title: Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12.

text: DAP12 is an ITAM-containing adapter that associates with receptors in myeloid and NK cells. DAP12-associated receptors can give activation signals leading to cytokine production; however, in some situations, DAP12 inhibits cytokine production stimulated through TLRs and FcRs. Here we show that Triggering Receptor Expressed on Myeloid cells (TREM)-2 is responsible for the DAP12-mediated inhibition in mouse macrophages. A chimeric receptor composed of the extracellular domain of TREM-2 and the cytoplasmic domain of DAP12 inhibited the TLR- and FcR-induced TNF production of DAP12-deficient macrophages, whereas a TREM-1 chimera did not. In wild-type macrophages, TREM-2 knockdown increased TLR-induced TNF production. A TREM-2 Fc fusion protein bound to macrophages, indicating that macrophages express a TREM-2 ligand. Thus, the interaction of TREM-2 and its ligand results in an inhibitory signal that can reduce the inflammatory response.


title: EUS-guided choledochoduodenostomy for malignant distal biliary obstruction using a lumen-apposing fully covered metal stent after failed ERCP.

text: BACKGROUND A novel lumen-apposing, self-expanding metal stent to perform EUS-guided drainage procedures has been recently developed. The aim of this study was to analyze the safety, technical and clinical effectiveness of this device for EUS-guided choledochoduodenostomy (EUS-CD) with palliative intent. METHODS Retrospective analysis of all consecutive patients with unresectable malignant distal bile duct obstruction who, between March 2012 and September 2014, underwent EUS-CD using the study devices (AXIOS™ and Hot AXIOS™, Xlumena Inc., Mountain View, CA, USA) after unsuccessful ERCP in seven European centers was carried out. RESULTS Fifty-seven patients (M/F 31/26; median age 73) underwent EUS-CD using the AXIOS™ stent or the Hot AXIOS™ delivery system. ERCP failure was due to duodenal obstruction in 41 patients (71.9 %) and to inability to cannulate the papilla in the remaining 16 patients (28.1 %). The procedure was technically successful in 56/57 patients (98.2 %), with a mean procedural time of 22.4 min (range 11-65). Clinical success was achieved in 54 of these 56 patients (96.4 %; 94.7 % of the entire cohort). Overall major procedural complication rate was 7 % (two duodenal perforations, one bleeding and one transient cholangitis). During follow-up, 5 out of 54 (9.3 %) patients with clinica success required re-intervention for stent migration in one case and a sump syndrome with transient increase in serum bilirubin concentrations with sludge in the distal duct reservoir in the remaining four patients. CONCLUSIONS Our study shows that EUS-CD using the AXIOS™ and the Hot AXIOS™ devices is a safe procedure, with high technical and clinical success rates.


title: Application of polymerase chain reaction for the correlation of Salmonella serovars recovered from greyhound feces with their diet.

text: The polymerase chain reaction was employed to correlate Salmonella serovars isolated from fecal material of greyhounds suffering from gastroenteritis with those isolated from the diet fed to the greyhounds prior to onset of diarrhea. Kennels around the Abilene, Kansas, area were contacted and supplied with materials needed to collect a portion of the diet each day. With the onset of diarrhea, the kennels were instructed to ship the fecal material and diet from the previous 10 days to the laboratory for testing. Forty-one fecal samples and corresponding diets were screened for Salmonella, Clostridium perfringens, Campylobacter jejuni, Staphylococcus aureus, Staphylococcus intermedius, and pathogenic (piliated) Escherichia coli by direct culture using standard procedures. The fecal material was also screened for coronavirus and parvovirus using electron microscopy. Thirty-five "normal" fecal samples were screened for all of the above mentioned microorganisms as a control. In addition, the fecal material was screened for E. coli verotoxins I and II and clostridial enterotoxins. A total of 61 Salmonella isolates were recovered from the 41 samples of feces and diet submitted for testing; 31 were recovered from the feces and 30 from the diet. Four Salmonella isolates were recovered from the normal fecal samples. Results obtained by PCR, plasmid profiles, antigenic analysis, and antibiogram profiles indicated that 16 of the 31 isolates recovered from the fecal material were the same strain as that recovered from the diet.


title: The effectiveness of surgical face masks: what the literature shows.

text: The use and withdrawal of surgical face masks in recent years has occurred in an ad hoc manner that is incompatible with evidence-based practice. Much of the literature on masks consists of anecdotal evidence or summaries of previous studies. The rationale for wearing masks has shifted from protection of the patient to protection of the health care professional wearing the mask. Currently there is little evidence that wearing a surgical mask provides sufficient protection from all the hazards likely to be encountered in an acute health care setting: the use of a respirator and face shield should be considered depending on the circumstances.


title: Consumer Health Informatics: Promoting Patient Self-care Management of Illnesses and Health.

text: Consumer health informatics (CHI) is propelling important changes for medical providers and the lives of patients through information and communications technology. Independently, medical consumers seek, collect, and use health information for decision making. However, when constructing a CHI-based medical platform, high technology must be applied in a fully understandable and usable format for both health care providers and consumers. This study examines the present status of CHI and its effect on medical consumers. For the development of CHI, we discuss the need for tailored health communications and capacity building with chronic patients at the medical center. First, empowerment is a key characteristic needed for medical consumer health care management. However, promoting patient self-care management of illnesses and health is necessary to create conjugation where cooperation with medical service providers is possible. Also, establishing a health care delivery system that will support cooperation is necessary. Second, tailored health communications can uniquely construct the health information of patients, which prevents unnecessary or excessive information from leading patients to confused and inappropriate decisions. Ultimately, through the present environment of health communication, the innovation of a consumer health care information system has become the tide of the times and the positive effect of improved health can be expected.


Hearing the Call of Duty: What We Must Do to Allow Medical Students to Respond to the COVID-19 Pandemic.


title: Robotic assisted versus pure laparoscopic surgery of the adrenal glands: a case-control study comparing surgical techniques.

text: PURPOSE The role of the da Vinci Robotic System ® in adrenal gland surgery is not yet well defined. The goal of this study was to compare robotic-assisted surgery with pure laparoscopic surgery in a single center. METHODS One hundred and 16 patients underwent minimally invasive adrenalectomies in our department between June 1994 and December 2014, 41 of whom were treated with a robotic-assisted approach (robotic adrenalectomy, RA). Patients who underwent RA were matched according to BMI, age, gender, and nodule dimensions, and compared with 41 patients who had undergone laparoscopic adrenalectomies (LA). Statistical analysis was performed using the Student's t test for independent samples, and the relationship between the operative time and other covariates were evaluated with a multivariable linear regression model. P < 0.05 was considered significant. RESULTS Mean operative time was significantly shorter in the RA group compared to the LA group. The subgroup analysis showed a shorter mean operative time in the RA group in patients with nodules ≥6 cm, BMI ≥ 30 kg/m2 and in those who had previous abdominal surgery (p < 0.05). Results from the multiple regression model confirmed a shorter mean operative time with RA with nodules ≥6 cm (p = 0.010). Conversion rate and postoperative complications were 2.4 and 4.8 % in the LA group and 0 and 4.8 % in the RA group. CONCLUSIONS In our experience, RA shows potential benefits compared to classic LA, in particular on patients with nodules ≥6 cm, BMI ≥ 30 kg/m2, and with previous abdominal surgery.


title: Immunome-derived vaccines.

text: Immune response to a subset of antigens and epitopes derived from an infectious pathogen may be sufficient for competent protection; immune recognition of every potential epitope derived from the pathogen's genome does not appear to be required. The pneumococcal and hepatitis vaccines, both of which are subunit vaccines, illustrate this premise. Similarly, 'immunome-derived vaccines' are based on the concept that response to the subset of antigens and epitopes that interface with the host immune system (the immunome) and not the whole organism (represented by the proteome or genome) can be sufficient for protection. Competent immune responses to cancer are also probably restricted to the neoplasm's 'immunome', although the set of antigens that drive successful immune response to cancer cells has proven more difficult to uncover. Researchers are now using bioinformatics sequence analysis tools, epitope mapping tools, microarrays and high-throughput immunology assays to discover the components of the immunome, which are then used to compose these new vaccines. At least one immunome-derived vaccine is in clinical trials and many others are in the vaccine pipeline. Due to the rapid improvement of immunoinformatics tools and immunological assays, the era of immunome-derived vaccines has begun.


title: Human-specific regulation of alpha 2-6-linked sialic acids.

text: Many microbial pathogens and toxins recognize animal cells via cell surface sialic acids (Sias) that are alpha 2-3- or alpha 2-8-linked to the underlying glycan chain. Human influenza A/B viruses are unusual in preferring alpha 2-6-linked Sias, undergoing a switch from alpha 2-3 linkage preference during adaptation from animals to humans. This correlates with the expression of alpha 2-6-linked Sias on ciliated human airway epithelial target cells and of alpha 2-3-linked Sias on secreted soluble airway mucins, which are unable to inhibit virus binding. Given several known differences in Sia biology between humans and apes, we asked whether this pattern of airway epithelial Sia linkages is also human-specific. Indeed, we show that since the last common ancestor with apes, humans underwent a concerted bidirectional switch in alpha 2-6-linked Sia expression between airway epithelial cell surfaces and secreted mucins. This can explain why the chimpanzee appears relatively resistant to experimental infection with human Influenza viruses. Other tissues showed additional examples of human-specific increases or decreases in alpha 2-6-linked Sia expression and only one example of a change specific to certain great apes. Furthermore, while human and great ape leukocytes both express alpha 2-6-linked Sias, only human erythrocytes have markedly up-regulated expression. These cell type-specific changes in alpha 2-6-Sia expression during human evolution represent another example of a human-specific change in Sia biology. Because the data set involves multiple great apes, we can also conclude that Sia linkage expression patterns can be conserved during millions of years of evolution within some vertebrate taxa while undergoing sudden major changes in other closely related ones.


