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BACKGROUND: The mouse double minute 2 homolog (MDM2) oncogene exerts oncogenic activities in many cancers and represents a potential therapeutic target. This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of alrizomadlin (APG-115), a novel MDM2/p53 inhibitor, in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with histologically confirmed advanced solid tumors who had progressed to standard treatment or lacked effective therapies were recruited. Alrizomadlin was administered once daily every other day for 21 days of a 28-day cycle until disease progression or intolerable toxicity. RESULTS: A total of 21 patients were enrolled and treated with alrizomadlin; 57.1% were male and the median age was 47 (25-60) years. The maximum tolerated dose of alrizomadlin was 150 mg and the recommended phase II dose was 100 mg. One patient in the 200-mg cohort experienced dose-limiting toxicity of thrombocytopenia and febrile neutropenia. The most common grade 3/4 treatment-related adverse events were thrombocytopenia (33.3%), lymphocytopenia (33.3%), neutropenia (23.8%), and anemia (23.8%). Alrizomadlin demonstrated approximately linear pharmacokinetics (dose range 100-200 mg) and was associated with increased plasma macrophage inhibitory cytokine-1, indicative of p53 pathway activation. Of the 20 assessable patients, 2 [10%, 95% confidence interval (CI) 1.2% to 31.7%] patients achieved partial response and 10 (50%, 95% CI 27.2% to 72.8%) showed stable disease. The median progression-free survival was 6.1 (95% CI 1.7-10.4) months, which was significantly longer in patients with wild-type versus mutant TP53 (7.9 versus 2.2 months, respectively; P < 0.001). Among patients with MDM2 amplification and wild-type TP53, the overall response rate was 25% (2/8) and the disease control rate was 100% (8/8). CONCLUSIONS: Alrizomadlin had an acceptable safety profile and demonstrated promising antitumor activity in MDM2-amplified and TP53 wild-type tumors. This study supports further exploration of alrizomadlin with recommended doses of 100 mg q.o.d. in 21 days on and 7 days off regimen.
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Three-wave (triad) resonance in a uniformly stratified fluid is investigated as a case study of energy transfer among oscillatory modes. The existence of a degenerate triad is demonstrated explicitly, where two components have identical group velocity. An illuminating example is a resonance involving waves from modes 1, 3, 5 families, but many other combinations are possible. The physical applications and nonlinear dynamics of rogue waves derived analytically in the literature are examined. Exact solutions with four free parameters (two related to the amplitudes of the background plane waves, two related to the frequencies of slowly varying envelopes) describe motions localized in both space and time. The differences between rogue waves of the degenerate versus the nondegenerate cases are highlighted. The phase and profile of the degenerate case rogue waves are correlated. The volume or energy of the rogue wave (defined as the total extent or energy contents of the fluid set in motion for the duration of the rogue wave) may change drastically, if the wave envelope parameters vary. Pulsating modes (breathers) have been studied previously by layered-fluid and modified Korteweg-de Vries models. Here we extend the consideration to stratified fluids but for the simpler case of nondegenerate triads. Instabilities of fission and fusion of breathers are confirmed computationally with Floquet analysis. This knowledge should prove useful for energy transfer processes in the oceans.
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PURPOSE: This research was performed to evaluate the relationship between hypertension (HTN) and abdominal obesity index in patients with type 2 diabetes mellitus (T2DM). METHODS: Totally 1657 participants with T2DM (mean age 54 ± 12 years; 38.02% female) were enrolled. They were divided into the groups of HTN (n = 775) and non-HTN (n = 882). Anthropometric and biochemical indicators were measured and collected. A bioelectrical impedance analyzer was used to measure visceral and subcutaneous fat areas. RESULTS: Compared with the HTN group, the non-HTN group had a lower level of Chinese visceral adiposity index (CVAI) (p < 0.001). Meanwhile, among tertiles of CVAI, as CVAI increased, the proportion of patients with HTN increased, which was 33.51%, 44.30%, and 62.50%, respectively. CVAI was shown to have a significant positive correlation with HTN. (r = 0.258, p < 0.001). CVAI was independently related to an elevated risk of HTN by binary logistic regression analyses, and the OR was (95% CI) 1.013 (1.010-1.016, p < 0.001) after adjustment. The area under the receiver operating characteristic curve (AUC) of CVAI predicted HTN in T2DM patients was greater than those of other abdominal obesity indices (p < 0.001). CONCLUSION: We found that CVAI was highly positively correlated with HTN in T2DM. Compared with other indices of abdominal obesity, such as WC, BMI, WHR, VAI, and LAP, the CVAI showed superior discriminative ability in T2DM complicated with HTN. Therefore, more attention should be paid to CVAI in T2DM.
