Antibiotics and Pesticides Enhancing the Transfer of Resistomes among Soil-Bayberry-Fruit Fly Food Chain in the Orchard Ecosystem.

While substantial amounts of antibiotics and pesticides are applied to maintain orchard yields, their influence on the dissemination and risk of antibiotic resisitome in the orchard food chain remains poorly understood. In this study, we characterized the bacterial and fungal communities and differentiated both antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) in the soil, Chinese bayberry (matured and fallen), and fruit fly gut, collected from five geographic locations. Our results showed that fruit fly guts and soils exhibit a higher abundance of ARGs and VFGs compared with bayberry fruits. We identified 112 shared ARGs and 75 shared VFGs, with aminoglycoside and adherence factor genes being among the most abundant. The co-occurrence network revealed some shared microbes, such as Bacillus and Candida, as potential hosts of ARGs, highlighting the vector risks for both above- and below-ground parts of the orchard food chain. Notably, the elevated levels of antibiotics and pesticide residues in orchard soils increase ARGs, mobile genetic elements (MGEs), and VFGs in the soil-bayberry-fruit fly food chain. Our study highlighted that agricultural management, including the overuse of antibiotics and pesticides, could be the key factor in accumulating resistomes in the orchard food chain.

Effect of concentration, temperature, and time on the stability of hepatitis C virus nucleic acid in serum.

To explore the influence of storage temperature and time on the stability of different concentrations of hepatitis C virus nucleic acid (HCV RNA) samples and to provide data reference for laboratory quality control. Serum samples of 10 patients with HCV RNA detection quantitation of 106-108 IU/mL were collected. The samples of each patient were diluted into three concentrations: high, medium, and low. Then the samples of each concentration were divided into 21, which were divided into three groups according to the storage conditions of -20°C, 4°C, and 25°C, with seven samples in each group. The samples were selected from each group for quantitative detection of HCV RNA on day 0, day 1, day 3, day 5, day 7, day 14, and day 30. The results of each concentration and storage temperature sample remained stable within 5 days. Based on the mixed-effect linear model, the main effects of temperature, time, and concentration were statistically significant (P < 0.01). There was an interaction effect between concentration and time (P = 0.0448), and there was also an interaction effect between temperature and time (P < 0.01). There was no interaction effect between concentration and temperature (P = 0.11) or between concentration, temperature, and time (P = 0.90). The results of serum samples with different concentrations of the HCV RNA remained stable within 5 days. The lower the initial concentration of HCV RNA serum sample, the worse the stability; the higher the storage temperature, the worse the stability. If conditions permit, the laboratory should store such samples at -20°C. IMPORTANCE: Previously, there were few reports about the influence of different concentrations of sample nucleic acid on the stability of samples at various temperatures and times in various literatures. Therefore, it is necessary to analyze the influence of concentration factors on the stability of samples and test results at different storage times and temperatures. This study took the concentration of hepatitis C virus nucleic acid as the research object to further understand the stability of hepatitis C virus nucleic acid test samples under various storage conditions, to provide data reference for the treatment of hepatitis C virus nucleic acid and RNA test samples before clinical laboratory test, and provide guidance and help for the improvement of laboratory quality control.

Association of crown-root ratio and tooth survival in Chinese patients with advanced periodontitis: An 11-year retrospective cohort study.

INTRODUCTION: Periodontitis is a chronic multifactorial inflammatory disease which eventually lead to tooth loss (TL). Therefore, a retrospective study was conducted to evaluate the status of tooth survival within 11 years after non-surgical periodontal treatment (NSPT) and to analyze the risk factors especially crown-root ratio (CRR) that affected TL in Chinese with advanced periodontitis. METHODS: 3481 teeth of 131 subjects who underwent NSPT were examined retrospectively within a mean follow-up period of 11.6 years. The association of risk factors including clinical and radiographic parameters with TL was assessed using univariate and multivariate Cox regression analyses. Smooth curve fitting and segmented regression model were conducted to show the nonlinear relationship and the threshold effect between CRR and the risk of TL. RESULTS: 347 teeth were lost in 97 patients in this study. Male, diabetes mellitus, heavy-smoker, molar, probing depth (PD), attachment loss (AL), bleeding on probing (BOP), tooth mobility, and radiographic bone loss were significantly associated with tooth loss (P < 0.05). A nonlinear relationship between CRR and the risk of TL was found, with different turning point values between molars and non-molars (1.9 vs. 2.76). CONCLUSIONS: The findings based on practice-based clinical and radiographic data do suggest a nonlinear relationship between CRR and the survival of teeth, and provide evidence to help clinicians to determine the prognosis of teeth for patients with advanced periodontitis. CLINICAL SIGNIFICANCE: Based on clinical and radiographic data, this study provides an individualized basis for clinicians to judge the dental prognosis of patients with advanced periodontitis according to the different tooth sites.

