Predicting first traversal times for virions and nanoparticles in mucus with slowed diffusion.

Particle-tracking experiments focusing on virions or nanoparticles in mucus have measured mean-square displacements and reported diffusion coefficients that are orders of magnitude smaller than the diffusion coefficients of such particles in water. Accurate description of this subdiffusion is important to properly estimate the likelihood of virions traversing the mucus boundary layer and infecting cells in the epithelium. However, there are several candidate models for diffusion that can fit experimental measurements of mean-square displacements. We show that these models yield very different estimates for the time taken for subdiffusive virions to traverse through a mucus layer. We explain why fits of subdiffusive mean-square displacements to standard diffusion models may be misleading. Relevant to human immunodeficiency virus infection, using computational methods for fractional subdiffusion, we show that subdiffusion in normal acidic mucus provides a more effective barrier against infection than previously thought. By contrast, the neutralization of the mucus by alkaline semen, after sexual intercourse, allows virions to cross the mucus layer and reach the epithelium in a short timeframe. The computed barrier protection from fractional subdiffusion is some orders of magnitude greater than that derived by fitting standard models of diffusion to subdiffusive data.

Integrating health and environmental impact analysis.

Scientific investigations have progressively refined our understanding of the influence of the environment on human health, and the many adverse impacts that human activities exert on the environment, from the local to the planetary level. Nonetheless, throughout the modern public health era, health has been pursued as though our lives and lifestyles are disconnected from ecosystems and their component organisms. The inadequacy of the societal and public health response to obesity, health inequities, and especially global environmental and climate change now calls for an ecological approach which addresses human activity in all its social, economic and cultural complexity. The new approach must be integral to, and interactive, with the natural environment. We see the continuing failure to truly integrate human health and environmental impact analysis as deeply damaging, and we propose a new conceptual model, the ecosystems-enriched Drivers, Pressures, State, Exposure, Effects, Actions or 'eDPSEEA' model, to address this shortcoming. The model recognizes convergence between the concept of ecosystems services which provides a human health and well-being slant to the value of ecosystems while equally emphasizing the health of the environment, and the growing calls for 'ecological public health' as a response to global environmental concerns now suffusing the discourse in public health. More revolution than evolution, ecological public health will demand new perspectives regarding the interconnections among society, the economy, the environment and our health and well-being. Success must be built on collaborations between the disparate scientific communities of the environmental sciences and public health as well as interactions with social scientists, economists and the legal profession. It will require outreach to political and other stakeholders including a currently largely disengaged general public. The need for an effective and robust science-policy interface has never been more pressing. Conceptual models can facilitate this by providing theoretical frameworks and supporting stakeholder engagement process simplifications for inherently complex situations involving environment and human health and well-being. They can be tools to think with, to engage, to communicate and to help navigate in a sea of complexity. We believe models such as eDPSEEA can help frame many of the issues which have become the challenges of the new public health era and can provide the essential platforms necessary for progress.

Building bridges between natural and social science disciplines: a standardized methodology to combine data on ecosystem quality trends.

Despite a growing interest in interdisciplinary research, systematic ways of how to integrate data from different disciplines are still scarce. We argue that successful resource management relies on two key data sources: natural science data, which represents ecosystem structure and processes, and social science data, which describes people's perceptions and understanding. Both are vital, mutually complementing information sources that can underpin the development of feasible and effective policies and management interventions. To harvest the added value of combined knowledge, a uniform scaling system is needed. In this paper, we propose a standardized methodology to connect and explore different types of quantitative data from the natural and social sciences reflecting temporal trends in ecosystem quality. We demonstrate this methodology with different types of data such as fisheries stocks and mangrove cover on the one hand and community's perceptions on the other. The example data are collected from three United Nations Educational Scientific and Cultural Organization (UNESCO) Biosphere reserves and one marine park in Southeast Asia. To easily identify patterns of convergence or divergence among the datasets, we propose heat maps using colour codes and icons for language- and education-independent understandability. Finally, we discuss the limitations as well as potential implications for resource management and the accompanying communication strategies. This article is part of the theme issue 'Nurturing resilient marine ecosystems'.

Economic valuation for the conservation of marine biodiversity.

