title: The early response to a novel coronavirus in the Middle East.

text: The detection of a novel coronavirus in patients from the Arabian Peninsula in late 2012 raised serious concerns of a possible international outbreak. Ministries of health of the three affected countries invited missions from the World Health Organization to participate in a review of data and capacity to detect and respond to further cases. Recommendations were made for investigations to answer critical questions about human-to-human transmission and the geographic extent of the virus. Additional recommendations were made to improve surveillance capacity by acquiring the capacity to test for the virus and enhance syndromic surveillance. Available evidence continues to suggest an unknown animal reservoir for the virus with sporadic zoonotic transmission the primary epidemiological pattern of transmission. Human-to-human transmission, while it can occur, does not appear to be sustained in the community.


title: Primary structure of the sialodacryoadenitis virus genome: sequence of the structural-protein region and its application for differential diagnosis.

text: Sialodacryoadenitis virus (SDAV) is a coronavirus that is commonly found in laboratory rats and that causes sialodacryoadenitis and respiratory illness. We cloned and sequenced the 3' terminal 9.8 kb of the genomic RNA and analyzed the structure of the viral genome. As with mouse hepatitis coronaviruses (MHVs), the SDAV genome was able to code for a spike protein, a small membrane protein, a membrane-associated protein, and a nucleocapsid protein. In addition, the hemagglutinin-esterase gene capable of encoding a protein of 439 amino acids (aa) was identified. The putative functional site for acetylesterase activity was present in the HE protein as Phe-Gly-Asp-Ser (FGDS), suggesting that the SDAV HE protein might have retained the esterase activity. Immediately upstream of the HE gene and downstream of the polymerase 1b gene, the NS2 nonstructural-protein gene was identified with a coding capacity of 274 aa. A motif of UCUAAAC was identified as a potential transcription signal for subgenomic mRNA synthesis. Large insertions of 172, 127, and 44 aa were detected in the N-terminal half of the predicted S protein of SDAV when its sequence was compared to the sequences of MHV 2, MHV JHM, and MHV A59, respectively. The sequence information on the SDAV S-protein gene was applied to a differential diagnostic PCR to detect and distinguish the rat coronavirus from mouse coronaviruses. This is the first report on the comprehensive genetic information of any rat coronavirus.


title: Extreme liver surgery as treatment of liver tumors involving the hepatocaval confluence.

text: OBJECTIVE Analyze the characteristics, surgical technique, morbidity and survival of patients treated with extreme liver surgery. MATERIALS AND METHODS We present a series of consecutive patients with malignant liver tumors in hepatocaval confluence treated in a single center with extreme liver surgery (April 2008-March 2015). Data were collected prospectively and analyzed with SPSS 21.0. RESULTS 12 patients were included. 50 % were male and 50 % were female with a mean age of 59 ± 10 years old. The median of comorbidities was 7 according to the Charlson Age Comorbidity Index. The 75 % of the tumors were metastases, most of them from colorectal cancer. Most of the patients received neoadjuvant chemotherapy and in 58 % preoperative portal embolization was performed. Major hepatectomies were performed (66.7 % extended right hepatectomy, 33.3 % left extended hepatectomy). The 83.3 % of the patients needed vascular reconstruction. Postoperative morbidity was more than grade II in 50 % of the patients according to Dindo-Clavien classification. There was no intraoperative mortality. The postoperative mortality rate at 90 days was 33 % due to hepatic failure and biliary fistula. In December 2015, 33 % of the patients are still alive with a mean survival of 19 months (13-23) with an ECOG Performance Status of 0. CONCLUSION Extreme liver surgery carries a high rate of morbidity and mortality that seem to increase with age and with higher tumor volumes, according to the literature. It is a therapeutic option to consider in patients with low comorbidity suffering from malignant neoplasms that involve the hepatocaval confluence, when no other treatment with curative intention can be performed.


title: [Clinical study on patients at early stage of severe acute respiratory syndrome].

text: OBJECTIVE To elucidate the clinical features of patients at early stage of severe acute respiratory syndrome (SARS). METHODS Fifty-three cases of early SARS were studied retrospectively. The data reviewed included those of epidemiology, clinical manifestations, laboratory investigation and roentgenology. RESULTS The patients consisted of 24 men and 29 women, aged 10.85 years (mean 38+/-16.7 years), including 9 infected health-care professionals (17.0%). The mean incubation period was 7.3+/-7.0 days (3.14 days). The onset symptoms were characterized by fever (100%), cough (49.1%), maylgia (24.5%), shortness of breath (20.8%), malaise (17.0%),and diarrhea (5.7%). Routine blood test during the first to the fifth day of the disease revealed WBCs less than 4.0x10(9) /L in 33 patients (62.3%), 4.0-10.0x10(9)/L in 18 patients (34.0%), lymphopenia in 36 patients (67.9%), and PLT less than 100.0x10(9) in 7 patients (13.2%). The main abnormal X-ray finding was single (75.4%) or bilateral (15.1%) localized patchy clouding opacity. The decrease of arterial partial pressure of oxygen occurred in 26 patients (49.1%). The damage of several organs was common, including the elevated ALT or AST in 20 patients (37.7%), elevated BUN or SCR in 6 patients (11.3%) and elevated LDH or CK or HBDH in 23 patients (43.4%). CONCLUSION The clinical manifestations of SARS at the early stage were complex. The close monitoring of the blood cell counts, the blood gas analysis and chest radiography might be crucial to the early diagnosis.


title: Surgery and Obstetric Care are Highly Cost-Effective Interventions in a Sub-Saharan African District Hospital: A Three-Month Single-Institution Study of Surgical Costs and Outcomes.

text: BACKGROUND The Lancet recently sponsored a commission examining the role of surgery in global health. There is a paucity of published information on the cost-effectiveness of surgery in low- and middle-income countries, a key metric in the prioritisation of limited resources. METHODS All patients undergoing emergency laparotomy, elective and emergency inguinal hernia repair, elective and emergency caesarean section, amputation, fracture manipulation, or fracture fixation over a 3 months period in a single district African hospital were assessed. World Health Organisation global burden of disease (GBD) methodology was used to calculate the disability-adjusted life years (DALYs) saved for each patient (using global and local life expectancy). Fully loaded costs were calculated for each patient’s care and providing the overall surgical service. Cost-effectiveness was calculated in year 2012 US$ per DALY saved for each procedure and overall. RESULTS A total of 428 patients were included, with an overall cost-effectiveness of $10.70 per DALY averted. The cost-effectiveness of individual procedures (global life expectancy) was: Amputation—$17.66; Emergency caesarean section—$7.42; Elective caesarean section—$20.50; Emergency laparotomy—$8.62; Elective hernia repair—$15.26; Emergency hernia repair—$4.36; Fracture/dislocation reduction—$69.03; Fracture/dislocation fixation—$225.89. CONCLUSIONS Surgery is a highly cost-effective healthcare measure in the setting of an African district hospital. The presented outcomes demonstrate that surgery is on a par with better-recognised and funded interventions such as HIV anti-retrovirals, malaria prevention and diarrhoea treatment. There are recognised limitations with the GBD methodology used here; however, this remains the best way to investigate the cost-effectiveness of health interventions. This study provides useful information on an, at present, under-studied field.


title: Inhibitor design for SARS coronavirus main protease based on "distorted key theory".

text: In order to find effective peptide inhibitors against SARS CoV M(pro), an analysis was performed for 11 oligo-peptides that can be cleaved by the SARS coronavirus main protease (CoV M(pro), or 3CL(pro)). Flexible molecular alignments of the 11 cleavable peptides have provided useful insights into the chemical properties of their amino acid residues close to the cleavage site. Moreover, it was found through the ligand-receptor docking studies that of the 11 cleavable peptides, NH2-ATLQ / AIAS-COOH and NH2-ATLQ / AENV-COOH had the highest affinity with SARS CoV M(pro). The two octapeptides were selected as initial templates for further chemical modification to make them become effective inhibitors against the SARS enzyme according to the "distorted key" theory [K. C. Chou, Analytical Biochemistry 233 (1996) 1-14]. The possible chemical modification methods are proposed and examined. The approach developed in this study and the findings thus obtained might stimulate new strategies and provide useful information for drug design against SARS.


title: [Dynamic changes of chest CT imaging in patients with COVID-19].

text: OBJECTIVE To analyze the dynamic changes of chest CT images of patients with coronavirus disease 2019 (COVID-19). METHODS Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. RESULTS The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare,the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). CONCLUSIONS The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.


title: [Pathologic study of circulating blood leukocytes in severe acute respiratory syndrome].

text: OBJECTIVE To study the pathologic characteristics and pathogenesis of circulating blood leucocytes infected by severe acute respiratory syndrome associated coronavirus (SARS CoV or SCV) in SARS patients. METHODS Blood samples of 22 SARS patients were studied, and 4 healthy blood samples were observed as negative controls. The white blood cells were collected from whole blood. The ultrastructural characteristics were observed by transmission electron microscopy. CD45RO antibody was used for pre-embedding immunoelectron microscopy. The SARS viral sequence was detected with real-time polymerase chain reaction (RT-PCR). RESULTS Coronavirus-like particles were founded in the leukocytes in 6 of the 22 blood samples. Five of them gave positive results in the real-time PCR. The number of granulocytes was increased (P < 0.05) and that of lymphocytes was decreased (P < 0.05) respectively. Immunoelectron microscopy showed that CD45RO positive T lymphocyte decreased to 6% - 7%. Circulating lymphocytes had the highest percentage of infection. The morphologic characteristics of coronavirus-like particles were spherical or oval in shape, about 80 - 120 nm in diameter, with a dense round core and a clear halo around the core. A distinct membrane and club-shaped surface projections were seen in the periphery. The particles were located in the cytoplasm, the cisternae of endoplasmic reticulum, Golgi apparatus and vesicles. Virus entered cells by endocytosis or membrane fusion and was released through a budding process. CONCLUSION Our data suggested that lymphocytes, particularly T cells, were probably the target cells of SARS CoV. The viruses may actively infected the immune cells during SARS CoV acute infection phase and the destruction of target cells may be one of the important reasons for the death of the circulating leukocytes in SARS.


title: A common RNA motif in the 3' end of the genomes of astroviruses, avian infectious bronchitis virus and an equine rhinovirus.

text: In the 3' non-coding region of the genomes of infectious bronchitis virus, an avian coronavirus and the picornavirus equine rhinovirus serotype 2, there is a motif with remarkable similarity, both in sequence and folding, to the second RNA stem-loop from the 3' end of the genomes of human astroviruses. This motif was also found in astroviruses of sheep, pig and turkey, suggesting that it is a common feature of all astroviruses. The conserved nature of the motif indicates that there has been strong selection for its preservation. There is significant homology between the regions flanking this motif in infectious bronchitis virus and a continuous RNA sequence at the same distance from the 3' poly(A) tail in some related mammalian coronaviruses. These observations suggest that the presence of the motif in these three viral families is the result of at least two separate RNA recombination events.


