title: Outbreaks in Quebec pig farms of respiratory and reproductive problems associated with encephalomyocarditis virus.

text: Encephalomyocarditis virus (EMCV) was isolated from tissues of aborted fetuses and weaned and suckling piglets from 4 different pig farms in Quebec. The farms were experiencing reproductive failure in sows of different parities concomitant to respiratory problems in suckling and postweaning piglets. At necropsy, gross lesions were confined to the lung and consisted of pulmonary congestion and edema of various degrees. Lesions of multifocal interstitial to proliferative pneumonia were found in the lungs of these piglets. Bacteriologic examination of various tissues from necropsied pigs yielded no pathogens in most cases. No significant antibody titers against 3 swine viruses (transmissible gastroenteritis virus, porcine parvovirus, and swine influenza virus) and two bovine viruses (bovine viral diarrhea and infectious bovine rhinotracheitis viruses) were detected in the sera of convalescent pigs. The Quebec EMCV isolates were antigenically related to the reference ATCC-VR129 strain of EMCV, as demonstrated by indirect immunofluorescence, serum neutralization (SN), and Western immunoblotting. However, one of the Quebec isolates could be distinguish by SN. EMCV-specific SN antibody titers up to 1:12,800 were detected in thoracic and ascitis fluids of aborted fetuses and in sera of convalescent pigs. A possible pneumotropic EMCV variant in swine may exist.


title: The papain-like protease of severe acute respiratory syndrome coronavirus has deubiquitinating activity.

text: Replication of the genomic RNA of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by replicase polyproteins that are processed by two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro). Previously, we showed that SARS-CoV PLpro processes the replicase polyprotein at three conserved cleavage sites. Here, we report the identification and characterization of a 316-amino-acid catalytic core domain of PLpro that can efficiently cleave replicase substrates in trans-cleavage assays and peptide substrates in fluorescent resonance energy transfer-based protease assays. We performed bioinformatics analysis on 16 papain-like protease domains from nine different coronaviruses and identified a putative catalytic triad (Cys1651-His1812-Asp1826) and zinc-binding site. Mutagenesis studies revealed that Asp1826 and the four cysteine residues involved in zinc binding are essential for SARS-CoV PLpro activity. Molecular modeling of SARS-CoV PLpro suggested that this catalytic core may also have deubiquitinating activity. We tested this hypothesis by measuring the deubiquitinating activity of PLpro by two independent assays. SARS CoV-PLpro hydrolyzed both diubiquitin and ubiquitin-7-amino-4-methylcoumarin (AMC) substrates, and hydrolysis of ubiquitin-AMC is approximately 180-fold more efficient than hydrolysis of a peptide substrate that mimics the PLpro replicase recognition sequence. To investigate the critical determinants recognized by PLpro, we performed site-directed mutagenesis on the P6 to P2' residues at each of the three PLpro cleavage sites. We found that PLpro recognizes the consensus cleavage sequence LXGG, which is also the consensus sequence recognized by cellular deubiquitinating enzymes. This similarity in the substrate recognition sites should be considered during the development of SARS-CoV PLpro inhibitors.


title: Detection of Chlamydia in formalin-fixed and paraffin-embedded avian tissue by in situ hybridization. A comparison between in situ hybridization and peroxidase-antiperoxidase labelling.

text: In situ hybridization, (ISH) using a digoxigenin-antisense RNA-probe to detect chlamydial rRNA was applied to post mortem tissue of birds. The technique was optimized and validated using tissue from experimentally-infected chicken embryos. Tissue sections were also tested by immunohistochemistry (peroxidase-antiperoxidase reaction, PAP) for the presence of chlamydial antigen using a genus specific monoclonal antibody. In the chicken embryo tissue, ISH and PAP were comparably sensitive and specific (100% and 100%, respectively). ISH and PAP in general were correlated to microscopic lesions. For further comparison, ISH with PAP was applied retrospectively to tissues of 82 birds from which Chlamydia had been isolated, or which were suggestive of chlamydiosis. Using in situ hybridization 47 of 82 birds were found to be positive, and as were 23 of 82 birds with PAP. None of the ISH-only positive cases were found to be strongly positive. On the other hand, cases which were found positive with the ISH were also positive with other methods (PAP and isolation of Chlamydiae from chicken embryos). There was no close correlation between the positive cells and histological lesions. In spite of the higher sensitivity and specificity of the ISH, this technique is not suitable for routine diagnostic investigations. ISH is expensive, laborious, and time consuming.


title: Ulcerative enterocolitis in two goats associated with enterotoxin- and beta2 toxin-positive Clostridium perfringens type D.

text: Enterotoxemia caused by Clostridium perfringens type D in sheep is believed to result from the action of epsilon toxin (ETX). However, the sole role of ETX in the intestinal changes of the acute and chronic forms of enterotoxemia in goats remains controversial, and the synergistic action of other C. perfringens toxins has been suggested previously. The current study examined 2 goats that were found dead without premonitory clinical signs. Gross lesions at necropsy consisted of multifocal fibrinonecrotic enterocolitis, edematous lungs, and excess pleural fluid. Histologically, there were multifocal fibrinonecrotic and ulcerative ileitis and colitis, edema of the colonic serosa, and proteinaceous interstitial edema of the lungs. Clostridium perfringens type D carrying the genes for enterotoxin (CPE) and beta2 toxin (CPB2) was cultured from intestinal content and feces of 1 of 2 goats, while C. perfringens type D CPB2-positive was isolated from the other animal. When multiple colonies of the primary isolations from both animals were tested by Western blot, most of the isolates expressed CPB2, and only a few isolates from the first case expressed CPE. Alpha toxin and ETX were detected in ileal and colonic contents and feces of both animals by antigen capture enzyme-linked immunosorbent assay. CPB2, but not CPE, was identified in the small and large intestines of both goats by immunohistochemistry. These findings indicate that CPB2 may have contributed to the necrotic changes observed in the intestine, possibly assisting ETX transit across the intestinal mucosa.


Severe acute respiratory syndrome revisited.


title: The structure of the endoribonuclease XendoU: From small nucleolar RNA processing to severe acute respiratory syndrome coronavirus replication.

text: Small nucleolar RNAs (snoRNAs) play a key role in eukaryotic ribosome biogenesis. In most cases, snoRNAs are encoded in introns and are released through the splicing reaction. Some snoRNAs are, instead, produced by an alternative pathway consisting of endonucleolytic processing of pre-mRNA. XendoU, the endoribonuclease responsible for this activity, is a U-specific, metal-dependent enzyme that releases products with 2'-3' cyclic phosphate termini. XendoU is broadly conserved among eukaryotes, and it is a genetic marker of nidoviruses, including the severe acute respiratory syndrome coronavirus, where it is essential for replication and transcription. We have determined by crystallography the structure of XendoU that, by refined search methodologies, appears to display a unique fold. Based on sequence conservation, mutagenesis, and docking simulations, we have identified the active site. The conserved structural determinants of this site may provide a framework for attempting to design antiviral drugs to interfere with the infectious nidovirus life cycle.


title: A major outbreak of severe acute respiratory syndrome in Hong Kong.

text: BACKGROUND There has been an outbreak of the severe acute respiratory syndrome (SARS) worldwide. We report the clinical, laboratory, and radiologic features of 138 cases of suspected SARS during a hospital outbreak in Hong Kong. METHODS From March 11 to 25, 2003, all patients with suspected SARS after exposure to an index patient or ward were admitted to the isolation wards of the Prince of Wales Hospital. Their demographic, clinical, laboratory, and radiologic characteristics were analyzed. Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed. RESULTS There were 66 male patients and 72 female patients in this cohort, 69 of whom were health care workers. The most common symptoms included fever (in 100 percent of the patients); chills, rigors, or both (73.2 percent); and myalgia (60.9 percent). Cough and headache were also reported in more than 50 percent of the patients. Other common findings were lymphopenia (in 69.6 percent), thrombocytopenia (44.8 percent), and elevated lactate dehydrogenase and creatine kinase levels (71.0 percent and 32.1 percent, respectively). Peripheral air-space consolidation was commonly observed on thoracic computed tomographic scanning. A total of 32 patients (23.2 percent) were admitted to the intensive care unit; 5 patients died, all of whom had coexisting conditions. In a multivariate analysis, the independent predictors of an adverse outcome were advanced age (odds ratio per decade of life, 1.80; 95 percent confidence interval, 1.16 to 2.81; P=0.009), a high peak lactate dehydrogenase level (odds ratio per 100 U per liter, 2.09; 95 percent confidence interval, 1.28 to 3.42; P=0.003), and an absolute neutrophil count that exceeded the upper limit of the normal range on presentation (odds ratio, 1.60; 95 percent confidence interval, 1.03 to 2.50; P=0.04). CONCLUSIONS SARS is a serious respiratory illness that led to significant morbidity and mortality in our cohort.


title: Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus.

text: Glycyrrhizin (GL) was shown to inhibit SARS-coronavirus (SARS-CoV) replication in vitro. Here the anti-SARS-CoV activity of 15 GL derivatives was tested. The introduction of 2-acetamido-beta-d-glucopyranosylamine into the glycoside chain of GL resulted in 10-fold increased anti-SARS-CoV activity compared to GL. Amides of GL and conjugates of GL with two amino acid residues and a free 30-COOH function presented up to 70-fold increased activity against SARS-CoV but also increased cytotoxicity resulting in decreased selectivity index.


title: Characterization of the S protein of enterotropic murine coronavirus strain-Y.

text: The pathogenesis of enterotropic murine coronavirus strain MHV-Y differs extensively from that of prototypic respiratory strains of murine coronaviruses. The S protein of MHV-Y was characterized as a first step towards identifying viral determinants of enterotropism. Immunoblots of MHV-Y virions using anti-S protein specific antiserum revealed that the MHV-Y S protein was inefficiently cleaved. The MHV-Y S gene was cloned and sequenced. It encodes a protein predicted to be 1361 amino acids long. The presence of several amino acids changes within and surrounding the predicted cleavage site of the MHV-Y S protein may contribute to its inefficient cleavage.


title: Identification and characterization of a Penaeus monodon lymphoid cell-expressed receptor for the yellow head virus.