The membrane-proximal external region of HIV-1 gp41: a vaccine target worth exploring.


title: Severe acute respiratory syndrome in surgical patients: a diagnostic dilemma.

text: BACKGROUND The diagnosis of severe acute respiratory syndrome (SARS) in surgical patients can potentially be missed based on current World Health Organization (WHO) case definitions. METHOD We report a retrospective case series of 10 surgical inpatients diagnosed with SARS following an outbreak in the surgical wards. Patients were included if they fulfilled the WHO case definition of probable SARS, had an active surgical problem and were admitted to the surgical wards during the outbreak period. Clinical histories, laboratory investigations and radiological findings were reviewed and analyzed. RESULTS The mean age of the cohort was 57.6 years (range: 38-78 years). Nine patients had concomitant medical conditions. Three patients were in the early postoperative period, while the remaining seven were admitted for surgical related infections. All patients presented with fever, but only eight had accompanying respiratory symptoms. Lymphopenia and raised lactate dehydrogenase (LDH) was seen in seven patients. Eight patients had positive bacterial cultures. The primary abnormality on chest radiograph was air-space opacification. Rapid progression of radiological changes was seen in seven patients. Mortality rate for our cohort is 20%. CONCLUSION The diagnosis of SARS in surgical patients differs from that previously described in normal patients. An apparent cause of fever and positive blood cultures cannot exclude a diagnosis of SARS. The current WHO case definition could result in delayed or even missed diagnosis. Early isolation of febrile patients with a positive contact history must be undertaken, even in the face of another identifiable cause.


Regulation of kinase activity.


title: Role for nonstructural protein 1 of severe acute respiratory syndrome coronavirus in chemokine dysregulation.

text: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus. Since its associated morbidity and mortality have been postulated to be due to immune dysregulation, we investigated which of the viral proteins is responsible for chemokine overexpression. To delineate the viral and cellular factor interactions, the role of four SARS coronavirus proteins, including nonstructural protein 1 (nsp-1), nsp-5, envelope, and membrane, were examined in terms of cytokine induction. Our results showed that the SARS coronavirus nsp-1 plays an important role in CCL5, CXCL10, and CCL3 expression in human lung epithelial cells via the activation of NF-kappaB.


title: Assembly in vitro of a spanning membrane protein of the endoplasmic reticulum: the E1 glycoprotein of coronavirus mouse hepatitis virus A59.

text: The E1 glycoprotein of coronavirus mouse hepatitis virus A59 was synthesized in vitro by translation of viral mRNA in the presence of dog pancreatic microsomes. Its disposition in the membrane was investigated by digestion with proteases and by selective NH2-terminal labeling. The protein spans the membrane, but only small portions from the NH2 and COOH terminus are exposed respectively in the lumenal and cytoplasmic domains; the bulk of the molecule is apparently buried in the membrane. The protein lacks a cleavable leader sequence and does not acquire its characteristic O-linked oligosaccharides in rough microsomes. It may enter the membrane at any stage during synthesis of the first 150 amino acid residues. These unusual features of the protein might help to explain why it is not transported to the cell surface in vivo but remains in intracellular membranes, causing the virus to bud there.


title: Structure-based drug design and structural biology study of novel nonpeptide inhibitors of severe acute respiratory syndrome coronavirus main protease.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) main protease (M(pro)), a protein required for the maturation of SARS-CoV, is vital for its life cycle, making it an attractive target for structure-based drug design of anti-SARS drugs. The structure-based virtual screening of a chemical database containing 58,855 compounds followed by the testing of potential compounds for SARS-CoV M(pro) inhibition leads to two hit compounds. The core structures of these two hits, defined by the docking study, are used for further analogue search. Twenty-one analogues derived from these two hits exhibited IC50 values below 50 microM, with the most potent one showing 0.3 microM. Furthermore, the complex structures of two potent inhibitors with SARS-CoV M(pro) were solved by X-ray crystallography. They bind to the protein in a distinct manner compared to all published SARS-CoV M(pro) complex structures. They inhibit SARS-CoV M(pro) activity via intensive H-bond network and hydrophobic interactions, without the formation of a covalent bond. Interestingly, the most potent inhibitor induces protein conformational changes, and the inhibition mechanisms, particularly the disruption of catalytic dyad (His41 and Cys145), are elaborated.


docid: aijxkadg

title: [Viral pneumonia].


title: Variation analysis of the severe acute respiratory syndrome coronavirus putative non-structural protein 2 gene and construction of three-dimensional model.

text: BACKGROUND The rapid transmission and high mortality rate made severe acute respiratory syndrome (SARS) a global threat for which no efficacious therapy is available now. Without sufficient knowledge about the SARS coronavirus (SARS-CoV), it is impossible to define the candidate for the anti-SARS targets. The putative non-structural protein 2 (nsp2) (3CL(pro), following the nomenclature by Gao et al, also known as nsp5 in Snidjer et al) of SARS-CoV plays an important role in viral transcription and replication, and is an attractive target for anti-SARS drug development, so we carried on this study to have an insight into putative polymerase nsp2 of SARS-CoV Guangdong (GD) strain. METHODS The SARS-CoV strain was isolated from a SARS patient in Guangdong, China, and cultured in Vero E6 cells. The nsp2 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into eukaryotic expression vector pCI-neo (pCI-neo/nsp2). Then the recombinant eukaryotic expression vector pCI-neo/nsp2 was transfected into COS-7 cells using lipofectin reagent to express the nsp2 protein. The expressive protein of SARS-CoV nsp2 was analyzed by 7% sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). The nucleotide sequence and protein sequence of GD nsp2 were compared with that of other SARS-CoV strains by nucleotide-nucleotide basic local alignment search tool (BLASTN) and protein-protein basic local alignment search tool (BLASTP) to investigate its variance trend during the transmission. The secondary structure of GD strain and that of other strains were predicted by Garnier-Osguthorpe-Robson (GOR) Secondary Structure Prediction. Three-dimensional-PSSM Protein Fold Recognition (Threading) Server was employed to construct the three-dimensional model of the nsp2 protein. RESULTS The putative polymerase nsp2 gene of GD strain was amplified by RT-PCR. The eukaryotic expression vector (pCI-neo/nsp2) was constructed and expressed the protein in COS-7 cells successfully. The result of sequencing and sequence comparison with other SARS-CoV strains showed that nsp2 gene was relatively conservative during the transmission and total five base sites mutated in about 100 strains investigated, three of which in the early and middle phases caused synonymous mutation, and another two base sites variation in the late phase resulted in the amino acid substitutions and secondary structure changes. The three-dimensional structure of the nsp2 protein was successfully constructed. CONCLUSIONS The results suggest that polymerase nsp2 is relatively stable during the phase of epidemic. The amino acid and secondary structure change may be important for viral infection. The fact that majority of single nucleotide variations (SNVs) are predicted to cause synonymous, as well as the result of low mutation rate of nsp2 gene in the epidemic variations, indicates that the nsp2 is conservative and could be a target for anti-SARS drugs. The three-dimensional structure result indicates that the nsp2 protein of GD strain is high homologous with 3CL(pro) of SARS-CoV urbani strain, 3CL(pro) of transmissible gastroenteritis virus and 3CL(pro) of human coronavirus 229E strain, which further suggests that nsp2 protein of GD strain possesses the activity of 3CL(pro).


title: Phenotypic and functional characterization of CD8+ T lymphocytes from the central nervous system of rats with coronavirus JHM induced demyelinating encephalomyelitis.

text: Intracerebral infection of Lewis (LEW) inbred rats with the neurotropic strain of the murine coronavirus JHM (JHMV) frequently results in a monophasic paralytic disease. In contrast, infection of Brown Norway (BN) inbred rats does not lead to clinical disease. Previous findings indicated that in both rat strains brain-infiltrating leukocytes consisted mainly of CD8+ T lymphocytes. Here, we phenotypically as well as functionally characterised this T cell subset after isolation from the central nervous system (CNS). Using JHMV-infected target cells, MHC class I restricted, cytotoxic T lymphocytes were demonstrated to be present in the leukocyte fraction from the CNS of both, susceptible LEW and disease-resistant BN rats. However, compared to infected, but healthy BN rats, diseased LEW rats generated an enhanced cytotoxic immune response which became most prominent at the maximum of neurological disease. Recently published observations from our laboratory demonstrated a strong virus-specific antibody response in the CNS of BN rats. In LEW rats, however, the response was delayed and of low magnitude. This suggests, that consequences of cytotoxic T lymphocyte action in JHMV-infected CNS tissue largely depend on the efficacy of an accompanying virus-specific humoral immune response.


title: ASSOCIATION BETWEEN MANNOSE-BINDING LECTIN GENE POLYMORPHISMS AND SUSCEPTIBILITY TO DENGUE VIRUS INFECTION: A PRELIMINARY REPORT.

text: Mannose-binding lectin (MBL) can bind with a wide range of pathogens and can activate through lectin pathway or enhances opsonophagocytosis. MBL is encoded by the MBL2 gene and single-nucleotide polymorphisms (SNPs) in the promoter and exon have functional effects on serum levels of MBL. MBL deficiency has been shown to predispose to infectious diseases. We assess whether or not, the variant MBL alleles are associated with susceptibility to dengue infection. Patients with confirmed dengue infection who were admitted to King Chulalongkorn Memorial Hospital during a calendar year were studied. Controls were patients without dengue infection. Deoxyribonucleic acid (DNA) was extracted from 50 μl of peripheral blood mononuclear cell (PBMC) using the DNA Blood Mini Kit. The SNPs in the promoter (-221 X/Y) and exon 1 (codon 54 A/B) of MBL2 gene were genotyped by using 2 separate cycling reactions of the TaqMan allele discrimination system. Serum levels of MBL were determined by double-antibody sandwich ELISA. Chi-square was used for statistical analysis. Serum MBL levels and genotypes were determined in 110 dengue patients (mean age 18.1 years; 62 males and 48 females) and 42 controls (mean age 25.8 years; males: females = 1:1). Our study showed that YB haplotype is associated with low serum levels of MBL. There was no association between MBL2 gene polymorphisms and susceptibility to dengue infection. The higher frequency of YB in dengue patients than in controls suggesting the likelihood of an association. Further studies are warranted.


