A Deep Learning Framework for Anesthesia Depth Prediction from Drug Infusion History.

In the target-controlled infusion (TCI) of propofol and remifentanil intravenous anesthesia, accurate prediction of the depth of anesthesia (DOA) is very challenging. Patients with different physiological characteristics have inconsistent pharmacodynamic responses during different stages of anesthesia. For example, in TCI, older adults transition smoothly from the induction period to the maintenance period, while younger adults are more prone to anesthetic awareness, resulting in different DOA data distributions among patients. To address these problems, a deep learning framework that incorporates domain adaptation and knowledge distillation and uses propofol and remifentanil doses at historical moments to continuously predict the bispectral index (BIS) is proposed in this paper. Specifically, a modified adaptive recurrent neural network (AdaRNN) is adopted to address data distribution differences among patients. Moreover, a knowledge distillation pipeline is developed to train the prediction network by enabling it to learn intermediate feature representations of the teacher network. The experimental results show that our method exhibits better performance than existing approaches during all anesthetic phases in the TCI of propofol and remifentanil intravenous anesthesia. In particular, our method outperforms some state-of-the-art methods in terms of root mean square error and mean absolute error by 1 and 0.8, respectively, in the internal dataset as well as in the publicly available dataset.

Systematic response of staurosporine scaffold-based inhibitors to drug-resistant cancer kinase mutations.

Human protein kinases have been established as promising druggable targets in cancer therapy. However, a large number of acquired drug-resistant kinase mutations are observed after first- and second-line kinase inhibitor treatments, largely limiting the application of small-molecule inhibitors in the targeted cancer therapy. Previously, the pan-kinase inhibitor staurosporine and its derivatives have been reported to selectively inhibit gatekeeper mutants over wild-type kinases, suggesting that the staurosporine scaffold is potentially helpful in developing wild-type-sparing inhibitors of drug-resistant kinase mutants. Here, a systematic response profile of 32 staurosporine scaffold-based inhibitors (SSBIs) for 61 ontology-enriched drug-resistant cancer kinase mutations is created using a combination of in silico analysis and in vitro assay, from which it is possible to identify those mutations that have the potential to cause resistance or confer sensitivity to SSBIs. The profile reveals that SSBIs exhibit distinct responses to kinase gatekeeper and nongatekeeper mutations, and SSBIs bearing p7 substituents can considerably influence their response to kinase gatekeeper mutations, particularly for the mutations of the Ile residue, which possesses a Cß methyl group that tends to cause steric clash with bound SSBIs. Nongatekeeper mutations generally have a moderate and unfavorable effect on SSBI activity, as most of them are outside the kinase active site and do not directly contact inhibitor ligands. In addition, it is found that resistance is commonly caused by mutation-induced hindrance effects, whereas sensitivity is primarily conferred by mutation-established additional interactions.

Clinical diagnostic value of viable Schistosoma japonicum eggs detected in host tissues.

BACKGROUND: Schistosomiasis, one of the neglected tropical diseases, is endemic in more than 70 countries. However, the clinical diagnosis of patients with a low degree of infection is an unsolved technical problem. In areas endemic for schistosomiasis japonica, proctoscopy detection of eggs has been one method used for clinical diagnosis. However, it is often a challenge to find typical live eggs and it is difficult to distinguish live eggs from large numbers of partially degraded and/or completely degraded eggs within colon biopsy tissue. To address this problem, we tested six different morphological and biochemical/molecular markers (ALP; morphological characteristics of egg; CalS (calcified substance); AOS (antioxidase); SDHG (succinic dehydrogenase) and SjR2 mRNA (retrotransposons 2 of S.japonicum genome mRNA)), including four new markers (CalS; AOS; SDHG and SjR2 mRNA.), to determine the viability of S. japonicum eggs deposited in human and mouse colon tissues. Our ultimate aim is to obtain a new method that is more sensitive, practical and accurate to clinically diagnose schistosomiasis. METHODS: Tissue samples were collected from mice at six different time points during S. japonicum infection with or without treatment with praziquantel (PZQ). Four new biochemical or molecular markers were used for the detection of egg viability from mouse liver and intestinal samples: CalS; AOS; SDHG and SjR2 mRNA. Subsequently, all markers were employed for the detection and analysis of eggs deposited in biopsy materials from patients with suspected schistosomiasis japonica for clinical evaluation. Microscopic examination of the egg morphology, worm burden in vivo and ALP (alkaline phosphatase) levels were used as a reference standard to evaluate the sensitivity and reliability of four new markers detecting egg viability. RESULTS: The results of the study showed that the morphology of S. japonicum eggs deposited in tissues of hosts with schistosomiasis, especially cases with chronic schistosomiasis, is complex and egg viability is difficult to judge morphologically, particularly eggs with a fuzzy structure or partially modified eggs. We found that the majority of the viable schistosome eggs determined by four new markers (CalS, AOS, SDHG and SjR2 mRNA) were morphologically difficult to identify. CONCLUSIONS: Among the markers, the most sensitive and specific method was the detection of SjR2 mRNA and the most simple, rapid and practical method was the detection of SDHG. Therefore, the detection of SDHG is the most practical for clinical application and its use could improve the accuracy in diagnosing active schistosome infection.

