Evaluating Surveillance Strategies for the Early Detection of Low Pathogenicity Avian Influenza Infections

In recent years, the early detection of low pathogenicity avian influenza (LPAI) viruses in poultry has become increasingly important, given their potential to mutate into highly pathogenic viruses. However, evaluations of LPAI surveillance have mainly focused on prevalence and not on the ability to act as an early warning system. We used a simulation model based on data from Italian LPAI epidemics in turkeys to evaluate different surveillance strategies in terms of their performance as early warning systems. The strategies differed in terms of sample size, sampling frequency, diagnostic tests, and whether or not active surveillance (i.e., routine laboratory testing of farms) was performed, and were also tested under different epidemiological scenarios. We compared surveillance strategies by simulating within-farm outbreaks. The output measures were the proportion of infected farms that are detected and the farm reproduction number (Rh). The first one provides an indication of the sensitivity of the surveillance system to detect within-farm infections, whereas Rh reflects the effectiveness of outbreak detection (i.e., if detection occurs soon enough to bring an epidemic under control). Increasing the sampling frequency was the most effective means of improving the timeliness of detection (i.e., it occurs earlier), whereas increasing the sample size increased the likelihood of detection. Surveillance was only effective in preventing an epidemic if actions were taken within two days of sampling. The strategies were not affected by the quality of the diagnostic test, although performing both serological and virological assays increased the sensitivity of active surveillance. Early detection of LPAI outbreaks in turkeys can be achieved by increasing the sampling frequency for active surveillance, though very frequent sampling may not be sustainable in the long term. We suggest that, when no LPAI virus is circulating yet and there is a low risk of virus introduction, a less frequent sampling approach might be admitted, provided that the surveillance is intensified as soon as the first outbreak is detected

Global Health: A Successful Context for Precollege Training and Advocacy

Despite a flourishing biomedical and global health industry [1] too few of Washington state's precollege students are aware of this growing sector and emerging ideas on bacteria, fungi, parasites and viruses. Against the backdrop of numerous reports regarding declining precollege student interest in science [2], a precollege program was envisioned at Seattle Biomedical Research Institute (as of 2010, Seattle BioMed) to increase youth engagement in biomedical research and global health, increase community interest in infectious diseases and mobilize a future biomedical workforce. Since 2005, 169 rising high school juniors have participated in the BioQuest Academy precollege immersion program at Seattle BioMed. Assembling in groups of 12, students conduct laboratory experiments (e.g., anopheline mosquito dissection, gene expression informed tuberculosis drug design and optimizing HIV immunization strategies) related to global health alongside practicing scientific mentors, all within the footprint the institute. Laudable short-term impacts of the program include positive influences on student interest in global health (as seen in the students' subsequent school projects and their participation in Seattle BioMed community events), biomedical careers and graduate school (e.g., 16.9% of teens departing 2008–2009 Academy report revised goals of attaining a doctorate rather than a baccalaureate diploma). Long-term, 97% of alumni (2005–2008) are attending postsecondary schools throughout North America; eight graduates have already published scientific articles in peer-reviewed journals and/or presented their scientific data at national and international meetings, and 26 have been retained by Seattle BioMed researchers as compensated technicians and interns. Providing precollege students with structured access to practicing scientists and authentic research environments within the context of advancing global health has been a robust means of both building a future pool of talented leaders and engaged citizenry and increasing the visibility of health disparities within the community

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

Study on the short-term effects of increased alcohol and cigarette consumption in healthy young men's seminal quality

Many studies have reported a negative impact of lifestyle factors on testicular function, spermatozoa parameters and pituitary-gonadal axis. However, conclusions are difficult to draw, since studies in the general population are rare. In this study we intended to address the early and late short-term impact of acute lifestyle alterations on young men's reproductive function. Thirty-six healthy male students, who attended the Portuguese academic festivities, provided semen samples and answered questionnaires at three time-points. The consumption of alcohol and cigarette increased more than 8 and 2 times, respectively, during the academic festivities and resulted in deleterious effects on semen quality: one week after the festivities, a decrease on semen volume, spermatozoa motility and normal morphology was observed, in parallel with an increase on immotile spermatozoa, head and midpiece defects and spermatozoa oxidative stress. Additionally, three months after the academic festivities, besides the detrimental effect on volume, motility and morphology, a negative impact on spermatozoa concentration was observed, along with a decrease on epididymal, seminal vesicles and prostate function. This study contributed to understanding the pathophysiology underlying semen quality degradation induced by acute lifestyle alterations, suggesting that high alcohol and cigarette consumption are associated with decreased semen quality in healthy young men.publishe

