title: Independent and competing disease risks: implications for host populations in variable environments.

text: Disease models usually assume disease to act independently of other mortality- and morbidity-causing factors. Alternatively, disease may function as a competing risk factor, for example, killing already moribund hosts. Using tuberculosis (TB) in African buffalo as a model system, we explore consequences of competing or independent disease effects for host population dynamics. We include scenarios with density-dependent and density-independent effects of environmental variation, exemplified by variable food availability (driven by rainfall) and catastrophic droughts, respectively. Independent disease effects reduce population size linearly with prevalence, irrespective of the nature of environmental variation. Competing disease risks alter population size only if density-independent variation is present; then, disease reduces population size nonlinearly. Field data indicate that the net effect of TB on buffalo likely falls between the extremes of total independence and competition with other risk factors: TB increases mortality and decreases fecundity in some prime-aged buffalo, suggesting independent disease risks in these individuals, while similar disease effects in senescent buffalo may act as competing risks. Moreover, increased survival and fecundity of TB-negative buffalo may compensate for some disease-related losses. Model assumptions on independent or competing disease risks and environmental variability should be considered explicitly when assessing disease effects on wildlife populations.


title: [Analysis on the multi-distribution and the major influencing factors on severe acute respiratory syndrome in Beijing].

text: OBJECTIVE To analyse the multi-dimension nature of severe acute respiratory syndrome (SARS) transmission. METHODS Based on the data of SARS in 2003 and the geographic information system of Beijing, as well as under the broad range of the theorems and techniques of data-driven and model-driven knowledge mining, hierarchical techniques were used to test the hot spots. Wavelet technique was also used to decompose Moran's I frequency to survey the spatial clustering process of SARS. For factors analysis, BW test was used to distinguish factors which influencing SARS process. In temporal aspects, susceptive-infective-removal model (SIR) without Taylor expansion was solved by a genetic-simulated annealing algorithm, that directly provided a new approach to obtain epidemic parameters from the SIR model. RESULTS Different order of spatial hot spots were noticed and the clustering were relevant with the means of transportation. Diffusion dynamics were changed along with the temporal process of SARS. Regarding factor analysis, geographic relationship, population density, the amount of doctors and hospitals appeared to be the key elements influencing the transmission of SARS. The predictable number of SARS cases evolving with time were also calculated. CONCLUSIONS Cluster detection of close contacts of SARS infective in Beijing revealed the spatial characters of urban population flow and having important implications in the prevention and control of this communicable diseases. Some human and physical environment factors played statistical significant roles in different periods during SARS epidemics. An efficient algorithm was developed to solve SIR model directly, enabling the estimation of epidemic parameters from SIR and early forecast.


title: Efficient homologous RNA recombination and requirement for an open reading frame during replication of equine arteritis virus defective interfering RNAs.

text: Equine arteritis virus (EAV), the prototype arterivirus, is an enveloped plus-strand RNA virus with a genome of approximately 13 kb. Based on similarities in genome organization and protein expression, the arteriviruses have recently been grouped together with the coronaviruses and toroviruses in the newly established order Nidovirales. Previously, we reported the construction of pEDI, a full-length cDNA copy of EAV DI-b, a natural defective interfering (DI) RNA of 5.6 kb (R. Molenkamp et al., J. Virol. 74:3156-3165, 2000). EDI RNA consists of three noncontiguous parts of the EAV genome fused in frame with respect to the replicase gene. As a result, EDI RNA contains a truncated replicase open reading frame (EDI-ORF) and encodes a truncated replicase polyprotein. Since some coronavirus DI RNAs require the presence of an ORF for their efficient propagation, we have analyzed the importance of the EDI-ORF in EDI RNA replication. The EDI-ORF was disrupted at different positions by the introduction of frameshift mutations. These were found either to block DI RNA replication completely or to be removed within one virus passage, probably due to homologous recombination with the helper virus genome. Using recombination assays based on EDI RNA and full-length EAV genomes containing specific mutations, the rates of homologous RNA recombination in the 3'- and 5'-proximal regions of the EAV genome were studied. Remarkably, the recombination frequency in the 5'-proximal region was found to be approximately 100-fold lower than that in the 3'-proximal part of the genome.


title: Training in environmental health research for action: the Shanghai-California Environmental Health Training Program.

text: The Shanghai Center for Disease Control and Prevention (SCDC) was created in 1998; in 2001, with support from Fogarty International Center, the intergovernmental Shanghai-California Environmental Health Training Program was formed. Providing U.S.-based training to SCDC managers allows them to return to Shanghai and share their knowledge. Indexing Chinese journals will enable more exchange of information and will support improvements in Chinese scholarship. Increased international contact will result in greater trust and more rapid warnings to international colleagues, with resultant faster responses to emerging public health threats. Building research capacity in SCDC will allow for more rapid translation of results to policy. The progress of the Program toward establishing a regional (Shanghai) biological specimen bank is an example of building institutional capacity to enhance research that can serve as a lasting foundation for public health research and policy decisions in both Shanghai and China.


title: Avian influenza virus (H5N1): a threat to human health.

text: Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, and the next pandemic may well arise from a low-pathogenicity virus. The rationale for particular concern about an H5N1 pandemic is not its inevitability but its potential severity. An H5N1 pandemic is an event of low probability but one of high human health impact and poses a predicament for public health. Here, we review the ecology and evolution of highly pathogenic avian influenza H5N1 viruses, assess the pandemic risk, and address aspects of human H5N1 disease in relation to its epidemiology, clinical presentation, pathogenesis, diagnosis, and management.


title: [Case of Recurrent Breast Cancer with BRCA2 Mutation Successfully Treated with Olaparib Therapy].

text: A 70-year-old woman was diagnosed with cT2N2M0 left triple negative breast cancer. She received neoadjuvant chemotherapy. Around 30 months after the surgery, she developed carcinomatous pericardial tamponade, carcinomatous pleurisy, and metastatic thyroid cancer due to the breast cancer. Around the same time, a BRCA2 mutation was confirmed. Thus, olaparib therapy was started. Around 45 days after the start of olaparib administration, the therapeutic effect was cPR. The treatment remains effective even after approximately 1 year.


title: SARS patients-derived human recombinant antibodies to S and M proteins efficiently neutralize SARS-coronavirus infectivity.

text: OBJECTIVE To develop a specific SARS virus-targeted antibody preparation for emergent prophylaxis and treatment of SARS virus infection. METHODS By using phage display technology, we constructed a naive antibody library from convalescent SARS patient lymphocytes. To obtain the neutralizing antibody to SARS virus surface proteins, the library panning procedure was performed on purified SARS virions and the specific Fab antibody clones were enriched by four rounds of repeated panning procedure and screened by highthroughput selection. The selected Fab antibodies expressed in the periplasma of E. coli were soluble and further purified and tested for their binding properties and antiviral function to SARS virus. The functional Fab antibodies were converted to full human IgG antibodies with recombinant baculovirus/insect cell systems and their neutralizing activities were further determined. RESULTS After four rounds of the panning, a number of SARS-CoV virus-targeted human recombinant Fab antibodies were isolated from the SARS patient antibody library. Most of these were identified to recognize both natural and recombinant SARS spike (S) proteins, two Fab antibodies were specific for the virus membrane (M) protein, only one bound to SARS-CoV nucleocapsid protein. The SARS-CoV S and M protein-targeted Fab or IgG antibodies showed significant neutralizing activities in cytopathic effect (CPE) inhibition neutralization test, these antibodies were able to completely neutralize the SARS virus and protect the Vero cells from CPE after virus infection. However, the N protein-targeted Fab or IgG antibodies failed to neutralize the virus. In addition, the SARS N protein-targeted human Fab antibody reacted with the denatured N proteins, whereas none of the S and M protein specific neutralizing antibodies did. These results suggested that the S and M protein-specific neutralizing antibodies could recognize conformational epitopes which might be involved in the binding of virions to cellular receptors and the fusion activity of the virus. CONCLUSION The SARS-CoV spike protein and membrane proteins are able to elicite efficient neutralizing antibodies in SARS patients. The neutralizing antibodies we generated in this study may be more promising candidates for prophylaxis and treatment of SARS infection.


title: Application of the analytic hierarchy process to a risk assessment of emerging infectious diseases in Shaoxing city in southern China.

text: This study aimed to assess the likelihood of an outbreak or epidemic of emerging infectious diseases (EIDs) in Shaoxing city, China, and its resulting impact to provide decision makers with quantitative, directive results. Factors related to the risk of EIDs were selected through meeting with experts and were arranged in a hierarchical structure. These evaluation factors were also weighted to allow the use of a point system for evaluation. As a result, 14 evaluation factors comprising a 3-layer hierarchy were generated. The riskiest top 10 EIDs were HIV/AIDS (consistency index [CI] = 3.206), cholera (CI = 3.103), SARS (CI = 2.804), acute schistosomiasis (CI = 2.784), malaria (CI = 2.777), legionellosis (CI = 2.743), avian influenza A/H5N1 (CI = 2.734), dengue fever (CI = 2.702), Escherichia coli O157:H7 enteritis (CI = 2.593), and plague (CI = 2.553). The risk assessment was specifically intended to support local and national government agencies in the management of high risk EIDs in their efforts to (i) make resource allocation decisions, (ii) make high-level planning decisions, and (iii) raise public awareness of the EID risk. The results showed that the EID risk in Shaoxing could be effectively assessed through an analytic hierarchy process.