The effect of hetrombopag combined with conventional treatment on immune function and quality of life in patients with severe aplastic anemia.

This study aimed to investigate the effect of hetrombopag combined with conventional treatment on immune function in patients with severe aplastic anemia (SAA). Patients were categorized into the control group (n = 50, receiving conventional treatment only) and experimental group (n = 50, receiving hetrombopag combined with conventional treatment). Before treatment and at weeks 18, 24, and 52 after treatment, the two groups were compared in routine blood test indicators, natural killer (NK) cell activity, and peripheral blood inflammatory factor levels. The overall remission rate and incidence of adverse events were also compared between the two groups. Outpatient or telephone follow-up was performed before treatment and at weeks 18, 24, and 52 after treatment to observe patients' immune function, treatment outcome, quality of life, and adverse events. Hemoglobin (Hb), and platelet count (PLT) (P < 0.05), and a rise in NK cell activity (P < 0.05). Interleukin (IL-10) levels were significantly higher, while IL-6 levels were significantly lower in the experimental group compared to the control group (P < 0.05). After receiving the treatment, all scores of SF-36 domains in both groups were higher than before treatment, particularly with higher scores in the experimental group (P < 0.05). Hetrombopag combined with conventional treatment improved the immune function and hematopoiesis of patients with SAA.

Enhanced Self-Cementation of Arsenic-Contaminated Soil via Activation of Non-Thermal Plasma-Irradiated Ferromanganese: A Mechanistic Investigation.

The self-cementation characteristics of arsenic (As)-contaminated soil were comprehensively investigated in this study. Different non-thermal plasma-irradiated binary (hydro)oxides of polyvalent ferromanganese (poly-Fe-Mn) were synthesized and exploratorily dispersed to soil samples to activate solidification and stabilization during the self-cemented process. The maximum compressive strength of 56.35 MPa and the lowest leaching toxicity of 0.004 mg/L were obtained in the proof test under optimal conditions (i.e., the mass ratio of the poly-Fe-Mn to the soil sample of 0.05; the mass ratio of the composite alkali activator (NaOH + CaO) to the soil sample of 0.25; the mass ratio of CaO to NaOH of 1.5; the mass ratio of the DI water to the binder of 0.515). The composite alkaline activator primarily contributed to the strength formation of the self-cemented matrix while the poly-Fe-Mn significantly influenced the reduction of the As-leaching toxicities. The poly-Fe-Mn maintained diffusion-controlled polycondensation and strengthened the nucleation process during self-cementation. The amount of water and the dosage of poly-Fe-Mn caused an interactive influence on the self-cemented solidification of contaminated soils. The solidified samples with poly-Fe-Mn exhibited better thermal decomposition than their counterparts, reflecting the enhancement of poly-Fe-Mn to the matrix. Some minerals including C-S-H, kaolinite, gehlenite, diopside sodian, augite, and albite were matched in the samples, directly demonstrating the geopolymerization-steered self-cementation of the As soil. The employment of poly-Fe-Mn not only reinforced the immobilization of As pollutants in the matrix but also induced the self-cementation of soils by intensifying the composite alkaline-activated geopolymerization kinetics.

Treatment with a combination of myricitrin and exercise alleviates myocardial infarction in rats via suppressing Nrf2/HO-1 antioxidant pathway.

Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.

Coping, connection appraisal, and well-being during COVID-19 in the U.S., Japan, and Mexico.

