AKT activation controls cell survival in response to HDAC6 inhibition.

HDAC6 is emerging as an important therapeutic target for cancer. We investigated mechanisms responsible for survival of tumor cells treated with a HDAC6 inhibitor. Expression of the 20 000 genes examined did not change following HDAC6 treatment in vivo. We found that HDAC6 inhibition led to an increase of AKT activation (P-AKT) in vitro, and genetic knockdown of HDAC6 phenocopied drug-induced AKT activation. The activation of AKT was not observed in PTEN null cells; otherwise, PTEN/PIK3CA expression per se did not predict HDAC6 inhibitor sensitivity. Interestingly, HDAC6 inhibitor treatment led to inactivating phosphorylation of PTEN (P-PTEN Ser380), which likely led to the increased P-AKT in cells that express PTEN. Synergy was observed with phosphatidylinositol 3-kinases (PI3K) inhibitor treatment in vitro, accompanied by increased caspase 3/7 activity. Furthermore, combination of HDAC6 inhibitor with a PI3K inhibitor caused substantial tumor growth inhibition in vivo compared with either treatment alone, also detectable by Ki-67 immunostaining and (18)F-FLT positron emission tomography (PET). In aggregate AKT activation appears to be a key survival mechanism for HDAC6 inhibitor treatment. Our findings indicate that dual inhibition of HDAC6 and P-AKT may be necessary to substantially inhibit growth of solid tumors

The feeding behaviour and Plasmodium infection of Anopheles mosquitoes in southern Ethiopia in relation to use of insecticide-treated livestock for malaria control.

Anopheles arabiensis and An. quadriannulatus species B mosquitoes were collected at sites of human and livestock housing and analysed for blood feeding patterns and infection with malaria sporozoites. A low percentage of human blood meals at some sites suggested that zooprophylaxis could be effective in reducing challenge from Plasmodium falciparum

Dynamic Variation in Sexual Contact Rates in a Cohort of HIV-Negative Gay Men

Human immunodeficiency virus (HIV) transmission models that include variability in sexual behavior over time have shown increased incidence, prevalence, and acute-state transmission rates for a given population risk profile. This raises the question of whether dynamic variation in individual sexual behavior is a real phenomenon that can be observed and measured. To study this dynamic variation, we developed a model incorporating heterogeneity in both between-person and within-person sexual contact patterns. Using novel methodology that we call iterated filtering for longitudinal data, we fitted this model by maximum likelihood to longitudinal survey data from the Centers for Disease Control and Prevention's Collaborative HIV Seroincidence Study (1992–1995). We found evidence for individual heterogeneity in sexual behavior over time. We simulated an epidemic process and found that inclusion of empirically measured levels of dynamic variation in individual-level sexual behavior brought the theoretical predictions of HIV incidence into closer alignment with reality given the measured per-act probabilities of transmission. The methods developed here provide a framework for quantifying variation in sexual behaviors that helps in understanding the HIV epidemic among gay men

Accidental Father-to-Son HIV-1 Transmission During the Seroconversion Period

A 4-year-old child born to an HIV-1 seronegative mother was diagnosed with HIV-1, the main risk factor being transmission from the child's father who was seroconverting at the time of the child's birth. In the context of a forensic investigation, we aimed to identify the source of infection of the child and date of the transmission event. Samples were collected from the father and child at two time points about 4 years after the child's birth. Partial segments of three HIV-1 genes (gag, pol, and env) were sequenced and maximum likelihood (ML) and Bayesian methods were used to determine direction and estimate date of transmission. Neutralizing antibodies were determined using a single cycle assay. Bayesian trees displayed a paraphyletic-monophyletic topology in all three genomic regions, with the father's host label at the root, which is consistent with father-to-son transmission. ML trees found similar topologies in gag and pol and a monophyletic-monophyletic topology in env. Analysis of the time of the most recent common ancestor of each HIV-1 gene population indicated that the child was infected shortly after the father. Consistent with the infection history, both father and son developed broad and potent HIV-specific neutralizing antibody responses. In conclusion, the direction of transmission implicated the father as the source of transmission. Transmission occurred during the seroconversion period when the father was unaware of the infection and was likely accidental. This case shows how genetic, phylogenetic, and serological data can contribute for the forensic investigation of HIV transmission.info:eu-repo/semantics/publishedVersio