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Diabetes Mellitus Tipo 2 , Hipertensión , Obesidad Mórbida , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Masculino , Obesidad Abdominal/complicaciones , Obesidad Abdominal/diagnóstico , Adiposidad , Índice de Masa Corporal , Obesidad/complicaciones , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/epidemiología , Obesidad Mórbida/complicaciones , China/epidemiologíaRESUMEN
OBJECTIVE: To construct a prediction model for fetal growth restriction (FGR) during the first trimester of pregnancy and evaluate its screening performance. METHODS: This was a prospective cohort study of singleton pregnancies that underwent routine ultrasound screening at 11 to 13 + 6 weeks at the Affiliated Suzhou Hospital of Nanjing Medical University between January 2019 and April 2022. Basic clinical information, ultrasound indicators and serum biomarkers of pregnant women were collected. Fetal weight assessment was based on the fetal growth curve for the Southern Chinese population. FGR was diagnosed according to Delphi consensus criteria. Least absolute shrinkage and selection operator (lasso) regression was used to select variables for inclusion in the model. Discrimination, calibration and clinical effectiveness of the model were evaluated in training and validation cohorts. RESULTS: A total of 1188 pregnant women were included, of whom 108 had FGR. Lasso regression identified seven predictive features, including history of maternal hypertension, maternal smoking or passive smoking, gravidity, uterine artery pulsatility index, ductus venosus pulsatility index and multiples of the median values of placental growth factor and soluble fms-like tyrosine kinase-1. The nomogram prediction model constructed from these seven variables accurately predicted FGR, and the area under the receiver-operating-characteristics curve in the validation cohort was 0.82 (95% CI, 0.74-0.90). The calibration curve and Hosmer-Lemeshow test demonstrated good calibration, and the clinical decision curve and clinical impact curve supported its practical value in a clinical setting. CONCLUSION: The multi-index prediction model for FGR has good predictive value during the first trimester. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Pueblo Asiatico , Retardo del Crecimiento Fetal , Embarazo , Femenino , Humanos , Retardo del Crecimiento Fetal/diagnóstico por imagen , Primer Trimestre del Embarazo , Estudios Prospectivos , Factor de Crecimiento PlacentarioRESUMEN
The construction of an intelligent remote management platform for respiratory therapy, utilizing artificial intelligence (AI) and the electronic medical record system (EMR), has significant potential to improve the management of respiratory therapy in critically ill patients. This platform includes the development of a dedicated respiratory therapy EMR, the integration of data from multiple mechanical ventilators from different vendors and models, and the utilization of AI-assisted analysis to understand the pathophysiology of respiratory diseases and the complex physiological factors that influence specific interventions, thereby supporting diagnosis, treatment guidance, and prognosis prediction. In addtion, a network will be established to provide seamless connectivity between hospitals and wards. The resulting platform enables the collection of medical device data from multiple points within the hospital, real-time data analysis, and timely alarms, thereby facilitating remote data access, centralization of information, and standardization of data. As a result, the platform enables efficient intra-hospital and inter-hospital doctor-patient management. Despite the benefits offered by this platform, certain challenges need to be addressed, including ensuring data privacy and security, as well as managing the financial and human resources required for its implementation and maintenance. Furthermore, continuous optimization of the platform is crucial, and the clinical use of the platform requires appropriate professional training.
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Inteligencia Artificial , Hospitales , Humanos , Ventiladores Mecánicos , Terapia RespiratoriaRESUMEN
A 69-year-old female patient presented to the ophthalmology department with complaints of blurred vision in the left eye for more than 10 days. Her medical history revealed a history of right renal tumor and left pheochromocytoma, which were treated with surgical resection at an external institution. Ophthalmic examination revealed a temporal superior cup-shaped optic disc pit in the left eye, along with a macular hole approximately 1/5 the size of the optic disc diameter in the macular region. Additionally, peripheral retinal examination at the 6 o'clock and 11 o'clock positions showed vascular tumors, each approximately 1.5 times the size of the optic disc diameter. Based on the patient's medical history, fundus findings, and auxiliary examination results, a diagnosis of macular hole in the left eye, optic disc pit in the left eye, and Von Hippel-Lindau (VHL) syndrome was established. Subsequently, the patient underwent left vitrectomy and macular hole repair surgery, leading to an improvement in visual acuity.
