title: Sexually transmitted infections in travelers: implications for prevention and control.

text: Sexually transmissible diseases (STDs), the most common notifiable infectious conditions, remain major threats to reproductive and public health worldwide. Travelers are particularly vulnerable to STDs, because of voluntary or involuntary sexual behavior while abroad, and are significant vectors who introduce new pathogens and resistant strains to unaffected parts of the world. This article outlines some key issues that travel medicine specialists and other clinicians should revisit when providing services to travelers. We discuss obstacles to promoting sexual health, including the diversity of the target group, unanticipated opportunities for sexual risk, ambivalent cooperation by the travel and tourism industries, poorly developed travel health sectors, illegal migration and sex tourism, and lack of research about the association between travel and STDs. We also outlined some programmatic aspects of public health that should be identified and addressed for the promotion of sexual health among travelers.


title: IL-13 genetic polymorphism identifies children with late wheezing after respiratory syncytial virus infection.

text: BACKGROUND The nature of wheezing after respiratory syncytial virus lower respiratory tract infection (RSV LRTI) is usually transient. However, some children will develop persistent or late wheezing. OBJECTIVE We hypothesized that early and late postbronchiolitis wheezing are determined by distinct clinical, immunologic, and genetic variables. METHODS A cohort of 101 children hospitalized for RSV LRTI was prospectively followed for 6 years. During RSV LRTI, cytokine studies were performed and genetic polymorphisms were determined. Parents performed daily log registration of respiratory symptoms during the first 3 years of follow-up and again at age 6 years during the winter season. RESULTS Distinctive associations for early and late postbronchiolitis wheezing were found. We previously showed that airflow limitation during RSV LRTI as well as convalescent monocyte IL-10 production are associated with early wheezing. These variables were not associated with late wheezing. On the other hand, atopic family history was not associated with early wheezing, but it was associated with late wheezing. Most importantly, the IL-13 Gln allele was associated with late wheezing (odds ratio 3.27, 95% confidence interval 1.32-8.06), but it was not associated with early wheezing. CONCLUSION This study revealed distinct clinical, immunologic, and genetic determinants of early and late wheezing after RSV LRTI, indicating distinct pathophysiological mechanisms. We conclude that late wheezing at age 6 years, but not early postbronchiolitis wheezing, is an asthmatic phenomenon and genetically related to a functional IL-13 polymorphism. CLINICAL IMPLICATIONS After RSV LRTI, wheezing at age 6 years is not related to early postbronchiolitis wheezing and represents a distinct disease entity.


title: Laboratory capability and surveillance testing for Middle East respiratory syndrome coronavirus infection in the WHO European Region, June 2013.

text: Since September 2012, over 90 cases of respiratory disease caused by a novel coronavirus, now named Middle East respiratory syndrome coronavirus (MERSCoV), have been reported in the Middle East and Europe. To ascertain the capabilities and testing experience of national reference laboratories across the World Health Organization (WHO) European Region to detect this virus, the European Centre for Disease Prevention and Control (ECDC) and the WHO Regional Office for Europe conducted a joint survey in November 2012 and a follow-up survey in June 2013. In 2013, 29 of 52 responding WHO European Region countries and 24 of 31 countries of the European Union/European Economic Area (EU/EEA) had laboratory capabilities to detect and confirm MERS-CoV cases, compared with 22 of 46 and 18 of 30 countries, respectively, in 2012. By June 2013, more than 2,300 patients had been tested in 23 countries in the WHO European Region with nine laboratory-confirmed MERS-CoV cases. These data indicate that the Region has developed significant capability to detect this emerging virus in accordance with WHO and ECDC guidance. However, not all countries had developed capabilities, and the needs to do so should be addressed. This includes enhancing collaborations between countries to ensure diagnostic capabilities for surveillance of MERS-CoV infections across the European Region.


title: Molecular diagnosis in lung diseases.

text: The development of different molecular biology techniques in the past decade has led to an explosion of new research in molecular pathology with consequent important applications to diagnosis, prognosis, and therapeutics, as well as a clearer concept of the disease pathogenesis. Many methods used in molecular pathology are now validated and used in several areas of pathological diagnosis, particularly on infectious and neoplastic diseases. The spectrum of infectious diseases, especially lung infective diseases, is now broadening and modifying, thus the pathologist is increasingly involved in the diagnosis of these pathologies. The precise tissue characterization of lung infections has an important impact on specific therapeutic treatment. Increased knowledge of significant alterations in lung cancer has led today to a better understanding of the pathogenic substrate underlying the development, progression and metastasis of neoplastic processes. Molecular tests are now routinely performed in different lung tumors allowing a more precise patient stratification in terms of prognosis and therapy. This review focuses on molecular pathology of the principal infective lung diseases and tumors.


title: Improvement of the specificity of enzyme immunoassays for the detection of rotavirus and adenovirus in fecal specimens.

text: A variable rate of false-positive results may be observed with commercial enzyme immunoassays (EIAs) for the detection of rotavirus and adenovirus antigen in stool specimens, depending on the quality of the reagents and the presence of potentially interfering substances in stool samples. The present study was performed in an attempt to improve the specificity of current commercial rotavirus and adenovirus EIAs without significant loss of sensitivity by optimizing the cut-off value. A collective of 174 stool samples obtained from children suffering from acute gastroenteritis was tested. Electron microscopy (EM) and PAGE were used as reference methods for rotavirus detection. For the evaluation of the adenovirus kits, virus isolation in cell culture and the polymerase chain reaction served as reference standards. The highest sensitivity for rotavirus and adenovirus detection was achieved by the Ridascreen(R) Rotavirus and Ridascreen Adenovirus. However, the Ridascreen(R) Rotavirus and Ridascreen Adenovirus produced the highest number of false-positive results (n = 9) for each rotavirus and adenovirus detection. Cross-reactivities to coronaviruses and reoviruses were observed with the rotavirus antigen EIAs. For Rotazyme II, Ridascreen Rotavirus and Ridascreen Adenovirus, the specificity could be markedly increased without loss of sensitivity by doubling the cut-off value. For the alternative immunoassays, which were overall more specific, it was not possible to significantly decrease the rate of false-positive results without impairment of sensitivity by raising the cut-off value. In conclusion, at least for some rotavirus and adenovirus antigen EIAs, the cut-off value set by the manufacturer may not permit an optimal differentiation between true-positive and -negative samples. By raising the cut-off value from 50 to 100%, the specificity of two rotavirus antigen and one adenovirus antigen EIA can be improved markedly without significant loss of sensitivity.


title: SARS and biothreat preparedness--a survey of ACT general practitioners.

text: In late 2003 and early 2004 the ACT Division of General Practice and ACT Health conducted two concurrent surveys designed to identify knowledge, attitudes and practices of Australian Capital Territory (ACT) general practitioners around severe acute respiratory syndrome (SARS) and biothreat preparedness. One survey asked individual general practitioners (GPs) about how they gathered information about SARS in 2003, how they preferred to receive information, current practices, and how they perceived the threat of SARS and other infectious agents. The second survey asked practice principals how they organised their practice to respond to the SARS threat in 2003, any difficulties they had with implementing this response, use of SARS infection control guidelines and current policies. The response rate for the individual GP survey was 48 per cent (184/381) and the response rate for the practice organisation survey was 54 per cent (74/136). GPS used many sources of information on SARS during the 2003 outbreak. Facsimiles from the ACT Division of General Practice were the primary source (17%) and facsimile was the preferred method of receiving information in future outbreaks. The majority of GP respondents felt adequately informed about SARS during the 2003 outbreak, but many general practices did not follow the national guidelines on telephone screening of patients, warning signs and having infection control kits available. The majority of practices reported that they had policies or procedures in place to isolate potentially infectious patients from others in the waiting room. GPs rated an influenza pandemic as a threat to themselves and their patients much more highly than SARS or bioterrorism. Suggestions and comments on how ACT GPs could be better prepared to respond to future outbreaks included the need for timeliness of information, information delivery mechanisms, communication issues, education, the availability of guidelines and protocols, planning, role delineation, the use of response teams, provision of equipment, and vaccination. Planning for future infectious disease outbreak events in the Australian Capital Territory should incorporate general practitioners so that the plans reflect what is a feasible response in the general practice setting.


title: Development of a Western blot assay for detection of antibodies against coronavirus causing severe acute respiratory syndrome.

text: To identify a major antigenic determinant for use in the development of a rapid serological diagnostic test for severe acute respiratory syndrome (SARS) coronavirus infection and to study the immune response during SARS coronavirus infection in humans, we cloned the full length and six truncated fragments of the nucleocapsid gene, expressed them, and purified them as glutathione S-transferase-tagged recombinant proteins. The reactivities of the recombinant proteins to a panel of antibodies containing 33 SARS coronavirus-positive sera and 66 negative sera and to antibodies against other animal coronaviruses were screened. A truncated 195-amino-acid fragment from the C terminus of the nucleocapsid protein (N195) was identified that had a strong ability to detect antibodies against SARS coronavirus. No cross-reaction was found between the N195 protein and antibodies against chicken, pig, and canine coronaviruses. The N195 protein was used to develop a Western blot assay to detect antibodies against SARS coronavirus in 274 clinically blinded samples. The specificity and sensitivity of this test were 98.3 and 90.9%, respectively. The correlation between our Western blotting assay and an immunofluorescence assay (IFA) was also analyzed. The results of our Western blot assay and IFA for the detection of SARS coronavirus-positive sera were the same. Thus, the N195 protein was identified as a suitable protein to be used as an antigen in Western blot and other possible assays for the detection of SARS coronavirus infection.


