Application of Modified Shell Vial Culture Procedure for Arbovirus Detection

The isolation of arboviruses from patient's low titer sera can be difficult. Here we compared the detection efficiency of Dengue (DEN), Yellow Fever (YF), Saint Louis Encephalitis (SLE), West Nile (WN), Ilheus (ILH), Group C (GC), Oropouche (ORO), Mayaro (MAY) and Venezuela Encephalitis Equine (VEE) viruses using a Modified Shell Vial Culture (MSVC) protocol to a Standard Cell Culture (SCC) protocol. First the MSVC and SCC protocols were compared using five dilutions for each of the following stock viruses: DEN-1, DEN-2, DEN-3, DEN-4, YF, SLE, WN, ILH, GC, ORO, MAY and VEE. Next, patients' original sera from which viruses (DEN-1, DEN-2, DEN-3, YF, GC, ORO, MAY and VEE) had been previously isolated were compare by the two methods using five sera dilutions. In addition, seven sera that were positive for DEN-3 by RT-PCR and negative by SCC were processed by MSVC. The MSVC protocol was consistently 1-2 logs higher virus dilution more sensitive for virus detection than the SCC protocol for all stock Flaviviruses tested (DEN-1, DEN-2, DEN-3, DEN-4, YF, SLE, WN and ILH). MSVC was equal to or one log more sensitive for virus detection than SCC for the stock Bunyaviruses (GC and ORO). For the stock Alphavirus MAY, MSVC was equally or one log more sensitive for virus detection than SCC, while for VEE SCC was equally or one log more sensitive for virus detection than MSVC. MSVC was consistently one to two sera dilutions more sensitive than SCC for the detection of Flaviviruses from patients' sera. Both methods were approximately equally sensitive for the detection of Bunyaviruses from patients' sera and equal or one dilution less sensitive for the detection of Alphaviruses from patients' sera. Additionally, MSVC detected DEN virus in five of seven DEN-3 RT-PCR positive, SCC negative patients' sera

A Unifying Theory of Biological Function

A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism’s fitness, and modulates the organism’s variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories

Non-invasive management of peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is common and symptoms can be debilitating and lethal. Risk management, exercise, radiological and surgical intervention are all valuable therapies, but morbidity and mortality rates from this disease are increasing. Circulatory enhancement can be achieved using simple medical electronic devices, with claims of minimal adverse side effects. The evidence for these is variable, prompting a review of the available literature. METHODS: Embase and Medline were interrogated for full text articles in humans and written in English. Any external medical devices used in the management of peripheral arterial disease were included if they had objective outcome data. RESULTS: Thirty-one papers met inclusion criteria, but protocols were heterogenous. The medical devices reported were intermittent pneumatic compression (IPC), electronic nerve (NMES) or muscle stimulators (EMS), and galvanic electrical dressings. In patients with intermittent claudication, IPC devices increase popliteal artery velocity (49-70 %) and flow (49-84 %). Gastrocnemius EMS increased superficial femoral artery flow by 140 %. Over 4.5-6 months IPC increased intermittent claudication distance (ICD) (97-150 %) and absolute walking distance (AWD) (84-112 %), with an associated increase in quality of life. NMES of the calf increased ICD and AWD by 82 % and 61-150 % at 4 weeks, and 26 % and 34 % at 8 weeks. In patients with critical limb ischaemia IPC reduced rest pain in 40-100 % and was associated with ulcer healing rates of 26 %. IPC had an early limb salvage rate of 58-83 % at 1-3 months, and 58-94 % at 1.5-3.5 years. No studies have reported the use of EMS or NMES in the management of CLI. CONCLUSION: There is evidence to support the use of IPC in the management of claudication and CLI. There is a building body of literature to support the use of electrical stimulators in PAD, but this is low level to date. Devices may be of special benefit to those with limited exercise capacity, and in non-reconstructable critical limb ischaemia. Galvanic stimulation is not recommended

Medical Students Educate Teens About Skin Cancer: What Have We Learned?

Skin cancer is a serious societal problem, and public awareness outreach, including to youth, is crucial. Medical students have joined forces to educate adolescents about skin cancer with significant impacts; even one 50-min interactive outreach session led to sustained changes in knowledge and behavior in a cohort of 1,200 adolescents surveyed. Medical students can act as a tremendous asset to health awareness public outreach efforts: enthusiastic volunteerism keeps education cost-effective, results in exponential spread of information, reinforces knowledge and communication skills of future physicians, and can result in tangible, life-saving benefits such as early detection of melanoma

Improving the use of research evidence in guideline development: 10. Integrating values and consumer involvement

