A dendritic cell vaccine pulsed with autologous hypochlorous Acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside.

PURPOSE: Whole tumor lysates are promising antigen sources for dendritic cell (DC) therapy as they contain many relevant immunogenic epitopes to help prevent tumor escape. Two common methods of tumor lysate preparations are freeze-thaw processing and UVB irradiation to induce necrosis and apoptosis, respectively. Hypochlorous acid (HOCl) oxidation is a new method for inducing primary necrosis and enhancing the immunogenicity of tumor cells. EXPERIMENTAL DESIGN: We compared the ability of DCs to engulf three different tumor lysate preparations, produce T-helper 1 (TH1)-priming cytokines and chemokines, stimulate mixed leukocyte reactions (MLR), and finally elicit T-cell responses capable of controlling tumor growth in vivo. RESULTS: We showed that DCs engulfed HOCl-oxidized lysate most efficiently stimulated robust MLRs, and elicited strong tumor-specific IFN-γ secretions in autologous T cells. These DCs produced the highest levels of TH1-priming cytokines and chemokines, including interleukin (IL)-12. Mice vaccinated with HOCl-oxidized ID8-ova lysate-pulsed DCs developed T-cell responses that effectively controlled tumor growth. Safety, immunogenicity of autologous DCs pulsed with HOCl-oxidized autologous tumor lysate (OCDC vaccine), clinical efficacy, and progression-free survival (PFS) were evaluated in a pilot study of five subjects with recurrent ovarian cancer. OCDC vaccination produced few grade 1 toxicities and elicited potent T-cell responses against known ovarian tumor antigens. Circulating regulatory T cells and serum IL-10 were also reduced. Two subjects experienced durable PFS of 24 months or more after OCDC. CONCLUSIONS: This is the first study showing the potential efficacy of a DC vaccine pulsed with HOCl-oxidized tumor lysate, a novel approach in preparing DC vaccine that is potentially applicable to many cancers. Clin Cancer Res; 19(17); 4801-15. ©2013 AACR.

Effect of the Contents and Form of Rabies Glycoprotein on the Potency of Rabies Vaccination in Cattle

One of the methods used for controlling cattle rabies in Brazil consists of vaccination. Sometimes, however, rabies occurs in cattle supposedly protected. Since rabies vaccine batches are officially controlled by tests performed on laboratory animals, it is questionable whether the minimal mandatory requirements really correspond to immunogenicity in the target species. We have analyzed the association among potencies of rabies vaccines tested by the NIH test, the contents and form (free-soluble or virus-attached) of rabies glycoprotein (G) in the vaccine batches, and the virus-neutralizing antibodies (VNA) titers elicited in cattle. No correlation was found between G contents in the vaccine batches and the NIH values, whatever the presentation of G. There was no correlation either between NIH values and VNA titers elicited in cattle. There was, however, a positive correlation (r = 0.8681; p = 0.0001) between the amounts of virion-attached G present in the vaccine batches and VNA elicited in cattle. This was not observed when the same analysis was performed with total-glycoprotein or free-soluble glycoprotein. The study demonstrated that NIH values can not predict the effect of the immunogen in cattle. On the other hand, the quantification of virus-attached rabies glycoprotein has a strong correlation with VNA elicited in cattle.

Oviposition Attractancy of Bacterial Culture Filtrates: response of Culex quinquefasciatus

Oviposition attractants could be used for monitoring as well as controlling mosquitoes by attracting them to lay eggs at chosen sites. In the present study, culture filtrates of seven bacterial species were tested for their attractancy against gravid females of Culex quinquefasciatus. When their oviposition active indices (OAI) were studied, the culture filtrates of Bacillus cereus and Pseudomonas fluorescens exhibited oviposition attractancy (OAI = >0.3) at 100 ppm and the OAI were respectively 0.70 and 0.47. Culture filtrates of B. thuringiensis var. israelensis (wild type), B. t. var. israelensis (mutant) and B. sphaericus showed attractancy at 2000 ppm with OAI of respectively 0.71, 0.59 and 0.68. However, the OAI of B. megaterium as well as Azospirillum brasilense was 0.13 (at 2000 ppm), which was less than 0.3 required to be considered them as attractants. When the oviposition attractancy of the bacterial culture filtrates were compared with that of a known oviposition attractant, p-cresol (at 10 ppm), the culture filtrates of B. t. var. israelensis (wild type) and B. cereus were found to be more active than p-cresol, respectively with 64.2 and 54.3% oviposition.