Policy makers are increasingly recognising the role of environmental valuation to guide and support the management and conservation of biodiversity. This paper presents a goods and services approach to determine the economic value of marine biodiversity in the UK, with the aim of clarifying the role of valuation in the management of marine biodiversity. The goods and services resulting from UK marine biodiversity are detailed, and 8 of the 13 services are valued in monetary terms. It is found that a decline in UK marine biodiversity could result in a varying, and at present unpredictable, change in the provision of goods and services, including reduced resilience and resistance to change, declining marine environmental health, reduced fisheries potential, and loss of recreational opportunities. The results suggest that this approach can facilitate biodiversity management by enabling the optimal allocation of limited management resources and through raising awareness of the importance of marine biodiversity.

[Bulbar urethral strictures : A trivial urological disease or a surgical challenge?] / Die bulbäre Harnröhrenstriktur : Banale urologische Erkrankung oder chirurgische Herausforderung?

Urethral strictures are often located in the bulbar urethra, and bulbar strictures are commonly due to urethral trauma. Diagnosis is confirmed by radiographic imaging of the urethra. In cases of short primary bulbar strictures, a simple internal urethrotomy may be curative. In contrast, open surgery should be performed in long segment or recurrent strictures because recurrence rates are near 100% in these cases. Depending of the actual findings and comorbidities, end-to-end anastomosis, graft urethroplasty, flap urethroplasty, or perineal urethrostomy may be used. If definitive treatment using open surgery is delayed and multiple endoscopic treatments are tried, urethroplasty becomes more complex and success rates of definitive treatment decline.

Identification, definition and quantification of goods and services provided by marine biodiversity: implications for the ecosystem approach.

This paper identifies and defines ecosystem goods and services provided by marine biodiversity. Case studies have been used to provide an insight into the practical issues associated with the assessment of marine ecosystem goods and services at specific locations. The aim of this research was to validate the definitions of goods and services, and to identify knowledge gaps and likely difficulties of quantifying the goods and services. A validated theoretical framework for the assessment of goods and services is detailed, and examples of the goods and services at a variety of case study areas are documented. These results will enable future assessments of marine ecosystem goods and services. It is concluded that the utilisation of this goods and services approach has the capacity to play a fundamental role in the Ecosystem Approach, by enabling the pressures and demands of society, the economy and the environment to be integrated into environmental management.

Heat shock protein (HSP-72) levels in skeletal muscle following work in heat.

INTRODUCTION: Acute bouts of heat stress and exercise have been shown to independently increase heat shock protein levels; however, the combination of these two stressors on HSP-72 expression in human skeletal muscle has not been established. The purpose of this study was to determine the effect of a bout of exercise in the heat on HSP-72 expression. METHODS: There were eight recreationally active men (Age = 26.4 +/- 3.1 yr, V(O2)peak = 4.01 +/- 0.25 L min(- 1)) who completed two 30-min bouts of cycle ergometry at 75% of V(O2)peak in a hot (39 degrees C; RH 30%) and cold (9 degrees C; RH 61%) environment. Muscle biopsies were obtained from the vastus lateralis prior to, 6 h post, and 24 h post-exercise to measure HSP-72 protein. Core rectal temperature (Tc), average skin temperature (T(SK)), intramuscular temperature (T(IM)), heart rate (HR), oxygen uptake (V(O2)), sweat rate (SR), and plasma cortisol were measured to determine thermal loads. RESULTS: No significant interactions were present between V(O2) (2.80 +/- 0.2 vs. 2.65 +/- 0.1 L min(-1)) or plasma cortisol (27.1 +/- 2 vs. 19.2 +/- 4 microg dl(-1)) when comparing HT and CD. HR (184 +/- 5 vs. 159 +/- 7 bpm), T(IM) (40.7 +/- 0.2 vs. 40.0 +/- 0.2 degrees C), Tc (38.3 +/- 0.2 vs. 37.9 +/- 0.1 degrees C), T(SK) (36.7 +/- 0.2 vs. 29.6 +/- 0.8 degrees C), and SR (2.0 +/- 0.2 vs. 1.2 +/- 0.2 L h(-1)) were significantly greater when comparing HT and CD. HSP-72 was not altered as a result of either treatment (4.04 +/- 0.87 vs. 2.91 +/- 1.58 ng microg(-1) protein for HT and CD at 6 h post-exercise). DISCUSSION: Exercise in the heat produced a greater thermal load than exercise in the cold; however, no significant increases in HSP-72 were seen when comparing hot and cold conditions.