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Anomalías del Ojo , Disco Óptico , Perforaciones de la Retina , Enfermedad de von Hippel-Lindau , Humanos , Femenino , Anciano , Fondo de OjoAsunto(s)
Huesos , Síndrome de Cushing , Humanos , Síndrome de Cushing/complicaciones , Huesos/metabolismoRESUMEN
To address the issue of low efficiency in extracting plasmid DNA (pDNA) from Lactobacillus plantarum by breaking the cell wall, we proposed an effective pretreatment scheme. This study investigated the impacts of lysozyme concentrations and glucose, as well as centrifugal forces during lysozyme removal in the pretreatment system. The efficiency of pDNA extraction was assessed using non-staining method, acridine orange staining method (AO staining) and agarose gel electrophoresis (AGE). Furthermore, the glucose high lysozyme method was compared to the commercial kit method and the lysozyme removal method using L. plantarum PC518, 9L15, JS193 and Staphylococcus aureus USA300. The results indicated that the pDNA extraction concentrations from the four tested strains were increased by 8.9, 7.2, 8.5, and 3.6 times, respectively, compared to the commercial kit method. Furthermore, they increased by 1.9, 1.5, 1.8, and 1.4 times, respectively, compared to the lysozyme removal method. The maximum average concentration of pDNA extraction (from L. plantarum PC518) reached 590.8 ± 31.9 ng/ul. In conclusion, the incorporation of sugar, high concentration lysozyme and mild lysozyme removal proved to be effective enhancements in improving the efficiency of pDNA extraction from L. plantarum. Using the pretreatment scheme, the concentration of pDNA extraction was significantly increased, approaching levels comparable to pDNA extraction from Gram-negative bacteria.
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Muramidasa , Azúcares , Muramidasa/genética , Plásmidos/genética , ADN , GlucosaRESUMEN
OBJECTIVES: Sarcopenia is recognized as a major public health concern because of its association with several adverse health events. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation reportedly delays the loss of muscle mass and function; however, the effect of HMB on sarcopenia remains inconclusive. We aimed to evaluate the impact of HMB intervention on muscle strength, physical performance, body compositions, and inflammatory factors in older adults with sarcopenia. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING AND PARTICIPANTS: This study included subjects aged ≥60 years with sarcopenia which were assigned to the HMB group (HMBG, n=18) and the placebo group (PG, n=16). INTERVENTION: The HMBG and PG were supplied with HMB and placebo products twice daily for 12 weeks, and both received resistance exercise training twice a week in 12 weeks. MEASUREMENTS: Hand grip strength was selected as the primary outcome; gait speed, five-time chair stand test, body composition and inflammatory indicators were selected as the secondary outcomes. The differences in changes from baseline between the two groups were analyzed using the analysis of covariance(ANCOVA). RESULTS: After the 12-week intervention, the HMBG demonstrated significantly greater improvements in handgrip strength (4.61(95%CI:2.93,6.28) kg, P<0.001), gait speed (0.11(95%CI:0.02,0.20)m/s, P=0.014), five-time chair stand test (-3.65 (95%CI:-5.72, -1.58)s, P=0.001), muscle quality (2.47(95%CI:1.15,3.80),kg.kg-1 P=0.001) and tumor necrosis factor-like weak inducer of apoptosis (-15.23(95%CI:-29.80,-0.66)pmol/mL, P=0.041) compared with the PG; no significant differences in skeletal muscle mass, skeletal muscle index, and other body composition parameters were found between the two groups. CONCLUSION: In older adults with sarcopenia, HMB significantly enhance the effect of resistance exercise training on muscle strength, physical performance, muscle quality, and reduced inflammatory factors. Therefore, HMB supplementation could be an effective treatment for sarcorpenia. The trial protocol was registered at http://www.chictr.org.cn/showproj.aspx?proj=47571 as ChiCTR2000028778.