Patterns of antibiotics susceptibility of isolates and plasmid analysis of Staphylococcus from surgical site infections in Nigeria

There has been a significant increase in resistance of common bacterial isolates from surgical site infections in our community resulting in prolonged hospital stay, disability and deaths of patients. In this vein,we surveyed the antibiotic susceptibility profiles of aerobic bacterial isolates from postoperative wound infections and determined whether resistance in Staphylococcus aureus was genetically mediated. A total of 161 isolates were obtained from 153 swab samples of infected wounds using cultural, morphological, and biochemical characteristics. The predominant bacterial isolates were: S. aureus (53.4%), Escherichia coli (23.0%), Staphylococcus epidermidis (11.2%), Pseudomonas aeruginosa (5.0%), and species of Klebsiella and Proteus 3.7% each. On the whole: Escherichia coli, Klebsiella and Proteus showed similar antibiotic susceptibility patterns viz: 66.7-100% for ciprofloxacin, 66.7-100% gentamicin and 50-80% augmentin; and less than 50% for amoxacillin, erythromycin, tetracycline, cotrimoxazole, cloxacillin and chloramphenicol. S. aureus showed percentage susceptibility of 50-100% and Staphylococcus epidermidis (50-100%) for cloxacillin and augmentin, and less than 60% for amoxacillin, erythromycin, tetracycline, cotrimoxazole, gentamicin and chloramphenicol. Multi drug resistance (MDR) of S. aureus strains to at least three classes of the antibiotics used was about 70.5%. Four out of the 11 MDR S. aureus strains were found to harbor plasmidswith varying molecular weights that ranged from 3.114 to 6.509 kb. One of the multi-drug resistant isolates still exhibited resistance even after curing. This showed that other genetic elements may also be involved in theacquisition of these forms of resistance other than plasmid elements.Key Words: Postoperative –Wounds-Aerobic bacteria-Staphylococcus aureus

The Influence of Pb and Zn Contaminated soil on the Germination and Growth of Bambara Nut (Vigna subterranea)

This research work takes a look at the possible phytotoxic effects of Pb and Zn as Pb(NO3)2 and Zn(NO3)2 on Bambara nut (Vigna subterranea) planted in polluted. Lead and zinc are common environmental contaminant found in soils. Unlike Zn, Pb has no biological role, and is potentially toxic to microorganisms. The bambara nut seedlings were irrigated with various concentrations of Pb and Zn (100,150 and 200mgkg-1) .Effect of these metals on the growth parameters (stem length/height, root length, leaf area, yellowness of leaves, fresh and dry weights) were measured. Influence of heavy metals on the microorganisms in the soil used for planting as well as the organic matter, pH and moisture content of the soil were also evaluated. The results showed that plant performance significantly reduced with increasing concentrations (100,150 and 200mgkg-1) of Pb and Zn contamination. The results show that a negative relationship existed between the different metal concentrations in the soil and the growth parameters (stem height, root length, leaf area, yellowness of leaves, fresh and dry weight) measured compared to control experiment. This study therefore reveals that these heavy metals have great implications on the sustainability of V. subterranea’s growth. These metals could pass down to humans through the food chain if animals eat such plants during grazing. This will affect their health, which may eventually lead to their death due to bio concentration and bioaccumulation. There would therefore be a need to explore ways of improving bambara nut production in areas of metal pollution. Keywords: V. subterranea, Bioaccumulation, Pollution, Phytotoxicity, Contamination, bioaccumulation

Prediction of Soil Temperature at Various Depths Using a Mathematical Model

This study discusses variation of soil temperature with depth using mathematical models at Ataoja School of Science, Osogbo, Osun State, Nigeria. Average conditions were assumed. The annual soil temperature cycles were modeled with fairly good accuracy. Differences in measured and predicted soil temperatures were determined at annual levels at depths 0cm (top soil), 10cm, 30cm and 50cm. For the annual cycle, the absolute errors ranged from 0.5oC to 7.8 oC with an average of 2.7 oC at the soil surface (0cm). At the 10cm depth, the errors ranged from 0.1 oC to 4.5 oC with an average value of 2.0 oC . At the 30cm depth, the absolute errors ranged from 0.05 oC to 2.9 oC with an average of 1.7 oC. The highest average absolute error was 2.7 oC while the lowest average absolute error was 1.7 oC.Keywords: Soil temperature, transient heat flow, simulation, homogenous