Reportable diseases.


title: Inefficient signalase cleavage promotes efficient nucleocapsid incorporation into budding flavivirus membranes.

text: The mechanism for efficient nucleocapsid (NC) uptake into flavivirus particles which form by budding through the membranes of the endoplasmic reticulum (ER) was investigated by using Murray Valley encephalitis virus as a model. Budding of flavivirus membranes is driven by the viral transmembrane proteins prM and E independently of NC interaction. We show that control of signalase cleavage of the multimembrane-spanning flavivirus polyprotein by the catalytic function of the viral protease is critical for efficient virus morphogenesis. In wild-type virus, signalase cleavage of prM remains inefficient until cleavage of capsid at the cytosolic side of the signal sequence separating the two proteins has occurred. This obligatory sequence of cleavages was uncoupled in a mutant virus with the consequence of greatly reduced incorporation of NC into budding membranes and augmented release of NC-free virus-like particles. Efficient signalase cleavage of prM in the mutant virus resulted in partial inhibition of cleavage of capsid by the viral NS2B-3 protease. Our results support a model for flavivirus morphogenesis involving temporal and spatial coordination of NC assembly and envelopment by regulated cleavages of an ER membrane-spanning capsid-prM intermediate.


title: Precautions When Providing Dental Care During Coronavirus Disease 2019 (COVID-19) Pandemic.

text: Transmission of coronavirus disease 2019 (COVID-19)-caused by novel severe acute respiratory syndrome coronavirus 2-through aerosolised saliva and respiratory droplets is possible when aerosol-generating dental procedures are performed. Consequently, dental practitioners are at increased risk of being infected when treating COVID-19 patients. A comprehensive review of the current literature on precautions when providing dental care during the COVID-19 pandemic is discussed and recommendations for dental practitioners are made. Dental practitioners should actively keep themselves abreast of the guidelines published by both national and international authorities and adhere strictly to them.


title: Structural maturation of the transmissible gastroenteritis coronavirus.

text: During the life cycle of the transmissible gastroenteritis coronavirus (TGEV), two types of virus-related particles are detected in infected swine testis cells: large annular viruses and small dense viruses. We have studied the relationships between these two types of particles. Immunoelectron microscopy showed that they are closely related, since both large and small particles reacted equally with polyclonal and monoclonal antibodies specific for TGEV proteins. Monensin, a drug that selectively affects the Golgi complex, caused an accumulation of large annular viral particles in perinuclear elements of the endoplasmic reticulum-Golgi intermediate compartment. A partial reversion of the monensin blockade was obtained in both the absence and presence of cycloheximide, a drug that prevented the formation of new viral particles. After removal of monensin, the Golgi complex recovered its perinuclear location, and a decrease in the number of perinuclear large viral particles was observed. The release of small dense viral particles into secretory vesicles and the extracellular medium was also observed, as was a partial recovery of infectivity in culture supernatants. Small viral particles started to be seen between the third and the fourth Golgi cisternae of normally infected cells. All of these data strongly indicate that the large annular particles are the immature precursors of the small dense viruses, which are the infectious TGEV virions. The immature viral particles need to reach a particular location at the trans side of the Golgi stack to complete their morphological maturation.


title: Urgent strategic research into influenza to inform health policy and protect the public.

text: The Australian management plan for pandemic influenza (2005) highlighted a number of areas where more information may yield better plans for protecting Australia. In 2005, the National Health and Medical Research Council (NHMRC) developed a special "urgent research" funding program to meet those information needs as quickly as possible. The funding program resulted in grants totalling $6.5 million being awarded for 33 research projects, in five broad areas: Detection and identification of the virus; Vaccine development and evaluation; Antiviral medication use and effectiveness; Public health interventions; and Understanding behavioural responses to achieve effective communication and staged implementation of public health strategies. Outcomes of the program will be evaluated formally in 2007.


title: SARS and health worker safety: lessons for influenza pandemic planning and response.

text: The outbreak of severe acute respiratory syndrome (SARS) in 2003 provided valuable lessons for protecting health workers during an influenza pandemic or other public health crisis. In its final report, the SARS Commission concluded that a key lesson in worker safety was the precautionary principle. It stated that reasonable actions to reduce risk should not await scientific certainty. As recommended by the SARS Commission, this principle has now been enshrined in the Health Protection and Promotion Act (2007), Ontario's public health legislation and in Ontario's influenza pandemic plan. Another vital lesson for worker safety involves the occupational hygiene concept of a hierarchy of controls. It takes a holistic approach to worker safety, addressing each hazard through control at the source of the hazard, along the path between the worker and the hazard and, lastly, at the worker. Absent such an approach, the SARS Commission said worker safety may focus solely on a particular piece of personal protective equipment, such as an N95 respirator (important as it may be), or on specific policies and procedures, such as fit testing the N95 respirator to the wearer (significant as it may be). In worker safety, said the commission, the integrated whole is greater than the uncoordinated parts. The third and final worker safety lesson of SARS is the importance of having a robust safety culture in the workplace in which workers play an integral role in promoting a safe workplace.


title: [The complex etiology of epidemic diseases in calves on large-capacity farms and their clinical and epizootic characteristics].

text: It is not easy to exactly diagnose the etiology of the mass infections of new-born calves on large farms where considerable losses are suffered. On the basis of the complex epizootological, clinical and laboratory examination in four large calf-rearing facilities, rotaviruses, coronaviruses, the infectious bovine rhinotracheitis (IBR) virus and the bovine viral diarrhoea (BVD) virus, and in some cases also the enteropathogenic E. coli, were found to be etiologically involved in the mass rise of diarrhoea, complicated by respiratory symptoms already during the first days after birth. The clinical picture of the disease, therapeutically difficult and reminding of "pneumoenteritis", has often been observed in stocks where, in addition to rotaviruses and coronaviruses in the faeces, the IBR or BVD viruses (sometimes both at the same time) were detected and identified in the respiratory and enteral tract. The serological examination of a higher number of animals in the stocks of calves under study confirmed the considerable rate of spreading of all the four viruses in the cattle population and, at the same time, demonstrated the very unfavourable immunological profile of the herds. The high percentage of animals low in antibody titres and the serologically negative animals constitute the infection-sensitive part of population in the affected herds. With the high culling rate and with the open herd turnover it is impossible to reach the required immunity through natural disinfection. Loss-free rearing of healthy calves will be achieved on the basis of a well-oriented vaccination programme with a good combination of inoculants.


title: Role of terminal and anastomotic circulation in the patency of arteries jailed by flow-diverting stents: animal flow model evaluation and preliminary results.

text: OBJECTIVE The authors describe herein the creation of an animal model capable of producing quantifiable data regarding blood flow rate and velocity modifications in terminal and anastomotic types of cerebrofacial circulation. They also present the preliminary results of a translational study aimed at investigating the role of terminal and anastomotic types of circulation in arterial branches jailed by flow-diverting stents as factors contributing to arterial patency or occlusion. METHODS Two Large White swine were used to validate a terminal-type arterial model at the level of the right ascending pharyngeal artery (APhA), created exclusively by endovascular means. Subsequently 4 Large White swine, allocated to 2 groups corresponding to the presence (Group B) or absence (Group A) of terminal-type flow modification, underwent placement of flow-diverting stents. Blood flow rates and velocities were quantified using a dedicated time-resolved 3D phase-contrast MRA sequence before and after stenting. Three months after stent placement, the stented arteries were evaluated with digital subtraction angiography (DSA) and scanning electron microscopy (SEM). Patent (circulating) ostia quantification was performed on the SEM images. RESULTS Terminal-type flow modification was feasible; an increase of 75.8% in mean blood velocities was observed in the right APhAs. The mean blood flow rate for Group A was 0.31 ± 0.19 ml/sec (95% CI -1.39 to 2.01) before stenting and 0.21 ± 0.07 ml/sec (95% CI -0.45 to 0.87) after stenting. The mean blood flow rate for Group B was 0.87 ± 0.32 ml/sec (95% CI -1.98 to 3.73) before stenting and 0.76 ± 0.13 ml/sec (95% CI -0.41 to 1.93) after stenting. Mean flow rates after stenting showed a statistically significant difference between Groups A and B (Welch test). Mean and maximal blood velocities were reduced in Group A cases and did not decrease in Group B cases. Control DSA and SEM findings showed near occlusion of the jailed APhAs in both cases of anastomotic circulation (mean patent ostium surface 32,776 μm2) and patency in both cases of terminal-type circulation (mean patent ostium surface 422,334 μm2). CONCLUSIONS Terminal-type arterial modification in swine APhAs is feasible. Sufficient data were acquired to perform an a priori analysis for further research. Flow diversion at the level of the APhA ostium resulted in significant stenosis in cases of anastomotic circulation, while sufficient patency was observed in terminal-type circulation.


title: Identification of new morphological and life-cycle stages of Cochlosoma anatis and experimental transmission using pseudocyst.

text: Cochlosoma anatis is a flagellated intestinal parasite that infects a variety of avian species. C. anatis infections have been associated with decreased weight gain and increased morbidity and mortality. Conditions favoring the growth of this organism in birds are current pathogenic intestinal infections and/or young age. There is little data describing the life cycle of this parasite. In this study, electron microscopy images are presented that document longitudinal binary fission of the trophozoite stage and outline the events of pseudocyst formation, which includes a rounding stage. Evidence provided here indicates that the pseudocyst stage may be a mechanism for transmission of this organism. The observations reported here provide additional evidence of homology between Cochlosoma and members of the trichomonad order.


title: Longitudinal analysis of Severe Acute Respiratory Syndrome (SARS) coronavirus-specific antibody in SARS patients.

text: The serum antibodies to severe acute respiratory syndrome (SARS) coronavirus of 18 SARS patients were checked at 1 month and every 3 months after disease onset. All of them except one, who missed blood sampling at 1 month, tested positive for the immunoglobulin G (IgG) antibody at 1 month. Fifteen out of 17 tested positive for the IgM antibody at 1 month. The serum IgM antibody of most patients became undetectable within 6 months after the onset of SARS. The IgG antibody of all 17 patients, whose serum was checked 1 year after disease onset, remained positive.


title: Caspases: the enzymes of death.

text: The caspases are a unique family of cysteine proteases, which cleave proteins next to an aspartate residue. Among all known mammalian proteases, only the serine protease granzyme B has similar substrate specificity. In addition to a central role of caspases in the initiation and execution phases of apoptosis, these enzymes have some other non-apoptotic functions in living cells. During apoptosis, upon activation, caspases cleave specific substrates and thereby mediate many of the typical biochemical and morphological changes in apoptotic cells, such as cell shrinkage, chromatin condensation, DNA fragmentation and plasma-membrane blebbing. Thus, detection of activated caspases can be used as a biochemical marker for apoptosis induced by diverse stimuli in many types of cells.


