docid: jzxjsakv

title: Emerging waterborne infections: contributing factors, agents, and detection tools.

text: Because microorganisms are easily dispersed, display physiological diversity, and tolerate extreme conditions, they are ubiquitous and may contaminate and grow in water. The presence of waterborne enteric pathogens (bacteria, viruses, and protozoa) in domestic water supplies represents a potentially significant human health risk. Even though major outbreaks of waterborne disease are comparatively rare, there is substantial evidence that human enteric pathogens that are frequently present in domestic water supplies are responsible for low-level incidence of waterborne microbial disease. Although these diseases are rarely debilitating to healthy adults for more than a few hours to a few days, enteric pathogens can cause severe illness, even death, for young children, the elderly, or those with compromised immune systems. As the epidemiology of waterborne diseases is changing, there is a growing global public health concern about new and reemerging infectious diseases that are occurring through a complex interaction of social, economic, evolutionary, and ecological factors. New microbial pathogens have emerged, and some have spread worldwide. Alternative testing strategies for waterborne diseases should significantly improve the ability to detect and control the causative pathogenic agents. In this article, we provide an overview of the current state of knowledge of waterborne microbial pathogens, their detection, and the future of new methods in controlling these infectious agents.


Background paper. Functions of the coronavirus nucleocapsid protein.


National Notifiable Diseases Surveillance System tables.


Dangers of postoperative opioids: is there a cure?


title: Association study of ACE2 (angiotensin I-converting enzyme 2) gene polymorphisms with coronary heart disease and myocardial infarction in a Chinese Han population.

text: Results are accumulating that ACE2 (angiotensin I-converting enzyme 2) might act as a protective protein for cardiovascular diseases; however, only a few studies in human populations have been carried out. This prompted us to perform a case-control study to investigate the relationship of ACE2 polymorphisms with CHD (coronary heart disease) and MI (myocardial infarction). Three single nucleotide polymorphisms in the ACE2 gene (1075A/G, 8790A/G and 16854G/C) were genotyped by PCR-RFLP (restriction-fragment-length polymorphism) in 811 patients with CHD (of which 508 were patients with MI) and 905 normal controls in a Chinese population. The polymorphisms were in linkage disequilibrium (r(2)=0.854-0.973). Analyses were conducted by gender, because the ACE2 gene is on the X chromosome. In females, an association was detected with MI for 1075A/G (P=0.026; odds ratio=1.98) and 16854G/C (P=0.028; odds ratio=1.97) in recessive models after adjusting for covariates. In male subjects, two haplotypes (AAG and GGC) were common in frequency. In male subjects not consuming alcohol, the haplotype GGC was associated with a 1.76-fold risk of CHD [95% CI (confidence interval), 1.15-2.69; P=0.007] and a 1.77-fold risk of MI (95% CI, 1.12-2.81; P=0.015) with environmental factors adjusted, when compared with the most common haplotype AAG. In conclusion, the results of the present study indicate that common genetic variants in the ACE2 gene might impact on MI in females, and may possibly interact with alcohol consumption to affect the risk of CHD and MI in Chinese males.


title: General practice: professional preparation for a pandemic.

text: General practice will play a key role in both prevention and management of an influenza pandemic. Australian pandemic plans acknowledge a role for general practice, but there are few published data addressing the issues that general practitioners and their practices will face in dealing with such a crisis. The outcome will revolve around preparation in three key areas: Definition of the role of general practice within a broad primary care pandemic response, and adequate preparation within general practices so they can play that role well. Planning exercises and forums must include GPs, and rehearsals must include practical experience for general practices and their staff. Local Divisions of General Practice and GP practices can advocate for this, can define their role, and can prepare by using pandemic preparedness checklists; Definition and enactment of communication strategies to facilitate transfer of useful clinical and administrative data from practices and rapid dissemination of information into the community via general practice; Resource provision, which should be centrally funded but locally distributed, with personal protective equipment, vaccines and antivirals readily available for distribution. Resources must include support for human resource management to ensure appropriate health care professionals reach areas of workforce demand. Administrative, clinical and financial resources must be available to train GPs and practices in pandemic awareness and response.


Travel by air: health considerations.


title: Genetic variation in porcine reproductive and respiratory syndrome virus isolates in the midwestern United States.

text: The nucleotide sequence of a 3266 bp region encompassing open reading frames (ORFs) 2 through 7 of the porcine reproductive and respiratory syndrome virus (PRRSV) was determined for 10 isolates recovered from the midwestern United States. Pairwise comparisons showed that genetic distances between isolates ranged from 2.5% to 7.9% (mean 5.8% +/- 0.2%) whereas the Lelystad strain from Europe was, on average, 34.8% divergent from US clones. Thus, US and European PRRSV isolates represent genetically distinct clusters of the same virus. ORF 5, which encodes the envelope glycoprotein, was the most polymorphic [total nucleotide diversity (pi) = 0.097 +/- 0.007] and ORF 6, encoding the viral M protein, was the most conserved (pi = 0.038 +/- 0.003). The substantial differences in nucleotide diversity among ORFs suggests that the virus is evolving by processes other than simple accumulation of random neutral mutations. In support of this hypothesis, statistical analyses of the nucleotide sequence provided strong evidence for intragenic recombination or gene conversion in ORFs 2, 3, 4, 5 and 7, but not in ORF 6. An excess of synonymous (silent) substitutions was observed in all six ORFs, indicating an evolutionary pressure to conserve amino acid sequences. Taken together, the data indicate that despite intragenic recombination among extant PRRSV isolates, purifying selection has acted to maintain the primary structure of individual ORFs.


title: Contribution of passive immunity to porcine respiratory coronavirus to protection against transmissible gastroenteritis virus challenge exposure in suckling pigs.

text: OBJECTIVE To determine the ability of porcine respiratory coronavirus (PRCV) infections to induce passive immunity in suckling pigs to transmissible gastroenteritis virus (TGEV) challenge exposure. DESIGN AND ANIMALS: 4 TGEV seronegative sows and their litters (group A) served as controls, whereas 2 other groups (B and C) of sows (also TGEV seronegative) were oronasally inoculated with live PRCV during 1 or 2 subsequent pregnancies, respectively. PROCEDURE Effectiveness of passive immunity provided to pigs via colostrum and milk was assessed after TGEV challenge exposure, and TGEV antibody responses in colostrum and milk were analyzed. RESULTS Mortality in the 3 groups of young pigs correlated with severity of clinical signs of TGEV infection and was highest in control litters (86% in group-A pigs) and lowest in litters of sows inoculated with PRCV in 2 subsequent pregnancies (14% in group-C pigs). Virus-neutralization and IgA and IgG TGEV antibody titers of milk collected from sows at challenge exposure had significant positive correlation with litter survival. Significantly higher numbers of TGEV-specific IgA and IgG antibody-secreting cells were found in group-A pigs than in group-C pigs, suggesting that high titer of maternal antibodies (induced in group-C sows multiply exposed to PRCV) may interfere with active antibody responses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggest that, in PRCV-infected pig herds, multiple exposures of pregnant sows are associated with higher IgA and IgG antibody titers to TGEV in milk, and these titers contribute to protection against TGEV infection.


