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The gas sensing properties of pristine Sn3C2 monolayer and different transition metal adatom (TM-Sn3C2, where TM = Fe, Co, Ni, Cu, Ru, Rh, Pd and Ag) was investigated using van der Waals corrected density functional theory. The understanding and potential of use of Sn3C2 monolayers as sensors or adsorbent for CO, CO2, NO, NO2 and SO2 gaseous molecules is evaluated by calculating the adsorption and desorption energetics. From the calculated adsorption energies, we found that the pristine Sn3C2 monolayer and 3d TM has desirable properties for removal of the considered molecules based on their high adsorption energy, however the 4d TM is applicable as recoverable sensors. We applied an Arrhenius-type equation to evaluate the recovery time for the desorption of the molecules on the pristine and TM adatom on Sn3C2 monolayer. We found that the negative adsorption energies from −1 to −2 eV of the molecules resulted in easier recovery of the adsorbed gases at reasonable temperatures compared to adsorption energies in between 0 and −1 eV (weakly physiosorbed) and below −2 eV (strongly chemisorbed). Hence, we obtained that the Rh–Sn3C2, Ru–Sn3C2, Pd–Sn3C2, Pd–Sn3C2, and Rh–Sn3C2 monolayers are good recoverable scavengers for the CO, CO2, NO, NO2, and SO2 molecules. The current theoretical calculations provide new insight on the effect of TM adatoms on the structural, electronic, and magnetic properties of the Sn3C2 monolayer and different transition metal adatom as well as shed light on their application as gas sensors/scavengers. [ABSTRACT FROM AUTHOR]

Measuring empowerment is critical to understanding the level of control adolescents and young adults (AYA) have over their sexual and reproductive health (SRH) behaviors, and could provide a key window into addressing their unique SRH needs. We adapted the Sexual and Reproductive Empowerment (SRE) scale for AYA for use in an East African context. This multi-method qualitative study sampled 15-23 year-old female adolescents and young adults in Kisumu, Kenya. We conducted in-depth interviews (n = 30) and analyzed transcripts with an inductive, constant comparison approach. Empowerment domains were integrated with Kabeer's (1999) framework in a conceptual model, which we referenced to revise the original and develop new scale items. Items underwent expert review, and were condensed and translated through team-based consensus-building. We evaluated content validity in cognitive interviews (n = 25), during which item phrasing and word choice were revised to generate an adapted SRE scale. Participants (n = 55) had a median age of 18 (range 16-23), and 75% were under 19 years. We categorize three types of adaptations to the SRE scale: new item generation, item revision, and translation/linguistic considerations. We developed nine new items reflecting AYA's experiences and new domains of empowerment that emerged from the data; new domains relate to self-efficacy in accessing sexual and reproductive health care, and how material needs are met. All items were revised and translated to echo concepts and language relevant to participants, navigating the multilingualism common in many African countries. Centering the voices of female Kenyan AYA, this study provides insight into measuring the latent construct of adolescent sexual and reproductive empowerment in an East African setting, and supports the adapted SRE scale's content validity for Kenya. We detail our multi-method, theory-driven approach, contributing to limited methods guidance for measure adaptation across contexts and among diverse adolescent populations.

Abstract Background Alteration of signalling pathways regulating cell cycle progression is a common feature of cancer cells. Several drugs targeting distinct phases of the cell cycle have been developed but the inability of many of them to discriminate between normal and cancer cells has strongly limited their clinical potential because of their reduced efficacy at the concentrations used to limit adverse side effects. Mechanisms of resistance have also been described, further affecting their efficacy. Identification of novel targets that can potentiate the effect of these drugs or overcome drug resistance can provide a useful strategy to exploit the anti-cancer properties of these agents to their fullest. Methods The class II PI3K isoform PI3K-C2β was downregulated in prostate cancer PC3 cells and cervical cancer HeLa cells using selective siRNAs and the effect on cell growth was determined in the absence or presence of the microtubule-stabilizing agent/anti-cancer drug docetaxel. Mitosis progression was monitored by time-lapse microscopy. Clonogenic assays were performed to determine the ability of PC3 and HeLa cells to form colonies upon PI3K-C2β downregulation in the absence or presence of docetaxel. Cell multi-nucleation was assessed by immunofluorescence. Tumour growth in vivo was assessed using a xenograft model of PC3 cells upon PI3K-C2β downregulation and in combination with docetaxel. Results Downregulation of PI3K-C2β delays mitosis progression in PC3 and HeLa cells, resulting in reduced ability to form colonies in clonogenic assays in vitro. Compared to control cells, PC3 cells lacking PI3K-C2β form smaller and more compact colonies in vitro and they form tumours more slowly in vivo in the first weeks after cells implant. Stable and transient PI3K-C2β downregulation potentiates the effect of low concentrations of docetaxel on cancer cell growth. Combination of PI3K-C2β downregulation and docetaxel almost completely prevents colonies formation in clonogenic assays in vitro and strongly inhibits tumour growth in vivo. Conclusions These data reveal a novel role for the class II PI3K PI3K-C2β during mitosis progression. Furthermore, data indicate that blockade of PI3K-C2β might represent a novel strategy to potentiate the effect of docetaxel on cancer cell growth.

