Background

Malaria re-emerged in the Huang-Huai Plain of central China during 2006–2008, dominated with Anopheles sinensis as a vector. However, there is no information on strategies based on multi-factor analysis to effectively control the re-emergence of malaria in these areas. Previous experience indicates some relationship between the distribution of water bodies and malaria cases, but more detailed data are not available and in-depth studies have not been conducted up to now. The objective of this study was to identify the relationship between the distribution of water bodies and presentation of malaria cases using spatial analysis tools in order to provide guidance to help formulate effective strategies for use in controlling the sources of malaria infection, based on the identification of risk areas and population.

Methods

The geographic information of malaria cases and their surrounding water bodies were collected from Suixi, Guoyang, Guzhen, Yingshang, Fengyang and Yongqiao County in Anhui province, Yongcheng and Tongbai County in Henan province. All malaria cases distributed in 113 villages in these 8 counties were collected from the China Information System for Disease Control and Prevention and confirmed by household investigation. Data on GIS and malaria cases were mapped and analyzed with the software of ArcGIS 9.2 to identify the spatial correlation between malaria cases and water bodies. The distance from households with malaria cases to the nearest water bodies was used to calculate the OR value by Chi-square test. The risk area was identified through the comparison of OR values in different distances.

Results

357 malaria cases and their GPS data as well as surrounding water bodies were collected and analyzed. 74% of malaria cases were located within the extent of 60 m proximity to the water bodies. The risk rate of people living there and presenting with malaria was significantly higher than others (OR = 1.6,95%CI (1.042, 2.463),P < 0.05).

Conclusions

The results revealed that distribution of water bodies is an important factor influencing the occurrence and distribution of malaria cases in the An.sinensis areas, and implies that the scope and population within 60 m around water bodies are at risk and could be a targeted population for case management of malaria.

Our previous studies demonstrated that Ganoderma lucidum polysaccharides (Gl-PS) exhibit potent immunomodulating effects. Immunomodulation plays an important role in hematopoiesis. To investigate the possible mechanism by which Gl-PS promote myelopoiesis during myelosuppression induced by cyclophosphamide, mice were injected intraperitoneally (i.p.) once daily with 2.5 mg/kg of Gl-PS for 10 days and were treated i.p. once daily with cyclophosphamide (100 mg/kg) on days 2 through 4. In the present study in vivo and in vitro, we find that Gl-PS selectively bind to bone marrow stromal cells, stimulate the secretion of hematopoietic growth factors, and enhance the clonogenic activities of hematopoietic and stromal cells to promote hematopoiesis in myelosuppressed mice.

Background

The worldwide experience of surgical resection for isolated metastasis following liver transplantation (LT) for hepatocellular carcinoma (HCC) is limited.

Methods

The case of a 60-year-old patient performed successful surgical management for metachronous pulmonary and adrenal metastases from HCC after LT.

Results

Eighty months after LT, he was presently alive and disease-free with a normal AFP value.

Conclusion

The case is an interesting report on a somehow indolent metastatic spread of HCC after LT. It should be considered that metachronous metastatic resectable disease, with no data of recurrence at the primary site in an operable patient, is an indication to perform a surgical resection.

It has been reported that pretreatment of rats with lipopolysaccharide (LPS) increases myocardial functional recovery in ischemia/reperfusion (I/R) hearts. However, the mechanisms by which LPS induces cardioprotection against I/R injury have not been fully elucidated. In this study, we pretreated rats with LPS (1.0 mg/kg) 24 h before they were subjected to I/R injury, and then examined the roles of heat shock protein-70 (HSP70) and nucleus factor-κB (NF-κB) in LPS-induced cardioprotection. We observed that pretreatment with low-dose LPS resulted in significantly increased levels of HSP70 in the myocardium, which could dramatically inhibit NF-κB translocation and reduce degradation of inhibitory κB. Inhibition of NF-κB, in turn, attenuated release of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, and IL-6) and reduced apoptosis of myocardium and infarct area following I/R injury. Moreover, HSP70 could ameliorate oxidative stress following I/R injury. To further investigate whether increase of HSP70 might be responsible for protection of the myocardium against I/R injury, we co-administered the HSP70 inhibitor, quercetin, with LPS before I/R injury. We found that LPS-induced cardioprotection was attenuated by co-administration with quercetin. Herein, we concluded that increased levels of HSP70 through LPS pretreatment led to inhibition of NF-κB activity in the myocardium after I/R injury. Our results indicated that LPS-induced cardioprotection was mediated partly through inhibition of NF-κB via increase of HSP70, and LPS pretreatment could provide a means of reducing myocardial I/R injury.