Fundamental limits to the precision of early warning systems for epidemics of infectious diseases.


SARS outbreak in the Greater Toronto Area: the emergency department experience.


title: Identification of ADP-ribosylated peptides and ADP-ribose acceptor sites.

text: ADP-ribosylation is a post-translational modification of proteins that comprises the transfer of the ADP-ribose moiety from NAD+ to specific amino acid residues on substrate proteins or to ADP-ribose itself. It is catalyzed by ADP-ribosyltransferases, a family of currently 22 human proteins that all possess an ADP-ribosyltransferase catalytic domain. ADP-ribosylation is a reversible modification that can be hydrolyzed by ADP-ribosylhydrolases. In order to define the functional role of cellular ADP-ribosylation and the functional contribution of distinct ARTD family members, it is necessary to identify all ADP-ribosylated proteins, as well as their modified residues in the context of different cellular conditions and stresses. Here, we summarize the most recent progress in defining the cellular ADP-ribosylome and the efforts to detect ADP-ribose acceptor sites by enzymatic reactions and mass-spectrometry.


title: Mucosal immunization with surface-displayed severe acute respiratory syndrome coronavirus spike protein on Lactobacillus casei induces neutralizing antibodies in mice.

text: Induction of mucosal immunity may be important for preventing SARS-CoV infections. For safe and effective delivery of viral antigens to the mucosal immune system, we have developed a novel surface antigen display system for lactic acid bacteria using the poly-gamma-glutamic acid synthetase A protein (PgsA) of Bacillus subtilis as an anchoring matrix. Recombinant fusion proteins comprised of PgsA and the Spike (S) protein segments SA (residues 2 to 114) and SB (residues 264 to 596) were stably expressed in Lactobacillus casei. Surface localization of the fusion protein was verified by cellular fractionation analyses, immunofluorescence microscopy, and flow cytometry. Oral and nasal inoculations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and mucosal IgA, as demonstrated by enzyme-linked immunosorbent assays using S protein peptides. More importantly, these antibodies exhibited potent neutralizing activities against severe acute respiratory syndrome (SARS) pseudoviruses. Orally immunized mice mounted a greater neutralizing-antibody response than those immunized intranasally. Three new neutralizing epitopes were identified on the S protein using a peptide neutralization interference assay (residues 291 to 308, 520 to 529, and 564 to 581). These results indicate that mucosal immunization with recombinant L. casei expressing SARS-associated coronavirus S protein on its surface provides an effective means for eliciting protective immune response against the virus.


title: Infection with Porcine reproductive and respiratory syndrome virus stimulates an early gamma interferon response in the serum of pigs.

text: The early release of cytokines by cells involved in innate immunity is an important host response to intracellular pathogens. Gamma interferon (IFN-gamma) is an important cytokine produced during the early stages of an infection by macrophages, natural killer (NK) cells, and other cell types, and it is also a central cytokine mediator for the induction of cellular or Th1 immunity. To better understand innate and adaptive immune responses after infection with Porcine reproductive and respiratory syndrome virus (PRRSV), we investigated serum IFN-gamma concentrations and the duration of viremia. For 2 strains of atypical PRRSV, IFN-gamma was detectable in swine serum soon after infection and lasted for approximately 3 wk. Serum concentrations of IFN-gamma peaked at about 10 d after inoculation and returned to approximately baseline levels by day 22. However, individual pigs manifested short, sporadic increases in the serum concentration of IFN-gamma from 18 to 50 d after inoculation. Prior vaccination blocked the serum IFN-gamma response associated with homologous virus challenge and altered the kinetics of the response after heterologous challenge. Two other respiratory viruses of pigs, Porcine respiratory coronavirus and Swine influenza virus, do not appear to induce serum IFN-gamma. The early production of IFN-gamma in PRRSV-infected pigs might result from activation of NK cells, a response that is more characteristic of immune pathways stimulated by intracellular bacterial and protozoan infections.


title: Lessons learned from Asian H5N1 outbreak control.

text: Numerous lessons have been learned so far in controlling H5N1 avian influenza in Asia. Early detection of incursions of virus prevented establishment of the disease in several countries, notably Japan, South Korea, and Malaysia. In countries where detection of early cases was delayed, infection is endemic and has been for three or more years. Control measures implemented in these countries need to reflect this finding. Vaccination will continue to be one of the key measures used in these endemically infected countries. Used alone, vaccination will not result in elimination of H5N1 viruses from a country, but, if used correctly, it will markedly reduce the prevalence of and susceptibility to infection. Vaccination has already played a valuable role in reducing the adverse effects of H5N1 viruses. Mass culling also reduces the level of infection in infected areas. However, the long-term benefits are limited in endemically infected countries owing to the high probability of reinfection on restocking unless other measures are used in parallel. Full epidemiological studies have not been conducted in many infected countries. Nevertheless, it is recognized that the number of clinical cases does not truly reflect the levels of infection. Domestic ducks and large live poultry markets have played a key role in the persistence of infection, because they can be infected silently. In tackling this disease, countries should adopt integrated control programs using the combination of measures best suited to the local environment. All surveillance data should be shared, both positive and negative, and should include information on cases of infection and disease. Socioeconomic and ecological implications of all control measures should be assessed before implementation, especially the impact on the rural poor.


title: Staple Line Reinforcement During Laparoscopic Sleeve Gastrectomy: Absorbable Monofilament, Barbed Suture, Fibrin Glue, or Nothing? Results of a Prospective Randomized Study.

text: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is associated with serious complications, such as staple line (SL) leaks and bleeding. In order to prevent the occurrence of these complications, surgeons have advocated the need to strengthen the staple line. The aim of this randomized controlled study was to compare the efficacy of three different ways of strengthening of the SL in LSG in preventing surgical post-operative complications. METHODS Between April 2012 and December 2014, 600 patients (pts) scheduled for LSG were prospectively randomized into groups without SL reinforcement (group A) or with SL reinforcement including fibrin glue coverage (group B), or oversewn SL with imbricating absorbable (Monocryl™; group C) or barbed (V lock®) running suture (group D). Primary endpoints were post-operative leaks, bleeding, and stenosis, while secondary outcomes consisted of the time to perform the staple line reinforcement (SLR) and total operative time. RESULTS Mean SLR operative time was lower for group B (3.4 ± 1.3 min) compared with that for groups C (26.8 ± 8.5 min) and D (21.1 ± 8.4 min) (p < 0.0001). Mean total operative time was 100.7 ± 16.4 min (group A), 104.4 ± 22.1 min (group B), 126.2 ± 18.9 min (group C), and 124.6 ± 22.8 (group D) (p < 0.0001). Post-operative leaks, bleeding, and stenosis were recorded in 14 pts (2.3 %), 5 pts (0.8 %), and 7 pts (1.1 %), respectively, without statistical difference between the groups. CONCLUSION Our study suggests that SLR during LSG, with an imbricating or non-imbricating running suture or with fibrin glue, is an unrewarding surgical act with the sole effect of prolonging the operative time.


title: Coronavirus (COVID-19): Let's Prevent Not Panic.

text: It was on 31st December 2019, that a cluster of pneumonia cases was reported to the World Health Organization (WHO) by China. The initial investigations revealed the cases to be due to a previously unknown "never before seen strain of coronavirus". Coronaviruses are a group of viruses, which are normally present among animals such as cows, bats, camels and cats. The disease was officially named COVID-19 by WHO on 11th February 2020. The International Committee on Taxonomy of Viruses named the virus as SARS-CoV-2 due to its resemblance to SARS coronavirus. According to WHO's Situation Report-28 as of 17th February 2020, globally there were 71,429 confirmed cases, which included both laboratories confirmed and clinically diagnosed cases (applicable only to Hubei province of China). Cases are clinically diagnosed based on their signs and symptoms and chest x-rays without laboratory testing. More than 99% of these are in China i.e. 70,635 and 794 are outside China. The cases reported outside of China belong to 25 countries in various regions of WHO: China having the epicenter of the disease bears the greatest brunt, with 1772 deaths. The three deaths outside China have been reported in Philippines, Japan and France. The case fatality rate of COVID-19 ranges between 2-3% A wide spectrum of disease, ranging from mild to severe, has been reported in confirmed cases of COVID-19. Respiratory symptoms, fever, cough, dyspnoea, myalgia, fatigue, breathing difficulties and bilateral lung infiltrates on C.T are common findings. Pakistan so far has not reported any confirmed case of COVID-19. Government is showing its commitment towards the threat of importation. This novel coronavirus, called as a "devil" by Chinese Prime Minister, Xi Ping is really an enigma.


title: Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: Implications for virus evolution and host persistence.

text: Discrete RNA secondary and higher-order structures, typically local in extent, play a fundamental role in RNA virus replication. Using new bioinformatics analysis methods, we have identified genome-scale ordered RNA structure (GORS) in many genera and families of positive-strand animal and plant RNA viruses. There was remarkably variability between genera that possess this characteristic; for example, hepaciviruses in the family Flaviviridae show evidence for extensive internal base-pairing throughout their coding sequences that was absent in both the related pestivirus and flavivirus genera. Similar genus-associated variability was observed in the Picornaviridae, the Caliciviridae, and many plant virus families. The similarity in replication strategies between genera in each of these families rules out a role for GORS in a fundamentally conserved aspect of this aspect of the virus life cycle. However, in the Picornaviridae, Flaviviridae, and Caliciviridae, the existence of GORS correlated strongly with the ability of each genus to persist in their natural hosts. This raises the intriguing possibility of a role for GORS in the modulation of innate intracellular defense mechanisms (and secondarily, the acquired immune system) triggered by double-stranded RNA, analogous in function to the expression of structured RNA transcripts by large DNA viruses. Irrespective of function, the observed evolutionary conservation of GORS in many viruses imposes a considerable constraint on genome plasticity and the consequent narrowing of sequence space in which neutral drift can occur. These findings potentially reconcile the rapid evolution of RNA viruses over short periods with the documented examples of extreme conservatism evident from their intimate coevolution with their hosts.