YY1 can inhibit c-Myc function through a mechanism requiring DNA binding of YY1 but neither its transactivation domain nor direct interaction with c-Myc.

The proto-oncoprotein c-Myc and the multifunctional transcriptional regulator YY1 have been shown previously to interact directly in a manner that excludes Max from the complex (Shrivastava et al., 1993). As binding to Max is necessary for all known c-Myc activities we have analysed the influence of YY1 on c-Myc function. We demonstrate that YY1 is a potent inhibitor of c-Myc transforming activity. The region in YY1 required for inhibition corresponds to a functional DNA-binding domain and is distinct from the domains necessary for direct binding to c-Myc. Furthermore the transactivation domain of YY1 was not necessary suggesting that gene regulation by YY1, for example through DNA bending or displacement of regulators from DNA, could be the cause for the negative regulation of c-Myc. This model of indirect regulation of c-Myc by YY1 was supported by the finding that although YY1 did not bind to the c-Myc transactivation domain (TAD) in vitro it was able to inhibit transactivation by Gal4-MycTAD fusion proteins in transient transfections. As for the inhibition of transformation, an intact DNA-binding domain of YY1 was necessary and sufficient for this effect. In addition YY1 did not alter c-Myc/Max DNA binding, further supporting an indirect mode of action. Our findings point to a role of YY1 as a negative regulator of cell growth with a possible involvement in tumor suppression.

Increased vagal tone during winter in subsyndromal seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is characterized by recurrent winter depression with summer remissions and/or hypomania. Further symptoms include hypersomnia, increased appetite, weight gain, fatigue, and social withdrawal, which may indicate autonomic changes during winter. METHODS: Measurements of respiratory sinus arrhythmia, heart rate (HR), and skin conductance level (SCL) were taken from 32 participants in subsyndromal SAD and control groups (eight male and eight female subjects in each group) in autumn and winter to determine any change in autonomic function. Measures were taken at baseline and during two stressor tasks. Single determinations of blood pressure, sublingual temperature, depression, aerobic fitness, and body mass index were also measured at each session. Replication in a second data collection period over subsequent winter and spring periods was conducted with an additional 32 participants to extend the findings and to counterbalance order effects in testing. Data were combined to produce "winter" and "nonwinter" test periods and statistically corrected for testing order. RESULTS: Respiratory sinus arrhythmia differences indicated that SAD subjects have increased vagal tone in winter. Both groups show a decrease for HR and increases for SCL and diastolic blood pressure in winter. CONCLUSIONS: Seasonal affective disorder may show similarities with hibernation, and the results may indicate mechanisms different from those of nonseasonal depression.

Variations in prescribing practices for novel antipsychotic medications among Veterans Affairs hospitals.

This study examined prescribing practices for antipsychotic medications at 13 Veterans Affairs (VA) medical centers and whether patients' sociodemographic characteristics were associated with receiving novel agents. Automated pharmacy data were used to identify 599 patients who had been diagnosed as having schizophrenia and who had received a prescription for an antipsychotic medication after their last discharge from a VA medical center in 1997. Novel antipsychotics were found to have been prescribed for almost half of the patients (47 percent). In logistic regression analysis, significant variations in prescription of novel agents were found among the facilities and among ethnic groups. The results of this study suggest that prescribing practices are influenced by both facility and patient characteristics.

Experimental effects of tributyltin (TBT) contaminated sediment on a range of meiobenthic communities.

