Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Cadmium mobility and health risk assessment in the soil-rice-human system using in vitro biaccessibility and in vivo bioavailability assay: Two year field experiment.

Humans are mainly exposed to cadmium (Cd) due to the rice consumption, however there exist considerable differences across rice cultivars in terms of Cd absorption and accumulation in the grains, and subsequent release after digestion (bioaccessibility), as well as uptake by Caco-2 cells of humans (bioavailability). This study comprised of field and lab simulation trials where in the field, firstly 39 mid-rice cultivars were screened for their phytoremediation potential coupled with safe production in relation to uptake and translocation of Cd. Lower Cd concentrations (˂0.2 mg kg-1) in polished rice of 74 % cultivars were ascribed to the increased root to straw translocation indicating that straw may acquire higher accumulation of Cd. Furthermore, the ionomic profile demonstrated that the spatial distribution of metals in different rice organs corresponds to the plant growth morphology. In the second year, in vitro-in vivo assay model was employed to assess the bioaccessibility and bioavailability of Cd in polished rice and to further estimate the daily Cd intake by humans through rice grains. The results of bioaccessibility and bioavailability assays and daily estimated Cd intake presented the corresponding values of 39.02-59.76 %, 8.69-24.26 %, and 0.0185-0.9713 µg kg-1 body weight day-1, respectively. There exists a strong connection between total Cd and bioaccessible Cd to humans (R2 = 0.94, P < 0.01). Polynomial fitting (R2 = 0.91, P < 0.01) showed a better statistically significant correlation between total Cd contents and bioavailable levels, suggesting that in vitro-in vivo assays should be considered in future studies. The results of field experiments and in vitro-in vivo assays recommended the Tianyouhuazhan (MR-29), Heliangyou1hao (MR-17), and Yongyou15 (MR-1) as suitable mid-rice cultivars for the phytoremediation of slightly Cd contaminated soils coupled with rice agro-production due to their high nutritional value and low total and bioavailable Cd for human.

Process design and techno-economic analysis of fuel ethanol production from food waste by enzymatic hydrolysis and fermentation.

In this study, fuel ethanol production from food waste using enzymatic hydrolysis and fermentation was evaluated from techno-economic viewpoint. The plant was designed with a capacity of 10 t/d food waste and a lifetime of 15-year. The total capital cost, annual operation cost and annual net profits of the plant were US$ 367,552, US$ 155,959 and US$ 74,995.57, respectively. The plant was economically viable as long as the internal rate of return remained below 29.8%. The shortest payback time was 5 years with discount rate of 5%. The price of fuel ethanol and food waste treatment fee were the most important variables for the economic performance of the plant by sensitivity analysis. This work could provide the basic knowledge for techno-economic analysis of food waste treatment and promote the industrial production of fuel ethanol.

Phytoremediation of Cd-contaminated farmland soil via various Sedum alfredii-oilseed rape cropping systems: Efficiency comparison and cost-benefit analysis.

Phytoremediation is a green technology for heavy metal removal from contaminated soil, and its remediation efficiency and economic feasibility in field trial should be evaluated before large-scale application. However, there is still lacking relevant analysis, especially for phytoremediation with different cropping patterns. In the present study, we performed phytoremediation on slightly Cd-contaminated farmland soil via three cropping systems, i.e. Sedum alfredii monoculture, oilseed rape monoculture, and S. alfredii-oilseed rape intercropping. Dry weights of S. alfredii and oilseed rape were both enhanced under intercropping pattern, while the highest total Cd extraction amount (148 g ha-1) were observed under S. alfredii monoculture. Furtherly, a cost-benefit analysis via Monta Carlo simulation in a ten-year lifetime was conducted. The benefits of S. alfredii monoculture and intercropping schemes would offset the total costs in 6 and 8 years, respectively. S. alfredii monoculture achieved a higher net present value of 1.88 × 104 US$ as compared with intercropping (9.53 × 103 US$). These results indicate that S. alfredii monoculture scheme could be a promising phytoremediation strategy for slightly Cd-contaminated soil owing to better remediation efficiency and economic feasibility. Moreover, the enhancement in mechanization level and the reduction of seedling cost could further improve its economic viability.

