title: Current initiatives in One Health: consolidating the One Health Global Network.

text: The Global Response to Avian Influenza has led to a longer-term One Health movement, which addresses risks, including zoonoses, at the human-animal- environment interface, and requires the development of innovative partnerships at the political, institutional and technical levels. One Health is a sustainable and rational option when the cumulative effects of health hazards on food and economic security are considered, but demands long-term financial investment. Projections of growth in the demand for livestock production and consumption in Asia and Africa also call for effective One Health responses. However, an effective response also requires validated evidence of the socio-economic value that the One Health approach can provide. Implementing the One Health approach depends on forging strong links between human and animal health services, the environment and public policy. The authors present a list of some of the national and transnational partnerships established since 2006. Political support, good governance and effective policies and networks are crucial building blocks for One Health sustainability. The Global Response to Avian Influenza was initially established under the joint leadership of the European Union, the United States and the United Nations System Influenza Coordination Office. Since then it has supported numerous initiatives, including the World Health Organization (WHO)/Food and Agriculture Organization of the United Nations (FAO)/World Organisation for Animal Health (OIE) Global Early Warning System (GLEWS). Indeed, the Global Response to Avian Influenza paved the way for an unprecedented WHO/FAO/OIE tripartite partnership, which promoted the integration of foodborne, neglected zoonotic and tropical diseases within the One Health movement and led to the tripartite High-Level Technical Meeting of 2011 in Mexico. The One Health Global Network, which began as a proposition at an Expert Consultation in Winnipeg, Canada, in 2009, is now a reality. While its Global Guidance Group takes shape, the choice of soft-governance--an approach which relies more on information and advisory guidelines than on hierarchy and legislation, and which aims to steer local organisations rather than to control them--remains challenging. Nonetheless, the emergence of One Health as a professional and academic discipline, together with the growing references to a One Health culture, also offers new opportunities.


title: Awareness among a Saudi Arabian university community of Middle East respiratory syndrome coronavirus following an outbreak.

text: This study aimed to measure the level of awareness of faculty members, staff and students in a female Saudi Arabian university community towards Middle East respiratory syndrome coronvirus (MERS-CoV) following an outbreak. A self-administered questionnaire containing knowledge questions was distributed and completed by the 1541 participants. The overall knowledge score was 43.2%. It was only significantly higher in participants from the health colleges (50.6%). The majority (78.9%) of the respondents recognized the typical symptoms of MERS-CoV but only 67.1% knew the recommended preventive hygiene practices. Awareness of disease epidemiology, severity, fatality rate and treatment was very low. The knowledge of health care workers/ students of the recommended precautions that should be applied when dealing with patients was poor (55.5%). Significant improvement in educational programmes for both the health care and non-health care professionals is warranted, particularly in crowded educational institutions or workplaces.


title: New Setting of Neurally Adjusted Ventilatory Assist during Noninvasive Ventilation through a Helmet.

text: BACKGROUND Compared to pneumatically controlled pressure support (PSP), neurally adjusted ventilatory assist (NAVA) was proved to improve patient-ventilator interactions, while not affecting comfort, diaphragm electrical activity (EAdi), and arterial blood gases (ABGs). This study compares neurally controlled pressure support (PSN) with PSP and NAVA, delivered through two different helmets, in hypoxemic patients receiving noninvasive ventilation for prevention of extubation failure. METHODS Fifteen patients underwent three (PSP, NAVA, and PSN) 30-min trials in random order with both helmets. Positive end-expiratory pressure was always set at 10 cm H2O. In PSP, the inspiratory support was set at 10 cm H2O above positive end-expiratory pressure. NAVA was adjusted to match peak EAdi (EAdipeak) during PSP. In PSN, the NAVA level was set at maximum matching the pressure delivered during PSP by limiting the upper pressure. The authors assessed patient comfort, EAdipeak, rates of pressurization (i.e., airway pressure-time product [PTP] of the first 300 and 500 ms after the initiation of patient effort, indexed to the ideal pressure-time products), and measured ABGs. RESULTS PSN significantly increased comfort to (median [25 to 75% interquartile range]) 8 [7 to 8] and 9 [8 to 9] with standard and new helmets, respectively, as opposed to both PSP (5 [5 to 6] and 7 [6 to 7]) and NAVA (6 [5 to 7] and 7 [6 to 8]; P < 0.01 for all comparisons). Regardless of the interface, PSN also decreased EAdipeak (P < 0.01), while increasing PTP of the first 300 ms from the onset of patient effort, indexed to the ideal PTP (P < 0.01) and PTP of the first 500 ms from the onset of patient effort, indexed to the ideal PTP (P < 0.001). ABGs were not different among trials. CONCLUSIONS When delivering noninvasive ventilation by helmet, compared to PSP and NAVA, PSN improves comfort and patient-ventilator interactions, while not ABGs. (Anesthesiology 2016; 125:1181-9).


title: Acute exacerbations of asthma in adults: role of Chlamydia pneumoniae infection.

text: Respiratory infections precipitate wheezing in many asthmatic patients and may be involved in the aetiopathogenesis of asthma. Several studies have demonstrated that viral infections may provoke asthma. Bacterial infections seem to play a minor role. However, Chlamydia pneumoniae has been recently reported as a possible cause of asthma. The aim of the present study was to evaluate the role of C. pneumoniae infection in acute exacerbations of asthma in adults. Seventy four adult out-patients with a diagnosis of acute exacerbation of asthma were studied. Acute and convalescent (> or = 3 weeks) serological determination of antibodies to cytomegalovirus, respiratory syncytial virus, adenovirus, influenza A and B, parainfluenza 1 and 3, Mycoplasma pneumoniae and Legionella pneumophila were performed by means of immunofluorescence tests. C. pneumoniae specific antibodies were detected by two microimmunofluorescence tests using a specific antigen (TW-183) and a kit with three chlamydial antigens. Pharyngeal swab specimens were also obtained for C. pneumoniae identification. Samples for bacterial culture were obtained in patients with productive cough (15 out of 74 patients). Fifteen patients (20%) presented seroconversion to at least one of the studied pathogens. Seven were found to be infected by virus, six by C. pneumoniae alone, and one by M. pneumoniae. One more patient showed seroconversion to C. pneumoniae and cytomegalovirus.(ABSTRACT TRUNCATED AT 250 WORDS)


title: Increasing incidence of Clostridium difficile infection, Australia, 2011-2012.

text: OBJECTIVES To report the quarterly incidence of hospital-identified Clostridium difficile infection (HI-CDI) in Australia, and to estimate the burden ascribed to hospital-associated (HA) and community-associated (CA) infections. DESIGN, SETTING AND PATIENTS Prospective surveillance of all cases of CDI diagnosed in hospital patients from 1 January 2011 to 31 December 2012 in 450 public hospitals in all Australian states and the Australian Capital Territory. All patients admitted to inpatient wards or units in acute public hospitals, including psychiatry, rehabilitation and aged care, were included, as well as those attending emergency departments and outpatient clinics. MAIN OUTCOME MEASURES Incidence of HI-CDI (primary outcome); proportion and incidence of HA-CDI and CA-CDI (secondary outcomes). RESULTS The annual incidence of HI-CDI increased from 3.25/10 000 patient-days (PD) in 2011 to 4.03/10 000 PD in 2012. Poisson regression modelling demonstrated a 29% increase (95% CI, 25% to 34%) per quarter between April and December 2011, with a peak of 4.49/10 000 PD in the October-December quarter. The incidence plateaued in January-March 2012 and then declined by 8% (95% CI, - 11% to - 5%) per quarter to 3.76/10 000 PD in July-September 2012, after which the rate rose again by 11% (95% CI, 4% to 19%) per quarter to 4.09/10 000 PD in October-December 2012. Trends were similar for HA-CDI and CA-CDI. A subgroup analysis determined that 26% of cases were CA-CDI. CONCLUSIONS A significant increase in both HA-CDI and CA-CDI identified through hospital surveillance occurred in Australia during 2011-2012. Studies are required to further characterise the epidemiology of CDI in Australia.


title: Discovery of a novel family of SARS-CoV protease inhibitors by virtual screening and 3D-QSAR studies.

text: The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) 3C-like protease (3CL(pro) or M(pro)) is an attractive target for the development of anti-SARS drugs because of its crucial role in the viral life cycle. In this study, a compound database was screened by the structure-based virtual screening approach to identify initial hits as inhibitors of SARS-CoV 3CL(pro). Out of the 59,363 compounds docked, 93 were selected for the inhibition assay, and 21 showed inhibition against SARS-CoV 3CL(pro) (IC(50) <or= 30 microM), with three of them having common substructures. Furthermore, a search for analogues with common substructure in the Maybridge, ChemBridge, and SPECS_SC databases led to the identification of another 25 compounds that exhibited inhibition against SARS-CoV 3CL(pro) (IC(50) = 3-1,000 microM). These compounds, 28 in total, were subjected to 3D-QSAR studies to elucidate the pharmacophore of SARS-CoV 3CL(pro).


title: First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013.

text: In May 2013, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection was diagnosed in an adult male in France with severe respiratory illness, who had travelled to the United Arab Emirates before symptom onset. Contact tracing identified a secondary case in a patient hospitalised in the same hospital room. No other cases of MERS-CoV infection were identified among the index case’s 123 contacts, nor among 39 contacts of the secondary case, during the 10-day follow-up period.


title: Clinical study on using thermal texture maps in SARS diagnosis.

text: This paper helps define infrared (IR) imaging as a complementary tool to high-speed computer tomography (CT) in the diagnosis of severe acute respiratory syndrome (SARS). We refer to the images captured from IR imaging as thermal texture maps (TTM). Although IR imaging has been criticized of generating high false alarm rate for the lack of quantitative measurement on the size, depth, and shape information of the tumor, we present a new methodology that reveals the depth information and the activity of tumor from processing the surface temperature. The derivation is obtained without solving the ill-posed inverse heat transfer problem. We evaluate the clinical value of TTM in SARS diagnosis and compare the performance with CT. The study took place at Beijing You An Hospital, Beijing, P. R. China. It was conducted on a group of 111 confirmed SARS patients between March 10, 2003 and June 18, 2003. Both CT and TTM are used on the same patient in diagnosis and monitoring. We conclude that TTM is able to depict the position, morphology, and progress of lesions with the same degree of success as CT. The combination of CT and TTM can improve the quality and accuracy of SARS diagnosis.