docid: xomtfnmi

title: Depression, anxiety, body image, sexual functioning, and dyadic adjustment associated with dialysis type in chronic renal failure.

text: OBJECTIVE Depression is the most widely studied complication in dialysis patients. In patients with chronic renal failure, changes in body image are considered to be associated with invasive treatment interventions. In addition, sexual problems are common in dialysis patients. In this study, hemodialysis and peritoneal dialysis patients are investigated for depression, anxiety, body image, sexual satisfaction, and dyadic adjustment. METHODS Hemodialysis patients (n = 36), peritoneal dialysis patients (n = 54), and healthy controls (n = 30) were included in the study. All the subjects were assessed with Structured Clinical Interview for DSM-IV, Body Image Scale, Beck Depression Inventory, Beck Anxiety Scale, Golombok-Rust Inventory for Sexual Satisfaction, and Dyadic Adjustment Scale. RESULTS Depression (20.64 +/- 15.20) and anxiety levels (14.72 +/- 12.36) were significantly higher in hemodialysis group compared to peritoneal dialysis (13.54 +/- 12.51; 12.74 +/- 11.21) and control groups (7.17 +/- 5.58; 9.86 +/- 9.19). In peritoneal dialysis group, as depression and anxiety levels increased, body image was disturbed and sexual satisfaction decreased. In peritoneal dialysis group, body image (86.98 +/- 23.63) was better than hemodialysis group (101.58 +/- 26.51) and was not different from the control group (83.67 +/- 22.11). In hemodialysis group, as depression and anxiety levels increased, body image was disturbed. In both groups, long-term dialysis disturbed body image. CONCLUSION Patients should be informed about the impacts of dialysis. Clinicians may wish to monitor dialysis-users for anxiety, depression, dyadic adjustment, and body image difficulties at follow-up appointments. Interventions that target intimate partner interventions, appearance-related beliefs, and anxiety depression may be of benefit to this population.


title: Histological changes in intestine in semichronic diarrhoea induced by lactose enriched diet in rats: effect of Diarex-Vet.

text: Efficacy of Diarex-Vet (The Himalaya Drug Company, Makali, Bangalore, India) was evaluated histologically in semichronic diarrhoea induced by lactose enriched diet in rats. The rats in different groups were given lactose enriched diet alone for 2 days before starting the treatment with Diarex-Vet at a dose of 250, 500 and 750 mg/kg body weight along with lactose enriched diet for 5 days. Animals were euthanised at the end of 5 days of treatment and histological changes were observed in the ileum, caecum and colon. Semiquantitative analysis of goblet cells in intestines showed dose dependent response among the treated groups. The morphological changes were comparable to normal in the group given 750 mg/kg body wt Diarex-Vet. The effects observed were attributed to the lactase like analogous activity of Diarex-Vet or the inhibition of the osmotic processes in the intestinal lumen thereby reducing the morphological changes in the intestines.


title: Correlation of quantitative dynamic contrast-enhanced MRI with microvascular density in necrotic, partial necrotic, and viable liver tumors in a rabbit model.

text: The purpose of this study was to examine the correlation of quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) with microvessel density (MVD) in necrotic, partial necrotic, and viable tumors using a rabbit VX2 liver tumor model. Nine rabbits were used for this study. The complete necrotic area (CNA), partial necrotic area (PNA), and viable tumor area (VTA) of liver tumors were experimentally induced by radiofrequency ablation (RFA). DCE-MRI data were processed based on the extended Kety model to estimate Ktrans, ve and vp parameters. The boundaries among CNA, PNA, and VTA were delineated based on H&E stain images, and MVD was assessed for each subregion of each VX2 tumor based. There were no correlations between ph-parameters (Ktrans, ve, and vp) and MVD for CNA. For PNA, the Ktrans values were positively correlated with the MVD (r = 0.8124, p < 0.001). For VTA, we found a positive correlation between Ktrans values and the MVD (r = 0.5743, p < 0.05). Measuring from both the PNA and the VTA, mean Ktrans values were positively correlated with mean MVD (r = 0.8470, p < 0.0001). In a rabbit VX2 liver tumor model, Ktrans values correlated well with MVD counts of PNA and VTA in liver tumors.


title: Malaysia Stroke Council guide on acute stroke care service during COVID-19 Pandemic.

text: On the 18th of March 2020, the Malaysia government declared a movement control order (MCO) due to the unprecedented COVID-19 pandemic. Although the majority of patients presented with respiratory-related symptoms, COVID-19 patients may present atypically with neurological manifestations and may even have an increased risk of stroke. The Malaysia Stroke Council is concerned regarding the level of care given to stroke patients during this pandemic. During the recent National Stroke Workflow Steering Committee meeting, a guide was made based on the currently available evidences to assist Malaysian physicians providing acute stroke care in the hospital setting in order to provide the best stroke care while maintaining their own safety. The guide comprises of prehospital stroke awareness, hyperacute stroke care, stroke care unit and intensive care unit admission, post-stroke rehabilitation and secondary prevention practice. We urge continuous initiative to provide the best stroke care possible and ensure adequate safety for both patients and the stroke care team.


title: Prokaryote phylogeny without sequence alignment: from avoidance signature to composition distance.

text: This is a review of a new and essentially simple method of inferring phylogenetic relationships from complete genome data without using sequence alignment. The method is based on counting the appearance frequency of oligopeptides of a fixed length (up to K = 6) in the collection of protein sequences of a species. It is a method without fine adjustment and choice of genes. Applied to prokaryotic genomes it has led to results comparable with the bacteriologists' systematics as reflected in the latest 2002 outline of the Bergey's Manual of Systematic Bacteriology. The method has also been used to compare chloroplast genomes and to the phylogeny of Coronaviruses including human SARS-CoV. A key point in our approach is subtraction of a random background from the original counts by using a Markov model of order K-2 in order to highlight the shaping role of natural selection. The implications of the subtraction procedure is specially analyzed and further development of the new approach is indicated.


World no-tobacco day.


title: [Study on the changing regularity of special antibody and expression of stomach and enteric involvement on SARS-coronavirus infection in the recovery period of severe acute respiratory syndrome].