We have investigated the transition pressure p, of bulk GaAs from the zinc-blende (B3) to the rocksalt (B1) structure using the local-density approximation (LDA), Perdew-Burke-Ernzerhof generalized gradient approximation (PBE-GGA), and diffusion Monte Carlo (DMC). We took into account finite temperature effects (zero-point vibrational effects) as well as finite-size corrections. Our DMC calculation using GGA trial nodal surface supports the higher value of the transition pressure, ˜17 GPa, than the lower value of ˜12 GPa, both of which are experimentally reported values. This projection increases the transition pressure pt from DFT predictions, being of the same tendency as that for Si bulk crystal. The choice of the exchange-correlation functional in DFT was found to significantly determine the phase-transition pressure, while DMC gave more accurate results for this transition pressure. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-1beta is a cytokine released as part of the innate immune response to Plasmodium falciparum. Because the role played by IL-1beta polymorphic variability in conditioning the immunopathogenesis of severe malarial anemia (SMA) remains undefined, relationships between IL-1beta promoter variants (-31C/T and -511A/G), SMA (hemoglobin [Hb] level <6.0 g/dL), and circulating IL-1beta levels were investigated in children with parasitemia (n= 566) from western Kenya. The IL-1beta promoter haplotype -31C/-511A (CA) was associated with increased risk of SMA (Hb level <6.0 g/dL; odds ratio [OR], 1.98 [95% confidence interval {CI}, 1.55-2.27]; P < .05) and reduced circulating IL-1beta levels (p <.05). The TA (-31T/-511A) haplotype was nonsignificantly associated with protection against SMA (OR, 0.52 [95% CI, 0.18-1.16]; p =.11) and elevated IL-1beta production ( p<.05). Compared with the non-SMA group, children with SMA had significantly lower IL-1beta levels and nonsignificant elevations in both IL-1 receptor antagonist (IL-1Ra) and the ratio of IL-1Ra to IL-1beta. The results presented demonstrate that variation in IL-1beta promoter conditions susceptibility to SMA and functional changes in circulating IL-1beta levels. [ABSTRACT FROM AUTHOR]

Mild gestational hyperglycemia is often associated with fetal overgrowth that can predispose the offspring to metabolic diseases later in life. We hypothesized that unfavorable intrauterine environment may compromise the development of placenta and contribute to fetal overgrowth. Therefore, we developed a rat model and investigated the effects of maternal dysglycemia on fetal growth and placental gene expression. Female rats were treated with single injection of nicotinamide plus streptozotocin (N-STZ) 1-week before mating and were studied at gestational day 21. N-STZ pregnant females displayed impaired glucose tolerance that is associated with a lower insulin secretion. Moderate hyperglycemia induced fetal overgrowth in 40% of newborns, from pregnancies with 10 to 14 pups. The incidence of macrosomia was less than 5% in the N-STZ pregnancies when the litter size exceeds 15 newborns. We found that placental mass and the labyrinthine layer were increased in macrosomic placentas. The expression of genes involved in placental development and nutrient transfer was down regulated in the N-STZ placentas of macrosomic and normosomic pups from pregnancies with 10 to 14 ones. However, we observed that lipoprotein lipase 1 (LPL1) gene expression was significantly increased in the N-STZ placentas of macrosomic pups. In pregnancies with 15 pups or more, the expression of IGFs and glucose transporter genes was also modulated in the control placentas with no additional effect in the N-STZ ones. These data suggest that placental gene expression is modulated by gestational conditions that might disrupt the fetal growth. We described here a new model of maternal glucose intolerance that results in fetal overgrowth. We proposed that over-expression of LPL1 in the placenta may contribute to the increased fetal growth in the N-STZ pregnancies. N-STZ model offers the opportunity to determinate whether these neonatal outcomes may contribute to developmental programming of metabolic diseases in adulthood.