Coronavirus Disease 2019 (COVID-19): Prevention and Control in the Radiology Department.


title: Coronavirus IBV: structural characterization of the spike protein.

text: The spike protein (S; surface projection) of avian infectious bronchitis virus (IBV) strain M41 comprises two glycopolypeptides, S1 (mol. wt. 90 X 10(3] and S2 (mol. wt. 84 X 10(3], in equimolar proportions. The apparent mol. wt. of S was calculated as 354 (+/- 17) X 10(3) following co-sedimentation with catalase in sucrose gradients. Incubation of radiolabelled IBV with urea resulted in the removal of most S1, but none of S2, from the virus particle. A similar result was obtained using low concentrations of SDS, although some nucleocapsid, but not matrix, protein was also released. 2% SDS alone was as effective as 2% SDS plus 2% 2-mercaptoethanol for the separation of S1 and S2 prior to SDS-polyacrylamide gel electrophoresis. Dithiothreitol did not remove S from virions but did decrease the buoyant density of the virus from 1.18 g/ml to 1.16 g/ml, and changed the configuration of S. It is concluded that IBV S protein is an oligomer comprising two copies of each of S1 and S2, although the possibility that there are three copies of each glycopolypeptide cannot be discounted. S is attached to the membrane by S2, while S1 has little or no contact with the membrane and may form the major part of the bulbous end of S. Interpeptide disulphide bonds do not occur in S, and the association of S1 and S2 is weak.


title: Incidence of end-stage renal disease attributed to diabetes among persons with diagnosed diabetes --- United States and Puerto Rico, 1996-2007.

text: During 2007, approximately 110,000 persons in the United States and Puerto Rico began treatment for end-stage renal disease (ESRD) (i.e., kidney failure requiring dialysis or transplantation). Diabetes is the leading cause of ESRD in the United States, accounting for 44% of new cases in 2007. Although the number of persons initiating treatment for kidney failure each year who have diabetes listed as a primary cause (ESRD-D) has increased since 1996, ESRD-D incidence among persons with diagnosed diabetes has declined since 1996. To determine whether this decline occurred in every U.S. region and in every state, CDC analyzed 1996-2007 data from the U.S. Renal Data System (USRDS) and the Behavioral Risk Factor Surveillance System (BRFSS). During the period, the age-adjusted rate of ESRD-D among persons with diagnosed diabetes declined 35% overall, from 304.5 to 199.1 per 100,000 persons with diagnosed diabetes, and declined in all U.S. regions and in most states. No state showed a significant increase in the age-adjusted ESRD-D rate. Continued awareness of risk factors for kidney failure and interventions to improve diabetes care are needed to sustain and improve these trends.


title: Australia's notifiable disease status, 2010: annual report of the National Notifiable Diseases Surveillance System.

text: In 2010, 65 diseases and conditions were nationally notifiable in Australia. States and territories reported a total of 209,079 notifications of communicable diseases to the National Notifiable Diseases Surveillance System, a decrease of 12% on the number of notifications in 2009. This decrease was largely due to a reduction of influenza compared with the influenza A(H1N1) pandemic 2009. In 2010, the most frequently notified diseases were sexually transmissible infections (86,620 notifications, 41.4% of total notifications), vaccine preventable diseases (61,964 notifications, 29.6% of total notifications), and gastrointestinal diseases (31,548 notifications, 15.1% of total notifications). There were 18,302 notifications of bloodborne diseases; 8,244 notifications of vectorborne diseases; 1,866 notifications of other bacterial infections; 532 notifications of zoonoses and 3 notifications of quarantinable diseases.


title: Characterization of the nonstructural and spike proteins of the human respiratory coronavirus OC43: comparison with bovine enteric coronavirus.

text: The nucleotide sequence of the region between the spike (S) and the membrane (M) protein genes, and sequences of the S and ns2 genes of the OC43 strain of human coronavirus (HCV-OC43) were determined. The ns2 gene comprises an open reading frame (ORF) encoding a putative nonstructural (ns) protein of 279 amino acids with a predicted molecular mass of 32-kDa. The S gene comprises an ORF encoding a protein of 1353 amino acid residues, with a predicted molecular weight of 149,918. Sequence comparison between HCV-OC43 and the antigenically related bovine coronavirus (BCV) revealed more sequence divergence in the putative bulbous part of the S protein (S1) than in the stem region (S2). The cysteine residues near the transmembrane domain and the internal predicted protease cleavage site are conserved in the HCV-OC43 S protein. Nucleotide sequence analysis of the region between the S and M gene loci revealed the presence of an unexpected intragenomic partial leader sequence and two ORFs encoding potential proteins of 12.9 and 9.5-kDa. These two proteins were identified as nonstructural by comparison with the homologous BCV genes. In vitro translation analyses demonstrated that the HCV-OC43 9.5-kDa protein, like its BCV counterpart, is poorly translated when situated down-stream of the 12.9-kDa ORF, but is expressed in infected cells, as shown by immunofluorescence. Interestingly, two ORFs, potentially encoding 4.9 and 4.8-kDa ns proteins in BCV are absent in HCV-OC43, indicating that they are not essential for viral replication in HRT-18 cells.


title: [Carrier state of enteric viruses in Ivory Coast pregnant women in good health].

text: The present work emphasize the great diversity of the viral species encountered in pregnant women (Rotavirus, Coronavirus, Adenovirus, Poliovirus, Coxsackievirus). In each of the different regions studied, one or two viral types are usually predominant. In Man (West Ivory Coast) region for instance, Rotaviruses and Coronaviruses were mainly encountered; in Bouaké, Polioviruses and Adenoviruses were predominant whereas in Bondoukou and Odienné respectively Coxsackieviruses and Adenoviruses were predominantly identified. Multiple viral infections were also evidenced: Rotaviruses + Coronaviruses, Rotaviruses + Polioviruses, Coronaviruses + Polioviruses, Polioviruses and Adenoviruses. The greatest number of multiple infections was found in Man (8 cases). Inapparent infections were mainly detected in Man where the prevalence for at least one viral type is very high 91.6%; in Bouaké, prevalence of at least one viral type is around 36%. The least level of prevalence was recorded in Bondoukou (East of Ivory Coast) and Odienné (North-West) respectively 17% and 20%.


title: Murine hepatitis virus replicase protein nsp10 is a critical regulator of viral RNA synthesis.

text: Coronavirus replication requires proteolytic processing of the large polyprotein encoded by ORF1a/ab into putative functional intermediates and eventually approximately 15 mature proteins. The C-terminal ORF1a protein nsp10 colocalizes with viral replication complexes, but its role in transcription/replication is not well defined. To investigate the role of nsp10 in coronavirus transcription/replication, alanine replacements were engineered into a murine hepatitis virus (MHV) infectious clone in place of conserved residues in predicted functional domains or charged amino acid pairs/triplets, and rescued viruses were analyzed for mutant phenotypes. Of the 16 engineered clones, 5 viable viruses were rescued, 3 mutant viruses generated no cytopathic effect but were competent to synthesize viral subgenomic RNAs, and 8 were not viable. All viable mutants showed reductions in growth kinetics and overall viral RNA synthesis, implicating nsp10 as being a cofactor in positive- or negative-strand synthesis. Viable mutant nsp10-E2 was compromised in its ability to process the nascent polyprotein, as processing intermediates were detected in cells infected with this virus that were not detectable in wild-type infections. Mapping the mutations onto the crystal structure of severe acute respiratory syndrome virus nsp10 identified a central core resistant to mutation. Mutations targeting residues in or near either zinc-binding finger generated nonviable phenotypes, demonstrating that both domains are essential to nsp10 function and MHV replication. All mutations resulting in viable phenotypes mapped to loops outside the central core and were characterized by a global decrease in RNA synthesis. These results demonstrate that nsp10 is a critical regulator of coronavirus RNA synthesis and may play an important role in polyprotein processing.


Extract from SARS in Hong Kong: from experience to action.


title: Plankton effect on cod recruitment in the North Sea.

text: The Atlantic cod (Gadus morhua L.) has been overexploited in the North Sea since the late 1960s and great concern has been expressed about the decline in cod biomass and recruitment. Here we show that, in addition to the effects of overfishing, fluctuations in plankton have resulted in long-term changes in cod recruitment in the North Sea (bottom-up control). Survival of larval cod is shown to depend on three key biological parameters of their prey: the mean size of prey, seasonal timing and abundance. We suggest a mechanism, involving the match/mismatch hypothesis, by which variability in temperature affects larval cod survival and conclude that rising temperature since the mid-1980s has modified the plankton ecosystem in a way that reduces the survival of young cod.


title: Morbidity, mortality and coronavirus antigen in previously coronavirus free kittens placed in two catteries with feline infectious peritonitis.

text: Serologically coronavirus free kittens were placed in 2 catteries with a history of feline infectious peritonitis (FIP), each cattery representing 1 of the 2 different predominant clinical characteristics of FIP--effusive and granulomatous. The kittens were clinically observed for 100 days. A 100% morbidity and a 90% mortality was observed. The first signs were observed after 14 and 27 days respectively. The clinical pattern of the disease was similar in all kittens and showed a pattern of recurrent periods of conjunctivitis, upper respiratory and gastrointestinal signs. Once developed, wasting and signs of CNS disturbances were consistent. The "effusive strain" had a 2 weeks earlier onset of signs and death, and a 40% outcome of effusive FIP. Mean survival times during the observation period were 57 +/- 26 and 57 +/- 16 (mean +/- SD in days), respectively. The death rates were similar in both groups. Feline coronavirus (FCoV) antigen was immunohistochemically detected using indirect immunofluorescence and was present in all kittens and in 93% of the 5 investigated organs (lung, liver, spleen, kidney, and mesenteric lymph node).


Biosecurity. Researchers urge U.S. to keep SARS off select agent list.


title: [Older people with complex, combined care needs: the need for tailored collaborative care].

text: Older patients with combined psychiatric, physical and cognitive health problems - patients who need double care - benefit from integrated medical and psychiatric care. The characteristics of these patients, as well as the problems that may exist in offering them adequate integrated care, are illustrated on the basis of a case description. Improvement of existing regional arrangements, premised on a collaborative care model, and involving hospital care, mental health services, nursing home care and community care services, is recommended. In settings that offer 24 hour long-term residential care and treatment, the expertise of mental health services and nursing homes must be structurally combined.


Construction of a recombinant adenovirus for the expression of the glycoprotein S antigen of porcine respiratory coronavirus.


title: Clinical value and pitfalls of fluorescent cholangiography during single-incision laparoscopic cholecystectomy.

text: PURPOSE To clarify the clinical value and pitfalls of fluorescent cholangiography (FC) during single-incision laparoscopic cholecystectomy (SILC). METHODS Our SILC procedure utilized the SILS-Port with additional 5-mm forceps through an umbilical incision. A laparoscopic fluorescent imaging system developed by Karl Storz Endoskope was utilized for fluorescent cholangiography. RESULTS We performed fluorescent cholangiography during SILC in 21 patients. All procedures were completed successfully without biliary injury. The detectability of the running course of the cystic duct, the confluence between the cystic duct and the common hepatic duct, and the common hepatic duct before the dissection in Calot's triangle was 47.6, 71.4, and 81.0 %, respectively. The detectability of biliary structures was worse in 9 obese patients (body mass index ≥ 25.0 kg/m2) than in 12 non-obese patients. The mean operative time for the patients in whom fluorescent cholangiography could identify the running course of the cystic duct before dissection in Calot's triangle (68 ± 16 min) was shorter than that for the other patients (91 ± 35 min; p = 0.037). CONCLUSIONS Fluorescent cholangiography can prevent biliary injury during SILC and facilitate SILC. Obesity is the most important factor that can prevent identification of biliary structures under fluorescent cholangiography.


