Predicting Pneumonia and Influenza Mortality from Morbidity Data

BACKGROUND: Few European countries conduct reactive surveillance of influenza mortality, whereas most monitor morbidity. METHODOLOGY/PRINCIPAL FINDINGS: We developed a simple model based on Poisson seasonal regression to predict excess cases of pneumonia and influenza mortality during influenza epidemics, based on influenza morbidity data and the dominant types/subtypes of circulating viruses. Epidemics were classified in three levels of mortality burden (“high”, “moderate” and “low”). The model was fitted on 14 influenza seasons and was validated on six subsequent influenza seasons. Five out of the six seasons in the validation set were correctly classified. The average absolute difference between observed and predicted mortality was 2.8 per 100,000 (18% of the average excess mortality) and Spearman's rank correlation coefficient was 0.89 (P = 0.05). CONCLUSIONS/SIGNIFICANCE: The method described here can be used to estimate the influenza mortality burden in countries where specific pneumonia and influenza mortality surveillance data are not available

Neuroimaging in cluster headache and other trigeminal autonomic cephalalgias

The central nervous system mechanisms involved in trigeminal autonomic cephalalgias, a group of primary headaches characterized by strictly unilateral head pain that occurs in association with ipsilateral craniofacial autonomic features, are still not comprehensively understood. However, functional imaging methods have revolutionized our understanding of mechanisms involved in these primary headache syndromes. The present review provides a brief overview of the major modern functional neuroimaging techniques used to examine brain structure, biochemistry, metabolic state, and functional capacity. The available functional neuroimaging data in cluster headache and other TACs will thus be summarized. Although the precise brain structures responsible for these primary headache syndromes still remain to be determined, neuroimaging data suggest a major role for posterior hypothalamus activation in initiating and maintaining attacks. Furthermore, pathophysiological involvement of the pain neuromatrix and of the central descending opiatergic pain control system was observed. Given the rapid advances in functional and structural neuroimaging methodologies, it can be expected that these non-invasive techniques will continue to improve our understanding into the nature of the brain dysfunction in cluster headache and other trigeminal autonomic cephalalgias

Population density and group size effects on reproductive behavior in a simultaneous hermaphrodite

<p>Abstract</p> <p>Background</p> <p>Despite growing evidence that population dynamic processes can have substantial effects on mating system evolution, little is known about their effect on mating rates in simultaneous hermaphrodites. According to theory, mating rate is expected to increase with mate availability because mating activity is primarily controlled by the male sexual function. A different scenario appears plausible in the hermaphroditic opisthobranch <it>Chelidonura sandrana</it>. Here, field mating rates are close to the female fitness optimum, suggesting that mating activity remains unresponsive to variation in mate availability.</p> <p>Results</p> <p>Applying an experimental design that aims at independent experimental manipulation of density and social group size, we find substantial increases in mate encounter rate with both factors, but no statistically detectable effects on mating rate in <it>C. sandrana</it>. Instead, mating rate remained close to the earlier determined female fitness optimum.</p> <p>Conclusions</p> <p>We demonstrate that mating rate in <it>C. sandrana </it>is largely unresponsive to variation in mate availability and is maintained close to the female fitness optimum. These findings challenge the prevailing notion of male driven mating rates in simultaneous hermaphrodites and call for complementary investigations of mating rate effects on fitness through the male sexual function.</p

Increased expression of urokinase plasminogen activator and its cognate receptor in human seminomas