SARS outbreak. Flood of sequence data yields clues but few answers.


title: Testing for COVID-19: a few points to remember.

text: Diagnostic approaches to COVID-19 include clinical history, PCR tests for the presence of SARS-CoV-2 virus and detection of antibodies. By combining these three approaches, the seroprevalence of anti-SARS-CoV-2 antibodies can be examined in healthcare teams. The aim of the study was to examine the seroprevalence of anti-SARS-CoV-2 antibodies in a population of healthcare professionals 6 - 8 weeks after the first COVID-19 case was detected in the Czech Republic. A total of 269 subjects were enrolled in the study (187 women, 82 men) with a median age of 45.9 years (21 - 71 years). We used a questionnaire to ascertain travel history and clinical signs of any respiratory tract infection. Blood samples were collected, and IgG levels were analysed in all samples. The level of IgA antibodies was analysed in those positive for IgG. PCR testing was performed in cases testing positive for presence of antibodies. The enzyme-linked immunosorbent assay (ELISA) test system for SARS-CoV-2 from Euroimmun (Germany) was used to analyse immunoglobulin levels. 17 % of the tested cohort reported symptoms compatible with COVID-19 and 35.8 % reported history of international travel. There were 5 subjects positive IgG cases (of 269; 1.85 %), and one IgA positive and IgG borderline positive subject (0.37 %). There was only one PCR positive subject. Anti SARS-CoV-2 antibodies were thus detected in 2.22% of participating health professionals. This article shows the pitfalls of the testing methods and highlights the necessity of using a correct testing algorithm, considering the character of the tested population and the expected low prevalence.


Coronaviruses and their diseases.


title: [COVID-19 : Intensive care management].

text: The SARS-coronavirus 2 disease initially reported in December 2019 in China (COVID-19) represents a major challenge for intensive care medicine, due to the high number of ICU admission and the prolonged stay for many patients. Up to 5 % of COVID-19 infected patients develop severe acute hypoxemic respiratory failure requiring invasive mechanical ventilation as supportive treatment. Apart from early antiviral and anti-inflammatory treatment, the management of COVID-19 patients is mainly applying protective mechanical ventilation, to support the injured lungs. However recently acquired data and clinical experience suggest that COVID-19-related ARDS presents some specificities that will be summarized in the present article.


title: Attitudes toward the use of quarantine in a public health emergency in four countries.

text: Countries worldwide face the threat of emerging infectious diseases. To understand the public's reaction to the use of widespread quarantine should such an outbreak occur, the Harvard School of Public Health, with the U.S. Centers for Disease Control and Prevention, undertook a survey of residents of Hong Kong, Taiwan, Singapore, and the United States. A sizable proportion of the public in each country opposed compulsory quarantine. Respondents were concerned about overcrowding, infection, and inability to communicate with family members while in quarantine. Officials will need specific plans to deal with the public's concerns about compulsory quarantine policies.


We still need to ask 'what is disease?'.


title: [Severe acute respiratory syndrome (SARS). The questions raised by the management of a patient in Besançon and Strasbourg].

text: INTRODUCTION In mid-June 2003, 8500 probable cases of Severe Acute respiratory Syndrome (SARS) responsible for 800 deaths in 29 countries were reported by the World Health Organization (WHO). In France, 5 probable cases of SARS were diagnosed until May 2003. We report the case of one of the 5 French cases, hospitalized successively in Besançon then in Strasbourg. OBSERVATION This 54 year-old man was infected during the Air France flight from Hanoi to Paris via Bangkok by the index case, who himself had been contaminated at the French hospital in Hanoi and who was hospitalized in a critical state in the Tourcoing hospital shortly after his arrival in France. The first clinical signs (fever and dry cough) appeared 4 days after contact with the index case. The chest X-ray showed a pulmonary consolidation 6 days after the first clinical symptoms. Blood test revealed deep lymphopenia and elevated LDH. The patient finally recovered with a treatment combining ribavirin and steroids. CONCLUSION The clinical symptoms of SARS are unspecific and its evolution may be misleading. The epidemiological context (contact with the index case) is a key point for the diagnosis. The management of such a patient requires the careful protection of contacts, the adequation between medical and paramedical staff and excess work and communication to the general public.


[Glycyrrhiza glabra L].


Syndromic surveillance.


title: European Society of Gastrointestinal Endoscopy - Establishing the key unanswered research questions within gastrointestinal endoscopy.

text: Background and study aim: Gastrointestinal endoscopy is a rapidly evolving research field. The European Society of Gastrointestinal Endoscopy (ESGE) plays a key role in shaping opinion and endoscopy activity throughout Europe and further afield. Establishing key unanswered questions within the field of endoscopy and prioritizing those that are important enables researchers and funders to appropriately allocate resources. Methods: Over 2 years, the ESGE Research Committee gathered information on research priorities and refined them through a modified Delphi approach. Consultations were held with the ESGE Governing Board and Quality Improvement Committee to identify important unanswered questions. Research workshops were held at the 21st United European Gastroenterology Week. Research questions were refined by the ESGE Research Committee and Governing Board, compiled into an online survey, and distributed to all ESGE members, who were invited to rank each question by priority. Results: The final questionnaire yielded 291 responses from over 60 countries. The three countries with the highest response rates were Spain, Italy, and United Kingdom. Most responders were from teaching hospitals (62 %) and were specialist endoscopists (51 %). Responses were analyzed with weighted rankings, resulting in prioritization of 26 key unanswered questions. The top ranked generic questions were: 1) How do we define the correct surveillance interval following endoscopic diagnosis? 2) How do we correctly utilize advanced endoscopic imaging? 3) What are the best markers of endoscopy quality? Conclusion: Following this comprehensive process, the ESGE has identified and ranked the key unanswered questions within the field of gastrointestinal endoscopy. Researchers, funders, and journals should prioritize studies that seek to answer these important questions.


title: Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells.

text: Neurotropic coronavirus infection induces expression of both beta interferon (IFN-beta) RNA and protein in the infected rodent central nervous system (CNS). However, the relative contributions of type I IFN (IFN-I) to direct, cell-type-specific virus control or CD8 T-cell-mediated effectors in the CNS are unclear. IFN-I receptor-deficient (IFNAR(-/-)) mice infected with a sublethal and demyelinating neurotropic virus variant and those infected with a nonpathogenic neurotropic virus variant both succumbed to infection within 9 days. Compared to wild-type (wt) mice, replication was prominently increased in all glial cell types and spread to neurons, demonstrating expanded cell tropism. Furthermore, increased pathogenesis was associated with significantly enhanced accumulation of neutrophils, tumor necrosis factor alpha, interleukin-6, chemokine (C-C motif) ligand 2, and IFN-gamma within the CNS. The absence of IFN-I signaling did not impair induction or recruitment of virus-specific CD8 T cells, the primary adaptive mediators of virus clearance in wt mice. Despite similar IFN-gamma-mediated major histocompatibility complex class II upregulation on microglia in infected IFNAR(-/-) mice, class I expression was reduced compared to that on microglia in wt mice, suggesting a synergistic role of IFN-I and IFN-gamma in optimizing class I antigen presentation. These data demonstrate a critical direct antiviral role of IFN-I in controlling virus dissemination within the CNS, even in the presence of potent cellular immune responses. By limiting early viral replication and tropism, IFN-I controls the balance of viral replication and immune control in favor of CD8 T-cell-mediated protective functions.


title: Etiological agents of lower respiratory tract infections in Japanese children.

text: To investigate the etiology of pediatric community-acquired pneumonia and bronchitis, we conducted a prospective, population-based study covering the total population < 15 years of age in 16 municipalities in Hokkaido, Japan, during the period of April 2000 to March 2001. Chest radiographs were available for all cases (n = 921; 398 as pneumonia and 523 as bronchitis) and paired sera for serologic assays were available for more than half of the cases. The following specimens were also collected: nasopharyngeal swabs for viral, bacteriological, mycoplasmal and chlamydial studies, blood for serology and blood culture. The children were then followed-up on days 3, 7 and 14. Specific infecting organisms were identified in a total of 853 (92.6%) out of 921 patients (398 cases of pneumonia and 523 cases of bronchitis) including 205 with mixed infection as follows: Mycoplasma pneumoniae, 252 (274%) patients; respiratory syncytial (RS) virus, 188 (20.4%); influenza A virus, 110 (11.9%); Streptococcus pneumoniae, 95 (10.3%); Haemophilus influenzae, 90 (9.8%); Haemophilus parainfluenzae, 35 (3.8%); Staphylococcus aureus, 29 (3.1%); adenovirus, 27 (2.9%); Moraxella catarrhalis, 12 (1.3%); Pseudomonas aeruginosa , 7 (0.8%); Chlamydia pneumoniae, 6 (0.7%); and other agents, 2 (0.2%). Mycoplasma infections were seen even in patients less than 5 years and RS and influenza A virus infections in patients more than 5 years of age. The importance of M. pneumoniae and RS virus in the etiology of lower respiratory infections in Japanese children was confirmed.


title: Modeling the worldwide spread of pandemic influenza: baseline case and containment interventions.

text: BACKGROUND The highly pathogenic H5N1 avian influenza virus, which is now widespread in Southeast Asia and which diffused recently in some areas of the Balkans region and Western Europe, has raised a public alert toward the potential occurrence of a new severe influenza pandemic. Here we study the worldwide spread of a pandemic and its possible containment at a global level taking into account all available information on air travel. METHODS AND FINDINGS We studied a metapopulation stochastic epidemic model on a global scale that considers airline travel flow data among urban areas. We provided a temporal and spatial evolution of the pandemic with a sensitivity analysis of different levels of infectiousness of the virus and initial outbreak conditions (both geographical and seasonal). For each spreading scenario we provided the timeline and the geographical impact of the pandemic in 3,100 urban areas, located in 220 different countries. We compared the baseline cases with different containment strategies, including travel restrictions and the therapeutic use of antiviral (AV) drugs. We investigated the effect of the use of AV drugs in the event that therapeutic protocols can be carried out with maximal coverage for the populations in all countries. In view of the wide diversity of AV stockpiles in different regions of the world, we also studied scenarios in which only a limited number of countries are prepared (i.e., have considerable AV supplies). In particular, we compared different plans in which, on the one hand, only prepared and wealthy countries benefit from large AV resources, with, on the other hand, cooperative containment scenarios in which countries with large AV stockpiles make a small portion of their supplies available worldwide. CONCLUSIONS We show that the inclusion of air transportation is crucial in the assessment of the occurrence probability of global outbreaks. The large-scale therapeutic usage of AV drugs in all hit countries would be able to mitigate a pandemic effect with a reproductive rate as high as 1.9 during the first year; with AV supply use sufficient to treat approximately 2% to 6% of the population, in conjunction with efficient case detection and timely drug distribution. For highly contagious viruses (i.e., a reproductive rate as high as 2.3), even the unrealistic use of supplies corresponding to the treatment of approximately 20% of the population leaves 30%-50% of the population infected. In the case of limited AV supplies and pandemics with a reproductive rate as high as 1.9, we demonstrate that the more cooperative the strategy, the more effective are the containment results in all regions of the world, including those countries that made part of their resources available for global use.