text: The yellow head virus is a positive-sense, single-stranded RNA virus that causes significant mortality in farmed penaeid shrimp. This study sought to isolate and characterize the receptor protein used by the virus to gain entry into Penaeus monodon Oka (lymphoid) organ cells, a primary target of yellow head virus infections. Virus overlay protein binding assay on Oka organ membrane preparations identified a 65-kDa protein, and antibodies raised against this protein inhibited virus entry in primary Oka cell cultures by approximately 80%. N-terminal sequence analysis of the 65-kDa protein generated a 17-amino acid peptide fragment which was used to design degenerate primers that amplified a 1.5-kbp product from Oka organ total RNA, which was cloned and sequenced. Northern analysis and PCR were used to confirm a single RNA transcript that was expressed in most tissues. Subsequently, the mature cDNA was recloned and the expressed protein shown to cross-react with the antibody raised against the original virus binding band. Down regulation of the message through double-stranded RNA-mediated RNA interference silencing resulted in the complete inhibition of virus entry. While the identity of the clone remains unknown, it nevertheless represents the first invertebrate Nidovirus receptor isolated to date.


title: A novel approach using Neuron 6F guiding catheter for the embolization of intracranial aneurysm with coiling of the parent internal carotid artery.

text: To describe our initial experience and early outcomes with distal placement of the Neuron 6F guiding catheter through coiled ICA for aneurysmal EVT. We examined the utility of the Neuronf 70 6F guiding catheter for the embolization procedure in such cases, fourteen cases of aneurysm with coiling of the parent ICA are presented via traditional guiding catheters. With the support of 8F ENVOY guiding catheter as a shuttle sheath, the Neuron(TM) 70 6F guiding catheter was successfully placed through coiled extracranial ICA, so the mirocatheter could be delivered to a more strategic position for embolization of the aneurysm. Coiling of extracranial ICA was found as parent artery on angiogram in all patients with ruptured aneurysms. Even where there were two curvatures of more than 360° in the coiled segment of the ICA, Neuron(TM) 70 6F guiding catheter could be placed through the coiling to a distal position and enabled EVT of intracranial aneurysms with no related neurological complications. Neuron guiding catheter is a useful device for embolization of aneurysm where there is coiling of parent ICA, easily placed through the coiling of the ICA and provided robust anatomical support via enhanced catheter-to-vessel wall engagement.


In vivo and in vitro models of demyelinating diseases--VIII: Genetic, immunologic and cellular influences on JHM virus infection of rats.


Hidradenitis Suppurativa: Radical Cure in a Patient with a Malignant Course.


Streamlining ethics review for multisite quality and safety initiatives: national bariatric surgery registry experience.


title: Screening for HIV protease inhibitors by protection against activity-mediated cytotoxicity in Escherichia coli.

text: Expressed retroviral proteases are often cytotoxic to the hosts. The cytotoxicity of a tethered dimer HIV protease described previously is particularly severe that transformed Escherichia coli cells could not survive the bactericidal activity of the low-level protease produced under uninduced conditions. The presence of HIV protease inhibitors protected the transformed cells from cytotoxic effects and allowed the growth of these cells on plates and in broth. A high throughput screening method was developed to seek compounds that served as "growth factors" for the HIV protease restricted cells. Several compounds identified by this screening supported the growth of these cells, preserved their viability, and inhibited HIV protease. This assay could be used as a general method for screening for inhibitors of recombinant enzymes that produce a cytotoxic phenotype in host cells.


Government action needed to step up research and development for world's most neglected diseases.


title: Congenital fixation of the head of the stapes in three family members.

text: We conducted a retrospective chart review at a university hospital on a family that exhibited a rare cause of conductive hearing loss. Four male patients of this family had congenital conductive hearing loss. Three of these family members underwent bilateral ossiculoplasty, a father and two of his three sons. All three were found to have mild or moderate conductive hearing loss due to fixation of the head of the stapes by a bony bar that extended from the head of the stapes to the posterior ear canal wall. Surgical removal of the bony bar improved hearing in all cases. This family exhibits autosomal-dominant inheritance of this abnormality. Fixation of the head of the stapes by a bony bar that extends to the posterior ear canal wall is a rare cause of congenital, autosomal-dominant, mild or moderate conductive hearing loss that can be surgically corrected.


title: Use of diagnostic algorithms and new technologies to study the incidence and prevalence of viral upper respiratory tract infections and their complications in high risk populations.

text: PURPOSE OF REVIEW Most studies on the natural history of viral upper respiratory tract infections and their complications rely for ascertainment on self-assessed cold/flu illness or the identification of presumed complications. The criteria for cold/flu definition, however, are variable within and between individuals and illness is not prerequisite for a viral upper respiratory tract infection. These factors bias estimates of the incidence and prevalence of viral upper respiratory tract infections and their complications. Here we review new methodologies that can be adapted for use in future studies to refine those estimates. RECENT FINDINGS We present a theoretical basis for standardized assignment of cold/flu episodes using a minimal algorithm template that operates on a structured set of symptoms/signs. We emphasize the greater accuracy of information derived from longitudinal studies that incorporate identification algorithms and assay of nasal secretions for causal virus by polymerase chain reaction and for proinflammatory chemicals to confirm nasal inflammation. SUMMARY The methodologies and sampling strategies that we describe hold promise for better characterizing the incidence of complications for symptomatic and asymptomatic expressions of a viral upper respiratory tract infection caused by specific viruses. These data can then be used to estimate the efficacy and efficiency in a specified target population of prophylactic or intercurrent treatments to prevent the complications.


title: [Important aspects of prevention of health personnel in hospitals during the epidemic novel coronavirus 2019.]

text: Today, the novel coronavirus has spread widely throughout the world and poses new challenges to ensure the health and safety of health personnel. Because health personnel are at the frontlines in the fight against the novel coronavirus, which is one of the groups most affected and vulnerable during the pandemic, it is necessary to remind that the preventive measures adopted by health personnel are essential. Especially in emergency situations, essential measures must be taken to prevent occupational exposure during the novel coronavirus pandemic. Health professionals are working with great intensity and enormous social responsibility. In addition to the applause, they deserve more attention.


title: [Expression of SARS-CoV in various types of cells in lung tissues].

text: OBJECTIVE To investigate the cell types infected by severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in lung tissues and explore the mechanism of lung injury in SARS. METHODS In-situ hybridization(ISH) and immunohistochemistry(IHC) double staining was applied to study the lung tissues from 7 SARS cases of Beijing and one of Anhui province. According to SARS-CoV genome sequence, the cDNA probe was synthesized and labelled by digoxin. Immunohistochemically, antibodies of cytokeratin(CK), CD34, CD68, Vimentin and CD3 were applied to demonstrate bronchial epithelial cells, type II pneumocytes, endothelial cells, macrophages, fibroblasts and T cells respectively. RESULTS The positive results of in-situ hybridization showed that the lung tissues of all cases expressed SARS-CoV RNA, and positive signals displayed in cytoplasms (purple-blue, NBP-BCIP. ISH-IHC double staining showed that positive signals of both ISH (purple-blue NBT-BCIP and IHC (red-brown, AEC expressed in the cytoplasms (purple and red). The positive results of double staining indicated that bronchial epithelial cells, type II pneumocytes, endothelial cells, macrophages, fibroblasts and T lymphocytes were diffusely infected by SARS-CoV. CONCLUSION This study of ISH-IHC double staining in lung tissues of SARS patients showed that bronchial epithelial cells, type II pneumocytes, endothelial cells, macrophages, T lymphocytes and fibroblasts were attacked diffusely in SARS lungs. Various types of cells damaged by SARS-CoV and inflammatory mediators released by those cells play an important role in the pathogenesis of lung injury in SARS.


title: [Study on the epidemic development of COVID-19 in Hubei province by a modified SEIR model].

text: OBJECTIVE To establish a SEIR epidemic dynamics model that can be used to evaluate the COVID-19 epidemic, and to predict and evaluate the COVID-19 epidemic in Hubei province using the proposed model. METHODS COVID-19 SEIR transmission dynamics model was established, which took transmission ability in latent period and tracking quarantine interventions into consideration. Based on the epidemic data of Hubei province from January 23, 2020 to February 24, 2020, the parameters of the newly established modified SEIR model were fitted. By using Euler integral algorithm to solve the modified SEIR dynamics model, the epidemic situation in Hubei province was analyzed, and the impact of prevention and control measures such as quarantine and centralized treatment on the epidemic development was discussed. RESULTS The theoretical estimation of the epidemic situation by the modified SEIR epidemic dynamics model is in good agreement with the actual situation in Hubei province. Theoretical analysis showed that prevention and control quarantine and medical follow-up quarantine played an important inhibitory effect on the outbreak of the epidemic.The centralized treatment played a key role in the rapid decline in the number of infected people. In addition, it is suggested that individuals should improve their prevention awareness and take strict self-protection measures to curb the increase in infected people. CONCLUSIONS The modified SEIR model is reliable in the evaluation of COVID-19 epidemic in Hubei province, which provides a theoretical reference for the decision-making of epidemic interventions.


title: The infectivity and pathogenicity of a group 2 bovine coronavirus in pups.

text: Canine respiratory coronavirus (CRCoV), which is more closely related to the bovine coronavirus (BCoV), has recently been detected in dogs. In this study, we examined whether BCoV was capable of infecting and exhibiting pathogenicity in dogs. Three 1-month-old pups were oronasally given field isolates of BCoV, and were kept together with 2 control animals. As a result, increases in BCoV-neutralizing antibody titers were confirmed in all pups in the challenged and control groups. Moreover, the virus gene was also detected in oral and rectal swabs by RT-PCR. These results indicate that BCoV infects dogs, and easily infects other dogs that are kept together. However, no clinical symptoms such as respiratory symptoms and diarrhea were observed.


docid: olmoscaf

title: Coronavirus-, calicivirus-, and astrovirus-like particles associated with acute porcine gastroenteritis.


title: Rotavirus shedding in feces of gnotobiotic calves orally inoculated with a commercial rotavirus-coronavirus vaccine.