text: OBJECTIVE To study the change of special antibodies titer IgG, IgM and nucleocapsid to SARS coronavirus (CoV) and observing the expression of stomach and enteric involvement on SARS-CoV infection by monoclonal antibody against N protein of SARS-CoV in the 7-year recovery period among family clustering cases of severe acute respiratory syndrome. METHODS Special antibody titer to SARS-CoV of 14 patients from 5 different families and their 10 kinfolks continuously tested by IFA and antigen-capturing ELISA methods. Samples were taken in the 1(st) - 7(th) year periods after SARS patients infected by SARS-CoV, being diluted and measured on it titers of three kinds of antibodies. Immunochemical staining with monoclonal antibody (mAb) against N protein of SARS-CoV was used to determine the stomach and enteric tissues among 5 SARS patients with their nucleocapsid antibody titer ascended obviously after 1(st)-7(th) year. RESULTS When testing the IgG antibody titer of the 14 SARS patients by IFA method, the average titer was 1/71 (95%CI: 1/58 - 1/85) in the 1(st) year, but began to descend in the following years, and the IgG antibody of the most SARS patients disappeared in the 7(th) year. Regarding the IgM titer, it disappeared in most of the SARS patients 1 year later. The average value of nucleocapsid antibody titer was 1/146 (95%CI: 1/122 - 1/171) in the 1(st) year, and it descended as the IgG antibody titer did. In 5 cases, differences appeared. The nucleocapsid antibody titer was between 1/156 and 1/210 in 3 cases, and 2 cases were normal. Immunochemical staining with mAb against N protein of SARS-CoV was identified in the stomach and enteric tissues of 5 SARS patients with the nucleocapsid antibody titer increased significantly, 1(st)-7(th) year later. The five patients were detected by gastroscopy detection and cell immunohistochemistry test. 3 cases showed N protein antibody positive in the serum, and positive immunohistochemical expression in most of the cytoplasm in the gastric tissue mucous gland epithelial cells. 1 case also expressed in the intestinal tissue slurry columnar epithelium and interstitial cells. The other two cases showed negative on both serum N protein antibody and immunohistochemical expression. The biopsy results of the 5 patients were as follows: 1 case diagnosed as "signet-ring cell carcinoma of the stomach and rectum multiple transfer", 1 case of gastric polyp, 1 case of superficial antral gastritis and 2 cases were normal. CONCLUSION By testing the special IgG, IgM, nucleocapsid antibody to SARS-CoV of the 14 family clustering cases, we found that they all decreased in the 7(th) year, and most of them disappeared. The nucleocapsid antibody titer was related to pathogenetic condition. SARS-CoV was proved to be still present in stomach and enteric tissues of SARS patients with the nucleocapsid antibody titer increased significantly after the 7(th) year.


title: Comparative analysis of techniques to prevent laparoscopic fogging.

text: PURPOSE To evaluate the efficiency and efficacy of two common and commercially available methods to resolve lens fogging: a Fluid Warming System (O.R. Solutions, Chantilly, VA) and the Clearify Visualization System (Covidien, Mansfield, MA). MATERIAL AND METHODS We prospectively evaluated 40 patients undergoing laparoscopic renal procedures with the Fluid Warming System (first 20 cases) and then the Clearify Visualization System (second 20 cases). We utilized the standard Fluid Warming System per a 30-second modified protocol established in our laboratory. We used the Clearify according to manufacturer instructions. For each procedure we documented the etiology of each episode of visual obstruction, procedure type and surgery duration. We performed a cost analysis. For all cases we used the same insufflator, insufflation trocar location and trocar configuration. RESULTS All 40 patients completed the study protocol without incident. The mean fogging events per hour for the Fluid Warming System and Clearify Visualization System were 0.7 (0-2.52) and 1.4 (0-5.02), respectively (P = 0.045). Surgery duration and cost per procedure were similar for both systems. CONCLUSION The Fluid Warming System with modified technique was found to have less fogging events than the Clearify Visualization System, with no difference in operative time or cost.


docid: utlfprdi

title: Mild dilatation of renal pelvis in term neonates with urinary tract infection.

text: The purpose of this study was to assess the incidence and evolution of mild dilatation confined to the renal pelvis in term neonates with urinary tract infection developing within 2 weeks from birth. Twenty-two neonates with mild dilatation of the renal pelvis out of 180 neonates with urinary tract infection were identified giving an incidence of 12.2% for this finding. Male to female ratio was 6.3:1. The left kidney was twice as frequently involved (68 vs. 32%). At follow-up, the dilatation had disappeared in 20 neonates (90.9%) by a mean age of 2.7 years with only one neonate developing two further episodes of urinary tract infection in the infantile period. No other morbidity was noted.


title: Severe acute respiratory syndrome coronavirus Orf3a protein interacts with caveolin.

text: The orf3a (also called X1 or U274) gene is the largest unique open reading frame in the severe acute respiratory syndrome coronavirus genome and has been proposed to encode a protein with three transmembrane domains and a large cytoplasmic domain. Recent work has suggested that the 3a protein may play a structural role in the viral life cycle, although the mechanisms for this remain uncharacterized. Here, the expression of the 3a protein in various in vitro systems is shown, it has been localized to the Golgi region and its membrane topology in transfected cells has been confirmed. Three potential caveolin-1-binding sites were reported to be present in the 3a protein. By using various biochemical, biophysical and genetic techniques, interaction of the 3a protein with caveolin-1 is demonstrated. Any one of the potential sites in the 3a protein was sufficient for this interaction. These results are discussed with respect to the possible roles of the 3a protein in the viral life cycle.


title: Care for adult non-ICU Covid-19 patients: early experiences from a Belgian tertiary care centre.

text: The current Covid-19 outbreak poses many challenges on hospital organisation and patient care. Our hospital lies at the epicentre of the Belgian epidemic. On April 1st, a total of 235 Covid-19 patients had been admitted to our hospital. This demanded an unprecedented adaptation of our hospital organisation, and we have met many clinical issues in the care for Covid-19 patients. In this article, we share our experience in the handling of some of the practical and organisational issues in the care for Covid-19 patients.


title: Homo-oligomerization of the porcine reproductive and respiratory syndrome virus nucleocapsid protein and the role of disulfide linkages.

text: As a step toward understanding the assembly pathway of the porcine reproductive and respiratory syndrome virus (PRRSV), the oligomeric properties of the nucleocapsid (N) protein were investigated. In this study, we have demonstrated that under nonreducing conditions the N protein forms disulfide-linked homodimers. However, inclusion of an alkylating agent (N-ethylmaleimide [NEM]) prevented disulfide bond formation, suggesting that these intermolecular disulfide linkages were formed as a result of spurious oxidation during cell lysis. In contrast, N protein homodimers isolated from extracellular virions were shown to have formed NEM-resistant intermolecular disulfide linkages, the function of which is probably to impart stability to the virion. Pulse-chase analysis revealed that N protein homodimers become specifically disulfide linked within the virus-infected cell, albeit at the later stages of infection, conceivably when the virus particle buds into the oxidizing environment of the endoplasmic reticulum. Moreover, NEM-resistant disulfide linkages were shown to occur only during productive PRRSV infection, since expression of recombinant N protein did not result in the formation of NEM-resistant disulfide-linked homodimers. Mutational analysis indicated that of the three conserved cysteine residues in the N protein, only the cysteine at position 23 was involved in the formation of disulfide linkages. The N protein dimer was shown to be stable both in the presence and absence of intermolecular disulfide linkages, indicating that noncovalent interactions also play a role in dimerization. Non-disulfide-mediated N protein interactions were subsequently demonstrated both in vitro by the glutathione S-transferase (GST) pull-down assay and in vivo by the mammalian two-hybrid assay. Using a series of N protein deletion mutants fused to GST, amino acids 30 to 37 were shown to be essential for N-N interactions. Furthermore, since RNase A treatment markedly decreased N protein-binding affinity, it appears that at least in vitro, RNA may be involved in bridging N-N interactions. In cross-linking experiments, the N protein was shown to assemble into higher-order structures, including dimers, trimers, tetramers, and pentamers. Together, these findings demonstrate that the N protein possesses self-associative properties, and these likely provide the basis for PRRSV nucleocapsid assembly.