title: Consortia's critical role in developing medical countermeasures for re-emerging viral infections: a USA perspective.

text: Viral infections, such as Ebola, severe acute respiratory syndrome/Middle East respiratory syndrome and West Nile virus have emerged as a serious health threat with no effective therapies. These infections have little commercial potential and are not a high priority for the pharmaceutical industry. However, the academic community has been active in this area for many years. The challenge is how to take this academic virology knowledge into a drug discovery and development domain. One approach is the use of consortia and public-private partnerships - this article highlights ongoing efforts in the USA. Public funds, such as those from government sources, can support research efforts that do not to appear to have commercial value. The key to success is finding a way to combine the different cultural and operational values and reward systems into a productive collaboration to identify new antivirals.


title: Aspirin allergy desensitization in cerebrovascular disease. A report of two cases, literature review and management guide for the neurointerventionalist.

text: Aspirin (ASA) is the mainstay of treatment in cerebrovascular and systemic vascular disease. ASA hypersensitivity can pose a challenge to achieving optimum medical management prior to and after neurointerventional treatment. Desensitization to ASA is well described in the allergy and cardiovascular literature, but there are no similar discussions specific to neurointervention. The purpose of our study was to describe our experience with ASA hypersensitivity management and review the relevant literature. Two cases of patients with symptomatic cerebrovascular disease requiring neurointervention who were successfully desensitized to their ASA hypersensitivity prior to treatment are described. The subsequent literature is reviewed. Several ASA desensitization protocols exist and have been proven to successfully treat ASA hypersensitivity and allow for ASA therapy to be safely initiated. We describe several previously published protocols. ASA desensitization is a safe and simple way to manage ASA hypersensitivity. We provide comprehensive management guidelines for the neurointerventionalist engaging in ASA desensitization.


title: Antiviral activity of human Vδ2 T-cells against WNV includes both cytolytic and non-cytolytic mechanisms.

text: West Nile virus (WNV) causes a severe central nervous system infection in humans, primarily in the elderly and immunocompromised subjects. Human γδ T-cells play a critical role in the immune response against viruses, and studies of WNV meningoencephalitis in laboratory mice described a role of γδ T-cells in the protective immune response. Aim of this study was to analyze the cytolytic and non-cytolytic antiviral activity of human Vδ2 T-cells against WNV replication. The anti-WNV activity of soluble factor released by zoledronic acid (ZA)-activated Vδ2 T-cell lines and the cytotoxic capability of Vδ2 T-cell lines against WNV-infected cells were tested in vitro. The activation of Vδ2 T-cell lines was able to inhibit WNV replication through the release of soluble factors. IFN-γ is massively released by activated Vδ2 T-cell lines and is involved in the anti-WNV activity. Moreover, the Vδ2 T-cell lines can efficiently kill WNV-infected cells possibly through perforin-mediated mechanism. Altogether, our results provide insight into the effector functions of human Vδ2 T-cells against WNV. The possibility to target these cells by ZA, a commercially available drug used in humans, could potentially offer a new immunotherapeutic strategy for WNV infection.


title: Laparoscopic uterine ventrosuspension procedure by using anterior mesh incorporated with bilateral round ligamentopexy: Kahyaoglu technique.

text: A number of vaginal and abdominal surgical techniques have been described for the treatment of apical uterine prolapse. A 38-year-old parous woman has been operated laparoscopically due to grade 3 apical uterine prolapse. A new surgical technique for the treatment of apical uterine prolapse performed by incorporation of the lateral arms of anteriorly anchored uterine polypropylene mesh to bilateral round ligaments has been developed. Due to the young age of the patient and lack of any other uterine pathology, a laparoscopic uterine ventrosuspension procedure combined with bilateral round ligamentopexy has been performed as a low risk uterine prolapse surgery.


title: A serologic survey of wild felids from central west Saudi Arabia.

text: Forty-five wildcats (Felis silvestris), 17 sand cats (Felis margarita), and 17 feral domestic cats were captured in central west Saudi Arabia, between May 1998 and April 2000, with the aim to assess their exposure to feline immunodeficiency virus/puma lentivirus (FIV/PLV), feline leukaemia virus (FeLV), feline herpesvirus (FHV-1), feline calicivirus (FCV), feline coronavirus (FCoV), and feline panleukopenia virus (FPLV). Serologic prevalence in wildcats, sand cats, and feral domestic cats were respectively: 6%, 0%, 8% for FIV/PLV; 3%, 8%, 0% for FeLV; 5%, 0%, 15% for FHV-1; 25%, 0%, 39% for FCV; 10%, 0%, 0% for FCoV; and 5%, 0%, 8% for FPLV. We recorded the first case of FeLV antigenemia in a wild sand cat. Positive results to FIV/PLV in wildcats and feral cats confirmed the occurrence of a feline lentivirus in the sampled population.


title: Infectious and parasitic diseases and contaminant-related problems of North American river otters (Lontra canadensis): a review.

text: The aquatic North American river otter (Lontra canadensis), a charismatic nonendangered mustelid, presently occupies a greatly reduced range. The species is common in zoos and has economic value as a furbearer. At least 17 states and one Canadian province have undertaken recent reintroduction programs. Nevertheless, little has been published on nonparasitic diseases of river otters, and little is known of the clinical significance of most of their parasitic infections. Records of environmental contaminant-related diseases and traumatic injuries in free-ranging North American river otters are also rare. This paper reviews present knowledge of North American river otter diseases, especially those with the greatest potential for impacting reintroduction programs.


Severe acute respiratory syndrome: vaccine on the way.


title: Anti-herpes virus type 1 activity of oleanane-type triterpenoids.

text: The anti-herpes simplex virus type 1 (HSV-1) activity of 15 oleanan-type triterpenoides including glycyrrhizin and its sapogenol was examined and their structure-activity relationships were discussed. Although glycyrrhizin which exhibited in vivo efficacy against HSV-1 replication showed moderate in vitro anti-HSV-1 activity, its sapogenol, glycyrrhetic acid, showed 10 times greater action than glycyrrhizin. Therefore, the in vivo anti-HSV-1 activity of glycyrrhizin administered orally could be reasonably attributed to glycyrrhetic acid generated by hydrolysis by intestinal bacteria. Since the activity of soyasapogenol A was less than 1/20 of that of soyasapogenol B, the hydroxylation at C-21 seemed to reduce anti-HSV-1 activity. Since kudzusapogenol A, abrisapogenols B and C lacked the activity, the C-29 hydroxy group would eliminate anti-HSV-1 activity. On the other hand, since the methylesters of kudzusapogenol B and glycyrrhetic acid exhibited greater action, a methoxy carboxy group at C-20 might enhance activity.


An outbreak of the severe acute respiratory syndrome: predictors of health behaviors and effect of community prevention measures in Hong Kong, China.


title: [Preparation of monoclonal antibodies against SARS coronavirus and staining usage in lung autopsy specimens].

text: OBJECTIVE To prepare monoclonal antibodies against SARS coronavirus (SARS-CoV) on the purpose to explore the diagnosis methods of SARS. METHODS Female BALB/C mice were immunized with disinfected SARS-CoV (PUMC01) and the spleen cells were fused with myeloma NS-1 cells. The hybridoma cell strains were screened by enzyme-linked immunosorbent assay (ELISA), indirect fluorescent-antibody assay (IFA) and Western blotting. Autopsy lung tissue sections from SARS patients were stained with ascites of monoclonal antibody (M2 strain) by immunohistochemical technique. RESULTS Six strains of hybridomas that produced the monoclonal antibodies against SARS-CoV were obtained. The hybridomas were tested to have specific reactions with SARS-CoV and no cross-reactivates with other common respiratory disease causing pathogens. Of the 6 strains, 1 was identified as the immunoglobulin G3 (IgG3) isotype, 5 were IgG1. Western blotting showed that one strain (M2) reacted with 68000- Dalton (68KD) protein and four strains with 27000-dalton (27KD) protein. Band of M4 stain was not got by western blotting. Brown particles were seen in macrophages and pneumocytes in autopsy lung tissues from SARS patients. CONCLUSION Monoclonal antibodies we made were specific to the SARS-CoV, and they had been used to detect SARS-CoV in autopsy lung tissues specimens with positive results.


title: Human rhinoviruses, allergy, and asthma: a clinical approach.

text: The prevalence of allergic diseases is increasing in Lithuania as in the world. The prevalence of allergic sensitization is often higher than 50% of the population. The "hygiene hypothesis" proposed that reduced immune-stimulation by infections may have resulted in the more widespread clinical expression of atopic disease. However, it alone does not provide an adequate explanation for the observed increase of allergic diseases. Human rhinovirus infections are the major infections with a worldwide distribution. Viral infections of the respiratory tract are the most common triggers of acute asthma exacerbations. These exacerbations are poorly responsive to current asthma therapies and new approaches to therapy are needed. The aim of this review is to present the current knowledge and clinical implications of human rhinovirus infection in allergy and asthma development and needs for further research. Recent evidence has shown that the immune responses to human rhinoviruses differ between asthmatic and nonasthmatic subjects. Novel insights into the mechanisms of virus-induced asthma exacerbations support the possibility that viral infections may be involved in the epithelial cells damage, inflammation, and airway hyperresponsiveness as well as in profibrotic response and induction of airway remodeling. The data of original investigations support the concept that the immune stimulation by rhinovirus infections contributes to the development of asthma, when an atopic host is infected with human rhinoviruses. Early rhinoviral wheezing is the predictor of subsequent asthma development in high-risk children. Synergistic effect of allergic sensitization, allergen exposure, and viral infection was suggested in the increased risk of hospitalization for asthma in both children and adults. Timing of allergen exposure may be important in a synergistic outcome. The increased susceptibility to rhinovirus infections was identified in atopic asthma. This review also presents the current options on the treatment and prevention of virus-induced asthma. Further studies are needed in order to differentiate between the response to viruses of healthy and atopic or nonatopic asthmatic children and adults. New research data may lead to novel strategies in treatment and prevention of asthma exacerbations as well as prevention of asthma induction.


title: Infant deaths associated with cough and cold medications--two states, 2005.

