A plague on five of your houses - statistical re-assessment of three pneumonic plague outbreaks that occurred in Suffolk, England, between 1906 and 1918

<p>Abstract</p> <p>Background</p> <p>Plague is a re-emerging disease and its pneumonic form is a high priority bio-terrorist threat. Epidemiologists have previously analysed historical outbreaks of pneumonic plague to better understand the dynamics of infection, transmission and control. This study examines 3 relatively unknown outbreaks of pneumonic plague that occurred in Suffolk, England, during the first 2 decades of the twentieth century.</p> <p>Methods</p> <p>The Kolmogorov-Smirnov statistical test is used to compare the symptomatic period and the length of time between successive cases (i.e. the serial interval) with previously reported values. Consideration is also given to the case fatality ratio, the average number of secondary cases resulting from each primary case in the observed minor outbreaks (termed <it>R</it>_{<it>minor</it>}), and the proportion of individuals living within an affected household that succumb to pneumonic plague via the index case (i.e. the household secondary attack rate (SAR)).</p> <p>Results</p> <p>2 of the 14 cases survived giving a case fatality ratio of 86% (95% confidence interval (CI) = {57%, 98%}). For the 12 fatal cases, the average symptomatic period was 3.3 days (standard deviation (SD) = 1.2 days) and, for the 11 non index cases, the average serial interval was 5.8 days (SD = 2.0 days). <it>R</it>_{<it>minor </it>}was calculated to be 0.9 (SD = 1.0) and, in 2 households, the SAR was approximately 14% (95% CI = {0%, 58%}) and 20% (95% CI = {1%, 72%}), respectively.</p> <p>Conclusions</p> <p>The symptomatic period was approximately 1 day longer on average than in an earlier study but the serial interval was in close agreement with 2 previously reported values. 2 of the 3 outbreaks ended without explicit public health interventions; however, non-professional caregivers were particularly vulnerable - an important public health consideration for any future outbreak of pneumonic plague.</p

Inverse association of NSAID use and ovarian cancer in relation to oral contraceptive use and parity

We examined the association between non-steroidal anti-inflammatory drug (NSAID) use and ovarian cancer by potential effect modifiers, parity and oral contraceptive use, in a population-based case–control study conducted in Wisconsin and Massachusetts. Women reported prior use of NSAIDs and information on risk factors in a telephone interview. A total of 487 invasive ovarian cancer cases and 2653 control women aged 20–74 years were included in the analysis. After adjustment for age, state of residence and other covariates, ever use of NSAIDs was inversely associated with ovarian cancer in never users of oral contraceptives (odds ratio (OR)=0.58, 95% confidence interval (CI) 0.42–0.80) but not for ever users (OR=0.98, 95% CI 0.71–1.35) (P-interaction=0.03). A reduced risk with NSAID use was also noted in nulliparous women (OR=0.47, 95% CI 0.27–0.82) but not among parous women (OR=0.81, 95% CI 0.64–1.04) (P-interaction=0.05). These results suggest that use of NSAIDs were beneficial to women at greatest risk for ovarian cancer

Transient Receptor Potential Ion Channels Control Thermoregulatory Behaviour in Reptiles

Biological functions are governed by thermodynamics, and animals regulate their body temperature to optimise cellular performance and to avoid harmful extremes. The capacity to sense environmental and internal temperatures is a prerequisite for the evolution of thermoregulation. However, the mechanisms that enable ectothermic vertebrates to sense heat remain unknown. The recently discovered thermal characteristics of transient receptor potential ion channels (TRP) render these proteins suitable to act as temperature sensors. Here we test the hypothesis that TRPs are present in reptiles and function to control thermoregulatory behaviour. We show that the hot-sensing TRPV1 is expressed in a crocodile (Crocodylus porosus), an agamid (Amphibolurus muricatus) and a scincid (Pseudemoia entrecasteauxii) lizard, as well as in the quail and zebrafinch (Coturnix chinensis and Poephila guttata). The TRPV1 genes from all reptiles form a unique clade that is delineated from the mammalian and the ancestral Xenopus sequences by an insertion of two amino acids. TRPV1 and the cool-sensing TRPM8 are expressed in liver, muscle (transversospinalis complex), and heart tissues of the crocodile, and have the potential to act as internal thermometer and as external temperatures sensors. Inhibition of TRPV1 and TRPM8 in C. porosus abolishes the typically reptilian shuttling behaviour between cooling and heating environments, and leads to significantly altered body temperature patterns. Our results provide the proximate mechanism of thermal selection in terrestrial ectotherms, which heralds a fundamental change in interpretation, because TRPs provide the mechanism for a tissue-specific input into the animals' thermoregulatory response