Introduction: The COVID-19 pandemic has affected nearly every facet of life, constituting a "new normal" and prompting an ongoing collective psychological crisis. People's ways of coping with the pandemic and corresponding well-being are of particular research interest; however, these constructs have largely been examined using deductive quantitative approaches, deficit-based lenses, and mononational samples. Methods: The current mixed-methods study used inductive-sequential (QUAL → QUAN) approaches to explore positive coping strategies (approach coping style and COVID-related connection appraisal) and well-being (loneliness, distress, and happiness) across individuals from the United States, Japan, and Mexico. Qualitative data were gathered from N = 141 U.S., Japanese, and Mexican adults to examine how people perceived connection during the pandemic. Results: Qualitative analyses illuminated common themes in which people appraised the pandemic as an opportunity for connection and strengthened interpersonal relationships. Quantitative measures, including a newly-developed questionnaire on COVID-related connection appraisal, were then administered to a separate sample of N = 302 adults in the U.S, Japan, and Mexico to assess associations among approach coping style, COVID-related connection appraisal, and well-being outcomes (loneliness, distress, happiness). Quantitative analyses found significant associations among approach coping style, COVID-related connection appraisal, and all well-being outcomes. Of note, these associations did not differ by country. COVID-related connection appraisal mediated the relationship between approach coping style and two well-being outcomes (loneliness and happiness). Discussion: Findings point to approach coping style and connection appraisal as pathways for resilience and growth in the face of global suffering.

Body composition trajectories during childhood predict skeletal maturation at puberty: A longitudinal study.

Nutritional status significantly impacts linear bone growth. We aimed to determine the relationship between the trajectories of four body composition indicators and pubertal advanced bone age. Trajectories of body mass index z-score (BMI z-score), visceral fat area z-score (VFA z-score), fat mass index z-score (FMI z-score), and fat-free mass index z-score (FFMI z-score) were identified based on three body composition measurements conducted from October 2018 to April 2023 within a pediatric cohort (the PROC study). We assessed pubertal bone age using the Tanner-Whitehouse 3-Chinese Radius-Ulna-Short (TW3-C RUS) method among 1402 primary school children. Children with a trajectory of higher BMI z-score, VFA z-score, FMI z-score, and FFMI z-score since childhood were more likely to have advanced bone age. The risk of advanced bone age was higher in children who were consistently in the high VFA z-score group (odds ratio [OR] = 6.73) or consistently in the high BMI z-score group (OR = 5.57), as compared to those in the low VFA z-score and low BMI z-score groups. Regular monitoring and maintenance of normal VFA during childhood may reduce the risk of advanced bone age at puberty. Furthermore, BMI monitoring is optional, especially in cases where specialized body composition equipment is not available.

A produce prescription program for patients with low incomes in North Carolina resulted in increased produce purchases.

OBJECTIVES: To assess if participation in a North Carolina produce prescription program for Supplemental Nutrition Assistance Program (SNAP) participants with diet-sensitive health conditions (SuperSNAP) is associated with changes in purchase composition and spending source. METHODS: This study used loyalty-card transaction data (October 2019-April 2022). We applied a linear mixed-effects model with overlap weights to perform a difference-indifferences analysis of purchases by SuperSNAP program enrollees compared to the control group. RESULTS: The sample included 1440 SuperSNAP shoppers and 45,851 control shoppers. Compared to shoppers only on SNAP, SuperSNAP shoppers spent $82.98 (95% CI (75.6, 90.3), p-value <0.001) more per month, $76.09 (95% CI (69.4, 82.8), pvalue <0.001) of which were spent strictly on food and beverage products. Among SuperSNAP shoppers, out of the $40 SuperSNAP benefit each month, an estimated $34.86 (95% CI (33.9, 35.8), p-value <0.001) of it was spent on fruits and vegetables. CONCLUSIONS: This study shows the promise of targeted produce prescription programs for SNAP participants in encouraging shifts in purchase composition.

Soil keystone viruses are regulators of ecosystem multifunctionality.

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10-100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

Granulocyte colony-stimulating factor mediates bone loss via the activation of IL-1ß/JNK signaling pathway in murine Staphylococcus aureus-induced osteomyelitis.