Learning from low income countries: what are the lessons? Communities should decide priorities.


title: Smoking Cessation, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

text: Cigarette smoking has been implicated in causing many cancers and cancer deaths. There is mounting evidence indicating that smoking negatively impacts cancer treatment efficacy and overall survival. The NCCN Guidelines for Smoking Cessation have been created to emphasize the importance of smoking cessation and establish an evidence-based standard of care in all patients with cancer. These guidelines provide recommendations to address smoking in patients and outlines behavioral and pharmacologic interventions for smoking cessation throughout the continuum of oncology care.


title: Diagnosis and treatment of a dermal malignant melanoma in an African lion (Panthera leo).

text: A 13-yr-old intact male African lion (Panthera leo) presented with a 4-mo history of left maxillary lip swelling. On physical examination, a 10-cm-diameter, ulcerated, round, firm, and pigmented mass at the level of the left maxillary canine tooth was noticed. All other organ systems examined were within normal limits. Multiple biopsies of the mass were collected and fixed in 10% neutral buffered formalin. Histopathologic evaluation of the biopsies revealed a malignant dermal melanoma. Hematologic and plasma biochemical parameters were within normal reference ranges. Thoracic radiographs taken 3 days following initial presentation showed no evidence of metastasis of the tumor. Computed tomography of the skull and neck was performed to evaluate local tumor invasion and to plan for hypofractionated radiation therapy. Therapy included four weekly treatments of 8 gray external-beam hypofractionated radiation and four bimonthly immunotherapy treatments. Following this treatment regime, the tumor size was reduced by 50%, and surgical excision was performed. No major side effects associated with radiation or immunotherapy were seen. Six months after diagnosis, hematologic and plasma biochemical parameters were within normal limits, thoracic radiographs showed no evidence of metastasis, and the lion showed no clinical signs of disease. The lion will continue to receive immunotherapy every 6 mo for the rest of its life. To the authors' knowledge, this is the first report of a successful treatment of a malignant dermal melanoma with external-beam hypofractionated radiation, immunotherapy, and surgical excision in an African lion.


The complete nucleotide sequence of avian infectious bronchitis virus: analysis of the polymerase-coding region.


title: Inactivation of the tick-borne encephalitis virus by RNA-cleaving compounds.

text: The tick-borne encephalitis virus (TBEV) is an RNA-containing enveloped virus, which poses a major threat to the well-being and health of humans. In this study, we describe an approach to the inactivation of TBEV, which involves the degradation of viral RNA by artificial ribonucleases (aRNases, small organic compounds that exhibit ribonuclease activity in vitro). We demonstrate that the incubation of TBEV with aRNases lead to the total inactivation of the virus as indicated by the plaque formation assay data, but retain the viral immunogenic properties, as shown by the ELISA data. We propose that a possible mechanism of TBEV inactivation with aRNase, which includes: i) formation of local breaks in the lipid membrane of the virus caused by aRNase, ii) penetration of aRNase into the viral capsid, iii) degradation of genomic RNA by aRNase. These data suggest that the proposed approach can be used in the production of killed-virus vaccine.


title: Human coronavirus NL63 associated with lower respiratory tract symptoms in early life.

text: Coronavirus NL63 has been identified as a new member of the coronavirus genus, but its role as a cause of respiratory disease needs to be established. We studied the first episode of lower respiratory tract symptoms in a cohort of healthy neonates. NL63 was identified in 6 (7%) of 82 cases and was as frequent as other coronaviruses (9%). NL63 was recovered at the onset of symptoms and was cleared within 3 weeks in half of the cases. Our data suggests that coronavirus NL63 causes lower respiratory tract symptoms and is acquired in early life.


title: Beta interferon and gamma interferon synergize to block viral DNA and virion synthesis in herpes simplex virus-infected cells.

text: The capacity of herpes simplex virus type 1 (HSV-1) to replicate in vitro decreases tremendously when animal cell cultures are exposed to ligands of both the alpha/beta interferon (IFN-alpha/beta) receptor and IFN-gamma receptor prior to inoculation with low m.o.i.s of HSV-1. However, the available evidence provides no insight into the possible mechanisms by which co-activation of the IFN-alpha/beta- and IFN-gamma-signalling pathways produces this effect. Therefore, it has not been possible to differentiate between whether these observations represent an important in vitro model of host immunological suppression of HSV-1 infection or an irrelevant laboratory phenomenon. Therefore, the current study was initiated to determine whether co-activation of the host cell's IFN-alpha/beta and IFN-gamma pathways either (i) induced death of HSV-1-infected cells such that virus replication was unable to occur; or (ii) disrupted one or more steps in the process of HSV-1 replication. To this end, multiple steps in HSV-1 infection were compared in populations of Vero cells infected with HSV-1 strain KOS (m.o.i. of 2.5) and exposed to ligands of the IFN-alpha/beta receptor, the IFN-gamma receptor or both. The results demonstrated that IFN-beta and IFN-gamma interact in a synergistic manner to block the efficient synthesis of viral DNA and nucleocapsid formation in HSV-1-infected cells and do so without compromising host-cell viability. It was inferred that IFN-mediated suppression of HSV-1 replication may be a central mechanism by which the host immune system limits the spread of HSV-1 infection in vivo.


title: Characterization of two temperature-sensitive mutants of coronavirus mouse hepatitis virus strain A59 with maturation defects in the spike protein.

text: Two temperature-sensitive (ts) mutants of mouse hepatitis virus strain A59, ts43 and ts379, have been described previously to be ts in infectivity but unaffected in RNA synthesis (M. J. M. Koolen, A. D. M. E. Osterhaus, G. van Steenis, M. C. Horzinek, and B. A. M. van der Zeijst, Virology 125:393-402, 1983). We present a detailed analysis of the protein synthesis of the mutant viruses at the permissive (31 degrees C) and nonpermissive (39.5 degrees C) temperatures. It was found that synthesis of the nucleocapsid protein N and the membrane protein M of both viruses was insensitive to temperature. However, the surface protein S of both viruses was retained in the endoplasmic reticulum at the nonpermissive temperature. This was shown first by analysis of endoglycosidase H-treated and immunoprecipitated labeled S proteins. The mature Golgi form of S was not present at the nonpermissive temperature for the ts viruses, in contrast to wild-type (wt) virus. Second, gradient purification of immunoprecipitated S after pulse-chase labeling showed that only wt virus S was oligomerized. We conclude that the lack of oligomerization causes the retention of the ts S proteins in the endoplasmic reticulum. As a result, ts virus particles that were devoid of S were produced at the nonpermissive temperature. This result could be confirmed by biochemical analysis of purified virus particles and by electron microscopy.


Influenza epidemic or pandemic? Time to roll up sleeves, vaccinate patients, and hone osteopathic manipulative skills.


title: Antigenic comparison of feline coronavirus isolates: evidence for markedly different peplomer glycoproteins.

text: The antigenic relationships among seven feline coronavirus isolates were investigated by using a panel of 26 monoclonal antibodies (MAbs). The MAbs were categorized into five immunoreactive groups which were used to delineate two antigenic types of feline coronaviruses. One antigenic type included the more virulent feline infectious peritonitis virus (FIPV) isolates (FIPV-UCD-1, FIPV-UCD-4, FIPV-TN406, FIPV-DF2, and FIPV-79-1146), whereas the second antigenic type was composed of the avirulent isolate FIPV-UCD-2. The feline enteric coronavirus isolate FECV-79-1683 shared some characteristics of both of the major antigenic groups. Epitopes on the nucleocapsid and envelope polypeptides were in general highly conserved among both antigenic types, although a few type-specific antigenic sites were discriminated. The most striking finding was the marked antigenic difference in the peplomer (E2) glycoproteins between the two antigenic types. Seven anti-E2 MAbs reacted with one antigenic type of E2, whereas seven other anti-E2 MAbs recognized a different antigenic form of E2. None of the 14 anti-E2 MAbs reacted with all of the isolates.


title: Outcome of influenza A (H1N1) patients admitted to intensive care units in the Paraná state, Brazil.

text: OBJECTIVE This study aimed to analyze outcome, clinical and epidemiological characteristics and severity factors in adult patients admitted with a diagnosis of infection by virus A (H1N1) to public and private intensive care units, in Paraná, Brazil. METHODS Cohort study of medical charts of patients older than 12 years admitted to 11 intensive care units in 6 cities in the state of Parana, Brazil, during a period of 45 days, with diagnosis of swine influenza. The diagnosis of infection with A (H1N1) was made by real time polymerase chain reaction (RT-PCR) of nasopharyngeal secretion, or strong clinical suspicion when other causes had been ruled out (even with negative RT-PCR). Descriptive statistics were performed, analysis by the Chi square test was used to compare percentages and the Student's t test for continuous variables with univariate analysis, assuming a significance level of p <0.05. RESULTS There were 63 adult patients admitted with a diagnosis of H1N1, 37 (58.7%) being RT-PCR positive. Most patients were young adults (65% under 40 years of age) with no gender predominance and high incidence of obesity (27.0% with Body Mass Index > 30). Mean of the Acute Physiologic Chronic Health Evaluation II (APACHE II) score was 15.0 + 8.1. Mortality in the intensive care unit was 39.7%. The main factors associated with mortality were: positive RT-PCR, low levels of initial PaO2/FiO2, high initial levels of urea and lactate dehydrogenase, required level of positive end expiratory pressure, need for the prone position and vasopressors. CONCLUSIONS Adult patients with A (H1N1) virus infection admitted to intensive care units had a high risk of death, particularly due to respiratory impairment. Positive RT-PCR, urea and lactic dehydrogenase, low initial PaO2/FiO2 and high levels of PEEP were correlated with higher mortality.


title: Upper respiratory tract sampling in COVID-19.