title: Wild animal surveillance for coronavirus HKU1 and potential variants of other coronaviruses.

text: 1. Although CoV-HKU1 was not identified in any of the studied animals, a coronavirus closely related to SARS-CoV (bat-SARS-CoV) was identified in 23 (19%) of 118 wild Chinese horseshoe bats by reverse transcriptase polymerase chain reaction (RT-PCR). 2. Complete genome sequencing and phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b coronaviruses, distantly related to known group 2 coronaviruses. 3. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike gene. The presence of a29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. 4. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats using an enzyme immunoassay.Neutralising antibody to human SARS-CoV was also detected in those with lower viral loads.5. This study also revealed a previously unknown diversity of coronaviruses in bats, which are important natural reservoir for coronaviruses including SARS-CoV-like viruses.


title: [THE PSYCHOLOGICAL IMPACT OF A PANDEMIC OUTBREAK ON MEDICAL STAFF - LITERATURE REVIEW].

text: INTRODUCTION In January 2020, the World Health Organization (WHO) declared an international emergency due to the outbreak of COVID-19. In March 2020 the WHO announced that the epidemic could be characterized as a pandemic. Subsequently, the WHO acknowledged the importance of providing support to the medical teams, realizing the enormous burden and stress facing this group. The aim of the present study is to review the up-to-date professional literature dealing with the psychological impact of a pandemic outbreak on medical staff. The literature existing so-far is scarce. It does, however, provide evidence of the short- and long-term impact of such epidemics on the mental health of the medical teams. Direct exposure to affected patients, the risk of contagion, a subjectively negative perception of one's medical condition and being in isolation or quarantine, all constitute risk factors for mental symptoms such as depression, anxiety and post-trauma. A sense of control, especially regarding the means of protection and controlling infection, altruistic acceptance of the work-related risks, social support, good team-spirit in the medical unit and support from superiors are all protective factors.


title: Managing Prostate Cancer Surgical Patients during the COVID-19 Pandemic: A Brief Report of the Duke Cancer Institute's Initial Experience.

text: The coronavirus disease 2019 pandemic has rapidly placed tremendous stress on health systems around the world. In response, multiple health systems have postponed elective surgeries in order to conserve hospital beds and personal protective equipment, minimize patient traffic, and prevent unnecessary utilization and exposure of healthcare workers. The American College of Surgeons released the following statement on March 13, 2020: "Each hospital, health system and surgeon should thoughtfully review all scheduled elective procedures with a plan to minimize, postpone, or cancel electively scheduled operations, endoscopes, or other invasive procedures until we have passed the predicted inflection point in the exposure graph and can be confident that our health care infrastructure can support a potentially rapid and overwhelming uptick in critical patient care needs." In our state, North Carolina, Governor Roy Cooper requested that all hospitals postpone elective and non-urgent procedures and surgeries effective March 23, 2020.


title: Sequencing of coronavirus IBV genomic RNA: three open reading frames in the 5' 'unique' region of mRNA D.

text: The nucleotide sequence of a genomic cDNA clone corresponding to the 5' terminal domain of mRNA D of the Beaudette strain of infectious bronchitis virus (IBV) has been determined. This region contains three open reading frames which predict polypeptides of molecular weights 6700 (6.7K), 7.4K and 12.4K. The predicted 12.4K polypeptide has a codon usage very similar to that predicted for the products of the IBV nucleocapsid, membrane and spike genes. The sequence also predicts a hydrophobic, potentially membrane-anchoring, region in the N terminal half of the 12.4K polypeptide, and a hydrophilic C terminus.


Feline coronavirus in the intestinal contents of cats with feline infectious peritonitis.


title: Severe acute respiratory syndrome in Singapore.

text: AIMS To describe the epidemiological and clinical features of paediatric severe acute respiratory syndrome (SARS) in Singapore. METHODS The following data were retrospectively collected from the case records of all 71 patients (aged 7 months to 14 years) admitted from 23 March to 22 May 2003 to the SARS paediatric unit: patient demographics, contact history, clinical features, physiological parameters, investigations, treatment, and outcome. Using WHO criteria there were seven probable (P), 23 suspect (S), and 41 observe (O) cases. RESULTS Compared to the O cases P patients had a longer mean duration of fever (3.66 (SD 2.3) v 8.57 (SD 2.44) days), lower mean thrombocytopenia (248.3 (SD 82.7) v 173.7 (SD 49.0)x10(9)/l), leucopenia (8.19 (SD 4.45) v 3.06 (SD 1.02)x10(9)/l), lymphopenia (2.79 (SD 1.97) v 1.44 (SD 0.75)x10(9)/l), and neutropenia (4.48 (SD 2.88) v 1.24 (SD 0.43)x10(9)/l). Chest auscultation was abnormal in 71% of P patients, with mild crepitations detected. All had abnormal chest radiographs versus 39% of S cases, and 27% of O cases. CONCLUSIONS There are no distinguishing clinical features of paediatric SARS. The diagnosis is suggested by the paucity of clinical signs with an abnormal chest radiograph, and laboratory evidence of leucopenia, lymphopenia, and thrombocytopenia.


title: A cross-sectional study of primary-care physicians in Singapore on their concerns and preparedness for an avian influenza outbreak.

text: INTRODUCTION During an avian influenza (AI) pandemic, primary-care physicians (PCPs) are expected to play key roles in the prevention and control of the disease. Different groups of PCPs could have different concerns and preparedness level. We assessed the concerns, perceived impact and preparedness for an outbreak among PCPs in Singapore. MATERIALS AND METHODS A cross-sectional survey of PCPs working in private practice (n=200) and public clinics (n=205) from March to June 2006 with an anonymous self-administered questionnaire on concerns (12- items), perceived impact (10 items) and preparedness (10 items) for an outbreak. RESULTS Two hundred and eighty-five PCPs responded - 149 (response rate: 72.7%) public and 136 (response rate: 67.3%) private. The majority were concerned about risk to their health from their occupation (95.0%) and falling ill with AI (89.7%). Most (82.5%) accepted the risk and only 33 (11.8%) would consider stopping work. For perceived impact, most felt that people would avoid them (69.6%) and their families (54.1%). The majority (81.3%) expected an increased workload and feeling more stressed at work (86.9%). For preparedness, 78.7% felt personally prepared for an outbreak. Public PCPs were more likely to be involved in infection-control activities and felt that their workplaces were prepared. CONCLUSIONS Most PCPs felt personally prepared for an outbreak but were concerned about their exposure to AI and falling ill. Other concerns included social ostracism for themselves and their families. Public PCPs appeared to have a higher level of preparation. Addressing concerns and improving level of preparedness are crucial to strengthen the primary-care response for any AI outbreak.


title: Nucleotide sequence of the glycoprotein S gene of bovine enteric coronavirus and comparison with the S proteins of two mouse hepatitis virus strains.

