Lipase-Responsive Lignin Composite Nanoparticles for the Delivery of Insoluble Bioactives.

Low solubility and chemical instability are the main problems with insoluble bioactives. Lignin, with its exceptional biological properties and amphiphilicity, holds promise as a delivery system material. In this study, glycerol esters were incorporated into alkali lignin (AL) through ether and ester bonds, resulting in the successful synthesis of three hydrophobically modified alkali lignins (AL-OA, AL-OGL, and AL-SAN-OGL). Subsequently, lignin composite nanoparticles (LNPs@BC) encapsulating ß-carotene were prepared using antisolvent and sonication techniques. The encapsulation rates were determined to be 37.69 ± 2.21%, 84.01 ± 5.55%, 83.82 ± 5.23%, and 83.11 ± 5.85% for LNP@BC-1, LNP@BC-2, LNP@BC-3, and LNP@BC-4, respectively, with AL, AL-OA, AL-OGL, and AL-SAN-OGL serving as the wall materials under optimized preparation conditions. The antioxidant properties and UV-absorbing capacity of the four lignins were characterized, demonstrating their efficacy in enhancing the oxygen and photostability of ß-carotene. Following 6 h of UV irradiation, LNP@BC-4 exhibited a retention rate of 83.03 ± 2.85% for ß-carotene, while storage under light-protected conditions at 25 °C for 7 days retained 73.33 ± 7.62% of ß-carotene. Furthermore, the encapsulated ß-carotene demonstrated enhanced thermal and storage stability. In vitro release experiments revealed superior stability of LNPs@BC in simulated gastric fluid (SGF), with ß-carotene retention exceeding 77% in both LNP@BC-3 and LNP@BC-4. LNP@BC-4 exhibited the highest bioaccessibility in simulated intestinal fluid (SIF) at 46.96 ± 0.80%, that LNP@BC-1 only achieved 10.87 ± 0.90%. The enzymatic responsiveness of AL-OGL and AL-SAN-OGL was confirmed. Moreover, LNPs@BC exhibited no cytotoxicity toward L929 cells and demonstrated excellent hemocompatibility. In summary, this study introduces a novel enzyme-responsive modified lignin that has promising applications in the fields of food, biomedicine, and animal feed.

Association between TB delay and TB treatment outcomes in HIV-TB co-infected patients: a study based on the multilevel propensity score method.

BACKGROUND: HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. METHODS: We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). RESULTS: The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. CONCLUSIONS: HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.

Bacillus velezensis Strain HN-Q-8 Induced Resistance to Alternaria solani and Stimulated Growth of Potato Plant.

Bacillus velezensis HN-Q-8, isolated in our previous study, has an antagonistic effect on Alternaria solani. After being pretreated with a fermentation liquid with HN-Q-8 bacterial cell suspensions, the potato leaves inoculated with A. solani displayed smaller lesion areas and less yellowing than the controls. Interestingly, the activity levels of superoxide dismutase, peroxidase, and catalase in potato seedlings were enhanced by the addition of the fermentation liquid with bacterial cells. Additionally, the overexpression of key genes related to induced resistance in the Jasmonate/Ethylene pathway was activated by the addition of the fermentation liquid, suggesting that the HN-Q-8 strain induced resistance to potato early blight. In addition, our laboratory and field experiments showed that the HN-Q-8 strain can promote potato seedling growth and significantly increase tuber yield. The root activity and chlorophyll content of potato seedlings were significantly increased along with the levels of indole acetic acid, gibberellic acid 3, and abscisic acid upon addition of the HN-Q-8 strain. The fermentation liquid with bacterial cells was more efficient in inducing disease resistance and promoting growth than bacterial cell suspensions alone or the fermentation liquid without bacterial cells. Thus, the B. velezensis HN-Q-8 strain is an effective bacterial biocontrol agent, augmenting the options available for potato cultivation.

Formula Milk Supplementation and Bone Acquisition in 4-6 Years Chinese Children: A 12-Month Cluster-Randomized Controlled Trial.

