: prior to treatment (baseline), the mid-point of their chemotherapy cycle, 6 months, 1 year, and 2 years following the initiation of chemotherapy. Measures quantified included assessments of each of the PNS noted above and TL [using both a multiplex qPCR assay and a chromosome-specific fluorescence in situ hybridization (FISH) assay]. RESULTS: Variables associated with qPCR mean TLs were age (p = 0.004) and race (T/S ratios higher in Blacks than Whites; p = 0.019). Significant differences (mostly decreases) in chromosome-specific TLs were identified for 32 of the 46 chromosomal arms at the mid-chemo time-point (p = 0.004 to 0.049). Unexpectedly, the sequential administration of doxorubicin [Adriamycin], cyclophosphamide [Cytoxan], and docetaxel [Taxotere] (TAC regimen) was consistently associated with higher TLs, when compared to TLs in women receiving a docetaxel [Taxotere], Carboplatin [Paraplatin], and trastuzumab [Herceptin] [TCH] chemotherapy regimen [association was shown with both the qPCR and FISH assays (p = 0.036)]. Of the PNS, pain was significantly negatively associated with TL (higher pain; shorter telomeres) for a subset of chromosomal arms (5q, 8p, 13p, 20p, 22p, Xp, Xq) (p = 0.014-0.047). Chromosomal TLs were also associated with 7 of the 8 cognitive domains evaluated, with the strongest relationship being noted for chromosome 17 and the visual memory domain (shorter telomeres; lower scores). CONCLUSIONS: We showed that race and age were significantly associated with telomere length in women treated for early stage BC and that acquired telomere alterations differed based on the woman's treatment regimen. Our study also demonstrated that pain and cognitive domain measures were significantly related to telomere values in this study cohort. Expanding upon the knowledge gained from this longitudinal study could provide insight about the biological cascade of events that contribute to PNS related to BC and/or its treatment.