docid: jdxfwuft

title: Metered-dose inhaler with spacer instead of nebulizer during the outbreak of severe acute respiratory syndrome in Singapore.

text: BACKGROUND The use of metered-dose inhaler (MDI) with spacer instead of nebulizer may be important during an outbreak of an airborne infection. However, there is a paucity of data on patients' and nurses' abilities and perspectives on MDI with spacer for the treatment of acute airway obstruction during such an outbreak. METHODS We evaluated 50 consecutive MDI-with-spacer treatments administered in the respiratory wards of the National University Hospital of Singapore, and interviewed the patients after each treatment during the outbreak of severe acute respiratory syndrome (SARS). We also conducted interviews with 50 nurses who had experience in administering bronchodilators via both nebulizer and MDI with spacer. RESULTS Forty-six patients (92%) were able to use MDI with spacer effectively. Sixteen percent of the patients preferred nebulizer over MDI with spacer. Fifty-eight percent of the patients thought MDI with spacer was easier to use than nebulizer, and 34% thought MDI was as easy to use as nebulizer. Sixteen percent of the patients thought that nebulizer was more effective than MDI with spacer in relieving their symptoms. Ninety-six percent of the nurses preferred nebulizer over MDI with spacer. Forty-two nurses (84%) thought that nebulizer was more effective for treating acute airflow obstruction in the hospital. CONCLUSIONS In the in-patient setting during an outbreak of an airborne infection, for treatment of acute airflow obstruction, MDI with spacer was acceptable and preferred by a high percentage of patients. However, a high percentage of nurses had misconceptions regarding the efficacy of and patients' ability to use MDI with spacer.


title: Laparoscopic nephrectomy in a hemophilia B patient.

text: Surgery in patients with hemophilia is a serious challenge. It requires a comprehensive approach, as well as careful postoperative monitoring. We present here the first case of a transperitoneal laparoscopic radical nephrectomy (TLRN) for renal cell carcinoma, of the clear-cell type, performed in a hemophilia B patient. The level of factor IX clotting activity before surgery and on postoperative days 1-6 was maintained at 65-130% and at 30-40% on subsequent days until healing of the post-operative wound was achieved. The intraoperative and postoperative courses were uneventful. TLRN can therefore be considered safe and effective for renal cell carcinoma. In hemophilia patients, the TLRN procedure requires proper preparation, as well as adequate substitution therapy for the deficient coagulation factor provided by a multidisciplinary team in a comprehensive center.


title: Development of an empirical model to aid in designing airborne infection isolation rooms.

text: Airborne infection isolation rooms (AIIRs) house patients with tuberculosis, severe acute respiratory syndrome (SARS), and many other airborne infectious diseases. Currently, facility engineers and designers of heating, ventilation, and air-conditioning (HVAC) systems have few analytical tools to estimate a room's leakage area and establish an appropriate flow differential (DeltaQ) in hospitals, shelters, and other facilities where communicable diseases are present. An accurate estimate of leakage area and selection of DeltaQ is essential for ensuring that there is negative pressure (i.e., pressure differential [DeltaP]) between an AIIR and adjoining areas. National Institute for Occupational Safety and Health (NIOSH) researchers evaluated the relationship between DeltaQ and DeltaP in 67 AIIRs across the United States and in simulated AIIR. Data gathered in the simulated AIIR was used to develop an empirical model describing the relationship between DeltaQ, DeltaP, and leakage area. Data collected in health care facilities showed that the model accurately predicted the leakage area 44 of 48 times. Statistical analysis of the model and experimental validation showed that the model effectively estimated the actual leakage area from -39% to +22% with 90% confidence. The NIOSH model is an effective, cost-cutting tool that can be used by HVAC engineers and designers to estimate leakage area and select an appropriate DeltaQ in AIIRs to reduce the airborne transmission of disease.


title: Managing the effect of TRIPS on availability of priority vaccines.

text: The stated purpose of intellectual property protection is to stimulate innovation. The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires all Members of the World Trade Organization (WTO) to enact national laws conferring minimum standards of intellectual property protection by certain deadlines. Critics of the Agreement fear that such action is inconsistent with ensuring access to medicines in the developing world. A WHO convened meeting on intellectual property rights and vaccines in developing countries, on which this paper is based, found no evidence that TRIPS has stimulated innovation in developing market vaccine development (where markets are weak) or that protection of intellectual property rights has had a negative effect on access to vaccines. However, access to future vaccines in the developing world could be threatened by compliance with TRIPS. The management of such threats requires adherence of all countries to the Doha Declaration on TRIPS, and the protections guaranteed by the Agreement itself, vigilance on TRIPS-plus elements of free trade agreements, developing frameworks for licensing and technology transfer, and promoting innovative vaccine development in developing countries. The role of international organizations in defining best practices, dissemination of information, and monitoring TRIPS impact will be crucial to ensuring optimal access to priority new vaccines for the developing world.


docid: pgitvyyb

title: Wearing masks in a pediatric hospital: developing practical guidelines.

text: During the outbreak of Severe Acute Respiratory Syndrome (SARS) in the spring of 2003, strict infection control measures were implemented in Toronto and surrounding hospitals. These measures included extreme restrictions on those who would normally accompany patients to the hospital, screening for SARS, and protective attire for hospital staff, including masks, face shields, goggles, gloves and gowns. At Toronto's Hospital for Sick Children (HSC), patients could only be accompanied or visited by one person, often only in patients' rooms. For the first four weeks, patients and their designated parent had to wear masks in almost all areas of the hospital. Staff wore masks (and other appropriate protective clothing) whenever in contact with patients and in many patient care areas. Although these barriers were an important part of containing SARS, their use created significant challenges for patients and staff. This article focusses on the use of infection control masks in routine pediatric healthcare and the tools developed by HSC staff to reduce the negative psychosocial impact on children and families.


title: Progressive dyspnea associated with a crazy-paving appearance on a chest computed tomography scan.

text: A 'crazy-paving' appearance of the lungs on computed tomography scanning of the chest was first described nearly 20 years ago in patients with pulmonary alveolar proteinosis, and was thought to be characteristic of this condition. However, this pattern has subsequently been reported in a variety of pulmonary diseases and is now considered to be nonspecific. The present report describes a case of a 74-year-old man in whom congestive heart failure presented with a crazy-paving appearance of the lungs on a chest computed tomography scan. This uncommon association illustrates the importance of the correlation of clinical and radiographic information.


title: Cirrhosis associated with the Australia antigen in an infant who acquired hepatitis from her mother.

text: A 19-week-old English girl developed acute viral hepatitis, which became chronic with persistent hepatosplenomegaly and abnormal liver function tests. Liver biopsy at 1 year showed an active cirrhosis with multinucleated giant cells. The Australia (Au) antigen was detected repeatedly in the infant's serum by immunodiffusion and by electron microscopy at the time of the acute attack and during the development of cirrhosis. She had apparently acquired the hepatitis from her mother, who had had jaundice at the end of pregnancy and for one month thereafter, and who was subsequently shown to be a carrier of Au antigen. Particles with surface projections resembling paramyxoviruses were observed in two of the later specimens of the infant's serum.


title: Attitude, beliefs, and intentions to care for SARS patients among Korean clinical nurses: an application of theory of planned behavior.

text: PURPOSE This study examined Korean clinical nurses' intentions to care for SARS patients and identify determinants of the intentions. Theory of planned behavior was the framework to explain the intentions of Korean nurses for SARS patients care. METHODS A convenient sample of six hundreds and seventy nine clinical nurses from four university-affiliated hospitals located in Seoul and in Kyung-gi province was used. Self-administered (83-items) questionnaire was used to collect data. Intentions, attitude, subjective norm, perceive behavioral control, behavioral beliefs, normative beliefs, and control beliefs were the study variables. All items were measured using 7-point Likert scale (-3 to +3). Data were analyzed using descriptive statistics, Pearson correlation method, and stepwise multiple regression methods. RESULTS Intentions and attitudes toward SARS patient care among Korean clinical nurses were moderate, but their subjective norm and perceive behavioral control of SARS patients care were negative. Stepwise multiple regression analysis indicated that attitude toward SARS patient care, perceived behavioral control, subjective norm were the determinants of the intentions for SARS patients care as theory proposed. Among the behavioral beliefs, "SARS-patient caring would be a new experience", "during SARS-patient caring, I should be apart from my family", "after completing SARS-patient caring, I would be proud of myself being able to cope with a stressful event" and "with my SARS-patient caring, patients could recover from SARS" were the significant determinants. Among the normative beliefs, colleague approval, spouse approval, and physician approval were significant determinants of the intentions. Among the control beliefs, "SARS-patient caring would be a challenge" "SARS-patient caring is a professional responsibility", "tension during the care of SARS patients" and "support from team members" were the significant determinants of the intentions. CONCLUSIONS Korean clinical nurses in this study were not willing to care for SARS patients and showed negative attitude toward the care. They believed their friends and family were not approved their care for SARS patients. Nurses were in conflicts between professional responsibilities to care for SARS patients and personal safety. This study was the first to understand stress and burden of Korean clinical nurses who are in front line to care for newly developed communicable disease such as SARS. Under the circumstance where several fatal communicable diseases are predictable, conflicts between professional responsibility and their personal risks should be taken into considerations by nurses themselves and by nursing administrators in order to improve quality of care.


title: Infectious agents associated with respiratory disease in pheasants.