title: SARS preparedness. Revisiting the procedures to protect staff and help prevent or contain an outbreak.

text: Last year, more than 8,000 people worldwide contracted severe acute respiratory syndrome (SARS), leading to 774 deaths. Although transmission of the disease was quickly controlled, with the outbreak declared over by July, there is concern that SARS could in fact be a seasonal disease and that another outbreak could occur in 2004. In early January, Chinese health officials confirmed the first non-laboratory-related SARS case since the initial outbreak was contained. The threat of another outbreak underscores the importance of having a response plan in place to safeguard the health of your community and your staff. In this article, we discuss the latest information on the risks of acquiring SARS, review recent recommendations from the U.S. Centers for Disease Control and Prevention (CDC), discuss the role of hospital facility and clinical engineers in SARS preparations, and update ECRI's recommendations for infection control procedures during equipment servicing. (ECRI first addressed this issue in two June 2003 Health Devices Guidance Articles.) In two appendixes to the current article, we present CDC guidance on patient isolation in an airborne infection isolation room and offer a navigational guide to CDC's SARS Web site.


title: An outbreak of diarrhea in piglets caused by a coronavirus antigenically distinct from transmissible gastroenteritis virus.

text: Coronavirus-like particles were visualized by electron microscopy in the intestinal contents of piglets during a diarrheal outbreak on a Quebec pig farm. The precipitating antigens of transmissible gastroenteritis virus were not detected in the intestinal contents of diarrheic animals by counter-immunoelectrophoresis. Insignificant antibody titers against transmissible gastroenteritis virus were demonstrated in the sera of convalescent pigs by indirect immunofluorescence and these sera did not react with transmissible gastroenteritis virus when tested by immunoelectron microscopy. The causative agent could not be isolated in cell cultures. It was concluded that a coronavirus antigenically distinct from transmissible gastroenteritis virus was responsible for the enteric problems observed on this farm. The outbreak was controlled after oral inoculation of adult pigs with infected intestinal contents.


Disasters and humanitarian crises: a joint future for responders?


title: Association between adherence to the Mediterranean diet and semen quality parameters in male partners of couples attempting fertility.

text: STUDY QUESTION Is adherence to the Mediterranean diet (MedDiet) associated with better semen quality in men of subfertile couples attempting fertility? SUMMARY ANSWER Greater adherence to the MedDiet, as assessed through the validated Mediterranean diet score (MedDietScore), was significantly associated with higher sperm concentration, total sperm count and sperm motility. WHAT IS KNOWN ALREADY A-posteriori dietary pattern approaches have revealed that dietary patterns characterized by high intakes of fruits, vegetables, whole grains, fish and low intake of meat are associated with better semen quality. Yet, whether adherence to the MedDiet is associated with better semen profile remains largely unexplored. STUDY DESIGN, SIZE, AND DURATION This was a cross-sectional study of 225 men from couples attending a fertility clinic in Athens, Greece, recruited between November 2013 and May 2016. The study was designed to evaluate the influence of habitual dietary intake and lifestyle on fertility outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS Men aged 26-55 years, 51.1% overweight or obese, 20.9% smokers, with complete dietary data were analyzed. Diet was assessed via a food-frequency questionnaire and adherence to the MedDiet was assessed through the MedDietScore (range: 0-55; higher scores indicating greater adherence to MedDiet). Semen quality was evaluated according to World Health Organization 2010 guidelines. Multiple logistic regression analysis was used to evaluate associations between tertiles of the MedDietScore and the likelihood of having abnormal semen parameters, after adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE Compared to men in the highest tertile of the MedDietScore (≥37, N = 66), a higher percentage of men in the lowest tertile of the score (≤30, N = 76) exhibited below the WHO reference values for sperm concentration (47.4% vs 16.7%, P < 0.001), total sperm count (55.3% vs 22.7%, P < 0.001), total motility (65.8% vs 31.8%, P < 0.001), progressive motility (84.2 vs 62.1%, P = 0.011) and sperm morphology (50.0 vs 28.8%, P = 0.023). In the multivariable adjusted models, men in the lowest tertile of the MedDietScore had ~2.6 times higher likelihood of having abnormal sperm concentration, total sperm count and motility, compared to men in the highest tertile of the score. LIMITATIONS, REASONS FOR CAUTION The main limitation of the study stems from its cross-sectional nature, limiting our ability to determine causality. WIDER IMPLICATIONS OF THE FINDINGS The results suggest that greater compliance to the MedDiet may help improve semen quality. Whether this translates into differences in male fertility remains to be elucidated. Our findings are consistent with previous studies showing that dietary patterns with some of the characteristics of the MedDiet, i.e. rich in fruit, vegetables, legumes and whole grains, are associated with better measures of semen quality. STUDY FUNDING/COMPETING INTERESTS No funding was obtained. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER n/a.


title: [A follow up study of total IgM, IgG, nucleoprotein and spike protein antibodies against severe acute respiratory syndrome (SARS) coronavirus in patients with SARS].

text: OBJECTIVE To survey the dynamic changing and persistence of the special antibodies, including total IgM, IgG, nucleocapsid protein and spike protein antibodies, against severe acute respiratory syndrome coronavirus (SARS-CoV) in patients with SARS. METHODS 146 cases, all clinically diagnosed as SARS with positive SARS-CoV IgG, were followed up. 362 serum samples were collected from the onset of the disease to 660 days afterward. Total IgM and IgG against SARS-CoV were tested with commercial ELISA kits. For recombinant nucleoprotein and spike protein, we developed an ELISA to test these two antibodies. RESULTS Within 20 days of the onset, the positive rate of anti-SARS-CoV IgM was 46.5% (20/43); it reached a peak after 21 - 40 days (80.6%, 25/31). Then, the positive rate of IgM went down gradually to 8.2% (6/73) until 550 days after the onset. The patient's IgG positive rate was lower (34.9%, 15/43) than that of IgM within 20 days of the onset. Then it went up rapidly to 100%. It remained positive (98.6%, 70/71) until 600 - 660 days after the onset. When N-IgG and S-IgG were tested 40 days after the onset of the disease at three different times, the positive rate of N-IgG (92.5%, 37/40) was higher than that of S-IgG (67.5%, 27/40), but the two structure protein antibodies were always lower than the total IgG. CONCLUSIONS In SARS patients with definite clinical and etiological diagnosis, the highest positive rate of the antibodies against SARS-CoV was found at 21 - 40 days after the onset. IgM disappeared almost 500 days (91.8%) after the onset. Total IgG positive rate could reach 100% and 98.6% and the positivity might persist nearly two years. So it is speculated that the total IgG antibody may be positive 3 to 5 years after infection, but it seems that N-IgG and S-IgG keep positive shorter in time than total IgG antibody.


title: Isolation of subviral components from transmissible gastroenteritis virus.

text: Exposure of purified transmissible gastroenteritis virus, a porcine coronavirus, to non-ionic detergents resulted in the removal of the surface projections and greater than 98% of the virus lipid. Virus RNA was associated with a subviral particle which had a sedimentation coefficient of 650S, compared with 495S for the intact virion, and which banded in Cs2SO4 gradients at 1-295 g/ml. Negatively stained preparations of subviral particles were shown by electron microscopy to contain spherical particles of 60 to 70 nm diam., similar in appearance to those derived from oncornaviruses. Polyacrylamide gel electrophoresis of the polypeptides from isolated subviral particles showed that these structures contained three of the four major virus structural proteins, the arginine-rich polypeptide VP2 and the two membrane glycopolypeptides VP2 and 4. The detergent-liberated surface projections, composed of a single species of sulphated glycopolypeptide, VPI, were isolated by rate-zonal centrifugation through sucrose gradients followed by precipitation with ammonium sulphate in the presence of bovine serum albumin.


Generation from multiple sclerosis patients of long-term T-cell clones that are activated by both human coronavirus and myelin antigens.


title: Unintentional strangulation deaths from the "choking game" among youths aged 6-19 years--United States, 1995-2007.

text: The "choking game" is defined as self-strangulation or strangulation by another person with the hands or a noose to achieve a brief euphoric state caused by cerebral hypoxia. Participants in this activity typically are youths. Serious neurologic injury or death can result if strangulation is prolonged. In recent years, news media reports have described numerous deaths among youths attributed to the choking game. Because no traditional public health dataset collects mortality data on this practice, CDC used news media reports to estimate the incidence of deaths from the choking game. This report describes the results of that analysis, which identified 82 probable choking-game deaths among youths aged 6-19 years, during 1995-2007. Seventy-one (86.6%) of the decedents were male, and the mean age was 13.3 years. Parents, educators, and health-care providers should become familiar with warning signs that youths are playing the choking game.


title: Assessing the Impact of Frailty on Cognitive Function in Older Adults Receiving Home Care.

text: It is commonly accepted that frailty and dementia-related cognitive decline are strongly associated. However, degree of this association is often debated, especially in homebound elders with disabilities. Therefore, this study aimed to investigate the association of frailty on cognitive function in older adults receiving homecare. A screening for frailty and cognitive function was conducted at 12 primary healthcare settings of the nationally funded program "Help at Home" in Heraklion Crete, Greece. Cognitive function and frailty were assessed using the Montreal Cognitive Assessment questionnaire and the SHARE-f index, respectively. Barthel-Activities of Daily Living and the Charlson Comorbidity Index were also used for the identification of disability and comorbidity, respectively. The mean age of the 192 participants (66% female) was 78.04 ± 8.01 years old. In depth-analysis using multiple linear regression, revealed that frailty was not significantly associated with cognitive decline (frail vs. non-frail (B'=-2.39, p=0.246) even after adjusting for depression and multi-comorbidity. Importantly, as protective factors for cognitive decline progression and thus dementia development, was scientifically correlated with annual individual income >4500 (B'=2.31, p=0.005) -poverty threshold-compared to those with <4500 and, higher education level as compared to Uneducated (B'=2.94, p=0.019). However, depression was associated with cognitive decline regardless of socioeconomic variables. In conclusion, our results suggest that health professionals caring for frail people with cognitive impairment, must focus on early recognition and management of depression.


Improving the medicine administration process by reducing interruptions.


