The effects of live Streptococcus pneumoniae and tumor necrosis factor-α on neutrophil oxidative burst and β2-integrin expression

ObjectiveTo study the effects of TNF-α and live Streptococcus pneumoniae on human neutrophil oxidative burst and β2-integrin expression using flow cytometry.MethodsSix clinical isolates of S. pneumoniae (serotypes 3, 19A, 22F, 6A, 33P and 9N) from patients with bacteremic pneumonia or upper respiratory tract infections were studied. Whole blood was incubated either alone, with TNF-α or with S. pneumoniae or with both TNF-α and pneumococci at a ratio of one neutrophil per 1–5 bacteria. After 30 min of incubation, the tubes were put into ice, fixed and analysed.ResultsS. pneumoniae caused an increase in oxidative burst but not greater than that caused by TNF-α alone. When whole blood was preincubated with TNF-α for 30 min before the addition of pneumococci, a further increase in the oxidative burst response was seen. The variation in CD 11b expression was not significant. Both S. pneumoniae and TNF-α caused increases in CD18 expression. The addition of TNF-α directly with the bacteria caused no further increase, but preincubation of blood with TNF-α 30 min before the addition of the bacteria caused a significant increase in CD18 expression.ConclusionsLive S. pneumoniae stimulates polymorphonuclear leukocytes to produce an oxidative burst and increases expression of CD18, and these effects are enhanced by TNF-α

Trends in levels of self-reported psychological distress among individuals who seek psychiatric services over eight years: a comparison between age groups in three population surveys in Stockholm County

BACKGROUND: Psychiatric service use has increased in Sweden and in other developed countries, particularly among young people. Possible explanations include lower threshold for help-seeking among young people, but evidence is scarce. METHODS: We analysed the 2002, 2006 and 2010 Stockholm public health surveys for changes in the mean level of psychological distress among adult users of psychiatric in- and outpatient services in four age groups: 18-24, 25-44, 45-64 and ≥65 years. Psychological distress was measured via the 12-item General Health Questionnaire (GHQ-12), using the Likert scoring method 0-1-2-3. In- and out-patient psychiatric service use within 6 months from the surveys was obtained from registers. RESULTS: The mean level of distress among young adults 18-24 years who utilize psychiatric services decreased between 2002 (mean GHQ-12 score, 95% confidence interval 20.5, 18.1-23.0) and 2010 (16.2, 14.6-17.7), while it remained fairly stable in older age groups. Results were similar in sex-stratified analyses, although the decrease was statistically significant only among young women 18-24 years. At the end of the follow-up, the level of distress among patients was similar for all age-groups. CONCLUSIONS: There were no differences between age groups in the level of distress when seeking care at the end of the follow-up period, supporting that there is no age-specific over- or under-consumption of psychiatric care in later years. However, the lowered threshold for help-seeking among young adults over time might have contributed to increases in psychiatric service use in the young age group. Public health policy and service delivery planning should consider the needs of the widening group of young users of psychiatric services

Finite driving rate and anisotropy effects in landslide modeling

In order to characterize landslide frequency-size distributions and individuate hazard scenarios and their possible precursors, we investigate a cellular automaton where the effects of a finite driving rate and the anisotropy are taken into account. The model is able to reproduce observed features of landslide events, such as power-law distributions, as experimentally reported. We analyze the key role of the driving rate and show that, as it is increased, a crossover from power-law to non power-law behaviors occurs. Finally, a systematic investigation of the model on varying its anisotropy factors is performed and the full diagram of its dynamical behaviors is presented.Comment: 8 pages, 9 figure

Protein-Based Biostimulants to Enhance Plant Growth-State-of-the-Art and Future Direction with Sugar Beet as an Example

Protein-based biostimulants (PBBs) are derived from the hydrolysis of protein-rich raw materials of plant and/or animal origins, usually by-products or wastes from agro-industries. The active ingredients (AIs) produced by hydrolysis have the capacity to influence physiological and metabolic processes in plants, leading to enhanced growth, nutrient and water-use efficiency, tolerance to abiotic and biotic stresses, and improved crop yield and quality. This paper reviews the state-of-the-art and future opportunities for use of PBBs, based on potential effects on the soil, crops, and sustainability (social, economic, environmental). In this case, two examples of PBBs (hydrolyzed wheat gluten and potato protein) and their effects on the early growth of three sugar beet varieties are described and discussed. Both PBBs have a significant stimulating effect on early sugar beet growth and development. The opportunity to develop PBBs into superabsorbent polymers (SAPs) is discussed. To conclude, PBBs/SAPs developed from agro-industrial wastes have the potential for sustainably supplying water and nutrients in agricultural systems and for enhancing plant growth and development over a substantial period

Evaluating the Ability of Swell Prediction Models to Predict the Swell Behavior of Excessively High Plastic Soils