Dairy foods are crucial for adequate calcium intake in young children, but scarce data are available on the effects of formula milk on bone acquisition. This cluster-randomized controlled trial investigated the effects of the supplementation of formula milk on bone health in rural children accustomed to a low-calcium diet between September 2021 and September 2022. We recruited 196 healthy children aged 4-6 years from two kindergartens in Huining County, Northwest China. A class-based randomization was used to assign them to receive 60 g of formula milk powder containing 720 mg calcium and 4.5 µg vitamin D or 20-30 g of bread per day for 12 months, respectively. Bone mineral density (BMD) and bone mineral content (BMC) at the left forearm and calcaneus, bone biomarkers, bone-related hormones/growth factors, and body measures were determined at baseline, 6, and 12 months. A total of 174 children completed the trial and were included in the analysis. Compared with the control group, formula milk intervention showed significant extra increments in BMD (3.77% and 6.66%) and BMC (4.55% and 5.76%) at the left forearm at 6th and 12th months post-intervention (all p < 0.001), respectively. Similar trends were observed in BMD (2.83%) and BMC (2.38%) in the left calcaneus at 6 months (p < 0.05). The milk intervention (vs. control) also showed significant changes in the serum concentrations of osteocalcin level (-7.59%, p = 0.012), 25-hydroxy-vitamin-D (+5.54%, p = 0.001), parathyroid hormone concentration (-15.22%, p = 0.003), and insulin-like growth factor 1 (+8.36%, p = 0.014). The percentage increases in height were 0.34%, 0.45%, and 0.42% higher in the milk group than in the control group after 3-, 6-, and 9-month intervention, respectively (p < 0.05). In summary, formula milk supplementation enhances bone acquisition at the left forearm in young Chinese children.

Sunscreens: Misconceptions and Misinformation.

Over the past 70 years, sunscreens have evolved from beach products designed to prevent sunburn to more cosmetically elegant skincare products intended to protect against multiple long-term adverse consequences of characteristically low-intensity daily UV and visible light exposure. Sunscreen testing and labeling intended to quantify such protection are unfortunately often misunderstood by users and have also led to illegal misleading and potentially dangerous industry practices. Changes in regulatory requirements, better policing, and more informative sunscreen labeling would benefit users and their physician advisors.

A novel of new class II bacteriocin from Bacillus velezensis HN-Q-8 and its antibacterial activity on Streptomyces scabies.

Potato common scab is a main soil-borne disease of potato that can significantly reduce its quality. At present, it is still a challenge to control potato common scab in the field. To address this problem, the 972 family lactococcin (Lcn972) was screened from Bacillus velezensis HN-Q-8 in this study, and an Escherichia coli overexpression system was used to obtain Lcn972, which showed a significant inhibitory effect on Streptomyces scabies, with a minimum inhibitory concentration of 10.58 µg/mL. The stability test showed that Lcn972 is stable against UV radiation and high temperature. In addition, long-term storage at room temperature and 4°C had limited effects on its activity level. The antibacterial activity of Lcn972 was enhanced by Cu2+ and Ca2+, but decreased by protease K. The protein was completely inactivated by Fe2+. Cell membrane staining showed that Lcn972 damaged the cell membrane integrity of S. scabies. Scanning electron microscope (SEM) and transmission electron microscope (TEM) observations revealed that the hyphae of S. scabies treated with Lcn972 were deformed and adhered, the cell membrane was incomplete, the cytoplasm distribution was uneven, and the cell appeared hollow inside, which led to the death of S. scabies. In conclusion, we used bacteriocin for controlling potato common scab for the first time in this study, and it provides theoretical support for the further application of bacteriocin in the control of plant diseases.

Accurate identification of kidney injury progression via a fluorescent biosensor array.

Identifying the progress of kidney injury may aid the effective treatment and intervention. Herein, we developed a fluorescent biosensor array for instantaneous and accurate identification of the kidney injury progression via "doubled" signals. The multichannel biosensor array consisted of polydopamine-polyethyleneimine (PDA-PEI) and multicolor-labelled different length of DNAs including AAAAA-Cyanine7 (5A-Cy7), AAAAAAAAAA-Texas Red (10A-Texas Red), and AAAAAAAAAAAAAAAAAAAA-VIC (20A-VIC). Facing to the variety of protein in urine with alterable charge accompanied with different progress of kidney injury, the composition of urine replaces the DNA signal molecules, forming their special fluorescence patterns. Taking the size of protein into consideration, the original three variables induced by the protein charge were extended to six variables induced by the two factors of protein particle size and charge difference, which could provide a more accurate strategy to identify the progress of kidney injury. Notably, this strategy not only opened up new perspective for identification the progress of kidney injury via the size and charge of urine protein, but also improved the resolving power of sensor array by increasing the number of sensor elements for extending their potential application to various diseases.