First case of imported and confirmed COVID-19 in Tunisia.


title: Effective Mediastinal Lymphadenectomy for Esophageal Cancer Using Slender Tracheal Forceps in Prone Position Thoracoscopic Esophagectomy.

text: BACKGROUND/AIM Adequate mediastinal lymphadenectomy during thoracoscopic esophagectomy (TE) requires an extensive operating field. In order to rectify this problem, we developed slender tracheal forceps that can pass through a 12-mm trocar. PATIENTS AND METHODS TE in the prone position was performed in 58 patients with esophageal cancer using slender tracheal forceps. Perioperative and postoperative clinical data were compared against those of 61 patients who underwent transthoracic open esophagectomy (OE). RESULTS The mean duration of thoracic manipulation was significantly longer in the TE than OE group: 226.2 versus 171.3 minutes (p<0.0001). Mean blood loss was significantly lower in the TE than OE group: 39.9 versus 176.8 g (p<0.0001). A mean of 23.4 mediastinal lymph nodes were dissected in the TE group and 25.1 in the OE group. The timing of extubation tended to be earlier in the TE group. Postoperative morbidity did not differ between groups. CONCLUSION Slender tracheal forceps are acceptable for fine mediastinal lymphadenectomy in thoracoscopic surgery for esophageal cancer, and the technique could contribute to development of minimally invasive surgery.


title: Role of the endothelium and nitric oxide synthases in modulating superoxide formation induced by endotoxin and cytokines in porcine pulmonary arteries.

text: BACKGROUND The interactive roles of cytokines, endotoxins, superoxide (O(2)(*-) ) and nitric oxide (NO) in the pathogenesis of adult respiratory distress syndrome (ARDS) have not been fully elucidated. The effects of tumour necrosis factor-alpha (TNF-alpha), interleukin 1alpha (IL-1alpha), and lipopolysaccharide (LPS) and the role of NO and the endothelium in mediating O(2)(*-) formation were therefore investigated in intact porcine pulmonary arteries in vitro. METHODS Intrapulmonary artery (PA) segments were obtained from White Landrace pigs (25-35 kg) and incubated with LPS, IL-1alpha, and TNF-alpha and O(2)(*-) release was measured by the superoxide dismutase (SOD) inhibitable reduction of ferricytochrome c. The source of O(2)(*-) formation was determined using a number of enzyme inhibitors. The role of NO was explored using NO synthase (NOS) inhibitors and the distribution of NOS isoforms and peroxynitrite (ONOO(-), an index of NO-O(2)(*-) interactions) assessed by immunocytochemistry. RESULTS LPS, IL-1alpha, and TNF-alpha promoted the formation of O(2)(*-) from PA compared with untreated controls in a time and dose dependent manner, an effect markedly enhanced by removal of the endothelium but completely inhibited by the NADPH oxidase inhibitor diphenylene iodonium chloride (DPI). L-NAME and the eNOS inhibitor N(5)-(1-iminoethyl)-ornithine (L-NIO) enhanced O(2)(*-) formation from PA (with endothelium) in response to IL-1alpha and TNF-alpha but had no effect on LPS mediated O(2)(*-) formation, whereas L-NAME and the iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine-HCl (L-NIL) enhanced O(2)(*-) formation only in response to LPS. CONCLUSIONS LPS, IL-1alpha, and TNF-alpha promote O(2)(*-) formation through an upregulation of NADPH oxidase activity which is augmented by removal of the endothelium, as well as the inhibition of eNOS (in the case of cytokines) and iNOS (in the case of LPS). The concomitant expression of NOS isoforms (and NO formation) with that of NADPH oxidase may therefore constitute a protective system designed to remove O(2)(*-) through the formation of ONOO(-). If this is so, the integrity of the endothelium may be axiomatic in the progression and severity of ARDS.


title: [Health crisis and suicidal crisis: mirrored lighting].

text: The psychotherapeutic management of a suicidal crisis makes it possible to think of the health crisis linked to COVID-19 from a particular angle. In this article, we show the parallels but also the differences between these two types of crises. The sequential course of the crisis, the viral agent which acts as a triggering factor and the host of reactions which follow can thus evoke a suicidal crisis during which a subject often perceives an external event as a precipitating factor. However, unlike confinement in the case of the virus, it is the relationship, in particular the therapeutic relationship, which makes it possible to get through the crisis. This relationship should allow us to get to know our specific vulnerabilities, those on which the triggering factor has specifically acted.


title: Infectious bronchitis virus 3a protein localizes to a novel domain of the smooth endoplasmic reticulum.

text: All coronaviruses possess small open reading frames (ORFs) between structural genes that have been hypothesized to play important roles in pathogenesis. Infectious bronchitis virus (IBV) ORF 3a is one such gene. It is highly conserved among group 3 coronaviruses, suggesting that it has an important function in infection. IBV 3a protein is expressed in infected cells but is not detected in virions. Sequence analysis predicted that IBV 3a was a membrane protein; however, only a fraction behaved like an integral membrane protein. Microscopy and immunoprecipitation studies demonstrated that IBV 3a localized to the cytoplasm in a diffuse pattern as well as in sharp puncta in both infected and transfected cells. These puncta did not overlap cellular organelles or other punctate structures. Confocal microscopy demonstrated that IBV 3a puncta lined up along smooth endoplasmic reticulum (ER) tubules and, in a significant number of instances, were partially surrounded by these tubules. Our results suggest that IBV 3a is partially targeted to a novel domain of the smooth ER.


title: Acute Vision Loss in a Patient with COVID-19.

text: To date, there have been reports of neurologic manifestations in COVID-19 patients including ischemic strokes, Guillain-Barre Syndrome and anosmia. In this case report, we describe a patient who presented with dysosmia, dysgeusia, along with monocular peripheral vision loss after being diagnosed with COVID-19.


title: Identification of an antigenic determinant on the S2 domain of the severe acute respiratory syndrome coronavirus spike glycoprotein capable of inducing neutralizing antibodies.

text: Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by a newly identified coronavirus (CoV), SARS-CoV. The spike (S) glycoprotein of CoV is the major structural protein responsible for induction of host immune response and virus neutralization by antibodies. Hence, knowledge of neutralization determinants on the S protein is helpful for designing protective vaccines. To analyze the antigenic structure of the SARS-CoV S2 domain, the carboxyl-terminal half of the S protein, we first used sera from convalescent SARS patients to test the antigenicity of 12 overlapping fragments spanning the entire S2 and identified two antigenic determinants (Leu 803 to Ala 828 and Pro 1061 to Ser 1093). To determine whether neutralizing antibodies can be elicited by these two determinants, we immunized animals and found that both of them could induce the S2-specific antisera. In some animals, however, only one determinant (Leu 803 to Ala 828) was able to induce the antisera with the binding ability to the native S protein and the neutralizing activity to the SARS-CoV pseudovirus. This determinant is highly conserved across different SARS-CoV isolates. Identification of a conserved antigenic determinant on the S2 domain of the SARS-CoV S protein, which has the potential for inducing neutralizing antibodies, has implications in the development of effective vaccines against SARS-CoV.


title: Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs.

text: The etiology of nosocomial infections, the frequency of contaminated hands with the different nosocomial pathogens, and the role of health care workers' hands during outbreaks suggest that a hand hygiene preparation should at least have activity against bacteria, yeasts, and coated viruses. The importance of efficacy in choosing the right hand hygiene product is reflected in the new Centers for Disease Control and Prevention guideline on hand hygiene (J. M. Boyce and D. Pittet, Morb. Mortal. Wkly. Rep. 51:1-45, 2002). The best antimicrobial efficacy can be achieved with ethanol (60 to 85%), isopropanol (60 to 80%), and n-propanol (60 to 80%). The activity is broad and immediate. Ethanol at high concentrations (e.g., 95%) is the most effective treatment against naked viruses, whereas n-propanol seems to be more effective against the resident bacterial flora. The combination of alcohols may have a synergistic effect. The antimicrobial efficacy of chlorhexidine (2 to 4%) and triclosan (1 to 2%) is both lower and slower. Additionally, both agents have a risk of bacterial resistance, which is higher for chlorhexidine than triclosan. Their activity is often supported by the mechanical removal of pathogens during hand washing. Taking the antimicrobial efficacy and the mechanical removal together, they are still less effective than the alcohols. Plain soap and water has the lowest efficacy of all. In the new Centers for Disease Control and Prevention guideline, promotion of alcohol-based hand rubs containing various emollients instead of irritating soaps and detergents is one strategy to reduce skin damage, dryness, and irritation. Irritant contact dermatitis is highest with preparations containing 4% chlorhexidine gluconate, less frequent with nonantimicrobial soaps and preparations containing lower concentrations of chlorhexidine gluconate, and lowest with well-formulated alcohol-based hand rubs containing emollients and other skin conditioners. Too few published data from comparative trials are available to reliably rank triclosan. Personnel should be reminded that it is neither necessary nor recommended to routinely wash hands after each application of an alcohol-based hand rub. Long-lasting improvement of compliance with hand hygiene protocols can be successful if an effective and accessible alcohol-based hand rub with a proven dermal tolerance and an excellent user acceptability is supplied, accompanied by education of health care workers and promotion of the use of the product.


title: Nosocomial pulmonary infections in HIV-positive patients.

text: PURPOSE OF REVIEW Nosocomial infections (NI) constitute a significant public health problem and contribute to prolonged hospitalization, additional healthcare costs, and excess morbidity and mortality. Immunocompromised patients, including HIV-infected individuals, are at increased risk for NI, and 15-18.3% of them are represented by lower respiratory tract infections. Nosocomial pulmonary infections (NPI) appear to be more common in patients with acquired immunodeficiency syndrome (AIDS), as a result of the degree of immunosuppression, prior use of antibiotics, and exposure to invasive procedures. RECENT FINDINGS This article reviews the epidemiologic and clinical evidences and reports on the occurrence of NPI in HIV-infected inpatients. SUMMARY Although underestimated, NI occur commonly in HIV-infected patients, and among them nosocomial pneumonia, including tuberculosis and bacterial pneumonia, are associated with significant morbidity and mortality. The improvement of antiretroviral therapeutic options in developed countries has resulted in a decreased hospitalization rate of HIV-infected individuals. Healthcare delivery in the in- and outpatient setting represents a potential for infections, including lower respiratory tract ones, according to the degree of immunosuppression and the intensity of invasive procedures. To minimize the risk of acquisition of healthcare associated low respiratory tract infections, adherence of healthcare workers to common infection practices, specific respiratory precautions, and early identification of persons who have tuberculosis or are at high risk for active tuberculosis, should be strengthened.