text: The purpose of this study was to monitor by negative stain electron microscopy the shedding of rotavirus in the feces of gnotobiotic calves orally inoculated with a commercial modified live bovine rotavirus-bovine coronavirus vaccine. Negative stain electron microscopic examination detected vaccine rotavirus in only 1 of 41 daily fecal specimens collected from 3 gnotobiotic calves during the 2 weeks following oral inoculation with a US Department of Agriculture-licensed modified live bovine rotavirus-bovine coronavirus vaccine. In contrast, rotavirus was demonstrable by the same negative stain electron microscopic examination procedure in 17 of 19 fecal specimens collected from diarrheic gnotobiotic or colostrum-deprived calves during the first 8 days after inoculation with virulent bovine rotavirus field strains. Rotavirus was also detected by this procedure in 4 enzyme-linked immunosorbent assay positive fecal specimens collected from naturally-infected diarrheic dairy calves. These results suggest that fecal shedding of vaccine rotavirus demonstrable by electron microscopic examination is uncommon following oral inoculation of calves with the bovine rotavirus-bovine coronavirus vaccine.


title: Studies of respiratory viruses in personnel at an Antarctic base.

text: Thirteen men wintering on an Antarctic base were isolated from other human contact for 10 months. During this period Coxsackievirus A21 and later influenza A2 virus were administered to some of the men. Serum samples were collected from each of the men at monthly intervals.Coxsackievirus A21 produced symptoms and apparently spread to uninoculated men. It also appears that repeated re-infections occurred and that the virus persisted in this small community for most of the period of isolation. HI antibody responses in the absence of neutralizing antibody responses seem to be transient.The vaccine strain of influenza virus induced antibody responses but did not cause symptoms. There was no evidence of spread to uninoculated men.Antibody titres against influenza C, parainfluenzaviruses 1 and 2 and coronavirus OC43 did not fall significantly during isolation.An outbreak of respiratory illness occurred at the end of isolation and its origin was traced. No causative agent was detected.


docid: tgybigvn

title: Myositis, lameness, and recumbency after use of water-in-oil adjuvanted vaccines in near-term beef cattle.

text: A producer administered 2 US Department of Agriculture-licensed adjuvanted veterinary vaccines (inactivated bovine rotavirus-coronavirus vaccine; Clostridium perfringens type C-Escherichia coli bacterin-toxoid) into muscles of the left and right hips of 469 pregnant beef cows. Within 24 hours, 5 cattle were recumbent, and another 2 had non-weight bearing pelvic limb lameness (1.5% affected; 7/469). During the next 10 days, 50% of the herd developed firm swellings up to 24 cm in vaccination sites in muscles of the hip. Histological samples revealed granulomatous myositis with intralesional oil. Lesions resolved slowly during the next 6 months. Six cattle were injected experimentally with the vaccines. None became lame, but all developed foreign body granulomatous myositis similar to those in the affected herd. The maximum diameter of experimentally induced lesions in muscle at necropsy 60 days after injection with the recommended dose of the bacterin-toxoid vaccines was 12 cm. Histological examination revealed pyogranulomatous myositis, fibrosis, and myonecrosis. The inactivated viral vaccine induced milder granulomatous myositis with intralesional lipid and scant fibrosis. Acute transient lameness on the ranch was attributed to use of 2 irritating biological vaccines in the hip muscles of cows that were close to parturition.


title: A pneumo-virulent United States isolate of porcine reproductive and respiratory syndrome virus induces apoptosis in bystander cells both in vitro and in vivo.

text: Evidence of apoptosis was detected for the United States porcine reproductive and respiratory syndrome virus (PRRSV) in ATCC CRL11171 cells inoculated with strain ATCC VR2385 and in the tissues of pigs infected with the same strain. Apoptosis was detected by agarose gel electrophoresis, transmission electron microscopy and terminal deoxytransferase dUTP nick end labelling (TUNEL) techniques. By electron microscopy and double-labelling techniques, apoptosis was detected primarily in uninfected bystander cells in the continuous cell line rather than the PRRSV-infected cells. In the lungs, the apoptotic cells were predominantly alveolar and pulmonary intravascular macrophages, and mononuclear cells in the alveolar septa. In the lymph nodes, the apoptotic cells were predominantly tingible body macrophages and mononuclear cells. The induction of apoptosis in a large number of mononuclear cells in the lungs and lymph nodes appears to be a mechanism of PRRSV pathogenesis and might be an explanation for a dramatic reduction in the number of alveolar macrophages and circulating lymphocytes and monocytes in PRRSV-infected pigs.


title: HLA class I transgenic mice: development, utilisation and improvement.

text: Classical major histocompatibility complex (MHC) class I antigens are trimeric molecules found on the surface of nucleated cells in all jawed vertebrates. MHC I are recognised by two families of receptors: clonotypic T cell receptors expressed on the surface of CD8+ cytotoxic T lymphocytes (CTLs), and monomorphic receptors expressed by both natural killer cells and CTLs. The production of MHC I molecules within the cells is a sequential process performed with the help of interacting proteins: proteases, chaperones, transporters and so on. Although largely homologous in their structure, organisation and function, the human and mouse MHC I antigen processing and presentation machineries show fine differences. Transgenesis and 'knockout' or 'knock-in' technologies permit the addition of relevant human genes or the replacement of mouse genes by their human orthologues in order to produce immunologically humanised mice. Such experimental animals are especially relevant for the comparative evaluation of immunotherapies and for the characterisation of MHC I peptide epitopes. This review presents the similarities and differences between mouse and human MHC I antigen processing machinery, and describes the development and utilisation of improving mouse models of human cytotoxic T cell immunity.


title: The role of the obstetrician-gynecologist in emerging infectious diseases: monkeypox and pregnancy.

text: Early in June 2003, the Centers for Disease Control and Prevention (CDC) announced yet another unique infectious disease outbreak, the first evidence of community-acquired monkeypox in the United States. By July 8, 2003, a total of 71 cases had been reported to CDC from 6 states. When emerging infectious diseases are reported in the United States, particularly when these reports receive widespread media attention, obstetrician-gynecologists may be called upon to rapidly respond to queries from their patients and to address certain infectious disease risks within their clinical practices. In addition, obstetrician-gynecologists may have specific concerns about the implications for an infectious disease outbreak, such as monkeypox, for pregnant women. Therefore, it is important that obstetrician-gynecologists know how to gather up-to-date and accurate information about infectious disease outbreaks and that they be familiar with the public health response system for responding to such outbreaks.


title: Replicative adenoviruses for cancer therapy.

text: Rapid advances are being made in the engineering of replication-competent viruses to treat cancer. Adenovirus is a mildly pathogenic human virus that propagates prolifically in epithelial cells, the origin of most human cancers. While virologists have revealed many details about its molecular interactions with the cell, applied scientists have developed powerful technologies to genetically modify or regulate every viral protein. In tandem, the limited success of nonreplicative adenoviral vectors in cancer gene therapy has brought the old concept of adenovirus oncolysis back into the spotlight. Major efforts have been directed toward achieving selective replication by the deletion of viral functions dispensable in tumor cells or by the regulation of viral genes with tumor-specific promoters. However, the predicted replication selectivity has not been realized because of incomplete knowledge of the complex virus-cell interactions and the leakiness of cellular promoters in the viral genome. Capsid modifications are being developed to achieve tumor targeting and enhance infectivity. Cellular and viral functions that confer greater oncolytic potency are also being elucidated. Ultimately, the interplay of the virus with the immune system will likely dictate the success of this approach as a cancer therapy.


Fine structure of primary liver tumors and tumor-bearing livers in man.


title: [Field study of the prevalence and diagnosis of diarrhea-causing agents in the newborn calf in a Swiss veterinary practice area].

text: The prevalence of cryptosporidia, rotavirus, bovine coronavirus and Escherichia coli F5 (K99) in dairy calves with diarrhea and in healthy calves was established in a limited area served by a veterinary practice. Immuno-chromatographic rapid tests (FASTest Strips) were applied in the field and their results were compared to the ones obtained with standard methods (modified Ziehl-Neelsen stain, antigen-ELISA and cultivation). In 78% of the calves with diarrhea (n=46) and in 29% of the healthy calves (n=14), one or two agents were isolated. Of the diseased calves, 43% excreted cryptosporidia and in 46% rotavirus was isolated. Bovine corona virus and Escherichia coli F5 (K99) seemed to be of minor importance in the investigated population. Compared to the modified Ziehl-Neelsen stain or the antigen-ELISA, the FASTest Strips CRYPTO and ROTA were of very high diagnostic specificity of 100% each and their diagnostic sensitivity was 75% and 57%, respectively. Due to the low number of cases, the results of the FASTest Strips BCV and E.coli-K99 could not be interpreted. Although the diagnostic sensitivity of the FASTest Strips CRYPTO and ROTA--evaluated with standard methods--was not very high, their use in calves with acute diarrhea is recommended.


title: Reporting ethics committee approval and patient consent by study design in five general medical journals.

text: BACKGROUND Authors are required to describe in their manuscripts ethical approval from an appropriate committee and how consent was obtained from participants when research involves human participants. OBJECTIVE To assess the reporting of these protections for several study designs in general medical journals. DESIGN A consecutive series of research papers published in the Annals of Internal Medicine, BMJ, JAMA, Lancet and The New England Journal of Medicine between February and May 2003 were reviewed for the reporting of ethical approval and patient consent. Ethical approval, name of approving committee, type of consent, data source and whether the study used data collected as part of a study reported elsewhere were recorded. Differences in failure to report approval and consent by study design, journal and vulnerable study population were evaluated using multivariable logistic regression. RESULTS Ethical approval and consent were not mentioned in 31% and 47% of manuscripts, respectively. 88 (27%) papers failed to report both approval and consent. Failure to mention ethical approval or consent was significantly more likely in all study designs (except case-control and qualitative studies) than in randomised controlled trials (RCTs). Failure to mention approval was most common in the BMJ and was significantly more likely than in The New England Journal of Medicine. Failure to mention consent was most common in the BMJ and was significantly more likely than in all other journals. No significant differences in approval or consent were found when comparing studies of vulnerable and non-vulnerable participants. CONCLUSION The reporting of ethical approval and consent in RCTs has improved, but journals are less good at reporting this information for other study designs. Journals should publish this information for all research on human participants.


title: Globalization of infectious diseases: the impact of migration.

text: With up to 2% of the world's population living outside of their country of birth, the potential impact of population mobility on health and on use of health services of migrant host nations is increasing in its importance. The drivers of mobility, the process of the international movement, and the back-and-forth transitioning between differential risk environments has significance for the management of infectious diseases in migrant receiving areas. The management issues are broad, high-level, and cross-cutting, including policy decisions on managing the migration process for skilled-labor requirements, population demographic and biometric characteristics, and family reunification; to program issues encompassing health care professional education, training, and maintenance of competence; communication of global events of public health significance; development of management guidelines, particularly for nonendemic diseases; access to diagnostic and therapeutic interventions for exotic or rare clinical presentations; and monitoring of health service use and health outcomes in both the migrant and local populations.