text: In a case-control study of the infectious agents associated with natural outbreaks of respiratory disease in pheasants, 28 batches of birds from sites affected by disease and eight batches of birds from unaffected sites were examined by six veterinary laboratories in England, Wales and Scotland, and tested for mycoplasmas, other bacteria and viruses. Sinusitis was the commonest sign of disease and was associated with Mycoplasma gallisepticum as detected by PCR in the trachea (P < 0.05) and conjunctiva (P < 0.01). Sinusitis was also associated with pasteurella cultured from the sinus (P < 0.05), antibody to avian pneumovirus (APV) (P < 0.01) and avian coronaviruses as detected by reverse-transcriptase PCR (P < 0.05); there was no association between disease and APV as detected by PCR. Avian coronaviruses were the most common infectious agents detected. They were genetically close to infectious bronchitis virus (IBV) but differed in their gene sequence from all the serotypes of IBV previously identified in domestic fowl, and serological tests with six known IBV types showed little cross reactivity. Mycoplasma species other than M gallisepticum were cultured in 18 batches of pheasants but, with the exception of Mycoplasma gallinaceum, were not associated with disease.


title: [The first case of severe acute respiratory syndrome in Foshan].

text: OBJECTIVE To evaluate the epidemiologic feature, diagnosis and treatment of severe acute respiratory syndrome (SARS). METHODS To describe the epidemiologic and clinical features of the first case of SARS in Foshan city, Guangdong province retrospectively, and to review the diagnostic procedure. RESULTS This case had the following features: (1) a history of contact with mild cats and eating the animal's meat; (2) high fever (temperature, > 38 degrees C), followed by dry cough, rapid progression to respiratory failure, followed by radiographic evidence of bilateral air-space lesions; (3) no leukocytosis; (4) spread to 4 family members who had had direct contact with this patient; (5) the patient's serum SARS virus IgG was confirmed to be positive; (6) the patient was treated with anti-viral agents, antibiotics and mechanical ventilation and molecular adsorbent re-circulating system (MARS). CONCLUSIONS The clinical manifestations of the SARS case, which was highly infectious, met world health organization (WHO) criteria for the diagnosis of SARS. Early initiation of mechanical ventilation and supportive therapy contributed to the good prognosis of this critical case.


title: Norovirus and histo-blood group antigens.

text: Norovirus (NoV), a member of the family Caliciviridae, is a major cause of acute water- and food-borne nonbacterial gastroenteritis and forms antigenically diverse groups of viruses. Human NoVs are divided into at least three genogroups, genogroups I (GI), GII, and GIV, which contain at least 15, 18, and 1 genotypes, respectively. Except for a few genotypes, all NoVs bind to histo-blood group antigens (HBGAs), namely ABH antigens and Lewis antigens, in which carbohydrate core structures, (types 1 and 2) constitute antigenically distinct phenotypes. Volunteer challenge studies have indicated that carbohydrate binding is essential for genogroup I genotype 1 (GI/1) infection. Non-secretors who do not express FUT2 fucosyltransferase, and consequently do not express H type 1 or Lewis b antigens in the gut, are not infected after challenge with GI/1. NoV virus-like particles (VLPs), which are recombinant particles that are morphologically and antigenically similar to the native virion, display different ABH and Le carbohydrate-binding profiles in vitro. Epidemiological studies have shown that individuals with different ABH phenotypes are infected with NoV strains in a genotype-specific manner. On the other hand, an in vitro binding assay using NoV VLPs showed a uniform recognition pattern against type 1 and 2 core structures, and bind more tightly to type 1 carbohydrates than to type 2. Type 1 carbohydrates are expressed at the surface of the small intestine and are presumably targeted by NoV. This property may afford NoV tissue specificity. GII/4 includes global epidemic strains and binds to more HBGAs than other genogroups. This characteristic may be linked to the worldwide transmission of GII/4 strains. Although it is still unclear whether HBGAs act as primary receptors or enhance NoV infectivity, they are important factors in determining tissue specificity and the risk of transmission.


title: Use of tissue glues in endoscopic pituitary surgery: a cost comparison.

text: BACKGROUND Post-operative cerebrospinal fluid (CSF) leaks are a common complication of endoscopic pituitary surgery and account for a significant proportion of hospital costs associated with this procedure. Tisseel® is a tissue glue commonly used as an adjunct in dural repair but is not optimal for this purpose. DuraSeal® has several properties advantageous for dural repair but is not widely accepted in Canada partly due to its increased cost. OBJECTIVE A cost analysis of DuraSeal® versus Tisseel® in endoscopic pituitary surgery. METHODS A cost analysis was performed based on typical endoscopic pituitary surgery cases performed at our tertiary care institution. Operating room, hospital admission, and surgical sealant costs were obtained directly while estimates of patient recovery time and post-operative CSF leak rates were based on consensus values reported in the literature. Outcomes were reported for various possible clinical scenarios of sealant use. RESULTS In a model where surgical sealant is employed only in high-risk cases, use of DuraSeal® allows for a yearly cost savings of at least $4486.72. If surgical sealant is used in all cases, regular use of DuraSeal® versus Tisseel® either marginally reduces yearly costs or increases them by a maximum of $7619.25, depending on the case volume and estimated post-operative CSF leak rate. CONCLUSION In most clinical scenarios, use of DuraSeal® in endoscopic pituitary surgery may reduce overall yearly hospital costs compared to Tisseel®.


title: [Immunofluorescent diagnosis of rota-, corona- and pestivirus infections in calves].

text: Bovine hyperimmune fluorescent sera were obtained for indication of the rota- and corona-virus infections in calves, which were highly specific and of immunofluorescent titers within the 1:32-64 range. Their testing was carried out via the direct immunofluorescence method, using histologic cross-sectioned material and impression preparations of the mucous membrane of calves died of enteritis as well as cell cultures of fetal calf kidney and organic cultures of calf trachea all contaminated, resp., infected with feces. The study of the intestinal membrane of a total of 100 diseased calves, employing this method, has demonstrated a rotavirus antigen in 38.0 per cent of the cases, and a coronavirus one--in 37.0 per cent. The causative agent of mucous disease (a pestivirus) was demonstrated by means of the respective conjugate in 47.3 per cent of the cases, using abomasal membrane of a total of 55 calves. Rota- and corona-virus infections were also established in the abomasal membrane of diseased calves, and pesti-virus infections--in the intestinal mucosa as well. Established were also mixed infections with the three viruses taking part at various combinations. A celloidin method was worked out for making immunofluorescent preparations of infected monolayer cell cultures. In the cell cultures infected with feces the totavirus antigen was demonstrated in 19.4 per cent of the cases, and the coronavirus one--in 25.6 per cent.


title: [Medication and comedication in COVID-19 patients].

text: This paper discusses the possible effects of comedication on COVID-19 and the current treatment options for this infection. It is very doubtful that comedication has a disadvantageous effect on the course of the disease. NSAIDs should be avoided in any patient with a possible severe disease, because of potential side effects. Inhibitors of the renin-angiotensin aldosterone system should be continued when there is a solid indication, and stopped in case of hemodynamic problems. There is no preference for either ACE inhibitors or angiotensin II receptor inhibitors. Currently, chloroquine and remdesivir are possible treatment options. There is no sound evidence for either treatment. Chloroquine has side effects (nausea, QT prolongation) and there are several drug interactions. The treatment should be reconsidered in the event of side effects and when inferior medication for comorbidity must be prescribed because of possible interactions. Lopinavir/ritonavir is not effective. Supportive care is at present the mainstay of the treatment.


Technical considerations for developing enzyme immunohistochemical staining procedures on formalin-fixed paraffin-embedded tissues for diagnostic pathology.


title: The missing link between human ecology and public health: the case of cancer.

text: OBJECTIVES The primary role played by the 'ecological context' in clarifying the causes and dynamics of human health and disease is the topic of this article. It emphasizes that the challenging incidence of cancer and other diseases can be charged primarily to the effects of the worldwide dominant economic model. METHODS Human culture may act as a powerful force affecting the environment, biology and health of humans and other species. Human culture can be viewed as a special and extreme case of 'niche construction', where human-specific traits, technologies and beliefs act together. RESULTS The feedback between human activities and the environment can promote different trends in public health. This should provide the opportunity to rethink the consequences that our economic model produces both on the environment and on physical, mental and social health of our species.


docid: hfxlaxcj

title: Multigene RNA vector based on coronavirus transcription.

text: Coronavirus genomes are the largest known autonomously replicating RNAs with a size of ca. 30 kb. They are of positive polarity and are translated to produce the viral proteins needed for the assembly of an active replicase-transcriptase complex. In addition to replicating the genomic RNA, a key feature of this complex is a unique transcription process that results in the synthesis of a nested set of six to eight subgenomic mRNAs. These subgenomic mRNAs are produced in constant but nonequimolar amounts and, in general, each is translated to produce a single protein. To take advantage of these features, we have developed a multigene expression vector based on human coronavirus 229E. We have constructed a prototype RNA vector containing the 5' and 3' ends of the human coronavirus genome, the entire human coronavirus replicase gene, and three reporter genes (i.e., the chloramphenicol acetyltransferase [CAT] gene, the firefly luciferase [LUC] gene, and the green fluorescent protein [GFP] gene). Each reporter gene is located downstream of a human coronavirus transcription-associated sequence, which is required for the synthesis of individual subgenomic mRNAs. The transfection of vector RNA and human coronavirus nucleocapsid protein mRNA into BHK-21 cells resulted in the expression of the CAT, LUC, and GFP reporter proteins. Sequence analysis confirmed the synthesis of coronavirus-specific mRNAs encoding CAT, LUC, and GFP. In addition, we have shown that human coronavirus-based vector RNA can be packaged into virus-like particles that, in turn, can be used to transduce immature and mature human dendritic cells. In summary, we describe a new class of eukaryotic, multigene expression vectors that are based on the human coronavirus 229E and have the ability to transduce human dendritic cells.