Staphylococcus aureus (S. aureus)-induced bone loss is a significant challenge in the treatment of osteomyelitis. Our previous study was the first to confirm that granulocyte colony-stimulating factor (G-CSF) mediates S. aureus-induced bone loss. However, the underlying mechanism remains unknown. The objective of this study was to elucidate this. We found G-CSF mediated BMSC senescence and increased IL-1ß concentration of serum and bone marrow in mice after S. aureus infection. Furthermore, we demonstrated that G-CSF promoted the expression of IL1b in murine bone marrow-derived neutrophils. Notably, we identified that IL-1ß mediated BMSC (bone marrow mesenchymal stromal cell) senescence in mice after S. aureus infection. Importantly, IL-1ß neutralizing antibody effectively alleviated BMSC senescence and bone loss caused by S. aureus infection in mice. In terms of molecular mechanism, we found IL-1ß induced BMSC senescence by JNK/P53 and JNK/BCL2 pathways. Collectively, G-CSF promotes IL-1ß production which induces BMSC senescence via JNK/P53 and JNK/BCL2 pathways, leading to S. aureus-induced bone loss. This study identified novel targets for preventing and treating S. aureus-induced bone loss in osteomyelitis.

Giant viruses as reservoirs of antibiotic resistance genes.

Nucleocytoplasmic large DNA viruses (NCLDVs; also called giant viruses), constituting the phylum Nucleocytoviricota, can infect a wide range of eukaryotes and exchange genetic material with not only their hosts but also prokaryotes and phages. A few NCLDVs were reported to encode genes conferring resistance to beta­lactam, trimethoprim, or pyrimethamine, suggesting that they are potential vehicles for the transmission of antibiotic resistance genes (ARGs) in the biome. However, the incidence of ARGs across the phylum Nucleocytoviricota, their evolutionary characteristics, their dissemination potential, and their association with virulence factors remain unexplored. Here, we systematically investigated ARGs of 1416 NCLDV genomes including those of almost all currently available cultured isolates and high-quality metagenome-assembled genomes from diverse habitats across the globe. We reveal that 39.5% of them carry ARGs, which is approximately 37 times higher than that for phage genomes. A total of 12 ARG types are encoded by NCLDVs. Phylogenies of the three most abundant NCLDV-encoded ARGs hint that NCLDVs acquire ARGs from not only eukaryotes but also prokaryotes and phages. Two NCLDV-encoded trimethoprim resistance genes are demonstrated to confer trimethoprim resistance in Escherichia coli. The presence of ARGs in NCLDV genomes is significantly correlated with mobile genetic elements and virulence factors.

Deciphering microbial metabolic interactions and their implications for community dynamics in acid mine drainage sediments.

The microbially-mediated reduction processes have potential for the bioremediation of acid mine drainage (AMD), which represents a worldwide environment problem. However, we know little about the microbial interactions in anaerobic AMD sediments. Here we utilized genome-resolved metagenomics to uncover the nature of cooperative and competitive metabolic interactions in 90 AMD sediments across Southern China. Our analyses recovered well-represented prokaryotic communities through the reconstruction of 2625 population genomes. Functional analyses of these genomes revealed extensive metabolic handoffs which occurred more frequently in nitrogen metabolism than in sulfur metabolism, as well as stable functional redundancy across sediments resulting from populations with low genomic relatedness. Genome-scale metabolic modeling showed that metabolic competition promoted microbial co-occurrence relationships, suggesting that community assembly was dominated by habitat filtering in sediments. Notably, communities colonizing more extreme conditions tended to be highly competitive, which was typically accompanied with increased network complexity but decreased stability of the microbiome. Finally, our results demonstrated that heterotrophic Thermoplasmatota associated with ferric iron and sulfate reduction contributed most to the elevated levels of competition. Our study shed light on the cooperative and competitive metabolisms of microbiome in the hazardous AMD sediments, which may provide preliminary clues for the AMD bioremediation in the future.

Nutritional quality of food purchases during the COVID-19 public health crisis: An analysis of geographic disparities in North Carolina.