text: Cough and cold medications that contain nasal decongestants, antihistamines, cough suppressants, and expectorants commonly are used alone or in combination in attempts to temporarily relieve symptoms of upper respiratory tract infection in children aged <2 years. However, during 2004-2005, an estimated 1,519 children aged <2 years were treated in U.S. emergency departments for adverse events, including overdoses, associated with cough and cold medications. In response to reports of infant deaths after such events, CDC and the National Association of Medical Examiners (NAME) investigated deaths in U.S. infants aged <12 months associated with cough and cold medications. This report describes the results of that investigation, which identified deaths of three infants aged <6 months in 2005, for which cough and cold medications were determined by medical examiners or coroners to be the underlying cause. The dosages at which cough and cold medications can cause illness or death in children aged <2 years are not known. Food and Drug Administration (FDA)-approved dosing recommendations for clinicians prescribing cough and cold medications do not exist for this age group. Because of the risks for toxicity, absence of dosing recommendations, and limited published evidence of effectiveness of these medications in children aged <2 years, parents and other caregivers should not administer cough and cold medications to children in this age group without first consulting health-care provider and should follow the provider's instructions precisely. Clinicians should use caution when prescribing cough and cold medications to children aged <2 years. Moreover, clinicians should always ask caregivers about their use of over-the-counter combination medications to avoid overdose in children from multiple medications that contain the same ingredient.


title: Microbial subversion of heparan sulfate proteoglycans.

text: The interactions between the host and microbial pathogen largely dictate the onset, progression, and outcome of infectious diseases. Pathogens subvert host components to promote their pathogenesis and, among these, cell surface heparan sulfate proteoglycans are exploited by many pathogens for their initial attachment and subsequent cellular entry. The ability to interact with heparan sulfate proteoglycans is widespread among viruses, bacteria, and parasites. Certain pathogens also use heparan sulfate proteoglycans to evade host defense mechanisms. These findings suggest that heparan sulfate proteoglycans are critical in microbial pathogenesis, and that heparan sulfate proteoglycan-pathogen interactions are potential targets for novel prophylactic and therapeutic approaches.


title: Cerebral oxygen saturation is improved by xenon anaesthesia during carotid clamping.

text: INTRODUCTION The cerebral protective effect of xenon anesthesia could be of interest during carotid surgery. The purpose of this study was to compare the effects of xenon on cerebral oxygen saturation with those of propofol during carotid clamping. METHODS After approval of Research Ethics Board and patient informed consent, 74 patients scheduled for carotid endarterectomy were enrolled. Patients were not randomized but were well matched by preoperative characteristics. Patients in the Xenon group were the ones scheduled for surgery in the operative theater equipped with the xenon anesthesia system. Anesthesia was started with a target control infusion of propofol and remifentanil. Patients were then divided into the control group (37 patients) with anesthesia maintained with target control infusion propofol and remifentanil and the Xenon group with anesthesia maintained with xenon (target inspired concentration of 60%) and target control infusion remifentanil. Remifentanil and xenon or propofol were stopped at the end of skin closure. RESULTS A cerebral oxygen saturation decrease below 55% was less frequently observed in the Xenon group during carotid cross-clamping (7/37 patients vs 15/37; p=0.01). Compared with values observed before clamping, the decrease in cerebral oxygen saturation during clamping was significantly less important in the Xenon group (12±11% vs 17±14%, p=0.04). Blood pressure and heart rate were not different between groups during carotid clamping. CONCLUSIONS This pilot study suggests that xenon anesthesia may be associated to higher cerebral oxygen saturation values when compared to propofol anesthesia during cross-clamping for carotid endarterectomy.


title: Endoscopic treatment of obesity.

text: PURPOSE OF REVIEW Obesity and its comorbid illnesses affect millions worldwide and are one of the major causes of preventable death in the world. Bariatric surgery is currently offered to individuals with a BMI greater than 40 kg/m or greater than 35 kg/m with obesity-related comorbidities such as hypertension or diabetes. Endoscopic bariatric therapies, with their reduced invasiveness and potential reversibility, may complement surgical approaches for achieving weight loss. RECENT FINDINGS At the time of this writing, two endoscopically placed intragastric balloons and an endoscopically placed aspiration tube have been approved by the Food and Drug Administration for weight loss purposes. Some devices employ a suturing platform to create plications or to appose two surfaces. Other endoscopic strategies under investigation to treat obesity-related comorbidities such as diabetes include duodenal mucosal resurfacing and creation of a partial jejunoileal diversion using self-assembling magnets. SUMMARY Current endoscopic methods for the treatment of obesity utilize various mechanisms, including occupying gastric volume, reducing gastric capacity, altering caloric absorption, or aspirating gastric contents. The long-term outcomes and cost-effectiveness of these strategies remain to be fully elucidated. The landscape of endoscopic bariatric therapies continues to evolve.


title: Protective effect of vaccination in chicks with local infectious bronchitis viruses against field virus challenge.

text: Avian infectious bronchitis virus (IBV) causes tremendous economic losses to the poultry industry worldwide. Different serotypes of this virus show little cross-protection. The present study investigated the relationship between differences in the genotype based on the N-terminus of the spike protein and the protection provided by vaccination with IBVs. Cross-immunization tests were performed using both killed and live viruses in specific-pathogen-free chicks. One-day-old chicks were immunized with killed or high [10(5) 50% embryo infectious dose (EID50)] or low (10(3) EID50) doses of live IBV viruses and challenged with homologous or heterologous IBV strains. The immunization efficacy was evaluated by virus isolation from the challenged chicks. In the killed-virus and high-dose live-virus test groups, IBV vaccination protected against challenge by homologous but not heterologous IBV strains. However, a low dose of live IBV showed no protection against virulent IBV challenge. These results indicate that both the genotype based on the N-terminus of the spike protein and the virus dose are essential to IBV protection from immunization. Thus, development of vaccines from different local strains is necessary to control infectious bronchitis in poultry.


title: Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children.

text: BACKGROUND Asthma exacerbation is the most common cause of hospital admission in children. A study was undertaken to investigate the importance of allergen exposure in sensitised individuals in combination with viral infections and other potentially modifiable risk factors precipitating asthma hospital admission in children. METHODS Eighty four children aged 3-17 years admitted to hospital over a 1 year period with an acute asthma exacerbation (AA) were matched for age and sex with two control groups: stable asthmatics (SA) and children admitted to hospital with non-respiratory conditions (IC). Risk factors were assessed by questionnaires and determination of allergen sensitisation, home allergen exposure, pollen exposure, and respiratory virus infection. RESULTS Several non-modifiable factors (atopy, duration of asthma) were associated with increased risk. Among the modifiable factors, pet ownership, housing characteristics, and parental smoking did not differ between the groups. Regular inhaled corticosteroid treatment was significantly less common in the AA group than in the SA group (OR 0.2, 95% CI 0.1 to 0.6; p = 0.002). A significantly higher proportion of the AA group were virus infected (44%) and sensitised and highly exposed to sensitising allergen (76%) compared with the SA (18% and 48%) and IC groups (17% and 28%; both p<0.001). In a multiple conditional logistic regression (AA v SA), allergen sensitisation and exposure or virus detection alone were no longer independently associated with hospital admission. However, the combination of virus detection and sensitisation with high allergen exposure substantially increased the risk of admission to hospital (OR 19.4, 95% CI 3.7 to 101.5, p<0.001). CONCLUSIONS Natural virus infection and real life allergen exposure in allergic asthmatic children increase the risk of hospital admission. Strategies for preventing exacerbations will need to address these factors.


title: Investigation of appropriate sanitization frequency for rodent caging accessories: evidence supporting less-frequent cleaning.

text: The Guide for the Care and Use of Laboratory Animals states that sanitization of caging accessories (for example, filter tops and wire-bar lids) should be done every 2 wk. In this study we tested the hypothesis that organic contamination measured by the presence of ATP associated with organic material (measured with luciferase test swabs) and the number of bacterial colony-forming units (as determined by use of replicate organism detection and counting plates) on caging accessories did not differ significantly at 2 wk versus several months of use. The study evaluated 4 groups: mouse and rat ventilated and static wire-bar cages with or without filter tops (n = 10 per group). The cages were evaluated at several time points from 2 wk to 6 mo. For every cage type, ATP levels did not differ significantly between 14 and 90 d and, in most cases, between 14 and 180 d. In addition the number of bacterial colonies did not differ significantly between 14 and 120 d (and, in some cases, between 14 and 180 d). This study provides data relevant to establishing a validated frequency for sanitization of rodent caging accessories while controlling, and potentially decreasing, costs associated with sanitization.


title: Induction of demyelination by a temperature-sensitive mutant of the coronavirus MHV-A59 is associated with restriction of viral replication in the brain.

text: The neurovirulence of eight temperature-sensitive (ts) mutants of mouse hepatitis virus strain A59 in 4-week-old BALB/c mice was investigated. Whereas a dose of 100 p.f.u. of wild-type virus killed mice within a week, a 1000-fold higher dose of ts mutants did not. Three ts mutants induced demyelinating disease in the central nervous system (CNS). The pathology of the demyelinating disease caused by one mutant, designated ts-342, was studied in detail. Pathological changes, starting 3 days post-inoculation (p.i.), were characterized by inflammation and demyelination in the CNS. Antibody responses directed against all virus-specific structural proteins were present at 7 days p.i. No virus particles were observed by electron microscopy at 14 days p.i. However, macrophages and lymphocytes were abundant in the areas of demyelination. The growth kinetics in vivo of wild-type virus, ts-342 and a revertant of ts-342 were compared. Wild-type virus and the revertant replicated rapidly in the brain and spread to the liver causing a lethal hepatitis. Ts-342, however, replicated to a much lesser extent within the brain and could not be detected in the blood or liver. The ts lesion in the genome of ts-342 seems, therefore, to determine the outcome of the infection.