title: A trimerizing GxxxG motif is uniquely inserted in the severe acute respiratory syndrome (SARS) coronavirus spike protein transmembrane domain.

text: In an attempt to understand what distinguishes severe acute respiratory syndrome (SARS) coronavirus (SCoV) from other members of the coronaviridae, we searched for elements that are unique to its proteins and not present in any other family member. We identified an insertion of two glycine residues, forming the GxxxG motif, in the SCoV spike protein transmembrane domain (TMD), which is not found in any other coronavirus. This surprising finding raises an "oligomerization riddle": the GxxxG motif is a known dimerization signal, while the SCoV spike protein is known to be trimeric. Using an in vivo assay, we found that the SCoV spike protein TMD is oligomeric and that this oligomerization is driven by the GxxxG motif. We also found that the GxxxG motif contributes toward the trimerization of the entire spike protein; in that, mutations in the GxxxG motif decrease trimerization of the full-length protein expressed in mammalian cells. Using molecular modeling, we show that the SCoV spike protein TMD adopts a distinct and unique structure as opposed to all other coronaviruses. In this unique structure, the glycine residues of the GxxxG motif are facing each other, enhancing helix-helix interactions by allowing for the close positioning of the helices. This unique orientation of the glycine residues also stabilizes the trimeric bundle during multi-nanosecond molecular dynamics simulation in a hydrated lipid bilayer. To the best of our knowledge, this is the first demonstration that the GxxxG motif can potentiate other oligomeric forms beside a dimer. Finally, according to recent studies, the stabilization of the trimeric bundle is linked to a higher fusion activity of the spike protein, and the possible influence of the GxxxG motif on this feature is discussed.


title: Exceptional flexibility in the sequence requirements for coronavirus small envelope protein function.

text: The small envelope protein (E) plays a role of central importance in the assembly of coronaviruses. This was initially established by studies demonstrating that cellular expression of only E protein and the membrane protein (M) was necessary and sufficient for the generation and release of virus-like particles. To investigate the role of E protein in the whole virus, we previously generated E gene mutants of mouse hepatitis virus (MHV) that were defective in viral growth and produced aberrantly assembled virions. Surprisingly, however, we were also able to isolate a viable MHV mutant (DeltaE) in which the entire E gene, as well as the nonessential upstream genes 4 and 5a, were deleted. We have now constructed an E knockout mutant that confirms that the highly defective phenotype of the DeltaE mutant is due to loss of the E gene. Additionally, we have created substitution mutants in which the MHV E gene was replaced by heterologous E genes from viruses spanning all three groups of the coronavirus family. Group 2 and 3 E proteins were readily exchangeable for that of MHV. However, the E protein of a group 1 coronavirus, transmissible gastroenteritis virus, became functional in MHV only after acquisition of particular mutations. Our results show that proteins encompassing a remarkably diverse range of primary amino acid sequences can provide E protein function in MHV. These findings suggest that E protein facilitates viral assembly in a manner that does not require E protein to make sequence-specific contacts with M protein.


title: Severe acute respiratory syndrome in children.

text: BACKGROUND Severe acute respiratory syndrome (SARS) is a febrile, respiratory tract illness caused by infection with the newly identified SARS-associated coronavirus. A notable feature of the 2003 global SARS outbreak was the relative paucity of cases reported among children. We reviewed the epidemiologic and clinical features of SARS in children and discuss implications of these findings for diagnosis, treatment and prevention of SARS. METHODS We performed a literature search to identify reports of pediatric (younger than 18 years of age) patients meeting the World Health Organization case definitions for SARS and abstracted relevant clinical and epidemiologic information. RESULTS We identified 6 case series reporting 135 pediatric SARS patients (80 laboratory-confirmed, 27 probable and 28 suspect) from Canada, Hong Kong, Taiwan and Singapore. Among laboratory-confirmed and probable SARS cases, the most common symptoms included fever (98%), cough (60%) and nausea or vomiting (41%); 97% had radiographic abnormalities. The clinical presentation of SARS in patients older than 12 years of age was similar to that in adults. However, patients 12 years of age or younger had milder disease and were less likely than older children to be admitted to an intensive care unit, receive supplemental oxygen or be treated with methylprednisolone. No deaths were reported among children or adolescents with SARS, and at 6 months after illness only mild residual changes were reported in exercise tolerance and pulmonary function. There is only 1 published report of transmission of SARS virus from a pediatric patient. CONCLUSIONS Children and adolescents are susceptible to SARS-associated coronavirus infection, although the clinical course and outcome are more favorable in children younger than 12 years of age compared with adolescents and adults. Transmission of SARS from pediatric patients appears to be uncommon but is possible.


docid: oywbxcvg

title: Respiratory viruses predisposing to bacterial infections: role of neuraminidase.

text: BACKGROUND AND METHODS Viral-bacterial coinfections in humans are well-documented. Viral infections often lead to bacterial superinfections. In vitro and animal models for influenza, as well as molecular microbiology study of viruses and bacteria, provide an understanding of the mechanisms that explain how respiratory viruses and bacteria combine to cause disease. This article focuses on viral and bacterial combinations, particularly synergism between influenza and Streptococcus pneumoniae. RESULTS Potential mechanisms for synergism between viruses and bacteria include: virus destruction of respiratory epithelium may increase bacterial adhesion; virus-induced immunosuppression may cause bacterial superinfections; and inflammatory response to viral infection may up-regulate expression of molecules that bacteria utilize as receptors. Influenza and parainfluenza viruses possess neuraminidase (NA) activity, which appears to increase bacterial adherence after viral preincubation. Experimental studies demonstrate that viral NA exposes pneumococcal receptors on host cells by removing terminal sialic acids. Other studies show that inhibition of viral NA activity reduces adherence and invasion of S. pneumoniae, independently of effects on viral replication. Clinical studies reveal that influenza vaccination reduces the incidence of secondary bacterial respiratory tract infections. CONCLUSIONS Detection of viral factors (e.g. high NA activity) that increase the likely potential of epidemic/pandemic influenza strains for causing morbidity and mortality from secondary bacterial infections provides new possibilities for intervention. Additional study is needed to identify the mechanisms for the development of bacterial complications after infections with respiratory syncytial virus and other important respiratory viruses that lack NA activity. Prevention of bacterial superinfection is likely to depend on effective antiviral measures.


title: Genomic and bioinformatics analysis of HAdV-4, a human adenovirus causing acute respiratory disease: implications for gene therapy and vaccine vector development.

text: Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD.


SARS in Hong Kong.


title: A novel sutureless colonic anastomosis with self-gripping mesh: an experimental model.

text: INTRODUCTION Anastomotic leakage is one of the most feared complications of colorectal surgery. High morbidity and mortality rates are related to this complication and several studies had been performed to test new techniques which are suggested to reduce leakage rates. The aim of our study was to evaluate the safety and effectiveness of a novel technique sutureless anastomosis with self-gripping mesh in an animal model by examining wound healing process in anastomosis. METHODS In this study sixteen Norwegian Wistar Albino female rats were used. The rats' weights ranged from 250 to 300 g. The rats were divided into control and study groups. The control group underwent a colocolic anastomosis using the conventional method of hand-sewing with single-layer interrupted nonabsorbable sutures. The study group underwent a colocolic anastomosis using self-gripping mesh without sutures. These rats were sacrificed on the 10th postoperative day. The sample pieces obtained from the groups were subjected to anastomotic bursting pressure tests, to a test for hydroxyproline levels in the tissue and to histopathological examinations. The tissue was evaluated in terms of quantity of inflammatory cells, fibroblasts, neovascularization level and collagen content and classified according to the Ehrlich-Hunt model. Statistical analysis was done by using Mann-Whitney U test. RESULTS The burst pressure mean ± range of control and study groups were 162 ± 78 and 123 ± 35, respectively (P = 0.049). The mean peritoneal adhesion grades were 3.2 ± 0.7 in the study group and 2.3 ± 0.7 in the control group (P = 0.036). The operative time was significantly shorter in the study group. The difference between the groups by mean of hydroxyproline levels was found to be significant (P = 0.001). According to histopathological examinations by means of the Ehrlich-Hunt model, the fibroblast activation and collagen fiber ratio were higher in the study group and the difference between these measurements was statistically significant (P = 0.006; P = 0.028). CONCLUSION This study showed that use of self-gripping meshes for colocolic anastomosis in rats is a safe and feasible method. It is suggested that the most important advantage of this technique is the shorter operative time.


Chasing hyponatraemia in preterm infants.


title: Imported case of MERS-CoV infection identified in China, May 2015: detection and lesson learned.

text: At the end of May 2015, an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was confirmed in China. The patient is in a stable condition and is still undergoing treatment. In this report, we summarise the preliminary findings for this imported case and the results of contact tracing. We identified 78 close contacts and after 14 days of monitoring and isolation, none of the contacts presented symptoms and all tested negative for MERS-CoV.


title: Antigenic variations among calf diarrhea coronaviruses by immunodiffusion and counterimmunoelectrophoresis.

text: The antigenic relationship among five bovine coronavirus isolates was studied using the counterimmunoelectrophoresis (CIE) and immunodiffusion (ID) techniques. By CIE, two precipitating antigens were observed for each coronavirus isolate. One antigen identified as the "M" coronaviral antigen was found to be common to the five isolates while the second antigen identified as the "m" coronaviral antigen differed between the isolates. Considering the later antigen, the isolates studied were placed in two antigenic groups, members of the same group being indistinguishable for the two antigens. By ID, reactions of partial identity were noted between viruses of the different groups.


docid: uqctlgde

title: Development, characterization, and diagnostic applications of monoclonal antibodies against bovine rotavirus.

text: Hybridomas secreting monoclonal antibodies (MAbs) against the Nebraska calf diarrhea strain of bovine rotavirus (BRV) were characterized. Indirect fluorescent-antibody assay, immunodot assay, and immunoprecipitation were used to select hybridomas that produced anti-BRV MAbs. Seven of the MAbs were shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot assay to be reactive with the BRV outer capsid protein, VP7, which has a molecular mass of 37.5 kDa. None of the seven MAbs were reactive with canine rotavirus, bovine coronavirus, or uninfected Madin-Darby bovine kidney cells. Two clones, 8B4 (immunoglobulin G2a [IgG2a]) and 2B11 (IgG1), were found suitable for use in an antigen capture enzyme-linked immunosorbent assay for detecting BRV in bovine fecal samples. Both were subtype A specific (G6 subtype) but did not react with all isolates of BRV group A.