Having Your Cake and Eating It, Too: Can Regulatory Agencies Be Both Independent and Accountable?

Independent regulatory agencies (IRAs) were created in various sectors and on different governmental levels to implement liberalization policies. This paper investigates the link between IRAs' independence, which is said to promote regulatory credibility and the use of technical expertise, and their accountability, which is related to the need for controlling and legitimizing independent regulators. The literature on the regulatory state anticipates a positive relation between the independence and accountability of IRAs, but systematic empirical evidence is still lacking. To tackle this question, this paper measures and compares the independence and the accountability of IRAs in three differentially liberalized sectors in Switzerland (telecommunications, electricity and railways). With the application of Social Network Analysis, this piece of research shows that IRAs can be de facto independent and accountable at the same time, but the two features do not necessarily co-evolve in the same direction.

Effect of diflubenzuron on immature stages of Haematobia irritans (L.) (Diptera: Muscidae) in Uberlândia, State of Minas Gerais, Brazil

Horn fly immatures were raised in media containing different concentrations of diflubenzuron in order to verify their susceptibility to this insect growth regulator (IGR). The 50% and 95% lethal concentrations of diflubenzuron for the population (LC50, LC95) were determined as well as the effect of this IGR on the different immature horn fly stages. The tests were performed using the progeny of adults collected in the field. The immatures were maintained in a growth chamber at 25.0 ± 0.5ºC and 12-12 h photoperiod. IGR concentrations of 300 ppb, 100 ppb and 50 ppb were lethal for 100% of the sample. Pupae malformation occurred in the breeding media containing different diflubenzuron concentrations. Values for LC50 , LC95 (± 95% fiducial limits) and the slope of the regression line were respectively, 25.521 ± 1.981 ppb, 34.650 ± 2.001 ppb and 12.720 ± 1.096. The third larval instar was more sensitive to the sub-lethal concentration of the product than the first and second ones were. The results indicate that this IGR can be an important tool for controlling horn fly populations as well as for managing horn fly resistance to conventional insecticides against Haematobia irritans in Uberlândia, State of Minas Gerais.

The molluscicidal activity of niclosamide (Bayluscide WP70®) on Melanoides tuberculata (Thiaridae), a snail associated with habitats of Biomphalaria glabrata (Planorbidae)

The aim of this study was to determine the toxicity of niclosamide (Bayluscide ®) on Melanoides tuberculata and Biomphalaria glabrata under laboratory conditions. The latter species is the intermediate host of Schistosoma mansoni (Sambon 1917). M. tuberculata was successfully used as competitor of B. glabrata in biological control programs in French West Indies. Both molluscicide and biological control using M. tuberculata have proved to be successful in reducing the population density of B. glabrata. The associated use of molluscicide in this area would be an effective measure if M. tuberculata were less susceptibility to the molluscicide than B. glabrata. Three hundreds individuals each of B. glabrata and of M. tuberculata, collected in Sumidouro, State of Rio de Janeiro, were used in the experiment. The molluscs were exposed to 14 different concentrations of niclosamide as recommended by the World Health Organization. Probit analysis was used to determine the LC 50 and LC 90. The LC 50 and LC 90 values for B. glabrata were 0.077 mg/l and 0.175 mg/l, respectively and the LC 50 and LC 90 values for M. tuberculata were 0.082 mg/l and 0.221 mg/l respectively. As the lethal concentrations of niclosamide were approximately the same to both species, this could be a disadvantage when controlling B. glabrata with niclosamide in an area of M. tuberculata occurrence. It migth therefore be preferable to utilize the latex extracted from the Euphorbia splendens, which presented a much higher efficiency for B. glabrata than to M. tuberculata.