Achieving a balance.


title: Ex vivos models to teaching therapeutic endoscopic ultrasound (T-EUS).

text: BACKGROUND Endoscopic ultrasound training has a learning curve greater than the other endoscopic therapeutic techniques. One of the preclinical teaching methods is the use of ex vivo porcine models. AIM To describe five ex vivo porcine models for training in therapeutic echoendoscopic procedures. MATERIALS AND METHODS Using porcine digestive tract containing esophagus, stomach, duodenum, spleen, liver and gallbladder, five models for therapeutic echoendoscopy training were described. With other segments of the porcine pieces (such as the bladder, spleen segment and omentum segment) and with easily accessible materials (such as grape and ultrasound gel), lesions were simulated to be treated. These models were applied in the Hands on course at the IRCAD (Institut de recherche contre les cancers de l'appareil digestif) Barretos of 2017. Endoscopic equipment and instruments are the same as those used in clinical practice. RESULT The models are easily reproducible and do not require exchange during the hands on course period. Endoscopic and echographic imaging and tactile sensitivity are similar to the real one. CONCLUSION The models described in this study demonstrated to be realistic, easy to reproduce and allow repetition during the same session. However, comparative studies are necessary to verify the real impact on teaching.


title: The arterivirus replicase is the only viral protein required for genome replication and subgenomic mRNA transcription.

text: Equine arteritis virus (EAV) (ARTERIVIRIDAE:) encodes several structural proteins. Whether any of these also function in viral RNA synthesis is unknown. For the related mouse hepatitis coronavirus (MHV), it has been suggested that the nucleocapsid protein (N) is involved in viral RNA synthesis. As described for MHV, we established that the EAV N protein colocalizes with the viral replication complex, suggesting a role in RNA synthesis. Using an infectious cDNA clone, point mutations and deletions were engineered in the EAV genome to disrupt the expression of each of the structural genes. All structural proteins, including N, were found to be dispensable for genome replication and subgenomic mRNA transcription. We also constructed a mutant in which translation of the intraleader ORF was disrupted. This mutant had a wild-type phenotype, indicating that, at least in cell culture, the product of this ORF does not play a role in the EAV replication cycle.


title: Virological aspects of measles virus-induced encephalomyelitis in Lewis and BN rats.

text: Lewis and Brown Norway (BN) rats which are susceptible or resistant to autoimmune reactions against brain antigen, respectively, were inoculated intracerebrally with a neurotropic measles virus. Suckling rats died from a rapidly fatal acute encephalopathy (AE). With increasing age Lewis rats developed a subacute measles encephalomyelitis (SAME) whereas BN rats showed a clinically silent encephalitis (CSE). Infectious virus could occasionally be recovered from SAME animals using cocultivation techniques but not from BN rats with CSE. With monoclonal antibodies against measles virus, viral proteins were localized in brain tissue. Nucleocapsid and phosphoprotein were detected in infected brain cells of all animals with AE, SAME and CSE, whereas measles virus haemagglutinin, fusion and matrix proteins were either reduced or absent, suggesting a restricted synthesis of measles virus envelope proteins. These data suggest that the different diseases of the two rat strains are related to the immunogenetic background rather than to the replication of measles virus in the central nervous system. This animal model provides the opportunity to investigate further the events occurring during establishment of measles virus persistence in the brain, and the genetic control of associated immunological and immunopathological reactions.


title: Mitochondrial DNA diversity among three subpopulations of cynomolgus macaques (Macaca fascicularis) originating from the Indochinese region.

text: The cynomolgus macaque (Macaca fascicularis) has emerged as an important experimental animal model for biomedical research in various domains, necessitating the more extensive characterization of the genetic backgrounds influencing the macaque's response to drugs and sensitivity to experimental disease. The diversity of the variable mitochondrial DNA (mtDNA) D-loop region has been analyzed phylogenetically among geographically isolated populations or within subdivisions of the same regional population. However, the genetic differences among several substructures originating from a common population have not yet been investigated. By sequencing fragments of the mtDNA D-loop region from two subpopulations from the Indochinese region (Cambodian-Chinese and Vietnamese) along with two native Indonesian and Filipino populations, we identified 87 mtDNA D-loop haplotypes, of which 67 are new. The phylogenetic relationship suggests that the Indochinese haplotypes are intermingled in comparison to the distinct divergence of the Indonesian and Filipino lineages. The subpopulations were shown by estimation of evolutionary divergence and Wright's F-statistic (Fst) to have little genetic differentiation. Altogether, the subpopulations may be used in biomedical research, even though a slight difference is observed in haplotype frequencies among them. Therefore, genetic diversity analyses will be necessary for the elucidation of genetic differences among the populations, as well as to obtain a better understanding of genetic diversity for biomedical research. This will involve the selection of macaques and the monitoring of genetic heterogeneity among and within breeding facilities.


title: Epidemiology of acute lung injury and acute respiratory distress syndrome.

text: PURPOSE OF REVIEW Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are diseases with a significant influence in the public health. A better knowledge of their epidemiology could help to improve the outcome of these diseases. RECENT FINDINGS Although the clinical criteria of the American-European Consensus Conference definitions for ALI and ARDS are simple, there is a risk of misclassification due to a poor reliability. Except for new emerging infectious diseases, such as severe acute respiratory syndrome, the etiology of ALI/ARDS has remained the same for several years. The only recent innovation is the hypothesis that pulmonary ARDS and extrapulmonary ARDS could be different clinical entities. In recent years, there has been a special interest in the study of genetic predisposition to development ALI/ARDS. Recent studies have estimated the incidence of these diseases to be between 15 and 34 cases per 100,000 inhabitants per year. This wide range could stem from differences in the methodology used to calculate the incidence or could be a true variation due to regional differences. Mortality rate of ALI/ARDS have remained steady for several years. Respiratory failure is the cause of the death in less than 20% of the patients. SUMMARY The epidemiology of ALI and ARDS has some issues to improve, such as the accuracy of the clinical criteria of ALI/ARDS. Future research must to include study of genetic polymorphisms of the mediators involve in the development of ALI/ARDS. Studies to define better the population at risk are necessary to estimate better their true incidence.


title: A silkworm baculovirus model for assessing the therapeutic effects of antiviral compounds: characterization and application to the isolation of antivirals from traditional medicines.

text: Ganciclovir, foscarnet, vidarabine and ribavirin, which are used to treat viral infections in humans, inhibited the proliferation of a baculovirus (Bombyx mori nucleopolyhedrovirus) in BmN4 cells, a cultured silkworm cell line. These antiviral agents inhibited the proliferation of baculovirus in silkworm body fluid and had therapeutic effects. Using the silkworm infection model, the antiviral activity of Kampo medicines was screened and it was found that cinnamon bark, a component of the traditional Japanese medicine Mao-to, had a therapeutic effect. Based on the therapeutic activity, the antiviral substance was purified. Nuclear magnetic resonance analysis of the purified fraction revealed that the antiviral activity was due to cinnzeylanine, which has previously been isolated from Cinnamomum zeylanicum. Cinnzeylanine inhibits the proliferation of herpes simplex virus type 1 in Vero cells. These results suggest that the silkworm-baculovirus infection model is useful for screening antiviral agents that are effective for treating humans infected with DNA viruses.


title: Effectiveness of a surgical glove port with homemade trocars made of syringes for single incision laparoscopic cholecystectomy.

text: BACKGROUND/AIMS Single incision laparoscopic cholecystectomy (SILC) has two serious problems; its feasibility and cost. We report our experience and benefits of our original SILC procedure using homemade trocars that can solve those problems. METHODOLOGY SILC was attempted for thirty-four patients at our hospital. The SILST" Port (Covidien, Inc) was used in 16 patients (SPgroup) and the original method using a surgical glove port with homemade trocars was performed in 18 patients (GP-HT group). A homemade trocar was made ofa 2.5mL and a 5mL syringe. We performed the retrospective comparison of the operative and postoperative results between those two groups. RESULTS Thirty patients (14 in the SP group and 16 in the GP-HT group)successfully underwent SILC. No patient had a grade IIor more severe postoperative complication based on the Clavien-Dindo classification. Our original home made trocar was slim and compact enough to avoid clashes among surgical instruments and surgeon's hands. Operative time in the GP-HT group was significantly short-er than that in the SP group (p=0.0044). CONCLUSIONS Although further prospective studies of larger series should be performed, this simple and cost-effective system can be one of the promising ways for SILC.


title: Australia's notifiable disease status, 2012: Annual report of the National Notifiable Diseases Surveillance System.

text: In 2012, 65 diseases and conditions were nationally notifiable in Australia. States and territories reported a total of 243,822 notifications of communicable diseases to the National Notifiable Diseases Surveillance System, an increase of 2% on the number of notifications in 2011. In 2012, the most frequently notified diseases were sexually transmissible infections (99,250 notifications, 40.7% of total notifications), vaccine preventable diseases (85,810 notifications, 35.2% of total notifications), and gastrointestinal diseases (31,155 notifications, 12.8% of total notifications). There were 16,846 notifications of bloodborne diseases; 8,305 notifications of vector-borne diseases; 1,924 notifications of other bacterial infections; 578 notifications of zoonoses; and 5 notifications of quarantinable diseases.


title: Gastrointestinal Presentation in COVID-19 in Indonesia: A Case Report.