title: Demonstration of 7-nm projections on human and avian coronaviruses.

text: Direct electron microscopy (EM) of human coronavirus (HCV) strain OC43 and avian infectious bronchitis virus (IBV) strain F revealed particles with small granular projections about 7 nm in size in addition to the characteristic coronavirus particles with projections of 20 nm. Relationship of the short fringed form to the conventional coronavirus particle is established by ordinary immune electron microscopy (IEM) and immunosorbent electron microscopy (ISEM).


title: Telemedicine with clinical decision support for critical care: a systematic review.

text: BACKGROUND Telemedicine applications aim to address variance in clinical outcomes and increase access to specialist expertise. Despite widespread implementation, there is little robust evidence about cost-effectiveness, clinical benefits, and impact on quality and safety of critical care telemedicine. The primary objective was to determine the impact of critical care telemedicine (with clinical decision support available 24/7) on intensive care unit (ICU) and hospital mortality and length of stay in adults and children. The secondary objectives included staff and patient experience, costs, protocol adherence, and adverse events. METHODS Data sources included MEDLINE, EMBASE, CINAHL, Cochrane Library databases, Health Technology Assessment Database, Web of Science, OpenGrey, OpenDOAR, and the HMIC through to December 2015. Randomised controlled trials and quasi-experimental studies were eligible for inclusion. Eligible studies reported on differences between groups using the telemedicine intervention and standard care. Two review authors screened abstracts and assessed potentially eligible studies using Cochrane guidance. RESULTS Two controlled before-after studies met the inclusion criteria. Both were assessed as high risk of bias. Meta-analysis was not possible as we were unable to disaggregate data between the two studies. One study used a non-randomised stepped-wedge design in seven ICUs. Hospital mortality was the primary outcome which showed a reduction from 13.6 % (CI, 11.9-15.4 %) to 11.8 % (CI, 10.9-12.8 %) during the intervention period with an adjusted odds ratio (OR) of 0.40 (95 % CI, 0.31-0.52; p = .005). The second study used a non-randomised, unblinded, pre-/post-assessment of telemedicine interventions in 56 adult ICUs. Hospital mortality (primary outcome) reduced from 11 to 10 % (adjusted hazard ratio (HR) = 0.84; CI, 0.78-0.89; p = <.001). CONCLUSIONS This review highlights the poor methodological quality of most studies investigating critical care telemedicine. The results of the two included studies showed a reduction in hospital mortality in patients receiving the intervention. Further multi-site randomised controlled trials or quasi-experimental studies with accompanying process evaluations are urgently needed to determine effectiveness, implementation, and associated costs. TRIAL REGISTRATION PROSPERO CRD42014007406.


title: Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study.

text: We assessed late mortality in 854 individuals who had survived 2 or more years after autologous hematopoietic cell transplantation (HCT) for hematologic malignancies. Median age at HCT was 36.5 years, and median length of follow-up was 7.6 years. Overall survival was 68.8% +/- 1.8% at 10 years, and the cohort was at a 13-fold increased risk for late death (standardized mortality ratio [SMR] = 13.0) when compared with the general population. Mortality rates approached those of the general population after 10 years among patients at standard risk for relapse at HCT (SMR = 1.1) and in patients undergoing transplantation for acute myeloid leukemia (AML; SMR = 0.9). Relapse of primary disease (56%) and subsequent malignancies (25%) were leading causes of late death. Relapse-related mortality was increased among patients with Hodgkin disease (HD; relative risk [RR] = 3.6), non-Hodgkin lymphoma (NHL; RR = 2.1), and acute lymphoblastic leukemia (ALL; RR = 6.5). Total body irradiation (RR = 0.6) provided a protective effect. Nonrelapse-related mortality was increased after carmustine (RR = 2.3) and with use of peripheral blood stem cells (RR = 2.4). Survivors were more likely to report difficulty in holding jobs (RR = 9.4) and in obtaining health (RR = 7.7) or life insurance (RR = 8.4) when compared with siblings. Although mortality rates approach that of the general population after 10 years in certain subgroups, long-term survivors of autologous HCT continue to face challenges affecting their health and well-being.


Why SARS will not return: a polemic.


title: Thoracoscopic segmentectomy with intraoperative evaluation of sentinel nodes for stage I non-small cell lung cancer.

text: OBJECTIVES Segmentectomy is the treatment of choice for small-sized non-small cell lung cancer (NSCLC); however, it is difficult to decide the surgical procedure because accurate evaluation of hilar lymph node metastasis remains unclear. We here report the outcome of video-assisted thoracic surgery (VATS) segmentectomy with and without the assessment of sentinel nodes. MATERIALS AND METHODS Eighty-three patients with stage IA NSCLC underwent VATS segmentectomy between January 2003 and December 2010. Twenty patients underwent indocyanine green fluorescence imaging for sentinel node biopsy (SNB) and 63 did not. Intraoperative real-time quantitative RT-PCR to determine the expression of CK-19 was used for evaluation of metastasis. Perioperative outcome, local recurrence rates and survival were compared in both groups. RESULTS Sentinel lymph nodes were identified in 16 of 20 patients (80%) with segmentectomy in the SNB group. The false negative rate was 0%. By RT-PCR for CK-19 expression, only one of these patients showed positive sentinel nodes, which indicated isolated tumor cells; however, segmentectomy was not converted to lobectomy. Seven of 63 patients with VATS segementectomy without SNB and none of the SNB group relapsed. In the relapsed patients without SNB, 4 (6.3%) were local recurrences and 3 (4.7%) were distant metastases. Recurrence-free survival rates in both groups were not significantly different because of the short follow-up period of the SNB group. CONCLUSIONS Our study demonstrated that VATS segmentectomy with SNB was useful for deciding intraoperatively to perform segmentectomy with an accurate lymph node status.


title: Formation of plant RNA virus replication complexes on membranes: role of an endoplasmic reticulum-targeted viral protein.

text: The mechanisms that direct positive-stranded RNA virus replication complexes to plant and animal cellular membranes are poorly understood. We describe a specific interaction between a replication protein of an RNA plant virus and membranes in vitro and in live cells. The tobacco etch virus (TEV) 6 kDa protein associated with membranes as an integral protein via a central 19 amino acid hydrophobic domain. In the presence or absence of other viral proteins, fluorescent fusion proteins containing the 6 kDa protein associated with large vesicular compartments derived from the endoplasmic reticulum (ER). Infection by TEV was associated with a collapse of the ER network into a series of discrete aggregated structures. Viral RNA replication complexes from infected cells were also associated with ER-like membranes. Targeting of TEV RNA replication complexes to membranous sites of replication is proposed to involve post-translational interactions between the 6 kDa protein and the ER.


Despite doubts, containment plans for pandemic take shape.


Viewpoint: Pacific Voyages - Ships - Pacific Communities: A Framework for COVID-19 Prevention and Control.


title: An immunoturbidimetric assay for rapid quantitative measurement of feline alpha-1-acid glycoprotein in serum and peritoneal fluid.

text: BACKGROUND Alpha-1-acid glycoprotein (AGP) is an acute phase protein that increases in concentration in infectious and inflammatory conditions. The serum and peritoneal fluid concentrations of AGP may be useful in the diagnosis of feline infectious peritonitis (FIP), a lethal disease of cats. Currently AGP can be measured by radioimmunodiffusion (RID) assays, which are time consuming and difficult. OBJECTIVES The objectives of this study were to develop a rapid immunoturbidimetric assay for measurement of AGP in feline serum and peritoneal fluid and to compare the results with those obtained by RID. METHODS AGP was purified by perchloric acid precipitation and ion-exchange chromatography from a pool of peritoneal fluid obtained from cats with FIP, as determined by a panel of laboratory tests, including serum AGP concentration, albumin: globulin ratio, and total protein concentration, anti-coronavirus antibody titers, and effusion analysis. The purified AGP in a complete Freund's adjuvant and Tween 20 mixture was injected into a sheep and blood was collected at monthly intervals. Anti-AGP antiserum, as confirmed by ELISA and Western blot techniques, and a pool of peritoneal fluid from cats with FIP were used to prepare standards. Clinical samples of feline peritoneal fluid (n=55) and serum (n=59) were assayed for AGP and results from the immunoturbidimetric and RID methods were compared. RESULTS Significant correlation (P < .001) was obtained between methods for both peritoneal fluid (R2=.9259) and serum (R2=.9448) samples. Coefficients of variation for the immunoturbidimetric method were <5%. CONCLUSIONS This rapid immunoturbidimetric assay for measurement of feline AGP in serum and peritoneal fluid may be of value in the diagnosis of FIP and possibly other inflammatory diseases in cats.