Health-education package to prevent worm infections in Chinese schoolchildren.

BACKGROUND: Soil-transmitted helminths are among the most prevalent sources of human infections globally. We determined the effect of an educational package at rural schools in Linxiang City District, Hunan province, China, where these worms are prevalent. The intervention aimed to increase knowledge about soil-transmitted helminths, induce behavioral change, and reduce the rate of infection. METHODS: We conducted a single-blind, unmatched, cluster-randomized intervention trial involving 1718 children, 9 to 10 years of age, in 38 schools over the course of 1 school year. Schools were randomly assigned to the health-education package, which included a cartoon video, or to a control package, which involved only the display of a health-education poster. Infection rates, knowledge about soil-transmitted helminths (as assessed with the use of a questionnaire), and hand-washing behavior were assessed before and after the intervention. Albendazole was administered in all the participants at baseline and in all the children who were found to be positive for infection with soil-transmitted helminths at the follow-up assessment at the end of the school year. RESULTS: At the follow-up assessment, the mean score for the knowledge of helminths, calculated as a percentage of a total of 43 points on a questionnaire, was 90% higher in the intervention group than in the control group (63.3 vs. 33.4, P<0.001), the percentage of children who washed their hands after using the toilet was nearly twice as high in the intervention group (98.9%, vs. 54.2% in the control group; P<0.001), and the incidence of infection with soil-transmitted helminths was 50% lower in the intervention group than in the control group (4.1% vs. 8.4%, P<0.001). No adverse events were observed immediately (within 15 minutes) after albendazole treatment. CONCLUSIONS: The health-education package increased students' knowledge about soil-transmitted helminths and led to a change in behavior and a reduced incidence of infection within 1 school year. (Funded by UBS Optimus Foundation, Zurich, Switzerland; Australian New Zealand Clinical Trials Registry number, ACTRN12610000048088.).

Molecular design and genetic optimization of antimicrobial peptides containing unnatural amino acids against antibiotic-resistant bacterial infections.

Antimicrobial peptides (AMPs) have been the focus of intense research towards the finding of a viable alternative to current small-molecule antibiotics, owing to their commonly observed and naturally occurring resistance against pathogens. However, natural peptides have many problems such as low bioavailability and high allergenicity that largely limit the clinical applications of AMPs. In the present study, an integrative protocol that combined chemoinformatics modeling, molecular dynamics simulations, and in vitro susceptibility test was described to design AMPs containing unnatural amino acids (AMP-UAAs). To fulfill this, a large panel of synthetic AMPs with determined activity was collected and used to perform quantitative structure-activity relationship (QSAR) modeling. The obtained QSAR predictors were then employed to direct genetic algorithm (GA)-based optimization of AMP-UAA population, to which a number of commercially available, structurally diverse unnatural amino acids were introduced during the optimization process. Subsequently, several designed AMP-UAAs were confirmed to have high antibacterial potency against two antibiotic-resistant strains, i.e. multidrug-resistant Pseudomonas aeruginosa (MDRPA) and methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentration (MIC) < 10 µg/ml. Structural dynamics characterizations revealed that the most potent AMP-UAA peptide is an amphipathic helix that can spontaneously embed into an artificial lipid bilayer and exhibits a strong destructuring tendency associated with the embedding process. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 746-756, 2016.