Sensory Integration Regulating Male Courtship Behavior in Drosophila

The courtship behavior of Drosophila melanogaster serves as an excellent model system to study how complex innate behaviors are controlled by the nervous system. To understand how the underlying neural network controls this behavior, it is not sufficient to unravel its architecture, but also crucial to decipher its logic. By systematic analysis of how variations in sensory inputs alter the courtship behavior of a naïve male in the single-choice courtship paradigm, we derive a model describing the logic of the network that integrates the various sensory stimuli and elicits this complex innate behavior. This approach and the model derived from it distinguish (i) between initiation and maintenance of courtship, (ii) between courtship in daylight and in the dark, where the male uses a scanning strategy to retrieve the decamping female, and (iii) between courtship towards receptive virgin females and mature males. The last distinction demonstrates that sexual orientation of the courting male, in the absence of discriminatory visual cues, depends on the integration of gustatory and behavioral feedback inputs, but not on olfactory signals from the courted animal. The model will complement studies on the connectivity and intrinsic properties of the neurons forming the circuitry that regulates male courtship behavior

Prescriptions for selective cyclooxygenase-2 inhibitors, non-selective non-steroidal anti-inflammatory drugs, and risk of breast cancer in a population-based case-control study

INTRODUCTION. Non-steroidal anti-inflammatory drugs (NSAIDs) prevent the growth of mammary tumours in animal models. Two population-based case-control studies suggest a reduced risk of breast cancer associated with selective cyclooxygenase-2 (sCox-2) inhibitor use, but data regarding the association between breast cancer occurrence and use of non-selective NSAIDs are conflicting. METHODS. We conducted a population-based case-control study using Danish healthcare databases to examine if use of NSAIDs, including sCox-2 inhibitors, was associated with a reduced risk of breast cancer. We included 8,195 incident breast cancer cases diagnosed in 1991 through 2006 and 81,950 population controls. RESULTS. Overall, we found no reduced breast cancer risk in ever users (>2 prescriptions) of sCox-2 inhibitors (odds ratio (OR) = 1.08, 95% confidence interval (95% CI) = 0.99, 1.18), aspirin (OR = 0.98, 95% CI = 0.90-1.07), or non-selective NSAIDs OR = 1.04, (95% CI = 0.98, 1.10)). Recent use (>2 prescriptions within two years of index date) of sCox-2 inhibitors, aspirin, or non-selective NSAIDs was likewise not associated with breast cancer risk (Ors = 1.06 (95% CI = 0.96, 1.18), 0.96 (95% CI = 0.87, 1.06) and 0.99 (95% CI = 0.85, 1.16), respectively). Risk estimates by duration (<10, 10 to 15, 15+ years) or intensity (low/medium/high) of NSAID use were also close to unity. Regardless of intensity, shorter or long-term NSAID use was not significantly associated with breast cancer risk. CONCLUSIONS. Overall, we found no compelling evidence of a reduced risk of breast cancer associated with use of sCox-2 inhibitors, aspirin, or non-selective NSAIDs.Karen Elise Jensen Foundatio

Nature meets nurture: molecular genetics of gastric cancer

The immensity of genes and molecules implicated in gastric carcinogenesis is overwhelming and the relevant importance of some of these molecules is too often unclear. This review serves to bring us up-to-date with the latest findings as well as to look at the larger picture in terms of how to tackle the problem of solving this multi-piece puzzle. In this review, the environmental nurturing of intestinal cancer is discussed, beginning with epidemiology (known causative factors for inducing molecular change), an update of H. pylori research, including the role of inflammation and stem cells in premalignant lesions. The role of E-cadherin in the nature (genotype) of diffuse gastric cancer is highlighted, and finally the ever growing discipline of SNP analysis (including IL1B) is discussed

Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism

The process of axonal and dendritic development establishes the synaptic circuitry of the central nervous system (CNS) and is the result of interactions between intrinsic molecular factors and the external environment. One growth factor that has a compelling function in neuronal development is the neurotrophin brain-derived neurotrophic factor (BDNF). BDNF participates in axonal and dendritic differentiation during embryonic stages of neuronal development, as well as in the formation and maturation of dendritic spines during postnatal development. Recent studies have also implicated vesicular trafficking of BDNF via secretory vesicles, and both secretory and endosomal trafficking of vesicles containing synaptic proteins, such as neurotransmitter and neurotrophin receptors, in the regulation of axonal and dendritic differentiation, and in dendritic spine morphogenesis. Several genes that are either mutated or deregulated in neurodevelopmental disorders associated with mental retardation have now been identified, and several mouse models of these disorders have been generated and characterized. Interestingly, abnormalities in dendritic and synaptic structure are consistently observed in human neurodevelopmental disorders associated with mental retardation, and in mouse models of these disorders as well. Abnormalities in dendritic and synaptic differentiation are thought to underlie altered synaptic function and network connectivity, thus contributing to the clinical outcome. Here, we review the roles of BDNF and vesicular trafficking in axonal and dendritic differentiation in the context of dendritic and axonal morphological impairments commonly observed in neurodevelopmental disorders associated with mental retardation