text: The gene encoding the spike glycoprotein (S) of bovine enteric coronavirus (BECV) was cloned and its complete sequence of 4092 nucleotides was determined. This sequence contained a single long open reading frame with a coding capacity of 1363 amino acids (Mr 150,747). The predicted protein had 19 N-glycosylation sites. A signal sequence comprising 17 amino acids was observed starting from the first methionine residue. A potential peptidase cleavage site was located between amino acids 763 and 767. These cleavage explain the maturation of the primary product of the S gene to S1 (Mr 104,692) and S2 (Mr 84,175) spike structural proteins. Two amphipathic alpha-helices (amino acids 1007 to 1077 and 1269 to 1294) which may constitute the 12 nm stalk of the viral spike were also observed; another alpha-helix (amino acids 1305 to 1335) may be involved in the anchorage of the spike in the viral membrane. Comparison of this protein sequence to the described homologous mouse hepatitis (MHV) strain A59 and MHV-JHM S protein sequences led us to suggest that MHV-A59 and MHV-JHM S genes could be derived from a deletion of the BECV S gene.


title: Antigenic and genomic relatedness of turkey-origin coronaviruses, bovine coronaviruses, and infectious bronchitis virus of chickens.

text: In earlier studies in our laboratory, we found that bovine coronavirus (BCV) was pathogenic for 1-day-old turkey poults. This finding prompted us to study the antigenic and genomic relatedness of turkey origin coronaviruses (TOCVs) to BCV. A one-step reverse transcription (RT)-polymerase chain reaction (PCR) targeting a 730-base pair fragment of the nucleocapsid (N) gene of BCV and a nested PCR targeting a 407-base pair fragment of the N gene were used in an attempt to detect TOCV from North Carolina, Indiana, and a prototype turkey coronavirus (TCV) obtained from the American Type Culture Collection. Both the one-step RT-PCR and the nested PCR amplified cell culture-passaged isolates of calf diarrhea strains of BCV but none of the 15 tested TOCVs or transmissible gastroenteritis coronavirus of swine. TOCVs also did not cross-react in a BCV antigen-capture (AC) enzyme-linked immunosorbent assay (ELISA) system with monoclonal antibodies (MAbs) against N, spike glycoprotein, and hemagglutinin esterase glycoprotein proteins of BCV as coating antibodies. The same TOCVs could be detected with primers designed from the genome of infectious bronchitis virus (IBV) of chickens. These primers amplified a 1082-base pair region spanning portions of the membrane glycoprotein (M) and N protein genes of IBV and TCV. The TOCVs also cross-reacted in an AC-ELISA with MAbs against the M and subunit 2 of spike glycoprotein of IBV.


title: Antibody-dependent enhancement of hepatitis C virus infection.

text: Hepatitis C virus (HCV) often causes a persistent infection associated with hypergammaglobulinemia, high levels of antiviral antibody and circulating immune complexes, and immune complex disease. We previously reported that only a limited neutralizing activity to vesicular stomatitis virus or HCV pseudotype is generated in animals immunized with recombinant HCV envelope proteins and chronically infected HCV patient sera. Interestingly, when some of these neutralizing sera were diluted into a range of concentrations below those that reduced virus plaque number, an increase in pseudotype plaque formation was observed. Purified HCV E2-specific human monoclonal antibodies were used to further verify the specificity of this enhancement, and one- to twofold increases were apparent on permissive Huh-7 cells. The enhancement of HCV pseudotype titer could be inhibited by the addition of a Fc-specific anti-human immunoglobulin G Fab fragment to the virus-antibody mixture prior to infection. Treatment of cells with antibody to Fc receptor I (FcRI) or FcRII, but not FcRIII, also led to an inhibition of pseudotype titer enhancement in an additive manner. Human lymphoblastoid cell line (Raji), a poor host for HCV pseudotype infection, exhibited a four- to sixfold enhancement of pseudotype-mediated cell death upon incubation with antibody at nonneutralizing concentrations. A similar enhancement of cell culture-grown HCV infectivity by a human monoclonal antibody was also observed. Taken together, antibodies to viral epitopes enhancing HCV infection need to be taken into consideration for pathogenesis and in the development of an effective vaccine.


title: Critically ill patients with COVID-19 in Hong Kong: a multicentre retrospective observational cohort study

text: Objective To report the first eight cases of critically ill patients with coronavirus disease 2019 (COVID-19) in Hong Kong, describing the treatments and supportive care they received and their 28-day outcomes. Design Multicentre retrospective observational cohort study. Setting Three multidisciplinary intensive care units (ICUs) in Hong Kong. Participants All adult critically ill patients with confirmed COVID-19 admitted to ICUs in Hong Kong between 22 January and 11 February 2020. Main outcome measure 28-day mortality. Results Eight out of 49 patients with COVID-19 (16%) were admitted to Hong Kong ICUs during the study period. The median age was 64.5 years (range, 42–70) with a median admission Sequential Organ Failure Assessment (SOFA) score of 6 (IQR, 4–7). Six patients (75%) required mechanical ventilation, six patients (75%) required vasopressors and two (25%) required renal replacement therapy. None of the patients required prone ventilation, nitric oxide or extracorporeal membrane oxygenation. The median times to shock reversal and extubation were 9 and 11 days respectively. At 28 days, one patient (12%) had died and the remaining seven (88%) all survived to ICU discharge. Only one of the survivors (14%) still required oxygen at 28 days. Conclusion Critically ill patients with COVID-19 often require a moderate duration of mechanical ventilation and vasopressor support. Most of these patients recover and survive to ICU discharge with supportive care using lung protective ventilation strategies, avoiding excess fluids, screening and treating bacterial co-infection, and timely intubation. Lower rather than upper respiratory tract viral burden correlates with clinical severity of illness.


title: [Community-acquired pneumonia].

text: Pneumonias are inflammatory diseases of the lung parenchyma, infection is one of possible causes. With regard to the causes of community acquired pneumonias it is possible to distinguish those typical ones (caused by pneumococcus, legionella and other bacteria) and atypical ones (caused by mycoplasma, chlamydiae and others). Contrary to the atypical ones, typical pneumonias are characterized by sudden onset, high fever, chills, sometimes bloody expectoration and pains, as well as segmental or lobar changes and high leukocyte counts. Patients with tachycardia, diastolic blood pressure below 60 mm Hg and a blood urea nitrogen (BUN) of more than 7 mmol/l, as well as those with chronic basic diseases and a severe course should be hospitalized, further also those, who do not improve after 2 or 3 days therapy, in all cases of suspected pneumonia, with smokers and with patients aged over 40 years, a thorax X-ray should be executed. Typical pneumonias should be treated with penicillin or macrolide antibiotics, atypical ones with macrolide antibiotics, pneumonias with severe course additionally with a second generation cephalosporin. Where these simple rules are observed, a reduction of the still high mortality due to externally acquired pneumonias might be expected.


title: The broad anti-viral agent glycyrrhizin directly modulates the fluidity of plasma membrane and HIV-1 envelope.

