Pollution level and risk assessment of heavy metals in sewage sludge from eight wastewater treatment plants in Wuhu City, China

Aim of study: To investigate the content, contamination levels and potential sources of five heavy metals (Hg, Pb, Cd, Cr, As) in sewage sludge from eight wastewater treatment plants (W1 to W8).Area of study: Wuhu, located in southeastern Anhui Province, southeastern China.Material and methods: The sewage sludge pollution assessment employed the single-factor pollution index, Nemerow’s synthetic pollution index, monomial potential ecological risk coefficient and potential ecological risk index. The potential sources among the five heavy metals were determined using the Pearson’s correlation analysis and principal component analysis (PCA).Main results: The mean concentrations of the heavy metals were 0.27 mg/kg (Hg), 70.78 mg/kg (Pb), 3.48 mg/kg (Cd), 143.65 mg/kg (Cr) and 22.17 mg/kg (As). W1, W5 and W6 sewage sludge samples showed the highest levels of heavy metal contamination, and cadmium had the highest contamination level in the study area. Pearson’s correlation analysis and PCA revealed that Pb and Cd mainly derived from traffic emissions and the manufacturing industry and that As and Cr originated from agricultural discharges.Research highlights: The pollution of cadmium in Wuhu should be controlled preferentially. The heavy metal pollution of W1, W5 and W6 sewage treatment plants is relatively high, they should be key prevention targets

The feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform

Objective: Recent non-invasive prenatal testing (NIPT) technologies are based on next-generation sequencing (NGS). NGS allows rapid and effective clinical diagnoses to be determined with two common sequencing systems: Illumina and Ion Torrent platforms. The majority of NIPT technology is associated with Illumina platform. We investigated whether fetal trisomy 18 and 21 were sensitively and specifically detectable by semiconductor sequencer: Ion Proton. Methods: From March 2012 to October 2013, we enrolled 155 pregnant women with fetuses who were diagnosed as high risk of fetal defects at Xiamen Maternal & Child Health Care Hospital (Xiamen, Fujian, China). Adapter-ligated DNA libraries were analyzed by the Ion Proton??? System (Life Technologies, Grand Island, NY, USA) with an average 0.3 ?? sequencing coverage per nucleotide. Average total raw reads per sample was 6.5 million and mean rate of uniquely mapped reads was 59.0%. The results of this study were derived from BWA mapping. Z-score was used for fetal trisomy 18 and 21 detection. Results: Interactive dot diagrams showed the minimal z-score values to discriminate negative versus positive cases of fetal trisomy 18 and 21. For fetal trisomy 18, the minimal z-score value of 2.459 showed 100% positive predictive and negative predictive values. The minimal z-score of 2.566 was used to classify negative versus positive cases of fetal trisomy 21. Conclusion: These results provide the evidence that fetal trisomy 18 and 21 detection can be performed with semiconductor sequencer. Our data also suggest that a prospective study should be performed with a larger cohort of clinically diverse obstetrics patients.open2

Clinical effectiveness of calcitriol and calcium gluconate in treating older male patients with osteoporosis

Clinical studies on calcitriol in osteoporosis (OP) have been mostly conducted in postmenopausal women, with limited research reported in elderly male patients. In this study, we investigated the effects of combining calcitriol with calcium gluconate for treating OP in elderly men and compared it with calcium gluconate monotherapy to provide insights into the clinical treatment options for OP. A total of 86 elderly male OP patients were included in this study and randomly assigned to control or observation groups in a 1:1 ratio. The control group was given oral calcium gluconate (1.0 g, three times daily), while the observation group was given oral calcitriol capsule (0.25 μg twice daily) and oral calcium gluconate (1.0 g three times daily). The results indicated that treatment with single calcium gluconate for 6 months had minimal impact on the bone mineral density (BMD) of the lumbar spine, total hip and femoral neck, and balance function. In contrast, the combination of calcium gluconate and calcitriol significantly increased BMD and improved patients’ balance function. Both single calcium gluconate treatment and the combination of calcium gluconate and calcitriol affected various bone metabolism and turnover markers to varying degrees, including a decrease in the level of tartrate-resistant acid phosphatase-5b (TRAP-5b) and an increase in the levels of osteocalcin and calcium. Both calcium gluconate and calcitriol affect patients’ bone metabolism and turnover markers to varying degrees. Importantly, the combination of calcium gluconate and calcitriol had a significant effect on these markers compared to calcium gluconate monotherapy, and no significant difference in the incidence of adverse reactions was observed between the two groups during treatment. Calcium gluconate in combination with calcitriol in elderly male patients with OP may increase bone mineral density, improve bone metabolism, enhance bone turnover and maintain a high safety profile