Objective: To examine geographic disparities in the nutritional quality of food purchases during the COVID-19 public health crisis in North Carolina (NC). Methods: Using shopper-level longitudinal transaction records between October 2019- and December 2020 from NC's largest grocery retailer, we fit mixed-effect models to examine disparities in the nutritional quality of food purchases among shoppers in counties with different levels of socioeconomic development and how such disparities changed after March 2020, accounting for other observed and contextual factors. Results: Shoppers in counties with lower development levels purchased a larger share of calories from least healthy foods and a smaller share from healthier foods compared to shoppers in counties with higher development levels. These disparities were slightly attenuated for the least healthy foods and did not change for healthier foods after the onset of the COVID crisis. Conclusion: Despite existing nutritional disparities among shoppers in counties with different levels of socioeconomic development, we did not observe a large-scale accentuation of inequities in dietary quality during the COVID-19 crisis. This pattern may have resulted from programmatic responses to mitigate the adverse effects of the COVID crisis on vulnerable populations. Future work should further explore the role of such responses.

National age-specific mortality trends for cervical and breast cancers in urban-rural areas of China from 2009 to 2021: a population-based analysis.

BACKGROUND: Cervical and breast cancers are among the top 4 leading causes of cancer-related mortality in women. This study aimed to examine age-specific temporal trends in mortality for cervical and breast cancers in urban and rural areas of China from 2009 to 2021. METHODS: Age-specific mortality data for cervical and breast cancers among Chinese women aged 20-84 years were obtained from China's National Disease Surveillance Points system spanning the years 2009 to 2021. Negative binomial regression models were utilized to assess urban-rural differences in mortality rate ratios, while Joinpoint models with estimated average annual percent changes (AAPC) and slopes were employed to compare temporal trends and the acceleration of mortality rates within different age groups. RESULTS: From 2009 to 2021, there was a relative increase in age-specific mortality associated with the two cancers observed in rural areas compared with urban areas. A rising trend in the screening age of 35-64 [AAPC: 4.0%, 95% confidence interval (CI) 0.5-7.6%, P = 0.026] for cervical cancer was noted in rural areas, while a stable trend (AAPC: - 0.7%, 95% CI - 5.8 to 4.6%, P = 0.78) was observed in urban areas. As for breast cancer, a stable trend (AAPC: 0.3%, 95% CI - 0.3 to 0.9%, P = 0.28) was observed in rural areas compared to a decreasing trend (AAPC: - 2.7%, 95% CI - 4.6 to - 0.7%, P = 0.007) in urban areas. Urban-rural differences in mortality rates increased over time for cervical cancer but decreased for breast cancer. Mortality trends for both cervical and breast cancers showed an increase with age across 4 segments, with the most significant surge in mortality observed among the 35-54 age group across urban and rural areas, periods, and regions in China. CONCLUSIONS: Special attention should be given to women aged 35-54 years due to mortality trends and rural-urban disparities. Focusing on vulnerable age groups and addressing rural-urban differences in the delivery of cancer control programs can enhance resource efficiency and promote health equity.

Neutrophil Percentage to Albumin Ratio as a Predictor for Coronary Slow Flow Phenomenon in Patients with Myocardial Ischemia with No Obstructive Coronary Arteries.

Background: Accumulating evidences suggest that low-grade inflammatory response plays a key role in the pathophysiology of coronary slow flow phenomenon (CSFP). As a new hematological inflammatory indicator, the neutrophil percentage to albumin ratio (NPAR) and its role in the occurrence and development of CSFP remains unclear. In this study, we aimed to investigate the predictive value of NPAR in the presence of CSFP in patients with myocardial ischemia and no obstructive coronary arteries (INOCA). Methods: In total, 1323 individuals with INOCA were included in this study. 85 patients developed CSFP were included in the CSFP group. 1:2 age-and sex-matched patients were selected from the absence of CSFP, with normal blood flow, as the control group. Clinical characteristics, laboratory parameters, and angiographic findings were compared between groups. NPAR was also calculated to explore its relationship with CSFP. Results: NPAR was significantly higher in the CSFP patients than in the controls (19.3±2.5 vs 16.7±1.8, p<0.001). The NPAR increased with the number of coronary arteries involved in CSFP. Multivariate logistic regression analysis showed that an elevated NPAR level was an independent predictor of CSFP (OR 1.915, 95% CI 1.612-2.275, P < 0.001). The ROC curve showed that when NPAR was > 17.39, the sensitivity and specificity were 90.6% and 78.8%, respectively, and the area under the ROC curve (AUC) was 0.860 (95% CI: 0.811-0.909, P < 0.001). The AUC of neutrophil percentage was 0.845 (95% CI: 0.794-0.897, p < 0.001), and that of albumin was 0.808 (95% CI: 0.753-0.864, p < 0.001). Conclusion: Elevated NPAR levels are an independent predictor of CSFP in patients with INOCA. NPAR could improve the predictive value of CSFP compared with neutrophil percentage or albumin ratio alone.