text: Cell entry of enveloped viruses requires a wide-fusion-pore mechanism, involving clustering of fusion-activated proteins and fluidization of the plasma membrane and viral envelope. In the present study, GL (glycyrrhizin) is reported to lower membrane fluidity, thus suppressing infection by HIV, influenza A virus and vesicular stomatitis virus, but not by poliovirus. GL-treated HIV-1 particles showed reduced infectivity. GL also inhibited cell-to-cell fusion induced by HIV-1 and HTLV-I (human T-cell leukaemia virus type I). However, when cells treated with 1 mg/ml GL were placed in GL-free medium, they showed increased susceptibility to HIV-1 infection and HTLV-I fusion due to enhancement of membrane fluidity. The membrane dependence of GL and GL removal experiments suggest that GL does affect the cell entry of viruses. HIVs with more gp120 were less dependent on temperature and less sensitive to GL treatment than those with less gp120, indicating that the existence of more gp120 molecules resulted in a higher probability of forming a cluster of fusion-activated proteins.


title: Dissemination of multisusceptible methicillin-resistant Staphylococcus aureus in Singapore.

text: Analysis of hospital-acquired methicillin-resistant Staphylococcus aureus strains isolated from a tertiary public hospital in Singapore revealed that multisusceptible strains had gradually started to replace the endemic multiresistant strain (ST239-MRSA-III) since 2002. Molecular typing showed that this was a predominantly clonal outbreak of a UK-EMRSA-15 strain (ST22-MRSA-IV).


title: Natural killer cell activation after infection with lactate dehydrogenase-elevating virus.

text: Early after infection, lactate dehydrogenase-elevating virus (LDV) alters the immune system by polyclonally activating B lymphocytes, which leads to IgG2a-restricted hypergammaglobulinaemia, and by suppressing the secretion of Th2 cytokines. Considering that these alterations may involve cells of the innate immune system and cytokines such as interferon-gamma (IFN-gamma), we analysed the effect of LDV on natural killer (NK) cells. Within a few days of infection, a strong and transient NK cell activation, characterized by enhanced IFN-gamma message expression and cytolysis, was observed. LDV triggered a large increase in serum IFN-gamma levels. Because NK cells and IFN-gamma may participate in the defence against virus infection, we analysed their possible role in the control of LDV titres with a new agglutination assay. Our results indicate that neither the activation of NK cells nor the IFN-gamma secretion affect the early and rapid virus replication that follows LDV inoculation.


title: [Studying the possibility of respiratory immunization against tick-borne encephalitis].

text: There are known 3 likely mechanisms of virus conveyance into the central nervous system (CNS). These include hematogenic penetration, spread along the peripheral nerves, and the olfactory pathway which begins from the infected olfactory neuroepithelial cells. The possibility of viral spread into CNS via the olfactory pathway was shown for the representatives of togaviruses, herpesviruses, coronaviruses, rhabdoviruses, and for some others. This study suggests that the olfactory pathway of viral conveyance into CNS may be blocked by specific mucosal antibodies in the nasal mucosa. The recombinant TK- variant of WR vaccinia strain with inserted genes coding structural and nonstructural proteins of TBE virus is accumulated in the branches of the respiratory tract only while the parenteral vaccinia strain is detected in the brain regions, spleen, respiratory tract, and in blood. The protective activity of recombinant strain and inactivated TBE vaccine after mice immunization by escarification or intranasally, or subcutaneously was comparatively studied. The findings indicate that intranasal immunization by recombinant strain is the most protective against intraperitoneal challenge by TBE virus. The mucosal and humoral immune response that was induced by intranasal immunization seems to provide the highest levels of protection, which was experimentally observed.


title: Comparison of the replication of distinct strains of human coronavirus OC43 in organotypic human colon cells (Caco-2) and mouse intestine.

text: Three strains of human coronavirus (HCV) OC43 were compared for their ability to cause enteric infections and to induce interferon alpha (IFN alpha) using the Caco-2 human colon carcinoma cell line which exhibits spontaneous epithelial differentiation in vitro. MRC-5 cell culture grown stocks were prepared from: 1. CV Paris, a strain of OC43 recovered from an outbreak of necrotizing enterocolitis in newborns. 2. CV Mb, a neurotropic strain of OC43 which exhibits strict neuronal specificity in murine neuronal cell cultures. 3. CV Rd, a strain of OC43 which grows to a high titer in human rhabdomyosarcoma (RD) cells. Immunofluorescent staining for nucleocapsid antigen and plaque assay in MRC-5 cells was used to detect viral replication. BG-9 (human foreskin) cells challenged with vesicular stomatitis virus were used to detect IFN alpha production by human peripheral blood monocytes (PBMC) stimulated by virus infected Caco-2 cells. Caco-2 cells infected with virus at a multiplicity of infection of 0.5 yielded 10(4.6) and 10(4.4) plaque forming units/ml (pfu/ml) with CV Rd and CV Paris respectively, while CV Mb yielded only 10(3) pfu/ml. Caco-2 cells infected with CV Rd induced 64 IU/ml of IFN alpha in PBMC while these cells infected with CV Paris induced less than 2 IU/ml IFN alpha. In cells infected with CV Mb 4 IU/ml IFN alpha was detected. The results suggest that a lack of IFN alpha induction by CV Paris may be an indicator of its enteropathogenic potential.(ABSTRACT TRUNCATED AT 250 WORDS)


title: Severe acute respiratory syndrome coronavirus 7a accessory protein is a viral structural protein.

text: Severe acute respiratory syndrome coronavirus (SCoV) 7a protein is one of the viral accessory proteins. In expressing cells, 7a protein exhibits a variety of biological activities, including induction of apoptosis, activation of the mitogen-activated protein kinase signaling pathway, inhibition of host protein translation, and suppression of cell growth progression. Analysis of SCoV particles that were purified by either sucrose gradient equilibrium centrifugation or a virus capture assay, in which intact SCoV particles were specifically immunoprecipitated by anti-S protein monoclonal antibody, demonstrated that 7a protein was associated with purified SCoV particles. Coexpression of 7a protein with SCoV S, M, N, and E proteins resulted in production of virus-like particles (VLPs) carrying 7a protein, while 7a protein was not released from cells expressing 7a protein alone. Although interaction between 7a protein and another SCoV accessory protein, 3a, has been reported, 3a protein was dispensable for assembly of 7a protein into VLPs. S protein was not required for the 7a protein incorporation into VLPs, and yet 7a protein interacted with S protein in coexpressing cells. These data established that, in addition to 3a protein, 7a protein was a SCoV accessory protein identified as a SCoV structural protein.


title: Mapping membrane activity in undiscovered peptide sequence space using machine learning.