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a widespread infection in the world. During the pandemic, physicians may need to raise the index of suspicion earlier in at-risk patients presenting with gastrointestinal symptoms, which are uncommon findings in coronavirus disease 2019 (COVID-19) patients. We report a patient in Indonesia with chest pain and gastrointestinal symptoms who was later confirmed to have SARS-CoV-2 infection after spending days of hospitalisation in the standard ward.


title: Influenza and seasonal influenza vaccination among diabetics in Singapore: knowledge, attitudes and practices.

text: INTRODUCTION Seasonal influenza vaccination is recommended for diabetics; however, the vaccination uptake rate among diabetics remains low. This study explored the knowledge, attitudes and practices among diabetics in Singapore with regard to influenza and influenza vaccination. METHODS A survey was conducted among type 1 and 2 diabetes mellitus patients who attended three management centres of the Diabetic Society of Singapore in January 2007. The pilot-tested questionnaire covered influenza and influenza vaccination in terms of the patient demographics, medical history and knowledge, attitudes and practices. RESULTS A total of 307 diabetics participated in the study. Of these, 139 (45.3 percent) claimed to know the difference between influenza and the common cold, while 98 (31.9 percent) and 18 (5.9 percent) participants thought that influenza vaccines protected against all influenza strains and provided lifelong immunity, respectively. 247 (80.4 percent) participants were aware that they were at a moderate or higher risk for influenza-related complications, while 181 (58.9 percent) considered vaccination to be effective in preventing influenza and its complications. Only 94 (30.6 percent) participants were previously vaccinated. Among those unvaccinated, 117 (54.9 percent) did not think vaccination was necessary, while 104 (48.8 percent) had never considered it. As observed from the multivariate analysis, income was a key predictor of influenza vaccination. While 241 (78.5 percent) participants cited healthcare professional advice as the main guiding factor for getting vaccinated, 199 (64.8 percent) had never been advised on influenza vaccination. Of the 108 (35.1 percent) participants who had received previous advice on influenza vaccination, the majority had received it from their healthcare professionals. CONCLUSION Uptake of influenza vaccination among diabetics in Singapore is low, and the key predictor is income. Perception and knowledge are the main barriers, and hence, healthcare professionals should educate and encourage vaccination among diabetics.


title: Tree decomposition based fast search of RNA structures including pseudoknots in genomes.

text: Searching genomes for RNA secondary structure with computational methods has become an important approach to the annotation of non-coding RNAs. However, due to the lack of efficient algorithms for accurate RNA structure-sequence alignment, computer programs capable of fast and effectively searching genomes for RNA secondary structures have not been available. In this paper, a novel RNA structure profiling model is introduced based on the notion of a conformational graph to specify the consensus structure of an RNA family. Tree decomposition yields a small tree width t for such conformation graphs (e.g., t = 2 for stem loops and only a slight increase for pseudo-knots). Within this modelling framework, the optimal alignment of a sequence to the structure model corresponds to finding a maximum valued isomorphic subgraph and consequently can be accomplished through dynamic programming on the tree decomposition of the conformational graph in time O(k(t)N(2)), where k is a small parameter; and N is the size of the projiled RNA structure. Experiments show that the application of the alignment algorithm to search in genomes yields the same search accuracy as methods based on a Covariance model with a significant reduction in computation time. In particular; very accurate searches of tmRNAs in bacteria genomes and of telomerase RNAs in yeast genomes can be accomplished in days, as opposed to months required by other methods. The tree decomposition based searching tool is free upon request and can be downloaded at our site h t t p ://w.uga.edu/RNA-informatics/software/index.php.


title: Sinomenine activates astrocytic dopamine D2 receptors and alleviates neuroinflammatory injury via the CRYAB/STAT3 pathway after ischemic stroke in mice.

text: BACKGROUND Astrocyte-mediated neuroinflammation plays a critical role in ischemic stroke-induced secondary cerebral injury. Previous studies have suggested that the dopamine D2 receptor (DRD2) acts as a key target in regulating the neuroinflammatory response. However, the underlying molecular mechanisms are still unknown, and effective DRD2 agonists are lacking. In the present study, we examined the anti-inflammatory and neuroprotective effects of sinomenine (Sino), a monomeric compound with potential immunoregulatory properties in nervous system. METHODS TTC staining, apoptosis assay, evaluation of brain edema, and neurological assessment were performed in the middle cerebral artery occlusion (MCAO) mouse model. Primary astrocytes exposed to oxygen glucose deprivation (OGD) were used in the in vitro experiments. Quantitative PCR was applied to assess the levels of inflammatory cytokines. Multi-labeling immunofluorescence, Western blot, co-immunoprecipitation, and electrophoretic mobility shift assay (EMSA) were also used to investigate the molecular mechanisms underlying the Sino-mediated anti-inflammatory effects in vivo and in vitro. RESULTS Sino remarkably attenuated the cerebral infarction and neuronal apoptosis, reduced the levels of inflammatory cytokines, and alleviated neurological deficiency in MCAO mice. Sino significantly inhibited astrocytic activation and STAT3 phosphorylation as well as increased DRD2 and αB-crystallin (CRYAB) expression after MCAO. In vitro, Sino blocked OGD-induced activation of STAT3 and generation of pro-inflammatory cytokines in primary astrocytes, and these effects were significantly abolished by either DRD2 or CRYAB knockdown. Additionally, Sino induced up-regulation and nuclear translocation of CRYAB in astrocytes and enhanced the interaction between CRYAB and STAT3, which further inhibited the activation and DNA-binding activity of STAT3. CONCLUSIONS Our study demonstrates that Sino activates astrocytic DRD2 and thereby suppresses neuroinflammation via the CRYAB/STAT3 pathway, which sheds some light on a promising therapeutic strategy for ischemic stroke.


title: Evaluation of the brain anaesthesia response monitor during anaesthesia for cardiac surgery: a double-blind, randomised controlled trial using two doses of fentanyl.

text: The brain anaesthesia response (BAR) monitor uses a method of EEG analysis, based on a model of brain electrical activity, to monitor the cerebral response to anaesthetic and sedative agents via two indices, composite cortical state (CCS) and cortical input (CI). It was hypothesised that CCS would respond to the hypnotic component of anaesthesia and CI would differentiate between two groups of patients receiving different doses of fentanyl. Twenty-five patients scheduled to undergo elective first-time coronary artery bypass graft surgery were randomised to receive a total fentanyl dose of either 12 μg/kg (fentanyl low dose, FLD) or 24 μg/kg (fentanyl moderate dose, FMD), both administered in two divided doses. Propofol was used for anaesthesia induction and pancuronium for intraoperative paralysis. Hemodynamic management was protocolised using vasoactive drugs. BIS, CCS and CI were simultaneously recorded. Response of the indices (CI, CCS and BIS) to propofol and their differences between the two groups at specific points from anaesthesia induction through to aortic cannulation were investigated. Following propofol induction, CCS and BIS but not CI showed a significant reduction. Following the first dose of fentanyl, CI, CCS and BIS decreased in both groups. Following the second dose of fentanyl, there was a significant reduction in CI in the FLD group but not the FMD group, with no significant change found for BIS or CCS in either group. The BAR monitor demonstrates the potential to monitor the level of hypnosis following anaesthesia induction with propofol via the CCS index and to facilitate the titration of fentanyl as a component of balanced anaesthesia via the CI index.


title: Factors associated with length of hospital stay in children with respiratory disease.

text: OBJECTIVES To explore factors associated with length of stay, and secondarily to explore the potential of enhanced diagnostics to address respiratory disease burden in children. DESIGN Prospective study. SETTING A university teaching hospital in Hong Kong. PATIENTS Data from 475 children with respiratory tract symptoms or fever admitted to Prince of Wales Hospital, Hong Kong from November 2005 to April 2007. MAIN OUTCOME MEASURES Aetiological diagnoses based on enhanced diagnostics and their association with clinical information. RESULTS Data from 469 subjects showed that major presentations were fever (84%), cough (72%), and runny nose (64%). The median length of stay was longest (3 days) for adenovirus, metapneumovirus and mycoplasma infections, while children with negative aetiological results had a median length of stay of 2 days. Fever duration during admission (P<0.001), the highest recorded temperature during admission (P < 0.001), use of antibiotics during admission (P<0.001), ear pain before admission (P = 0.019), and high white cell counts (P = 0.021) were associated with increased length of stay (univariate analysis). Identifying an aetiological agent did not affect length of stay. Comparison of children with a positive immunofluorescence test result (rapidly available) with those in whom the test was negative though a positive multiplex polymerase chain reaction ensued (result not available to clinicians) also showed no association with length of stay. CONCLUSION Although rapid enhanced diagnostics may not have a major influence on length of stay, these data form an integral part of enhanced sentinel surveillance systems.


title: Mapping of equine lentivirus receptor 1 residues critical for equine infectious anemia virus envelope binding.

text: The equine lentivirus receptor 1 (ELR1), a member of the tumor necrosis factor receptor (TNFR) protein family, has been identified as a functional receptor for equine infectious anemia virus (EIAV). Toward defining the functional interactions between the EIAV SU protein (gp90) and its ELR1 receptor, we mapped the gp90 binding domain of ELR1 by a combination of binding and functional assays using the EIAV SU gp90 protein and various chimeric receptor proteins derived from exchanges between the functional ELR1 and the nonbinding homolog, mouse herpesvirus entry mediator (murine HveA). Complementary exchanges of the respective cysteine-rich domains (CRD) between the ELR1 and murine HveA proteins revealed CRD1 as the predominant determinant of functional gp90 binding to ELR1 and also to a chimeric murine HveA protein expressed on the surface of transfected Cf2Th cells. Mutations of individual amino acids in the CRD1 segment of ELR1 and murine HveA indicated the Leu70 in CRD1 as essential for functional binding of EIAV gp90 and for virus infection of transduced Cf2Th cells. The specificity of the EIAV SU binding domain identified for the ELR1 receptor is fundamentally identical to that reported previously for functional binding of feline immunodeficiency virus SU to its coreceptor CD134, another TNFR protein. These results indicate unexpected common features of the specific mechanisms by which diverse lentiviruses can employ TNFR proteins as functional receptors.


title: Accumulation of recombinant SARS-CoV spike protein in plant cytosol and chloroplasts indicate potential for development of plant-derived oral vaccines.

text: Plants are promising candidates as bioreactors for the production of oral recombinant proteins in the biopharmaceutical industry. As an initial step toward provision of an oral vaccine against the severe acute respiratory syndrome coronavirus (SARS-CoV), we have expressed a partial spike (S) protein of SARS-CoV in the cytosol of nuclear-transformed plants and in the chloroplasts of plastid-transformed plants. In the construction of both nuclear and plastid transformation vectors, a 2-kilobase nucleotide sequence encoding amino acids 1-658 of the SARS-CoV spike protein (S1) was modified with nucleotide changes, but not amino acid changes, to optimize codon usage for expression in plants. To investigate the subcellular localization of S1 during transient expression in tobacco leaves, a translational fusion consisting of S1 and the green fluorescent protein (GFP) was generated. Following agroinfiltration of tobacco leaves, analysis by laser confocal scanning microscopy revealed that the S1:GFP fusion protein was localized to the cytosol. In stable transgenic tobacco plants and lettuce plants generated by Agrobacterium-mediated transformation, tobacco and lettuce leaves were observed to express the S1 at high levels from the Cauliflower Mosaic Virus 35S promoter with Northern blot analysis. When the S1 was expressed in transplastomic tobacco, S1 messenger RNA and its corresponding protein were detected on Northern and Western blot analyses, respectively. Our results demonstrate the feasibility of producing S1 in nuclear- and chloroplast-transformed plants, indicating its potential in subsequent development of a plant-derived and safe oral recombinant subunit vaccine against the SARS-CoV in edible plants.