Abstract Background Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT) has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL) is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers’ knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers’ knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets. Methods A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits) providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials) and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription), was collected. Results Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100%) in public and majority (98.4%) in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039) and severe malaria (P P = 0.002) in children and adults, respectively. Most (82.3%) of private outlets sell partial packs of AL while 72.4% do not request for written prescription for AL. In-service training influenced request for written prescription (P = 0.001), AL prescription (P P Conclusion Public-sector providers have higher knowledge on treatment policy and dosing regimen on recommended anti-malarials. Changes in treatment guidelines should be accompanied by subsequent implementation activities involving all sector players in unbiased strategies.

Abstract Background Over the years, reports implicate improper anti-malarial use as a major contributor of morbidity and mortality amongst millions of residents in malaria endemic areas, Kenya included. However, there are limited reports on improper use of Artemisinin-based Combination Therapy (ACT) which is a first-line drug in the treatment of malaria in Kenya. Knowing this is important for ensured sustainable cure rates and also protection against the emergence of resistant malarial parasites. We therefore investigated ACT adherence level, factors associated with non-adherence and accessibility in households (n = 297) in rural location of Southeast Alego location in Siaya County in western Kenya. Methods ACT Adherence level was assessed with reference to the duration of treatment and number of tablets taken. Using systematic random sampling technique, a questionnaire was administered to a particular household member who had the most recent malaria episode ( Results Adherence to ACT prescription remained low at 42.1% and 57.9% among individuals above 13 and less than 13 years, respectively. Stratification by demographic and socio-economic characteristics in relation to ACT adherence revealed that age (P = 0.011), education level (P P P = 0.002) significantly affected the level of ACT adherence. Consistently, logistic regression model demonstrated that low age (OR, 0.571, 95% CI, 0.360-0.905; P = 0.017), higher education level (OR, 0.074; 95% CI 0.017-0.322; P P 9000; OR, 0.340; 95% CI, 0.167-0.694; P = 0.003) were associated with ACT adherence. In addition, about 52.9% of the respondents reported that ACT was not always available at the source and that drug availability (P = 0.020) and distance to drug source (P Conclusions This study demonstrates that more than half of those who get ACT prescription do not take recommended dose and that accessibility is of concern. The findings of this study suggest a potential need to improve accessibility and also initiate programmatic interventions to encourage patient-centred care.

Abstract Background Plasmodium falciparum infection leads to alterations in B cell subset distribution. During infancy, development of peripheral B cell subsets is also occurring. However, it is unknown if infants living a malaria endemic region have alterations in B cell subsets that is independent of an age effect. Methods To evaluate the impact of exposure to P. falciparum on B cell development in infants, flow cytometry was used to analyse the distribution and phenotypic characteristic of B cell subsets in infant cohorts prospectively followed at 12, 18 and 24 months from two geographically proximate regions in western Kenya with divergent malaria exposure i.e. Kisumu (malaria-endemic, n = 24) and Nandi (unstable malaria transmission, n = 21). Results There was significantly higher frequency and absolute cell numbers of CD19+ B cells in Kisumu relative to Nandi at 12(p = 0.0440), 18(p = 0.0210) and 24 months (p = 0.0493). No differences were observed between the infants from the two sites in frequencies of naïve B cells (IgD+CD27-) or classical memory B cells (IgD-CD27+). However, immature transitional B cells (CD19+CD10+CD34-) were higher in Kisumu relative to Nandi at all three ages. In contrast, the levels of non-class switched memory B cells (CD19+IgD+CD27+) were significantly lower overall in Kisumu relative to Nandi at significantly at 12 (p = 0.0144), 18 (p = 0.0013) and 24 months (p = 0.0129). Conclusions These data suggest that infants living in malaria endemic regions have altered B cell subset distribution. Further studies are needed to understand the functional significance of these changes and long-term impact on ability of these infants to develop antibody responses to P. falciparum and heterologous infections.

