The peptidoglycan recognition proteins PGRPLA and PGRPLB regulate Anopheles immunity to bacteria and affect infection by Plasmodium

Peptidoglycan recognition proteins (PGRPs) form a family of immune regulators that is conserved from insects to mammals. In the malaria vector mosquito Anopheles coluzzii , the peptidoglycan receptor PGRPLC activates the Imd pathway limiting both t he microbiota load and Plasmodium infection. Here, we carried out an RNAi screen to examine the rol e of all seven Anopheles PGRPs in infections with Plasmodium berghei and Plasmodium falciparum . We show that, in addition to PGRPLC, PGRPLA and PGRPS2/S3 also participate in antiparas itic defenses, and that PGRPLB promotes mosquito permissiveness to P. falciparum . We also demonstrate that following a mosquito blood feeding, which promotes growth of the gut microbiota, PGRPLA and PGRPLB positively and negatively regulate the activation of the Imd pathway, respective ly. Our data demonstrate that PGRPs are important regulators of the mosquito epithelial immunity and vector comp etence

Influence of two different resection techniques (conventional liver resection versus anterior approach) of liver metastases from colorectal cancer on hematogenous tumor cell dissemination – prospective randomized multicenter trial

<p>Abstract</p> <p>Background</p> <p>Surgical hepatic resection remains the treatment of choice for patients with liver metastases from colorectal cancer despite the use of alternative therapeutic strategies. Although this procedure provides long-term survival in a significant number of patients, 50–75% of the patients develop intra- and/or extrahepatic recurrence. One possible reason for tumor recurrence may be intraoperative hematogenous tumor cell dissemination due to mechanical manipulation of the tumor during hepatic resection. Surgical technique may have an influence on hematogenous tumor cell spread. We hypothesize that hematogenous tumor cell dissemination may be reduced by using the anterior approach technique compared to conventional liver resection.</p> <p>Methods/Design</p> <p>This is a multi-centre prospective randomized controlled, superiority trial to compare two liver resection techniques of liver metastases from colorectal cancer. 150 patients will be included and randomized intraoperatively after surgical exploration just prior to resection. The primary objective is to compare the anterior approach with the conventional liver resection technique with regard to intraoperative haematogenous tumor cell dissemination. As secondary objectives we examine five year survival rates (OS and DFS), blood loss, duration of operation, requirement of blood transfusions, morbidity rate, prognostic relevance of tumor cell detection in blood and bone marrow and the comparison of tumor cell detection by different detection methods.</p> <p>Conclusion</p> <p>This trial will answer the question whether there is an advantage for the anterior approach technique compared to the conventional resection group with regard to tumor cell dissemination. It will also add further information about prognostic differences, safety, advantages and disadvantages of each technique.</p> <p>Trial registration</p> <p>Current controlled trials – <b>ISRCTN45066244</b></p

The Role of Primary Care in Service Provision for People with Severe Mental Illness in the United Kingdom

Severe mental illness is a serious and potentially life changing set of conditions. This paper describes and analyses patient characteristics and service usage over one year of a representative cohort of people with a diagnosis of severe mental illness across England, including contacts with primary and secondary care and continuity of care

Extended Esophagectomy in Elderly Patients with Esophageal Cancer: Minor Effect of Age Alone in Determining the Postoperative Course and Survival

Elderly patients who undergo esophagectomy for cancer often have a high prevalence of coexisting diseases, which may adversely affect their postoperative course. We determined the relationship of advanced age (i.e., a parts per thousand yen70 years) with outcome and evaluated age as a selection criterion for surgery. Between January 1991 and January 2007, we performed a curative-intent extended transthoracic esophagectomy in 234 patients with cancer of the esophagus. Patients were divided into two age groups: <70 years (group I; 170 patients) and a parts per thousand yen70 years (group II; 64 patients). Both groups were comparable regarding comorbidity (American Society of Anesthesiologists classification), and tumor and surgical characteristics. The overall in-hospital mortality rate was 6.2% (group I, 5%, vs. group II, 11%, P = 0.09). Advanced age was not a prognostic factor for developing postoperative complications (odds ratio, 1.578; 95% confidence interval, 0.857-2.904; P = 0.143). The overall number of complications was equal with 58% in group I vs. 69% in group II (P = 0.142). Moreover, the occurrence of complications in elderly patients did not influence survival (P = 0.174). Recurrences developed more in patients <70 years (58% vs. 42%, P = 0.028). The overall 5-year survival was 35%, and, when included, postoperative mortality was 33% in both groups (P = 0.676).The presence of comorbidity was an independent prognostic factor for survival (P = 0.002). Advanced age (a parts per thousand yen70 years) has minor influence on postoperative course, recurrent disease, and survival in patients who underwent an extended esophagectomy. Age alone is not a prognostic indicator for survival. We propose that a radical resection should not be withheld in elderly patients with limited frailty and comorbidity