Identification of novel candidate genes and small molecule drugs in ovarian cancer by bioinformatics strategy.

Background: Ovarian cancer (OC) is the most lethal type of malignancies in the female reproductive system. This study aimed to identify novel biomarkers and potential small molecule drugs in OC by integrating two expression profile datasets. Methods: GSE18520 and GSE14407 from the Gene Expression Omnibus (GEO) database were selected and the overlapped differentially expressed genes (DEGs) were detected. The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis were performed to establish the protein-protein interaction (PPI) network of DEGs and identified the hub genes. Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine database and The Human Protein Atlas (HPA) were used to validate the expression of the identified hub genes. The prognostic value of these hub genes were evaluated by the Kaplan Meier plotter online tool. The expression of NCAPG was further explored by immunohistochemistry in our OC tissues. Moreover, CMap database was used to look for prospective small compounds with therapeutic efficacy based on OC RNA-seq. Results: A total of 433 DEGs were identified. The DEGs were mainly enriched in negative regulation of transcription and pathways in cancer. A PPI network was constructed with 344 nodes and 1,596 interactions. The top ten module genes were chosen as hub genes. Among which, survival analysis showed that patients with high expression of CCNB1, TOP2A, NUSAP1, NCAPG, KIF20A and DLGAP5 had poorer survival results than those with low expression. These six genes were all overexpressed in OC tissue by means of bioinformatics analysis. In our clinical patients, the expression rate of NCAPG in OC tissues was significantly higher than that in benign serous ovarian cystadenoma and borderline serous ovarian cystadenoma tissues. Meanwhile, several small molecules with potential therapeutic efficacy against OC were identified in our study. Conclusions: By means of bioinformatics analysis, we identified six real hub genes and indicated a group of candidate small molecule drugs as adjunctive agents for OC. They could be the potential novel biomarkers for the diagnosis and promising therapeutic targets of OC.

Structure-guided and phage-assisted evolution of a therapeutic anti-EGFR antibody to reverse acquired resistance.

Acquired resistance to cetuximab in colorectal cancers is partially mediated by the acquisition of mutations located in the cetuximab epitope in the epidermal growth factor receptor (EGFR) ectodomain and hinders the clinical application of cetuximab. We develop a structure-guided and phage-assisted evolution approach for cetuximab evolution to reverse EGFRS492R- or EGFRG465R-driven resistance without altering the binding epitope or undermining antibody efficacy. Two evolved cetuximab variants, Ctx-VY and Ctx-Y104D, exhibit a restored binding ability with EGFRS492R, which harbors the most common resistance substitution, S492R. Ctx-W52D exhibits restored binding with EGFR harboring another common cetuximab resistance substitution, G465R (EGFRG465R). All the evolved cetuximab variants effectively inhibit EGFR activation and downstream signaling and induce the internalization and degradation of EGFRS492R and EGFRG465R as well as EGFRWT. The evolved cetuximab variants (Ctx-VY, Ctx-Y104D and Ctx-W52D) with one or two amino acid substitutions in the complementarity-determining region inherit the optimized physical and chemical properties of cetuximab to a great extent, thus ensuring their druggability. Our data collectively show that structure-guided and phage-assisted evolution is an efficient and general approach for reversing receptor mutation-mediated resistance to therapeutic antibody drugs.

Facile Generation of Potent Bispecific Fab via Sortase A and Click Chemistry for Cancer Immunotherapy.