title: Infectious and parasitic diseases of captive carnivores, with special emphasis on the black-footed ferret (Mustela nigripes).

text: Captive carnivores are susceptible to a wide array of infectious and parasitic diseases, which reflects the diversity of the seven families of Carnivora. Unfortunately, relatively few in-depth studies have been conducted on diseases of non-domestic carnivores, and much remains to be learned, especially regarding diseases of small carnivores (e.g. mustelids, viverrids and procyonids). The more important infectious diseases of carnivores include rabies, canine distemper, and diseases caused by parvoviruses, coronaviruses and herpesviruses. Few parasitic or bacterial pathogens are significant in captive populations, and appropriate husbandry, therapy, vaccines and quarantine minimize the risk of disease. Extrapolations from one species to another regarding disease susceptibility may be incorrect. The black-footed ferret (Mustela nigripes) serves as an example of a carnivore significantly affected by infectious diseases, some of which were expected while others could not have been predicted from generalized knowledge of diseases of mustelids. This highlights the need to understand the natural history of each species maintained in captivity.


docid: rtlkxioh

title: Altered metabolism, acute shock, and therapeutic response in a calf with severe coronavirus-induced diarrhea.

text: Acute shock and metabolic failure appeared in a diarrheic calf being studied intensively to determine kinetics of glucose and lactate metabolism. Intravenous therapy significantly improved its condition. During metabolic failure, the rapid increase in blood lactate and concomitant decrease in glucose were due to inhibited gluconeogenesis, as glucose entry and lactate oxidation were not modified. Therapy restored metabolic activity and decreased the severe hyperkalemia.


title: Population proteomics: addressing protein diversity in humans.

text: In the past several years, proteomics and its subdiscipline clinical proteomics have been engaged in the discovery of the next generation protein of biomarkers. As the effort and the intensive debate it has sparked continue, it is becoming apparent that a paradigm shift is needed in proteomics in order to truly comprehend the complexity of the human proteome and assess its subtle variations among individuals. This review introduces the concept of population proteomics as a future direction in proteomics research. Population proteomics is the study of protein diversity in human populations. High-throughput, top-down mass spectrometric approaches are employed to investigate, define and understand protein diversity and modulations across and within populations. Population proteomics is a discovery-oriented endeavor with a goal of establishing the incidence of protein structural variations and quantitative regulation of these modifications. Assessing human protein variations among and within populations is viewed as a paramount undertaking that can facilitate clinical proteomics' effort in discovery and validation of protein features that can be used as markers for early diagnosis of disease, monitoring of disease progression and assessment of therapy. This review outlines the growing need for analyzing individuals' proteomes and describes the approaches that are likely to be applied in such a population proteomics endeavor.


title: New antiviral drugs, vaccines and classic public health interventions against SARS coronavirus.

text: Severe acute respiratory syndrome (SARS) is caused by one of two recently discovered coronaviruses. The virus is emergent from South East (SE) Asian mammals: either the civet cat, a related species or a rat species. The virus has a long incubation period and low reproduction number (R0 value) and hence the first outbreak in 2004 was controlled by hygiene and quarantine. However, the healthcare system was compromised and the economic cost was extremely high. Fortunately, the virus is easily cultivated in Vero E6 cells and therefore the search for new antivirals and vaccines was initiated within weeks of the discovery of the virus using classic techniques of cell culture and electron microscopy. Molecular diagnostics facilitated rapid and accurate diagnosis, a key factor in containing the outbreak. The broad-spectrum molecule ribavirin was used in SE Asia in infected patients alongside corticosteroids. In retrospect, many patients survived due to careful nursing. The only currently accepted intervention is interferon. Coronavirus replicon systems should facilitate rapid screening of new inhibitors and the complex mechanism of viral replication will ensure that drugs are developed against at least five molecular targets, in particular the viral protease.


title: Dynamic observation of the three-dimensional distribution of labeled liposomes using the novel high-resolution single-photon emission computed tomography.

text: The aim of this study was to show that the multipinhole technique (high-resolution single-photon emission computed tomography [HiSPECT]) is suitable for dynamic imaging of both biodistribution and temporal uptake behavior of radiolabeled cationic liposomes in Balb/c-mice. HiSPECT uses multipinhole collimators adapted to a clinical SPECT scanner, together with a dedicated iterative reconstruction program. This technique provides both high spatial resolution and an improvement in sensitivity. Six male Balb/c mice received 9.8 +/- 4.0 MBq of the In 111-labeled liposomes. The measurements started directly after the injection and tomographic data were acquired in steps of 5 minutes. The regional evaluation displayed a high initial uptake of liposomes in the lungs (45.4%), which decreased to 25.1% after 30 minutes and to below 2% after 48 hours. In contrast, liver uptake increased in the first 30 minutes from 13.1 to 21.2% and remained relatively stable at 24.4% (24 hours) and 18.8% (48 hours). The data are interpreted as a slow shift of liposomes from the lungs into the liver and later to other organs such as the spleen and bladder. This study shows that the HiSPECT technique is capable of dynamically visualizing the uptake behavior of radioactively labeled liposomes in vivo with high temporal and spatial resolution.


title: Coronaviruslike particles in human gastrointestinal disease. Epidemiologic, clinical, and laboratory observations.

text: Coronaviruslike particles (CVLPs) were visualized by direct electron microscopy (EM) of diarrheal stools in 49 of 126 infants and children between 1 month and 12 years of age during a three-year observation period. The clinical and epidemiologic features of these patients were analyzed and compared with patients with diarrhea who were shedding rotaviruses, or whose stools were negative for enteric viruses by EM. Seasonal and age distributions for CVLP shedding were similar to those for rotaviruses (in most cases less than 1 year of age; peak months were September through January), as were the symptoms and median durations of illness. Prospective studies of three subsequent patients suggest that the duration of shedding in acute illness is five to at least 25 days. Multiple attempts to cultivate the CVLPs were unsuccessful. In addition, partial purification of CVLPs from stool specimens was performed, and immunologic analysis by immunoelectron microscopy and radial immunodiffusion showed no antigenic relatedness to prototype human (OC43 and 229E) or animal (bovine and canine) coronaviruses. These findings suggest that CVLPs may be an important cause of acute gastrointestinal illness in infancy, and may represent a virus antigenically unrelated to known human and animal coronaviruses.


docid: xpzggzrc

title: The mental health of hospital workers dealing with severe acute respiratory syndrome.

text: BACKGROUND The aim of this study was to explore the impact of the severe acute respiratory syndrome (SARS) on health care workers in Taiwan. The possible predisposing and perpetuating factors in developing mental symptoms were investigated. METHODS Participantsconsisted of 135 health care workers who had had contact with or took care of patients who were probable or suspected SARS cases, during the SARS outbreak, at a teaching hospital in southern Taiwan. All participants completed questionnaires, including the Chinese Health Questionnaire, Eysenck Personality Questionnaire and Parental Bonding Instrument. RESULTS Twenty-two participants (17.3%) developed significant mental symptoms, and 105 participants (82.7%) showed no obvious symptoms. The structural equation model showed that maternal care (beta = -0.18, p = 0.011) and neuroticism (beta = 0.54, p < 10(-6)) directly influenced the ability of health care workers to deal with the impact of SARS. Maternal overprotection (beta = 0.30, p < 10(-4)) had an indirect influence on the ability to cope with the impact of SARS. CONCLUSION Both neuroticism and maternal attachment influenced the mental health of health care workers during the SARS epidemic. The results can be a helpful reference for intervention and prevention programs for health care workers facing disasters in the future.


title: The hazards of surgical smoke.

text: Surgical smoke is a part of the environment during operative and invasive procedures. As lasers and electrosurgery have become commonplace, perioperative practitioners are at increased risk for health concerns associated with exposure to surgical smoke. Since the mid 1970s, the body of evidence documenting the hazardous components of surgical smoke has continued to grow. Despite the evidence and recommendations of a variety of organizations, there are no uniform requirements mandating surgical smoke evacuation. This article reviews current research to identify the potential health hazards as well as the current recommendations related to the filtration and evacuation of surgical smoke.


title: Ethical considerations in the management of Ebola virus disease.

text: Is it ethically appropriate in some circumstances for HCWs to decline to care for patients with EVD? How should treatment decisions be made regarding limitation of therapy for patients with EVD? There are two main ethical questions regarding the critical care of patients with EVD in an Australian setting: Is it ethically appropriate in some circumstances for HCWs to decline to care for patients with EVD? How should treatment decisions be made regarding limitation of therapy for patients with EVD? The key concern is ensuring that no patient is denied therapy that should be provided, while preventing unnecessary risk to HCWs. It is imperative to develop an approach that facilitates rigorous, evidence-based and ethically justifiable decision making, which should include a predetermined, institutionally endorsed process for assessing difficult clinical scenarios as they arise.


title: Hemagglutinin (HA) proteins from H1 and H3 serotypes of influenza A viruses require different antigen designs for the induction of optimal protective antibody responses as studied by codon-optimized HA DNA vaccines.

text: Effective antibody responses provide crucial immunity against influenza virus infection. The hemagglutinin (HA) protein is the major target of protective antibody responses induced by viral infection and by vaccination with both inactivated and live-attenuated flu vaccines, but knowledge about the optimal designs of protective HA antigens from different flu serotypes is still limited. In this study, we have significantly improved the immunogenicity of HA-expressing DNA vaccines by using codon-optimized HA sequences for either an H1 serotype (A/NewCal/20/99) or an H3 serotype (A/Panama/2007/99) human influenza A virus and then used these constructs as model antigens to identify the optimal HA antigen designs to elicit high-level protective antibody responses. Two forms of HA antigen, a wild-type, full-length HA and a secreted form with transmembrane (TM) domain-truncated HA, were produced. Both forms of HA DNA vaccines, from either H1 or H3 serotypes, were able to elicit high levels of HA-specific immunoglobulin G responses in immunized rabbits as measured by enzyme-linked immunosorbent assay. Interestingly, the abilities of H1 HA and H3 HA antigens to elicit hemagglutination inhibition (HI) and neutralizing antibody (NAb) responses differ. For the H1 HA antigens, the full-length HA induced significantly higher HI and NAb responses than did the TM-truncated HA. For the H3 HA antigen, both the full-length HA and TM-truncated HA induced high levels of HI and NAb responses. These data indicate that H1 and H3 antigens have different expression requirements for the induction of an optimal protective antibody response and that the structure integrity of HA antigens is critical for eliciting type-specific protective antibody responses. Our findings will have an important impact on future subunit-based flu vaccine development.