Self-Reported Serious Illnesses in Rural Cambodia: A Cross-Sectional Survey

BACKGROUND: There is substantial evidence that ill-health is a major cause of impoverishment in developing countries. Major illnesses can have a serious economic impact on poor households through treatment costs and income loss. However, available methods for measuring the impact of ill-health on household welfare display several shortcomings and new methods are thus needed. To understand the potential complex impact of major illnesses on household livelihoods, a study on poverty and illness was conducted in rural Cambodia, as part of an international comparative research project. A cross-sectional survey was performed to identify households affected by major illness for further in-depth interviews. METHODOLOGY AND PRINCIPAL FINDINGS: 5,975 households in three rural health districts were randomly selected through a two-stage cluster sampling and interviewed. 27% of the households reported at least one member with a serious illness in the year preceding the survey and 15% of the household members reported suffering from at least one serious illness. The most reported conditions include common tropical infectious diseases, chronic diseases (notably hypertension and heart diseases) and road traffic accidents. Such conditions were particularly concentrated among the poor, children under five, women, and the elderly. Poor women often reported complications related to pregnancy and delivery as serious illnesses. CONCLUSIONS AND SIGNIFICANCE: Despite some methodological limitations, this study provides new information on the frequency of self-reported serious illnesses among the rural Cambodia's population, which serves as a basis for further in-depth investigation on 'major illnesses' and their economic consequences on poor households. This can in turn help policy makers to formulate appropriate interventions to protect the poor from the financial burden associated with ill-health. Our findings suggest that every year a considerable proportion of rural population in Cambodia, especially the poor and vulnerable, are affected by serious illnesses, both communicable and non-communicable diseases

The rate of cellular hydrogen peroxide removal shows dependency on GSH: Mathematical insight into in vivo H2O2 and GPx concentrations

Although its concentration is generally not known, glutathione peroxidase-1 (GPx-1) is a key enzyme in the removal of hydrogen peroxide (H2O2) in biological systems. Extrapolating from kinetic results obtained in vitro using dilute, homogenous buffered solutions, it is generally accepted that the rate of elimination of H2O2 in vivo by GPx is independent of glutathione concentration (GSH). To examine this doctrine, a mathematical analysis of a kinetic model for the removal of H2O2 by GPx was undertaken to determine how the reaction species (H2O2, GSH, and GPx-1) influence the rate of removal of H2O2. Using both the traditional kinetic rate law approximation (classical model) and the generalized kinetic expression, the results show that the rate of removal of H2O2 increases with initial GPxr, as expected, but is a function of both GPxr and GSH when the initial GPxr is less than H2O2. This simulation is supported by the biological observations of Li et al.. Using genetically altered human glioma cells in in vitro cell culture and in an in vivo tumour model, they inferred that the rate of removal of H2O2 was a direct function of GPx activity × GSH (effective GPx activity). The predicted cellular average GPxr and H2O2 for their study are approximately GPxr ≤ 1 μm and H2O2 ≈ 5 μm based on available rate constants and an estimation of GSH. It was also found that results from the accepted kinetic rate law approximation significantly deviated from those obtained from the more generalized model in many cases that may be of physiological importance

Polymorphisms of the TUB Gene Are Associated with Body Composition and Eating Behavior in Middle-Aged Women

BACKGROUND: The TUB gene, encoding an evolutionary conserved protein, is highly expressed in the hypothalamus and might act as a transcription factor. Mutations in TUB cause late-onset obesity, insulin-resistance and neurosensory deficits in mice. An association of common variants in the TUB gene with body weight in humans has been reported. METHODS/FINDINGS: The aim was to investigate the relationship of single nucleotide polymorphisms (SNPs) of the TUB gene (rs2272382, rs2272383 and rs1528133) with both anthropometry and self-reported macronutrient intake from a validated food frequency questionnaire. These associations were studied in a population-based, cross-sectional study of 1680 middle-aged Dutch women, using linear regression analysis. The minor allele C of the rs1528133 SNP was significantly associated with increased weight (+1.88 kg, P = 0.022) and BMI (+0.56 units, P = 0.05). Compared with non-carriers, both AG heterozygotes and AA homozygotes of the rs2272382 SNP derived less energy from fat (AG: -0.55+/-0.28%, P = 0.05, AA: -0.95+/-0.48%, P = 0.047). However, both genotypes were associated with an increased energy intake from carbohydrates (0.69+/-0.33%, P = 0.04 and 1.68+/-0.56%, P = 0.003, respectively), mainly because of a higher consumption of mono- and disaccharides. Both these SNPs, rs2272382 and rs1528133, were also associated with a higher glycemic load in the diet. The glycemic load was higher among those with AG and AA genotypes for the variant rs2272382 than among the wild types (+1.49 (95% CI: -0.27-3.24) and +3.89 (95% CI: 0.94-6.85) units, respectively). Carriers of the minor allele C of rs1528133 were associated with an increased glycemic load of 1.85 units compared with non-carriers. CONCLUSIONS: Genetic variation of the TUB gene was associated with both body composition and macronutrient intake, suggesting that TUB might influence eating behavior

Predation Risk Shapes Social Networks in Fission-Fusion Populations

Predation risk is often associated with group formation in prey, but recent advances in methods for analysing the social structure of animal societies make it possible to quantify the effects of risk on the complex dynamics of spatial and temporal organisation. In this paper we use social network analysis to investigate the impact of variation in predation risk on the social structure of guppy shoals and the frequency and duration of shoal splitting (fission) and merging (fusion) events. Our analyses revealed that variation in the level of predation risk was associated with divergent social dynamics, with fish in high-risk populations displaying a greater number of associations with overall greater strength and connectedness than those from low-risk sites. Temporal patterns of organisation also differed according to predation risk, with fission events more likely to occur over two short time periods (5 minutes and 20 minutes) in low-predation fish and over longer time scales (>1.5 hours) in high-predation fish. Our findings suggest that predation risk influences the fine-scale social structure of prey populations and that the temporal aspects of organisation play a key role in defining social systems