Quantitative Static and Dynamic Assessment of Balance Control in Stroke Patients.

In patients with stroke, damage to the central nervous system (CNS) can affect the postural stability and increase the risk of falling. Therefore, accurately assessing the balance is important to understand the type, extent, and causes of balance deficit, and to identify individualized interventions. Clinical assessment methods for balance function can be broadly divided into observation, scale assessment, and balance instrument testing. Here, a clinical protocol is presented for static and dynamic balance assessment in stroke patients, which includes three semiquantitative balance function scale assessments (i.e., Berg Balance Scale, Timed Up and Go Test, and Fugl-Meyer Assessment) and three quantitative instrumental balance evaluation (i.e., Stability Assessment Module, Proprioceptive Assessment Module, and Limit of Stability Module). It is recommended that clinicians consider the use of both classic clinical balance scales and instrumental balance measurements when assessing stroke patients to improve the accuracy of assessments, leading to a better individualized treatment plan.

Diagnostic performance of convolutional neural network-based Tanner-Whitehouse 3 bone age assessment system.

BACKGROUND: Bone age can reflect the true growth and development status of a child; thus, it plays a critical role in evaluating growth and endocrine disorders. This study established and validated an optimized Tanner-Whitehouse 3 artificial intelligence (TW3-AI) bone age assessment (BAA) system based on a convolutional neural network (CNN). METHODS: A data set of 9,059 clinical radiographs of the left hand was obtained from the picture archives and communication systems (PACS) between January 2012 and December 2016. Among these, 8,005/9,059 (88%) samples were treated as the training set for model implementation, 804/9,059 (9%) samples as the validation set for parameters optimization, and the remaining 250/9,059 (3%) samples were used to verify the accuracy and reliability of the model compared to that of 4 experienced endocrinologists and 2 experienced radiologists. The overall variation of TW3-metacarpophalangeal, radius, ulna and short bones (RUS) and TW3-Carpal bone score, as well as each bone (13 RUS + 7 Carpal) between reviewers and the AI, were compared by Bland-Altman (BA) chart and Kappa test, respectively. Furthermore, the time consumption between the model and reviewers was also compared. RESULTS: The performance of TW3-AI model was highly consistent with the reviewers' overall estimation, and the root mean square (RMS) was 0.50 years. The accuracy of the BAA of the TW3-AI model was better than the estimate of the reviewers. Further analysis revealed that human interpretations of the male capitate, hamate, the first distal and fifth middle phalanx and female capitate, the trapezoid, and the third and fifth middle phalanx, were most inconsistent. The average image processing time was 1.5±0.2 s in the TW3-AI model, which was significantly shorter than manual interpretation. CONCLUSIONS: The diagnostic performance of CNN-based TW3 BAA was accurate and timesaving, and possesses better stability compared to diagnostics made by experienced experts.

Synthesis and assessment of CTAB and NPE modified organo-montmorillonite for the fabrication of organo-montmorillonite/alginate based hydrophobic pharmaceutical controlled-release formulation.

The research goal of the present study was to develop a carrier for loading and controlled -release of the hydrophobic drug with the combined use of organo-montmorillonite (OMMT) and alginate. The OMMT was synthesized through the intercalation modification of sodium montmorillonite (Na-MMT) with cationic cetyltrimethylammonium bromide (CTAB), nonionic nonylphenol polyoxyethylene ether (NPE) and the mixture of them via simple and convenient wet ball-milling method. Furthermore, the organo-montmorillonite/alginate (OMMT/Alg) composite hydrogel beads with slow and controlled release properties were constructed by using alginate as a coating material under the exogenous cross-linking of calcium ions. The physical and chemical properties of OMMT were comparatively evaluated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analyzer (TGA), BET-specific surface area measurements, and drug adsorption experiments. Experimental results showed that the presence of CTAB was able to facilitate the intercalation of CTAB/NPE into Na-MMT through the cation exchange reaction. And the cationic CTAB and nonionic NPE were adsorbed or intercalated into the MMT lamellar structure through the wet ball-milling process, which could change the hydrophilic nature of Na-MMT and improve its affinity to the hydrophobic drug molecules. In addition, the OMMT/Alg composite hydrogel beads displayed superior sustained-release properties than Na-MMT/Alg, mainly ascribed to the good affinity of OMMT to hydrophobic drug that retarded the drug diffusion. In particular, CTA/NPE-MMT/Alg with the highest loading capacity (LC) and encapsulation efficiency (EE) revealed the optimal controlled performance for the release of hydrophobic ibuprofen. The release followed the Korsmeyer-Peppas model suggested non-Fickian diffusion release mechanism. Based on the high drug loading capacity and excellent controlled drug release properties, the CTA/NPE-MMT/Alg incorporating hydrophobic drugs into hydrophilic matrices could be a highly promising material for use in hydrophobic drug delivery.