The psychological impact of SARS: a matter of heart and mind.


title: Neutralization-resistant variants of a neurotropic coronavirus are generated by deletions within the amino-terminal half of the spike glycoprotein.

text: Neuroattenuated variants of mouse hepatitis virus type 4 (MHV-4) selected for resistance to neutralizing monoclonal antibodies (R.G. Dalziel, P.W. Lampert, P. J. Talbot, and M. J. Buchmeier, J. Virol. 59:463-471, 1986) were found to harbor large deletions in both mRNA 3 and its protein product, the 180-kilodalton viron spike (S) glycoprotein. By using antipeptide antibodies directed against selected portions of the chain, deletions were mapped to the middle of the amino-terminal S1 fragment, one of the two posttranslational cleavage products of S, and involved omission of 15 kilodaltons of protein. Deletion mutants could be selected only after multiple passage of virus through cultured cell lines; minimally passaged MHV-4 stocks contained putative point mutants selectable by neutralizing monoclonal antibodies but no deletions. Enhanced growth of deletion mutants relative to wild-type virus was observed in four cell lines used for virus propagation and was attributed to delayed and diminished cytopathic effects that allowed cultures to support virus production for prolonged periods. This hypothesis was reinforced by the finding that no selective advantage for the deletion mutants was observed in two cell lines resistant to virus-induced cytopathic effects. These results indicate that the passaging of MHV-4 in culture generates heterogeneity in S structure and eventually selects for rare neutralization-resistant deletion mutants with decreased virulence properties.


title: Pulmonary function and exercise capacity in survivors of severe acute respiratory syndrome.

text: The aim of this study was to investigate pulmonary function and exercise capacity in a group of survivors of the severe acute respiratory syndrome (SARS). At 3 months after hospital discharge, 46 survivors of SARS underwent the following evaluation: spirometry, static lung volumes and carbon monoxide transfer factor (TL,CO). In total, 44 of these patients underwent cardiopulmonary exercise testing. No abnormalities were detected in the pulmonary function tests in 23 (50%) of the patients. Abnormalities of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC and TL,CO were detected in seven (15%), 12 (26%), one (2%) and 18 (39%) patients, respectively. All of these abnormalities were mild except in one case. In 18 patients (41%), the maximum aerobic capacity was below the lower limit of the normal range. Breathing reserve was low in four patients and significant oxygen desaturation was detected in a further four patients. Comparison of the measured exercise capacity with resting pulmonary function tests showed many cases of discordance in impairment. In conclusion, pulmonary function defects were detected in half of the recovered severe acute respiratory syndrome patients 3 months after hospital discharge, but the impairment was mild in almost all cases. Many patients had reduced exercise capacity that cannot be accounted for by impairment of pulmonary function.


title: Immunity to fungal infections.

text: The topic of immunity to fungal infections is of interest to a wide range of disciplines, from microbiology to immunology. It is of particular interest in terms of therapy of HIV-infected individuals, and patients with cancer or individuals who have received transplants. Understanding the nature and function of the immune response to fungi is an exciting challenge that might set the stage for new approaches to the treatment of fungal diseases, from immunotherapy to vaccines. The past decade has witnessed the development of a wide range of new approaches to elucidate events that occur at the host-fungus interface.


title: SARS: an emerging global microbial threat.

text: In March 2003, the Institute of Medicine published an update to its 1992 landmark report on emerging infections. The new report, Microbial Threats to Health: Emergence, Detection, and Response, describes the current spectrum of global microbial threats, factors affecting their emergence or resurgence, and measures that should be undertaken to effectively address them. Coincident with this publication came increasing reports of severe atypical pneumonia of unknown etiology among persons in southeast Asia. This new disease, designated severe acute respiratory syndrome (SARS), spread globally in a matter of weeks, infecting primarily close contacts of index patients (e.g., household members and healthcare workers caring for index patients) but also resulting in community transmission in some areas. An unprecedented worldwide collaborative effort was undertaken to determine the cause of the illness and implement prevention measures. A previously unrecognized coronavirus was identified as the causative agent, and health officials throughout the world struggled to implement measures to contain its spread, including isolation of suspect SARS cases and quarantine of exposed persons. The emergence of SARS is a timely reminder of the need to expect the unexpected and to ensure strong national and global public health partnerships when preparing for and responding to infectious diseases. Effectively addressing the threat of SARS will require enhanced global infectious disease surveillance, the development of rapid diagnostics, new therapies, and vaccines, implementation of aggressive evidence-based infection control strategies, and effective communication.


title: Chest radiographic findings of a case of severe acute respiratory syndrome (SARS) in Singapore.

text: A new form of atypical pneumonia was reported in the East Asian region beginning from early 2003. This was later termed by the World Health Organisation as Severe Acute Respiratory Syndrome (SARS). The diagnosis of SARS relies on a combination of clinical features and chest radiographic findings. A preliminary review of SARS in Singapore shows chest radiographic findings of patchy airspace shadowing with severe cases progressing to diffuse air-space shadowing. We illustrate these findings with temporal correlation in our case report. As SARS is a contagious, rapidly progressive and potentially fatal condition, early diagnosis is crucial for prompt management and isolation of patients. Recognition of chest radiographic findings aids in the early diagnosis and containment of SARS.


title: [Clinical features of 77 patients with severe acute respiratory syndrome].

text: OBJECTIVE To analyze the clinical features of the severe acute respiratory syndrome (SARS) and the value for caring of patients suspected of having this disease. METHODS The data of the clinical presentations and course of disease in 77 epidemiologically linked patients (27 men and 50 women, 15 to 74 years old) in whom SARS was diagnosed after April 16, 2003 in Tianjin, China were summarized. RESULTS Exposure to ailing patients and occurrence of the disease ranged from minimal to close contact, such as between patient and health care personnel. The incubation period ranged from 1 to 11 days. All patients presented fever, and some of them complained of rigor, dry cough, dyspnea, malaise, headache, and hypoxemia. Physical examination of the chest revealed bubbling rales and dullness on percussion. Lymphopenia was observed in 80% of all patients, and some patients had mildly elevated aminotransferase levels but normal serum creatinine levels. Serial chest radiographs showed progressive inflammatory changes. One patient died of progressive respiratory failure; pathological examination of the lung showed diffuse alveolar damage. One patient died of suicide. There was no evidence of infection by Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila. All patients received corticosteroid and ribavirin therapy for a mean of (18.6+/-5.4) days after the onset of symptoms, and were treated with a combination of beta-lactams and macrolide early for (4.0+/-1.9)days, but with no clinical or radiologic evidences of improvement. CONCLUSION The combination treatment, especially including corticosteroid and ribavirn, is efficient.


Alcohol Policy and Coronavirus: An Open Research Agenda.


title: COVID-19 and pregnancy: a review of current knowledge.

text: BACKGROUND Since December 2019, coronavirus disease 2019 (COVID-19) has become a major health problem that is spreading all over the world. Several viral infections such as SARS, MERS, and influenza have been associated with adverse pregnancy outcomes. The question arises whether pregnant women are at greater risk of complications related to COVID-19 compared to other people What complications should we expect in the fetuses whose mothers were infected? AIMS This review aims to provide a summary of studies on symptoms of COVID-19 and the possible risks of COVID-19 among pregnant women, as well as complications in fetuses and neonates whose mothers were infected with COVID-19. METHODS The included data were provided from Web of Science, Cochrane, PubMed, and Scopus which are extracted from the published studies in English until April 2nd, 2020 that contained data on the risk of COVID-19 in pregnancy. RESULTS The early symptoms of patients with COVID-19 were fever, cough, dyspnea, myalgia, and fatigue; while production of sputum, headache, hemoptysis, and diarrhea were other symptoms which were less common. There is no evidence of vertical maternal-fetal transmission in pregnant women with COVID-19. CONCLUSIONS The clinical findings in pregnant women with COVID-19 are not significantly different compared to other patients, and pregnant women with COVID-19 are not at a higher risk of developing critical pneumonia compared to non-pregnant women. Although, there has been no sign of vertical infection in infants, but maternal infection can cause serious problems such as preterm labour and fetal distress.


Medicine's Challenges: Vaping and Coronavirus.


Suspected allergic reactions after vaccination in 85 dogs in Japan.


title: [Clinical analysis of complications after non- invasive positive pressure ventilation and an inquiry into the respiratory treatment strategy in patients with SARS].

text: OBJECTIVE To analyze the clinical data of severe acute respiratory syndrome (SARS) patients with pneumothorax and mediastinal emphysema occurring after the non-invasive positive pressure ventilation (NIPPV), and to inquire into relevant strategy in respiratory treatment in the SARS patients. METHODS Twenty-seven serious cases of SARS undergone NIPPV were analyzed retrospectively. RESULTS Pneumothorax and mediastinal emphysema occurred in 7 of 27 serious cases of SARS with NIPPV, and mediastinal emphysema occurred in 1 of 189 cases of SARS without mechanical ventilation (MV). The incidence of pneumothorax and mediastinal emphysema in serious cases of SARS with NIPPV was significantly higher (chi2=25.052, P<0.01) than that in cases of SARS without receiving MV. The peripheral blood oxygen saturation level was not changed significantly after reasonable adjustment of ventilation pressure and increase in oxygen concentration inhaled. Seven cases of pneumothorax and mediastinal emphysema improved gradually. CONCLUSION The incidence of pneumothorax and mediastinal emphysema in serious SARS patients with NIPPV is significantly higher than that in SARS patients without receiving MV. This might be related to SARS related pulmonary injuries, intensive cough and high mechanical ventilation pressure. The pneumothorax and mediastinal emphysema improve gradually in all cases after reasonable adjustment of mechanical ventilative pressure. So when NIPPV is used in the treatment of serious SARS patients to improve hypoxemia, optimized mechanical ventilative pressure should be acquired in order to avoid pneumothorax and mediastinal emphysema.