Microcosm experiments have been carried out with whole natural meiobenthic communities to look at the effects of TBT sediment contamination on the community structure of the dominant nematode component of the meiobenthos. TBT has a high affinity for aquatic sediments, yet this is the first study of the effects of this contaminant in sediment on natural benthic communities. Three communities were studied from contrasting locations in south-west England: the intertidal of the Lynher estuary (muddy sediment) and the Exe estuary (sandy sediment) and the subtidal (50m depth) at Rame Head off Plymouth (muddy sand). Fresh sediment with natural meiobenthic communities was incubated for 2 months with TBT-contaminated sediment (three dose levels) in bottles. Nematodes were identified and enumerated and subjected to multivariate data analysis. The sandy Exe estuary fauna was significantly affected by TBT-contaminated sediment at all three doses (0.3, 0.6 and 0.9 microg g(-1) dry wt (as Sn) sediment), whereas the offshore fauna from Rame Head was significantly affected only at the highest dose. The muddy Lynher estuary meiofauna was affected (somewhat peculiarly) at the medium dose level only. Meiobenthic nematodes may not be as sensitive to TBT-contaminated sediment as other infaunal benthos but exhibited responses to levels of contamination still persisting in some UK estuaries and harbours. Comparing the effects of TBT with those of copper and zinc in the same laboratory experiments, our observations suggest that the relative impact of TBT on meiobenthic community structure is not as great as these contaminants in marine sediments. Although there are very few observations of TBT toxicity in sediment, it appears that TBT is toxic at much lower concentrations in seawater (ppb) than it is in sediment (ppm).

Oceans and Human Health: a rising tide of challenges and opportunities for Europe.

The European Marine Board recently published a position paper on linking oceans and human health as a strategic research priority for Europe. With this position paper as a reference, the March 2014 Cornwall Oceans and Human Health Workshop brought together key scientists, policy makers, funders, business, and non governmental organisations from Europe and the US to review the recent interdisciplinary and cutting edge research in oceans and human health specifically the growing evidence of the impacts of oceans and seas on human health and wellbeing (and the effects of humans on the oceans). These impacts are a complex mixture of negative influences (e.g. from climate change and extreme weather to harmful algal blooms and chemical pollution) and beneficial factors (e.g. from natural products including seafood to marine renewable energy and wellbeing from interactions with coastal environments). Integrated approaches across disciplines, institutions, and nations in science and policy are needed to protect both the oceans and human health and wellbeing now and in the future.

Effect of prior exercise on postprandial triglycerides in overweight young women after ingesting a high-carbohydrate meal.

To examine the effect of prior exercise on the postprandial lipid response to a high-carbohydrate meal in normal-weight (NW=BMI <25) and overweight (OW=BMI >or= 25) women (age 18-25), 10 NW and 10 OW participants completed 2 conditions separated by 1 month. In the morning, the day after control (CT=no exercise) or exercise conditions (EX=60 min cycling at 60% VO(2peak)), participants consumed a high-carbohydrate meal (80% CHO, 15% protein, 5% fat; 75 kJ/kg BM) followed by 6 hr of hourly blood sampling. Blood was analyzed for triglycerides (TG), blood glucose (BG), and insulin (IN). TG levels over the 6-hr period were lower in NW than OW (p= .021) and lower in EX than in CT (p= .006). Area under the curve (AUC) for TG was lower in NW than OW (p= .016) and EX than CT (p= .003). There were nonsignificant tendencies for reduced BG over time (p= .053) and AUC (p= .083), and IN AUC was lower in EX than in CT (p= .040) for both groups and lower in NW than in OW (p= .039). Prior exercise improved TG levels after a high-carbohydrate meal in both groups, and OW women demonstrated a greater postprandial lipemic response than NW regardless of condition. There were tendencies for improved glucose removal with prior exercise in NW vs. OW. Acute exercise can improve postprandial TG responses and might also improve postprandial BG and IN after a large meal in NW and OW young women.

Secondary malignancies in different forms of urinary diversion using isolated gut.