Missouri Rapid Rural Population Health Response to the COVID-19 Pandemic.


Causes of coral reef degradation.


title: Severe acute respiratory syndrome in dialysis patients.

text: Reviewed are the clinical features and outcome of 12 chronic dialysis patients (six men) who contracted severe acute respiratory syndrome (SARS) compared with 23 sex- and age-matched nonuremic SARS patients as controls. Eight were on peritoneal dialysis (PD) and four on hemodialysis. Mean age was 58 +/- 12 yr for the dialysis patients, and 57 +/- 12 yr for the controls. The presenting symptoms of dialysis patients were similar to the controls. With appropriate protection measures, hemodialysis was performed in a dedicated area of the SARS isolation ward, while PD was continued as intermittent PD. In all seven patients with PD effluent tested, SARS-related coronavirus (CoV) could not be identified by polymerase chain reaction (PCR) or viral culture. Three dialysis patients had persistent positive stool PCR after 5 wk, whereas all nondialysis patients had negative stool PCR after 1 wk. Despite dosage adjustment, ribavirin-induced hemolytic anemia was more severe in the dialysis patients. Dialysis patients required longer hospitalization than the controls, but the mortality was similar. With appropriate protective measures, dialysis could be safely performed. Dialysis patients with SARS often require prolonged hospitalization. Furthermore, these patients may have an extended period of viral shedding, which should be carefully monitored for the purpose of infection control.


title: Coronavirus M proteins accumulate in the Golgi complex beyond the site of virion budding.

text: The prevailing hypothesis is that the intracellular site of budding of coronaviruses is determined by the localization of its membrane protein M (previously called E1). We tested this by analyzing the site of budding of four different coronaviruses in relation to the intracellular localization of their M proteins. Mouse hepatitis virus (MHV) and infectious bronchitis virus (IBV) grown in Sac(-) cells, and feline infectious peritonitis virus (FIPV) and transmissible gastroenteritis virus (TGEV) grown in CrFK cells, all budded exclusively into smooth-walled, tubulovesicular membranes located intermediately between the rough endoplasmic reticulum and Golgi complex, identical to the so-called budding compartment previously identified for MHV. Indirect immunofluorescence staining of the infected cells showed that all four M proteins accumulated in a perinuclear region. Immunogold microscopy localized MHV M and IBV M in the budding compartment; in addition, a dense labeling in the Golgi complex occurred, MHV M predominantly in trans-Golgi cisternae and trans-Golgi reticulum and IBV M mainly in the cis and medial Golgi cisternae. The corresponding M proteins of the four viruses, when independently expressed in a recombinant vaccinia virus system, also accumulated in the perinuclear area. Quantitative pulse-chase analysis of metabolically labeled cells showed that in each case the majority of the M glycoproteins carried oligosaccharide side chains with Golgi-specific modifications within 4 h after synthesis. Immunoelectron microscopy localized recombinant MHV M and IBV M to the same membranes as the respective proteins in coronavirus-infected cells, with the same cis-trans distribution over the Golgi complex. Our results demonstrate that some of the M proteins of the four viruses are transported beyond the budding compartment and are differentially retained by intrinsic retention signals; in addition to M, other viral and/or cellular factors are probably required to determine the site of budding.


[NOVEL CORONAVIRUS THAT RECENTLY EMERGED IN CHINA].


title: [Follow-up testing of viral nucleic acid in discharged patients with moderate type of 2019 coronavirus disease (COVID-19)].

text: OBJECTIVE To investigate the clinical outcome of patients with moderate type of corona virus disease 2019 (COVID-19) after discharge by retesting viral nucleic acid. METHODS Seven patients with moderate COVID-19 met the discharge criteria enacted by National Health Commission were quarantine in hospital for 7 days, then continuously quarantined at home for 4 weeks after discharged. During the three weeks of quarantined period, the symptoms and signs were documented; and sputum or nasal swab and feces samples were collected to test SARS-COV-2 nucleic acid by RT-PCR method. RESULTS There were no symptoms and signs during the quarantine period in all 7 patients. However, respiratory swabs from 3 patients were confirmed positive of SARS-COV-2 nucleic acid at 5 to 7 days after they met the discharge criteria. CONCLUSIONS The study indicates that there is a relatively high incidence of positive viral nucleic acid in patients met the discharge criteria, and it is suggested that patients met the current discharge criteria should be quarantined in hospital for another 7 days and the follow-up viral testing is necessary.


title: A novel approach to mechanical prophylaxis: calf impulse technology mimics natural ambulation more effectively than sequential calf compression.

text: BACKGROUND The risk of thrombosis can be reduced by mechanical compression, but the optimal device is unknown. OBJECTIVES To record the effect of natural ambulation on deep venous flow, providing a reference for evaluating the efficacy of mechanical compression systems, assuming that ambulation is the gold standard against which such systems should be compared; and to compare the hemodynamic effect of the A-V Impulse System CalfPad garment (A-VI) (Orthofix Vascular Novamedix, United Kingdom) with the SCD Express calf compression garment (SCD) (Covidien, USA). METHODS Twelve healthy volunteers were recruited and randomly assigned to either A-VI or SCD in a two-device, two-period crossover design. Peak femoral velocity (PFV) was calculated using custom ultrasound software and compared with baseline values. Ultrasound images were recorded. RESULTS A-VI augmented the mean (± SD) PFV to 59.79±29.07 cm/s compared with 22.86±5.73 cm/s for SCD. The actual percentage increase from baseline was approximately five times greater for A-VI (mean increase 385%±260%) than SCD (mean increase 81%±53%). Using an analysis of covariance model, with baseline fitted as a covariate, a highly statistically significant difference in favour of A-VI was detected (P=0.0002). Least square (adjusted) means (±95% CIs) were 37.24 cm/s (21.39 cm/s to 64.84 cm/s) for A-VI and 6.71 cm/s (3.86 cm/s to 11.69 cm/s) for SCD, representing more than fivefold greater improvement in PFV from rest with the A-VI device than with the SCD device. CONCLUSION Pulsatile impulse calf compression (A-VI) more closely mimics PFV of normal ambulation than slow-squeeze sequential compression (SCD). Pulsatile calf compression may provide superior protection against thrombosis in immobile patients.


title: Accessing the human repertoire for broadly neutralizing HIV antibodies.

text: The human antibody response has special significance in the ongoing efforts to develop a protective HIV vaccine. The observation that a subset of HIV infected individuals, who do not develop AIDS, have a broadly neutralizing antibody response has drawn attention to deciphering the nature of this response. It is hoped that an understanding of these protective antibodies, developed over time in response to the ongoing accumulation of mutations in the infecting virus, will facilitate the development of a vaccine that can elicit a similar response. This strategy will be greatly aided by the identification of broadly neutralizing monoclonal HIV antibodies from infected individuals. Several methods have been utilized to isolate and characterize individual antibodies from the human repertoire and each of these methods has been applied to the generation of broadly neutralizing HIV antibodies, albeit with differing rates of success. This review describes several of these methods including human hybridoma; EBV transformation; non-immortalized B cell culture; clonal sorting; and combinatorial display. Key considerations used in the comparison of different methods includes: efficiency of interrogation of an individual's entire repertoire; assay formats that can be used to screen for antibodies of interest (i.e., binding versus biological assays); and the ability to recover native antibody heavy and light chain pairs.


title: A human norovirus-like particle vaccine adjuvanted with ISCOM or mLT induces cytokine and antibody responses and protection to the homologous GII.4 human norovirus in a gnotobiotic pig disease model.

text: We inoculated gnotobiotic pigs orally/intranasally with human norovirus GII.4 HS66 strain virus-like particles (VLP) and immunostimulating complexes (ISCOM) or mutant E. coli LT toxin (mLT, R192G) as mucosal adjuvants, then assessed intestinal and systemic antibody and cytokine responses and homologous protection. Both vaccines induced high rates of seroconversion (100%) and coproconversion (75-100%). The VLP+mLT vaccine induced Th1/Th2 serum cytokines and cytokine secreting cells, whereas the VLP+ISCOM vaccine induced Th2 biased responses with significantly elevated IgM, IgA and IgG antibody-secreting cells in intestine. Nevertheless, both vaccines induced increased protection rates against viral shedding and diarrhea (75-100%) compared to controls; however, only 57% of controls shed virus.


title: Analysis of Borna disease virus-specific RNAs in infected cells and tissues.

text: Borna disease virus (BDV) is an infectious agent that causes profound disturbances in motor function and behaviour in a wide range of animal species and possibly humans. The infectious nature of BDV has long been established, but the aetiological agent has not been isolated or classified. Recently, we have reported the isolation of BDV-specific cDNA clones using subtractive libraries constructed from mRNA from infected material. Here we describe studies on one of these cDNA clones, B8, and confirm its specificity by in situ hybridization on sections of BDV-infected brain. The complete nucleotide sequence of BDV-specific clone B8 was determined. Oligonucleotides of positive and negative polarity synthesized from sequences from the 5' and 3' ends, as well as the central part, of clone B8 identified both positive- and negative-strand BDV-specific RNAs in infected rat brain. All B8 sequences used as oligonucleotide probes were found to be contained in the larger positive- and negative-strand RNAs. Thus, the structure of the BDV-specific RNAs appears to be a nested set of multiple, overlapping subgenomic positive- and negative-strand RNA transcripts.