Quality Of Attachment, Perinatal Risk, And Mother-Infant Interaction In A High-Risk Premature Sample

Thirty-three families, each with a premature infant born less than 33 gestational weeks, were observed in a longitudinal exploratory study. Infants were recruited in a neonatal intensive care unit, and follow-up visits took place at 4 months and 12 months of corrected age. The severity of the perinatal problems was evaluated using the Perinatal Risk Inventory (PERI; A.P. Scheiner & M.E. Sexton, 1991). At 4 months, mother infant play interaction was observed and coded according to the CARE-index (P.M. Crittenden, 2003); at 12 months, the Strange Situation Procedure (SSP; M.D.S. Ainsworth, M.C. Blehar, E. Waters. & S. Wall, 1978) was administered. Results indicate a strong correlation between the severity of perinatal problems and the quality of attachment at 12 months. Based on the PERI, infants with high medical risks more frequently tended to be insecurely attached. There also was a significant correlation between insecure attachment and dyadic play interaction at 4 months (i.e., maternal controlling behavior and infant compulsive compliance). Moreover, specific dyadic interactive patterns could be identified as protective or as risk factors regarding the quality of attachment. Considering that attachment may have long-term influence on child development, these results underline the need for particular attention to risk factors regarding attachment among premature infants.

Comparison of the clientele of an anonymous HIV test centre and persons tested in the general population.

This study compares the clientele of a Swiss anonymous test centre with the general population tested. Information was obtained through similar questionnaires submitted to two samples of HIV-tested people aged from 17 to 45 years: the first administered in the context of a general population telephone survey (n = 245) and the second completed during face-to-face interviews of the clientele of an anonymous test centre (n = 250). The test centre sample has higher proportions of younger and single people. Attenders for anonymous testing were more likely to have acquired a new regular partner during the year preceding the interview (48.0% versus 14.4%). These differences remain when controlling for age and gender. Decision to test comes mostly from the respondent's own initiative, but suggestion from a doctor is more frequent in the general population (23.8% versus 0.8%), whereas suggestion from partner or friends is more frequent in the anonymous centre (44.4% versus 3.0%). The anonymous test centre clientele is not different from the general population tested except for the relational situation and origin of decision for testing. The test centre has become a place where the general population finds a response to a situation-specific need for HIV testing.

Neither Private nor Public: The Effects of Communal Provision of Water on Child Health in Peru

The literature on local services has focused on the effects of privatization and, if anything, has compared the effects of private and mixed public-private systems versus public provision. However, alternative forms of provision such as cooperatives, which can be very prevalent in many developing countries, have been completely ignored. In this paper, we investigate the effects of communal water provison (Comités Vecinales and Juntas Administrativas de Servicios de Saneamiento) on child health in Peru. Using detailed survey data at the household- and child-level for the years 2006-2010, we exploit the cross-section variability to assess the differential impact of this form of provision. Despite controlling for a wide range of household and local characteristics, the municipalities served by communal organizations are more likely to have poorer health indicators, what would result in a downward bias on the absolute magnitude of the effect of cooperatives. We rely on an instrumental variable strategy to deal with this potential endogeneity problem, and use the personnel resources and the administrative urban/rural classi fication of the municipalities as instruments for the provision type. The results show a negative and signi cant effect of comunal water provision on diarrhea among under- five year old children. Keywords: water utilities, cooperatives, child health, regulation, Peru. JEL Classi fication Numbers: L33; L50; L95

Achievements of schistosomiasis control in China

The control of schistosomiasis has been spectacularly successful in terms of controlling endemicity and severity of the disease during the last 50 years. It can be categorized into two stages. From 1955 through 1980, the transmission-control strategy had been widely and successfully carried out. By the end of 1980, the epidemic of schistosomiasis was successfully circumscribed in certain core regions including areas at the middle and low reaches of the Yangtze River and some mountainous areas in Sichuan and Yunnan provinces, where control of schistosomiasis had been demonstrated to be very difficult to be sustained. Therefore, since 1980, schistosomiasis control in China has been modified to employ a stepwise strategy, based on which morbidity control has been given priorities and if possible transmission control has been pursued. However, since snail-ridden areas remain unchanged so far, reinfections occur frequently. This necessitates a maintenance phase to consolidate the achievements in the control of schistosomiasis. In the mean time, we are challenged with some environmental, social and economical changes in terms of controlling schistosomiasis. Successfully controlling schistosomiasis in China is still a long-term task but will be achieved without doubt along with the economic development and the promotion of living and cultural standard of people.