SARS-associated coronavirus quasispecies in individual patients.


title: Quantification of Tomographic Patterns associated with COVID-19 from Chest CT.

text: PURPOSE To present a method that automatically segments and quantifies abnormal CT patterns commonly present in coronavirus disease 2019 (COVID-19), namely ground glass opacities and consolidations. MATERIALS AND METHODS In this retrospective study, the proposed method takes as input a non-contrasted chest CT and segments the lesions, lungs, and lobes in three dimensions, based on a dataset of 9749 chest CT volumes. The method outputs two combined measures of the severity of lung and lobe involvement, quantifying both the extent of COVID-19 abnormalities and presence of high opacities, based on deep learning and deep reinforcement learning. The first measure of (PO, PHO) is global, while the second of (LSS, LHOS) is lobewise. Evaluation of the algorithm is reported on CTs of 200 participants (100 COVID-19 confirmed patients and 100 healthy controls) from institutions from Canada, Europe and the United States collected between 2002-Present (April, 2020). Ground truth is established by manual annotations of lesions, lungs, and lobes. Correlation and regression analyses were performed to compare the prediction to the ground truth. RESULTS Pearson correlation coefficient between method prediction and ground truth for COVID-19 cases was calculated as 0.92 for PO (P < .001), 0.97 for PHO(P < .001), 0.91 for LSS (P < .001), 0.90 for LHOS (P < .001). 98 of 100 healthy controls had a predicted PO of less than 1%, 2 had between 1-2%. Automated processing time to compute the severity scores was 10 seconds per case compared to 30 minutes required for manual annotations. CONCLUSION A new method segments regions of CT abnormalities associated with COVID-19 and computes (PO, PHO), as well as (LSS, LHOS) severity scores.


title: Structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV, or SCV), which caused a world-wide epidemic in 2002 and 2003, binds to a receptor, angiotensin-converting enzyme 2 (ACE2), through the receptor-binding domain (RBD) of its envelope (spike, S) glycoprotein. The RBD is very immunogenic; it is a major SCV neutralization determinant and can elicit potent neutralizing antibodies capable of out-competing ACE2. However, the structural basis of RBD immunogenicity, RBD-mediated neutralization, and the role of RBD in entry steps following its binding to ACE2 have not been elucidated. By mimicking immune responses with the use of RBD as an antigen to screen a large human antibody library derived from healthy volunteers, we identified a novel potent cross-reactive SCV-neutralizing monoclonal antibody, m396, which competes with ACE2 for binding to RBD, and determined the crystal structure of the RBD-antibody complex at 2.3-A resolution. The antibody-bound RBD structure is completely defined, revealing two previously unresolved segments (residues 376-381 and 503-512) and a new disulfide bond (between residues 378 and 511). Interestingly, the overall structure of the m396-bound RBD is not significantly different from that of the ACE2-bound RBD. The antibody epitope is dominated by a 10-residue-long protruding beta6-beta7 loop with two putative ACE2-binding hotspot residues (Ile-489 and Tyr-491). These results provide a structural rationale for the function of a major determinant of SCV immunogenicity and neutralization, the development of SCV therapeutics based on the antibody paratope and epitope, and a retrovaccinology approach for the design of anti-SCV vaccines. The available structural information indicates that the SCV entry may not be mediated by ACE2-induced conformational changes in the RBD but may involve other conformational changes or/and yet to be identified coreceptors.


title: Knowledge, Attitude And Practice Of Common Cold And Its Management Among Doctors Of Pakistan.

text: BACKGROUND Antibiotic misuse for upper respiratory tract infections such as the common cold is widespread in clinical practice. Excessive prescription of antibiotics by doctors has resulted in increased antimicrobial resistance. This led to our objective of determining the percentage of doctors in Pakistan prescribing antibiotics for the treatment of common cold and to know about their knowledge in preventing the spread of this disease. METHODS It was a cross-sectional descriptive study, conducted in 9 cities of Pakistan including Rawalpindi, Islamabad, Peshawar, Lahore, Karachi, Faisalabad, Sargodha, Multan and D.G. Khan over a period of 03 months -from October to December, 2013. Questionnaire regarding the disease spread and its treatment was distributed among 300 randomly selected doctors in nine cities of Pakistan from both public and private sector. RESULTS Eighteen percent of the doctors prescribe antibiotics for common cold. Only 113 (37.7%) doctors correctly responded that mean incubation period for common cold was 1-2 days. Two hundred and nine (69.7%) answered correctly that cold weather increases susceptibility to common cold. Only 84 (28%) responded correctly by choosing that regular and frequent hand-washing with good quality soaps was the most effective way to prevent spread of this disease in day-to-day life. CONCLUSIONS Antibiotics are being prescribed for treatment of common cold by a large proportion of doctors. There is insufficient knowledge among our doctors regarding the factors which aggravate or alleviate common cold symptoms as well as the methods by which these infections can be prevented.


title: [Expression, purification and identification of recombinant SARS coronavirus membrane protein].

text: A novel coronavirus (SARS-coronavirus, SARS-CoV) was discovered as the pathogen of the severe acute respiratory syndrome (SARS). According to studies with other coronaviruses, the membrane protein (M protein) is the main structural protein and the recombinant M protein may be useful as an antigen for detecting antibodies against coronavirus and for preparing vaccine. In this work, the M protein of SARS-CoV was expressed in E. coli as fusion protein with maltose binding protein at N-terminus and MxeGyrA intein CBD at C-terminus. The recombinant protein was identified by Western blot and mass spectrometry. The soluble parts of the cell crude extract were then partially purified by MBP affinity chromatography. The purified protein will be used for the studies on M protein's structure and the development of diagnostic method of SARS.


title: Using the Barrel Technique with the LVIS Jr (Low-profile Visualized Intraluminal Support) Stent to Treat a Wide Neck MCA Bifurcation Aneurysm.

text: The treatment of wide-neck bifurcation cerebral aneurysms is challenging especially if at least one of the arteries arise from an obtuse angle. These wide-neck bifurcation aneurysms are difficult to treat with the usual balloon and stent assisted coiling, including Y stenting or double-barrel stent techniques [1, 2]. Other available options include using current devices with the waffle cone or double waffle cone techniques [3, 4]. Novel devices that are in development include intrasaccular devices and the barrel bifurcation vascular reconstruction device (Covidien) [5, 6, 7]. We report the use of a novel barrel technique using the LVIS (low-profile visualized intraluminal support) Jr stent for the treatment of a wide-neck bifurcation aneurysm.


Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions.


title: Viral encephalitis: a review of diagnostic methods and guidelines for management.

text: Viral encephalitis is a medical emergency. The spectrum of brain involvement and the prognosis are dependent mainly on the specific pathogen and the immunological state of the host. Although specific therapy is limited to only several viral agents, correct immediate diagnosis and introduction of symptomatic and specific therapy has a dramatic influence upon survival and reduces the extent of permanent brain injury in survivors. We searched MEDLINE (National Library of Medicine) for relevant literature from 1966 to May 2004. Review articles and book chapters were also included. Recommendations are based on this literature based on our judgment of the relevance of the references to the subject. Recommendations were reached by consensus. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. Diagnosis should be based on medical history, examination followed by analysis of cerebrospinal fluid for protein and glucose contents, cellular analysis and identification of the pathogen by polymerase chain reaction (PCR) amplification (recommendation level A) and serology (recommendation level B). Neuroimaging, preferably by magnetic resonance imaging, is an essential aspect of evaluation (recommendation level B). Lumbar puncture can follow neuroimaging when immediately available, but if this cannot be obtained at the shortest span of time it should be delayed only in the presence of strict contraindications. Brain biopsy should be reserved only for unusual and diagnostically difficult cases. All encephalitis cases must be hospitalized with an access to intensive care units. Supportive therapy is an important basis of management. Specific, evidence-based, anti-viral therapy, acyclovir, is available for herpes encephalitis (recommendation level A). Acyclovir might also be effective for varicella-zoster virus encephalitis, gancyclovir and foscarnet for cytomegalovirus encephalitis and pleconaril for enterovirus encephalitis (IV class of evidence). Corticosteroids as an adjunct treatment for acute viral encephalitis are not generally considered to be effective and their use is controversial. Surgical decompression is indicated for impending uncal herniation or increased intracranial pressure refractory to medical management.


title: Identification, molecular characterization, and experimental transmission of a new hemoplasma isolate from a cat with hemolytic anemia in Switzerland.