Effects of Microtus fortis lymphocytes on Schistosoma japonicum in a bone marrow transplantation model.

Microtus fortis is a non-permissive host for Schistosoma japonicum. While M. fortis lymphocytes are known to provide natural resistance against S. japonicum, the specific mechanism remains unclear. A bone marrow transplantation (BMT) model was established using immunodeficient mice, either nude (experiment 1) or V(D)J recombination activation gene deficient mice (RAG-1(-/-)) (experiment 2) as recipients and M. fortis or C57BL/6 mice as donors. The growth and development of S. japonicum were evaluated in each group to assess the role of M. fortis lymphocytes in the response to infection. Lymphocyte ratios and S. japonicum-specific antibody production in transplanted groups increased significantly compared to those in non-transplanted group. Spleen indices and density of splenic lymphocytes in transplanted RAG-1(-/-) mice were higher than those in non-transplanted RAG-1(-/-) mice. No difference in the worm burden was observed among group A (transplants derived from M. fortis), B (transplants derived from C57BL/6 mouse) and C (non-transplanted mice), although worms in group A were shorter than those in other groups, except non-transplanted RAG-1(-/-) mice. Reproductive systems of worms in mice (nude or RAG-1(-/-)) transplanted from M. fortis were not as mature as those in mice (nude or RAG-1(-/-)) transplanted from C57BL/6 mouse and non-transplanted nude mice, but they were more mature than worms in non-transplanted RAG-1(-/-) mice. Therefore, the transplantation model using nude and RAG-1(-/-) mice was successfully established. The M. fortis lymphocytes did not appear to affect the S. japonicum worm burden, but they led to schistosome shortening and a significant reduction in parasite spawning. Thus, M. fortis cellular and humoral immunity provides a defense against schistosomes by negatively impacting the parasite growth and reproductive development.

[Influence factors of Schistosoma japonicum infection among fishermen in eastern Dongting Lake Region].

OBJECTIVE: To investigate schistosome infection among the professional fishermen in Yueyang County, East Dongting Lake Region and its influence factors. METHODS: A total of 275 fishermen from two fisherman villages in Yueyang County were selected in 2009. They were investigated by fecal examination and questionnairing. The stool-egg positive individuals were detected by B ultrasound. The multivariate unconditional Logistic regression analysis was used to explore the related factors of schistosome infection and liver in fishermen. RESULTS: The total infection rate in fishermen was 40.4% (111/275), and the geometric mean of EPG was 17.4 +/- 4.4. B ultrasound data showed among 111 egg positive individuals, 39 (35.1%) cases manifested as hepatomegaly, 22 (19.8%) had splenomegaly, 11 (9.9%) had portal vein expansion and 65 (58.6%) had hepatic fibrosis. Multivariate unconditional Logistic regression analysis showed that age groups (OR = 0.630), fishing working years (OR = 2.470), chemotherapy frequency (OR = 0.425) and chemotherapy in 2008 (OR = 0.290) were the influence factors on schistosome infection (P < 0.01). CONCLUSION: Schistosome infection rate is high, Schistosoma japonicum-induced liver and spleen injuries are still severe in fisherman of Eastern Dongting Lake Region.

A Transformer-Based Prediction Method for Depth of Anesthesia During Target-Controlled Infusion of Propofol and Remifentanil.

Accurately predicting anesthetic effects is essential for target-controlled infusion systems. The traditional (PK-PD) models for Bispectral index (BIS) prediction require manual selection of model parameters, which can be challenging in clinical settings. Recently proposed deep learning methods can only capture general trends and may not predict abrupt changes in BIS. To address these issues, we propose a transformer-based method for predicting the depth of anesthesia (DOA) using drug infusions of propofol and remifentanil. Our method employs long short-term memory (LSTM) and gate residual network (GRN) networks to improve the efficiency of feature fusion and applies an attention mechanism to discover the interactions between the drugs. We also use label distribution smoothing and reweighting losses to address data imbalance. Experimental results show that our proposed method outperforms traditional PK-PD models and previous deep learning methods, effectively predicting anesthetic depth under sudden and deep anesthesia conditions.

Quality Information Detection of Agaricus bisporus Based on a Portable Spectrum Acquisition Device.