Lest we forget.


title: The avian reovirus genome segment S1 is a functionally tricistronic gene that expresses one structural and two nonstructural proteins in infected cells.

text: The avian reovirus S1 gene contains three partially overlapping, out-of-phase open reading frames (ORFs) that the highly conserved in all avian reovirus strains examined to date. The three S1 ORFs of the avian reovirus strain S1133 were individually expressed in bacterial cells, and their purified translation products used as antigens to raise specific polyclonal antibodies. With these antibodies we were able to demonstrate that all three S1 ORFs from different avian reovirus strains are translatable in infected cells. Proteins p10 and p17, which are specified by ORF1 and ORF2, respectively, are nonstructural proteins which associate with cell membranes, whereas ORF3 directs the synthesis of protein sigma C, a structural oligomeric protein responsible for cell attachment. While intracellular synthesis of protein sigma C was demonstrated a long time ago and that of protein p10 was reported recently, this is the first time that expression of the S1 ORF2 has been demonstrated experimentally. Thus, the previously reported coding capacity of the avian reovirus genome is now expanded to 14 proteins, of which ten are structural (lambda A, lambda B, lambda C, microA, microB, microBC, microBN, sigma A, sigma B, and sigma C) and four are nonstructural (microNS, sigma NS, p17, and p10). Finally, protein p10, but not p17 or sigma C, induces cell-cell fusion when transiently expressed in mammalian cells, supporting a previously published observation that the polypeptide encoded by the S1 ORF1 plays an important role in the syncytial phenotype displayed by avian reoviruses.


Canada insists that it is a safe place to visit.


Epidemic infections and their relevance to the Gulf and other Arabian Peninsula countries.


Overlapping agendas or serendipitous synergism.


title: Inhibition of Epstein-Barr virus replication by small interfering RNA targeting the Epstein-Barr virus protease gene.

text: BACKGROUND The Epstein-Barr virus (EBV) protease (PR), coded by the BVRF2 gene, is essential for the maturation of the viral capsid and viral DNA packaging during the late stage of the EBV lytic cycle. Like the other herpesvirus serine PRs, EBV PR could be a target for the inhibition of EBV replication. To date, no data have been reported on the inhibition of EBV PR messenger RNA (mRNA) by small interfering RNA (siRNA). METHODS In this study, siRNAs targeting EBV PR were delivered to the epithelial 293 cell line stably transfected with the complete B95-8 EBV episome. EBV DNA and PR mRNA were quantified by real-time PCR in cells and supernatant, protein expression was assessed by immunoblotting, and production of EBV infectious particles in the culture medium was measured by Raji cell superinfection. RESULTS The EBV PR mRNA within the cells was reduced by 73%, the PR protein by 35% and the amount of virus in the cell supernatant was drastically decreased by 86% or 95%, depending on the method. CONCLUSIONS The strong effect of the siRNA targeting EBV PR on EBV replication attests to the crucial role played by EBV PR in the production of infectious particles and suggests that targeting this enzyme can be a new strategy against EBV-associated diseases where virus replication occurs.


title: A review of the safety of favipiravir - a potential treatment in the COVID-19 pandemic?

text: Background Repurposing broad-spectrum antivirals is an immediate treatment opportunity for 2019 coronavirus disease (COVID-19). Favipiravir is an antiviral previously indicated for influenza and Ebola, which has shown some promise in early trials for treatment of COVID-19. We aim to review existing favipiravir safety evidence, which is vital to informing the potential future use of favipiravir in COVID-19. Methods A search was conducted across EMBASE and MEDLINE databases, supplemented by relevant grey-literature and ClinicalTrials.gov. All studies assessing the use of favipiravir in humans by 27 March 2020 were considered for inclusion. Further analysis of available safety data from phase 2 and 3 studies was undertaken. Data extracted were adverse events (AEs) grade 1-4, serious AEs and discontinuation for AEs. Specific AEs of interest highlighted in early-phase studies, including gastrointestinal AEs and hyperuricaemia, were also examined. Results Twenty-nine studies were identified as potential sources of evidence of the clinical safety of favipiravir. Six were phase 2 and 3 studies reporting relevant safety data for statistical comparison, representing a total of 4299 participants, an estimated 175 person-years-of-follow-up (PYFU). Comparator drugs were oseltamivir, umifenovir, lopinavir/ritonavir or placebo. Study follow-up was between 5 and 21 days. The proportions of grade 1-4 AEs on favipiravir was 28.2% vs 28.4% (P = n.s.) in the comparison arms. The proportion of discontinuations due to AEs on favipiravir was 1.1% vs 1.2% (P = n.s.) in the comparison arms. For serious AEs the proportion was 0.4% in both arms (P = n.s.). There were significantly fewer gastrointestinal AEs occurring on favipiravir vs comparators [8.7% vs 11.5%; P = 0.003]. Favipiravir showed significantly more uric acid elevations than comparators [5.8% vs 1.3%; P<0.0001]. Conclusions Favipiravir demonstrates a favourable safety profile regarding total and serious AEs. However, safety concerns remain: hyperuricaemia, teratogenicity and QTc prolongation have not yet been adequately studied. Favipiravir may be safe and tolerable in short-term use, but more evidence is needed to assess the longer-term effects of treatment. Given the limitations of the evidence and unresolved safety concerns, caution is warranted in the widespread use of favipiravir against pandemic COVID-19.


title: Community-acquired pneumonia: what is relevant and what is not?

text: PURPOSE OF REVIEW Community-acquired pneumonia is associated with significant morbidity and mortality and is the most common cause of death from infectious diseases in North America. The purpose of this review is to highlight recent advances in epidemiology, risk factors, severity criteria and antibiotic therapeutic regimens used for community-acquired pneumonia management. RECENT FINDINGS All guidelines recommend early and appropriate empiric therapy directed against common typical organisms, such as Streptococcus pneumoniae, and other atypical organisms, but clinicians should be aware of newer emerging pathogens such as community-acquired methicillin-resistant Staphylococcus aureus and Gram-negative pathogens. SUMMARY The optimum outcome in community-acquired pneumonia can be achieved by careful risk stratification using prediction rules together with appropriate antibiotic regimens. The mainstay of community-acquired pneumonia prevention is influenza and pneumococcal immunization. Promotion of smoking cessation will also help curtail the incidence of pneumococcal disease.


title: Meloxicam and surgical denervation of the coxofemoral joint for the treatment of degenerative osteoarthritis in a Bengal tiger (Panthera tigris tigris).

text: An adult male white Bengal tiger (Panthera tigris tigris) with pronounced atrophy of the pelvic musculature was diagnosed with degenerative osteoarthritis of the coxofemoral joints. Initial management with the nonsteroidal anti-inflammatory drug meloxicam and a semisynthetic sodium pentosan polysulfate resulted in clinical improvement and radiographic stabilization of the arthritic condition over several months. However, because pain was still evident, bilateral denervation of the coxofemoral joints was performed, successfully ameliorating the signs of osteoarthritic pain in the tiger. Meloxicam has shown good clinical efficacy for the treatment of osteoarthritis and other painful conditions in large felids. Coxofemoral joint denervation offers many advantages for the treatment of osteoarthritis in exotic carnivore species, and should be considered a viable treatment modality.


title: Children's vaccines do not induce cross reactivity against SARS-CoV.

text: In contrast with adults, children infected by severe acute respiratory syndrome-corona virus (SARS-CoV) develop milder clinical symptoms. Because of this, it is speculated that children vaccinated with various childhood vaccines might develop cross immunity against SARS-CoV. Antisera and T cells from mice immunised with various vaccines were used to determine whether they developed cross reactivity against SARS-CoV. The results showed no marked cross reactivity against SARS-CoV, which implies that the reduced symptoms among children infected by SARS-CoV may be caused by other factors.


Emerging opportunities to prevent occupational lung disease.


Airborne transmission of communicable infection--the elusive pathway.


title: Nuclear localization of flavivirus RNA synthesis in infected cells.

text: Flaviviral replication is believed to be exclusively cytoplasmic, occurring within virus-induced membrane-bound replication complexes in the host cytoplasm. Here we show that a significant proportion (20%) of the total RNA-dependent RNA polymerase (RdRp) activity from cells infected with West Nile virus, Japanese encephalitis virus (JEV), and dengue virus is resident within the nucleus. Consistent with this, the major replicase proteins NS3 and NS5 of JEV also localized within the nucleus. NS5 was found distributed throughout the nucleoplasm, but NS3 was present at sites of active flaviviral RNA synthesis, colocalizing with NS5, and visible as distinct foci along the inner periphery of the nucleus by confocal and immunoelectron microscopy. Both these viral replicase proteins were also present in the nuclear matrix, colocalizing with the peripheral lamina, and revealed a well-entrenched nuclear location for the viral replication complex. In keeping with this observation, antibodies to either NS3 or NS5 coimmunoprecipitated the other protein from isolated nuclei along with newly synthesized viral RNA. Taken together these data suggest an absolute requirement for both of the replicase proteins for nucleus-localized synthesis of flavivirus RNA. Thus, we conclusively demonstrate for the first time that the host cell nucleus functions as an additional site for the presence of functionally active flaviviral replicase complex.


title: Hematopoietic stem and progenitor cells: clinical and preclinical regeneration of the hematolymphoid system.

text: A vast literature exists on the biology of blood formation and regeneration under experimental and clinical conditions. The field of hematopoiesis was recently advanced by the capacity to purify to homogeneity primitive hematopoietic stem and progenitor cells. Isolation of cells at defined maturational stages has enhanced the understanding of the fundamental nature of stem cells, including how cell fate decisions are made, and this understanding is relevant to the development of other normal as well as malignant tissues. This review updates the basic biology of hematopoietic stem cells (HSC) and progenitors, the evolving use of purified HSC as grafts for clinical hematopoietic cell transplantation (HCT) including immune tolerance induction, and the application of HSC biology to other stem cell fields.


title: Simultaneous detection of influenza viruses A and B using real-time quantitative PCR.