text: Recently, there has been a growing interest in hemotropic mycoplasmal species (also known as the hemoplasmas), the causative agents of infectious anemia in several mammalian species. In felids, two different hemoplasma species have been recognized: Mycoplasma haemofelis (formerly Haemobartonella felis) and "Candidatus Mycoplasma haemominutum." Recently developed molecular methods have allowed sensitive and specific identification and quantification of these agents in feline blood samples. In applying these methods to an epidemiological study surveying the Swiss pet cat population for hemoplasma infection, we discovered a third novel and unique feline hemoplasma isolate in a blood sample collected from a cat that had exhibited clinical signs of severe hemolytic anemia. This agent was readily transmitted via intravenous inoculation to two specific-pathogen-free cats. One of these cats was immunocompromised by the administration of methylprednisolone acetate prior to inoculation, and this cat developed severe anemia. The other immunocompetent cat showed a moderate decrease in packed cell volume. Additionally, an increase in red blood cell osmotic fragility was observed. Sequencing of the entire 16S rRNA gene of the new hemoplasma isolate and phylogenetic analysis showed that the isolate was most closely related to two rodent hemotropic mycoplasmal species, M. coccoides and M. haemomuris. A quantitative real-time PCR assay specific for this newly discovered agent was developed, which will be a prerequisite for the diagnosis of infections with the new hemoplasma isolate.


title: Forecast and control of epidemics in a globalized world.

text: The rapid worldwide spread of severe acute respiratory syndrome demonstrated the potential threat an infectious disease poses in a closely interconnected and interdependent world. Here we introduce a probabilistic model that describes the worldwide spread of infectious diseases and demonstrate that a forecast of the geographical spread of epidemics is indeed possible. This model combines a stochastic local infection dynamics among individuals with stochastic transport in a worldwide network, taking into account national and international civil aviation traffic. Our simulations of the severe acute respiratory syndrome outbreak are in surprisingly good agreement with published case reports. We show that the high degree of predictability is caused by the strong heterogeneity of the network. Our model can be used to predict the worldwide spread of future infectious diseases and to identify endangered regions in advance. The performance of different control strategies is analyzed, and our simulations show that a quick and focused reaction is essential to inhibiting the global spread of epidemics.


Coronavirus subgenomic replicons as a mechanism for mRNA amplification.


title: Triaryl pyrazoline compound inhibits flavivirus RNA replication.

text: Triaryl pyrazoline {[5-(4-chloro-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-phenyl-methanone} inhibits flavivirus infection in cell culture. The inhibitor was identified through high-throughput screening of a compound library using a luciferase-expressing West Nile (WN) virus infection assay. The compound inhibited an epidemic strain of WN virus without detectable cytotoxicity (a 50% effective concentration of 28 microM and a compound concentration of >or=300 microM required to reduce 50% cell viability). Besides WN virus, the compound also inhibited other flaviviruses (dengue, yellow fever, and St. Louis encephalitis viruses), an alphavirus (Western equine encephalitis virus), a coronavirus (mouse hepatitis virus), and a rhabdovirus (vesicular stomatitis virus). However, the compound did not suppress an orthomyxovirus (influenza virus) or a retrovirus (human immunodeficiency virus type 1). Mode-of-action analyses in WN virus showed that the compound did not inhibit viral entry or virion assembly but specifically suppressed viral RNA synthesis. To examine the mechanism of inhibition of dengue virus, we developed two replicon systems for dengue type 1 virus: (i) a stable cell line that harbored replicons containing a luciferase reporter and a neomycin phosphotransferase selection marker and (ii) a luciferase-expressing replicon that could differentiate between viral translation and RNA replication. Analyses of the compound in the dengue type 1 virus replicon systems showed that it weakly suppressed viral translation but significantly inhibited viral RNA synthesis. Overall, the results demonstrate that triaryl pyrazoline exerts a broad spectrum of antiflavivirus activity through potent inhibition of viral RNA replication. This novel inhibitor could be developed for potential treatment of flavivirus infection.


title: Adverse events of stapling in thoracic surgery: relations between an incidence of adverse events and a stapling volume.

text: PURPOSE The use of staplers for thoracic surgery has been widely accepted and regarded as a safe procedure. However, sometimes adverse events (AEs) of stapling are experienced. The aim of the present study was to retrospectively analyze AEs of stapling in thoracic surgery. METHODS A retrospective multi-institutional review was conducted by the 27 institutions of the Central Japan Lung Cancer Surgery Study Group. Between January 2009 and December 2010, 4495 patients underwent thoracic surgery using mechanical stapling. RESULTS Stapling of various tissues was performed 16403 times. Total number of AEs related to stapling was 126 (0.77%). One hundred and nine events occurred intraoperative and 17 events occurred postoperative. The AE rates ranged from 0% to 1.8%. No relationship was seen between the incidence of AE and a stapling volume of thoracic surgery. CONCLUSION We have investigated intraoperative and postoperative AEs of stapling. Generally, stapling in thoracic surgery was safe. An AE rate of stapling in thoracic surgery is not influenced by the numbers of stapling in institutions.


title: Microwave versus saline-linked radiofrequency (Aquamantys) assisted liver resection in a porcine liver resection model. A safety and feasibility pilot study.

text: PURPOSE The aim of this study was to compare the feasibility, efficacy and safety of microwave ablation and saline-linked radiofrequency (Aquamantys) in liver resection. METHODS Sixteen domestic pigs (8 per group) underwent thermoablations. Group A consisted of 8 pigs in which microwave left lateral liver resection was performed. Group B consisted of 8 pigs which underwent left lateral liver resection by the Aquamantys system. After 28 days of close follow-up, the animals were sacrificed in order to study the macroscopic and microscopic findings of each intervention on the liver edge. RESULTS An average of 47.13 min was enough for the entire operation to take place using Aquamantys, whereas an average of 59.13 min was needed in the microwave liver resection group. Mean blood loss was 40 ml (range 5-85) with Aquamantys whereas mean blood loss was 72.37 ml (range 42-100) using microwave. Postoperative complications rates were extremely low in both groups. There was no intra- or postoperative mortality. CONCLUSIONS Our study demonstrated that left lateral liver resection using Aquamantys system is technically feasible in the porcine model and proved to be highly effective and a safer hemostatic method compared to microwave ablation.


title: Clinical manifestation, diagnosis, prevention and control of SARS-CoV-2 (COVID-19) during the outbreak period.

text: The novel coronavirus SARS-CoV-2 (Covid-19), spreading from Wuhan, China, is one of the causes of respiratory infections that can spread to other people through respiratory particles, and can cause symptoms such as fever, dry cough, shortness of breath, anorexia, fatigue and sore throat in infected patients. This review summarizes current strategies on the diagnosis. Additionally, treatments, infection prevention and control of the SARS-CoV-2 are addressed. In addition to the respiratory system, this virus can infect the digestive system, the urinary system and the haematological system, which causes to observe the virus in the stool, urine and blood samples in addition to throat sample. The SARS-CoV-2 causes changes in blood cells and factors and makes lung abnormalities in patients, which can be detected by serological, molecular, and radiological techniques by detecting these changes and injuries. Radiological and serological methods are the most preferred among the other methods and the radiological method is the most preferred one which can diagnose the infection quickly and accurately with fewer false-negatives, that can be effective in protecting the patient's life by initiating treatment and preventing the transmission of infection to other people.


title: The immunology of virus infection in asthma.

text: The respiratory tract is commonly infected by a range of viruses with overlapping pathologies. The majority of episodic exacerbations of asthma are associated with viral infection, in particular with rhinovirus infections. Experimental rhinovirus infection in human volunteers provides a useful model of natural virus-induced asthma. The asthmatic airway is characterized by an infiltrate of eosinophils and T-lymphocytes expressing the type 2 cytokines interleukin (IL)-4, IL-5 and IL-13. An effective antiviral immune response requires early viral clearance and appropriate termination of the immune response to minimize associated immunopathology and tissue damage. The antiviral immune response is made up of innate (nonspecific) and specific components, and requires the coordinated actions of many different cell types including neutrophils, macrophages, eosinophils, dendritic cells, epithelial cells, mast cells, natural killer cells and B- and T-lymphocytes. Coordination of this response involves numerous cytokines and chemokines. T-lymphocytes expressing type 1 cytokines including interferon-gamma play a key role. Pre-existing asthmatic inflammation in the lower airway may modify the immune response to viral infection by altering the balance of T-cell cytokine expression from type 1 towards a type 2 in what is always a mixed response. The consequence is delayed viral clearance, persistent virus-induced inflammation and amplification of the allergic inflammation.


Controlling immune response may cut bird flu death rate.


Influenza C virus infection in children, Spain.


title: Neuropathological findings in cats with clinically suspect but histologically unconfirmed feline spongiform encephalopathy.

text: Central nervous system (CNS) tissues from 192 cats with neurological signs were examined histologically, and tissues from 173 of them were later examined immunohistochemically as part of a survey to determine the prevalence of feline spongiform encephalopathy (FSE). One of the cats was from Norway and the others were from Great Britain. The most commonly recorded clinical signs were ataxia, behavioural changes and epilepsy, but none of the cats had histopathological evidence of FSE. The most common organic CNS lesions were non-suppurative encephalomyelitis in 28 per cent, neoplasia in 15 per cent and a heterogeneous group of degenerative encephalopathies in 9 per cent of the cats. A range of minor histological lesions of uncertain significance was also observed. No histological lesions were observed in the tissues of 63 (33 per cent) of the cats. Disease-specific prion protein (PrP(Sc)) was observed in only one of the 173 cats examined by immunohistochemistry.


title: SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF IMIDAZO[2,1- b][1,3,4]THIADIAZOLE DERIVATIVES.

text: In this paper, a series of imidazo[2,l-b][1,3,4]thiadiazoles have been prepared by reacting 2-amino-1,3,4-thiadiazole with various phenacyl bromides in alcohol. The structures of all the derivatives were con- firmed by IR, NMR and mass spectroscopy. All the derivatives have been tested for cytostatic activity against human T-lymphocyte cells (CEM), human cervix carcinoma cells (HeLa), murine leukemia cell line (L1210), and antiviral activity. Among the tested compounds, derivatives 5b, 5c, and 7a were cytostatic between 49-63 mM against Hela and 7g was cytotoxic at 23 mM against L1210 and CEM cell lines. Compounds 5h and 7h emerged as antiviral agents with slight activity against influenza A and B.


title: Plasma-derived proteins in airway defence, disease and repair of epithelial injury.