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 10(th )of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on integrating values and consumers in guideline development. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We reviewed the titles of all citations and retrieved abstracts and full text articles if the citations appeared relevant to the topic. We checked the reference lists of articles relevant to the questions and used snowballing as a technique to obtain additional information. We did not conduct a full systematic review ourselves. Our conclusions based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We did not find a systematic review of methods for integrating values in guidelines, but we found several systematic reviews that dealt with related topics. Whose values should WHO use when making recommendations? • Values, the relative importance or worth of a state or consequences of a decision (outcomes relating to benefits, harms, burden and costs), play a role in every recommendation. Ethical considerations, concepts that determine what is right, also play a role. • The values used in making recommendations should reflect those of the people affected. Judgements should be explicit and should be informed by input from those affected (including citizens, patients, clinicians and policy makers). • When differences in values may lead to different decisions or there is uncertainty about values, this should also be explicit. If differences in values are likely to affect a decision, such that people in different setting would likely make different choices about interventions or actions based on differences in their values, global recommendations should be explicit in terms of which values were applied and allow for adaptation after incorporating local values. How should WHO ensure that appropriate values are integrated in recommendations? • All WHO guideline groups should uniformly apply explicit, transparent and clearly described methods for integrating values. • WHO should consider involving relevant stakeholders if this is feasible and efficient. • WHO should develop a checklist for guidelines panels to help them to ensure that ethical considerations relevant to recommendations are addressed explicitly and transparently. How should users and consumers be involved in generating recommendations? • Including consumers in groups that are making global recommendations presents major challenges with respect to the impossibility of including a representative spectrum of consumers from a variety of cultures and settings. Nonetheless, consideration should be given to including consumers in groups who are able to challenge assumptions that are made about the values used for making recommendations, rather than represent the values of consumers around the world. • WHO should establish a network to facilitate involvement of users. • Draft recommendations should be reviewed by consumers, who should be asked explicitly to consider the values that were used. How should values be presented in recommendations? • Recommendations should include a description of how decisions were made about the relative importance of the consequences (benefits, harms and costs) of a decision. • Values that influence recommendations should be reported along with the research evidence underlying recommendations. • When differences in values would lead to different decisions or there is important uncertainty about values that are critical to a decision, this should be flagged and reflected in the strength of the recommendation. • Adaptable guideline templates that allow for integration of different values should be developed and used when differences in values are likely to be critical to a decision

Peer substance use overestimation among French university students: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Normative misperceptions have been widely documented for alcohol use among U.S. college students. There is less research on other substances or European cultural contexts. This study explores which factors are associated with alcohol, tobacco and cannabis use misperceptions among French college students, focusing on substance use.</p> <p>Methods</p> <p>12 classes of second-year college students (n = 731) in sociology, medicine, nursing or foreign language estimated the proportion of tobacco, cannabis, alcohol use and heavy episodic drinking among their peers and reported their own use.</p> <p>Results</p> <p>Peer substance use overestimation frequency was 84% for tobacco, 55% for cannabis, 37% for alcohol and 56% for heavy episodic drinking. Cannabis users (p = 0.006), alcohol (p = 0.003) and heavy episodic drinkers (p = 0.002), are more likely to overestimate the prevalence of use of these consumptions. Tobacco users are less likely to overestimate peer prevalence of smoking (p = 0.044). Women are more likely to overestimate tobacco (p < 0.001) and heavy episodic drinking (p = 0.007) prevalence. Students having already completed another substance use questionnaire were more likely to overestimate alcohol use prevalence (p = 0.012). Students exposed to cannabis prevention campaigns were more likely to overestimate cannabis (p = 0.018) and tobacco use (p = 0.022) prevalence. Other identified factors are class-level use prevalences and academic discipline.</p> <p>Conclusions</p> <p>Local interventions that focus on creating realistic perceptions of substance use prevalence could be considered for cannabis and alcohol prevention in French campuses.</p

In vitro hypoxia-conditioned colon cancer cell lines derived from HCT116 and HT29 exhibit altered apoptosis susceptibility and a more angiogenic profile in vivo

Hypoxia is an important selective force in the clonal evolution of tumours. Through HIF-1 and other transcription factors combined with tumour-specific genetic alterations, hypoxia is a dominant factor in the angiogenic phenotype. Cellular adaptation to hypoxia is an important requirement of tumour progression independent of angiogenesis. The adaptive changes, insofar as they alter hypoxia-induced apoptosis, are likely to determine responsiveness to antiangiogenic strategies. To investigate this adaptation of tumour cells to hypoxia, we recreated in vitro the in vivo situation of chronic intermittent exposure to low-oxygen levels. The colon carcinoma cell lines HT29 and HCT116 were subjected to 40 episodes of sublethal hypoxia (4 h) three times a week. The resulting two hypoxia-conditioned cell lines have been maintained in culture for more than 2 years. In both cell lines changes in doubling times occurred: in HT29 an increase, and in HCT116 a decrease. Cell survival in response to hypoxia and to DNA damage differed strikingly in the two cell lines. The HT29 hypoxia-conditioned cells were more resistant than the parental line to a 24 h hypoxic challenge, while those from HCT116 surprisingly were more sensitive. Sensitivity to cisplatin in vitro was also significantly different for the hypoxia-conditioned compared with the parental lines, suggesting a change in pathways leading to apoptosis following DNA damage signaling. The growth of both conditioned cell lines in vivo as xenografts in immunodeficient (SCID) mice was more rapid than their parental lines, and was accompanied in each by evidence of enhanced vascular proliferation as a consequence of the hypoxia-conditioning. Thus the changes in apoptotic susceptibility were independent of altered angiogenesis. The derivation of these lines provides a model for events within hypoxic regions of colon cancers, and for the acquisition of resistance and sensitivity characteristics that may have therapeutic implications for the use of antiangiogenesis drugs

Antibody Inhibition of a Viral Type 1 Interferon Decoy Receptor Cures a Viral Disease by Restoring Interferon Signaling in the Liver

Type 1 interferons (T1-IFNs) play a major role in antiviral defense, but when or how they protect during infections that spread through the lympho-hematogenous route is not known. Orthopoxviruses, including those that produce smallpox and mousepox, spread lympho-hematogenously. They also encode a decoy receptor for T1-IFN, the T1-IFN binding protein (T1-IFNbp), which is essential for virulence. We demonstrate that during mousepox, T1-IFNs protect the liver locally rather than systemically, and that the T1-IFNbp attaches to uninfected cells surrounding infected foci in the liver and the spleen to impair their ability to receive T1-IFN signaling, thus facilitating virus spread. Remarkably, this process can be reversed and mousepox cured late in infection by treating with antibodies that block the biological function of the T1-IFNbp. Thus, our findings provide insights on how T1-IFNs function and are evaded during a viral infection in vivo, and unveil a novel mechanism for antibody-mediated antiviral therapy