Tackling infectious diseases threats in the Asia-Pacific through regional and international collaboration.


title: Depletion of blood-borne macrophages does not reduce demyelination in mice infected with a neurotropic coronavirus.

text: Mice infected with the neurotropic coronavirus mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating disease with symptoms of hindlimb paralysis. Histological examination of the brains and spinal cords of these animals reveals the presence of large numbers of activated macrophages/microglia. In two other experimental models of demyelination, experimental allergic encephalomyelitis and Theiler's murine encephalomyelitis virus-induced demyelination, depletion of hematogenous macrophages abrogates the demyelinating process. In both of these diseases, early events in the demyelinating process are inhibited by macrophage depletion. From these studies, it was not possible to determine whether infiltrating macrophages were required for late steps in the process, such as myelin removal. In this study, we show that when macrophages are depleted with either unmodified or mannosylated liposomes encapsulating dichloromethylene diphosphate, the amount of demyelination detected in MHV-infected mice is not affected. At a time when these cells were completely depleted from the liver, approximately equivalent numbers of macrophages were present in the spinal cords of control and drug-treated animals. These results suggest that blood-borne macrophages are not required for MHV-induced demyelination and also suggest that other cells, such as perivascular macrophages or microglia, perform the function of these cells in the presence of drug.


title: RNAi and miRNA in viral infections and cancers.

text: Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.


title: Pulmonary sequelae in convalescent patients after severe acute respiratory syndrome: evaluation with thin-section CT.

text: PURPOSE To prospectively evaluate lung parenchyma on paired inspiration-expiration thin-section computed tomographic (CT) scans in patients recovering from severe acute respiratory syndrome (SARS). MATERIALS AND METHODS After the institutional review board approved the study and written consent was obtained from patients, 40 patients (25 female, 15 male; mean age, 42.8 years +/- 12.3 [standard deviation]) underwent thin-section CT at 51.8 days +/- 20.2 after onset of SARS symptoms. Twenty of the 40 patients underwent follow-up thin-section CT at 140.7 days +/- 26.7 after symptom onset. Lung findings were scored according to extent and then grouped in three categories (ground-glass opacity, interstitial opacity, and air trapping) for analysis. Mean CT scores for each finding in the various patient subgroups were compared by using the Mann-Whitney test. Clinical parameters and scores were evaluated for correlation by using Spearman rank correlation analysis. Mean scores for each finding were compared between the two serial examinations by using the Wilcoxon matched-pairs signed rank test. RESULTS Air trapping, ground-glass opacity, and reticulation were found in 37 (92%), 36 (90%), and 28 (70%) of 40 patients, respectively, at initial thin-section CT examination and in 16 (80%), 14 (70%), and 10 (50%) of 20 patients, respectively, at follow-up examination. Scans from patients with adult respiratory distress syndrome (ARDS) had a significantly higher score for ground-glass opacity than did those from patients without ARDS (P = .009). A comparison of scores for the serial thin-section CT examinations indicated a significant reduction in the extent of ground-glass opacity (P < .001) and interstitial opacity (P < .001) but not in that of air trapping (P = .38) at follow-up examination. At initial thin-section CT, scores for ground-glass opacity, interstitial opacity, and air trapping correlated with age; those for ground-glass opacity and air trapping, with peak C-reactive protein level. At the second examination, scores for ground-glass opacity and interstitial opacity correlated with peak lactate dehydrogenase level; that for air trapping, with age and peak C-reactive protein level. CONCLUSION Thin-section CT scores correlated with clinical and laboratory parameters in patients after SARS. Although ground-glass opacity and interstitial opacity resolve over time, air trapping persists.


From national to international--challenges in cross-border multi-country, multi-vehicle foodborne outbreak investigations.


title: Crystal structure of infectious bursal disease virus VP2 subviral particle at 2.6A resolution: implications in virion assembly and immunogenicity.

text: The structural protein VP2 of infectious bursal disease virus (IBDV) spontaneously forms a dodecahedral T=1 subviral particle (SVP), and is a primary immunogen of the virus. In this study, the structure of IBDV SVP was determined in a cubic crystal and refined to 2.6A resolution. It contains 20 independent VP2 subunits in a crystallographic asymmetric unit. Each subunit is folded mainly into a shell domain and a protrusion domain, both with the Swiss-roll topology, plus a small helical base domain. Three VP2 subunits constitute a tight trimer, which is the building block of IBDV (sub)viral particles. The structure revealed a calcium ion bound to three pairs of symmetry-related Asp31 and Asp174 to stabilize the VP2 trimer. Our results of treatment of SVP with EGTA, a Ca(2+)-chelating reagent, indicated that the metal-ion may be important not only in maintaining highly stable quaternary structure but also in regulating the swelling and dissociation of the icosahedral particles. A Ca(2+)-dependent assembly pathway was thus proposed, which involves further interactions between the trimers. The 20 independent subunits showed conformational variations, with the surface loops of the protrusion domain being the most diverse. These loops are targets of the neutralizing antibodies. Several common interactions between the surface loops were clearly observed, suggesting a possible major conformation of the immunogenic epitopes.


Canine fatalities associated with the use of a modified live vaccine administered during late stages of pregnancy.


title: Serologic survey and serum biochemical reference ranges of the free-ranging mountain lion (Felis concolor) in California.

text: Serum samples from 58 mountain lions (Felis concolor) in California (USA) were collected between April 1987 and February 1990. Nineteen serum samples were used for serum biochemistry determinations; the ranges were similar to reference values in domestic cats, captive exotic felidae and free-ranging mountain lions. A serological survey was conducted to determine whether antibodies were present against selected infectious agents. Fifty-four (93%) of 58 sera had antibodies against feline panleukopenia virus. Fifteen (68%) of 22, 16 (28%) of 58, 11 (19%) of 58, and 10 (17%) of 58 had serum antibodies against feline reovirus, feline coronavirus, feline herpes virus, and feline calicivirus, respectively. Twenty-three (40%) of 58 and 21 (58%) of 36 had serum antibodies against Yersinia pestis and Toxoplasma gondii, respectively. Only one of 22 sera had antibodies against the somatic antigen of Dirofilaria immitis. Feline leukemia virus and feline immunodeficiency virus antigens were not detected in any mountain lion's sera. All 58 sera samples were negative for antibodies to feline immunodeficiency virus and Chlamydia psittaci.


title: Zanamivir: an influenza virus neuraminidase inhibitor.

text: Zanamivir is the first of two registered neuraminidase inhibitors for the treatment and prophylaxis of influenza. Relenza, an orally inhaled powder form of zanamivir, is currently approved in 19 countries for treatment, and in two for prophylaxis. Relenza reduces the time to alleviation of symptoms by 1 to 2 days in the influenza-positive population, if taken within 48 h of symptom onset, and in prophylaxis in family settings, it confers an 80% reduction in the odds of contracting influenza. The resistance profile of zanamivir is encouraging in the sense that there are still no reports of patients on acute therapy shedding drug-resistant virus. However, patient uptake of the inhaled drug has been insufficient to conclude that drug resistance will not be an issue in the future. All zanamivir-resistant variants selected in the laboratory so far have diminished viability.


title: The influence of a sense of time on human development.

text: The subjective sense of future time plays an essential role in human motivation. Gradually, time left becomes a better predictor than chronological age for a range of cognitive, emotional, and motivational variables. Socioemotional selectivity theory maintains that constraints on time horizons shift motivational priorities in such a way that the regulation of emotional states becomes more important than other types of goals. This motivational shift occurs with age but also appears in other contexts (for example, geographical relocations, illnesses, and war) that limit subjective future time.


title: An immunofluorescence test for detection of serum antibody to rodent coronaviruses.

text: An indirect immunofluorescence test, using cultured cells infected with two strains of mouse hepatitis virus, was developed for detection of antibody to rodent coronaviruses. The immunofluorescence test detected serum antibody to mouse hepatitis virus and rat sialodacryoadenitis virus earlier than the neutralization test. In the case of mouse hepatitis virus, the results of the immunofluorescence test closely paralleled those obtained with a commercially available enzyme-linked immunosorbent assay.


title: Structural aspects of recently discovered viral deubiquitinating activities.

text: Protein ubiquitination has been identified as a regulatory mechanism in key cellular activities, and deubiquitination is recognized as an important step in processes governed by ubiquitin and ubiquitin-like modifiers. Viruses are known to target ubiquitin and ubiquitin-like modifier pathways using various strategies, including the recruitment of host deubiquitinating enzymes. Deubiquitinating activities have recently been described for proteins from three different virus families (adenovirus, coronavirus and herpesvirus), and predicted for others. This review centers on structural-functional aspects that characterize the confirmed viral deubiquitinating enzymes, and their relationships to established families of cellular deubiquitinating enzymes.


title: Surgical results of the Hypoglossal-Facial nerve Jump Graft technique.

text: BACKGROUND The Hypoglossal-Facial nerve crossover has appeared as a surgical option for those scenarios where the facial nerve is injured in its intracranial course, but the conventional technique unequivocally leads to twelfth cranial nerve deficit. In recent years a number of different surgical approaches have been introduced with a view to avoiding the complete section of the hypoglossal nerve, such as the Jump Graft technique. This paper aims to present the results of the Hypoglossal-Facial nerve Jump Graft technique in relation to facial musculature reanimation capability and hemitongue function preservation. METHODS A retrospective analysis of the records of eight patients submitted to Hypoglossal-Facial nerve Jump Graft technique was performed. The surgical approach was characterised by the interposition of a short graft sutured to the distal stump of the transected facial nerve and sutured end-to-side to the hypoglossi, with cutting of only a third of the diameter of the latter. FINDINGS The facial nerve injuries were secondary to temporal bone trauma in five cases and to cerebellopontine angle tumour surgery in three. Grafts were harvested from the greater auricular nerve in six patients and from the sural nerve in two. The results of facial reanimation demonstrated facial symmetry and improvement in the facial tone in all cases, and classified as House-Brackmann grade IV in three (37.5%) and grade III in five (62.5%) patients. There was no incidence of definitive hemitongue atrophy and no patient complaint of swallowing or speech difficulty. CONCLUSIONS The modification of the conventional technique of Hypoglossal-Facial nerve anastomosis by means of sectioning one third of the hypoglossal nerve area does not lead to dysfunction of this nerve and the surgical results in terms of facial reanimation are satisfactory.


title: Review of infectious bronchitis virus around the world.

text: Infectious bronchitis virus (IBV) is a gamma coronavirus that causes a highly contagious disease in chickens. The virus can affect the upper respiratory tract and the reproductive tract, and some strains can cause a nephritis. Different serotypes and genetic types of the virus have been identified worldwide and for the most part do not cross-protect. In addition, new types of the virus continue to arise due to mutations and recombination events in the viral genome, making this virus difficult to identify and extremely difficult to control. Surveillance and identification of IBV types is extremely important for control of the disease and the advancement of molecular methods have aided in this pursuit. Genetic typing of IBV, which involves reverse transcription-PCR amplification and sequence analysis of the S1 glycoprotein gene, has revolutionized diagnosis and identification of this virus by making it possible to type and compare the relatedness of a large number of virus isolates in a short period of time. The purpose of this review is to give an update on the strains of IBV currently circulating in commercial chickens worldwide and hopefully to present a clear picture of the relationship between many of these viruses. The information on IBV types presented herein is from published manuscripts, submissions to GenBank, our own unpublished data, and personal communications with scientists and diagnosticians working with IBV worldwide.


title: Absence of N-linked glycans from the F2 subunit of the major baculovirus envelope fusion protein F enhances fusogenicity.