title: Characterization of protection against coronavirus infection by noninternal image antiidiotypic antibody.

text: Previously, we have reported protective vaccination of mice against a coronavirus infection using rabbit polyclonal noninternal image Ab2gamma anti-idiotypic (anti-Id) antibody specific for a virus-neutralizing and protective monoclonal antibody (mAb) 7-10A against the viral surface S glycoprotein. To characterize further the mechanisms involved in the induction of protective immunity by this noninternal image anti-Id, plasma and splenocytes from Ab2gamma-immunized BALB/c mice were passively transferred to naive BALB/c mice, followed by viral challenge. A reproducible significant delay in mortality observed in mice to which plasma was passively transferred, together with the presence of specific in vitro neutralizing antiviral Ab3 identified the humoral immune response as the major element responsible for protection. The activation of specific and cross-reactive T lymphocytes by both virus and anti-Id in immunized mice and the absence of adoptive transfer of protection by splenocytes suggested the participation of T helper activity in the induction of protective virus-neutralizing Ab3. To obtain more defined monoclonal reagents for a better understanding of anti-Id-induced protection, mAb2 were generated against the same mAb1 7-10A and characterized. We report the successful generation of mAb2 of the gamma type. However, unlike the polyclonal Ab2gamma, they were not capable of inducing a protective immune response.


title: Generation of a chickenized catalytic anti-nucleic acid antibody by complementarity-determining region grafting.

text: In contrast to a number of studies on the humanization of non-human antibodies, the reshaping of a non-human antibody into a chicken antibody has never been attempted. Therefore, nothing is known about the animal species-dependent compatibility of the framework regions (FRs) that sustain the appropriate conformation of the complementarity-determining regions (CDRs). In this study, we attempted the reshaping of the variable domains of the mouse catalytic anti-nucleic acid antibody 3D8 (m3D8) into the FRs of a chicken antibody (“chickenization”) by CDR grafting, which is a common method for the humanization of antibodies. CDRs of the acceptor chicken antibody that showed a high homology to the FRs of m3D8 were replaced with those of m3D8, resulting in the chickenized antibody (ck3D8). ck3D8 retained the biochemical properties (DNA binding, DNA hydrolysis, and cellular internalizing activities) and three-dimensional structure of m3D8 and showed reduced immunogenicity in chickens. Our study demonstrates that CDR grafting can be applied to the chickenization of a mouse antibody, probably due to the interspecies compatibility of the FRs.


Where is SARS now?


title: Effect of sialodacryoadenitis virus exposure on acinar epithelial cells from the rat lacrimal gland.

text: Sialodacryoadenitis virus (SDAV), a RNA coronavirus, induces degenerative, necrotic and atrophic alterations in acinar epithelial cells of the rat lacrimal gland. To begin to explore the underlying mechanism(s) of this viral effect, we sought in the present study to: (1) determine whether SDAV invades and replicates in lacrimal gland acinar cells in vitro and (2) assess whether short-term SDAV challenge interferes with the viability or function of acinar cells in vitro. For comparison we also evaluated the relative infectivity of SDAV in acinar epithelial cells from lacrimal, submandibular and parotid glands, given that salivary tissues are known to be highly susceptible to SDAV infection in vivo. Acinar epithelial cells from lacrimal, submandibular or parotid glands were isolated from male rats, exposed briefly to SDAV or control cell antigen and then cultured for four, eight or twelve days. At experimental termination, SDAV titers in both media and sonicated cell extracts were evaluated by plaque assay titration on mouse L2 cell monolayers. To evaluate functional aspects of lacrimal gland acinar cells, SDAV-infected cells were incubated in the presence or absence of dihydrotestosterone and culture media were analyzed by RIA to measure the extent of the androgen-induced increase in secretory component (SC) production. Our results showed that: (1) SDAV invades and replicates in lacrimal gland acinar cells, Viral challenge resulted in a significant, time-dependent increase in SDAV titers, that were primarily cell-associated and greatly exceeded amounts contained in the original inoculum; (2) SDAV infection did not compromise lacrimal acinar cell viability or prevent the cellular SC response to androgens. Viral presence, though, did often attenuate the magnitude of this hormone action; and (3) SDAV infects salivary acinar cells, but the kinetics and magnitude or viral replication in lacrimal, submandibular and parotid cells showed considerable variations. These findings demonstrate that SDAV invades and replicates in acinar epithelial cells from lacrimal and salivary glands. The resulting release of infectious progeny may play a role in the SDAV-induced pathology of exocrine tissues in vivo.


title: Characterization and phylogenetic analysis of new bat astroviruses detected in Gabon, Central Africa.

text: Astroviruses are emerging RNA viruses that cause enteropathogenic infections in humans and in other mammals. The identification of astroviruses in a wide range of animals highlights the zoonotic importance of these viruses. Bats can harbor many different viruses, among which some are highly pathogenic for humans (for instance, Nipah, Ebola and SARS coronavirus), and also several astroviruses. As some RNA viruses can be directly transmitted from bats to humans, it is crucial to collect data about their frequency, genetic diversity and phylogenetic characterization. In this study, we report the molecular identification of 44 new astroviruses (with a detection rate of 4.5%) in 962 apparently healthy bats that belong to five different species and that were captured in different caves in North-East Gabon, Central Africa. Our results show that bat astroviruses form a group that is genetically distinct from astroviruses infecting other mammals. Moreover, these astroviruses showed an important genetic diversity and low host restriction in bat species.


title: Maturation of the polymerase polyprotein of the coronavirus MHV strain JHM involves a cascade of proteolytic processing events.

text: The RNA polymerase gene of the murine coronavirus mouse hepatitis virus (MHV) encodes a polyprotein of greater than 750 kDa. The amino-terminal cleavage product of the MHV polymerase polyprotein, p28, has been shown to be cleaved from the polyprotein by the virus-encoded protease PCP-1. We aim to identify the MHV-JHM proteolytic products downstream of p28 and to determine which viral proteinase domains are responsible for generating each of them. To this end, we have generated antisera directed at specific MHV-JHM ORF1a regions and have used these antisera to identify six viral proteins, representing a large portion of ORF1a, from MHV-JHM-infected cells. These proteins include p28, p72, p65, p250, p210, and p27.


title: [Campylobacter fetus ssp. jejuni, Aeromonas hydrophila, helicoidal bacteria and coronavirus in the murine intestine].

text: Intestinal contents of 28 laboratory-bred white mice and 6 wild-caught rats were extracted and observed with phase-contrast and transmission electron microscopy; cultures were made in Butzler agar and aeromonas, incubated in microaerobiosis, at 37 degrees C for 5 days. In three mice and two rats, helicoidal bacteria were observed, with 8 to 11 periplasmic fibers and terminal branches of 8 to 11 structures, similar to flagella. In one of the rats, coronavirus-like particles were observed. Campylobacter fetus ssp. jejuni was isolated in cultures from two mice and Aeromonas hydrophila from two rats.


title: An ecological perspective on Brucella abortus in the western United States.

text: After a hiatus during the 1990s, outbreaks of Brucella abortus in cattle are occurring more frequently in some of the western states of the United States, namely, Montana, Wyoming and Idaho. This increase is coincidentwith increasing brucellosis seroprevalence in elk (Cervus elaphus), which is correlated with elk density. Vaccines are a seductive solution, but their use in wildlife systems remains limited by logistical, financial, and scientific constraints. Cattle vaccination is ongoing in the region. Livestock regulations, however, tend to be based on serological tests that test for previous exposure and available vaccines do not protect against seroconversion. The authors review recent ecological studies of brucellosis, with particular emphasis on the Greater Yellowstone Area, and highlight the management options and implications of this work, including the potential utility of habitat modifications and targeted hunts, as well as scavengers and predators. Finally, the authors discuss future research directions that will help us to understand and manage brucellosis in wildlife.


title: Jejunostomy tube feeding in patients undergoing esophagectomy.

text: BACKGROUND Surgical jejunostomy tubes are a routine part of elective esophagectomies in patients with carcinomas and provide a route for nutritional support in those who experience complications. We wished to determine how frequently oral intake is delayed and the amount of nutrition delivered via the jejunostomy tube. METHODS We reviewed the charts of all adults undergoing esophagectomy for carcinoma between January 2000 and June 2008. We determined the proportion of patients unable to resume oral nutrition after 8 days and the amount of nutrition delivered in each of the 8 days. RESULTS In all, 111 patients underwent elective esophagectomy for carcinoma, and 103 had a jejunostomy tube placed. The mean age was 67 ± 10.8 years. The median time to oral intake was 7 (interquartile range 7-11) days. Seventy-four (67%) patients resumed oral intake within 8 days. The mean nutrition delivered by jejunostomy within the first 8 days as a percentage of the target was 45.6% (95% confidence interval 41.2%-49.9%). Six (5.4%) patients experienced complications attributable solely to the jejunostomy tube; 3 (2.9%) required surgery. Forty (38.8%) patients had abdominal issues serious enough to warrant delaying the progression of feeding. CONCLUSION Two-thirds of patients undergoing elective esophagectomy were tolerating oral intake by the end of the eighth postoperative day, and less than half of the target nutrition was delivered over the first 8 days. We now selectively place surgical jejunostomy tubes in patients undergoing elective esophagectomies.


Low serum creatine kinase activity in hospital patients.


Infectious diseases: fortieth and final annual review of significant publications.