Abstract Background Plasmodium falciparum malaria remains a leading cause of morbidity and mortality among African children. Innate immunity provides the first line of defence against P. falciparum infections, particularly in young children that lack naturally-acquired malarial immunity, such as the population examined here. Consistent with the fact that elevated interleukin (IL)-12 is an important component of the innate immune response that provides protective immunity against malaria, we have previously shown that suppression of IL-12 in African children is associated with the development of severe malarial anaemia (SMA). Since the role of IL12B variants in conditioning susceptibility to SMA remains largely unexplored, the association between a single nucleotide polymorphism (1188A→C, rs3212227), SMA (Hb Results Multivariate logistic regression analysis in children with acute malaria (n = 544) demonstrated that carriers of the C allele had increased susceptibility to SMA (CC: OR, 1.674; 95% CI, 1.006-2.673; P = 0.047, and AC: OR, 1.410; 95% CI, 0.953-2.087; P = 0.086) relative to wild type (AA). Although children with SMA had lower IL-12p40/p70 levels than the non-SMA group (P = 0.037), levels did not differ significantly according to genotype. Longitudinal analyses in the entire cohort (n = 756) failed to show any significant relationships between rs3212227 genotypes and either susceptibility to SMA or all-cause mortality throughout the three year follow-up. Conclusion The rs3212227 is a marker of susceptibility to SMA in children with acute disease, but does not appear to mediate functional changes in IL-12 production or longitudinal outcomes during the acquisition of naturally-acquired malarial immunity.

Abstract Background The appropriate use of anti-malarial drugs determines therapeutic efficacy and the emergence and spread of drug-resistant malaria. Strategies for improving drug compliance require accurate information about current practices at the consumer level. This is to ascertain that the currently applied new combination therapy to malaria treatment will achieve sustained cure rates and protection against parasite resistance. Therefore, this cross-sectional study was designed to determine knowledge and behaviour of the consumers in households (n = 397) in peri-urban location in a malaria holoendemic region of western Kenya. Methods The knowledge and behaviour associated with anti-malarial use were evaluated. Using clusters, a questionnaire was administered to a particular household member who had the most recent malaria episode (within Results Consumers' knowledge on dosage and duration/frequency demonstrated that only 29.4% used the correct artemisinin-based combination therapy (ACT) dosage. Most respondents who used quinine identified the correct duration of use (96.4%) since its administration was entirely at health facilities. To assess behaviours during use of anti-malarial drugs, respondents were stratified into those who took drugs with prescription (39.4%) and without prescription (61.6%). For those without prescription, the reasons given were; procedure of acquisition less costly (39.0%), took same drug for similar symptoms (23.0%), not satisfied with health services (15.5%), neighbour/friend/relative previously taken the same drug (12.5%) and health institution was far from their location (10%). Conclusion Majority of consumers in the study area were knowledgeable on the symptoms of malaria. In addition, majority acquired ineffective anti-malarial drugs for treatment and reported sub-optimal treatment regimens with the currently recommended drugs. Furthermore, behaviours which constrain the successful up-scaling of ACT were common, creating a challenge in the desire to turn efficacy to effectiveness of the combination therapy programme. It will be important to direct and focus interventions in creating awareness on the importance of using recommended drugs to lessen the use of less efficacious anti-malarials. In addition, the consumers need to be educated on the importance of drug adherence in such areas to reduce the emergence and spread of drug-resistant malaria.