PURPOSE: Tumor development following ureterosigmoidostomy is a worldwide accepted late complication. In contrast, tumor risk in other forms of urinary diversion with the separation of urine and feces is still unclear. We present a complete and detailed analysis of all reported tumors following urinary diversions using isolated gut segments in the literature. We estimated the tumor risk in comparison to ureterosigmoidostomies and to the general population. MATERIALS AND METHODS: We reviewed the world literature up to April 2003 via MEDLINE for secondary tumors in urinary diversions using isolated intestinal segments. RESULTS: We found 81 tumor case reports following urinary diversion using isolated intestinal segments. Tumors developed in 18 conduits, 45 cystoplasties, 5 rectal bladders, 3 neobladders, 6 colonic pouches and 4 ileal ureter replacements. CONCLUSIONS: All urinary diversions using bowel with or without separation of urine and feces carry a significantly higher tumor risk for intestinal tumor development compared to the general population. The tumor spectrum and tumor location in isolated gut segments are different than tumors following ureterosigmoidostomies but the total tumor risk is probably similar. The latency period depends on the initial diagnosis with malignant diseases leading to a shorter induction time. Concerning etiology, many theories exist but the exact mechanism remains unclear. Regular endoscopic control beginning with postoperative year 3 for early detection of secondary malignancies is mandatory.

Characterization of the transcriptional regulator YY1. The bipartite transactivation domain is independent of interaction with the TATA box-binding protein, transcription factor IIB, TAFII55, or cAMP-responsive element-binding protein (CPB)-binding protein.

YY1 is a multifunctional transcription factor implicated in both positive and negative regulation of gene expression as well as in initiation of transcription. We show that YY1 is ubiquitously expressed in growing, differentiated, and growth-arrested cells. The protein is phosphorylated and has a half-life of 3.5 h. To define functional domains, we have generated a large panel of YY1 mutant proteins. These were used to define precisely the DNA-binding domain, the region responsible for nuclear localization, and the transactivation domain. The two acidic domains at the N terminus each provide about half of the transcriptional activating activity. Furthermore, the spacer region between the Gly/Ala-rich and zinc finger domains has accessory function in transactivation. YY1 has been shown previously to bind to TAFII55, TATA box-binding protein, transcription factor IIB, and p300. In addition, we identified cAMP-responsive element-binding protein (CBP)-binding protein as a YY1 binding partner. Surprisingly, these proteins did not bind to the domains involved in transactivation, but rather to the zinc finger and Gly/Ala-rich domains of YY1. Thus, these proteins do not explain the transcriptional activating activity of YY1, but rather may be involved in repression or in initiation.

Fatal head injuries in Cape Town.

Between 1 July 1983 and 30 June 1985 there were 563 cases of fatal head injuries in people over the age of 15 years recorded at the Salt River Police Mortuary, Cape Town. The demographic character of these cases was reviewed according to: (i) age, race and sex; (ii) date, day and time of injury; (iii) cause of death; and (iv) positive blood alcohol test. Assaults and transport-related accidents in association with a positive blood alcohol test in coloured males aged 40-60 years were a major characteristic.

Identification and characterization of specific DNA-binding complexes containing members of the Myc/Max/Mad network of transcriptional regulators.

In the past, eukaryotic cell-derived complexes of the Myc/Max/Mad network of transcriptional regulators have largely been refractory to DNA binding studies. We have developed electrophoretic mobility shift assay conditions to measure specific DNA binding of Myc/Max/Mad network complexes using a COS7 cell-based overexpression system. With the established protocol, we have measured on- and off-rates of c-Myc/Max, Max/Max, and Mad1/Max complexes and determined relative affinities. All three complexes appeared to bind with comparable affinity to a Myc E-box sequence. Furthermore, our data derived from competition experiments suggested that the Mad3/Max and Mad4/Max complexes also possess comparable DNA binding affinities. The conditions established for COS7 cell-overexpressed proteins were then used to identify c-Myc/Max, Max/Max, and Mnt/Max complexes in HL-60 cells. However, no Mad1/Max could be detected, despite the induction of Mad1 expression during differentiation. Whereas the DNA binding activity of c-Myc/Max complexes was down-regulated, Max/Max binding increased, and Mnt/Max binding remained unchanged. In addition, we have also tested for upstream stimulatory factor (USF) binding and observed that, in agreement with published data, USF comprises a major Myc E-box-binding factor that is more abundant than any of the Myc/Max/Mad network complexes. Similar to the Mnt/Max complex, the binding activity of USF remained constant during HL-60 differentiation. Our findings establish conditions for the analysis of DNA binding of Myc/Max/Mad complexes and indicate posttranslational regulation of the Max/Max complex.