text: There are some ∼1,100 known antimicrobial peptides (AMPs), which permeabilize microbial membranes but have diverse sequences. Here, we develop a support vector machine (SVM)-based classifier to investigate ⍺-helical AMPs and the interrelated nature of their functional commonality and sequence homology. SVM is used to search the undiscovered peptide sequence space and identify Pareto-optimal candidates that simultaneously maximize the distance σ from the SVM hyperplane (thus maximize its "antimicrobialness") and its ⍺-helicity, but minimize mutational distance to known AMPs. By calibrating SVM machine learning results with killing assays and small-angle X-ray scattering (SAXS), we find that the SVM metric σ correlates not with a peptide's minimum inhibitory concentration (MIC), but rather its ability to generate negative Gaussian membrane curvature. This surprising result provides a topological basis for membrane activity common to AMPs. Moreover, we highlight an important distinction between the maximal recognizability of a sequence to a trained AMP classifier (its ability to generate membrane curvature) and its maximal antimicrobial efficacy. As mutational distances are increased from known AMPs, we find AMP-like sequences that are increasingly difficult for nature to discover via simple mutation. Using the sequence map as a discovery tool, we find a unexpectedly diverse taxonomy of sequences that are just as membrane-active as known AMPs, but with a broad range of primary functions distinct from AMP functions, including endogenous neuropeptides, viral fusion proteins, topogenic peptides, and amyloids. The SVM classifier is useful as a general detector of membrane activity in peptide sequences.


title: Hot-cold empathy gaps and medical decision making.

text: Prior research has shown that people mispredict their own behavior and preferences across affective states. When people are in an affectively "cold" state, they fail to fully appreciate how "hot" states will affect their own preferences and behavior. When in hot states, they underestimate the influence of those states and, as a result, overestimate the stability of their current preferences. The same biases apply interpersonally; for example, people who are not affectively aroused underappreciate the impact of hot states on other people's behavior. After reviewing research documenting such intrapersonal and interpersonal hot-cold empathy gaps, this article examines their consequences for medical, and specifically cancer-related, decision making, showing, for example, that hot-cold empathy gaps can lead healthy persons to expose themselves excessively to health risks and can cause health care providers to undertreat patients for pain.


Long-term cure of disseminated Mycobacterium avium infection in a cat.


Immunomodulatory activities of the herbal formula Kwan Du Bu Fei Dang in healthy subjects: a randomised, double-blind, placebo-controlled study.


title: High prevalence of the CD14-159CC genotype in patients infected with severe acute respiratory syndrome-associated coronavirus.

text: To investigate whether genetic factors of innate immunity might influence susceptibility and/or progression in individuals infected with SARS, we evaluated the CD14 gene polymorphism in 198 Hong Kong blood donors and 152 Hong Kong severe acute respiratory syndrome (SARS) patients who were previously genotyped for FcgammaRIIA polymorphisms. The prevalence of the CD14-159CC polymorphism was significantly higher in the patients with severe SARS than in the those with mild SARS or controls (31% versus 15% [mild SARS] or 20% [controls]; mild SARS: P = 0.029; odds ratio, 2.74; 95% confidence interval, 1.15 to 6.57; controls, P = 0.04; odds ratio, 2.41; 95% confidence interval, 1.05 to 5.54), and both CD14-159CC and FcgammaRIIA-RR131 are risk genotypes for severe SARS-CoV infection.


title: In vivo and in vitro models of demyelinating disease: a phosphoprotein phosphatase in host cell endosomes dephosphorylating the nucleocapsid protein of coronavirus JHM.

text: We have identified a phosphoprotein phosphatase which dephosphorylates efficiently the NC protein of coronavirus JHM. The activity was found in L-2 murine fibroblasts, Wistar Furth rat neonatal brain extracts, Wistar Furth rat oligodendrocyte primary cells and in Roc-1 cells, an oligodendrocytic hybrid cell line. In both L-2 cells and Roc-1 cells the enzyme was found to be localized predominantly in the endosomal fraction. The enzyme is optimally active at pH 7.0 and has a requirement for Mn++ ions. This PPPase activity is distinguishable from acidic and alkaline phosphatases. In view of the specificity of the endosomal PPPase for the phosphory-lated NC protein it is hypothesized that this enzyme may have a function during early stages of coronavirus infection.


title: Comparative study between meshes of polyester with collagen and polytetrafluoroethylene in the repair of defects produced in abdominal wall of rats.

text: PURPOSE To study the intraperitoneal use of polyester with collagen and polytetrafluoroethylene meshes in the correction of total ventral wall defects in rats. METHODS Thirty two rats were evaluated and divided randomly into four groups and underwent laparotomy and preparation of total defects of the abdominal wall. Next, the correction of the defect with the intraperitoneal placement of the chosen mesh was performed. The rats were submitted to euthanasia at 30 and 90 days after surgery. Were analyzed the macroscopic adhesions and microscopic aspects, and applied stress rupture test RESULTS All animals showed intraperitoneal adhesions in varying degrees, with no statistical significance difference. There was no difference also between groups in the evaluation of stress rupture tests. On the microscopic aspect, the A30 group had less inflammatory reaction and less formation of granulomas and foreign body reaction that the B30 group, with significant difference. CONCLUSIONS There was no difference in intraperitoneal adhesion and tensile rupture strength among groups. Group B30 presented granulomatous inflammatory reaction at the site of mesh attachment to the wall significantly higher than the A30.


title: Multiple sclerosis and Kaposi's sarcoma--chronic diseases associated with new human herpesviruses?

text: Two diseases that for many years have been suspected to be of viral origin are multiple sclerosis (MS) and Kaposi's sarcoma (KS). With the use of a new technique called representational difference analysis both these diseases have recently been associated with new lymphotropic herpesviruses, i.e. human herpesviruses (HHV) 6 and 8. HHV-6 is a ubiquitous virus and the etiological agent of exanthema subitum. Viral neuroinvasion occurs frequently in primary HHV-6 infection, and meningitis, encephalitis and demyelination have been described as rare complications. A relation with MS has been suggested for HHV-6, as the virus has been detected in MS plaques in the brain. Data from different studies are, however, conflicting and a definitive role for HHV-6 in MS pathogenesis has not been established. HHV-8 is believed to be the causative agent of KS, and is also associated with some rare hematological malignancies. The viral genome contains several potential oncogenes that are believed to have been picked up from the human genome during evolution. The role of HHV-8 in healthy, immunocompetent individuals is however uncertain. In conclusion, the full spectrum of human diseases associated with these new viruses is not yet understood, and rapid developments in molecular biology will continue to shed new light on the interactions between herpesviruses and their hosts.


title: Review of safety and minimum pricing of nitazoxanide for potential treatment of COVID-19.