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Sarcopenia , Humanos , Anciano , Sarcopenia/tratamiento farmacológico , Fuerza de la Mano/fisiología , Fuerza Muscular/fisiología , Músculo Esquelético/fisiología , Método Doble Ciego , Suplementos DietéticosRESUMEN
Objective: To investigate the risk factors of diabetic nephropathy (DN) in primary type 2 diabetes mellitus (T2DM) patients and to quantitatively analyze the risk of DN by nomogram modeling. Methods: A total of 1 588 primary T2DM patients from 17 townships and streets in Zhejiang Province were enrolled from June 2018 to August 2018 in this cross-sectional study, with an average age of (56.8±10.1) years (50.06% male) and a mean disease duration of 9 years. The clinical data, biochemical test results, and fundus photographs of all T2DM patients were collected, and logistic regression analysis was used to screen the risk factors of DN. Then, a nomogram model was used to quantitatively analyze the risk of DN. Results: DN occurred in 27.71% (440/1 588 cases) primary type 2 diabetes patients. Hemoglobin A1c (HbA1c) (OR=1.159, 95%CI 1.039-1.292), systolic blood pressure (OR=1.041, 95%CI 1.031-1.051), serum creatinine (Scr) (OR=1.011, 95%CI 1.004-1.017), serum globulin (GLOB) (OR=1.072, 95%CI 1.039-1.105), diabetic retinopathy (DR) (OR=1.463, 95%CI 1.073-1.996), education level of more than junior high school (OR=2.018, 95%CI 1.466-2.777), and moderate-intensity exercise (OR=0.751, 95%CI 0.586-0.961) were influencing factors of DN. Nomogram model analysis showed that the total score of each factor of DN ranged from 64-138 points, and the corresponding risk rate ranged from 0.1-0.9. The nomogram model also predicted a C-index value of 0.753 (95%CI 0.726-0.781) and an area under the receiver operating characteristic curve of DN of 0.753. Internal verification of the C-index reached 0.738. The model displayed medium predictive power and could be applied in clinical practice. Conclusions: HbA1c, systolic blood pressure, Scr, GLOB, DR, and more than a junior high school education are independent risk factors of DN. Nomogram modeling can more intuitively evaluate the risk of DN in primary T2DM patients.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Neuropatías Diabéticas , Retinopatía Diabética , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/epidemiología , Nomogramas , Estudios Transversales , Factores de Riesgo , Nefropatías Diabéticas/etiología , Retinopatía Diabética/epidemiología , Retinopatía Diabética/complicacionesRESUMEN
Objective: To evaluate the efficacy and safety of different medical treatment in advanced or unresectable angiosarcoma. Methods: This study was a single-center retrospective clinical study. Fifty-five advanced or unresectable angiosarcoma patients treated in Sun-Yat Sen University Cancer Center from January 2005 to August 2020 were enrolled. There were 34 patients who received first-line doxorubicin-based chemotherapy (doxorubicin group), 12 patients received first-line doxorubicin or liposome doxorubicin plus paclitaxel or albumin bound paclitaxel chemotherapy (combination therapy group), and 4 patients received first-line paclitaxel-based treatment (paclitaxel group). There were 6 patients who received anti-angiogenesis targeted therapy, another 2 patients received anti-PD-1 antibody plus anti-angiogenesis targeted therapy. Targeted therapy and immunotherapy plus targeted therapy included 5 cases of first-line therapy and 3 cases of second-line therapy. The therapeutic effect was evaluated by RECIST 1.1 standard. The adverse reactions were evaluated by CTCAE4.0 standard. Kaplan-Meier survival analysis was evaluated with Log rank test. Cox proportional hazard model was used to analyze the influencing factors. Results: There were 18 patients achieved partial response (PR) in 34 patients in the doxorubicin group, median progression-free survival (mPFS) was 4.5 months, and median overall survival (mOS) was 15 months. Four patients achieved PR in 12 patients in the combination therapy group, mPFS and mOS were 4 months and 19 months. Two patients achieved PR in 4 patients in the paclitaxel group, mPFS and mOS were 3 months and 9 months. However, only 1 in 6 patients achieved PR for anti-angiogenesis targeted therapy, mPFS and mOS were 3 months and 16 months. Two patients who received anti-PD-1 immunotherapy combined with anti-angiogenesis targeted therapy acquired PR for 17 months and more than 16 months. Median PFS (7.5 months) were longer in those with primary liver, lung and spleen angiosarcoma than in those with other primary site (3.0 months, P=0.028). The mOS (20 months) was longer in females than that in males (12 months, P=0.045). Primary tumor site, sex, age and treatment were not independent prognostic factors for angiosarcoma patients (P>0.05). Grade 3-4 cardiac toxicity was found in 2 patients in the combination therapy group. Conclusions: Doxorubicin-based and paclitaxel-based chemotherapy are the most important treatment for advanced angiosarcoma. Potential efficacy for targeted therapy combined with anti-PD-1 immunotherapy are showed in some patients with long duration of response and moderate adverse event.
