3D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defects.

BACKGROUND: Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (IBD). METHODS: PLGA scaffolds were produced using the 3D printing method. Drug release of linezolid was analyzed by elution and high-performance liquid chromatography assay. PLGA, PLGA-HA, and linezolid-loaded PLGA-HA scaffolds, were implanted into the defect site of a rabbit radius defect model. Micro-CT, H&E, and Masson staining, and immunohistochemistry were performed to analyze bone infection and bone healing. Evaluation of viable bacteria was performed. The cytocompatibility of 3D-printed composite scaffolds in vitro was detected using human bone marrow mesenchymal stem cells (BMSCs). Long-term safety of the scaffolds in rabbits was evaluated. RESULTS: The linezolid-loaded PLGA-HA scaffolds exhibited a sustained release of linezolid and showed significant antibacterial effects. In the IBD rabbit models implanted with the scaffolds, the linezolid-loaded PLGA-HA scaffolds promoted bone healing and attenuated bone infection. The PLGA-HA scaffolds carrying linezolid upregulated the expression of osteogenic genes including collagen I, runt-related transcription factor 2, and osteocalcin. The linezolid-loaded PLGA-HA scaffolds promoted the proliferation and osteogenesis of BMSCs in vitro via the PI3K/AKT pathway. Moreover, the rabbits implanted with the linezolid-loaded scaffolds showed normal biochemical profiles and normal histology, which suggested the safety of the linezolid-loaded scaffolds. CONCLUSION: Overall, the linezolid-loaded PLGA-HA scaffolds fabricated by 3D printing exerts significant bone repair and anti-infection effects.

A global perspective on bacterial diversity in the terrestrial deep subsurface.

While recent efforts to catalogue Earth's microbial diversity have focused upon surface and marine habitats, 12-20 % of Earth's biomass is suggested to exist in the terrestrial deep subsurface, compared to ~1.8 % in the deep subseafloor. Metagenomic studies of the terrestrial deep subsurface have yielded a trove of divergent and functionally important microbiomes from a range of localities. However, a wider perspective of microbial diversity and its relationship to environmental conditions within the terrestrial deep subsurface is still required. Our meta-analysis reveals that terrestrial deep subsurface microbiota are dominated by Betaproteobacteria, Gammaproteobacteria and Firmicutes, probably as a function of the diverse metabolic strategies of these taxa. Evidence was also found for a common small consortium of prevalent Betaproteobacteria and Gammaproteobacteria operational taxonomic units across the localities. This implies a core terrestrial deep subsurface community, irrespective of aquifer lithology, depth and other variables, that may play an important role in colonizing and sustaining microbial habitats in the deep terrestrial subsurface. An in silico contamination-aware approach to analysing this dataset underscores the importance of downstream methods for assuring that robust conclusions can be reached from deep subsurface-derived sequencing data. Understanding the global panorama of microbial diversity and ecological dynamics in the deep terrestrial subsurface provides a first step towards understanding the role of microbes in global subsurface element and nutrient cycling.

STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in a validation dataset derived from the screened population of the STATIN study. METHODS: This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. RESULTS: The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. CONCLUSION: The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Twin pregnancy with two live fetuses at 11-13 weeks: effect of one fetal death on pregnancy outcome.

OBJECTIVES: First, to compare the incidence of single and double fetal death between monochorionic (MC) and dichorionic (DC) twin pregnancies with two live fetuses at 11-13 weeks' gestation and no major abnormalities. Second, to investigate the relationship between gestational age at single fetal death and interval to delivery of the cotwin. Third, to determine the rate of early preterm birth in DC and MC twin pregnancies with two live fetuses and those with single fetal death. METHODS: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. The outcome measures, which were stratified by chorionicity, were: first, death of both fetuses at presentation or death of one fetus followed by delivery of a live or dead cotwin within the subsequent 3 days at < 34 weeks' gestation; second, in pregnancies with single fetal death at < 34 weeks' gestation and a live cotwin ≥ 3 days later, the subsequent risk of fetal death and gestational-age distribution at birth of the cotwin; and, third, the gestational-age distribution at birth in pregnancies with two live fetuses. RESULTS: The main findings of this study of 4896 DC and 1329 MC twin pregnancies with two live fetuses at 11-13 weeks' gestation were: first, the rate of death of both twins or death of one fetus and delivery of the live or dead cotwin within 3 days was higher in MC than in DC twin pregnancies; second, the rate of single fetal death with a live cotwin ≥ 3 days later was higher in MC than in DC twin pregnancies, but the rate of subsequent cotwin death in MC twin pregnancies was not significantly different from that in DC twin pregnancies; third, in pregnancies with two live fetuses, the rate of early preterm birth was significantly higher in MC than in DC twin pregnancies; fourth, the rate of early preterm birth in pregnancies with single fetal death and a live cotwin ≥ 3 days later was not significantly different between MC and DC twin pregnancies but the rates were substantially higher than in those with two live fetuses; and, fifth, in both MC and DC pregnancies with single fetal death and a live cotwin ≥ 3 days later, there was a significant inverse association between gestational age at death and interval to delivery (mean interval of 19 weeks for death at 15 weeks and mean interval of 2.5 weeks for death at 30 weeks). CONCLUSIONS: First, in MC twin pregnancies, the risk of single or double fetal death is higher than in DC twins. Second, in both MC and DC twin pregnancies, the rate of early preterm birth is higher in those with one fetal death than in those with two live fetuses. Third, in both MC and DC twins with one fetal death, the interval to delivery is related inversely to gestational age at fetal death. These data should be useful in counseling parents as to the likely outcome of their pregnancy after single fetal death and in defining strategies for surveillance in the management of these types of twin pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Biodegradation of thiocyanate by a novel strain of Burkholderia phytofirmans from soil contaminated by gold mine tailings.