text: One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.


title: [The Isolation and Identification of Infectious Bronchitis Virus PTFY Strain in Muscovy Ducks].

text: In July 2009, some farms of breeding Muscovy ducks on the peak of egg laying suffered the decrease of hatching rate and the quality of the eggs showing low mortality and no evident respiratory symptoms. The swelling and congestive ovary was visible after autopsy. This study was brought out for the diagnosis of these cases. The virus was isolated and identified by the methods of virus culture in chicken embryo, physical and chemical properties test, hemagglutinin test, NDV (Newcastle diseases Virus) interference test, electron microscope observation, pathogenicity test and the gene sequence analysis. The results indicated the virus showed the characters of inducing dwarf embryo after inocubation, the sensibility to lipid solvent and the hemagglutination capacity after pancreatic enzyme treatment, the typical morphology of coronavirus, the interference to NDV replication and the homology among 84.7% - 99% of the particial N gene sequences to the reference IBV (Avian infectious bronchitis virus) strains. The strain was identified as IBV isolate and this study confirmed the pathogenicity of IBV to Muscovy ducks.


title: Carotid artery intima media thickness, plaque and Framingham cardiovascular score in Asia, Africa/Middle East and Latin America: the PARC-AALA study.

text: OBJECTIVE The PARC-AALA (Paroi artérielle et Risque Cardiovasculaire in Asia Africa/ Middle East and Latin America) study was designed to evaluate the correlation between intima-media thickness of the common carotid artery (CCAIMT), carotid plaque and absolute cardiovascular risk in a multi-ethnic population. METHODS An international, cross-sectional, study including 79 centres from 21 countries in Asia, Africa, the Middle East and Latin America. Two thousand three hundred and twenty-eight subjects, meeting all inclusion criteria, were stratified by risk factors groups (no modifiable factor or at least both uncontrolled hypertension and hypercholesterolemia). CCAIMT, presence of plaque and cardiovascular risk factors were assessed for each individual. RESULTS Some intergeographical characteristics in demographics, and risk factors were found accompanying early atherosclerosis marker differences. In Asia where the subjects were at lower risk, the mean CCAIMT was 4% lower than in Africa/Middle East and Latin America. On multiple linear regression analysis CCAIMT and carotid plaque were independently associated with increased Framingham cardiovascular score (FCS) without heterogeneity across geographic regions. CCAIMT and carotid plaque explained roughly 20% of the FCS in both genders. CONCLUSION The PARC-AALA study confirms the correlation between CCAIMT and FCS in three different populations. Intima-media thickness (IMT) and plaque evaluation may represent a complementary predictive tool for detection of cardiovascular disease in individuals.


title: Renal denervation: a new therapeutic approach for resistant hypertension.

text: OBJECTIVE To review the advances in studies on renal denervation. DATA SOURCES References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. STUDY SELECTION Articles with keywords "renal denervation" and "resistant hypertension" were selected. RESULTS Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformité Européenne mark is also included in this review. CONCLUSIONS Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.


title: Biological invasions: recommendations for U.S. policy and management.

text: The Ecological Society of America has evaluated current U.S. national policies and practices on biological invasions in light of current scientific knowledge. Invasions by harmful nonnative species are increasing in number and area affected; the damages to ecosystems, economic activity, and human welfare are accumulating. Without improved strategies based on recent scientific advances and increased investments to counter invasions, harm from invasive species is likely to accelerate. Federal leadership, with the cooperation of state and local governments, is required to increase the effectiveness of prevention of invasions, detect and respond quickly to new potentially harmful invasions, control and slow the spread of existing invasions, and provide a national center to ensure that these efforts are coordinated and cost effective. Specifically, the Ecological Society of America recommends that the federal government take the following six actions: (1) Use new information and practices to better manage commercial and other pathways to reduce the transport and release of potentially harmful species; (2) Adopt more quantitative procedures for risk analysis and apply them to every species proposed for importation into the country; (3) Use new cost-effective diagnostic technologies to increase active surveillance and sharing of information about invasive species so that responses to new invasions can be more rapid and effective; (4) Create new legal authority and provide emergency funding to support rapid responses to emerging invasions; (5) Provide funding and incentives for cost-effective programs to slow the spread of existing invasive species in order to protect still uninvaded ecosystems, social and industrial infrastructure, and human welfare; and (6) Establish a National Center for Invasive Species Management (under the existing National Invasive Species Council) to coordinate and lead improvements in federal, state, and international policies on invasive species. Recent scientific and technical advances provide a sound basis for more cost-effective national responses to invasive species. Greater investments in improved technology and management practices would be more than repaid by reduced damages from current and future invasive species. The Ecological Society of America is committed to assist all levels of government and provide scientific advice to improve all aspects of invasive-species management.


title: Screening and identification of severe acute respiratory syndrome-associated coronavirus-specific CTL epitopes.

text: Severe acute respiratory syndrome (SARS) is a highly contagious and life-threatening disease that emerged in China in November 2002. A novel SARS-associated coronavirus was identified as its principal etiologic agent; however, the immunopathogenesis of SARS and the role of special CTLs in virus clearance are still largely uncharacterized. In this study, potential HLA-A*0201-restricted spike (S) and nucleocapsid protein-derived peptides were selected from an online database and screened for potential CTL epitopes by in vitro refolding and T2 cell-stabilization assays. The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-gamma ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2(+) SARS-recovered donors. A novel HLA-A*0201-restricted decameric epitope P15 (S411-420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain. P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-gamma-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo. Furthermore, significant P15-specific CTLs were induced from HLA-A2.1-transgenic mice immunized by a DNA vaccine encoding the S protein; suggesting that P15 was a naturally processed epitope. Thus, P15 may be a novel SARS-associated coronavirus-specific CTL epitope and a potential target for characterization of virus control mechanisms and evaluation of candidate SARS vaccines.


docid: xzuqeunb

title: COVID-19 Teaches Hard Lessons.


title: Onyx Embolization as Single Rescue Treatment for Ruptured Abdominal Aortic Aneurysm After EVAR.

text: A 76-year-old man who had undergone endovascular repair for an infrarenal aortic aneurysm, presented with a late type Ia endoleak 3 years after his operation. Deployment of an aortic cuff did not achieve a better seal at the proximal neck, and the aneurysm developed a rupture. We successfully treated the ruptured aneurysm using transcatheter Onyx embolization only. At 6-month and 1-year follow-ups with contrast-enhanced duplex scanning, no endoleak was seen and sac shrinkage was observed. Onyx is a relatively new liquid embolic agent that is slowly transformed into a solid state by contact with blood. Owing to this unique characteristic, Onyx embolization can be a useful technique for stopping bleeding from an aneurysm in an emergency situation. This is a unique case of the use of an embolization agent in the treatment of aortic aneurysm rupture.


title: Sensitivity of SARS/MERS CoV to interferons and other drugs based on achievable serum concentrations in humans.

text: A novel coronavirus (MERS-CoV) related to SARS-CoV recently emerged in the Middle East causing more than 400 deaths with a mortality rate of about 30%, much higher than SARS-CoV. Both viruses target epithelial cells in the respiratory tract, although utilizing different cellular receptors. Because of the sporadic nature of the MERS outbreak and difficulty in collecting randomized, controlled clinical data, the objective of this review was to focus on published in vitro and in vivo drug sensitivity data using both cell lines and available animal models of SARS/MERS CoV infection. Determination of drug activity was based on achievable serum levels in humans relative to in vitro IC50 (50% inhibitory concentration) or EC50 (50% effective concentration) drug concentrations. The most active drugs against SARS/MERS CoV at clinically achievable serum levels were type I interferons and a TLR3 agonist, interferon inducer/activator.


title: Novel 2019 coronavirus SARS-CoV-2 (COVID-19): An updated overview for emergency clinicians

text: The novel coronavirus, COVID-19, has quickly become a worldwide threat to health, travel, and commerce. This overview analyzes the best information from the early research, including epidemiologic and demographic features from SARS-CoV-1 and MERS-CoV viruses; lessons learned from the experience of an emergency physician in Northern Italy, where the outbreak has devastated the healthcare system; evidence on transmission and prevention through safe use of PPE; evidence and advice on SARS-CoV-2 testing and co-infection; management options; airway management options; steps for rapid sequence intubation in the ED and managing disaster ventilation; and information on managing pediatric and pregnant patients.


title: Structural requirements for multimerization of the pathogen receptor dendritic cell-specific ICAM3-grabbing non-integrin (CD209) on the cell surface.

text: The myeloid C-type lectin dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN, CD209) recognizes oligosaccharide ligands on clinically relevant pathogens (HIV, Mycobacterium, and Aspergillus). Alternative splicing and genomic polymorphism generate DC-SIGN mRNA variants, which have been detected at sites of pathogen entrance and transmission. We present evidence that DC-SIGN neck variants are expressed on dendritic and myeloid cells at the RNA and protein levels. Structural analysis revealed that multimerization of DC-SIGN within a cellular context depends on the lectin domain and the number and arrangement of the repeats within the neck region, whose glycosylation negatively affects oligomer formation. Naturally occurring DC-SIGN neck variants differ in multimerization competence in the cell membrane, exhibit altered sugar binding ability, and retain pathogen-interacting capacity, implying that pathogen-induced cluster formation predominates over the basal multimerization capability. Analysis of DC-SIGN neck polymorphisms indicated that the number of allelic variants is higher than previously thought and that multimerization of the prototypic molecule is modulated in the presence of allelic variants with a different neck structure. Our results demonstrate that the presence of allelic variants or a high level of expression of neck domain splicing isoforms might influence the presence and stability of DC-SIGN multimers on the cell surface, thus providing a molecular explanation for the correlation between DC-SIGN polymorphisms and altered susceptibility to HIV-1 and other pathogens.


Babesiosis in Fairfield County, Connecticut.