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Hemangiosarcoma , Masculino , Femenino , Humanos , Estudios Retrospectivos , Paclitaxel/efectos adversos , Doxorrubicina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Bovine mycoplasmosis is an important infectious disease of cattle caused by Mycoplasma bovis (M. bovis) which poses a serious threat to the breeding industry. Adhesin is involved in the initial process of M. bovis colonization, which is closely related to the infection, cell invasion, immune escape and virulence of this pathogenic microorganism. For the reason that M. bovis lacks a cell wall, its adhesin is predominantly located on the surface of the cell membrane. The adhesins of M. bovis are usually identified by adhesion and adhesion inhibition analysis, and more than 10 adhesins have been identified so far. These adhesins primarily bind to plasminogen, fibronectin, heparin and amyloid precursor-like protein-2 of host cells. This review aims to concisely summarize the current knowledge regarding the adhesins of M. bovis and their target proteins of the host cell. Additionally, the biological characteristics of the adhesin will be briefly analyzed.
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Enfermedades de los Bovinos , Infecciones por Mycoplasma , Mycoplasma bovis , Bovinos , Animales , Mycoplasma bovis/fisiología , Adhesinas Bacterianas/metabolismo , Plasminógeno/metabolismoRESUMEN
Objective: To investigate the occurrence of live-born twins with birth weight-discordance and its relationship to adverse birth outcomes. Methods: A retrospective analysis was performed on 4 011 pairs of live-born twins in the Third Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2020. Based on the birth-weight discordance (∆BW, ∆BW=(birth-weightbig-birth-weightsmall)/birth-weightbig×100%)), twins were divided into 4 groups, including ∆BW≤15%,>15%-20%,>20%-25%, and>25%. The differences in maternal and neonatal outcomes among 4 groups were explored. Then the correlation between ∆BW and neonatal adverse outcomes were explored. Results: The ΔBW was 9 (4, 16)% and males were accounted for 53.8% (4 315 cases) of 4 011 pairs of twins. The gestational age was (35.3±2.7) weeks at birth. There were 2 908 pairs (72.5%) of twins with ΔBW≤15%, 481 pairs (12.0%) with ΔBW>15%-20%, 281 pairs (7.0%) with ΔBW 20%-≤25%, and 341 twin pairs (8.5%) with ΔBW>25%. With ∆BW of 20% as the diagnostic cutoff, the incidence of birth weight discordance was 15.5% (622/4 011). The proportion of natural births in the ∆BW≤15% group was higher than that in the ∆BW>15%-20% group (10.5% (288/2 740) vs. 6.3% (29/463), P<0.008 3). The ∆BW>25% group had a significantly higher prevalence of maternal hypertensive disorders during pregnancy than that of the other 3 groups (25.5% (87/341) vs. 16.7% (47/281) vs.17.3% (83/480) vs. 13.8% (400/2 899), all P<0.008 3). Univariate analysis found that the ΔBW>25% group had a lower gestational age and a higher rate of preterm birth than the other groups. The rate of extremely low birth weight (ELBW) or very low birth weight (VLBW), small for gestational age (SGA), and transferring to the department of neonatology in the smaller twins were significantly different among the 4 groups (all P<0.05). Multivariate analysis showed that higher degree of birth weight discordance was all positively associated with the rate of ELBW, SGA, and transferring to the department of neonatology in smaller twin, even after adjusting maternal age and gestational hypertension, year of birth, mode of delivery, gender, and gestational age (all P<0.05). Moreover, the Mantel-Haenszel test also indicated that there were significantly low to moderate correlations between ΔBW and the unfavorable outcomes (r=0.22, 0.53, 0.21, all P<0.001, respectively). The receiver operating characteristic (ROC) curve found that adverse birth outcomes would be well predicted by birth weight-discordant when the diagnostic cut-off of ΔBW was 12%-17%, with an acceptable sensitivity (0.53-0.78) and a high specificity (0.72-0.79). Conclusions: Birth weight discordant is not uncommon in live-born twins, and is associated with adverse outcomes including ELBW, SGA, and transferring to the department of neonatology in the small twins. Besides, the risk is linearly related to the increase of ΔBW. In the future, more researches are needed to explore the underline mechanism and long-term impact of birth weight discordance, to guide the prevention and management.