text: Since influenza viruses can cause severe illness, timely diagnosis is important for an adequate intervention. The available rapid detection methods either lack sensitivity or require complex laboratory manipulation. This study describes a rapid, sensitive detection method that can be easily applied to routine diagnosis. This method simultaneously detects influenza viruses A and B in specimens of patients with respiratory infections using a TaqMan-based real-time PCR assay. Primers and probes were selected from highly conserved regions of the matrix protein gene of influenza virus A and the hemagglutinin gene segment of influenza virus B. The applicability of this multiplex PCR was evaluated with 27 influenza virus A and 9 influenza virus B reference strains and isolates. In addition, the specificity of the assay was assessed using eight reference strains of other respiratory viruses (parainfluenza viruses 1 to 3, respiratory syncytial virus Long strain, rhinoviruses 1A and 14, and coronaviruses OC43 and 229E) and 30 combined nose and throat swabs from asymptomatic subjects. Electron microscopy-counted stocks of influenza viruses A and B were used to develop a quantitative PCR format. Thirteen copies of viral RNA were detected for influenza virus A, and 11 copies were detected for influenza virus B, equaling 0.02 and 0.006 50% tissue culture infective doses, respectively. The diagnostic efficacy of the multiplex TaqMan-based PCR was determined by testing 98 clinical samples. This real-time PCR technique was found to be more sensitive than the combination of conventional viral culturing and shell vial culturing.


title: Identification of an ATPase activity associated with a 71-kilodalton polypeptide encoded in gene 1 of the human coronavirus 229E.

text: Human coronavirus 229E gene expression involves proteolytic processing of the gene 1-encoded polyproteins pp1a and pp1ab. In this study, we have detected a 71-kDa polypeptide in virus-infected cells that is released from pp1ab by the virus-encoded 3C-like proteinase and that has been predicted to contain both metal-binding and helicase domains. The polypeptide encompasses amino acids Ala-4996 to Gln-5592 of pp1ab and exhibits nucleic acid-stimulated ATPase activity when expressed as a fusion protein with the Escherichia coli maltose-binding protein. These data provide the first identification of a coronavirus open reading frame 1b-encoded enzymatic activity.


title: A new model for coronavirus transcription.

text: Coronaviruses contain an unusually long (27-32,000 ribonucleotide) positive sense RNA genome that is polyadenylated at the 3' end and capped at the 5' end. In addition to the genome, infected cells contain subgenomic mRNAs that form a 3' co-terminal nested set with the genome. In addition to their common 3' ends, the genome and the subgenomic mRNAs contain an identical 5' leader sequence. The transcription mechanism that coronaviruses use to produce subgenomic mRNA is not known and has been the subject of speculation since sequencing of the subgenomic mRNAs showed they must arise by discontinuous transcription. The current model called leader-primed transcription has subgenomic mRNAs transcribed directly from genome-length negative strands. It was based on the failure to find in coronavirus infected cells subgenome-length negative strands or replication intermediates containing subgenome-length negative strands. Clearly, these structures exist in infected cells and are transcriptionally active. We proposed a new model for coronavirus transcription which we called 3' discontinuous extension of negative strands. This model predicts that subgenome-length negative strands would be derived directly by transcription using the genome RNA as a template. The subgenome-length templates would contain the common 5' leader sequence and serve as templates for the production of subgenomic mRNAs. Our findings include showing that: 1. Replication intermediates (RIs) containing subgenome-length RNA exist in infected cells and are separable from RIs with genome-length templates. The RFs with subgenome-length templates are not derived by RNase treatment of RIs with genome-length templates. 2. The subgenome-length negative strands are formed early in infection when RIs are accumulating and the rate of viral RNA synthesis is increasing exponentially. 3. Subgenome-length negative strands contain at their 3' ends a complementary copy of the 72 nucleotide leader RNA that is found in the genome only at their 5' end. 4. RIs with subgenomic templates serve immediately as templates for transcription of subgenomic mRNAs. Because subgenomic mRNAs are not replicated, i.e., copied into negative strands that in turn are used as templates for subgenomic mRNA synthesis, we propose that the subgenome-length negative strands must arise directly by transcription of the genome and acquire their common 3' anti-leader sequence after polymerase jumping from the intergenic regions to the leader sequence at the 5' end of the genome. This would make negative strand synthesis discontinuous and subgenomic mRNA synthesis continuous, which is the opposite of what was proposed in the leader primed model.


docid: fqapepug

title: Evaluation of immunomodulators, interferons and known in vitro SARS-coV inhibitors for inhibition of SARS-coV replication in BALB/c mice.

text: Compounds approved for therapeutic use and in vitro inhibitors of severe acute respiratory syndrome coronavirus (SARS-CoV) were evaluated for inhibition in the mouse SARS-CoV replication model. A hybrid interferon, interferon alpha (IFN-alpha) B/D, and a mismatched double-stranded (ds) RNA interferon (IFN) inducer, Ampligen (poly I:poly C124), were the only compounds that potently inhibited virus titres in the lungs of infected mice as assessed by CPE titration assays. When mice were dosed intraperitoneally (i.p.) with IFN-alpha B/D once daily for 3 days beginning 4 h after virus exposure, SARS-CoV replication in the lungs of infected mice was reduced by 1 log10 at 10,000 and 32,000 IU; at the highest dose of 100,000 IU, virus lung titres were below detectable limits. Ampligen used i.p. at 10 mg/kg 4 h prior to virus exposure also reduced virus lung titres to below detectable limits. Nelfinavir, beta-D-N4-hydroxycytidine, calpain inhibitor VI, 3-deazaneplanocin A and Alferon (human leukocyte IFN-alpha-n3) did not significantly reduce lung virus titres in mice. Anti-inflammatory agents, chloroquine, amodiaquin and pentoxifylline, were also inactive in vivo, suggesting that although they may be useful in ameliorating the hyperinflammatory response induced by the virus infection, they will not significantly reduce the replication of the virus, the inducer of inflammatory response. Thus, anti-inflammatory agents may only be useful in treating virus lung infections if used in combination with agents that inhibit virus replication. In summary, the data suggest that induction of IFN by mismatched dsRNA or actual treatment with exogenous IFN-alpha can inhibit SARS-CoV replication in the lungs of mice.


title: Identification of novel inhibitors of the SARS coronavirus main protease 3CLpro.

text: SARS (severe acute respiratory syndrome) is caused by a newly discovered coronavirus. A key enzyme for the maturation of this virus and, therefore, a target for drug development is the main protease 3CL(pro) (also termed SARS-CoV 3CL(pro)). We have cloned and expressed in Escherichia coli the full-length SARS-CoV 3CL(pro) as well as a truncated form containing only the catalytic domains. The recombinant proteins have been characterized enzymatically using a fluorescently labeled substrate; their structural stability in solution has been determined by differential scanning calorimetry, and novel inhibitors have been discovered. Expression of the catalytic region alone yields a protein with a reduced catalytic efficiency consistent with the proposed regulatory role of the alpha-helical domain. Differential scanning calorimetry indicates that the alpha-helical domain does not contribute to the structural stability of the catalytic domains. Analysis of the active site cavity reveals the presence of subsites that can be targeted with specific chemical functionalities. In particular, a cluster of serine residues (Ser139, Ser144, and Ser147) was identified near the active site cavity and was susceptible to being targeted by compounds containing boronic acid. This cluster is highly conserved in similar proteases from other coronaviruses, defining an attractive target for drug development. It was found that bifunctional aryl boronic acid compounds were particularly effective at inhibiting the protease, with inhibition constants as strong as 40 nM. Isothermal titration microcalorimetric experiments indicate that these inhibitors bind reversibly to 3CL(pro) in an enthalpically favorable fashion, implying that they establish strong interactions with the protease molecule, thus defining attractive molecular scaffolds for further optimization.


title: Polymorphisms in the mannose binding lectin-2 gene and acute respiratory distress syndrome.

text: OBJECTIVE The variant alleles in the mannose binding lectin-2 (MBL-2) gene have been associated with MBL deficiency and increased susceptibility to sepsis. We postulate that the variant MBL-2 genotypes are associated with increased susceptibility to and mortality in acute respiratory distress syndrome (ARDS). DESIGN Nested case-control study. SETTING Tertiary academic medical center. PATIENTS Two hundred and twelve Caucasians with ARDS and 442 controls genotyped for the variant X, D, B, and C alleles of codon -221, 52, 54, and 57, respectively. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Patients homozygous for the variant codon 54B allele (54BB) had worse severity of illness on admission (p = .007), greater likelihood of septic shock (p = .04), and increased odds of ARDS (adjusted odds ratio, 6.7; 95% confidence interval, 1.5-31) when compared with heterozygotes and homozygotes for the wild-type allele. This association with ARDS was especially strong among the 311 patients with septic shock (adjusted odds ratio, 12.0; 95% confidence interval, 1.9-74). Among the patients with ARDS, the 54BB genotype was associated with more daily organ dysfunction (p = .01) and higher mortality (adjusted hazard rate, 4.0; 95% confidence interval, 1.6-10). Development of ARDS and outcomes in ARDS did not vary significantly with variant alleles of codon -221, 52, and 57, but the power to detect an effect was limited secondary to the low allele frequencies. CONCLUSIONS The MBL-2 codon 54BB genotype may be important in ARDS susceptibility and outcome. Additional studies are needed to confirm these findings in other populations.


title: Comparison of Transumbilical Laparoscopically Assisted Appendectomy to Conventional Laparoscopic Appendectomy in Children.

text: PURPOSE To compare surgical outcomes of children with appendicitis treated with the transumbilical laparoscopically assisted appendectomy (TULAA) versus the conventional 3-port laparoscopic appendectomy (TPLA). MATERIALS AND METHODS Retrospective study of pediatric patients with appendicitis treated with TULAA or TPLA between January 2010 and December 2015. Operative time (OT), length of stay, cost, and surgical site infection rate were compared between the 2 groups. RESULTS Six hundred twenty-five appendectomies were performed [263 TULAA, 362 TPLA: acute (457), gangrenous (39), and perforated (129)]. TULAA had a shorter OT (median, 40 vs. 67 min; P<0.001), a shorter length of stay (median, 20 vs. 23 h; P<0.001), and a lesser cost (median $6266 vs. $8927; P<0.001). Surgical site infection rate was slightly higher in the TULAA group (6% vs. 4%; P=0.19). CONCLUSIONS TULAA had a shorter OT and was less costly than conventional TPLA. TULAA should be considered as the first surgical approach at treating appendicitis in children.


title: Frequency of puncture holes in peritoneal dialysis catheters related to the beta cap adapter.

text: Between November 2009 and September 2011, 12 patients (6 women, 6 men) undergoing continuous peritoneal dialysis (PD) or automated PD developed puncture-like holes in the PD catheter near the interface of the adapter with the superior aspect of the Silastic PD catheter The adapter is used to connect the PD catheter to the PD transfer set. Over the course of 23 months, the 12 patients presented to the PD unit with 19 separate instances of catheter holes, for an event rate of 0.23 holes per patient-year Data including socio-demographic information, PD modality, need for antibiotic treatment, event recurrence, infectious complications, and time from catheter placement were collected from patients whose catheters did and did not develop holes. We observed no differences between patients whose catheters developed holes and those whose catheters did not. The location of the individual holes suggested a relationship between the adapter and the catheter holes. The holes, which led to increased patient morbidity and costs, may be related to structural changes made in 2006 to the adapter.