Performance measures for upper gastrointestinal endoscopy: A European Society of Gastrointestinal Endoscopy quality improvement initiative.


title: [The epidemiological study of adenovirus in children with respiratory tract infections in Nanjing area from 2010 to 2011].

text: UNLABELLED To investigate the epidemiological features and types of human adenoviruses (ADV) in children with acute respiratory tract infection in Nanjing area, China. Nasopharyngeal aspirates and nasopharyngeal swabs were collected from 644 outpatients or hospitalized pediatric patients with ARTI at the Children Hospital of Nanjing, Jiangsu Province, China, between August 2010 and July 2011. Adenoviruses were identified and typed from the collected clinical specimens by nested-PCR based on the partial region of the hexon gene. Other 12 respiratory viruses including human bocavirus (HBoV), respiratory syncytial virus (RSV), human rhinovirus (HRV), parainfluenza viruses 1-4 (PIV1-4), influenza virus A/B (IFVA/B), human metapneumovirus (HMPV), human coronavirus NL63 and HKU1 (HCoV-HKU1 and HCoV-NL63) were also identified by PCR method. All PCR positive products were sequenced and phylogenetic analysis was conducted. It was showed that adenoviruses were detected in 171 patients out of 644 (26. 55%) children, 120 (70.18%, 120/171) for ADV3, 16 (9.36%,16/171) for ADV7, 12 (7.02%, 12/171) for ADV1, 10 (5.85%, 10/171) for ADV2, 6 (3.51%, 6/171) for ADV5, 3 (1.75%, 3/171) for ADV6, 3 (1.75%, 3/171) for ADV57, and 1 (0.58%,1/171) for ADV41. ADV infection could occur in any season. There was a higher possibility of ADV infection from April to July in 2011. Most cases (96.49%) were younger than 7 years old. A total of 99 of the 171 ADV-positive children (57.89%) were co-infected with other respiratory viruses. Respiratory syncytial virus (RSV) and human rhinovirus (HRV) were the most common additional respiratory viruses, Lower respiratory tract infections were the most frequent diagnoses made in the hospital, in which there were 52 pneumonia (30.4%) cases. CONCLUSION ADV is one of the most important pathogens of acute respiratory tract infection in children in Nanjing area, and adenovirus type 3 was the most prevalent serotype. It is important to develop long-term surveillance.


title: E unum pluribus: multiple proteins from a self-processing polyprotein.

text: Many applications of genetic engineering require transformation with multiple (trans)genes, although to achieve these using conventional techniques can be challenging. The 2A oligopeptide is emerging as a highly effective new tool for the facile co-expression of multiple proteins in a single transformation step, whereby a gene encoding multiple proteins, linked by 2A sequences, is transcribed from a single promoter. The polyprotein self-processes co-translationally such that each constituent protein is generated as a discrete translation product. 2A functions in all the eukaryotic systems tested to date and has already been applied, with great success, to a broad range of biotechnological applications: from plant metabolome engineering to the expression of T-cell receptor complexes, monoclonal antibodies or heterodimeric cytokines in animals.


title: [Molecular typing of adenoviruses isolated from clinical specimens by PCR and DNA sequencing methods].

text: Adenoviruses are responsible for a broad spectrum of diseases, including upper and lower respiratory tract infections (URTIs and LRTIs, respectively), conjunctivitis, gastroenteritis, and hemorrhagic cystitis. The aim of this study was to determine the adenovirus (AdV) types isolated from clinical specimens by polymerase chain reaction (PCR) and DNA sequencing methods. A total of 22 AdV strains isolated between January 1st 2011 to May 31th 2011, from various samples (295 nasopharyngeal swabs, 42 conjunctival swabs, 13 stool) sent to our routine virology laboratory were included in the study. Of the 22 patients whose samples yielded adenovirus positivity, 8 were adult (4 were male; median age: 32.5 years) and 14 (7 were male; median age: 1 year) were children. Those specimens (14 nasopharyngeal swabs, 7 conjunctival swabs, 1 stool) were obtained from patients with URTIs (n= 6), LRTIs (n= 8), conjunctivitis (n= 7) and gastroenteritis (n= 1). For the isolation and identification of adenoviruses, rapid (shell vial) cell culture and direct immunofluorescence antibody methods were used, respectively. Molecular typing of adenoviruses were performed by PCR and sequencing of a partial region (hipervariable region 1-6) of the hexon gene. PCR primers (Adhex F1, Adhex R1) used for DNA amplification were from those described by Lu and Erdman, previously. If insufficient DNA was amplified from the first reaction for sequencing, a nested PCR was performed using Adhex F2 and Adhex R2 primers. Sequencing was performed using the amplification primers and Sequence Reagent Mix-DYEnamic ET Terminator Cycle Sequencing Kit (Amersham Pharmacia Biotech Inc, USA) on ABI PRISM 310 Genetic Analyzer (Applied Biosystems, USA). Obtained adenovirus sequences were typed by BLAST analysis and three AdV types namely type 3, 4, and 8 were identified. In our study, AdV type 3 was detected in a gastroenteritis case and six cases with URTIs and LRTIs (n= 7, 31.8%). AdV type 8 was identified as the cause of conjunctivitis in seven patients and of URTIs and LRTIs in five patients (n= 12, 54.5%). AdV type 4 was found to be associated with URTI in one, and LRTIs in two patients (n= 3; 13.7%). Our data indicated that AdV type 8 was the most prevalent type in patients with conjunctivitis and URTIs, while AdV type 3 was the most prevalent type in patients with LRTI. BLAST analysis was thought to be useful for the molecular typing of adenoviruses. In conclusion, advanced studies with large number of specimens are necessary to achive a reliable, detailed national adenovirus database.


title: Adult clinically amyopathic dermatomyositis with rapid progressive interstitial lung disease: a retrospective cohort study.

text: The aim of the study was to investigate the characteristics of adult clinically amyopathic dermatomyositis (CADM) with rapid progressive interstitial lung disease (ILD). Hospitalized patients with dermatomyositis (DM) and polymyositis (PM) between 1998 and 2005 in the Shanghai Renji Hospital were retrospectively studied. One hundred and forty-five patients were classified into CADM, classic DM or PM according to the modified Sontheimer's definition or Bohan-Peter's classification criteria. They were further stratified based on the presence or absence of clinical ILD. The Kaplan-Meier survival analysis and COX regression were performed. The predictive factors for ILD and other clinical properties of CADM-ILD were explored. The presence of clinical ILD was a significant risk factor for the poor outcome of DM/PM (OR = 4.237, CI 95%: 1.239-14.49, p = 0.021). Other risk factors are the presence of rashes and elevated urea nitrogen. Patients with DM/PM complicated by ILD had different clinical courses. Patients with CADM-ILD showed a rapidly progressive pattern with 6-month survival rate of 40.8%. The DM-ILD manifested a progressive pattern with a 5-year survival rate of 54%, while PM-ILD was chronic with 5- and 10-year survival rate of 72.4% and 60.3%, respectively. Better preserved muscle strength, elevated erythrocyte sedimentation rate, and hypoalbuminemia may herald ILD in DM/PM. Patients with CADM-ILD who later died had lower PO(2), higher lactate dehydrogenase, and prominent arthritis/arthralgia compared with those who survived. The presence of antinuclear antibody seems to be protective. Rapid progressive CADM-ILD is refractory to conventional treatment. ILD is a common complication in over 40% of our hospitalized DM/PM cohort and is also a prominent prognostic indicator. CADM is a special phenotype of DM/PM. CADM-ILD, which is usually rapidly progressive and fatal, requires further investigation.


title: Investigation of the molecular detection of vaccine-derived equine herpesvirus type 1 in blood and nasal secretions from horses following intramuscular vaccination.

text: The objective of this study was to investigate whether intramuscular vaccination of healthy adult horses with a killed or a modified live equine herpesvirus type 1 (EHV-1) vaccine could induce transient positive PCR results in either blood or secretions collected on a nasopharyngeal swab. Four horses in each group received either a single killed or a modified-live vaccine intramuscularly. Two local commingled and 2 distant nonvaccinated controls were included for each group. All horses were observed daily for evidence of clinical abnormalities throughout the study periods. Blood and nasopharyngeal swabs were collected twice before vaccination and once weekly for 4 weeks after vaccination and submitted for PCR testing for EHV-1 by 2 independent laboratories using different real-time PCR methodologies. Serum samples collected from all horses on the vaccination day and 21 days later were tested for antibodies against EHV-1 using a serum neutralization test. Whereas the 2 vaccine strains tested positive in both EHV-1 PCR assays, nasopharyngeal swabs and whole blood collected from vaccinated and control horses had negative PCR test results for EHV-1 during the entire study period. Serum neutralization testing revealed a 2- to 4-fold increase in titers for all vaccinated horses, whereas titers in control horses were largely unchanged. The use of seropositive horses before immunization and the sampling frequency of 7 days may have prevented the occasional molecular detection of the vaccine virus in whole blood and nasopharyngeal secretions. However, the study results demonstrate that detection of EHV-1 DNA by PCR in vaccinated and unvaccinated healthy horses is not a common event.


title: [Clinical and Biological Character in Mouse Models for Middle East Respiratory Syndrome Generated by Transduction with Different Doses of DPP4 Molecule].

text: In this study, we evaluated the difference ot biological characteristics in the MERS-CoV infected mice model in prior to transduction with different dosage of human DPP4. Firstly, we transduced different dosage of DPP4 (high or low) into mice, and then challenged them with MERS-CoV in order to establish the model. After establishment of mice model, we observed the clinical signs of disease, virus replication, immunopathogenesis and antibody response. The results indicated that the infected mice showed typical pneumonia, virus replication, histological lesions, and neutralizing antibody production. Moreover, the high dosage group was superior to the low dosage group. Fourteen days after infection, the specific antibody to virus structural protein and neutralizing antibody were analyzed, the high dosage group induced higher level antibody. In summary, the MERS-CoV infected mice model were established prior transduction with DPP4, and the level of DPP4 influenced the clinical signs of disease, virus replication and antibody response in this model.


title: Infectious diseases during wartime.

text: PURPOSE OF REVIEW The infectious disease challenges of war include pathogens endemic to the geographic area of operations as well as wound infections with common environmental microorganisms. This review summarizes papers, unpublished data and personal communications from 2004-2005 pertaining to infectious diseases during war with a focus on the current operations in Iraq and Afghanistan. RECENT FINDINGS To date, there have been several hundred cases of cutaneous leishmaniasis and five cases of visceral leishmaniasis among US military personnel serving in southwest Asia. There have been reports of malaria in soldiers serving in Afghanistan and an outbreak of acute eosinophilic pneumonia among soldiers serving in or near Iraq. Diarrheal illness is a well-known threat to military operations and remains problematic for combatants throughout the theater of operations. Infectious complications caused by multiply drug-resistant Acinetobacter baumannii have been particularly challenging for healthcare providers managing the wounded evacuated from Iraq. We are now facing outbreaks of nosocomial infection with this pathogen in military treatment facilities in Europe and the USA. SUMMARY Historically, infectious diseases have had significant impact on the conduct of military operations, and the conflict in southwest Asia is no exception. Physicians caring for returning military personnel should be aware of the diseases prevalent in this campaign, particularly cutaneous leishmaniasis and infections with multiply drug-resistant A. baumannii.