Abstract Background Interventions to reverse trends in malaria-related morbidity and mortality in Kenya focus on preventive strategies and drug efficacy. However, the pattern of use of anti-malarials in malaria-endemic populations, such as in western Kenya, is still poorly understood. It is critical to understand the patterns of anti-malarial drug use to ascertain that the currently applied new combination therapy to malaria treatment, will achieve sustained cure rates and protection against parasite resistance. Therefore, this cross-sectional study was designed to determine the patterns of use of anti-malarial drugs in households (n = 397) in peri-urban location of Manyatta-B sub-location in Kisumu in western Kenya. Methods Household factors, associated with the pattern of anti-malarials use, were evaluated. Using clusters, questionnaire was administered to a particular household member who had the most recent malaria episode (within Results Stratification of the type of anti-malarial drugs taken revealed that 37.0% used sulphadoxine/pyrimethamine (SP), 32.0% artemisinin-based combined therapy (ACT), 11.1% anti-pyretics, 7.3% chloroquine (CQ), 7.1% quinine, 2.5% amodiaquine (AQ), while 3.0% used others which were perceived as anti-malarials (cough syrups and antibiotics). In a regression model, it was demonstrated that age (P = 0.050), household size (P = 0.047), household head (P = 0.049), household source of income (P = 0.015), monthly income (P = 0.020), duration of use (P = 0.029), dosage of drugs taken (P = 0.036), and source of drugs (P = 0.005) significantly influenced anti-malarial drug use. Overall, 38.8% of respondents used drugs as recommended by the Ministry of Health. Conclusion This study demonstrates that consumers require access to correct and comprehensible information associated with use of drugs, including self-prescription. There is potential need by the Kenyan government to improve malaria care and decrease malaria-related morbidity and mortality by increasing drug affordability, ensuring that the recommended anti-malarial drugs are easily available in all government approved drug outlets and educates the local shopkeepers on the symptoms and appropriate treatment of malaria. Following a switch to ACT in national drug policy, education on awareness and behaviour change is recommended, since the efficacy of ACT alone is not sufficient to reduce morbidity and mortality due to malaria.

Abstract Background Endemic Burkitt's lymphoma (BL) is an extranodal tumor appearing predominantly in the jaw in younger children while abdominal tumors predominate with increasing age. Previous studies have identified elevated levels of antibodies to Plasmodium falciparum schizont extracts and Epstein-Barr virus (EBV) viral capsid antigens (VCA) in endemic BL relative to malaria exposed controls. However, these studies have neither determined if there were any differences based on the site of clinical presentation of the tumor nor examined a broader panel of EBV and P. falciparum antigens. Methods We used a suspension bead Luminex assay to measure the IgG levels against EBV antigens, VCA, EAd, EBNA-1 and Zta as well as P. falciparum MSP-1, LSA-1, and AMA-1 antigens in children with BL (n = 32) and in population-based age-and sex-matched controls (n = 25) from a malaria endemic region in Western Kenya with high incidence of BL. EBV viral load in plasma was determined by quantitative PCR. Results Relative to healthy controls, BL patients had significantly increased anti-Zta (p = 0.0017) and VCA IgG levels (p < 0.0001) and plasma EBV viral loads (p < 0.0001). In contrast, comparable IgG levels to all P. falciparum antigens tested were observed in BL patients compared to controls. Interestingly, when we grouped BL patients into those presenting with abdominal tumors or with jaw tumors, we observed significantly higher levels of anti-Zta IgG levels (p < 0.0065) and plasma EBV viral loads (p < 0.033) in patients with abdominal tumors compared to patients with jaw tumors. Conclusion Elevated antibodies to Zta and elevated plasma EBV viral load could be relevant biomarkers for BL and could also be used to confirm BL presenting in the abdominal region.

Context: An association between polycystic ovary syndrome (PCOS)and endometrial carcinoma was first suggested in 1949, 14 years after the original description of the syndrome. Since then several studies have been published that seem to support this association. The prescription of hormonal treatment to reduce the risk of this complication is supported by the Guidelines for Good Clinical Practice of the Royal College of Obstetricians and Gynaecologists, UK, the Health Information website of the National Library of Medicine, USA, and in textbooks of gynaecological oncology.Starting Point: A recent practice bulletin from the American College of Obstetricians and Gynecologists on the clinical management of PCOS (Obstet Gynecol 2002; 100: 1389-402) says that there is still no consensus on the "optimal progestin, duration and frequency of treatment to prevent endometrial cancer in women with PCOS". Chronic anovulation, obesity, and hyperinsulinaemia are all associated with PCOS as well as with endometrial carcinoma. It has been assumed that PCOS predisposes to endometrial cancer. However, the evidence for such an association is inconclusive. Although PCOS is associated with risk factors for endometrial cancer, it does not necessarily follow that the incidence or mortality from endometrial cancer is increased.Where Next: Large-scale studies of morbidity and mortality in unselected populations of women with PCOS are needed. Women with PCOS are increasingly aware of the possible risks, and it will be necessary to identify which of them, if any, are at increased risk and how this risk can be effectively reduced. [ABSTRACT FROM AUTHOR]