As one of the most popular edible fungi in the market, the quality of Agaricus bisporus will determine its sales volume. Therefore, to achieve rapid and nondestructive testing of the quality of Agaricus bisporus, this study first built a portable spectrum acquisition device for Agaricus bisporus. The Ocean Spectromeper was used to calibrate the spectral data of the device, and the linear regression analysis method was combined to analyze the two. The results showed that the Pearson correlation coefficient of significance between the two was 0.98. Then, the spectral data of Agaricus bisporus were collected, the spectral characteristic wavelength of Agaricus bisporus was extracted by the SPA and PCA algorithms, and the moisture content and whiteness prediction models based on a BP neural network and PLSR, respectively, were built. The parameters of the BP neural network model were optimized by SSA. The R2 values for the final moisture content and the predicted whiteness were 0.95 and 0.99, and the RMSE values were 5.04% and 0.60, respectively. The results show that the portable spectral acquisition and analysis device can be used for the accurate and rapid quality detection of Agaricus bisporus.

[Protective effect of SjC23-Hsp70 DNA vaccine and interleukin-12 on Schistosoma japonicum infection in water buffalos].

OBJECTIVE: To determine the immune-protective effect of Japan Schistosoma (Chinese mainland strain) 23 kD membrane protein-heat shock protein (SjC23-Hsp70) DNA vaccine plus adjuvantinduced interleukin-12 (IL-12) plasmid DNA on Schistosoma japonicum infection in water buffalos. METHODS: Forty-five health water buffalos (8-10 months old) in non-endemic area of schistosomiasis were randomly assigned into group A (SjC23-Hsp70+IL-12, 300 µg), group B (SjC23+IL-12, 300 µg) and group C (pVAX+IL-12, 300 µg), 15 in each group. Each buffalo was immuned by shoulder intramuscular injection for 3 times, at an interval of 28 days. Twenty-eight days after the last immunization, each buffalo was infected with 1000 Japan cercariae of Schistosoma. Fecal examinations were conducted 2 days and 1 day before the perfusion, and on the day of perfusion. The number of hatching miracidia and eggs per gram feces was recorded. Fifty-six days after the infection, the buffalos were sacrificed and perfused via the descending aorta. The recovered adult worms and eggs in the liver tissue were counted. RESULTS: We compared group A and B with group C: the estrogen reduction rate was 45.7% and 26.61%; bug reduction rate was 44.51% and 25.84%; the fecal egg reduction rate was 41.1% and 31.63%; the miracidium reduction rate was 48.11% and 38.07%; and the liver egg reduction rate was 43.39% and 31.95%. The above rates in group A were higher than those in group B (P<0.05). CONCLUSION: SjC23-Hsp70 DNA vaccine combined with IL-12 may have a significant immunoprotective effect on buffalos.

[Exploratory thinking on the control technologies of Schistosomiasis japonica].

In this paper, the authors elaborated the difficulties of schistosomiasis control and analyzed shortages and problems of the skills currently used. In order to consolidate the progress in schistosomiasis control and reach the transmission-blocking target, research priorities on the disease control technologies are proposed.

MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1.

PURPOSE: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor, the prognosis of which remains poor. Recently, microRNAs have been reported to play crucial functions in multiple tumors, including HCC. However, the molecular mechanisms of miR-370 in HCC still remain largely unknown. The present study focused on the effects of miR-370 on HCC migration, invasion, and epithelial-mesenchymal transition (EMT). MATERIALS AND METHODS: We investigated the key roles and possible regulatory mechanism of miR-370 in regulating HCC metastasis with functional assays, such as transwell assay. Quantitative real-time PCR (qRT-PCR) was used to detect miR-370 and guanylylcyclase domain containing 1 (GUCD1) expression in HCC tissues and cells. Subsequently, we performed transwell assays to determine the functions of miR-370 in HCC cell invasion and migration. Western blot was used to determine protein expressions of relevant genes. Luciferase reporter assays were conducted to confirm the target gene of miR-370. RESULTS: qRT-PCR analysis demonstrated that miR-370 was dramatically downregulated in HCC. Moreover, downregulated miR-370 was found to be associated with poor survival and adverse clinicopathologic characteristics of HCC patients. Transwell assays revealed that miR-370 overexpression dramatically suppressed HCC invasion and migration. Meanwhile, miR-370 restoration prominently inhibited EMT progression in HCC cells. Luciferase reporter assays confirmed GUCD1 as a downstream target gene of miR-370. GUCD1 expression in HCC tissues was prominently increased and inversely correlated with miR-370 expression. Furthermore, GUCD1 was verified as mediating the suppressive influence of miR-370 on cell metastasis and EMT in HCC. CONCLUSION: Taken together, our study confirmed that miR-370 suppressed HCC cell metastasis and EMT via regulating GUCD1. Accordingly, the miR-370/GUCD1 axis may potentially acts as attractive therapeutic targets and novel biomarkers for HCC treatment.