GLUT2, glucose sensing and glucose homeostasis.

The glucose transporter isoform GLUT2 is expressed in liver, intestine, kidney and pancreatic islet beta cells, as well as in the central nervous system, in neurons, astrocytes and tanycytes. Physiological studies of genetically modified mice have revealed a role for GLUT2 in several regulatory mechanisms. In pancreatic beta cells, GLUT2 is required for glucose-stimulated insulin secretion. In hepatocytes, suppression of GLUT2 expression revealed the existence of an unsuspected glucose output pathway that may depend on a membrane traffic-dependent mechanism. GLUT2 expression is nevertheless required for the physiological control of glucose-sensitive genes, and its inactivation in the liver leads to impaired glucose-stimulated insulin secretion, revealing a liver-beta cell axis, which is likely to be dependent on bile acids controlling beta cell secretion capacity. In the nervous system, GLUT2-dependent glucose sensing controls feeding, thermoregulation and pancreatic islet cell mass and function, as well as sympathetic and parasympathetic activities. Electrophysiological and optogenetic techniques established that Glut2 (also known as Slc2a2)-expressing neurons of the nucleus tractus solitarius can be activated by hypoglycaemia to stimulate glucagon secretion. In humans, inactivating mutations in GLUT2 cause Fanconi-Bickel syndrome, which is characterised by hepatomegaly and kidney disease; defects in insulin secretion are rare in adult patients, but GLUT2 mutations cause transient neonatal diabetes. Genome-wide association studies have reported that GLUT2 variants increase the risks of fasting hyperglycaemia, transition to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases. Individuals with a missense mutation in GLUT2 show preference for sugar-containing foods. We will discuss how studies in mice help interpret the role of GLUT2 in human physiology.

Genetic and epigenetic analysis of SSAT gene dysregulation in suicidal behavior.

It has recently been proposed that the SSAT gene plays a role in the predisposition to suicidal behavior. SSAT expression was found to be down-regulated in the brain of suicide completers. In addition, a single nucleotide polymorphism (SNP) rs6526342 was associated both with variation in SSAT expression and with suicidal behavior. In this study, we aimed to characterize the relationship between SSAT dysregulation and suicide behavior. To this end, we measured SSAT expression levels in the ventral prefrontal cortex (VPFC) of suicide completers (n = 20) and controls (n = 20) and found them to be significantly down-regulated in suicide victims (P = 0.007). To identify the basis of the regulation of SSAT expression, we performed an association analysis of 309 SNPs with SSAT transcript levels in 53 lymphoblastoid cell lines from the CEPH collection. We then examined the methylation status of the SSAT promoter region in males and females suicide completers and control subjects whose SSAT brain expression had been measured. We found no evidence to support a role for SNPs in controlling the level of SSAT expression. SSAT promoter methylation levels were not different between suicide completers and controls and did not correlate with SSAT expression levels. In addition, we found no indication of a genetic association between suicidal behavior and SNPs located within the SSAT gene. Our study provides new results which show that dysregulation of SSAT expression does play a role in suicide behavior. However, our data do not support any association between rs6526342 and variation in SSAT expression or suicidal behavior.

Review of Measures to Reduce Costs in the Private Health Insurance Market 2013

This report was prepared independently by Mr McLoughlin with the insurers support, for consideration by the Minister for Health and the insurers.  All parties were very conscious of the importance of respecting competition law when dealing with issues such as prices and costs. The Phase 1 report contains 32 recommendations under 9 headings as follows: Most of the recommendations in the Phase 1 report could be implemented on an administrative basis, while a small number, if adopted, would require legislation. Some of the key recommendations to drive down costs are can be summarised as follows: Controlling costs in private health insurance Care settings and use of resources Age structure of the market Clinical audit and utilisation management Industry approach to private psychiatry Fraud, waste and abuse Chronic disease management Claims processing Admission and discharge procedures and processes. Most of the recommendations in the Phase 1 report could be implemented on an administrative basis, while a small number, if adopted, would require legislation.