text: The F protein is the major glycoprotein present in the envelopes of budded virus (BV) of members of the family Baculoviridae. The F protein mediates low-pH-activated fusion with insect cell membranes. Baculovirus F proteins are synthesized as a precursor (F(0)) and cleaved post-translationally into two disulfide-bonded subunits, F(1) (C-terminal, large subunit) and F(2) (N-terminal, small subunit). Recently, N-linked glycosylation of the F(1) and F(2) subunits of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) was demonstrated [Long, G., Westenberg, M., Wang, H., Vlak, J. M. & Hu, Z. (2006). J Gen Virol 87, 839-846]. Sequence analysis frequently predicts that one or more N-linked glycosylation sites are present in the F(2) subunit of baculovirus F proteins. N-glycans on envelope fusion proteins are usually required for proper conformational integrity and biological function, such as infectivity. This study examined the importance of N-linked glycosylation of the F(2) subunit of HearNPV by site-directed mutagenesis. The only putative N-linked glycosylation site in F(2) was eliminated by mutating asparagine (N(104)) to glutamine (Q), resulting in the mutant HearNPV(fN104Q). When inserted into an f-null HearNPV and a gp64-null bacmid of Autographa californica multiple nucleopolyhedrovirus, infectious BV could be retrieved that contained unglycosylated F(2). The virulence of HearNPV(fN104Q) was enhanced, as BV was produced earlier after infection and yielded larger plaques than f-null HearNPV repaired with the wild-type f gene. HearNPV(fN104Q) BV also induced much more efficient low-pH-activated syncytium formation. These results indicate that N-linked glycosylation of the HearNPV baculovirus F(2) subunit is not essential for viral infectivity and suggest that it is involved in BV production and fusogenicity.


title: Needs assessment of persons with multiple sclerosis and significant others: using the literature review and focus groups for preliminary survey questionnaire development.

text: The purpose of this study was to conduct focus group interviews to obtain information for development of a needs assessment questionnaire. Four focus groups were conducted with 10 people with multiple sclerosis (MS) and five significant others. A facilitator from the learning services department at the hospital conducted the interviews guided by questions developed by the researcher. The focus group interviews were audiotaped and transcribed. The researcher analyzed the transcribed interviews. Content analysis was used to analyze the transcribed data creating categories from key words and phrases as they appeared. The findings were grouped by themes. The results highlighted the participants' experiences and needs regarding physical changes; sources of assistance; unmet needs; psychological, employment, leisure, and informational needs. A comparison of themes developed from the focus groups and in the literature captured categories for questionnaire development. One new theme, leisure, was not found in the literature and was incorporated based on the findings of this study. The final categories for questionnaire development were: physical, health, psychological, financial, employment/meaningful daytime activity and leisure, accessibility and information. A survey questionnaire was developed from the focus group data using the phraseology of the participants.


title: Temporal dissection of p53 function in vitro and in vivo.

text: To investigate the functions of the p53 tumor suppressor, we created a new knock-in gene replacement mouse model in which the endogenous Trp53 gene is substituted by one encoding p53ER(TAM), a p53 fusion protein whose function is completely dependent on ectopic provision of 4-hydroxytamoxifen. We show here that both tissues in vivo and cells in vitro derived from such mice can be rapidly toggled between wild-type and p53 knockout states. Using this rapid perturbation model, we define the kinetics, dependence, persistence and reversibility of p53-mediated responses to DNA damage in tissues in vivo and to activation of the Ras oncoprotein and stress in vitro. This is the first example to our knowledge of a new class of genetic model that allows the specific, rapid and reversible perturbation of the function of a single endogenous gene in vivo.


title: Radiology of severe acute respiratory syndrome (SARS): the emerging pathologic-radiologic correlates of an emerging disease.

text: Severe acute respiratory distress syndrome (SARS) caused by SARS-associated coronavirus (SARS-CoV) is a systemic infection that clinically manifests as progressive pneumonia. During the initial phases of infection the virus causes pauci-inflammatory alveolar and interstitial edema that result in imaging abnormalities dominated by ground glass opacities (GGO). Severe SARS cases can develop radiologic and pathologic findings of diffuse alveolar damage. Although radiologic evidence of acute bronchiolitis is absent, SARS-CoV also infects ciliated airway epithelium, probably accounting for respiratory transmissibility of the virus. Radiologic recovery from SARS can be complete, but computed tomography images often show persistent GGO and reticular opacities, some of which reflect pathologic findings of fibrosis. Long-term follow-up imaging of survivors shows gradual decrease of GGO and reticulation with persistent air trapping in some patients. The latter is evidence of small airway disease that is not radiologically evident at the onset of the disease.


title: The Spatial Dynamics of Poliomyelitis in the United States: From Epidemic Emergence to Vaccine-Induced Retreat, 1910-1971.

text: This article seeks to advance an understanding of the spatial dynamics of one of the great emergent viral diseases of the twentieth century-poliomyelitis. From an apparently rare clinical condition occurring only sporadically or in small outbreaks before the late nineteenth century, poliomyelitis had, by the early 1950s, developed into a globally distributed epidemic disease. But, from 1955, continued growth was suddenly and dramatically reversed by the mass administration of inactivated (killed) and live (attenuated) poliovirus vaccines. After almost half a century of vaccine control, the world now stands on the brink of the global eradication of the disease. Against this background, the article draws upon information included in the U.S. Public Health Service's Public Health Reports and the U.S. Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Report to examine the spatial dynamics of poliomyelitis during the phases of epidemic emergence (1910-1955) and vaccine-induced retreat (1955-1971) in the United States. It is shown that epidemic emergence was accompanied by shifts in the spatial center of activity from early diffusion poles in the northeastern states, to the western seaboard, and then finally to cover all the states of the Union. This was accompanied by accelerating epidemic propagation. The introduction of mass vaccination from the mid-1950s realigned spatial transmission of the disease, producing increased spatial volatility in the geographical center of activity and heightened dependence of epidemic outbreaks upon endemic reservoirs in the most populous states. Finally, the empirical results are generalized to suggest that the emergence and reemergence of many infectious diseases is a distinctively geographical process.


title: [Epidemiologic studies of the detection of viral infection agents in calf losses in the Weser-Ems region].

text: In 961 calves up to an age of 6 months which were sent to the animal health center in Oldenburg between March 1987 and March 1990 for necropsy the results of determination of different viruses were calculated: BVD-, rota-, corona-, parainfluenza-3- (PI-3)-, bovine herpes-1 (BHV-1)- and bovine respiratory syncytial virus (BRSV). In 122 and 104 randomly collected health calves of 22 farms antibodies against BRSV and bovine adeno virus-types 5, 7 and 8 were determined. 50.1% of the necropsied calves were one and two weeks old. In this group in 40.2% rotavirus and in 19.0% coronavirus could be isolated. All over the calves the frequencies of isolated viruses were 13.3% for BVDV, 4.6% for BRSV, 3.2% for BHV-1, and 2.1% for PI-3. The percentages of positive findings for rota- and coronavirus increased up to 7 days after birth, and thereafter both decreased. The frequencies of BVDV and BRSV were higher in older groups. The frequency of PI-3 was low and remained constantly. Infections with rota-, corona- and with both viruses were accompanied by BVDV in 11.3, 5.3 and 14.3%, respectively. Against bovine adenoviruses and BRSV in the first 8 weeks and after 14 weeks of life in more than 70% of the calves antibodies were detected.


title: SARS: current overview, aetiology and epidemiology.

text: At this moment, public health authorities, physicians and scientists around the world are struggling to cope with a severe and rapidly spreading new disease in humans called severe acute respiratory syndrome, or SARS. According to World Health Organisation (WHO) this appears to be the first severe and easily transmissible new disease to emerge in the 21st century. Though much about the disease remains poorly understood, including the details of the causative virus, we do know that it has features that allow it to spread rapidly along international air travel routes. As of 10 May 2003, a cumulative 7296 probable SARS cases with 526 deaths have been reported from 30 countries on three continents (WHO, ProMED). In the past week, more than 1000 new probable cases and 96 deaths were reported globally. This represents an increase of 119 new cases and 8 new deaths compared with 9 May 2003 (China (85), Taiwan (23), and Hong Kong (7) represented the overwhelming majority, with one additional case each reported from France, Malaysia, Singapore, and the United States). Only in China, as of 10 May 2003 (WHO) total of 4884 with 235 deaths have been reported. Some outbreaks have reassuring features.


title: The SARS-like coronaviruses: the role of bats and evolutionary relationships with SARS coronavirus.

text: Bats represent an order of great evolutionary success, with elevated geographical diffusion and species diversity. This order harbors viruses of high variability which have a great possibility of acquiring the capacity of infecting other animals,including humans. Bats are the natural reservoir for several viruses genetically closely related to the SARScoronavirus which is the etiological agent of severe acute respiratory syndrome (SARS), a human epidemic which emerged in China in 2002-2003. In the last few years, it has been discovered that the association between coronaviruses and bats is a worldwide phenomenon, and it has been hypothesised that all mammalian coronaviruses were derived from ancestral viruses residing in bats. This review analyzes the role of bats as a reservoir of zoonotic viruses focusing more extensively on SARS-related coronaviruses and taking into account the role of African and European strains in the evolutionary history of these viruses.


title: Microbial cellulose wound dressing in the treatment of skin tears in the frail elderly.

text: In a randomized trial of predominantly category II and III skin tears in a population of frail elderly nursing home residents, standard wound care (24 residents) with Xeroform™ and a secondary dressing (Tegaderm™) was compared with a single application of a microbial cellulose membrane Dermafill (27 residents). Outcomes included the time to wound closure, pain reduction, and ease of use. While wound area was slightly larger in the microbial cellulose treated group, the healing time was equivalent to controls. However, pain control, ease of use, and patient and nursing staff satisfaction were superior to control with the use of the microbial cellulose wound dressing.


title: The efficacy of traditional Chinese Medicine as an adjunctive therapy in nasopharyngeal carcinoma: a systematic review and meta-analysis.