text: INTRODUCTION To review the present literature on upper respiratory tract sampling in COVID-19 and provide recommendations to improve healthcare practices and directions in future studies. METHODS Twelve relevant manuscripts were sourced from a total of 7288 search results obtained using PubMed, Medline and Google Scholar. The search keywords used were COVID-19, nasopharyngeal, oropharyngeal, swabs, SARS and CoV2. Original manuscripts were obtained and analysed by all authors. The review included manuscripts which have not undergone rigorous peer-review process in view of the magnitude of the topic discussed. RESULTS The viral load of SARS-CoV-2 RNA in the upper respiratory tract was significantly higher during the first week and peaked at 4-6 days after onset of symptoms, during which it can be potentially sampled. Nasopharyngeal swab has demonstrated higher viral load than oropharyngeal swab, where the difference in paired samples is best seen at 0-9 days after the onset of illness. Sensitivity of nasopharyngeal swab was higher than oropharyngeal swabs in COVID-19 patients. Patient self-collected throat washing has been shown to contain higher viral load than nasopharyngeal or oropharyngeal swab, with significantly higher sensitivity when compared with paired nasopharyngeal swab. RECOMMENDATIONS Routine nasopharyngeal swab of suspected COVID-19 infection should take anatomy of the nasal cavity into consideration to increase patient comfort and diagnostic yield. Routine oropharyngeal swab should be replaced by throat washing which has demonstrated better diagnostic accuracy, and it is safe towards others.


title: [Obesity and risk of severe COVID-19].

text: Obesity represents a higher risk of severe COVID-19 infection, which may lead to the requirement of a mechanical ventilation in intensive care units and premature death. The underlying mechanisms are multiple: alteration of the respiratory performance, presence of comorbidities such as diabetes, hypertension or obstructive sleep apnea, finally inadequate and excessive immunological responses, possibly aggravated by ectopic intrathoracic fat depots. Thus, COVID-19 may challenge the so-called « obesity paradox » commonly reported by intensivists in patients with acute respiratory distress syndrome. These findings require reinforced preventive and curative measures among obese patients to limit the risk of progression towards an unfavorable outcome in case of COVID-19.


title: Differentiation between transmissible gastroenteritis virus and porcine respiratory coronavirus using a cDNA probe.

text: A plasmid, pG3BS, containing a cDNA clone from the 5' coding region of the peplomer glycoprotein gene appears to be specific for enteric transmissible gastroenteritis virus (TGEV) strains and for live-attenuated TGEV vaccines. This cDNA probe is used to differentiate porcine respiratory coronavirus (PRCV) isolates from TGEV field and vaccine strains by a slot blot hybridization assay. Probe pG3BS also hybridizes to canine coronavirus (CCV) RNA but does not hybridize to antigenically related feline infectious peritonitis virus (FIPV) RNA. The RNAs of 13 enteric TGEV isolates from the United States, Japan, and England, 4 US-licensed live-attenuated TGEV vaccines, and antigenically closely related CCV were detected by pG3BS. The RNAs of FIPV and 3 US isolates of PRCV did not react with pG3BS but were detected by a TGEV-derived plasmid, pRP3. Pigs infected with either PRCV or TGEV test serologically positive for TGEV antibody by the serum neutralization test. Characterization of the virus circulating in a swine herd by the pG3BS probe will differentiate between an enteric TGEV and a respiratory PRCV infection.


title: COVID-19 in the Americas: We Are in This Together.

text: COVID-19 has upended the world's healthcare infrastructures and its economies, casting a glaring light on the failings and flaws already in place, all suffered unequally. This has forced leaders and the public at large to face the stark contrast between human society as it exists and the society that is possible, with both the world's majority and the planet leaping to the top of a new agenda...an agenda as urgently needed as a new vaccine.


[Ⅰ.Current Treatment Strategies for Transplant-Eligible Newly Diagnosed Multiple Myeloma].


title: uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery.

text: Pre- and intraoperative diagnostic techniques facilitating tumor staging are of paramount importance in colorectal cancer surgery. The urokinase receptor (uPAR) plays an important role in the development of cancer, tumor invasion, angiogenesis, and metastasis and over-expression is found in the majority of carcinomas. This study aims to develop the first clinically relevant anti-uPAR antibody-based imaging agent that combines nuclear (111In) and real-time near-infrared (NIR) fluorescent imaging (ZW800-1). Conjugation and binding capacities were investigated and validated in vitro using spectrophotometry and cell-based assays. In vivo, three human colorectal xenograft models were used including an orthotopic peritoneal carcinomatosis model to image small tumors. Nuclear and NIR fluorescent signals showed clear tumor delineation between 24h and 72h post-injection, with highest tumor-to-background ratios of 5.0 ± 1.3 at 72h using fluorescence and 4.2 ± 0.1 at 24h with radioactivity. 1-2 mm sized tumors could be clearly recognized by their fluorescent rim. This study showed the feasibility of an uPAR-recognizing multimodal agent to visualize tumors during image-guided resections using NIR fluorescence, whereas its nuclear component assisted in the pre-operative non-invasive recognition of tumors using SPECT imaging. This strategy can assist in surgical planning and subsequent precision surgery to reduce the number of incomplete resections.


title: Treatment of Crimean-Congo hemorrhagic fever.

text: Crimean-Congo hemorrhagic fever (CCHF) has the most extensive geographic range of the medically significant tick-borne viruses, occurring from western China across southern Asia to eastern Europe and South Africa. The causative agent is a negative-sense, single-stranded RNA virus in the genus Nairovirus, family Bunyaviridae. In published reports, the case fatality rate has generally ranged from 10% to 50%. Sporadic cases and outbreaks of the disease have increased during the past decade across the endemic region. CCHF was first diagnosed in Turkey in 2002, but since then more than 1100 cases have been confirmed by IgM serology or RT-PCR, with a fatality rate of just over 5%. Simple methods are available for the in vitro evaluation of antiviral drugs, but because CCHF virus does not cause disease in its reservoir species or in laboratory animals other than suckling mice, methods are lacking for in vivo efficacy testing. Intravenous or oral ribavirin has been used in several countries to treat the disease for more than 20 years. Evidence of its efficacy is limited to observational studies, and placebo-controlled trials may be impossible to perform for ethical reasons. However, careful analysis of properly stratified observational studies can be used to assess the effects of treatment. This article reviews current approaches to the treatment of CCHF, focusing on the use of ribavirin and hematological support, and discusses prospects for future research.


title: Survey of zoonoses recorded in Scotland between 1993 and 2002.

text: All the human and animal laboratory reports of zoonoses sent to Health Protection Scotland between 1993 and 2002 were identified. There were 24,946 reports from veterinary laboratories, and 94,718 (20 per cent) of the 468,214 reports from medical laboratories were considered to be zoonotic. The most common reports of zoonoses from people were Campylobacter, Salmonella, Cryptosporidium and Giardia species and Escherichia coli o157. The most common reports of zoonoses from animals were Salmonella, Cryptosporidium, Chlamydia and Campylobacter species and Mycobacterium avium paratuberculosis. For all the zoonoses in people, the National Health Service Board areas Borders, Dumfries and Galloway, Forth Valley, Grampian, Lanarkshire and Lothian had a higher than expected standardised incidence rate of infection, whereas Ayrshire and Arran, Fife, Greater Glasgow, Shetland, Tayside and Western Isles had a lower than expected rate. The organisms and diseases considered to be new and emerging were Rhodococcus species, Cyclospora cayetanensis, Leishmania species, Pneumocystis carinii (jiroveci) and bovine spongiform encephalopathy/variant Creutzfeldt-Jakob disease.


title: Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors.

text: One of the hallmark findings in patients suffering from SARS (severe acute respiratory syndrome) is lymphopenia, which is the result of massive lymphocyte death. SARS-CoV (SARS coronavirus), a novel coronavirus that has been etiologically associated with SARS cases, is homologous with MHV (murine hepatitis coronavirus), and MHV small envelope E protein is capable of inducing apoptosis. We hypothesized that SARS-CoV encodes a small envelope E protein that is homologous with MHV E protein, thus inducing T-cell apoptosis. To test this hypothesis, a cDNA encoding SARS-CoV E protein was created using whole gene synthesis. Our results showed that SARS-CoV E protein induced apoptosis in the transfected Jurkat T-cells, which was amplified to higher apoptosis rates in the absence of growth factors. However, apoptosis was inhibited by overexpressed antiapoptotic protein Bcl-xL. Moreover, we found that SARS-CoV E protein interacted with Bcl-xL in vitro and endogenous Bcl-xL in vivo and that Bcl-xL interaction with SARS-CoV E protein was mediated by BH3 (Bcl-2 homology domain 3) of Bcl-xL. Finally, we identified a novel BH3-like region located in the C-terminal cytosolic domain of SARS-CoV E protein, which mediates its binding to Bcl-xL. These results demonstrate, for the first time, a novel molecular mechanism of T-cell apoptosis that contributes to the SARS-CoV-induced lymphopenia observed in most SARS patients.


title: [Prevalence of depressive disorders in patients with end-stage renal failure].

text: AIM The depressive symptoms are common in patients with end-stage kidney disease but they are often undiagnosed and can complicate the renal replacement therapy. The aim of this study was to identify significant differences in frequency and severity of depressive symptoms among patients with end-stage renal disease depending on what form of treatment they are undergoing--hemodialysis, peritoneal dialysis and patients after kidney transplantation. METHODS 323 patients with end-stage renal failure were examined. Among them 206 patients were hemodialysed, 64--undergoing the peritoneal dialysis and 53 patients were the recipients of kidney transplants. We used a self-constructed questionnaire and Beck Depression Inventory (BDI). RESULTS Beck Depression Inventory reflects mild and moderate intensification of symptoms. The results obtained by the use of BDI show the mild and moderate intensification of the depressive symptoms in the study group. The majority of patients suffering from depression were found in the group of patients undergoing peritoneal dialysis, to a lesser degree in the hemodialysis subgroup and among these, depression had moderate intensity. Patients after kidney transplantation were found to be at a smaller risk of depression comparing to dialysed patients. CONCLUSIONS End-stage renal disease may affect the occurrence of depressive symptoms, the treatment may also play a role in the formation and intensity. We formulated the conclusions of our study carefully, taking into account a multitude of other existing causal factors.


