Cytokine expression in malaria-infected non-human primate placentas

Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM) leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal models for studying placental malaria can provide novel ways of circumventing problems experienced during placental malaria research in humans such as inaccurate estimation of gestational ages. Using the newly established olive baboon (Papio anubis)-Plasmodium knowlesi (P. knowlesi) H strain model of placental malaria, experiments were carried out to determine placental cytokine profiles underlying the immunopathogenesis of placental malaria. Four pregnant olive baboons were infected with blood stage P. knowlesi H strain parasites on the one fiftieth day of gestation while four other uninfected pregnant olive baboons were maintained as uninfected controls. After nine days of infection, placentas were extracted from all the eight baboons through cesarean surgery and used for the processing of placental plasma and sera samples for cytokine sandwich enzyme linked immunosorbent assays (ELISA). Results indicated that the occurrence of placental malaria was associated with elevated concentrations of tumour necrosis factor alpha (TNF-{\alpha}) and interleukin 12 (IL-12). Increased levels of IL-4, IL-6 and IL-10 and interferon gamma (IFN-{\gamma}) levels were detected in uninfected placentas. These findings match previous reports regarding immunity during PM thereby demonstrating the reliability of the olive baboon-P. knowlesi model for use in further studies.Comment: Open Veterinary Journal 1st June 2012. Seven pages, Three Figures. arXiv admin note: text overlap with arXiv:1201.323

Idealised EPR states from non-phase matched parametric down conversion

Entanglement of high dimensional states is becoming increasingly important for quantum communication and computing. The most common source of entangled photons is spontaneous parametric down conversion (SPDC), where the degree of frequency and momentum entanglement is determined by the non-linear interaction volume. Here we show that by reducing the length of a highly non-linear material to the micrometer scale it is possible to relax the longitudinal phase matching condition and reach record levels of transverse wavevector entanglement. From a micro-sized layer of lithium niobate we estimate the number of entangled angular modes to be over 1200. The entanglement is measured both directly using correlation measurements and indirectly using stimulated emission tomography. The high entanglement of the state generated can be used to massively increase the quantum information capacity of photons, but it also opens up the possibility to improve the resolution of many quantum imaging techniques.Comment: 5 pages, 5 figure

Switch from 200 to 350 CD4 baseline count: what it means to HIV care and treatment programs in Kenya

Introduction: With the increasing population of infected individuals in Africa and constrained resources for care and treatment, antiretroviralmanagement continues to be an important public health challenge. Since the announcement of World Health Organization recommendation andguidelines for initiation of antiretroviral Treatment at CD4 count below 350, many developing countries are adopting this strategy in their countryspecific guidelines to care and treatment of HIV and AIDS. Despite the benefits to these recommendations, what does this switch from 200 to 350CD4 count mean in antiretroviral treatment demand? Methods: A Multi-centre study involving 1376 patients in health care settings in Kenya. CD4count was carried out by flow cytometry among the HIV infected individuals in Kenya and results analyzed in view of the In-country and the newCD4 recommendation for initiation of antiretroviral treatment. Results: Across sites, 32% of the individual required antiretroviral at <200 CD4Baseline, 40% at <250 baseline count and 58% based on the new criteria of <350 CD4 Count. There were more female (68%) than Male(32%).Different from <200 and <250 CD4 baseline criteria, over 50% of all age groups required antiretroviral at 350 CD4 baseline. Age groupsbetween 41-62 led in demand for ART. Conclusion: With the new guidelines, demand for ARVs has more than doubled with variations notedwithin regions and age groups. As A result, HIV Care and Treatment Programs should prepare for this expansion for the benefits to be realized.Key words: CD4, New criteria, HIV, AIDS, care and treatment, ARV initiatio

HIV-1 subtype and viral tropism determination for evaluating antiretroviral therapy options: an analysis of archived Kenyan blood samples