A randomized, double-blind, placebo-controlled trial of safety and efficacy of combined praziquantel and artemether treatment for acute schistosomiasis japonica in China.

OBJECTIVE: To evaluate the safety and efficacy of combining artemether (AM) and praziquantel (PZQ) in different regimens for treating acute schistosomiasis japonica. METHODS: We undertook a randomized, double-blind, placebo-controlled trial within four specialized schistosomiasis hospitals in the Dongting Lake region, Hunan province, China, between May 2003 and December 2005. Study participants were randomized into one of four treatment regimes: group A received 60 mg/kg PZQ + 6 mg/kg AM; group B received 60 mg/kg PZQ + AM placebo; group C received 120 mg/kg PZQ + 6 mg/kg AM; and group D received 120 mg/kg PZQ + AM placebo. All participants were followed up over a 45-day period. The primary endpoint of the trial was human infection status (determined by positive stool examination). Secondary endpoints involved clinical observations and blood biochemistry, including monitoring haemoglobin and alanine aminotransferase levels over time. FINDINGS: Treatment efficacies of the four different treatment regimens were 98.0%, 96.4%, 97.7% and 95.7% for group A, B, C, and D respectively (P > 0.05). The group B had a greater treatment efficacy (96.4%) than the group D (95.7%) (P > 0.05). Group A treatment was better for clearance of fever (P < 0.05) and resulted in a shorter hospitalization time (P < 0.05). CONCLUSION: This is the first report of a randomized, double-blind, placebo-controlled trial for evaluating combined chemotherapy with AM and two different dosages (60 mg/kg and 120 mg/kg) of PZQ in the treatment of acute schistosomiasis japonica in China. The combination of AM and PZQ chemotherapy did not improve treatment efficacy compared with PZQ alone. PZQ given as a dosage of 60 mg/kg (1 day, 3 x 20 mg/kg doses at 4-5 hour intervals) may be as effective as a dosage of 120 mg/kg (6 days, 20 mg/kg for each day split into 3 doses at 4-5 hour intervals).

Rule of changes in serum GGT levels and GGT/ALT and AST/ALT ratios in primary hepatic carcinoma patients with different AFP levels.

OBJECTIVE: This study aims to explore the rule of changes in serum GGT activity, as well as GGT/ALT and AST/ALT ratios, in primary hepatic carcinoma (PHC) patients with different alpha-fetal protein (AFP) levels. METHODS: GGT, AST and ALT were detected in 370 PHC patients with positive HBs-Ag using a automatic biochemical analyzer, and AFP was detected using a Roche E170 modular analytics immunoassay analyzer. GGT level, as well as AST/ALT and GGT/ALT, ratios were compared among PHC patients with different AFP levels. RESULTS: As shown in Table 1, GGT levels were 109.59 ± 111.06, 151.13 ± 190.43, 135.86 ± 107.62, 151.36 ± 176.59 and 172.58 ± 188.84, respectively, in the groups of primary PHC patients with AFP levels of ⩽ 10, 10-100, 100-200, 200-400 and ⩾ 400 ng/ml; and the differences among these groups were not statistically significant (P> 0.05). AST/ALT ratios were 1.55 ± 1.02, 1.30 ± 0.81, 2.02 ± 1.89, 2.12 ± 1.11 and 1.73 ± 1.25, respectively; and the differences among these groups were not statistically significant (P> 0.05). GGT/ALT ratios were 3.43 ± 3.12, 3.57 ± 5.70, 3.57 ± 2.94, 3.89 ± 4.58 and 3.43 ± 3.61, respectively; and the differences among these groups were not statistically significant (P> 0.05). CONCLUSION: For patients with chronic hepatitis B and cirrhosis after hepatitis B, no matter how AFP level is, when liver function report reveals increased GGT, AST/ALT > 1 and GGT/ALT > 1 (that is, AST > ALT and GGT > ALT), even if AFP is negative, we should also be alert to the existence of PHC.