Arenavirus gene structure and organization.


title: Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants.

text: BACKGROUND 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol. Newer dietary approaches combining cholesterol-lowering foods may offer another option, but these approaches have not been compared directly with statins in the same persons. OBJECTIVE The objective was to compare, in the same subjects, the cholesterol-lowering potential of a dietary portfolio with that of a statin. DESIGN Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in random order as outpatients: a very-low-saturated-fat diet (control diet), the same diet plus 20 mg lovastatin (statin diet), and a diet high in plant sterols (1.0 g/1000 kcal), soy-protein foods (including soy milks and soy burgers, 21.4 g/1000 kcal), almonds (14 g/1000 kcal), and viscous fibers from oats, barley, psyllium, and the vegetables okra and eggplant (10 g/1000 kcal) (portfolio diets). Fasting blood samples were obtained at 0, 2, and 4 wk. RESULTS LDL-cholesterol concentrations decreased by 8.5+/-1.9%, 33.3+/-1.9%, and 29.6+/-1.3% after 4 wk of the control, statin, and portfolio diets, respectively. Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk (P=0.013), 9 participants (26%) achieved their lowest LDL-cholesterol concentrations with the portfolio diet. Moreover, the statin (n=27) and the portfolio (n=24) diets did not differ significantly (P=0.288) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff. CONCLUSIONS Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention. They may, therefore, bridge the treatment gap between current therapeutic diets and newer statins.


title: Swine in biomedical research: creating the building blocks of animal models.

text: The opportunities for utilizing swine biomedical models are immense, particularly in models that address lifestyle issues (nutrition, stress, alcohol, drugs of abuse, etc.). However, in order to fully capitalize upon the promise, there needs to be a more general recognition of these cofactors, such as nutrition, as key modulators of phenotype via genomic, epigenetic, and postgenomic mechanisms. Furthermore, increased interactions between nutrition scientists and clinical and fundamental researchers in other disciplines, including developmental biology, immunology, neuroscience, oncology, and cardiovascular and gastrointestinal physiology, are required. Closing discussions focused on the need for future conferences at more frequent intervals to support interactions between the various disciplines. This was especially critical because of the global distribution of investigators.


title: Expression of matrix metalloproteinases and their tissue inhibitor during viral encephalitis.

text: Matrix metalloproteinases (MMPs) participate in remodeling the extracellular matrix and facilitate entry of inflammatory cells into tissues. Infection of the murine central nervous system (CNS) with a neurotropic coronavirus induces encephalitis associated with increased levels of mRNA encoding MMP-3 and MMP-12. Whereas virus-induced MMP-3 expression was restricted to CNS resident astrocytes, MMP-12 mRNA was expressed by both inflammatory cells and CNS resident cells. Immunosuppression increased both MMP-3 and MMP-12 mRNA levels in CNS resident cells, suggesting that the presence of virus rather than inflammation induced protease up-regulation. MMP activity is partially regulated by a small family of genes encoding tissue inhibitors of matrix metalloproteinases (TIMPs); among the TIMPs, only TIMP-1 mRNA expression increased in the CNS following coronavirus infection. During inflammation TIMP-1 mRNA was most prominently expressed by infiltrating cells. By contrast, in the immunosuppressed host TIMP-1 mRNA was expressed by CNS resident cells. Analysis of cytokine and chemokine mRNA induction within the infected CNS of healthy and immunocompromised mice suggested a possible correlation between increased viral replication and increased levels of beta interferon, MMP-3, MMP-12, and TIMP-1 mRNA. CD4+ T cells which localize to the perivascular and subarachnoid spaces were identified as the primary source of TIMP-1 protein. By contrast, protein expression was undetectable in astrocytes or CD8+ T cells, the primary antiviral effectors that localize to the CNS parenchyma in response to infection. These data suggest that in contrast to the results seen with MMPs, inhibition of protease activity via TIMP-1 expression correlates with the differential tissue distribution of T-cell subsets during acute coronavirus-induced encephalitis.


title: Giant porokeratosis.

text: Porokeratosis is a disorder of keratinization characterized by annular plaques with an atrophic center surrounded by a raised, keratotic wall. It has several clinical forms including a porokeratosis of Mibelli, giant porokeratosis, linear porokeratosis, disseminated superficial actinic porokeratosis, palmoplantar porokeratosis and punctate porokeratosis. We report a patient with the rare condition of giant porokeratosis. Several variants of porokeratosis coexist in our patient.


title: Effects of creating a non-specific, virus-hostile environment in the nasopharynx on symptoms and duration of common cold.

text: The Common Cold remains the most frequent symptomatic viral infection in man. Current best therapies are all symptomatic. New pharmacological therapies are likely to be prescription-bound, and as most Common Cold infections are successfully treated without the intervention of a Physician, there is a need for effective non-prescription therapy options. Aim of this study is to propose a new type of approach, based on the concept of making a hostile biological environment for virus survival and spreading at the point of infection, the nasopharynx. The hypothesis was advanced that infections could be controlled using a physical biological approach to create an environment at the point of infection, that is inhibitory to the survival, and persistence of infecting virus, and of viruses newly released from infected mucosal epithelial cells. A nasal irrigation spray, designed to deliver a low pH gel to the nasal cavity, was developed and tested in this study. The study was a randomised, parallel, double-blind, placebo-controlled evaluation of three formulations of irrigation nasal spray in 441 subjects. The objective was to test whether the formulations reduced Cold severity and Cold duration compared to a placebo nasal spray. Subjects were recruited, and supplied with the product when healthy, and were instructed to begin treating and recording symptom severity once they experienced the "first signs" of a Common Cold. To qualify, subjects had to volunteer that they had at least one of the symptoms: sore/scratchy throat, runny nose or congested nose. The product was used 4 times daily, with at least 4 hours separating each dose, for a maximum of 7 days. Efficacy was assessed by an Interactive Voice Recall System whereby subjects were required to contact the investigation site, by telephone, twice daily when they were asked to assess the severity of their symptoms using a four point ordinal scale where 0 = "absent", and 3 = "severe". The symptoms assessed were sore throat, runny nose, blocked nose, cough and tired/run-down feeling. Two formulations demonstrated significant effects. A hydroxy methyl propyl cellulose based formulation reduced symptom severity compared with placebo by 17% and a Poloxamer based formulation reduced severity by 21%. Duration of illness was reduced with a hydroxy methyl propyl cellulose based formulation by 1.5 days to 2.4 days (according to the dose) and by a Poloxamer based formulation by 2.5 days. Results of this study suggest that the creation of a non virus-specific, inhibitory environment in the nasopharynx holds promise as an effective method of controlling the severity and duration of the Common Cold.


title: Urinary tract infection (UTI) in newborns: risk factors, identification and prevention of consequences.

text: The aim of the study is identification of urinary tract infections (UTI) and urinary tract anomalies (UTA) already in the perinatal period. The authors attempted to prevent serious consequences of the above conditions in the examined children. Family history data, certain conditions in pregnancy and appertaining symptoms in children were elaborated to specify selective distinctive criteria for children at risk. Newborns (1200) were selected for potential existence of a UTI. All the examined newborns underwent a urinalysis. Those with significant bacteriuria were taken urine specimens, C-reactive protein (RVP), Complete Blood Count (CBC) and bilirubin. The newborns with a UTI and a suspected UTA were sent to ultrasound examination, direct radio nuclide cystography and Tc99m MAG3 dynamic scanning. The frequency of a UTI in the perinatal period amounted to 4.5%. A UTA was found in 29.6% of the examinees. The infection was more likely to appear among newborns with a UTA in their families, a UTI, pre-eclampsia and a febrile infection in mother, intrauterine growth retardation, premature rupture of membranes (RVP), umbilical cord strangulation, jaundice, cyanosis, breathing difficulties, seizures and asphyxia.


title: Berne virus is not 'coronavirus-like'.

text: In infected embryonic mule skin cells, Berne virus directs the synthesis of two main polypeptides (22K, 20K); in addition, virus-specific proteins with apparent molecular weights of greater than 200K, 80K to 120K, 32K and 17K were detected after radioimmune precipitation. The replication of Berne virus was reduced more than 1000-fold by actinomycin D, when the drug (0.1 to 1.0 micrograms/ml) was added during the first 8 h after infection; alpha-amanitin (25 micrograms/ml) produced a similar though less pronounced effect. U.v. preirradiation of the cells for greater than or equal to 5 s led to a dramatic decrease in the production of extracellular virus. The results presented support our suggestion that Berne virus is a representative of a new family of animal viruses.


title: Effect of intravenous immunoglobulin on prednisone dose in patients with pemphigus vulgaris.

text: BACKGROUND Current therapeutic options for the treatment of pemphigus vulgaris (PV) are prednisone and immunosuppressants. Patients unresponsive to high-dose systemic corticosteroids and conventional immunosuppressants may respond to intravenous immunoglobulin (IVIG). OBJECTIVE The primary outcome was the change in prednisone dose at 6 months and 1 year post-IVIG administration. METHODS A retrospective chart review of PV patients treated at Sunnybrook and Women's College Health Sciences Centre between January 1999 and October 2004 was conducted. Demographic information, corticosteroid and IVIG use, dosage, and the timing of administration for all patients were obtained. RESULTS Eight PV patients, mean age of 50 years (+/- 14.7 years), were reviewed. There was a significant decrease in mean prednisone dose at 6 months (45%) and 12 months (71%) compared with the mean dose at the start of treatment (p < .05). LIMITATIONS Concomitant medication use may influence results. CONCLUSION This study demonstrates that IVIG can lower prednisone doses in PV patients.