text: PURPOSE The purpose of this systematic review was to assess the efficacy of traditional Chinese Medicine (TCM) as an adjunctive therapy to radiotherapy (RT) and/or chemotherapy (CT) for patients with nasopharyngeal carcinoma (NPC). METHODS Randomized controlled trials (RCTs) with TCM to treat NPC were extensively searched in eight databases. Two researchers independently assessed the quality and validity of the included trials and extracted outcome data. Thirteen RCTs were included for analysis. RESULTS Compared to using RT and/or CT, TCM combined with conventional cancer therapy had significantly improved Karnofsky performance status (KPS) [odds ratio (OR) 4.81, 95% confidence interval (CI) 3.06-7.56]. TCM as an adjunctive therapy significantly reduced the serious adverse effects of RT to the oral mucosa and skin so that grade I+II prevailed [OR 2.19, 95% CI 1.31-3.66; OR 8.63, 95% CI 3.28-22.70, respectively]. The combined therapy significantly enhanced immunoregulation, improving the levels of CD3, CD4 T cells (OR 10.08, 95% CI 1.38-18.78; OR 7.08, 95% CI 2.41-11.74, respectively). CONCLUSIONS This systematic review suggests that TCM as a therapy adjunctive to RT and/or CT vs only RT and/ or CT has significant efficacy in terms of improvement of quality of life (QoL), alleviation of acute adverse effects, and enhancement of immunoregulation.


title: [A Case of Squamous Cell Lung Cancer in an Elderly Patient with Low PD-L1 Expression Effectively Treated with Nab-Paclitaxel(Nab-PTX)plus Carboplatin (CBDCA)plus Pembrolizumab for a Recurrence after Operation].

text: An 81-year-old man was admitted to our medical center for dyspnea. He underwent right upper lobectomy due to squamous cell lung cancer 5 years ago. Chest computed tomography(CT)revealed stenosis ofthe right main bronchus, and pathological diagnosis ofthe lesion was squamous cell carcinoma and PD-L1 expression was low(tumor proportion score [TPS]: 1%). Because his performance status(PS)was 1, he underwent 4 courses ofnab -paclitaxel(nab-PTX)plus carboplatin( CBDCA)plus pembrolizumab chemotherapy and pembrolizumab maintenance chemotherapy. The stenosis ofthe right main bronchus was clear after chemotherapy, and his dyspnea was improved. Chemotherapy using nab-PTX plus CBDCA plus pembrolizumab may become one of the therapeutic choices for the recurrence after operation of an elderly person with squamous cell lung carcinoma and low PD-L1 expression.


title: Clinical practice guidelines for chronic obstructive pulmonary disease: a review and comparison of current resources.

text: The first clinical practice guidelines (CPGs) for the assessment and management of patients with chronic obstructive pulmonary disease (COPD) were published 30 years ago. These and subsequent CPGs issued by professional societies and other groups prior to 2000 were consensus recommendations based on expert opinion and available studies, and they have been criticized for being inconsistent and not explicitly evidence-based. The Global Initiative for Chronic Obstructive Lung Disease (GOLD), a joint project of the National Heart, Lung, and Blood Institute and the World Health Organization, released the first of a new generation of rigorous, evidence-based COPD guidelines in 2001. Since that time several other CPGs, notably those developed jointly by the American Thoracic Society (ATS) and the European Respiratory Society (ERS), and by the British National Collaborating Center for Chronic Conditions and Institute for Clinical Excellence, have also become available. While previous COPD guidelines had different severity-grading systems and differed in their therapy recommendations, the new CPGs are remarkably consistent and have very few areas of clinically relevant discrepancy. All are available free via the Internet, provide for regular revision and updating, and include materials for patients and the public, as well as for health-care providers. Although the GOLD and ATS-ERS guidelines both have international authorship and are intended for worldwide use, implementation of many of their recommendations (such as the requirement for spirometry in diagnosis and staging, an escalating management scheme that includes expensive inhaled medications and pulmonary rehabilitation, and consideration for lung-volume reduction surgery) remains beyond the reach of many patients and health care systems.


title: [A Case of 11-Year Patient Survival after the Resection of a Metastatic Pancreatic Tumor of Sigmoid Colon Cancer].

text: A 44-year-old woman underwent a sigmoidectomy for sigmoid colon cancer in March 2002. At 5 years after the primary surgery, she underwent 2 hepatectomies, 2 anastomotic resections, 1 lung resection, and 1 radiofrequency ablation. Computed tomography revealed a mass in the pancreatic tail in January 2008. We performed distal pancreatectomy. The specimen showed metastases ofthe sigmoid colon cancer. Computed tomography revealed metastases to the left iliac lymph node in September 2010. She underwent chemotherapy with IRIS for the lymph node metastases. After 16 chemotherapy sessions, the lymph node metastases disappeared. The patient is alive 11 years after the pancreatectomy. Resectable pancreatic metastasis from colorectal cancer is rare. Multimodal treatment that includes radical surgery may achieve long-term survival in some cases.


title: [Detection of feline coronavirus using RT-PCR: basis for the study of the pathogenesis of feline infectious peritonitis (FIP)].

text: The aim of this study was to further investigate the pathogenesis and epidemiology of feline coronavirus (FCoV)-infections and among others to determine the prognostic value of a positive result in the RT-PCR for FCoV in serum samples collected from cats with abdominal signs. Viral RNA was isolated from 100 microl of serum and subsequently amplified by a nested RT-PCR using primers binding to a highly conserved region of the 3'-end of the FCoV-genome. Sixty-three serum samples collected from 62 cats with abdominal signs were examined by RT-PCR and the clinical outcome was followed up. Four of these cats with a positive PCR-result are healthy more than 70 months after the collection of the blood sample. It can be concluded that viremia with FCoV does not necessarily lead to FIP and death. With respect to diagnosing FIP, a positive FCoV-RT-PCR is of low prognostic and diagnostic value. It can not be recommended to use this assay as sole indication to euthanize cats. Further studies will have to be carried out to demonstrate if the prognostic and diagnostic value of this PCR-assay in other samples such as peripheral blood mononuclear cells is more reliable. However, this method was found to be an important tool to further study the pathogenesis and epidemiology of FIP.


title: The JRS guidelines for the management of community-acquired pneumonia in adults: an update and new recommendations.

text: Community-acquired pneumonia (CAP) continues to be a major medical problem. Since CAP is a potentially fatal disease, early appropriate antibiotic treatment is vital. Epidemiologic studies have shown that in the combined cause-of-death category, pneumonia ranks fourth as the leading cause of death in Japan. Therefore, the Japanese Respiratory Society (JRS) provided guidelines for the management of CAP in adults in 2000. Because of evolving resistance to antimicrobials and advances in diagnosis, treatment and prevention of CAP, it is felt that an update should be provided every three years so that important developments can be highlighted and pressing questions can be answered. Thus, the guidelines committee updated its guidelines in 2005. The basic policy and main purposes of the JRS guidelines include; 1) prevention of bacterial resistance and 2) effective and long-term use of medical resources. The JRS guidelines have recommended the exclusion of potential and broad spectrum antibiotics, fluoroquinolones and carbapenems, from the list of first-choice drugs for empirical treatment. In addition, the JRS guidelines have recommended short-term usage of antibiotics of an appropriate dose and pathogen-specific treatment using rapid diagnostic methods if possible.


SARS respiratory protection.


title: Assessment of intervention measures for the 2003 SARS epidemic in Taiwan by use of a back-projection method.

text: OBJECTIVES To reconstruct the infection curve for the 2003 severe acute respiratory syndrome (SARS) epidemic in Taiwan and to ascertain the temporal changes in the daily number of infections that occurred during the course of the outbreak. METHOD Back-projection method. RESULTS The peaks of the epidemic correspond well with the occurrence of major infection clusters in the hospitals. The overall downward trend of the infection curve after early May corresponds well to the date (May 10) when changes in the review and classification procedure were implemented by the SARS Prevention and Extrication Committee. CONCLUSION The major infection control measures taken by the Taiwanese government over the course of the SARS epidemic, particularly those regarding infection control in hospitals, played a crucial role in containing the outbreak.


title: Initial experiences from patients with COVID-19 on ventilatory support in Denmark.

text: INTRODUCTION The coronavirus disease 2019 (COVID-19)pandemic reached Denmark in early 2020. This paper presents initial intensive-care unit (ICU) experiences with COVID-19 patients at Roskilde Hospital, which was the primary recipient of COVID-19 patients in need of intensive care in the Zealand Region, Denmark. METHODS An evaluation was conducted of the COVID-19 patients admitted to the ICU due to respiratory failure from 11 March 2020 to 01 April 2020. The number of ICU beds was increased from eight to 22 beds during this period. RESULTS Sixteen patients (four women) were evaluated. The median age was 69.5 years (range: 56-84 years). All the patients were admitted to the ICU for hypoxemic respiratory failure and all needed mechanical ventilation by orotracheal intubation. By 16 April, six patients were still admitted to the ICU, four patients had been discharged from the ICU and seven had died. At present, the average length of ICU stay is 14 ± 9 days (mean ± standard deviation). One patient has remained on ventilatory support for 31 days. The evaluation revealed four key themes. COVID-19 patients 1) had greatly increased C-reactive protein levels, 2) needed a significant inspiratory O2fraction, 3) were highly positive end-expiratory pressure (PEEP) dependent on ventilatory support and 4) suffered highly fluctuating respiratory failure requiring ventilatory support for a significantly longer period of time than non-COVID-19 patients. CONCLUSIONS COVID-19 patients have characteristic reproducible laboratory findings and present a major challenge due to their illness severity and required treatment length. FUNDING none. TRIAL REGISTRATION not relevant.


A simple technique for knot tying in single incision laparoscopic surgery (SILS).


Severe acute respiratory syndrome: Did quarantine help?


title: Effect of intonation on cantonese lexical tones.

text: In tonal languages, there are potential conflicts between the FO-based changes due to the coexistence of intonation and lexical tones. In the present study, the interaction of tone and intonation in Cantonese was examined using acoustic and perceptual analyses. The acoustic patterns of tones at the initial, medial, and final positions of questions and statements were measured. Results showed that intonation affects both the FO level and contour, while the duration of the six tones varied as a function of positions within intonation contexts. All six tones at the final position of questions showed rising FO contour, regardless of their canonical form. Listeners were overall more accurate in the identification of tones presented within the original carrier than of the same tones in isolation. However, a large proportion of tones 33, 21, 23, and 22 at the final position of questions were misperceived as tone 25 both within the original carrier and as isolated words. These results suggest that although the intonation context provided cues for correct tone identification, the intonation-induced changes in FO contour cannot always be perceptually compensated for, resulting in some erroneous perception of the identity of Cantonese tone.