[Study on the relationship between the degree of periportal fibrosis, hepatic parenchymatous fibrosis and diameter of portal vein in Schistosoma japonicum infection].

The degree of periportal fibrosis, hepatic parenchymatous fibrosis and the diameter of portal vein in fishermen from highly endemic area of schistosomiasis japonica in Dongting Lake region were measured. The results showed a significant correlation between the degree of periportal fibrosis and parenchymatous fibrosis and the portal venous diameter with a correlation coefficient of 0.375 and 0.332 respectively. The authors consider that the diameter of the portal vein can be used to assess the hepatic morbidity of patients.

[Protective effects of co-immunization with SjCTPI-Hsp70 and interleukin-12 DNA vaccines against Schistosoma japonicum challenge infection in water buffalo].

OBJECTIVE: To induce protective effect of co-immunization with S. japonicum triose-phosphate isomerase fused to heat shock protein 70 (SjCTPI-Hsp70) plasmid and interleukin-12 (IL-12) DNA vaccines against Schistosoma japonicum (Chinese strain) infection in water buffalo. METHODS: Forty-five 8-10 months-old water buffalo from a nonendemic area were divided into three treatment groups each with fifteen buffalo: experimental group A (SjCTPI-Hsp70+IL-12, 300 microg), experimental group B (SjCTPI+IL-12, 300 microg), and control group C (pVAX+IL-12, 300 microg). All buffalo were immunized with a series of 3 intramuscular injections administered once every four weeks. Twenty-eight days postvaccination, water buffalo were percutaneously challenged with 1000 S. japonicum cercariae. Fecal examinations were conducted two days prior, one day prior, and on perfusion day, and the number of hatching miracidia and eggs per gram feces were recorded. Fifty-six days post-infection, the buffalo were sacrificed and perfused via the descending aorta. The recovered adult worms and eggs in liver tissue were counted. RESULTS: Groups A and B showed a worm reduction rate of 51.2% and 41.5% (chi2=1.89, P>0.05)), female worm reduction of 48.9% and 44.7% (chi2=0.35,P>0.05), fecal egg reduction of 52.1% and 38.3% (chi2=3.84,P<0.05), a reduction of miracidia-hatching rate by 52.1% and 33.2% (chi2=7.30, P<0.01), and liver egg reduction of 61.5% and 42.0% (chi2=7.61 , P<0.01), respectively. CONCLUSION: Co-immunization with SjCTPI-Hsp70 and IL-12 DNA vaccines induces protective immunity against S. japonicum in water buffalo.

Impact of parasitic infections and dietary intake on child growth in the schistosomiasis-endemic Dongting Lake Region, China.

The simultaneous impacts of parasitic infections and dietary intake on growth patterns were investigated for 427 children aged 10-13 years in the schistosomiasis-endemic Dongting Lake region of China. Height, weight, mid-upper arm circumference, and skinfold thicknesses (triceps, biceps, and subscapular) were measured, and eggs of Schistosoma japonicum, Ascaris lumbricoides, Trichuris trichiura, and Fasciolopsis buski in the collected stool samples of each subject were detected by Kato-Katz thick smear technique. Long-term dietary intake of each subject was assessed with a semiquantitative food frequency questionnaire. The results demonstrate that the study children were retarded in growth compared with the standards of Chinese rural children; among them, the girls were more frequently infected for S. japonicum and had lower intakes of protein and energy. Reduced height, weight, and mid-upper arm circumference were noted in children infected with S. japonicum, most severely in the girls with the least energy and protein intakes. Multiple stepwise regression analysis indicated that growth retardation was significantly and substantially associated with S. japonicum infection and lack of protein-energy intakes. For child health programs, regular schistosomiasis screening and treatment in schoolchildren needs to be complemented by health and nutrition education for both children and parents. Also, special attention should be paid to educating parents about the needs of girls.

Sex differences in the malnourished status of Chinese children due to schistosomiasis infections and inadequate dietary intake.