Obesity increases your risk of developing diabetes

There are an estimated 69,000 adults and 1092 children living with diabetes in Northern Ireland in 2010. The number of adults with diabetes in Northern Ireland has increased by 34% since 2004. Many of these cases are preventable and related to obesity. With this in mind, during Diabetes Week (12 - 18 June 2011) the Public Health Agency is encouraging everyone across Northern Ireland to be aware of how diabetes can be prevented and what the signs and symptoms of diabetes are to ensure early diagnosis and good diabetic care.Type 1 diabetes cannot be prevented. It usually occurs in children and young adults. Type 2 diabetes typically occurs after the age of 40, but may occur at a younger age, and can often be prevented - mainly by keeping your weight within the normal range for your height. Dr Brid Farrell, Consultant in Public Health Medicine, PHA, said: "The increase of diabetes occurring in the population can be explained by rising levels of obesity, people living longer and improved detection and diagnosis of diabetes in primary care."The symptoms of diabetes can include increased thirst, passing urine more frequently (bedwetting in children), extreme tiredness, slow healing infections, blurred vision and significant or unexplained weight loss. Symptoms of diabetes can develop quickly over days or weeks, and sometimes with Type 2 diabetes, a person may have no symptoms. Early diagnosis is important. If you think you have diabetes speak to your GP or pharmacist.Dr Farrell continued: "Diabetes is a lifelong condition, but complications can be prevented or delayed by controlling your blood sugar, and treating high blood pressure and high cholesterol. If you have diabetes, a healthy diet and regular exercise is very important."Health Minister Edwin Poots said:"Diabetes is a serious condition, which affects many thousands of people across Northern Ireland. While not all diabetes is preventable, we all have a responsibility to look after our own health. "By making healthier lifestyle choices such as eating a healthy, well-balanced diet and taking regular exercise, we can reduce our risk of developing potentially life threatening conditions such as type 2 diabetes. I would urge everyone to take every possible step to improve their health and avoid developing preventable illnesses."Ends

Prevent type 2 diabetes by preventing obesity

In 2011 nearly 73,000 adults in Northern Ireland are registered as having diabetes. Many cases of diabetes are preventable and are the result of obesity. With this in mind, on World Diabetes Day, 14 November 2011, the Public Health Agency is encouraging everyone across Northern Ireland to be aware of how Type 2 diabetes can be prevented, the dangers it can cause to your health and what the signs and symptoms of diabetes are to ensure early diagnosis.The links between type 2 diabetes and obesity are firmly established. Without the intervention of a healthy diet and appropriate exercise, obesity may develop into diabetes over a relatively short period of time. According to the International Diabetes Federation (IDF), worldwide 80 per cent of people with Type 2 diabetes are overweight or obese at the time of diagnosis.If you are overweight, or obese the key step to preventing or delaying the onset of Type 2 diabetes is to lose a small amount of weight by making healthy food choices and being physically active 30 minutes a day, 5 days a week.Diabetes, if left untreated can cause serious long term health complications such as heart disease, kidney damage, eye problems, which can affect vision, and foot problems leading to amputation.Dr Brid Farrell, Consultant in Public Health Medicine, PHA, said: "The increase of diabetes occurring in the population can be explained by rising levels of obesity, people living longer and improved detection and diagnosis of diabetes in primary care."Having a family history of Type 2 diabetes increases your chances of developing diabetes. Take the first step today toward lowering your risk for Type 2 diabetes and improving your health and the health of future generations." The symptoms of diabetes can include increased thirst, passing urine more, frequently (bedwetting in children), extreme tiredness, slow healing infections, blurred vision and significant or unexplained weight loss. Symptoms of diabetes can develop quickly over days or weeks, and sometimes with Type 2 diabetes, a person may have no symptoms. Early diagnosis is important. If you think you have diabetes speak to your GP or pharmacist.Dr Farrell continued: "Diabetes is a lifelong condition, but complications can be prevented or delayed by controlling your blood sugar, and treating high blood pressure and high cholesterol. If you have diabetes, a healthy diet and regular exercise is very important."Health Minister Edwin Poots said:"Diabetes is a serious condition, which affects many thousands of people across Northern Ireland. While not all diabetes is preventable, we all have a responsibility to look after our own health. "By making healthier lifestyle choices such as eating a healthy, well-balanced diet and taking regular exercise, we can reduce our risk of developing potentially life threatening conditions such as type 2 diabetes. I would urge everyone to take every possible step to improve their health and avoid developing preventable illnesses