Involvement of viral and cellular factors in processing of polyprotein encoded by ORF1a of the coronavirus IBV.


title: Tea catechins as a potential alternative anti-infectious agent.

text: Besides well-known health benefits, green tea catechins exert antimicrobial and antiviral activities against a variety of infectious agents. Although the detailed mechanism of the antimicrobial activity of tea catechins remains to be explored, the broad-spectrum activity of catechins may involve common target(s), such as the cell membrane, in addition to specific targets for each pathogen. This extends to antiviral activities, where many pronounced activities were reported for enveloped viruses. Yet, the effectiveness of tea catechins as antimicrobials is compromised by relative chemical instability and poor bioavailability. Whether tea catechins will emerge as a viable option as alternative medicine or as a synergistic combination therapy with pre-existing antivirals or antibiotics must therefore depend on a method of delivery that ensures its stability and bioavailability. However, green tea may provide an option for mitigating the health and economic burdens associated with emerging and re-emerging infectious diseases, especially considering the paucity of effective control measures. Considering the zoonotic nature of newly arising infectious diseases, the dual use of green tea components in both humans and livestock may reduce animal-human transmission, which would complement the current management of infectious diseases.


Antigenic and genomic variations among cytopathic and non-cytopathic strains of bovine enteric coronavirus.


title: A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2.

text: The coronavirus spike (S) protein mediates infection of receptor-expressing host cells and is a critical target for antiviral neutralizing antibodies. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for the coronavirus (severe acute respiratory syndrome (SARS)-CoV) that causes SARS. Here we demonstrate that a 193-amino acid fragment of the S protein (residues 318-510) bound ACE2 more efficiently than did the full S1 domain (residues 12-672). Smaller S protein fragments, expressing residues 327-510 or 318-490, did not detectably bind ACE2. A point mutation at aspartic acid 454 abolished association of the full S1 domain and of the 193-residue fragment with ACE2. The 193-residue fragment blocked S protein-mediated infection with an IC(50) of less than 10 nm, whereas the IC(50) of the S1 domain was approximately 50 nm. These data identify an independently folded receptor-binding domain of the SARS-CoV S protein.


title: Characterization of the IgA and subclass IgG responses to neutralizing epitopes after infection of pregnant sows with the transmissible gastroenteritis virus or the antigenically related porcine respiratory coronavirus.

text: In this study, we have investigated the characteristics of secreted IgA and other classes of Ig induced after vaccination of sows with transmissible gastroenteritis virus (TGEV) or the antigenically related porcine respiratory coronavirus (PRCV). Both viruses induced the secretion of neutralizing antibodies of different classes in the sows' milk, but these protected suckling piglets against TGEV to different degrees. Quantitative differences in the induction of IgA by both viruses were found among the different viral antigenic sites and subsites of glycoprotein S. In TGEV-vaccinated sows, antigenic subsite A was the best inducer of IgA, followed by antigenic site D. After vaccination with PRCV, lower levels of IgA were detected on colostrum and milk, antigenic site D and subsite Ab being the immunodominant sites. This quantitative difference in epitope recognition could explain the differences in newborn piglet protection found using Ig classes purified from the milk of sows immunized with both viruses. Apparently only IgA recognizing at least antigenic sites A and D confers good protection in vivo, whereas any Ig class recognizing only one antigenic site may neutralize the virus in cell culture. These results indicate that the formulation of a subunit vaccine against TGEV has to consider the inclusion of more than one antigenic site involved in virus neutralization.


Fatal fungemia due to Phaeoacremonium inflatipes in a child with severe aplastic anemia.


title: Videoconferences of Infectious Diseases: An educational tool that transcends borders. A useful tool also for the current COVID-19 pandemic.

text: Not available.


title: Pharmacological interventions for delirium in intensive care patients: a protocol for an overview of reviews.

text: BACKGROUND The prevalence of delirium in intensive care unit (ICU) patients is high. Delirium has been associated with morbidity and mortality including more ventilator days, longer ICU stay, increased long-term mortality and cognitive impairment. Thus, the burden of delirium for patients, relatives and societies is considerable. Today, reviews of randomised clinical trials are produced in large scales sometimes making it difficult to get an overview of the available evidence. A preliminary search identified several reviews investigating the effects of pharmacological interventions for the management and prevention of delirium in ICU patients. The conclusions of the reviews showed conflicting results. Despite this unclear evidence, antipsychotics, in particular, haloperidol is often the recommended pharmacological intervention for delirium in ICU patients. The objective of this overview of reviews is to critically assess the evidence of reviews of randomised clinical trials on the effect of pharmacological management and prevention of delirium in ICU patients. METHODS/DESIGN We will search for reviews in the following databases: Cochrane Library, MEDLINE, EMBASE, Science Citation Index, BIOSIS, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature, and Allied and Complementary Medicine Database. Two authors will independently select references for inclusion using Covidence, extract data and assess the methodological quality of the included systematic reviews using the ROBIS tool. Any disagreement will be resolved by consensus. We will present the data as a narrative synthesis and summarise the main results of the included reviews. In addition, we will present an overview of the bias risk assessment of the systematic reviews. DISCUSSION Results of this overview may establish a way forward to find and update or to design a high quality systematic review assessing the effects of the most promising pharmacological intervention for delirium in ICU patients. SYSTEMATIC REVIEW REGISTRATION PROSPERO - CRD42016046628 .


title: Proteolytic processing and deubiquitinating activity of papain-like proteases of human coronavirus NL63.

text: Human coronavirus NL63 (HCoV-NL63), a common human respiratory pathogen, is associated with both upper and lower respiratory tract disease in children and adults. Currently, no antiviral drugs are available to treat CoV infections; thus, potential drug targets need to be identified and characterized. Here, we identify HCoV-NL63 replicase gene products and characterize two viral papain-like proteases (PLPs), PLP1 and PLP2, which process the viral replicase polyprotein. We generated polyclonal antisera directed against two of the predicted replicase nonstructural proteins (nsp3 and nsp4) and detected replicase proteins from HCoV-NL63-infected LLC-MK2 cells by immunofluorescence, immunoprecipitation, and Western blot assays. We found that HCoV-NL63 replicase products can be detected at 24 h postinfection and that these proteins accumulate in perinuclear sites, consistent with membrane-associated replication complexes. To determine which viral proteases are responsible for processing these products, we generated constructs representing the amino-terminal end of the HCoV-NL63 replicase gene and established protease cis-cleavage assays. We found that PLP1 processes cleavage site 1 to release nsp1, whereas PLP2 is responsible for processing both cleavage sites 2 and 3 to release nsp2 and nsp3. We expressed and purified PLP2 and used a peptide-based assay to identify the cleavage sites recognized by this enzyme. Furthermore, by using K48-linked hexa-ubiquitin substrate and ubiquitin-vinylsulfone inhibitor specific for deubiquitinating enzymes (DUBs), we confirmed that, like severe acute respiratory syndrome (SARS) CoV PLpro, HCoV-NL63 PLP2 has DUB activity. The identification of the replicase products and characterization of HCoV-NL63 PLP DUB activity will facilitate comparative studies of CoV proteases and aid in the development of novel antiviral reagents directed against human pathogens such as HCoV-NL63 and SARS-CoV.


title: Identifying respiratory findings in emergency department reports for biosurveillance using MetaMap.

text: Clinical conditions described in patients' dictated reports are necessary for automated detection of patients with respiratory illnesses such as inhalational anthrax and pneumonia. We applied MetaMap to emergency department reports to extract a set of 71 clinical conditions relevant to detection of a lower respiratory outbreak. We indexed UMLS terms in emergency department reports with MetaMap, filtered the indexed output with a specialized lexicon of UMLS terms for the domain, and mapped the clinical conditions of interest to concepts in the lexicon. We compared MetaMap's ability to accurately identify the conditions against a physician's manual annotations and evaluated incorrectly indexed features to determine what additional processing is necessary. MetaMap identified the clinical conditions with a recall of 0.72 and a precision of 0.56. Necessary processing beyond MetaMap's indexing includes finding validation, temporal discrimination, anatomic location discrimination, finding-disease discrimination, and contextual inference. Successful identification of clinical conditions in an emergency department report with MetaMap requires processing techniques specific to the clinical question of interest.


Genomic organisation of a virulent isolate of porcine transmissible gastroenteritis virus.


title: Yellow head virus from Thailand and gill-associated virus from Australia are closely related but distinct prawn viruses.

text: Corresponding genomic regions of isolates of yellow head virus (YHV) from Thailand and gill-associated virus (GAV) from Australia were compared by RT-PCR and sequence analysis. PCR primers designed from sequences in the GAV ORF1b polyprotein gene amplified the corresponding 577 nucleotide region of the YHV genome. Comparison of the amplified region indicated 85.1% nucleotide and 95.8% amino acid sequence identity. YHV PCR primers designed to amplify a 135 nucleotide product previously described as a YHV diagnostic probe failed to amplify the corresponding product from GAV RNA. However, the cognate GAV sequence for this and another recently reported YHV sequence were located in an upstream region of the ORF1b gene. A comparison of these sequences indicated identities of 83.0 and 80.9% at the nucleotide level and 86.7 and 86.5% at the amino acid level, respectively. The data indicate that GAV and YHV are closely related but distinct viruses for which differential diagnostic probes can be applied.


title: Infectious bronchitis virus: S1 gene characteristics of vaccines used in China and efficacy of vaccination against heterologous strains from China.

text: The entire S1 protein genes of eight infectious bronchitis (IB) vaccine strains used in China were compared with those of the IB virus isolates present in the field in China. The nucleotide and amino acid similarities between the eight IB vaccine strains and the field strain, tl/CH/LDT3/03, which was isolated from a teal (Anas sp.), were not more than 81.1% and 79.2%, respectively. Phylogenetic analysis based on the S1 genes showed that the vaccines and field strains belonged to different clusters and showed larger evolutionary distances, and indicated that they were of different genotypes. Four out of the eight vaccines, in addition to the Massachusetts type vaccine H120, were used for protection tests against challenge by the IB virus isolate tl/CH/LDT3/03. This revealed that each of the five IB vaccines induced poor protection against the teal isolate, as assessed by respiratory protection, clinical signs and mortality, indicating the necessity of developing vaccines from local strains for IB control in China.