Bispecific antibodies (BsAbs) for T cell engagement have shown great promise in cancer immunotherapy, and their clinical applications have been proven in treating hematological malignance. Bispecific antibody binding fragment (BiFab) represents a promising platform for generating non-Fc bispecific antibodies. However, the generation of BiFab is still challenging, especially by means of chemical conjugation. More conjugation strategies, e.g., enzymatic conjugation and modular BiFab preparation, are needed to improve the robustness and flexibility of BiFab preparation. We successfully used chemo-enzymatic conjugation approach to generate bispecific antibody (i.e., BiFab) with Fabs from full-length antibodies. Paired click handles (e.g., N3 and DBCO) was introduced to the C-terminal LPETG tag of Fabs via sortase A mediated transpeptidation, followed by site-specific conjugation between two click handle-modified Fabs for BiFab generation. Both BiFabCD20/CD3 (EC50 = 0.26 ng/mL) and BiFabHer2/CD3 exhibited superior efficacy in mediating T cells, from either PBMC or ATC, to kill target tumor cell lines while spared antigen-negative tumor cells in vitro. The BiFabCD20/CD3 also efficiently inhibited CD20-positive tumor growth in mouse xenograft model. We have established a facile sortase A-mediated click handle installation to generate homogeneous and functional BiFabs. The exemplary BiFabs against different targets showed superior efficacy in redirecting and activating T cells to specifically kill target tumor cells, demonstrating the robustness of sortase A-mediated "bio-click" chemistry in generating various potent BiFabs. This approach also holds promise for further efficient construction of a Fab derivative library for personalized tumor immunotherapy in the future.

A nanosensor for precise discrimination of nephrotoxic drug mechanisms via dynamic fluorescence fingerprint strategy.

Drug-induced kidney injury causes structural or functional abnormalities of kidney, seriously affecting clinical practice and drug discovery. However, rapid and effective identification of nephrotoxic drug mechanisms is yet a challenging task arising from the complexity and diversity of various nephrotoxic mechanisms. Herein, we have constructed a polydopamine-polyethyleneimine/quantum dots sensor to instantaneously read out the nephrotoxic drugs mechanisms based on the disparate cell surface phenotypes. Cell surface components induced by multiple nephrotoxic drugs can change the fluorescence emission of multicolor quantum dots, generating their corresponding fluorescent fingerprints. The fluorescence response signatures induced by different nephrotoxic agents are gained with 84% accuracy via linear discriminant analysis. Furthermore, taking the time-toxicity relationship into consideration, dynamic fluorescent fingerprint is obtained through continuous monitoring the progress of renal cell damage, achieving 100% precise classification for nephrotoxic mechanisms of four types of antibiotics. Notably, the fluorescent fingerprint-based high-throughput sensor has been demonstrated by successfully distinguishing nephrotoxic drugs in seconds, employing a promising protocol to discriminate the specific mechanism of nephrotoxic drugs, as well as drug safety evaluation.

Evaluation of fecal immunoassays for canine Echinococcus infection in China.

Human echinococcosis is present worldwide but it is in China that disease prevalence is the highest. In western China, especially in the Tibetan Plateau, the burden of echinococcosis is the most important. Dogs are a major definitive host of Echinococcus and monitoring the presence of Echinococcus worms in dogs is therefore essential to efficiently control the disease. Detection kits based on three different technologies including sandwich ELISA, (indirect) ELISA, and gold immunodiffusion, are currently marketed and used in China. The objective of this work was to assess the efficacy of these kits, in particular with respect to sensitivity and specificity. Four fecal antigen detection kits for canine infection reflecting the three technologies were obtained from companies and tested in parallel on 220 fecal samples. The results indicate that the performance is lower than expected, in particular in terms of sensitivity. The best results were obtained with the sandwich ELISA technology. The gold immunofiltration yielded the poorest results. In all cases, further development is needed to improve the performance of these kits which are key components for the control of echinococcosis.

Psychometric properties of the simplified Chinese version of the observer OPTION5 scale.

BACKGROUND: OPTION5 is a scale used to evaluate shared decision making (SDM) in health care from an observer's perspective; however, to date, there is no simplified Chinese version of this scale. OBJECTIVES: This study aims to produce a simplified Chinese version of the OPTION5 scale and to test its psychometric properties. METHODS: One rater observed and audio-recorded consultations between general practitioners (GPs) and chronically ill patients in a Beijing community health service center (CHSC) from May to June 2019. Meanwhile, demographic data of the patients and GPs were collected via information forms. Two raters assessed inter- and intra-rater reliability by calculating the intraclass correlation coefficient (ICC) and weighted Cohen's Kappa values. Internal consistency was assessed using Cronbach's α value. Concurrent was calculated by Spearman's rank correlation coefficient. RESULTS: A total of 209 consultations were recorded and evaluated. As concerns inter-rater reliability, the ICC of the OPTION5 was 0.859 on the total score level, with Cohen's weighted k ranging from 0.376 (item 5) to 0.649 (item 2) on the single item level. With regard to intra-rater reliability, the ICC was 0.945 on the total score level, with Cohen's weighted k ranging from 0.469 (item 5) to 0.883 (item1) on the single item level. Cronbach's α value of all 5 items amounted to 0.746. Spearman's rank correlation coefficient between OPTION5 and OPTION12 for Chinese versions was 0.660. CONCLUSIONS: The simplified Chinese version of the OPTION5 scale, developed using stringent translation procedures, demonstrated satisfactory psychometric characteristics. Specifically, inter- and intra-rater reliabilities were excellent, while criterion validity was moderate. The simplified Chinese version of the OPTION5 scale can be implemented in clinical settings to evaluate SDM of treatment during consultations between GPs and chronically ill patients.