DRDB: An Online Date Palm Genomic Resource Database.

Background: Date palm (Phoenix dactylifera L.) is a cultivated woody plant with agricultural and economic importance in many countries around the world. With the advantages of next generation sequencing technologies, genome sequences for many date palm cultivars have been released recently. Short sequence repeat (SSR) and single nucleotide polymorphism (SNP) can be identified from these genomic data, and have been proven to be very useful biomarkers in plant genome analysis and breeding. Results: Here, we first improved the date palm genome assembly using 130X of HiSeq data generated in our lab. Then 246,445 SSRs (214,901 SSRs and 31,544 compound SSRs) were annotated in this genome assembly; among the SSRs, mononucleotide SSRs (58.92%) were the most abundant, followed by di- (29.92%), tri- (8.14%), tetra- (2.47%), penta- (0.36%), and hexa-nucleotide SSRs (0.19%). The high-quality PCR primer pairs were designed for most (174,497; 70.81% out of total) SSRs. We also annotated 6,375,806 SNPs with raw read depth≥3 in 90% cultivars. To further reduce false positive SNPs, we only kept 5,572,650 (87.40% out of total) SNPs with at least 20% cultivars support for downstream analyses. The high-quality PCR primer pairs were also obtained for 4,177,778 (65.53%) SNPs. We reconstructed the phylogenetic relationships among the 62 cultivars using these variants and found that they can be divided into three clusters, namely North Africa, Egypt - Sudan, and Middle East - South Asian, with Egypt - Sudan being the admixture of North Africa and Middle East - South Asian cultivars; we further confirmed these clusters using principal component analysis. Moreover, 34,346 SSRs and 4,177,778 SNPs with PCR primers were assigned to shared cultivars for cultivar classification and diversity analysis. All these SSRs, SNPs and their classification are available in our database, and can be used for cultivar identification, comparison, and molecular breeding. Conclusion:DRDB is a comprehensive genomic resource database of date palm. It can serve as a bioinformatics platform for date palm genomics, genetics, and molecular breeding. DRDB is freely available at http://drdb.big.ac.cn/home.

The pilot study of DXA assessment in chinese HIV-infected men with clinical lipodystrophy.

The aim of this study was to evaluate human immunodeficiency virus (HIV)-infected patient's body composition changes by dual-energy X-ray absorptiometry (DXA) and to analyze factors associated with lipodystrophy (LD). Total-body composition was measured by DXA in HIV-infected men and healthy men. HIV-infected men were divided into LD patients and non-LD patients according to whether they were complicated with LD. Healthy men were selected as controls. Fat mass (FM) of HIV-infected patients correlated negatively with the duration of HIV infection and with the duration of highly active antiretroviral therapy regimen (r(s)=-0.448 and -0.563; p=0.032 and 0.000, respectively). Multiple linear regression results showed that FM had positive correlation with weight and bone mineral content (BMC) and had negative correlation with lean mass (LM). Total body and regional FMs were found to be significantly different among LD patients, non-LD patients, and controls-the lowest in LD patients and the highest in controls (p<0.05). Total body, trunk, and leg BMCs of LD patients were lower than those of controls (p<0.05). Lumbar bone mineral density of LD patients was lower than that of non-LD patients and controls (p=0.04 and 0.007). LM of LD patients was higher than that of non-LD patients, and trunk LM had statistical difference between the 2 groups (p=0.003). Applying DXA to assess HIV-infected patient's body composition changes could provide objective information for physicians to prevent LD and osteoporosis.