Boiling and Bacillus spores.


title: Research on the Mechanism of Cross-species Infection and Transmission for Animal-origin Emerging and Re-emerging Zoonosis Has Won Support by the National Key Research and Development Program of China.

text: Emerging and re-emerging zoonotic diseases caused by pathogens such as Middle East respiratory syndrome coronavirus (MERS-CoV), West Nile virus (WNV) or Chikungunya virus (CHIKV) pose considerable threats to public health worldwide. Research on the mechanism of cross-species infection and transmission for animal-origin emerging and re-emerging zoonosis (2016YFD0500300) has won support by the National Key Research and Development Program of China. Professor Wenjie Tan (National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention) was the primary principal investigator of this research group. Focusing on the mechanism of transmission and infection for emerging and re-emerging zoonosis, this research will provide an important. foundation for the prevention and control of zoonosis.


title: Thin-film technology for direct visual detection of nucleic acid sequences: applications in clinical research.

text: Certain optical conditions permit the unaided eye to detect thickness changes on surfaces on the order of 20 A, which are of similar dimensions to monomolecular interactions between proteins or hybridization of complementary nucleic acid sequences. Such detection exploits specific interference of reflected white light, wherein thickness changes are perceived as surface color changes. This technology, termed thin-film detection, allows for the visualization of subattomole amounts of nucleic acid targets, even in complex clinical samples. Thin-film technology has been applied to a broad range of clinically relevant indications, including the detection of pathogenic bacterial and viral nucleic acid sequences and the discrimination of sequence variations in human genes causally related to susceptibility or severity of disease.


Spread of SARS slows.


title: Emergence and predominance of an H5N1 influenza variant in China.

text: The development of highly pathogenic avian H5N1 influenza viruses in poultry in Eurasia accompanied with the increase in human infection in 2006 suggests that the virus has not been effectively contained and that the pandemic threat persists. Updated virological and epidemiological findings from our market surveillance in southern China demonstrate that H5N1 influenza viruses continued to be panzootic in different types of poultry. Genetic and antigenic analyses revealed the emergence and predominance of a previously uncharacterized H5N1 virus sublineage (Fujian-like) in poultry since late 2005. Viruses from this sublineage gradually replaced those multiple regional distinct sublineages and caused recent human infection in China. These viruses have already transmitted to Hong Kong, Laos, Malaysia, and Thailand, resulting in a new transmission and outbreak wave in Southeast Asia. Serological studies suggest that H5N1 seroconversion in market poultry is low and that vaccination may have facilitated the selection of the Fujian-like sublineage. The predominance of this virus over a large geographical region within a short period directly challenges current disease control measures.


title: Respiratory viruses and cot death.

text: Respiratory viruses and histological appearances of the lung were studied prospectively in an unselected series of 104 children who died between 1 week and 2 years of age. Thirty-one of the cases were cot deaths. Seven of these showed evidence of active virus infection in the lower respiratory tract. Similar evidence was found in two children who died from known causes and did not have a severe respiratory illness terminally. Although in some cases of cot death respiratory viruses may be responsible for a severe and rapidly overwhelming illness, the present results are compatible with an alternative hypothesis-namely, that minor respiratory illness may trigger sudden apnoea.


Invited commentary: real-time tracking of control measures for emerging infections.


title: Detection of rodent coronaviruses in tissues and cell cultures by using polymerase chain reaction.

text: A polymerase chain reaction (PCR) method was developed for the detection of rodent coronaviruses in biological material by using reverse transcriptase and two primers which flanked an M gene sequence of 375 bp. PCR detected all of 11 different strains of mouse hepatitis virus (MHV) as well as rat sialodacryoadenitis virus but not bovine coronavirus or human coronavirus strains OC43 and 229E. The M gene sequences of bovine coronavirus and human coronavirus OC43 are homologous to that of MHV, but minor differences exist in the primer regions, preventing annealing of the primers. For detecting MHV-Y in tissue samples, PCR was faster than and at least as sensitive as either of the two bioassays (infant mouse bioassay and mouse antibody production test) currently used for MHV diagnostic purposes.


title: Adaptation of coronavirus JHM to persistent infection of murine sac(-) cells.

text: Coronaviruses can establish persistent infections in the central nervous system of rodents, and these are associated with demyelinating encephalomyelitis. The effects of persistence on the virus are difficult to study in vivo but may have a crucial influence on the course of infection. We therefore produced a persistent infection in vitro using the neurotropic coronavirus JHM, in order to investigate the events underlying the establishment of such an infection and the adaptation of the virus to persistence. The persistent infection was maintained for over 115 passages and continued to release high levels of infectious virus. During the 18 months of culture the number of cells expressing virus antigen detected by indirect immune fluorescence decreased to 40%. Analysis showed that the carried virus contained a significant proportion of heterogeneous temperature-sensitive mutants. All virus clones isolated possessed the capacity to induce a more productive growth cycle, a less pronounced cytopathic effect and showed a much reduced neurovirulence when inoculated into newborn and weanling rats. Evidence for structural changes involving the surface peplomer protein (E2) was obtained using hybridoma antibodies, which neutralized the parental JHM virus but not the JHM-Pi virus. Defective interfering particles and interferon activities have been excluded as possible agents instrumental in the establishment and maintenance of the chronic infection, and we suggest that the emergence of virus variants of lowered virulence is central to these processes.


title: A social explanation for the rise and fall of global health issues.

text: This paper proposes an explanation concerning why some global health issues such as HIV/AIDS attract significant attention from international and national leaders, while other issues that also represent a high mortality and morbidity burden, such as pneumonia and malnutrition, remain neglected. The rise, persistence and decline of a global health issue may best be explained by the way in which its policy community--the network of individuals and organizations concerned with the problem--comes to understand and portray the issue and establishes institutions that can sustain this portrayal. This explanation emphasizes the power of ideas and challenges interpretations of issue ascendance and decline that place primary emphasis on material, objective factors such as mortality and morbidity levels and the existence of cost-effective interventions. This explanation has implications for our understanding of strategic public health communication. If ideas in the form of issue portrayals are central, strategic communication is far from a secondary public health activity: it is at the heart of what global health policy communities do.


The dietary fibre debate: more food for thought.


title: The international response to the outbreak of SARS in 2003.

text: The sudden arrival of an internationally spreading outbreak of a newly identified infectious disease in early 2003, severe acute respiratory syndrome (SARS), provided an opportunity for a coordinated international response based on information and evidence obtained in real time through standard and electronic communications. Its containment represents a new way of working internationally, and demonstrates how intense collaboration in virology, clinical medicine and epidemiology can rapidly provide the information necessary to create and implement evidence-based control measures. The SARS outbreak serves as a reminder of the need for a strong national surveillance and response to infectious diseases, evidence-based international travel recommendations, and a global alert and response network to serve as a safety net when national surveillance fails.


title: Diagnostic and public health dilemma of lactose-fermenting Salmonella enterica serotype Typhimurium in cattle in the Northeastern United States.

text: The presence of lactose-fermenting Salmonella strains in clinical case materials presented to microbiology laboratories presents problems in detection and identification. Failure to detect these strains also presents a public health problem. The laboratory methods used in detecting lactose-fermenting Salmonella enterica serotype Typhimurium from six outbreaks of salmonellosis in veal calves are described. Each outbreak was caused by a multiply-resistant and lactose-fermenting strain of S. enterica serotype Typhimurium. The use of Levine eosin-methylene blue agar in combination with screening of suspect colonies for C8 esterase enzyme and inoculation of colonies into sulfide-indole-motility medium for hydrogen sulfide production was particularly effective for their detection. A hypothesis for the creation of lactose-fermenting salmonellae in the environment is presented. It is proposed that the environment and husbandry practices of veal-raising barns provide a unique niche in which lactose-fermenting salmonellae may arise.


Filling the hole: evidence of a small molecule binding to the fusion core pocket in human respiratory syncytial virus.


title: [Mouse hepatitis virus].

text: Mouse hepatitis virus (MHV), the coronavirus of the mouse (mus musculus), is one of the most important viral pathogens in contemporary laboratory mouse colonies. It is a highly mutable virus consisting of numerous antigenically distinct serotypes with different pathology. These can be divided according to their tissue tropism into respiratory and enterotropic strains. The course of an MHV infection is dependent on virus strain and host factors. Generally MHV causes an acute, self limiting infection which is inapparent in adult mice. Neonates are highly susceptible to disease and show high mortality. In an enzootically infected colony however, they are protected by maternally derived passive immunity. MHV's importance in biomedical research on one hand stems from its potential as an interfering agent, mainly in the field of immunology. On the other hand MHV serves as a model for coronaviruses of other species including man in studies on virus replication and tissue tropism. Since MHV infections are usually subclinical, detection depends on serological screening of colonies using Enzyme-linked immunosorbent assay (ELISA) or immunofluorescence. MHV is controlled by culling and rederivation of the affected colony using hysterectomy or embryo transfer or by elimination by cessation of breeding.


title: Carotid Artery Stenosis with Acute Ischemic Stroke: Stenting versus Angioplasty.

text: BACKGROUND When a patient with carotid artery stenosis presents emergently with acute ischemic stroke, the optimum treatment plan is not clearly defined. If intervention is warranted, and open surgery is prohibitive, endovascular revascularization may be performed. The use of stents places the patient at additional risk due to their thrombogenic potential. The intent of this study was to compare outcomes following endovascular approaches (angioplasty alone vs. stent) in the setting of acute stroke. METHODS We extracted a population from the National Inpatient Sample (2012) and the Nationwide Inpatient Sample (2003-2011) composed of patients with carotid artery stenosis with infarction that were admitted nonelectively and received endovascular revascularization. Patients treated with mechanical thrombectomy or thrombolysis were excluded. Categorical variables were compared between treatment groups with Chi-squared tests. Binary logistic regression was performed to evaluate mortality and iatrogenic stroke while controlling for age, case severity, and comorbidity burden. RESULTS About 6,333 admissions met our criteria. A majority were treated via stenting (89%, n = 5,608). The angioplasty-alone group had significantly higher mortality (9.0% vs. 3.8%, p < 0.001) and iatrogenic stroke rate (3.9% vs. 1.9%, p < 0.001) than the stent group. The adjusted odds ratios of mortality and iatrogenic stroke for patients treated with angioplasty alone were 1.953 (p < 0.001) and 1.451 (p = 0.105), respectively, in comparison to patients treated with carotid stenting. CONCLUSION Multivariate analysis found the risk of mortality to be elevated following angioplasty alone. This may represent selection bias, but it also may indicate that symptomatic patients with stroke suffer from severe stenosis and unstable plaques that would benefit from stent placement. These results would caution angioplasty alone as an arm of a future randomized trial involving this severely burdened patient population requiring urgent intervention.