Lightly loaded structures underneath expansive soils encounter severe damage due to the swell/shrink nature of expansive soils resulting from moisture variations. Billions of dollars are spent every year to repair the damages caused by these soils in the U.S. and worldwide. Designing structures to accommodate the swelling strains is a major challenge as predicting the swelling potential of these soils accurately is not easy. A wide variety of swell prediction models have been introduced by various researchers to predict the behavior of these often-problematic expansive soils. These models include various properties of soils such as, plasticity characteristics, compaction conditions, consolidation characteristics, moisture content variations, matric suction, and clay mineralogical characteristics. However, these models are generally developed with typical moderate to high plastic soils in mind whose plasticity indices range from 25 to 45. Their applicability to soils that have liquid limits in the order of 200% is not well understood. In this paper, the ability of these models to predict the behavior of excessively high plastic soils with plasticity indices ranging from 45 to 85 were evaluated. For this purpose, four existing analytical prediction models that use combinations of above-mentioned properties were selected and used to predict the one-dimensional and three-dimensional swelling strains on three high swelling soils. These predictions were verified by conducting one-dimensional and three-dimensional swell tests on the three soil types. The swell tests were conducted at three different initial moisture contents to observe how well the models could predict different levels of moisture absorption. The ability of each of the four selected methods in predicting both 1D and 3D swell strains was discussed and their relative merits and demerits are highlighted. In addition, finite element modeling was performed to simulate one-dimensional and three-dimensional swell tests by using material models that use volumetric and suction changes with moisture contents to simulate expansive soil behavior within the finite element model. The results indicated that while the analytical prediction models gave reasonable results the finite element analysis predicted results were closest to the laboratory measure soils in case both 1D and 3D analyses. Among other analytical models the ones that incorporated mineralogical and suction data exhibited better results

Ice-lens formation and geometrical supercooling in soils and other colloidal materials

We present a new, physically-intuitive model of ice-lens formation and growth during the freezing of soils and other dense, particulate suspensions. Motivated by experimental evidence, we consider the growth of an ice-filled crack in a freezing soil. At low temperatures, ice in the crack exerts large pressures on the crack walls that will eventually cause the crack to split open. We show that the crack will then propagate across the soil to form a new lens. The process is controlled by two factors: the cohesion of the soil, and the geometrical supercooling of the water in the soil; a new concept introduced to measure the energy available to form a new ice lens. When the supercooling exceeds a critical amount (proportional to the cohesive strength of the soil) a new ice lens forms. This condition for ice-lens formation and growth does not appeal to any ad hoc, empirical assumptions, and explains how periodic ice lenses can form with or without the presence of a frozen fringe. The proposed mechanism is in good agreement with experiments, in particular explaining ice-lens pattern formation, and surges in heave rate associated with the growth of new lenses. Importantly for systems with no frozen fringe, ice-lens formation and frost heave can be predicted given only the unfrozen properties of the soil. We use our theory to estimate ice-lens growth temperatures obtaining quantitative agreement with the limited experimental data that is currently available. Finally we suggest experiments that might be performed in order to verify this theory in more detail. The theory is generalizable to complex natural-soil scenarios, and should therefore be useful in the prediction of macroscopic frost heave rates.Comment: Submitted to PR

PTEN and DNA-PK determine sensitivity and recovery in response to WEE1 inhibition in human breast cancer

Inhibition of WEE1 kinase by AZD1775 has shown promising results in clinical cancer trials, but markers predicting AZD1775 response are lacking. Here we analysed AZD1775 response in a panel of human breast cancer (BC) cell lines by global proteome/transcriptome profiling and identified two groups of basal-like BC (BLBCs): ‘PTEN low’ BLBCs were highly sensitive to AZD1775 and failed to recover following removal of AZD1775, while ‘PTEN high’ BLBCs recovered. AZD1775 induced phosphorylation of DNA-PK, protecting cells from replication-associated DNA damage and promoting cellular recovery. Deletion of DNA-PK or PTEN, or inhibition of DNA-PK sensitized recovering BLBCs to AZD1775 by abrogating replication arrest, allowing replication despite DNA damage. This was linked to reduced CHK1 activation, increased cyclin E levels and apoptosis. In conclusion, we identified PTEN and DNA-PK as essential regulators of replication checkpoint arrest in response to AZD1775 and defined PTEN as a promising biomarker for efficient WEE1 cancer therapy

Task shifting and integration of HIV care into primary care in South Africa: The development and content of the streamlining tasks and roles to expand treatment and care for HIV (STRETCH) intervention

Background: Task shifting and the integration of human immunodeficiency virus (HIV) care into primary care services have been identified as possible strategies for improving access to antiretroviral treatment (ART). This paper describes the development and content of an intervention involving these two strategies, as part of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) pragmatic randomised controlled trial. Methods: Developing the intervention: The intervention was developed following discussions with senior management, clinicians, and clinic staff. These discussions revealed that the establishment of separate antiretroviral treatment services for HIV had resulted in problems in accessing care due to the large number of patients at ART clinics. The intervention developed therefore combined the shifting from doctors to nurses of prescriptions of antiretrovirals (ARVs) for uncomplicated patients and the stepwise integration of HIV care into primary care services. Results: Components of the intervention: The intervention consisted of regulatory changes, training, and guidelines to support nurse ART prescription, local management teams, an implementation toolkit, and a flexible, phased introduction. Nurse supervisors were equipped to train intervention clinic nurses in ART prescription using outreach education and an integrated primary care guideline. Management teams were set up and a STRETCH coordinator was appointed to oversee the implementation process. Discussion: Three important processes were used in developing and implementing this intervention: active participation of clinic staff and local and provincial management, educational outreach to train nurses in intervention sites, and an external facilitator to support all stages of the intervention rollout

Murine Microenvironment Metaprofiles Associate with Human Cancer Etiology and Intrinsic Subtypes

Ionizing radiation is a well established carcinogen in rodent models and a risk factor associated with human cancer. We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53 null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in naïve hosts. We asked whether expression metaprofiles could discern radiation-preceded human cancer or be informative in sporadic breast cancers