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Enfermedades del Recién Nacido , Nacimiento Prematuro , Peso al Nacer , Femenino , Retardo del Crecimiento Fetal , Edad Gestacional , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos , GemelosRESUMEN
Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children (n = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (r: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (r: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.
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Infecciones Comunitarias Adquiridas , Microbiota , Neumonía , Antibacterianos/uso terapéutico , Niño , Preescolar , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Humanos , Lactante , Neumonía/tratamiento farmacológico , beta-Lactamas/uso terapéuticoRESUMEN
Plant zinc-finger proteins play a crucial role in biosynthesis and plant development. However, it is not known whether certain zinc-finger proteins play a role in rice chloroplast development. In this study, a novel rice zinc-finger protein mutant asl4 (albino seedling lethality4), which exhibits an albino lethal phenotype at the seedling stage, was used. Chlorophyll fluorescence analysis and TEM were used to investigate features of the asl4 mutant. The genetic behaviour and function of ASL4 gene were then analysed thorough map-based cloning, transgenic complement and subcellular localization. The albino lethal phenotype was caused by a single nucleotide (G*) deletion mutation on the exon of the ASL4 (LOC_Os09g21710) gene. The ASL4 gene encoded a novel zinc-finger protein containing two ZnF-AN1 domains, which was localized to the nucleocytoplasm. The ASL4 transcripts were highly expressed in all leaves but relatively less in other tissues, suggesting its tissue-specific expression. The transcript levels of associated genes for Chl biosynthesis, photosynthesis and chloroplast development were severely suppressed in asl4 mutants. In conclusion, the absence of ASL4 function caused a defect in chloroplast development and seedling lethality. This is the first published report on the importance of the ZnF-AN1 type zinc-finger protein gene in chloroplast development in rice.
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Oryza , Cloroplastos/metabolismo , Regulación de la Expresión Génica de las Plantas , Mutación , Oryza/genética , Oryza/metabolismo , Fenotipo , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantones/genética , Plantones/metabolismo , ZincAsunto(s)
Tumores del Estroma Gastrointestinal , Neoplasias Primarias Múltiples , Humanos , Tumores del Estroma Gastrointestinal/complicaciones , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Ultrasonografía , Medios de ContrasteRESUMEN
Enhanced osseointegration and a shortened healing time are required for dental implant treatment. The aim of this study was to evaluate whether topical application of the osteogenic inducer (OI) sustained-release system over the implant promotes early bone remodeling around the implant. The mandibular canines of 15 New Zealand White rabbits were extracted. After 3 months of healing, implants coated with poly(lactic-co-glycolic acid) (PLGA)+OI, PLGA alone, or no material (control) were inserted into the canine sites. After 4 weeks, specimens were harvested from the three groups and evaluated. Implant stability recorded by Periotest revealed significantly higher values for the PLGA + OI group (-2.61 ± 0.43) than for the PLGA (-1.47 ± 0.45) and control groups (-1.08 ± 0.19) (P < 0.001). Moreover, the PLGA+OI group had improved bone volume and structural parameters around the implants at 4 weeks, as shown by significantly increased BV/TV, BSA/BV, Tb.Th, and BIC (P < 0.05), as well as decreased Tb.Sp (P = 0.010) compared with the other groups. The histological results showed more trabecular bone and bone matrix around the implants in the PLGA+OI group. Therefore, local application of the OI sustained-release system might be able to promote early bone remodeling around titanium implants and facilitate faster and better osseointegration.