Changing virulence of the SARS virus: the epidemiological evidence.


title: Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China.

text: A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory syndrome (SARS). SCoV-like viruses were isolated from Himalayan palm civets found in a live-animal market in Guangdong, China. Evidence of virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the same market. All the animal isolates retain a 29-nucleotide sequence that is not found in most human isolates. The detection of SCoV-like viruses in small, live wild mammals in a retail market indicates a route of interspecies transmission, although the natural reservoir is not known.


Molecular evolution of corona- and toroviruses.


title: Epidemiologic linkage and public health implication of a cluster of severe acute respiratory syndrome in an extended family.

text: Severe acute respiratory syndrome (SARS) is highly contagious. Mandatory home confinement of 10 days has generally been recommended to quarantine close contacts of SARS cases. We report the epidemiologic linkage of SARS within an extended family. The estimated incubation period was beyond 10 days in some of the affected members. One child was identified as the source of SARS transmission to another household.


Evaluation and research.


Caring for transplant recipients in a nontransplant setting.


title: [Gene sequence analysis of SARS-associated coronavirus by nested RT-PCR].

text: OBJECTIVE To explore an effective means for the detection of Severe Acute Respiratory Syndrome (SARS)- associated coronavirus. METHODS The RNAs of the virus contained in the sputum samples from established SARS patients were extracted and reversely transcripted, followed by nested PCR using the reversely transcripted cDNA as the template. The PCR products were cloned then into the pMD18-T vectors, followed by sequence analysis. RESULTS Specific fragments were amplified from the sputum samples of SARS patients, which were confirmed by DNA cloning and sequencing to belong to SARS-associated coronavirus. The Result of Blast shows only the difference in one nucleic acid from the TOR2 strain of SARS-associated coronavirus. CONCLUSION Sequence analysis has confirmed the existence of SARS-associated coronavirus in the sputum samples of SARS patients, and nested RT-PCR is a quick, easy, and convenient way for the detection of the virus.


Thank You to Our 2016 Reviewers.


Nematodirosis frequently diagnosed in lambs.


title: Children with developmental and behavioural concerns in Singapore.

text: INTRODUCTION Childhood developmental and behavioural disorders (CDABD) have been increasingly recognised in recent years. This study evaluated the profiles and outcomes of children referred for developmental and behavioural concerns to a tertiary child developmental centre in Singapore. This is the first such regional database. METHODS Baseline information, obtained through a questionnaire, together with history at first consultation, provided information for referral, demographic and presentation profiles. Clinical formulations were then made. Definitive developmental and medical diagnoses, as well as outcomes based on clinical assessment and standardised testing, were recorded at one year post first consultation. RESULTS Out of 1,304 referrals between January 1, 2003 and December 1, 2004, 45% were 2-4 years old and 74% were boys. The waiting time from referral to first consultation exceeded four months in 52% of children. Following clinical evaluation, 7% were found to be developmentally appropriate. The single most common presenting concern was speech and language (S&L) delay (29%). The most common clinical developmental diagnosis was autism spectrum disorder (ASD) (30%), followed by isolated S&L disorder, global developmental delay (GDD) and cognitive impairment (CI). Recommendations included S&L therapy (57%), occupational therapy (50%) and psychological/behavioural services (40%). At one year, ASD remained the most common definitive developmental diagnosis (31%), followed by S&L disorder, CI and GDD. Most were children with high-prevalence, low-moderate severity disorders who could potentially achieve fair-good prognosis with early intervention. CONCLUSION Better appreciation of the profile and outcome of children with CDABD in Singapore could enable better resource planning for diagnosis and intervention.


Strongyloides stercoralis infection as a manifestation of immune restoration syndrome?


title: Percutaneous Transhepatic Embolization of Bleeding Rectal Varices Using A New Embolic And Sclerotic Mixture Augmented By Amplatzer Vascular Plug 2.

text: We report a case of 59-year-old female with non-alcoholic-steato-hepatitis (NASH) induced cirrhosis, who presented with hematochezia. The patient had a history of bleeding esophageal varices treated with endoscopic variceal ligation (EVL). Colonoscopy showed large rectal varices which were the source of her lower gastrointestinal bleeding (LGIB). Since endoscopic treatment for LGIB are limited, and because the patient had portal vein thrombosis which contraindicated transjugular intrahepatic portosystemic shunt (TIPS), we performed percutaneous transhepatic embolization of her rectal varices using a new mixture of embolic and sclerotic agents, followed by Amplatzer plug 2 (AVP 2). To our knowledge, the use of this new mixture with the AVP 2 in the rectal varices treatment has not been previously published in literature. Our case provides an alternative treatment modality that can be used for rectal varices treatment, when TIPS and endoscopic management fails or is contraindicated.


[Principles in health policy during the SARS-CoV-2 outbreak - major lessons from South East-Asia].


title: Coagulation Panel in Patients with SARS-CoV2 Infection (COVID-19).

text: The 2019 novel coronavirus (SARS-CoV2) is the causal agent of the newly-termed Coronavirus Disease 2019 (COVID-19). In January 2020, the World Health Association (WHO) declared the CO-VID-19 as an epidemic. Abnormal coagulation parameters in COVID-19 patients currently are considered as prognostic factors of severity. Our aim is to summarize the current data available in the literature. MATERIALS AND METHODS An electronic search was performed in the Database of publications on coronavirus disease (COVID-19) of the World Health Organization. Thrombin Time (TT), Prothrombin Time (PT), Fibrinogen (FIB), Activated Partial Thromboplastin Time (APPT), and D-Dimer have been detected as parameters to study in every COVID-19 patient. CLINICAL APPLICATION The coagulation function panel has been described to be altered in critical COVID-2019 patients. DIC, which plays an important role in advanced stage, is known to be associated with sepsis. Anticoagulant therapy, mainly with low molecular weight heparin (LMWH), appears to be associated with better prognosis in patients with severe COV-ID-19. DISCUSSION Coagulation function in patients with SARS-CoV2 infection is significantly deranged compared with normal patients. FIB and D-Dimer/FDP are the most significantly altered values and the early deetection of alteration could be useful to address therapies. D-Dimer/FDP (DD/FDP) alteration correlates with severity. Markedly elevated D-Dimer can be used to guide the introduction of anticoagulation therapy and evaluate prognosis of COVID-19. In every patient admitted with SARS-CoV2 infection PT, FIB, D-Dimer/FDP, and platelets must be ordered. We suggest daily extraction for every patient admitted and tested positive for COVID-19.


title: Control of influenza virus infection by immunity to conserved viral features.

text: Influenza has circulated among humans for centuries and kills more people than many newly emerging diseases. The present methods for control of influenza are not adequate, especially for dealing with a pandemic. In the face of a rapidly spreading outbreak, a race to isolate the virus and prepare a vaccine would probably not succeed in time to avoid great losses. Thus, additional anti-infection strategies are needed. Broad cross-protection against widely divergent influenza A subtypes is readily achieved in animals by several means of immunization. How does cross-protection work in animals, and can we apply what we have learned about it to induce broad cross-protection in humans?


title: [Immunisation strategies for the management of severe acute respiratory syndrome (SARS)].

text: Most patients with severe acute respiratory syndrome (SARS) develop antibodies against the SARS coronavirus and survive the infection. This suggests that active or passive immunisation might be an effective option in preventing or treating SARS. Therefore, the development of SARS vaccination strategies belongs to the most important targets of SARS research. The present study analyses data-bases for the current knowledge on vaccination strategies. Both, passive and active immunisation protocols are presently being developed. Passive immunisation with sera from surviving patients leads to partial success. Whereas the passive immunisation exhibits a promising therapeutic tool, only active immunisation can successfully prevent infection. A number of approaches has been used on the basis of inactivated SARS coronaviruses, recombinant subunits, recombinant DNA, and viral vectors. However, all recently developed candidates need to be evaluated critically before clinical use. The so-called "antibody-dependent enhancement" can improve viral uptake into host cells resulting in increased viral load and exacerbation of disease.


SARS-struck nations step up surveillance efforts.


title: [Laparoscopic cholecystectomy with single incision laparoscopic surgery].

text: UNLABELLED For the last seventeen years laparoscopic cholecystectomy has remained the gold standard procedure for gallbladder surgery The single incision laparoscopic surgery (SILS) approach is a step toward less invasive surgery and the intraumbilical access improves the cosmetic effect (no scar surgery). The aim of the study was to present our preliminary experience in laparoscopic cholecystectomy through single intraumbilical incision. MATERIAL AND METHODS Three patients with gallbladder symptoms (2 female, 1 male) underwent surgery through single intraumbilical incision. In two cases the procedure was performed with three 5 mm Dexide port approach and in one, with a flexible rubber/gel SILSTM-Port (Covidien, USA) access. A simple 5 mm optics was employed. In two procedures the following disposable instruments were used: roticulator Endo dissect, roticulator Endo grasp, mini Sears scissors as well as standard hook and clips while for the third procedure, a conventional multi-use grasp and roticular Endo dissect. The gallbladder was elevated to the integuments by two sutures to expose Calot's triangle and bladder site. Following exposure, the bile duct and the vesical artery were clipsed and cut routinely to remove the gallbladder in a plastic bag through the bell-button. After procedures no drains were left in the peritoneal cavities. RESULTS In all three cases the laparoscopic procedure was performed. The median operative time was 88 min. In one female patient, bleeding into the peritoneal cavity was reported and called for laparotomy within a few hours of laparoscopic procedure. Intraoperatively, the branch of vesical artery was sutured to arrest bleeding. The median hospital stay following procedure was 3, 8 and 5 days respectively. After the procedure, the last female patient was observed to have pharyngitis and enlarged jugular lymph nodes that abated after antibiotic therapy. CONCLUSIONS Single-incision laparoscopic cholecystectomy should be performed by experienced laparoscopic surgeons. For adequate evaluation of the efficacy and safety of this procedure it is necessary to perform further clinical studies on a larger number of patients.


title: 2019 Novel Coronavirus Pandemic: What Do We Know?