The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1β

BACKGROUND: Cartilage loss is a hallmark of arthritis and follows activation of catabolic processes concomitant with a disruption of anabolic pathways like insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products of South American origin, would limit cartilage degradation by respectively suppressing catabolism and activating local IGF-1 anabolic pathways. One extract, derived from cat's claw (Uncaria guianensis, vincaria(®)), is a well-described inhibitor of NF-κB. The other extract, derived from the vegetable Lepidium meyenii (RNI 249), possessed an uncertain mechanism of action but with defined ethnomedical applications for fertility and vitality. METHODS: Human cartilage samples were procured from surgical specimens with consent, and were evaluated either as explants or as primary chondrocytes prepared after enzymatic digestion of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under basal conditions and in the presence of IL-1β. RESULTS: RNI 249 enhanced basal IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1 production by RNI 249 alone and together with vincaria, was confirmed in both explants and in primary chondrocytes (P <0.05). As expected, IL-1β exposure completely silenced IGF-1 production by chondrocytes. However, in the presence of IL-1β both RNI 249 and vincaria protected IGF-1 production in an additive manner (P <0.01) with the combination restoring chondrocyte IGF-1 production to normal levels. Cartilage NO production was dramatically enhanced by IL-1β. Both vincaria and RNI 249 partially attenuated NO production in an additive manner (p < 0.05). IL-1β – induced degradation of cartilage matrix was quantified as glycosaminoglycan release. Individually RNI 249 or vincaria, prevented this catabolic action of IL-1β. CONCLUSION: The identification of agents that activate the autocrine production of IGF-1 in cartilage, even in the face of suppressive pro-inflammatory, catabolic cytokines like IL-1β, represents a novel therapeutic approach to cartilage biology. Chondroprotection associated with prevention of the catabolic events and the potential for sustained anabolic activity with this natural product suggests that it holds significant promise in the treatment of debilitating joint diseases

Intimate partner violence against women in rural Vietnam - different socio-demographic factors are associated with different forms of violence: Need for new intervention guidelines?

Background: This population-based study investigated the different forms, magnitude and risk factors of men's violence against women in intimate relationships in a rural part of northern Vietnam and whether a difference in risk factors were at hand for the different forms of violence. Vietnam has undergone a rapid transition in the last 20 years, moving towards a more equal situation for men and women however, Confucian doctrine is still strong and little is known about men's violence against women within the Vietnamese family. Methods: This is a cross-sectional population-based study that used a questionnaire developed by the World Health Organisation for investigating women's health and violence against women in different settings. Face-to face structured interviewing was performed and 883 married women, aged 17 to 60 participated. Bi- and multivariate analyses was used for risk factor assessment. Results: The lifetime prevalence of physical violence was 30.9 percent and past year prevalence was 8.3 per cent, while the corresponding figures for physical and sexual violence combined was 32.7 and 9.2 percent. The lifetime prevalence was highest for psychological abuse ( 27.9 percent) as a single entity. In most cases the violence was of a severe nature and exercised as repeated acts over time. Woman's low educational level, husband's low education, low household income and the husband having more than one wife/partner were risk factors for lifetime and past year physical/sexual violence. The pattern of factors associated with psychological abuse alone was however different. Husband's low professional status and women's intermediate level of education appeared as risk factors. Conclusion: Men's violence against women in intimate relationships is commonly occurring in rural Vietnam. There is an obvious need of preventive and treatment activities. Our findings point at that pure psychological abuse is different from physical/sexual violence in terms of differing characteristics of the perpetrators and it might be that also different strategies are needed to reduce and prevent this violence

Effects of chemokines on proliferation and apoptosis of human mesangial cells

BACKGROUND: Proliferation and apoptosis of mesangial cells (MC) are important mechanisms during nephrogenesis, for the maintenance of glomerular homeostasis as well as in renal disease and glomerular regeneration. Expression of chemokines and chemokine receptors by intrinsic renal cells, e.g. SLC/CCL21 on podocytes and CCR7 on MC is suggested to play a pivotal role during these processes. Therefore the effect of selected chemokines on MC proliferation and apoptosis was studied. METHODS: Proliferation assays, cell death assays including cell cycle analysis, hoechst stain and measurement of caspase-3 activity were performed. RESULTS: A dose-dependent, mesangioproliferative effect of the chemokine SLC/CCL21, which is constitutively expressed on human podocytes was seen via activation of the chemokine receptor CCR7, which is constitutively expressed on MC. In addition, in cultured MC SLC/CCL21 had a protective effect on cell survival in Fas-mediated apoptosis. The CXCR3 ligands IP-10/CXCL10 and Mig/CXCL9 revealed a proproliferative effect but did not influence apoptosis of MC. Both the CCR1 ligand RANTES/CCL5 and the amino-terminally modified RANTES analogue Met-RANTES which blocks CCR1 signalling had no effect on proliferation and apoptosis. CONCLUSIONS: The different effects of chemokines and their respective receptors on proliferation and apoptosis of MC suggest highly regulated, novel biological functions of chemokine/chemokine receptor pairs in processes involved in renal inflammation, regeneration and glomerular homeostasis

Inversion of the balance between hydrophobic and hydrogen bonding interactions in protein folding and aggregation.

Identifying the forces that drive proteins to misfold and aggregate, rather than to fold into their functional states, is fundamental to our understanding of living systems and to our ability to combat protein deposition disorders such as Alzheimer's disease and the spongiform encephalopathies. We report here the finding that the balance between hydrophobic and hydrogen bonding interactions is different for proteins in the processes of folding to their native states and misfolding to the alternative amyloid structures. We find that the minima of the protein free energy landscape for folding and misfolding tend to be respectively dominated by hydrophobic and by hydrogen bonding interactions. These results characterise the nature of the interactions that determine the competition between folding and misfolding of proteins by revealing that the stability of native proteins is primarily determined by hydrophobic interactions between side-chains, while the stability of amyloid fibrils depends more on backbone intermolecular hydrogen bonding interactions