Anti-virulence potential of iclaprim, a novel folic acid synthesis inhibitor, against Staphylococcus aureus.

Infections caused by Staphylococcus aureus pose a significant global public problem. Therefore, new antibiotics and therapeutic strategies are needed to combat this pathogen. This investigation delves into the effects of iclaprim, a newly discovered inhibitor of folic acid synthesis, on S. aureus virulence. The phenotypic and genotypic effects of iclaprim were thoroughly examined in relation to virulence factors, biofilm formation, and dispersal, as well as partial virulence-encoding genes associated with exoproteins, adherence, and regulation in S. aureus MW2, N315, and ATCC 25923. Then, the in vivo effectiveness of iclaprim on S. aureus pathogenicity was explored by a Galleria mellonella larvae infection model. The use of iclaprim at sub-inhibitory concentrations (sub-MICs) resulted in a reduction of α-hemolysin (Hla) production and a differential effect on the activity of coagulase in S. aureus strains. The results of biofilm formation and eradication assay showed that iclaprim was highly effective in depolymerizing the mature biofilm of S. aureus strains at concentrations of 1 MIC or greater, however, inhibited the biofilm-forming ability of only strains N315 and ATCC 25923 at sub-MICs. Interestingly, treatment of strains with sub-MICs of iclaprim resulted in significant stimulation or suppression of most virulence-encoding genes expression. Iclaprim did not affect the production of δ-hemolysin or staphylococcal protein A (SpA), nor did it impact the total activity of proteases, nucleases, and lipases. In vivo testing showed that sub-MICs of iclaprim significantly improves infected larvae survival. The present study offered valuable insights towards a better understating of the influence of iclaprim on different strains of S. aureus. The findings suggest that iclaprim may have potential as an anti-virulence and antibiofilm agent, thus potentially mitigating the pathogenicity of S. aureus and improving clinical outcomes associated with infections caused by this pathogen. KEY POINTS: • Iclaprim effectively inhibits α-hemolysin production and biofilm formation in a strain-dependent manner and was an excellent depolymerizing agent of mature biofilm • Iclaprim affected the mRNA expression of virulence-encoding genes associated with exoproteins, adherence, and regulation • In vivo study in G. mellonella larvae challenged with S. aureus exhibited that iclaprim improves larvae survival.

Four-Year Treatment Effect of Custom-Made Foot Orthosis on Pediatric Symptomatic Accessory Navicular Bone Combined with Flexible Flatfoot.

Purpose: Congenital accessory navicular bone (ANB) is a common variant in the foot and is prone to cause several clinical symptoms. Wearing custom-made foot orthosis is considered a desirable option; however, there is limited evidence of its effectiveness. This study aims to report the mid-term effect of foot orthosis for symptomatic pediatric ANBs. Methods: School-age children with symptomatic ANBs combined with flexible flatfoot in the authors' institute were recruited and got custom-made foot orthosis treatment. They were followed up over 4 years. The general characteristics of these children were collected before treatment, including age, gender, and body mass index (BMI). The indicators of foot symptoms, including frequency and location of pain, visual analogue scale (VAS), arch index (AI), and hind foot valgus angle (HVA), were measured during pretreatment and at the last follow-up. Results: Twenty-seven children were recruited for this study. After 4 years of custom-made foot orthosis treatment, significant improvements showed in pain frequency, VAS, AI, and HVA (P < 0.001). Type II ANBs showed a higher pain index pretreatment (P < 0.001) and reduced after treatment (P < 0.001). Conclusion: Mid-term effect of custom-made foot orthosis is inspiring in clinical symptoms of pediatric congenital ANBs combined with flexible flatfoot and may be an optional nonoperative treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-024-01210-7.

Daily Sedation Interruption vs Continuous Sedation in Pediatric Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis.