Correlation of genomic detection of feline coronavirus with various diagnostic assays for feline infectious peritonitis.


title: Investigation of calf health and welfare on dairy farms in south-west England.

text: A questionnaire was designed to investigate calf health and welfare on dairy farms in the south west of England with regard to the degree of compliance with the Welfare of Farmed Animals (England) Regulations 2000. The level of veterinary involvement in calf rearing and management on dairy farms in the south west of England was also assessed. The questionnaire was sent to 32 large animal practices in the catchment area of the Veterinary Laboratories Agency--Langford. Compliance with the regulations was found to be variable. The requirements for the isolation of sick calves, provision of bovine colostrum within six hours of birth, the provision of fresh, clean water and restrictions concerning tethering were not well complied with. However, the requirements for twice-daily feeding and inspection, visual and tactile contact between calves, access to forage and the provision of clean, dry bedding were well complied with. The results also suggested that there was some lack of veterinary input into the health and welfare of calves on dairy farms visited by the practices routinely and non-routinely.


title: Immunohistochemical study of severe acute respiratory syndrome-associated coronavirus in tissue sections of patients.

text: BACKGROUND AND PURPOSE Severe acute respiratory syndrome (SARS) is a life-threatening and highly contagious disease caused by the novel SARS coronavirus (SARS-CoV). Immunohistochemical staining for SARS-CoV in the tissue sections of SARS patients is helpful in investigations of the biologic behavior of this virus in human tissue, and to determine the target cells of this virus in different organs. METHODS We studied the pathologic specimens from 6 SARS patients by immunohistochemical staining using a specific antibody against SARS-CoV. RESULTS Positive viral staining was only found in the lung tissue taken from the patients who died in the early stage of the disease, usually less than 10 days after symptom onset. No positive staining was found in the lung tissue specimens collected in the mid-to-late stage of the disease. The SARS-CoV-infected cells had a patchy distribution and tended to be present in the periphery of the lung. Immunohistochemically, these viral-infected cells were located mainly along the alveolar space, had a cuboidal appearance, and were reactive to cytokeratin and surfactant protein C. This suggested that type II pneumocytes are the main target cell of SARS-CoV in the lung. Occasional intra-alveolar macrophages were also weakly reactive to SARS-CoV antibody. In addition to the lung, positive viral staining was also found in the mucosal epithelium of the large intestine in another patient who had the clinical symptom of diarrhea. No evidence of viral staining was found in other organs including kidney, liver, lymph node and spleen. The skeletal muscle specimens of 2 patients who had rhabdomyolysis were also negative for SARS-CoV. CONCLUSIONS SARS-CoV is mainly present in the cytoplasm of type II pneumocytes and can only be detected in the lung tissue during the early stage of the disease. In the patient who had symptoms of diarrhea, SARS-CoV staining was also identified in the mucosal epithelium of the colon.


title: [Fatal outcome of coronavirus disease 2019 in a previously healthy 50-year-old man].

text: In this case report, a 50-year-old man who had no medical history, presented with multiple cardiac arrests following a week with progressing symptoms of pneumonia. After achieving return of spontaneous circulation he presented with respiratory failure with severe hypoxia, septic shock, and multiple organ failure. A chest X-ray showed signs of acute respiratory distress syndrome. Despite aggressive intensive care management, the patient died 7.5 hours after admission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was later confirmed, and the presumed cause of death was SARS-CoV-2 pneumonia. In conclusion: coronavirus disease 2019 (COVID-19) can lead to a fatal outcome in younger healthy residents, who are not treated timely in case of severe symptoms like dyspnoea.


Mutation of the immunodominant CD8+ epitope in the MHV-4 spike protein.


title: A Nationwide Analysis of Kidney Autotransplantation.

text: There are limited data regarding outcomes of patients underwent kidney autotransplantation. This study aims to investigate outcomes of such patients. The nationwide inpatient sample database was used to identify patients underwent kidney autotransplantation during 2002 to 2012. Multivariate analyses using logistic regression were performed to investigate morbidity predictors. A total of 817 patients underwent kidney autotransplantation from 2002 to 2012. The most common indication of surgery was renal artery pathology (22.7%) followed by ureter pathology (17%). Overall, 97.7 per cent of operations were performed in urban teaching hospitals. The number of procedures from 2008 to 2012 were significantly higher compared with the number of them from 2002 to 2007 (473 vs 345, P < 0.01). The overall mortality and morbidity of patients were 1.3 and 46.2 per cent, respectively. The most common postoperative complications were transplanted kidney failure (10.7%) followed by hemorrhagic complications (9.7%). Obesity [adjusted odds ratio (AOR): 9.62, P < 0.01], fluid and electrolyte disorders (AOR: 3.67, P < 0.01), and preoperative chronic kidney disease (AOR: 1.80, P = 0.03) were predictors of morbidity in patients. In conclusion, Kidney autotransplantation is associated with low mortality but a high morbidity rate. The most common indications of kidney autotransplantation are renal artery and ureter pathologies, respectively. A kidney transplant failure rate of 10.7 per cent was observed in patients with kidney autotransplantation. The most common postoperative complication was hemorrhagic in nature.


title: Mitochondrial location of severe acute respiratory syndrome coronavirus 3b protein.

text: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV), a distant member of the Group 2 coronaviruses, has recently been identified as the etiological agent of severe acute respiratory syndrome (SARS). The genome of SARS-CoV contains four structural genes that are homologous to genes found in other coronaviruses, as well as six subgroup-specific open reading frames (ORFs). ORF3 encodes a predicted 154-amino-acid protein that lacks similarity to any known protein, and is designated 3b in this article. We reported previously that SARS-CoV 3b is predominantly localized in the nucleolus, and induces G0/G1 arrest and apoptosis in transfected cells. In this study, we show that SARS-CoV 3b fused with EGFP at its N- or C- terminus co-localized with a mitochondria-specific marker in some transfected cells. Mutation analysis of SARS-CoV 3b revealed that the domain spanning amino acids 80 to 138 was essential for its mitochondria localization. These results provide new directions for studies of the role of SARS-CoV 3b protein in SARS pathogenesis.


title: Nuclear magnetic resonance structure of the N-terminal domain of nonstructural protein 3 from the severe acute respiratory syndrome coronavirus.

text: This paper describes the structure determination of nsp3a, the N-terminal domain of the severe acute respiratory syndrome coronavirus (SARS-CoV) nonstructural protein 3. nsp3a exhibits a ubiquitin-like globular fold of residues 1 to 112 and a flexibly extended glutamic acid-rich domain of residues 113 to 183. In addition to the four beta-strands and two alpha-helices that are common to ubiquitin-like folds, the globular domain of nsp3a contains two short helices representing a feature that has not previously been observed in these proteins. Nuclear magnetic resonance chemical shift perturbations showed that these unique structural elements are involved in interactions with single-stranded RNA. Structural similarities with proteins involved in various cell-signaling pathways indicate possible roles of nsp3a in viral infection and persistence.


title: Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.

text: Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity.


title: Neurological manifestations of COVID-19.

text: The COVID-19 pandemic, which started in China, has spread rapidly to affect the entire world in a matter of months. Main manifestations of the disease include a febrile syndrome accompanied by respiratory symptoms; however, cases of systemic involvement are increasingly being reported, including cardiac and central nervous system compromise. In the series by Ling M. et al., 214 patients with COVID-19 were studied; 78 (36.4 %) had neurologic manifestations, which were classified into four main groups: acute cerebrovascular disease, impaired consciousness, peripheral nervous system involvement and muscular manifestations. Another report published by Li et al. describes that, out of 221 patients with COVID-19, 13 developed acute cerebrovascular disease with cerebral infarction, venous thrombosis and intracerebral hemorrhage.


title: Chlamydophila pneumoniae infection among Basic Underwater Demolition/SEAL (BUD/S) candidates, Coronado, California, July 2008.

text: Community-acquired pneumonia can compromise readiness of recruits and service members operating in confined spaces. Often respiratory pathogens are implicated in outbreaks. In July 2008, 5 Basic Underwater Demolition/SEAL students entering an intense period of training at Naval Amphibious Base Coronado reported with clinical symptoms and chest radiographs consistent with pneumonia. Throat and nasal swabs were tested for respiratory pathogens. Molecular evidence indicated that they were infected with the atypical bacterium Chlamydophila pneumoniae. Thirty contemporaneous Basic Underwater Demolition/SEAL students were tested to determine the extent of C pneumoniae infection burden. Five additional cases were captured within this group. The 10 individuals diagnosed with C pneumoniae were treated with a course of azithromycin, Avelox (moxifloxacin hydrochloride), and doxycycline. The cases ended following the isolation of cases and prophylaxis with oral antibiotics. This work highlights the importance of rapid respiratory disease diagnoses to guide the clinical response following the emergence of respiratory infections among military trainees.


title: Information technologies for vaccine research.

text: Vaccinology is a combinatorial science which studies the diversity of pathogens and the human immune system, and formulations that can modulate immune responses and prevent or cure disease. Huge amounts of data are produced by genomics and proteomics projects and large-scale screening of pathogen-host and antigen-host interactions. Current developments in computational vaccinology mainly support the analysis of antigen processing and presentation and the characterization of targets of immune response. Future development will also include systemic models of vaccine responses. Immunomics, the large-scale screening of immune processes which includes powerful immunoinformatic tools, offers great promise for future translation of basic immunology research advances into successful vaccines.


title: SARS: the new challenge to international health and travel medicine.

