Sarcoidosis of the hypothalamus and pituitary stalk

We report a rare case of sarcoidosis of the hypothalamic and suprasellar region, with clinical course and the magnetic resonance imaging follow-up

The Broad-Spectrum Antimicrobial Potential of [Mn(CO)(4)(S2CNMe(CH2CO2H))], a Water-Soluble CO-Releasing Molecule (CORM-401): Intracellular Accumulation, Transcriptomic and Statistical Analyses, and Membrane Polarization

Aims: Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM. Results: [Mn(CO)(4)S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. CORM-401 releases CO that binds oxidases in vivo, but is an ineffective respiratory inhibitor. Extensive CORM accumulation (assayed as intracellular manganese) accompanies antimicrobial activity. CORM-401 stimulates respiration, polarizes the cytoplasmic membrane in an uncoupler-like manner, and elicits loss of intracellular potassium and zinc. Transcriptomics and mathematical modeling of transcription factor activities reveal a multifaceted response characterized by elevated expression of genes encoding potassium uptake, efflux pumps, and envelope stress responses. Regulators implicated in stress responses (CpxR), respiration (Arc, Fnr), methionine biosynthesis (MetJ), and iron homeostasis (Fur) are significantly disturbed. Although CORM-401 reduces bacterial growth in combination with cefotaxime and trimethoprim, fractional inhibition studies reveal no interaction. Innovation: We present the most detailed microbiological analysis yet of a CORM that is not a ruthenium carbonyl. We demonstrate CO-independent striking effects on the bacterial membrane and global transcriptomic responses. Conclusions: CORM-401, contrary to our expectations of a CO delivery vehicle, does not inhibit respiration. It accumulates in the cytoplasm, acts like an uncoupler in disrupting cytoplasmic ion balance, and triggers multiple effects, including osmotic stress and futile respiration

Flagellin outer domain dimerization modulates motility in pathogenic and soil bacteria from viscous environments.

Flagellar filaments function as the propellers of the bacterial flagellum and their supercoiling is key to motility. The outer domains on the surface of the filament are non-critical for motility in many bacteria and their structures and functions are not conserved. Here, we show the atomic cryo-electron microscopy structures for flagellar filaments from enterohemorrhagic Escherichia coli O157:H7, enteropathogenic E. coli O127:H6, Achromobacter, and Sinorhizobium meliloti, where the outer domains dimerize or tetramerize to form either a sheath or a screw-like surface. These dimers are formed by 180° rotations of half of the outer domains. The outer domain sheath (ODS) plays a role in bacterial motility by stabilizing an intermediate waveform and prolonging the tumbling of E. coli cells. Bacteria with these ODS and screw-like flagellar filaments are commonly found in soil and human intestinal environments of relatively high viscosity suggesting a role for the dimerization in these environments

Experimental evidence that livestock grazing intensity affects cyclic vole population regulation processes

Peer reviewedPublisher PD

Climate and Dispersal: Black-Winged Stilts Disperse Further in Dry Springs

Climate affects the abundance and distribution of many species of wildlife. Nevertheless, the potential effects of climate on dispersive behaviour remain unstudied. Here, I combine data from (i) a long-term Black-winged Stilt (Himantopus himantopus) monitoring program, (ii) a capture-recapture marking program in Doñana, and (iii) reports from the Rare Birds Committee in the United Kingdom to analyse at different geographical scales the relationship between climate, survival, philopatry, and dispersive behaviour. Black-winged Stilt populations varied in size in consonance with changes in both the North Atlantic Oscillation (NAO) and local rainfall during the breeding season. Changes in population size are related to changes in philopatry and increases in dispersal beyond the traditional range of the species. The results indicate that climatic conditions influence the dispersive behaviour of individual birds, explaining rapid changes in the local population of this species breeding in unstable Mediterranean wetlands

Effects of Sample Size on Estimates of Population Growth Rates Calculated with Matrix Models

BACKGROUND: Matrix models are widely used to study the dynamics and demography of populations. An important but overlooked issue is how the number of individuals sampled influences estimates of the population growth rate (lambda) calculated with matrix models. Even unbiased estimates of vital rates do not ensure unbiased estimates of lambda-Jensen's Inequality implies that even when the estimates of the vital rates are accurate, small sample sizes lead to biased estimates of lambda due to increased sampling variance. We investigated if sampling variability and the distribution of sampling effort among size classes lead to biases in estimates of lambda. METHODOLOGY/PRINCIPAL FINDINGS: Using data from a long-term field study of plant demography, we simulated the effects of sampling variance by drawing vital rates and calculating lambda for increasingly larger populations drawn from a total population of 3842 plants. We then compared these estimates of lambda with those based on the entire population and calculated the resulting bias. Finally, we conducted a review of the literature to determine the sample sizes typically used when parameterizing matrix models used to study plant demography. CONCLUSIONS/SIGNIFICANCE: We found significant bias at small sample sizes when survival was low (survival = 0.5), and that sampling with a more-realistic inverse J-shaped population structure exacerbated this bias. However our simulations also demonstrate that these biases rapidly become negligible with increasing sample sizes or as survival increases. For many of the sample sizes used in demographic studies, matrix models are probably robust to the biases resulting from sampling variance of vital rates. However, this conclusion may depend on the structure of populations or the distribution of sampling effort in ways that are unexplored. We suggest more intensive sampling of populations when individual survival is low and greater sampling of stages with high elasticities