Importance: The effectiveness of daily sedation interruption (DSI, defined as temporary interruption of sedation) has yet to be demonstrated in critically ill pediatric patients. Objective: To compare the clinical outcomes of DSI vs continuous intravenous (IV) sedation in patients receiving invasive mechanical ventilation (MV) support in the pediatric intensive care unit (PICU). Data Sources: A systematic search for studies was conducted using predefined keywords and Medical Subject Headings in 5 major databases (PubMed, Embase, Web of Science, CINAHL [Cumulated Index to Nursing and Allied Health Literature], and Cochrane Central Register of Controlled Trials) from database inception to October 31, 2023. Study Selection: Retrospective and prospective observational studies, randomized clinical trials (RCTs), and systematic reviews were assessed for inclusion. Studies were eligible if they compared DSI to continuous IV sedation in patients aged 18 years or younger requiring MV in the PICU. Data Extraction and Synthesis: Study characteristics, including the types of sedation, sedation protocols, and clinical outcomes, were extracted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. A random-effects model was used to pool results from articles for the meta-analysis. Main Outcomes and Measures: The primary outcomes of interest were duration of MV and length of PICU stay. Secondary outcomes included total sedative dose requirement, adverse events (eg, complications associated with MV, withdrawal, and delirium), and mortality. Results: A total of 6 RCTs with 2810 pediatric patients (1569 males [55.8%]; mean age, 26.5 [95% CI, 15.0-37.9] months) were included in the final analysis; patients had a mean PRISM (Pediatric Risk of Mortality) score of 13.68 (95% CI, 10.75-16.61). Compared with continuous IV sedation, DSI was associated with a reduction in length of PICU stay (5 studies, n = 2770; mean difference [MD], -1.45 [95% CI, -2.75 to -0.15] days; P = .03]. There was no difference in MV duration (5 studies, n = 2750; MD, -0.93 [95% CI, -1.89 to 0.04] days; P = .06), total doses of midazolam (3 studies, n = 191; MD, -1.66 [95% CI, -3.95 to 0.63] mg/kg) and morphine used (2 studies, n = 189; MD, -2.63 [95% CI, -7.01 to 1.75] mg/kg), or adverse events (risk ratio [RR], 1.03 [95% CI, 0.74-1.42]; P = .88). There was no difference in mortality between patients exposed vs not exposed to DSI (RR, 0.89 [95% CI, 0.55-1.46]; P = .65). Conclusions and Relevance: This systematic review and meta-analysis found that use of DSI in pediatric patients was associated with reduced length of PICU stay with no increase in adverse events. Further research is needed to ascertain whether this strategy is associated with improved neurodevelopmental outcomes in PICU survivors.

Metabolically healthy obesity and left ventricular geometric remodelling in Chinese children.

AIM: To investigate the association between metabolically healthy obesity (MHO) and left ventricular geometric remodelling in Chinese children. MATERIALS AND METHODS: This cross-sectional study used data from two population-based samples in China, including 2871 children aged 6-11 years. Weight status was defined based on body mass index according to the World Health Organization growth chart. Metabolic status was defined based on the 2018 consensus-based criteria proposed by Damanhoury et al. Obes Rev 2018;19:1476-1491 (blood pressure, lipids and glucose). Left ventricular geometric remodelling was determined as concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. Multinomial logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for the association between categories of weight and metabolic status and left ventricular geometric remodelling. RESULTS: Compared with children with metabolically healthy normal weight, those with MHO had higher odds of left ventricular geometric remodelling, with adjusted ORs (95% CIs) of 2.01 (1.23-3.28) for concentric remodelling, 6.36 (4.03-10.04) for eccentric hypertrophy, and 17.07 (7.97-36.58) for concentric hypertrophy. Corresponding ORs (95% CIs) were 2.35 (1.47-3.75), 10.85 (7.11-16.55), and 18.56 (8.63-39.94), respectively, for children with metabolically unhealthy obesity. In contrast, metabolically unhealthy normal weight was not associated with higher odds of left ventricular geometric remodelling. Findings were consistent in sensitivity analyses that used different definitions of weight and metabolic status and left ventricular geometric remodelling. CONCLUSIONS: Children with MHO had higher odds of left ventricular geometric remodelling than their metabolically healthy normal weight counterparts. Our findings suggest MHO may not be a benign condition for cardiac health in children.