<p>Abstract</p> <p>Background</p> <p>Infection with HIV-1 is characterized by genetic diversity such that specific viral subtypes are predominant in specific geographical areas. The genetic variation in HIV-1 <it>pol </it>and <it>env </it>genes is responsible for rapid development of resistance to current drugs. This variation has influenced disease progression among the infected and necessitated the search for alternative drugs with novel targets. Though successfully used in developed countries, these novel drugs are still limited in resource-poor countries. The aim of this study was to determine HIV-1 subtypes, recombination, dual infections and viral tropism of HIV-1 among Kenyan patients prior to widespread use of antiretroviral drugs.</p> <p>Methods</p> <p>Remnant blood samples from consenting sexually transmitted infection (STI) patients in Nairobi were collected between February and May 2001 and stored. Polymerase chain reaction and cloning of portions of HIV-1 <it>gag</it>, <it>pol </it>and <it>env </it>genes was carried out followed by automated DNA sequencing.</p> <p>Results</p> <p>Twenty HIV-1 positive samples (from 11 females and 9 males) were analyzed. The average age of males (32.5 years) and females (26.5 years) was significantly different (p value < 0.0001). Phylogenetic analysis revealed that 90% (18/20) were concordant HIV-1 subtypes: 12 were subtype A1; 2, A2; 3, D and 1, C. Two samples (10%) were discordant showing different subtypes in the three regions. Of 19 samples checked for co-receptor usage, 14 (73.7%) were chemokine co-receptor 5 (CCR5) variants while three (15.8%) were CXCR4 variants. Two had dual/mixed co-receptor use with X4 variants being minor population.</p> <p>Conclusion</p> <p>HIV-1 subtype A accounted for majority of the infections. Though perceived to be a high risk population, the prevalence of recombination in this sample was low with no dual infections detected. Genotypic co-receptor analysis showed that most patients harbored viruses that are predicted to use CCR5.</p

Blood Stage Malaria Vaccine Eliciting High Antigen-Specific Antibody Concentrations Confers No Protection to Young Children in Western Kenya

The antigen, falciparum malaria protein 1 (FMP1), represents the 42-kDa C-terminal fragment of merozoite surface protein-1 (MSP-1) of the 3D7 clone of P. falciparum. Formulated with AS02 (a proprietary Adjuvant System), it constitutes the FMP1/AS02 candidate malaria vaccine. We evaluated this vaccine's safety, immunogenicity, and efficacy in African children.A randomised, double-blind, Phase IIb, comparator-controlled trial.The trial was conducted in 13 field stations of one mile radii within Kombewa Division, Nyanza Province, Western Kenya, an area of holoendemic transmission of P. falciparum. We enrolled 400 children aged 12-47 months in general good health.Children were randomised in a 1ratio1 fashion to receive either FMP1/AS02 (50 microg) or Rabipur(R) rabies vaccine. Vaccinations were administered on a 0, 1, and 2 month schedule. The primary study endpoint was time to first clinical episode of P. falciparum malaria (temperature >/=37.5 degrees C with asexual parasitaemia of >/=50,000 parasites/microL of blood) occurring between 14 days and six months after a third dose. Case detection was both active and passive. Safety and immunogenicity were evaluated for eight months after first immunisations; vaccine efficacy (VE) was measured over a six-month period following third vaccinations.374 of 400 children received all three doses and completed six months of follow-up. FMP1/AS02 had a good safety profile and was well-tolerated but more reactogenic than the comparator. Geometric mean anti-MSP-1(42) antibody concentrations increased from1.3 microg/mL to 27.3 microg/mL in the FMP1/AS02 recipients, but were unchanged in controls. 97 children in the FMP1/AS02 group and 98 controls had a primary endpoint episode. Overall VE was 5.1% (95% CI: -26% to +28%; p-value = 0.7).FMP1/AS02 is not a promising candidate for further development as a monovalent malaria vaccine. Future MSP-1(42) vaccine development should focus on other formulations and antigen constructs.Clinicaltrials.gov NCT00223990

Pancreatic enzyme replacement therapy in patients with pancreatic cancer: A national prospective study

Objective: UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. Design: RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. Results: Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5–7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). Conclusion: Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required

Democratic Education: A Theoretical Review (2006–2017)

This theoretical review examines how democratic education is conceptualized within educational scholarship. Three hundred and seventy-seven articles published in English language peer-reviewed journals between 2006 and 2017 are discursively analyzed. Democratic education functions as a privileged nodal point of different political discourses. Two discourses against (elitist and neoliberal) and six discourses pro democratic education (liberal, deliberative, multiculturalist, participatory, critical, and agonistic) construct its meaning. It is argued that the different versions of democratic education respond to various (a) ontological and epistemological assumptions, (b) normative approaches to democracy, and (c) conceptions of the relationship between education and politics. For educational policy, the review provides a critique of elitist and neoliberal policies and support for participatory decision making across discourses. Recommendations for educational practice are made by identifying pedagogies across democratic education scholarship as well as specific pedagogies for each discourse