UNLABELLED: A novel B. phytofirmans strain with the capacity to degrade thiocyanate was isolated from pH approximately 6·5 soil contaminated by effluent from gold mine tailings. This Burkholderia strain uses thiocyanate as its sole nitrogen source and can grow on acetate as a sole carbon source in a minimal medium. While biodegradation of thiocyanate has been reported to occur within alkaline environments (e.g. soda lakes and wastewater from coking plants), this work presents the first observation of thiocyanate degradation by Burkholderia at pH <9·0. Our findings therefore inform remediation strategies for thiocyanate contamination in nonalkaline soils and waters impacted by gold-mining activities. SIGNIFICANCE AND IMPACT OF THE STUDY: This work describes thiocyanate biodegradation by a novel Burkholderia phytofirmans strain isolated from circumneutral pH gold mining-contaminated soils. Previous reports of bacterial thiocyanate degradation have mainly focused on alkaline environments or culturing conditions (pH ≥ 9). Because cyanidation is used globally in gold mining, with thiocyanate as the major contaminant, our results will interest those working on biotechnological approaches to gold mine waste remediation.

Preserved contractile function despite atrophic remodeling in unloaded rat hearts.

The present study was designed to determine whether myocardial atrophy is necessarily associated with changes in cardiac contractility. Myocardial unloading of normal hearts was produced via heterotopic transplantation in rats. Contractions of isolated myocytes (1.2 mM Ca2+; 37 degrees C) were assessed during field stimulation (0.5, 1.0, and 2.0 Hz), and papillary muscle contractions were assessed during direct stimulation (2.0 mM Ca2+; 37 degrees C; 0.5 Hz). Hemodynamic unloading was associated with a 41% decrease in median myocyte volume and proportional decreases in myocyte length and width. Nevertheless, atrophic myocytes had normal fractional shortening, time to peak contraction, and relaxation times. Despite decreases in absolute maximal force generation (F(max)), there were no differences in F(max)/ area in papillary muscles isolated from unloaded transplanted hearts. Therefore, atrophic remodeling after unloading is associated with intact contractile function in isolated myocytes and papillary muscles when contractile indexes are normalized to account for reductions in cell length and cross-sectional area, respectively. Nevertheless, in the absence of compensatory increases in contractile function, reductions in myocardial mass will lead to impaired overall work capacity.

Expression of allograft inflammatory factor-1 is a marker of activated human vascular smooth muscle cells and arterial injury.

The cytokine-induced activation and proliferation of medial vascular smooth muscle cells (VSMCs) leading to intimal hyperplasia is one of the most critical cellular events in the formation of transplant arteriopathy and balloon angioplasty-induced restenosis. Allograft inflammatory factor-1 (AIF-1) is a calcium-binding protein that we have previously shown to be expressed in balloon angioplasty-injured rat carotid arteries. We hypothesized that AIF-1 expression may be associated with the VSMC response to injury. In this study, we examined AIF-1 expression in immunologic and mechanical models of arterial injury. Reverse transcription-polymerase chain reaction and Western analysis demonstrated that AIF-1 is acutely and transiently expressed in aortic medial smooth muscle cells of rat cardiac allografts, with mRNA and protein peaking at 3 to 7 days after transplant and declining by 10 days after transplant. Immunohistochemical analysis identified abundant AIF-1 in the medial VSMCs of these vessels. Immunohistochemical analysis of balloon angioplasty-injured swine coronary arteries also demonstrates an acute AIF-1 expression detectable by 24 hours and continuing up to 14 days after the procedure. AIF-1 in these vessels also localizes to the medial VSMCs and cells of the developing neointima. AIF-1 protein is not expressed in quiescent cultured human VSMCs but is induced in cells challenged with various inflammatory cytokines, primarily by interferon-gamma, interleukin-1beta, and T-cell-conditioned media. Transfection and overexpression of AIF-1 in human VSMCs result in enhanced growth of these cells. Taken together, these data indicate that AIF-1 expression is associated with vascular trauma and suggest that this protein may play a role in VSMC activation subsequent to arterial injury.