text: Severe acute respiratory syndrome (SARS), the first severe new infectious disease of this millennium, caused widespread public disruption. By July 2003, 8427 probable SARS cases had been reported from 29 countries with a case fatality rate of 9.6%. The new febrile respiratory illness spread around the world along the routes of international air travel, with outbreaks concentrated in transportation hubs or densely populated areas. The etiologic agent was identified as a novel coronavirus, SARS-CoV. The disease is transmissible person-to-person through direct contact, large droplet contact and indirect contact from fomites and unwashed hands. Saudi Arabia successfully prevented the entry of the disease by imposing travel restrictions, special entry requirements, screening procedures at airports, including temperature checks, and quarantine. Ongoing efforts are aimed at developing case investigation, case management and surveillance protocols for SARS.


title: Matched-pair comparison of radioembolization plus best supportive care versus best supportive care alone for chemotherapy refractory liver-dominant colorectal metastases.

text: PURPOSE This study was designed to evaluate overall survival after radioembolization or best supportive care (BSC) in patients with chemotherapy-refractory liver-dominant metastatic colorectal cancer (mCRC). METHODS This was a matched-pair comparison of patients who received radioembolization plus BSC or BSC alone for extensive liver disease. Twenty-nine patients who received radioembolization were retrospectively matched with a contemporary cohort of >500 patients who received BSC from 3 centers in Germany. Using clinical databases, patients were initially matched for prior treatments and tumor burden and then 29 patients were consecutively identified with two or more of four matching criteria: synchronous/metachronous metastases, tumor burden, increased ALP, and/or CEA >200 U/ml. Survival was calculated from date of progression before radioembolization or BSC by using Kaplan-Meier analysis. RESULTS Of 29 patients in each study arm, 16 pairs (55.2%) matched for all four criteria, and 11 pairs (37.9%) matched three criteria. Patients in both groups had a similar performance status (Karnofsky index, median 80% [range, 60-100%]). Compared with BSC alone, radioembolization prolonged survival (median, 8.3 vs. 3.5 months; P < 0.001) with a hazard ratio of 0.3 (95% confidence interval, 0.16-0.55; P < 0.001) in a multivariate Cox proportional hazard model. Treatment-related adverse events following radioembolization included: grade 1-2 fatigue (n = 20, 69%), grade 1 abdominal pain/nausea (n = 14, 48.3%), and grade 2 gastrointestinal ulceration (n = 3, 10.3%). Three cases of grade 3 radiation-induced liver disease were symptomatically managed. CONCLUSIONS Radioembolization offers a promising addition to BSC in treatment-refractory patients for whom there are limited options. Survival was prolonged and adverse events were generally mild-to-moderate in nature and manageable.


title: Human infection with a novel avian-origin influenza A (H7N9) virus: serial chest radiographic and CT findings.

text: BACKGROUND Rapidly progressive pneumonia infection with H7N9 virus is a novel disease, and limited information is available concerning serial chest radiographic and computed tomography (CT) findings. The aim of this study was to evaluate the changes in serial radiologic findings in patients with H7N9 pneumonia. METHODS The two institutional ethics review boards approved this retrospective study. This study included 10 patients with H7N9 pneumonia. All patients underwent chest radiologic examinations at different time points. Serial radiologic images were systematically analyzed. RESULTS All patients showed abnormal results on initial chest radiography and CT. The initial radiographic abnormalities were unilateral (n = 9) and bilateral (n = 1), including ground-glass opacities (GGOs) (n = 5) and consolidation (n = 5). The initial CT findings consisted of unilateral (n = 6) and bilateral (n = 4), including consolidation (n = 10), GGOs (n = 10), reticular opacities (n = 2), and pleural effusion (n = 3). Follow-up radiologic findings showed rapid development of consolidation or GGOs within two weeks after illness onset. Pneumomediastinum with secondary subcutaneous emphysema and pneumothorax were noted in two patients. Follow-up high resolution computed tomography (HRCT) after two weeks showed slow improvement in both size and opacity of the lesions. On HRCT after discharge, patients had substantial residual lesions such as irregular linear opacities, reticular opacities, parenchymal bands, traction bronchiectasis, and cystic lesions. CONCLUSIONS The most common radiologic findings at presentation are multifocal or diffuse areas of consolidation and GGOs in H7N9 pneumonia. HRCT in sequence can show more changes in rapid progression of disease and a slow decrease of both size and opacity of the lesions plays an important role in the evaluation of H7N9 pneumonia.


title: 2019 Novel Coronavirus Outbreak: SOS Alert for Dentists.

text: On January 31, 2020, novel coronavirus (nCoV), a zoonotic virus yet to be identified into the taxonomy, created a powerful ripple through mankind that the World Health Organization has declared a global health emergency.1 This is definitely not the first time that an alarm has been rung by this family of viruses. Epidemic impact of severe acute respiratory syndrome (SARS) due to SARS CoV and Middle East respiratory syndrome (MERS) by MERS CoV has engraved their place in the scientific literature.2 In general, CoV is known to cause respiratory diseases in humans and accounts for one-third of common cold infections.3 The current outbreak by 2019 nCoV in the Chinese city of Wuhan began in December 2019, has infected nearly 102,188 with 3,491 deaths reported as of March 7, 2020, and has spread to nearly 92 countries.1,4 An assumed incubation period between 2 and 14 days, with flu-like symptoms, may progress into severe pneumonia or acute respiratory distress syndrome which may be the reason for mortality.5,6.


title: Introducing new vaccines in developing countries: concepts and approaches to estimating burden of Haemophilus influenzae type b-associated disease.

text: In the past 30 years, great strides have been made in immunizing infants and children routinely in developing countries under the Expanded Programme on Immunization. Despite this, the introduction of Haemophilus influenzae type b (Hib) vaccines has progressed rather slowly compared to previously-introduced vaccines for infant immunizations. This slower uptake has been attributed partly to the need for data on the burden of invasive Hib disease. To understand this need, conceptual underpinnings and prerequisites were explored for Hib disease-burden studies. Methodological approaches were also reviewed for conducting Hib disease-burden studies that may be considered in developing countries. Potential studies span a range of designs that provide varying levels of clinical, laboratory and epidemiologic evidence of the burden of invasive Hib disease. Carefully-conducted studies can lay the foundation for complementary studies of long-term disability due to invasive Hib disease, national economic analysis, and field evaluations of vaccine. Studies done in collaboration with national agencies and clinical investigators will maximize study value and provide critical data for national decision-makers who make choices regarding the introduction of Hib vaccines.


title: Upgraded software changes the oxygen sensor calibration procedure in Covidien's Puritan Bennett 840 ventilator.

text: Users need to be aware that once Covidien's Puritan Bennett 840 ventilators have received upgraded software for the neonatal configuration, a different procedure will usually be required when calibrating the units' oxygen sensor for neonatal use. Since the function of the previous "100% O2/cal 2 min" key--which some users employed for this calibration--has now changed, users should instead perform calibration through the "More Settings" menu.


COVID-19: Utilizing local experience to suggest optimal global strategies to prevent and control the pandemic.


title: Delivering health care.

text: A website dedicated to sharing good and innovative healthcare practice involving IT has been launched by NHS Education for Scotland.


title: Investigation of antimicrobial and protease-inhibitory activity from cultured cyanobacteria.

text: A culture collection of cyanobacteria has been established at the University of Illinois at Chicago. This collection includes marine, terrestrial, and freshwater strains and contains representatives of the five orders of cyanobacteria: Chroococcales, Pleurocapsales, Oscillatoriales, Nostocales, and Stigonematales. In this study, extracts from a subset of 61 strains, 16 marine and 45 freshwater/terrestrial, were evaluated against three current protease targets, i.e. 20S proteasome and two SARS viral proteases, two important bacterial targets, i.e. Mycobacterium tuberculosis and Bacillus anthracis, and in the Artemia salina toxicity assay. In total, extracts of 12 strains possessed significant levels of activity in one or more targets. The overwhelming majority of active extracts (11 of 12) were from either freshwater or terrestrial forms of cyanobacteria, with the greater part of these (9 of 12) being heterocyst-forming strains. These results further support the use of cultured cyanobacteria as a source of biologically active natural products.


title: Septicemic salmonellosis in two cats fed a raw-meat diet.

text: Salmonella gastroenteritis and septicemia were diagnosed in two cats presented for necropsy. Both cats resided in the same household and were fed a home-prepared, raw meat-based diet. Salmonella was isolated from multiple organs in both cats and from samples of raw beef incorporated into the diet fed to one of the cats. Subtyping of the bacterial isolates yielded Salmonella newport from one cat and from the diet it had been fed. This report provides evidence that the practice of feeding raw meat-based diets to domestic cats may result in clinical salmonellosis.


title: Recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in early 2003 to cause a very severe acute respiratory syndrome, which eventually resulted in a 10% case-fatality rate. Owing to excellent public health measures that isolated focus cases and their contacts, and the use of supportive therapies, the epidemic was suppressed to the point that further cases have not appeared since 2005. However, despite intensive research since then (over 3500 publications), it remains an untreatable disease. The potential for re-emergence of the SARS-CoV or a similar virus with unknown but potentially serious consequences remains high. This is due in part to the extreme genetic variability of RNA viruses such as the coronaviruses, the many animal reservoirs that seem to be able host the SARS-CoV in which reassortment or recombination events could occur and the ability coronaviruses have to transmit relatively rapidly from species to species in a short period of time. Thus, it seems prudent to continue to explore and develop antiviral chemotherapies to treat SARS-CoV infections. To this end, the various efficacious anti-SARS-CoV therapies recently published from 2007 to 2010 are reviewed in this article. In addition, compounds that have been tested in various animal models and were found to reduce virus lung titers and/or were protective against death in lethal models of disease, or otherwise have been shown to ameliorate the effects of viral infection, are also reported.


title: Computational identification of inhibitors of protein-protein interactions.

text: The ability to control protein-protein interactions (PPIs) for therapeutic purposes is attractive since many processes in cells involve such interactions. Recent successes in the discovery of small molecules that target protein-protein interactions for drug development have shown that targeting these interactions is indeed feasible. In the present review the use of computer-aided drug design (CADD) via database screening or docking algorithms for identifying inhibitors of protein-protein interactions is introduced. The principles of database screening and a practical protocol for targeting PPIs are described. The recent applications of these approaches to different systems involving protein-protein interactions, including BCL-2, S100B, ERK and p56lck, are presented and provide valuable examples of inhibitor discovery and design.