‘1L=10L for Africa’: Corporate social responsibility and the transformation of bottled water into a ‘consumer activist’ commodity

In recent years, it has become an increasingly common marketing practice to connect the sale of consumer products to corporate social responsibility (CSR) initiatives, such as aid and development projects in so-called ‘developing’ countries. One example is Volvic’s pioneering ‘1L=10L for Africa’ campaign (2005–2010), which linked the sale of each liter of bottled water in ‘developed’ countries with the promise by Danone, Volvic’s owner, to provide 10 liters of drinking water in Africa. In this article, we engage with this ‘cause-related marketing’ campaign, using critical discourse analysis (CDA) to uncover its mechanisms and ideological functioning. We show how Volvic was able to transform an ordinary commodity, bottled water, into a consumer activist brand through which consumers could take part in solving global social problems, such as the access to safe drinking water in ‘developing’ countries. Our analysis of this exemplary case shows the ways that CSR often operates to deflect ethical critiques, consolidate brand loyalty and corporate profits, and defuse political struggles around consumption. By doing so, we suggest that CSR forms part of a complex strategy deployed to legitimize particular brands and commodities. In this way CSR can be seen as playing an important role in the ideological makeup of contemporary consumer capitalism. </jats:p

Patient Discomfort Associated with the Use of Intra-arterial Iodinated Contrast Media: A Meta-Analysis of Comparative Randomized Controlled Trials

<p>Abstract</p> <p>Background</p> <p>Discomfort characterized by pain and warmth are common adverse effects associated with the use of intra-arterial iodinated contrast media (CM). The objective of this review was to pool patient-reported outcomes available from head-to-head randomized controlled trials (RCTs) and to compare the discomfort rates associated with iso-osmolar contrast media (IOCM; i.e., iodixanol) to those reported with various low-osmolar contrast media (LOCM).</p> <p>Methods</p> <p>A review of the literature published between 1990 and 2009 available through Medline, Medline Preprints, Embase, Biological Abstracts, BioBase, Cab Abstracts, International Pharmaceutical Abstracts, Life Sciences Collection, Inside Conferences, Energy Database, Engineering Index and Technology Collection was performed to compare rates of discomfort associated with the use of the IOCM (iodixanol) vs. various LOCM agents in head-to-head RCTs. All trials with a Jadad score ≥2 that reported patient discomfort data following intra-arterial administration of CM were reviewed, coded, and extracted.</p> <p>Results</p> <p>A total of 22 RCTs (n = 8087) were included. Overall discomfort (regardless of severity) was significantly different between patients receiving IOCM and various LOCMs (risk difference [RD] -0.049; 95% confidence interval [CI]: -0.076, -0.021; p = 0.001). IOCM was favored over all LOCMs combined with a summary RD value of -0.188 (95% CI: -0.265, -0.112; p < 0.001) for incidence of pain, regardless of severity. A greater reduction in the magnitude of pain was observed with IOCM (iodixanol), particularly with selective limb and carotid/intracerebral procedures. Similarly, the meta-analysis of warmth sensation, regardless of severity, favored IOCM over LOCMs with an RD of -0.043 (95% CI: -0.074, -0.011; p = 0.008). A positive linear relationship was observed between the discomfort effect size and age and a negative relationship with increasing proportion of women. The opposite trends were observed with warmth sensation.</p> <p>Conclusions</p> <p>IOCM was associated with less frequent and severe patient discomfort during intra-arterial administration. These data support differences in osmolality as a possible determinant of CM discomfort.</p

Immune Boosting Explains Regime-Shifts in Prevaccine-Era Pertussis Dynamics

Understanding the biological mechanisms underlying episodic outbreaks of infectious diseases is one of mathematical epidemiology’s major goals. Historic records are an invaluable source of information in this enterprise. Pertussis (whooping cough) is a re-emerging infection whose intermittent bouts of large multiannual epidemics interspersed between periods of smaller-amplitude cycles remain an enigma. It has been suggested that recent increases in pertussis incidence and shifts in the age-distribution of cases may be due to diminished natural immune boosting. Here we show that a model that incorporates this mechanism can account for a unique set of pre-vaccine-era data from Copenhagen. Under this model, immune boosting induces transient bursts of large amplitude outbreaks. In the face of mass vaccination, the boosting model predicts larger and more frequent outbreaks than do models with permanent or passively-waning immunity. Our results emphasize the importance of understanding the mechanisms responsible for maintaining immune memory fo