Cost-effectiveness analysis of routine 13-valent pneumococcal conjugate vaccinations in Chinese infants

Background: This study aimed to evaluate the cost-effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV-13) compared to a no vaccination strategy in Chinese infants. Methods: A Markov process model was developed to examine the outcomes of PCV-13 against a no vaccination strategy using data and assumptions adapted for relevance to China. Outcomes over a lifetime horizon are presented. One-way and probabilistic sensitivity analyses were performed to determine the uncertainty. Results: Compared to no vaccination, a PCV-13 vaccination program would provide a gain of 0.009 additional quality-adjusted life years (QALYs) per subject. From the health care and societal perspectives, the incremental costs per QALY were $20,709 and 18,483, respectively. When herd effect was included, the cost effectiveness of the PCV-13 vaccination strategy was notably improved. The lower price of PCV-13 will improve the cost-effectiveness. Conclusions: The PCV-13 vaccination is likely to be cost-effective at the current Chinese prices and ceiling threshold ($8,382)

Conferring the binding properties of the mouse MHC class I-related receptor, FcRn, onto the human ortholog by sequential rounds of site-directed mutagenesis

The MHC class I-related receptor, FcRn, is involved in binding and transporting immunoglobulin G (IgG) within and across cells. In contrast to mouse FcRn, which binds to IgGs from multiple different species, human FcRn is surprisingly stringent in binding specificity. For example, human FcRn does not bind to mouse IgG1 or IgG2a and interacts only weakly with mouse IgG2b. Here, we have used site-directed mutagenesis in combination with interaction (surface plasmon resonance) studies, with the goal of generating human FcRn variants that more closely resemble mouse FcRn in binding specificity. Our studies show that residues encompassing and extending away from the interaction site on the α2 helix of FcRn play a significant and most likely indirect role in FcRn-IgG interactions. Further, by combining mutations in the α2 helix with those in a non-conserved region of the α1 helix encompassing residues 79-89, we have generated a human FcRn variant that has properties very similar to those of mouse FcRn. These studies define the molecular basis for the marked difference in binding specificity between human and rodent FcRn, and give insight into how human FcRn recognizes IgGs.</p

Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans

IgG is the most abundant serum antibody and is an essential component of the humoral immune response. It is known that the 'neonatal' Fc receptor (FcRn) plays a role in maintaining constant serum IgG levels by acting as a protective receptor which binds and salvages IgG from degradation. However, the cellular mechanism that is involved in serum IgG homeostasis is poorly understood. In the current study we address this issue by analyzing the intracellular fate in human endothelial cells of IgG molecules which bind with different affinities to FcRn. The studies show that IgG which do not bind to FcRn accumulate in the lysosomal pathway, providing a cellular explanation for short serum persistence of such antibodies. We have also investigated the saturability of the homeostatic system and find that it has limited capacity. Our observations have direct relevance to the understanding and treatment of IgG deficiency, and to the effective application of therapeutic antibodies.</p

Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels

We have engineered the Fc region of a human immunoglobulin G (IgG) to generate a mutated antibody that modulates the concentrations of endogenous IgGs in vivo. This has been achieved by targeting the activity of the Fc receptor, FcRn, which serves through its IgG salvage function to maintain and regulate IgG concentrations in the body. We show that an IgG whose Fc region was engineered to bind with higher affinity and reduced pH dependence to FcRn potently inhibits FcRn-IgG interactions and induces a rapid decrease of IgG levels in mice. Such FcRn blockers (or 'Abdegs,' for antibodies that enhance IgG degradation) may have uses in reducing IgG levels in antibody-mediated diseases and in inducing the rapid clearance of IgG-toxin or IgG-drug complexes.</p