title: Heterogeneous influenza activity across Europe during the winter of 2002-2003.

text: Influenza activity varied across Europe during the 2002-2003 season both in terms of the intensity of clinical activity and the circulating virus types/subtypes. Influenza B was generally predominant in the 'western' parts of Europe (Portugal, Spain, the United Kingdom and Ireland) and influenza A (H3N2) in the 'central' and 'eastern' areas (Germany, Italy, Denmark, Switzerland, Poland, Slovenia, the Slovak Republic, the Netherlands). A number of countries experienced mixed seasons, first experiencing activity associated with influenza B and then with influenza A (Belgium, France and Spain). Generally, countries where influenza B was predominant had low (compared to historical data) levels of intensity (a mild season) and longer periods of influenza activity compared to countries where influenza A (H3N2) was predominant. A number of countries, all where influenza A (H3N2) was predominant, reported high levels of intensity compared to historical data: the Czech Republic, Denmark, Germany and Poland. In the six countries where age-specific incidence rates were available, the highest rates were observed among those aged 0-14 years. The influenza virus strains circulating in Europe had a good match with the virus strains in the influenza vaccine. A small number of isolates (A/Fujian/411/2002 (H3N2)-like) were reported at the end of the season that had a reduced reactivity to anti-sera of the vaccine strain. The composition of the 2003-2004 influenza vaccine is the same as during the 2002-2003 season.


title: Double-stranded RNA stimulates the expression of monocyte chemoattractant protein-1 in BEAS-2B bronchial epithelial cells.

text: BEAS-2B bronchial epithelial cells were treated with polyinosinic-polycytidylic acid (poly IC), a synthetic double-stranded RNA (dsRNA) analog, and the expressions of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein were analyzed by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. Poly IC enhanced the expression of MCP-1 and release of mononuclear cell chemotactic activity, which were inhibited by dexamethasone pre-treatment. The poly IC-induced up-regulation of MCP-1 was blocked by 2-aminopurine, a specific inhibitor of dsRNA-dependent protein kinase, but not by nuclear factor (NF)-kappaB inhibitor SN50.


title: Development and application of a Saccharomyces cerevisiae-expressed nucleocapsid protein-based enzyme-linked immunosorbent assay for detection of antibodies against infectious bronchitis virus.

text: A Saccharomyces cerevisiae-expressed nucleocapsid (N) polypeptide of the M41 strain of infectious bronchitis virus (IBV) was used as antigen in a recombinant yeast-expressed N protein-based enzyme-linked immunosorbent assay (Y-N-ELISA). The Y-N-ELISA was rapid, sensitive, and specific for detecting chicken serum antibodies to IBV, and it compared favorably with a commercial ELISA.


title: Comparison of Cryptosporidium parvum viability and infectivity assays following ozone treatment of oocysts.

text: Several in vitro surrogates have been developed as convenient, user-friendly alternatives to mouse infectivity assays for determining the viability of Cryptosporidium parvum oocysts. Such viability assays have been used increasingly to determine oocyst inactivation following treatment with chemical, physical, or environmental stresses. Defining the relationship between in vitro viability assays and oocyst infectivity in susceptible hosts is critical for determining the significance of existing oocyst inactivation data for these in vitro assays and their suitability in future studies. In this study, four viability assays were compared with mouse infectivity assays, using neonatal CD-1 mice. Studies were conducted in the United States and United Kingdom using fresh (<1 month) or environmentally aged (3 months at 4 degrees C) oocysts, which were partially inactivated by ozonation before viability and/or infectivity analyses. High levels of variability were noted within and between the viability and infectivity assays in the U.S. and United Kingdom studies despite rigorous control over oocyst conditions and disinfection experiments. Based on the viability analysis of oocyst subsamples from each ozonation experiment, SYTO-59 assays demonstrated minimal change in oocyst viability, whereas 4',6'-diamidino-2-phenylindole-propidium iodide assays, in vitro excystation, and SYTO-9 assays showed a marginal reduction in oocyst viability. In contrast, the neonatal mouse infectivity assay demonstrated significantly higher levels of oocyst inactivation in the U.S. and United Kingdom experiments. These comparisons illustrate that four in vitro viability assays cannot be used to reliably predict oocyst inactivation following treatment with low levels of ozone. Neonatal mouse infectivity assays should continue to be regarded as a "gold standard" until suitable alternative viability surrogates are identified for disinfection studies.


title: Management protocols for animals in captive propagation and reintroduction programmes.

text: Species Survival Plans in North America--and comparable programmes in other parts of the world--address the management issues related to maintaining populations of endangered species in captivity. The need has been recognized for universal methods of assessing, evaluating, monitoring and preventing the transmission of disease to naive wildlife by reintroduced species. Standardized protocols are presented for evaluation of the health status of captive animals intended for release.


title: [Viruses and bats: rabies and Lyssavirus].

text: Recent emerging zoonoses (hemorrhagic fevers due to Ebola or Marburg virus, encephalitis due to Nipah virus, severe acute respiratory syndrome due to SRAS virus...) outline the potential of bats as vectors for transmission of infectious disease to humans. Such a potential is already known for rabies encephalitis since seven out of the eight genotypes of Lyssavirus are transmitted by bats. In addition, phylogenetic reconstructions indicate that Lyssavirus have evolved in chiropters before their emergence in carnivores. Nevertheless, carnivores remain the most critical vectors for public health, in particular dogs that are originating 55.000 rabies deaths per year, essentially in developing countries. Rabies control in carnivores by parenteral (dog) or oral (wild carnivores) vaccination is efficacious and campaigns start to be more widely applied. On the other hand, rabies control in bat still remains non realistic, particularly as the pathogenicity of bat Lyssavirus for bats is still under debate, suggesting that a "diplomatic relationship" between partners would have arisen from a long term cohabitation. While comparing the interactions that humans and bats establish with Lyssavirus, scientists try to understand the molecular basis ofpathogenicity in man, a indispensable prerequisite to identify antiviral targets in a perspective of therapy.


title: The role of type I interferon production by dendritic cells in host defense.

text: Type I interferons (IFN) and dendritic cells (DC) share an overlapping history, with rapidly accumulating evidence for vital roles for both production of type 1 IFN by DC and the interaction of this IFN both with DC and components of the innate and adaptive immune responses. Within the innate immune response, the plasmacytoid DC (pDC) are the "professional" IFN producing cells, expressing specialized toll-like receptors (TLR7 and -9) and high constitutive expression of IRF-7 that allow them to respond to viruses with rapid and extremely robust IFN production; following activation and production of IFN, the pDC subsequently mature into antigen presenting cells that help to shape the adaptive immune response. However, like most cells in the body, the myeloid or conventional DC (mDC or cDC) also produce type I IFNs, albeit typically at a lower level than that observed with pDC, and this IFN is also important in innate and adaptive immunity induced by these classic antigen presenting cells. These two major DC subsets and their IFN products interact both with each other as well as with NK cells, monocytes, T helper cells, T cytotoxic cells, T regulatory cells and B cells to orchestrate the early immune response. This review discusses some of the converging history of DC and IFN as well as mechanisms for IFN induction in DC and the effects of this IFN on the developing immune response.


title: Diagnostic investigation of bovine viral diarrhea infection in a Minnesota dairy herd.

text: Bovine viral diarrhea (BVD) virus infection was diagnosed in neonatal calves with enteritis. Successful diagnostic procedures included direct immunofluorescence of frozen tissue sections, histopathology, and virus isolation. Virus isolation from buffy coats and serum was successful in detecting infected animals, whereas direct immunofluorescence of buffy coat samples was found to be less reliable. Virus was not isolated from any fecal samples. Booster vaccinations and the culling of animals shedding virus resulted in improved calf viability in this herd. It is suggested that procedures for the diagnosis of BVD virus infection should always be included in the diagnosis of neonatal calf enteritis.


Do respirators protect health-care workers from airborne infectious diseases?


A question of age.


title: Pandemic influenza and its implications for transplantation.

text: Influenza viruses are important infections in transplant recipients. They may lead to complications including viral pneumonia, secondary bacterial infections and graft dysfunction. There has been a recent widespread outbreak of highly pathogenic H5N1 avian influenza among domestic poultry and wild birds along with a number of human cases with severe disease and high mortality. Genetic changes in the H5N1 virus may lead to efficient human-to-human transmission, heralding the onset of the next influenza pandemic. Discussed are the implications that such a pandemic may have on transplant patients. Logical inferences can be made from data on influenza in transplant patients and from experience with other respiratory virus outbreaks. In the event of a pandemic, it is likely that transplant patients will have more severe disease and higher mortality as compared to the general population. Vaccination and antiviral strategies may be less effective in this population. Implications for transplant programs in general are also discussed.


title: Outbreak of adenovirus type 1 severe pneumonia in a French intensive care unit, September-October 2012.

text: We herein describe and analyse the first outbreak of severe pneumonia caused by human adenovirus type1 (HAdV C type 1), which included immunocompetent patients in an intensive care unit (ICU) of Marseille, France, and occurred between September and October 2012. Seven successive patients were diagnosed by HAdV specific real-time polymerase chain reaction with a positive bronchoalveolar lavage. After the collection of nasopharyngeal swabs from healthcare workers, three nurses working night shifts tested positive for HAdV C including one that had exhibited respiratory signs while working one week before the outbreak. She was the most likely source of the outbreak. Our findings suggest that HAdV-1 could be considered as a possible cause of severe pneumonia even in immunocompetent patients with a potential to cause outbreaks in ICUs. HAdV rapid identification and typing is needed to curtail the spread of this pathogen. Reinforcing hand hygiene with antiseptics with demonstrated activity against non-enveloped viruses and ensuring that HCWs with febrile respiratory symptoms avoid direct patient contact are critical measures to prevent transmission of HAdV in healthcare settings.


title: Prediction of consensus RNA secondary structures including pseudoknots.

text: Most functional RNA molecules have characteristic structures that are highly conserved in evolution. Many of them contain pseudoknots. Here, we present a method for computing the consensus structures including pseudoknots based on alignments of a few sequences. The algorithm combines thermodynamic and covariation information to assign scores to all possible base pairs, the base pairs are chosen with the help of the maximum weighted matching algorithm. We applied our algorithm to a number of different types of RNA known to contain pseudoknots. All pseudoknots were predicted correctly and more than 85 percent of the base pairs were identified.


title: Serologic survey for viral and bacterial infections in western populations of Canada lynx (Lynx canadensis).

text: A serologic survey for exposure to pathogens in Canada lynx (Lynx canadensis) in western North America was conducted. Samples from 215 lynx from six study areas were tested for antibodies to feline parvovirus (FPV), feline coronavirus, canine distemper virus, feline calicivirus, feline herpesvirus, Yersinia pestis, and Francisella tularensis. A subset of samples was tested for feline immunodeficiency virus; all were negative. For all other pathogens, evidence for exposure was found in at least one location. Serologic evidence for FPV was found in all six areas but was more common in southern populations. Also, more males than females showed evidence of exposure to FPV. Overall, prevalences were low and did not exceed 8% for any of the pathogens tested. This suggests that free-ranging lynx rarely encounter common feline pathogens.