Fertility and population policy in two counties in China 1980-1991.

A survey of women in two highly developed rural counties of China, Sichuan and Jiangsu Provinces, was carried out in late 1991, to gain information about demographic and economic change between 1980 and 1990. Three separate surveys were conducted: the first a questionnaire administered to married women aged 30-39, eliciting information about childbearing and contraception, as well as the social and economic background of the respondents; the second, focus group interviews emphasizing the motivation for childbearing. Official information about the selected villages, townships and counties was also collected. National level data in 1987 show that individual reproductive behaviour in China failed to conform to a universal, effectively implemented, population policy. They imply either a spatial range of policies, or great diversity in the demand for children, or perhaps a combination of both. Such diversity in reproductive behaviour is also found in the study area. The purpose of the analysis was to examine the diversity in reproductive behaviour and contraceptive practice, and to discover whether differentials are influenced by area, or else exist between individuals within areas. If the former, then the explanation may be found in differences in policy formulation and implementation between areas: and if the latter, to demand for children, or else differential application of policy restrictions. The main findings were that: (1) the explanation of the pattern of fertility and contraceptive use is to be found at the individual level (within locations) rather than in policy differences between administrative units; (2) the association between income and number of children is negative, as is that between income and the propensity for uniparous women to remain unsterilized. The theory that privilege may be exercised to gain concessions from birth planning cadres is therefore not supported; (3) ideal family size differentials are largely absent, showing that social (education) and economic (income, occupation) characteristics are not responsible for differences in reproductive motivations, and implying that the nature of the demand for children is very different from that in most rural areas of the Third World; (4) data on ideal family size by sex of the existing offspring indicate only a weak preference for sons. The low demand for children, and the weak son preference, may both be explained by the social acceptability of uxorilocal marriages, and of village endogamy, together with the prohibitive costs of children, and especially of sons. This partly results from the expense of education, but most mothers emphasize marriage costs. It is speculated that the circumstances responsible for the escalating costs of children in the two countries are likely to pertain in growing areas of the country, with the privatization of education and health services, the declining support of collective institutions, and the replacement of this function by kinship networks. These on-going changes imply that any policy of reproductive restriction for the purposes of population control is likely soon to meet with diminishing resistance; and it may later be rendered unnecessary in the eyes of government officials, as fulfilled reproductive intentions lead to a fertility level below replacement level.

PIP: This survey examined the diversity in reproductive behavior and contraceptive practice to determine whether their differentials are influenced by area or those between individuals within the areas. Data were collected from three separate surveys of women in two highly developed rural counties of China, Sichuan and Jiangsu Provinces carried out in late 1991. The main findings established were: 1) the pattern of fertility and contraceptive use was found at the individual level rather than in policy differences between administrative units; 2) the association between income and number of children was negative, as that between income and propensity for uniparous women to remain unsterilized; 3) the ideal family size differentials were largely absent, showing that social and economic characteristics were not responsible for differences in reproductive motivations, and implying that the nature of the demand for children was very different from that in most rural areas of the Third World; 4) data on ideal family size by sex of the existing offspring indicate only a weak preference for sons.

[Clinical analysis of pulmonary infection in patients with acquired immunodeficiency syndrome (AIDS)].

OBJECTIVE: This clinical analysis is made to achieve a better understanding of the opportunistic infection of patients with AIDS, especially pulmonary infection. METHOD: 32 cases of patients with AIDS are analyzed. RESULT: The clinical manifestations of the 32 cases are: fever, tiredness, loss of weight, night sweat, cough, sputum, and generalized pain. Among the 32 cases, 24 suffered for tuberculosis, constituting 78% of the total. The other patients suffered for bacterial infection and pneumocystis carinii pneumonia. These patients are complicated with skin infection and impairment of the heart, liver, kidney and other organs. CONCLUSION: Pulmonary infection is a major opportunistic infection of AIDS patients at late stage. Patients with AIDS can be easily infected with tuberculosis and complicated with multi-organ impairments, which are very difficult to treat.