Specific Inhibition of Tumor Growth by T Cell Receptor-Drug Conjugates Targeting Intracellular Cancer-Testis Antigen NY-ESO-1/LAGE-1.

Despite the significant therapeutic advances in T-cell immunotherapy, many malignancies remain unresponsive, which might be because of the negative regulation of T cells by the tumor microenvironment (TME). T cells discriminate tumor cells and normal cells through T-cell receptors (TCRs); therefore, we generated a novel type of TCR-drug conjugates (TDCs) by referring antibody-drug conjugations (ADCs) to overcome the effects of the TME on T cells while preserving the specificity of TCR for tumor recognition. We selected HLA-A2/NY-ESO-1157-165 (peptide NY-ESO-1157-165 in complex with human leukocyte antigen serotype HLA-A*02:01) as the antigen and the antigen-specific TCR (1G4113) as the carrier. By sortase A-mediated ligation, we obtained three NY-TCR-vcMMAEs and further studied their properties, antitumor activity, and toxicity in vitro and in vivo. We found that all the NY-TCR-vcMMAEs had high endocytosis efficiency and specifically killed HLA-A2/NY-ESO-1157-165 positive tumor cells. In xenograft models, one of the TDCs, NY-TCR-2M, was effectively and specifically distributed into tumor tissues and inhibited tumor growth without inducing obvious toxicity. Our results demonstrated that TCRs can be carriers of toxic payloads and that the TDCs thus formed can specifically inhibit tumor growth, neglecting the immune microenvironment.

Rapid and sensitive detection of NGAL for the prediction of acute kidney injury via a polydopamine nanosphere/aptamer nanocomplex coupled with DNase I-assisted recycling amplification.

Early detection of acute kidney injury (AKI) is important, as early intervention and treatment can prevent further kidney injury and improve kidney health. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as the earliest and promising non-invasive biomarker of AKI in urine, and has been used as a new predictive biomarker of AKI in the bench-to-bedside journey. In this work, a nanocomplex composed of a polydopamine nanosphere (PDANS) and a fluorophore-labelled aptamer has been constructed for the detection of NGAL using a DNase I-assisted recycling amplification strategy. After the addition of NGAL, the fluorescence intensity increases linearly over the NGAL concentration range from 12.5 to 400 pg mL-1. The limit of detection of this strategy is found to be 6.25 pg mL-1, which is almost 5 times lower than that of the method that does not involve DNase I. The process can be completed within 1 h, indicating a fast fluorescence response. Furthermore, the method using the nanocomplex coupled with DNase I has been successfully utilized for the detection of NGAL in the urine from cisplatin-induced AKI and five-sixths nephrectomized mice, demonstrating its promising ability for the early prediction of AKI. This method also demonstrates the protective effect of the Huangkui capsule on AKI, and provides an effective way to screen potentially protective drugs for renal disease.

Integrating the Polydopamine Nanosphere/Aptamers Nanoplatform with a DNase-I-Assisted Recycling Amplification Strategy for Simultaneous Detection of MMP-9 and MMP-2 during Renal Interstitial Fibrosis.

Matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) play important roles in the progression of renal interstitial fibrosis (RIF). There is an increasing demand to construct a novel method for the simultaneous detection of MMP-9 and MMP-2 to monitor the progression of RIF. Herein, a strategy based on the nanoplatform composed of the polydopamine nanosphere and fluorescence-labeled aptamers is developed to simultaneously detect MMP-9 and MMP-2 with DNase-I-assisted recycling signal amplification. In the light of tracing the recovered fluorescence intensity at 520 and 610 nm upon adding MMP-9 and MMP-2, the increased fluorescence intensity is linear to the different concentrations of MMP-9 and MMP-2 with the detection limits of 9.6 and 25.6 pg/mL for MMP-9 and MMP-2, respectively. More intriguingly, the results of unilateral ureteral obstruction mice show that the concentration of MMP-9 in urine is increased with the extension of ligation time while the concentration of MMP-2 is reversed, indicating that the ratio of MMP-9 to MMP-2 could be considered as the potential urinary biomarker to evaluate the progress of RIF and the therapeutic effect of Huangkui capsule on RIF. Therefore, this study provides a paradigmatic strategy for the simultaneous detection of the dual markers of RIF, which is promising for the auxiliary clinical diagnosis and assessment of the prognosis of chronic kidney disease.