New insights into the mechanisms of RNA recombination.


title: Equine arteritis virus subgenomic mRNA synthesis: analysis of leader-body junctions and replicative-form RNAs.

text: In addition to the genomic RNA, a 3' coterminal nested set of six subgenomic mRNAs is produced in equine arteritis virus (EAV)-infected cells. The seven viral RNAs are also 5' coterminal, since they all contain a 206-nucleotide common leader sequence which is identical to the 5' end of the genome. A conserved penta-nucleotide sequence motif, 5' UCAAC 3', was shown to be present at the junctions between the leader and body sequences in each of the mRNAs. In addition, two alternative junction sites were detected for mRNA 3. Seven replicative-form (RF) RNAs (RFs I to VII), corresponding to the genomic RNA and each of the subgenomic EAV mRNAs, could be prepared from lysates of infected cells. The minus-strand RNA contents of these RF RNAs were analyzed by using an RNase protection assay with an RNA probe containing the mRNA 2 leader-body junction. It was established that RF II contained a negative-stranded copy of mRNA 2, including a complementary leader sequence. The presence of subgenomic minus-strand RNA in RFs is indicative of a function as a transcription template during the production of EAV subgenomic mRNAs.


title: Plasma Concentration of Meloxicam in Pediatric Rats.

text: In this study, we compared the plasma concentrations of meloxicam in pediatric rat pups (ages: 7, 14, 21, and 28 d) with those of young adult rats. Adult rats received 1.34 mg/kg SC meloxicam to determine the target peak plasma concentration (Cmax) for comparison with the pediatric animals. Pediatric rats received 1.34 mg/kg SC meloxicam, and in all age groups, Cmax met or exceeded that in adults (11.5 ±2.7 μg/mL). Plasma concentrations were similar between male and female pups within age groups, and peak plasma concentration was achieved more rapidly in rat pups than adults. The analgesic efficacy of this dose was not evaluated in this study.


title: Allergens, viruses, and asthma exacerbations.

text: In adults and children with asthma, viral infections (rhinovirus [RV] infection being the most prevalent) will often trigger an increase in symptomatology. The mechanisms responsible for viral-induced exacerbations remain uncertain. Proposed mechanisms include direct infection of the lower respiratory tract, the inflammatory response to viruses, increases in bronchial responsiveness and up-regulation of intercellular adhesion molecule-1 expression in bronchial epithelium. In addition, exposure to allergens, especially seasonal allergens, in sensitized asthmatic individuals have been implicated in asthma attacks. Increased levels of exposure in sensitized asthmatics have been related to increases in hospital admissions and emergency room visits, increased bronchial hyperresponsiveness, increased levels of exhaled nitric oxide, lower levels of lung function, increased treatment requirements, and even increased mortality. In recent years studies have suggested that viruses and allergens may have a synergistic effect on individuals with asthma, thus having a greater influence on exacerbation rate together than either factor alone. Models of experimentally induced RV infection in both allergic and nonallergic individuals using bronchoalveolar lavage and segmental allergen challenge have helped researchers to investigate the possibility of an interaction between allergen sensitization, exposure, and virus infection and their role in the induction of an asthma exacerbation. This review aims to summarize the evidence supporting the role of viruses (in particular RV) as well as the role of, and interaction with, allergen sensitization and exposure on exacerbations of asthma.


Inclusion of patients in clinical trial analysis: the intention-to-treat principle.


Parental origin of chromosome 15 deletion in Prader-Willi syndrome.


title: Planning for the unexpected: Ebola virus, Zika virus, what's next?

text: Since 2000 we have witnessed global pandemics and public health emergencies of international concern. This review details which viruses are likely to caused further outbreaks and looks at the strategies and tools available to UK medical professionals to mitigate the threat posed.


title: Refining the approach to vaccines against influenza A viruses with pandemic potential.

text: Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on global disease and virologic surveillance. Experience with seasonal influenza vaccines guided the initial development of pandemic influenza vaccines. A large investment in pandemic influenza vaccines in the last decade has resulted in much progress and a body of information that can now be applied to refine the established paradigm. Critical and complementary considerations for pandemic influenza vaccines include improved assessment of the pandemic potential of animal influenza viruses, proactive development and deployment of pandemic influenza vaccines, and application of novel platforms and strategies for vaccine production and administration.


Actions Taken by the Turkish Surgical Society on COVID-19.


title: Glycoconjugate glycans as viral receptors.

text: The carbohydrate parts of cell surface glycoproteins, glycolipids, and proteoglycans constitute receptors for many enveloped as well as non-enveloped human viruses. The majority of viral receptors of carbohydrate nature are negatively charged, including sulfated glycosaminoglycans (GAGs) or glycans containing sialic acid. Not uncommonly, virus-carbohydrate interactions are responsible for specific tissue tropism, where the affinity of influenza virus for glycans in the respiratory tract containing (a2-6)-linked sialic acid is an important example. Similarly, the number and spacing of sulfates may guide viruses to optimal GAG molecules, although this remains unproven on tissue level. A further understanding of structure and tissue distribution of carbohydrate virus receptors and their viral ligands is essential for elucidating the pathogenesis of such viruses. Also neutral glycans such as histo-blood group substances may function as virus receptors. Here, natural resistance to a given viral disease may occur in a human subpopulation due to lack of such receptors caused by deletion-mutants in critical human genes. As regards antiviral applications, the receptor-destroying enzymes, in contrast to receptor binding proteins, at the surface of, for example, influenza virus have proven to be an excellent target for intervention, which is why sialic acid analogues are now in clinical use both for prophylaxis and treatment.


title: Murine coronavirus nonstructural protein p28 arrests cell cycle in G0/G1 phase.

text: Murine coronavirus mouse hepatitis virus (MHV) gene 1 encodes several nonstructural proteins. The functions are unknown for most of these nonstructural proteins, including p28, which is encoded at the 5' end of the MHV genome. Transient expression of cloned p28 in several different cultured cells inhibited cell growth, indicating that p28 expression suppressed cell proliferation. Expressed p28 was exclusively localized in the cytoplasm. Cell cycle analysis by flow cytometry demonstrated that p28 expression induced G(0)/G(1) cell cycle arrest. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that p28 expression resulted in an accumulation of hypophosphorylated retinoblastoma protein (pRb), tumor suppressor p53, and cyclin-dependent kinase (Cdk) inhibitor p21(Cip1). Expression of p28 did not alter the amount of p53 transcripts yet increased the amount of p21(Cip1) transcripts, suggesting that p28 expression increased p53 stability and that p21(Cip1) was transcriptionally activated in a p53-dependent manner. Our present data suggest the following model of p28-induced G(0)/G(1) cell cycle arrest. Expressed cytoplasmic p28 induces the stabilization of p53, and accumulated p53 causes transcriptional upregulation of p21(Cip1). The increased amount of p21(Cip1) suppresses cyclin E/Cdk2 activity, resulting in the inhibition of pRb hyperphosphorylation. Accumulation of hypophosphorylated pRb thus prevents cell cycle progression from G(0)/G(1) to S phase.


Global Health Diplomacy: A Closer Look.


title: A leucine zipper structure present in the measles virus fusion protein is not required for its tetramerization but is essential for fusion.

text: The biological role of a leucine zipper motif present in the measles virus fusion (F) protein has been investigated. This motif is present in all paramyxovirus F proteins, all coronavirus spike proteins and many if not all retrovirus envelope proteins. By analogy to its role in certain transcription factors, it has been suggested that the motif may be responsible for the oligomerization of these viral membrane proteins. In this study, one, two or four heptadic leucines in the motif were substituted using site-directed mutagenesis. We found that fusion is prevented when all four heptadic leucines present in the motif are mutated whereas cellular transport and the oligomeric state of the F protein are unaffected.


title: Transfusion of blood products affects outcome in cardiac surgery.

text: There remains controversy as to when patients undergoing cardiac surgery should receive a transfusion and whether a low hematocrit and its treatment with a transfusion of red cells influences outcome. The data related to this controversy are reviewed. Although the risk of known viral transmission is currently low, stored red cells do not function normally, and each unit contains activated inflammatory cells and mediators. These changes cause limited oxygen release, impaired microcirculatory flow, and immune suppression. A number of studies have observed decreased survival associated with transfusions in trauma, coronary artery bypass grafting, and intensive care unit patients. Studies that show an adverse outcome associated with low hematocrit are not definitive, because they fail to distinguish between the impact of low hematocrit per se and the possible adverse effects of transfusion, for what the low hematocrit may simply be a surrogate. The observation that a low hematocrit is associated with an adverse outcome does not necessarily prove that "treatment" of the anemia with a red cell transfusion will improve the outcome. Stored platelets contain a highly activated mixture of platelets with storage lesions and inflammatory mediators. Two retrospective post hoc multifactorial analyses suggest that platelet transfusions are associated with substantial increased morbidity and mortality. Clearly, large prospective studies are required to define the proper trigger for blood product transfusion to balance the adverse effects of anemia and platelet deficiency or dysfunction with the adverse effects of transfusion of blood products on morbidity and mortality associated with cardiac surgery and anesthesia.