<p>Abstract</p> <p>Background</p> <p>The urokinase plasminogen activating system (uPAS) is implicated in neoplastic progression and high tissue levels of uPAS components correlate with a poor prognosis in different human cancers. Despite that, relative few studies are available on the expression and function of the uPAS components in human seminomas. In the present study we characterized the expression of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR) and the uPA inhibitors PAI-1 and PAI-2 in normal human testis and seminomas.</p> <p>Methods</p> <p>The expression of the above genes was evaluated by means of quantitative RT-PCR, western blot, zymographic analysis and immunohistochemistry.</p> <p>Results</p> <p>Quantitative RT-PCR analysis of 14 seminomas demonstrated that uPA and uPAR mRNAs were, with respect to control tissues, increased in tumor tissues by 3.80 ± 0.74 (p < 0.01) and 6.25 ± 1.18 (p < 0.01) fold, respectively. On the other hand, PAI-1 mRNA level was unchanged (1.02 ± 0.24 fold), while that of PAI-2 was significantly reduced to 0.34 ± 0.18 (p < 0.01) fold. Western blot experiments performed with protein extracts of three seminomas and normal tissues from the same patients showed that uPA protein levels were low or undetectable in normal tissues and induced in tumor tissues. On the same samples, zymographic analysis demonstrated increased uPA activity in tumor tissue extracts. Western blot experiments showed that also the uPAR protein was increased in tumor tissues by 1.83 ± 0.15 fold (p < 0.01). The increased expression of uPA and uPAR was further confirmed by immunohistochemical staining performed in 10 seminomas and autologous uninvolved peritumoral tissues. Finally, variation in the mRNA level of PAI-1 significantly correlated with tumor size.</p> <p>Conclusions</p> <p>We demonstrated the increased expression of uPA and uPAR in human seminomas with respect to normal testis tissues, which may be relevant in testicular cancer progression.</p

HUWE1 E3 ligase promotes PINK1/PARKINindependent mitophagy by regulating AMBRA1 activation via IKKa

The selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells

Are there any differences in clinical and laboratory findings on admission between H1N1 positive and negative patients with flu-like symptoms?

<p>Abstract</p> <p>Background</p> <p>The World Health Organization alert for the H1N1 influenza pandemic led to the implementation of certain measures regarding admission of patients with flu-like symptoms. All these instructions were adopted by the Greek National Health System. The aim of this study was to retrospectively examine the characteristics of all subjects admitted to the Unit of Infectious Diseases with symptoms indicating H1N1 infection, and to identify any differences between H1N1 positive or negative patients. Patients from the ED (emergency department) with flu-like symptoms (sore throat, cough, rhinorhea, or nasal congestion) and fever >37.5°C were admitted in the Unit of Infectious diseases and gave pharyngeal or nasopharyngeal swabs. Swabs were tested with real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR).</p> <p>Findings</p> <p>Patients were divided into two groups. Group A comprised 33 H1N1 positive patients and Group B (control group) comprised of 27 H1N1 negative patients. The two groups did not differ in terms of patient age, co-morbidities, length of hospitalization, temperature elevation, hypoxemia, as well as renal and liver function. There were also no significant differences in severity on admission. C-reactive protein (CRP) (mean 12.8 vs. 5.74) and white blood count (WBC) (mean 10.528 vs. 7.114) were significantly higher in group B than in group A upon admission. Obesity was noted in 8 patients of Group A (mean 31.67) and 14 patients of Group B (mean 37.78). Body mass index (BMI) was lower in H1N1 positive than in H1N1 negative patients (mean 31.67 vs. 37.78, respectively; p = 0.009).</p> <p>Conclusions</p> <p>The majority of patients in both groups were young male adults. CRP, WBC and BMI were higher among H1N1 negative patients. Finally, clinical course of patients in both groups was mild and uneventful.</p

A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model

Symbiotic gut microorganisms (microbiome) interact closely with the mammalian host's metabolism and are important determinants of human health. Here, we decipher the complex metabolic effects of microbial manipulation, by comparing germfree mice colonized by a human baby flora (HBF) or a normal flora to conventional mice. We perform parallel microbiological profiling, metabolic profiling by 1H nuclear magnetic resonance of liver, plasma, urine and ileal flushes, and targeted profiling of bile acids by ultra performance liquid chromatography–mass spectrometry and short-chain fatty acids in cecum by GC-FID. Top-down multivariate analysis of metabolic profiles reveals a significant association of specific metabotypes with the resident microbiome. We derive a transgenomic graph model showing that HBF flora has a remarkably simple microbiome/metabolome correlation network, impacting directly on the host's ability to metabolize lipids: HBF mice present higher ileal concentrations of tauro-conjugated bile acids, reduced plasma levels of lipoproteins but higher hepatic triglyceride content associated with depletion of glutathione. These data indicate that the microbiome modulates absorption, storage and the energy harvest from the diet at the systems level