Cephalosporin Resistance in Escherichia coli Isolated from Children with Septicemia in Mainland China from 2007 to 2017: A Systematic Review and Meta-Analysis.

Background: Septicemia in children in mainland China has recently become a public health concern. Methods: A meta-analysis was performed on studies investigating the prevalence of cephalosporin-resistant Escherichia coli isolated from children with septicemia in mainland China from 2007 to 2017 following a search of relevant databases. Results: A total of 43 articles reporting 11 cephalosporins were included in the review. The results of the meta-analysis revealed that for the first-generation cephalosporins, the pooled summarized prevalence of resistance to cefazolin was 74.96% (95% confidence interval [CI]: 64.79-83.91) and cephalothin resistance was 62.28% (95% CI: 36.45-100). Regarding the second-generation cephalosporins, cefoxitin-resistant E. coli comprised 23.85% (95% CI: 10.60-40.40) and cefuroxime resistance was 60.32% (95% CI: 51.25-68.73). For the third-generation cephalosporins, the pooled summarized prevalence of resistance was 51.34% for cefotaxime (95% CI: 40.08-62.54), 40.43% for ceftazidime (95% CI: 31.07-50.15), 45.51% for cefoperazone (95% CI: 20.41-70.61), 12.10% for cefoperazone/sulbactam (95% CI: 6.55-18.76), 62.99% for ceftriaxone (95% CI: 55.00-70.98), and 0% for cefotetan. Among the fourth-generation cephalosporins, resistance to cefepime was 34.08% (95% CI: 25.91-43.31). Conclusions: Most third-generation cephalosporins (e.g., cefotaxime and ceftriaxone) retained high resistance rates throughout the 11-year study period without significant changes. The new fourth-generation cephalosporin, cefepime, is rapidly gaining resistance. Interestingly, ceftazidime, cefepime, and cefoperazone/sulbactam showed a recent decreasing trend of drug resistance. These situations may present a risk for treating children with septicemia and should be closely monitored and treated.

The effect of prosthetic alignment on hip and knee joint kinetics in individuals with transfemoral amputation.

BACKGROUND: Prosthetic alignment directly affects the biomechanical loading in individuals with lower-limb amputation, and improper alignment may be contribute to the high incidence of hip and knee osteoarthritis (OA). The biomechanical changes caused by different alignments should be considered in prosthetic fitting. However, the quantitative effect of alignment on the kinetic features of individuals with transfemoral amputation remains unclear. RESEARCH QUESTION: As important kinetics indexes, how are the hip and knee joint moments affected by prosthetic alignment in individuals with transfemoral amputation? METHODS: Gait tests of ten individuals with transfemoral amputation and fifteen individuals without amputation (control group) were performed. Several prosthetic alignment conditions were used, including the so-called "initial" alignment and eight malalignments. The hip and knee joint moments of the individuals with amputation under various alignments were analysed and compared with those of the control group. Statistical analyses were performed by one-way ANOVA, repeated measure multivariate ANOVA, and paired t tests. RESULTS: The peaks and impulses of the hip abductor and external rotator moments on the residual side were significantly smaller than those of the control group (P < 0.0056). The peaks of the hip extensor, adductor and external rotator moments on the intact side were significantly larger than those on the residual side (P < 0.05). Alignment significantly affected the intact hip and knee joint moments for each individual with amputation (P < 0.00625), but there was no consistent effect among individuals. SIGNIFICANCE: The significantly larger hip joint moment on the intact side of individuals with transfemoral amputation may be associated with the higher incidence of hip OA on the intact side. Alignment significantly affects the hip and knee joint moments of each individual with transfemoral amputation, but the individual responses to alignment changes are different. This situation may imply that the method for optimizing alignment should be personalized.