Conceptualizing cultures of violence and cultural change

The historiography of violence has undergone a distinct cultural turn as attention has shifted from examining violence as a clearly defined (and countable) social problem to analysing its historically defined 'social meaning'. Nevertheless, the precise nature of the relationship between 'violence' and 'culture' is still being established. How are 'cultures of violence' formed? What impact do they have on violent behaviour? How do they change? This essay examines some of the conceptual aspects of the relationship between culture and violence. It brings together empirical research into nineteenth-century England with recent research results from other European contexts to examine three aspects of the relationship between culture and violence. These are organised under the labels 'seeing violence', 'identifying the violent' and 'changing violence'. Within a particular society, narratives regarding particular kinds of behaviour shape cultural attitudes. The notion 'violence' is thus defined in relation to physically aggressive acts as well as by being connected to other kinds of attitudes and contexts. As a result, the boundaries between physical aggression which is legitimate and that which is illegitimate (and thus 'violence') are set. Once 'violence' is defined, particular cultures form ideas about who is responsible for it: reactions to violence become associated with social arrangements such as class and gender as well as to attitudes toward the self. Finally, cultures of violence make efforts to tame or eradicate illegitimate forms of physical aggression. This process is not only connected to the development of new forms of power (e.g., new policing or punishment strategies) but also to less tangible cultural influences which aim at changing the behaviour defined as violence (in particular among the social groups identified as violent). Even if successful, this three-tiered process of seeing violence, identifying the violent and changing violence continues anew, emphasising the ways that cultures of violence develop through a continuous process of reevaluation and reinvention

Measuring patient-perceived quality of care in US hospitals using Twitter

BACKGROUND: Patients routinely use Twitter to share feedback about their experience receiving healthcare. Identifying and analysing the content of posts sent to hospitals may provide a novel real-time measure of quality, supplementing traditional, survey-based approaches. OBJECTIVE: To assess the use of Twitter as a supplemental data stream for measuring patient-perceived quality of care in US hospitals and compare patient sentiments about hospitals with established quality measures. DESIGN: 404 065 tweets directed to 2349 US hospitals over a 1-year period were classified as having to do with patient experience using a machine learning approach. Sentiment was calculated for these tweets using natural language processing. 11 602 tweets were manually categorised into patient experience topics. Finally, hospitals with ≥50 patient experience tweets were surveyed to understand how they use Twitter to interact with patients. KEY RESULTS: Roughly half of the hospitals in the US have a presence on Twitter. Of the tweets directed toward these hospitals, 34 725 (9.4%) were related to patient experience and covered diverse topics. Analyses limited to hospitals with ≥50 patient experience tweets revealed that they were more active on Twitter, more likely to be below the national median of Medicare patients (p<0.001) and above the national median for nurse/patient ratio (p=0.006), and to be a non-profit hospital (p<0.001). After adjusting for hospital characteristics, we found that Twitter sentiment was not associated with Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) ratings (but having a Twitter account was), although there was a weak association with 30-day hospital readmission rates (p=0.003). CONCLUSIONS: Tweets describing patient experiences in hospitals cover a wide range of patient care aspects and can be identified using automated approaches. These tweets represent a potentially untapped indicator of quality and may be valuable to patients, researchers, policy makers and hospital administrators

Effect of Branched and Straight Chained Alcohols on Performance of Crude oil Demulsifiers

Unwanted crude oil emulsions occur in many stages of oil production,  transportation, and processing. The huge cost resulting from corrosion of transport system and production facilities, because of the presence of water is a major challenge to the oil industry and the global economy. However, the addition of alcohols to demulsifiers has been reported to enhance their efficiency in removing water from emulsions. There is therefore the need to identify the best type of alcohols and optimize this process of addition.  Consequently in this work, the effect of different straight and branched chain alcohols on the performance enhancement of demulsifiers was investigated using four different crude oil emulsion samples. The results showed that straight alcohols performed better when compared to branched chain alcohols under all conditions of temperature. This may be due to their slow mobility particularly in stable emulsions.Keywords: Crude Oil, Emulsion, Emulsifiers, Demulsifiers, Alcohols