text: The pandemic caused by SARS-COV2 Virus/COVID-19, which was initially reported in China in December 2019, has become a major global health concern. COVID-19 can manifest with cytokine storm - an exaggerated systemic inflammatory phenomenon due to over-production of proinflammatory cytokines by immune cells that results in diffuse inflammatory lung disease and acute respiratory distress syndrome. It may be complicated by septic shock and subsequent multi-organ failure. Based on the most recently published evidence, this article will review and discuss comprehensive information on its clinical manifestations, laboratory tests, potential therapeutics, and prevention guidelines.


title: A hospital outbreak of Legionella from a contaminated water supply.

text: The authors performed a cross-sectional epidemiological survey to investigate the source of a hospital Legionella outbreak originating in contaminated water. Water temperature and air humidity were measured around possible contamination sources. A dead-end pipe was found to contain Legionella pneumophila serogroup 1. All individuals who acquired legionellosis had spent at least 30 min within 2 m of the contamination source. Among staff, 41 of 71 were exposed, and 31 of these fell ill. All 7 patients exposed to the contaminated water acquired legionellosis. None of the 94 bed-ridden patients from the same units developed the disease. An aerosol with 60% relative air humidity was formed near the suspect water faucets, but the humidity fell rapidly farther from the water source, suggesting that desiccation decreased the risk of infection. The healthy personnel and patients closest to the source acquired legionellosis, suggesting that risk was related less to compromised patients than to exposure.


title: [Human coronavirus-NL63 was detected in specimens from children with acute respiratory infection in Beijing, China].

text: OBJECTIVE A new human coronavirus, HCoV-NL63, was identified recently from two Dutch children with acute respiratory infection (ARI) by two scientists in the Netherlands in 2004. To investigate if this newly discovered virus is associated with acute respiratory infections in pediatric patients in Beijing, tests were developed to detect HCoV-NL63 gene fragments from throat swab and nasopharyngeal aspirates collected from children in outpatient and inpatient departments with ARI in Beijing from Dec. 2003 to Mar. 2004. METHODS A total of 245 clinical samples, which were negative either for diagnostic tests of human respiratory syncytial virus, influenza virus A and B, adenovirus, parainfluenza virus 1, 2 and 3 by indirect immunofluorescence assay or human metapneumovirus by RT-PCR, were screened for HCoV-NL63 by nested PCR amplifying gene fragments located on the 1b and 1a genes. Amplicon of PCR from 1a gene of HCoV-NL63 was sequenced and the sequences were compared with those in GenBank nucleotide sequence database. RESULTS Three (1.2%) out of the 245 samples were positive for HCoV-NL63 by nested-PCR using primers on 1b gene. These three samples also showed positive results on nested PCR in which primers were designed with sequences complementary to 1a gene segments. These positive samples were collected from hospitalized children under 2 years of age with pneumonia, bronchiolitis and bronchitis, respectively. The partial 1a gene sequences from two positive samples (BJ3140 and BJ3787) of HCoV-NL63 showed 100% homology between each other and high homology (98%-99%) with the sequences of 1a gene of HCoV-NL63 reported from different countries in GenBank. Phylogenetic analysis showed that BJ3140 and BJ3787 fell into the same genetic cluster (group 1). CONCLUSIONS These data suggest that some of acute respiratory infections in young children in Beijing area are related to the newly identified HCoV-NL63.


title: Efficacy of vaccination of sows with serologically related coronaviruses for control of transmissible gastroenteritis in nursing pigs.

text: Three groups of pregnant sows were vaccinated at 8 and 2 weeks before parturition with tissue culture-adapted feline infectious peritonitis (FIP) virus, porcine transmissible gastroenteritis (TGE) small-plaque (SP) virus from a persistently infected cell line, or noninfected cell culture fluids (controls). Pigs nursing vaccinated sows were orally challenge exposed with virulent TGE virus when they were 1 to 3 days old. The morbidity of the nursing pigs was 48% in the SP-TGE group, 82% in the FIP group, and 93% in the controls. The survival rate among the nursing pigs was 77% in the SP-TGE groups, 48% in the FIP group, and 14% in the controls. Virus-neutralizing antibodies of immunoglobulin A were detected in colostrum and milk of the SP-TGE group, but not in the FIP or control groups.


title: Vaccination in conservation medicine.

text: Unprecedented human population growth and anthropogenic environmental changes have resulted in increased numbers of people living in closer contact with more animals (wild, domestic, and peridomestic) than at any other time in history. Intimate linkage of human and animal health is not a new phenomenon. However, the global scope of contemporary zoonoses has no historical precedent. Indeed, most human infectious diseases classed as emerging are zoonotic, and many of these have spilled over from natural wildlife reservoirs into humans either directly or via domestic or peridomestic animals. Conservation medicine has recently emerged as a meaningful discipline to address the intersection of animal, human, and ecosystem health. Interest in the development of novel vaccines for wildlife encounters important challenges that may prevent progress beyond the conceptual phase. Although notable examples of successful wildlife immunisation programmes exist, depending upon key considerations, vaccination may or may not prove to be effective in the field. When implemented, wildlife vaccination requires a combination of novel zoonosis pathogen management strategies and public education to balance conservation, economic, and public health issues.


title: Brazilian recommendations of mechanical ventilation 2013. Part 2.

text: Perspectives on invasive and noninvasive ventilatory support for critically ill patients are evolving, as much evidence indicates that ventilation may have positive effects on patient survival and the quality of the care provided in intensive care units in Brazil. For those reasons, the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB) and the Brazilian Thoracic Society (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT), represented by the Mechanical Ventilation Committee and the Commission of Intensive Therapy, respectively, decided to review the literature and draft recommendations for mechanical ventilation with the goal of creating a document for bedside guidance as to the best practices on mechanical ventilation available to their members. The document was based on the available evidence regarding 29 subtopics selected as the most relevant for the subject of interest. The project was developed in several stages, during which the selected topics were distributed among experts recommended by both societies with recent publications on the subject of interest and/or significant teaching and research activity in the field of mechanical ventilation in Brazil. The experts were divided into pairs that were charged with performing a thorough review of the international literature on each topic. All the experts met at the Forum on Mechanical Ventilation, which was held at the headquarters of AMIB in São Paulo on August 3 and 4, 2013, to collaboratively draft the final text corresponding to each sub-topic, which was presented to, appraised, discussed and approved in a plenary session that included all 58 participants and aimed to create the final document.


State of Missouri Supported by Four Essential Pillars for COVID-19 Response.


title: Outcome of abdominal wall hernia repair with Permacol™ biologic mesh.

text: The use of biologic mesh in abdominal wall operations has gained popularity despite a paucity of outcome data. We aimed to review the experience of a large healthcare organization with Permacol™. A retrospective study was conducted of patients who underwent abdominal hernia repair with Permacol™ in 14 Southern California hospitals. One hundred ninety-five patients were analyzed over a 4-year period. Operations included ventral/incisional hernia repairs, ostomy closures, parastomal hernia repairs, and inguinal hernia repairs. In 50 per cent of the patients, Permacol™ was used to reinforce a primary fascial repair and in 50 per cent as a fascial bridge. The overall complication rate was 39.5 per cent. The complication rate was higher in patients with infected versus clean wounds, body mass index (BMI) 40 kg/m(2) or greater versus BMI less than 40 kg/m(2), in patients with prior mesh repair, and when mesh was used as a fascial bridge. With a mean follow-up of 2.1 years, morbid obesity was associated with a higher recurrence. To date this is the largest study on the use of Permacol™ in abdominal wall hernia repair. In our patient population undergoing heterogeneous operations with a majority of wounds as Class II or higher, use of Permacol™ did not eliminate wound morbidity or prevent recurrence, especially in morbidly obese patients.


World Health Organization.


title: Inhibition of N-nitrosodimethylamine metabolism in rats by ether anesthesia.

text: Short-term exposure to diethyl ether strongly inhibits the metabolism of N-nitrosodimethylamine (NDMA). Twenty-six 6-week-old male Fischer 344 rats were exposed to ether vapor until their righting reflex was lost (approximately 2 min). The animals were removed from the ether and NDMA was immediately administered by i.v. bolus injection at a dose of 300 microgram/kg via a cannula surgically inserted 20 h earlier. A second group of 28 rats received injections of NDMA in an identical manner but without ether exposure. In the unanesthetized animals blood levels of NDMA declined with a half-life of 11 min; by contrast essentially constant blood levels of NDMA were observed in ether-treated animals for 120 min after removal from the anesthetic. The apparent total systemic clearance for the 5-h experiment was reduced from 43 ml/min/kg without ether to 5 ml/min/kg with ether. Diethyl ether has been found previously to inhibit the metabolism of other drugs requiring oxidative metabolism but the suppression of clearance documented here appears to be unusually pronounced. It is recommended that ether's potential for altering metabolic rates be carefully considered when planning or interpreting animal experiments.


title: Induction of a protective immune response to murine coronavirus with non-internal image anti-idiotypic antibodies.

text: Neurotropic murine coronaviruses (MHV) provide an excellent animal model to study experimental modulation of the immune response to a viral pathogen with anti-idiotypic antibodies. It is known that among the various types of anti-idiotypic antibodies (anti-Id), those designated beta (beta) or internal image can molecularly mimic the antigen and induce biological activities such as anti-viral protection and neutralization. We have recently shown that polyclonal non-internal image anti-idiotypic antibodies of the gamma-type could induce protective anti-coronavirus immunity. In the present study, a polyclonal anti-Id (Ab2) was induced against a neutralizing murine monoclonal antibody (MAb1), designated 5B170.11. Mice immunized with this affinity-purified rabbit Ab2 alpha, a non-internal image antibody, were partially protected against lethal infection by the JHM strain of MHV. However, other polyclonal and monoclonal non-internal image Ab2 induced against another neutralizing Mab1, designated 4-11G.6, were not able to protect mice against lethal infection with the A59 strain of MHV. These results demonstrate that anti-viral protection by altering the idiotypic network with non-internal image-bearing anti-idiotype reagents can be achieved even with some anti-Id of the alpha-type.


title: In vitro antiviral activity of plant extracts on goatpox virus replication.