OBJECTIVE

Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects.

RESEARCH DESIGN AND METHODS

Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m2) and 379 never-overweight control subjects (BMI <25 kg/m2). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with ∼550,000 SNP markers. The CNV calls were generated by PennCNV software.

RESULTS

CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5–5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2–infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5–27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting UCP1 and IL15.

CONCLUSIONS

Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study.

Large-scale genome-wide association studies (GWAS) have identified many loci associated with body mass index (BMI), but few studies focused on obesity as a binary trait. Here we report the results of a GWAS and candidate SNP genotyping study of obesity, including extremely obese cases and never overweight controls as well as families segregating extreme obesity and thinness. We first performed a GWAS on 520 cases (BMI>35 kg/m2) and 540 control subjects (BMI<25 kg/m2), on measures of obesity and obesity-related traits. We subsequently followed up obesity-associated signals by genotyping the top ∼500 SNPs from GWAS in the combined sample of cases, controls and family members totaling 2,256 individuals. For the binary trait of obesity, we found 16 genome-wide significant signals within the FTO gene (strongest signal at rs17817449, P = 2.5×10−12). We next examined obesity-related quantitative traits (such as total body weight, waist circumference and waist to hip ratio), and detected genome-wide significant signals between waist to hip ratio and NRXN3 (rs11624704, P = 2.67×10−9), previously associated with body weight and fat distribution. Our study demonstrated how a relatively small sample ascertained through extreme phenotypes can detect genuine associations in a GWAS.

Background

FTO is a gene located in chromosome region 16q12.2. Recently two studies have found associations of several single nucleotide polymorphisms (SNPs) in FTO with body mass index (BMI) and obesity, particularly rs1421085, rs17817449, and rs9939609.

Methods

We examined these three SNPs in 583 extremely obese women with current BMI greater than 35 kg/m2 and lifetime BMI greater than 40 kg/m2, and 544 controls who were currently normal weight (BMI<25 kg/m2) and had never been overweight during their lifetimes.

Results

We detected highly significant associations of obesity with alleles in all three SNPs (p < 10-9). The strongest association was with rs1421085 (p = 3.04 × 10-10, OR = 1.75, CI = 1.47–2.08). A subset of 99 cases had extremely discordant sisters with BMI<25 kg/m2. The discordant sisters differed in allele and genotype frequencies in parallel with the overall case and control sample. The strongest association was with rs17817449 (z = 3.57, p = 3.6 × 10-4).

Conclusion

These results suggest common variability in FTO is associated with increased obesity risk or resistance and may in part account for differences between closely related individuals.

Proteasomes degrade most of the proteins inside eukaryotic cells, including transcription factors and regulators of cell cycle progression. Here we show that nanomolar concentrations of lactacystin, a specific irreversible inhibitor of the 20S proteasome, inhibit development of the exoerythrocytic and erythrocytic stages of the malaria parasite. Although lactacystin-treated Plasmodium berghei sporozoites are still invasive, their development into exoerythrocytic forms (EEF) is inhibited in vitro and in vivo. Erythrocytic schizogony of P. falciparum in vitro is also profoundly inhibited when drug treatment of the synchronized parasites is prior, but not subsequent, to the initiation of DNA synthesis, suggesting that the inhibitory effect of lactacystin is cell cycle specific. Lactacystin reduces P. berghei parasitemia in rats, but the therapeutic index is very low. Along with other studies showing that lactacystin inhibits stage-specific transformation in Trypanosoma and Entamoeba spp., these findings highlight the potential of proteasome inhibitors as drugs for the treatment of diseases caused by protozoan parasites.