Based on nutritional and parasitological examinations of 389 children aged 10-13 years in five primary schools in the schistosomiasis endemic Dongting Lake region of China, the causal factors of their retarded growth, represented by height, weight, mid-upper arm circumference and body mass index, were investigated. Among the four parasites, schistosomiasis infection due to Schistosoma japonicum played a significant role, with higher rates in girls than in boys. Praziquantel treatment of schistosomiasis decreased the infection rate and improved the children's growth. For dietary intake factors, the contribution of protein to total energy intake, which was lower in girls than in boys, had the greatest effect on the growth patterns. The sex difference in growth retardation is judged to be attributable to the traditional norms, such as girls spending more time in infested environments and gender discrimination in food distribution.

[Study on the relationship of immune status with severity of schistosomiasis japonica in fishermen in the Dongting Lake].

OBJECTIVE: To investigate the relationship of the immune status and the intensity of infection or the severity of the hepatosplenic pathology among fishermen with schistosomiasis japonica in the Dongting Lake region. METHODS: Inquiring and physical examination (IPE), stool examination, B-ultrasonography of the liver and spleen, flow cytometry, turbidimetry and ELISA were undertaken to acquire or determine the intensity of infection (EPG in stool), pathological change in the liver and spleen and the level of cellular and humoral immunity. Data were analyzed with SPSS 10.0 statistics software. RESULTS: Compared with subjects from non-endemic area, the CD4+ T cells and the CD4+/CD8+ ratio in fishing population in the endemic area significantly decreased. The decrease of the CD4+/CD8+ ratio was more significant among population with positive stool exam and with the increase of EPG and/or severity of pathological change in the liver and spleen. Contrarily, the level of the total IgM and the anti-SEA IgG in serum from fishing population in the endemic area was significantly higher than those from non-endemic area. High level serum antibodies in those stool positives were remarkable with the increase of EPG and/or the severity of hepatosplenic pathological change. The total IgA increased considerably in the subjects with significant pathological change of the liver and spleen. A high total IgG was only detected in those stool positives. CONCLUSION: The immune status in fishermen with schistosomiasis in the Dongting Lake showed a suppressed cellular immunity and a hyper functioning humoral immune response. The imbalance of the immunity was related to the increase of the intensity of infection and the progress of the hepatosplenic pathology.

DNA detection of Schistosoma japonicum: diagnostic validity of a LAMP assay for low-intensity infection and effects of chemotherapy in humans.

BACKGROUND: Schistosomiasis has decreased significantly in prevalence and intensity of infection in China, thus more accurate and sensitive methods are desperately needed for the further control of schistosomiasis. The present work aimed to assess the utility of the loop-mediated isothermal amplification (LAMP) for detection of light intensity infection or false-negative patients and patients post-treatment, targeting the highly repetitive retrotransposon SjR2 of Schistosoma japonicum. METHODOLOGY/ PRINCIPAL FINDINGS: LAMP was first assessed in rabbits with low intensity infection (EPG<10). Then 110 patient sera from Hunan Province, China, and 47 sera after treatment by praziquantel were used to evaluate the diagnostic validity of LAMP. Meanwhile, 42 sera from healthy individuals in a non-endemic area, and 60 sera from "healthy" residents who were identified as being negative for feces examination and immuno-methods in an endemic area were also examined. The results showed that LAMP could detect S. japonicum DNA in sera from rabbits at 3rd day post-infection. Following administration of praziquantel, the S. japonicum DNA in rabbit sera became negative at 10 weeks post-treatment. Of 110 sera from patients, LAMP showed 95.5% sensitivity, and even for 41 patients with less than 10 EPG, the sensitivity of LAMP still reached to 95.1%. For 47 patients after treatment, the negative conversion rate of S. japonicum DNA in patient sera increased from 23.4%, 61.7% to 83.0% at 3 months, 6 months and 9 months post-treatment, respectively. No false-positive result was obtained for 42 human sera from non-endemic area, while for the 60 "healthy" individuals from endemic area, 10 (16.7%) individuals were positive by LAMP, which suggested that these individuals might be false-negative patients. CONCLUSIONS/ SIGNIFICANCE: The present study demonstrated that the LAMP assay is sensitive, specific, and affordable, which would help reduce schistosomiasis transmission through targeted treatment of individuals, particularly for those with negative stool examinations who may yet remain infected. The LAMP assay may provide a potential tool to support schistosomiasis control and elimination strategies.