text: Four plants having known medicinal properties were screened for inhibition of goatpox virus (GTPV) replication in vitro. Of the 4 plants, extract of Acacia arabica (Babul) and Eugenia jambolana (Jamun) leaves had inhibition (%) 99.70 and 99.92 at their maximum non toxic concentrations, 99.93 +/- 0.38 and 1999.73 +/- 0.50 microg/ml, respectively in all cytopathic effect (CPE) inhibition assays. Inhibition of GTPV virus replication was further confirmed by PCR and SYBR Green based quantitative real-time QPCR assays specific for GTPV. Results indicated that the extract of Acacia arabica and Eugenia jambolana leaves inhibited GTPV replication in vitro.


title: Core structure of S2 from the human coronavirus NL63 spike glycoprotein.

text: Human coronavirus NL63 (HCoV-NL63) has recently been identified as a causative agent of acute respiratory tract illnesses in infants and young children. The HCoV-NL63 spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This viral entry process is a primary target for vaccine and drug development. HCoV-NL63 S is expressed as a single-chain glycoprotein and consists of an N-terminal receptor-binding domain (S1) and a C-terminal transmembrane fusion domain (S2). The latter contains two highly conserved heptad-repeat (HR) sequences that are each extended by 14 amino acids relative to those of the SARS coronavirus or the prototypic murine coronavirus, mouse hepatitis virus. Limited proteolysis studies of the HCoV-NL63 S2 fusion core identify an alpha-helical domain composed of a trimer of the HR segments N57 and C42. The crystal structure of this complex reveals three C42 helices entwined in an oblique and antiparallel manner around a central triple-stranded coiled coil formed by three N57 helices. The overall geometry comprises distinctive high-affinity conformations of interacting cross-sectional layers of the six helices. As a result, this structure is unusually stable, with an apparent melting temperature of 78 degrees C in the presence of the denaturant guanidine hydrochloride at 5 M concentration. The extended HR regions may therefore be required to prime the group 1 S glycoproteins for their fusion-activating conformational changes during viral entry. Our results provide an initial basis for understanding an intriguing interplay between the presence or absence of proteolytic maturation among the coronavirus groups and the membrane fusion activity of their S glycoproteins. This study also suggests a potential strategy for the development of improved HCoV-NL63 fusion inhibitors.


title: Development of a respiratory virus panel test for detection of twenty human respiratory viruses by use of multiplex PCR and a fluid microbead-based assay.

text: Virology laboratories historically have used direct fluorescent-antibody assay (DFA) and culture to detect six or seven respiratory viruses. Following the discovery of five new human respiratory viruses since 2000, there is an increasing need for diagnostic tests to detect these emerging viruses. We have developed a new test that can detect 20 different respiratory virus types/subtypes in a single 5-h test. The assay employs multiplex PCR using 14 virus-specific primer pairs, followed by a multiplexed target-specific primer extension (TSPE) reaction using 21 primers for specific respiratory virus types and subtypes. TSPE products were sorted and identified by using a fluid microsphere-based array (Universal Array; TmBioscience Corporation, Toronto, Canada) and the Luminex x-MAP system. The assay detected influenza A and B viruses; influenza A virus subtypes H1, H3, and H5 (including subtype H5N1 of the Asian lineage); parainfluenza virus types 1, 2, 3, and 4; respiratory syncytial virus types A and B; adenovirus; metapneumovirus; rhinovirus; enterovirus; and coronaviruses OC43, 229E, severe acute respiratory syndrome coronavirus, NL63, and HKU1. In a prospective evaluation using 294 nasopharyngeal swab specimens, DFA/culture detected 119 positives and the respiratory virus panel (RVP) test detected 112 positives, for a sensitivity of 97%. The RVP test detected an additional 61 positive specimens that either were not detected by DFA/culture or were positive for viruses not tested for by DFA/culture. After resolution of discordant results by using a second unique PCR assay and by using a combined reference standard of positivity, the RVP test detected 180 of 183 true positives, for a sensitivity of 98.5%, whereas DFA and culture detected only 126 of 183 true positives, for a sensitivity of 68.8%. The RVP test should improve the capabilities of hospital and public health laboratories for diagnosing viral respiratory tract infections and should assist public health agencies in identifying etiologic agents in respiratory tract infection outbreaks.


title: Short-term outcomes after minimally invasive oesophagectomy.

text: INTRODUCTION Minimally invasive oesophagectomy (MIO) has gained increasing popularity. This study reports the results of the first patients operated using this technique at our department. METHODS All procedures were prospectively registered in a database. Patients were followed until death, two years after surgery or 1 January 2019. RESULTS A total of 150 procedures were performed (from 23 November 2015 to 27 February 2018). The median proced-ure time decreased from 350 minutes for the initial 75 pa-tients to 320 minutes for the final 75 patients (p < 0.05). Blood loss decreased from 200 ml to 100 ml (p < 0.05), respectively. The conversion rate for the abdominal procedure was 7% for the initial 75 patients and 8% for the final 75 patients (not significant (NS)). For the thoracic procedure, the corresponding figures were 11% and 7% (NS), respectively. Anastomotic leakage was seen in 17% (initial patients) and 11% (final patients) (NS); however, less than 20% of the leakages needed surgical treatment. The median length of post-operative stay was nine days for both groups. For all 150 patients, pulmonary complications were observed in 18% and cardiac complications in 11%. The 30-day mortality rate was 2% and the one-year survival rate was 86% (124 registered patients). CONCLUSIONS MIO was introduced at our department with acceptable morbidity and mortality rates and the short-term oncological result was not compromised. FUNDING none. TRIAL REGISTRATION The study was approved as a quality project by the Region of Southern Denmark (18/37355).


title: [Modelling epidemics: the case of severe acute respiratory syndrome in Canada].

text: OBJECTIVE Severe acute respiratory syndrome propagation in Canada during 2003 is analysed by means of simple models, comparing the influence of isolation measures on two epidemic waves. METHODS Deterministic susceptible-infected and susceptible-infected-removed models were used for both epidemic waves, using official published information. NLREG 6.2 was used for estimating deterministic parameters and analytical solutions were obtained with Maple 9 software. Dynamical indicators were obtained for the epidemic. RESULTS Suitable adjustment of the data was observed with both models, but smaller adjustment was observed during the second wave with the non- removed model. The highest rate of infectiousness was shown (35 new cases per 10 000 susceptible people) during the second wave (with R0 near to one), in spite of presenting greater incidence (8.8 cases per day), compensated for by a high rate of removal (11,5 cases per day) which lasted less than the epidemic (11,1 days), and a lower rate of attack (1 case per each 100 susceptible people). CONCLUSIONS The susceptible-infected model can be useful during an epidemic's initial phase (prior to removal); however, closer monitoring of an epidemic's development is required for modelling the strength of removal and deriving useful information for decision-making.


Mouse hepatitis virus-3 induced prothrombinase (Fgl2) maps to proximal chromosome 5.


title: Comparison of perioperative surgical outcomes between a bipolar device and an ultrasonic device during laparoscopic gastrectomy for gastric cancer.

text: BACKGROUND The use of energy devices during laparoscopic gastrectomy for gastric cancer has increased as the frequency of laparoscopic surgery has increased. Our aim was to compare the perioperative surgical outcomes between using a bipolar device and an ultrasonic device during laparoscopic gastrectomy. METHODS Retrospective review of a prospectively maintained database identified 186 patients who underwent laparoscopic gastrectomy performed by a single surgeon between November 2010 and August 2013. A bipolar device was used for 116 patients, and an ultrasonic device was used for 70 patients. Patient characteristics and perioperative surgical outcomes were compared between groups. RESULTS Clinicopathologic characteristics were similar for both groups. The bipolar group had a significantly shorter operation time (154.9 vs. 167.8 min, p = 0.028) and higher rate of D2 lymph node dissection (29.3 vs. 15.7 %, p = 0.012). The bipolar device group experienced significantly less pain at 12 h [visual analog scale (VAS) pain score: 3.9 vs. 4.7, p = 0.027) and 18 h (VAS pain score: 3.5 vs. 4.1, p = 0.036) postoperatively. The bipolar group had earlier abdominal drain removal (p = 0.001) and a shorter hospital stay (p = 0.024). No significant differences in laboratory value changes, morbidity, or mortality were observed between the groups. CONCLUSION Compared with the ultrasonic device, the bipolar device provided advantages in operation time, degree of postoperative pain, time of drain removal, and length of hospital stay. The bipolar device may be a useful and efficient energy device for laparoscopic gastrectomy. However, larger studies to confirm the safety of bipolar device during laparoscopic gastrectomy are warranted.


title: Mucosal and systemic isotype-specific antibody responses to bovine coronavirus structural proteins in naturally infected dairy calves.

text: Blood, feces, nasal secretions, and tears were collected weekly from 5 randomly selected 1- to 8-week-old calves in a large commercial dairy herd. Clinical signs and bovine coronavirus (BCV) shedding from the respiratory and enteric tracts of calves were monitored through the 8-week period by direct immunofluorescence of nasal epithelial cells, protein A-gold immunoelectron microscopy on feces, and ELISA on nasal secretions and feces. All samples were analyzed for antibody isotypes to BCV structural proteins by immunoblotting. All calves had BCV respiratory tract infections and 4 of 5 calves shed virus in feces. Several calves had multiple or prolonged periods of BCV respiratory tract or enteric tract shedding or both. All calves (except 1) had passive IgG1 antibodies to some BCV proteins (mainly the E2 and E3 proteins) in their serum when they were 1 week old. The presence of these passive serum antibodies (mainly to the E2 and E3 BCV proteins) was associated with decreased or delayed systemic and mucosal antibody responses in calves, in particular IgA responses in nasal secretions and tears to the E2 and E3 BCV proteins, but not to the N protein. Moderate amounts of maternal BCV E2- and E3-specific antibodies in serum did not prevent BCV enteric tract or respiratory tract infections in calves, but may have delayed the development of active antibody responses to these BCV proteins. However, calves with BCV respiratory tract or enteric tract infections had no detectable passive antibodies to any BCV proteins in nasal secretions or feces.


title: [Current Topics of Cancer and HIV].

text: Antiretroviral therapy(ART)has been associated with reduced AIDS- and non-AIDS-related morbidity and mortality in people living with HIV/AIDS(PLWH). Nevertheless, the incidence of many comorbid conditions remains higher in PLWH than in the general population, including AIDS-defining malignancies(ADM)as well as several non-AIDS-defining malignancies (NADM). It's important to prevent ADM/NADM, like periodic health checkup for early diagnosis, to quit smoking, and cooperation with cancer and HIV specialists.