text: Background Many treatments are being assessed for repurposing to treat coronavirus disease 2019 (COVID-19). One drug that has shown promising results in vitro is nitazoxanide. Unlike other postulated drugs, nitazoxanide shows a high ratio of maximum plasma concentration (Cmax), after 1 day of 500 mg twice daily (BD), to the concentration required to inhibit 50% replication (EC50) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Cmax : EC50 roughly equal to 14:1). As such, it is important to investigate the safety of nitazoxanide for further trials. Furthermore, treatments for COVID-19 should be cheap to promote global access, but prices of many drugs are far higher than the costs of production. We aimed to conduct a review of the safety of nitazoxanide for any prior indication and calculate its minimum costs of production. Methods A review of nitazoxanide clinical research was conducted using EMBASE and MEDLINE databases, supplemented by ClinicalTrials.gov. We searched for phase 2 or 3 randomised controlled trials (RCTs) comparing nitazoxanide with placebo or active control for 5-14 days in participants experiencing acute infections of any kind. Data extracted were grade 1-4 and serious adverse events (AEs). Data were also extracted on gastrointestinal (GI) AEs, as well as hepatorenal and cardiovascular effects.Active pharmaceutical ingredient cost data from 2016 to 2019 were extracted from the Panjiva database and adjusted for 5% loss during production, costs of excipients, formulation, a 10% profit margin and tax. Two dosages, at 500 mg BD and a higher dose of 1100 mg three times daily (TDS), were considered. Our estimated costs were compared with publicly available list prices from a selection of countries. Results Nine RCTs of nitazoxanide were identified for inclusion. These RCTs accounted for 1514 participants and an estimated 95.3 person-years-of-follow-up. No significant differences were found in any of the AE endpoints assessed, across all trials or on subgroup analyses of active- or placebo-controlled trials. Mild GI AEs increased with dose. No hepatorenal or cardiovascular concerns were raised, but few appropriate metrics were reported. There were no teratogenic concerns, but the evidence base was very limited.Based on a weighted-mean cost of US $61/kg, a 14-day course of treatment with nitazoxanide 500 mg BD would cost $1.41. The daily cost would therefore be $0.10. The same 14-day course could cost $3944 in US commercial pharmacies, and $3 per course in Pakistan, India and Bangladesh. At a higher dose of 1100 mg TDS, our estimated cost was $4.08 per 14-day course, equivalent to $0.29 per day. Conclusion Nitazoxanide demonstrates a good safety profile at approved doses. However, further evidence is required regarding hepatorenal and cardiovascular effects, as well as teratogenicity. We estimate that it would be possible to manufacture nitazoxanide as generic for $1.41 for a 14-day treatment course at 500 mg BD, up to $4.08 at 1100 mg TDS. Further trials in COVID-19 patients should be initiated. If efficacy against SARS-CoV-2 is demonstrated in clinical studies, nitazoxanide may represent a safe and affordable treatment in the ongoing pandemic.


Cellular receptors for viruses: links to tropism and pathogenesis.


title: Retained and fractured microcatheter: a cause of transient ischaemic attacks: endovascular management using carotid stents.

text: A retained microcatheter is a rare complication of endovascular treatment of cerebral aneurysms. We describe such a case that was complicated by delayed microcatheter fracture within the internal carotid artery and subsequent thrombo-embolism resulting in transient ischaemic attacks. We also describe endovascular management of this complication through the use of several carotid stents.


International Congress of Neurolmmunology Edinburgh, September 3 to 7, 2001.


title: Urgent and Emergent Eye Care Strategies to Protect Against COVID-19.

text: Objective This article presents additional strategies to the medical professional and support tactics to keep both the health care provider and patient as safe as possible during the COVID-19 pandemic. Observations Follicular conjunctivitis has been reported as an early sign of infection or during hospitalization for severe COVID-19 disease. It has been confirmed that COVID-19 is transmitted through both respiratory droplets and direct contact. Another possible route of viral transmission is entry through aerosolized droplets into the tears, which then pass through the nasolacrimal ducts and into the respiratory tract. For nonemergent care, eye care providers should use telehealth. Eye care providers should prioritize patient care in order of absolute necessity, such as sudden vision loss, sudden onset flashes and floaters, and eye trauma. In those cases, exposure should be minimized. The close proximity between eye care providers and their patients during slit-lamp examination may require further precautions, such as shields, barriers, and mask use to lower the risk of transmission via droplets or through hand to eye contact. Conclusions All nonemergent eye care appointments should be delayed or conducted remotely. For emergent in-person appointments, careful and appropriate adherence to Centers for Disease Control and Prevention recommendations may minimize exposure for both the health care provider and patient.


title: Cross-protection against a human enteric coronavirus and a virulent bovine enteric coronavirus in gnotobiotic calves.

text: A group 2 human coronavirus designated HECV-4408 was isolated from a child with acute diarrhea and is antigenically and genetically more closely related to bovine coronavirus (BCoV) than to human coronavirus OC43 (X. M. Zhang, W. Herbst, K. G. Kousoulas, and J. Storz, J. Med. Virol. 44:152-161, 1994). To determine whether HECV-4408 infects gnotobiotic calves and induces cross-protective immunity against the virulent enteric BCoV DB2 strain, gnotobiotic calves (n = 4) were orally inoculated with HECV-4408 and then challenged with BCoV DB2 at postinoculation day (PID) 21. All calves inoculated with HECV-4408 developed diarrhea at PID 3 to 4 lasting 5 to 9 days. Fecal and nasal virus shedding were first detected by reverse transcription-PCR at PID 3 to 4 and at PID 2 to 4, respectively. After challenge with bovine coronavirus, no diarrhea or virus shedding was detected in calves inoculated with HECV-4408, but a mock-inoculated calf developed diarrhea and fecal and nasal shedding. Fecal immunoglobulin A (IgA) and serum IgG antibodies were first detected at PID 7 and PID 14, respectively. At postchallenge day 7, serum IgG and fecal IgA antibody titers remained the same or increased only twofold compared to prechallenge titers. An additional two gnotobiotic calves were inoculated with HECV-4408 and euthanized at PID 5. Moderate villous atrophy was observed in the small intestines, and viral antigen was detected in villous enterocytes of the small and large intestines by immunohistochemistry. These results support and extend the previous report that HECV-4408 is likely a variant of bovine coronavirus. They confirm its infectivity for calves and complete cross-protection against a bovine coronavirus (DB2 strain) showing 98.2% amino acid identity to HECV-4408 in the S protein.


title: Utilization of monoclonal antibodies for antigenic characterization of coronaviruses.

text: Hybrid cells secreting monoclonal antibodies against Bovine Enteric Coronavirus (BECV strain G110) were obtained by fusion between SP2/O myeloma cells and splenocytes of mice hyperimmunized with purified virus. Specificity of 8 from the 12 monoclonal antibodies was established to be anti-GP105 by immunochemical staining of viral polypeptides and by immunoprecipitation of radioactive-labelled viral proteins. The reactivity of three BECV isolates (strain G110, F15 and NCDCV) with the different monoclonal antibodies was studied by indirect immunofluorescence (IIF), ELISA, hemagglutination-inhibition and seroneutralization. G110 and F15 interacted in a similar manner with the monoclonal antibodies, but NCDCV failed to react with A9 monoclonal antibody. IIF test allowed us to detect another difference between U.K. BECV isolate and other BECV, in that the U.K. isolate did not react with F7 monoclonal antibody. No differences could be seen by IIF in the reactivity of Danish BECV isolate, Human Enteric Coronavirus (HECV), Bovine Respiratory Coronavirus (BRCV) and our BECV strains, with the 12 monoclonal antibodies. Human Respiratory Coronavirus (OC43), Porcine Hemagglutinating Encephalitis Virus (HEV) and BECV share common antigenic determinants which are outlined by the 6 non-neutralizing monoclonal antibodies. On the basis of the reactivity of coronaviruses with anti-BECV monoclonal antibodies, a distinction can be easily made between BECV and other coronaviruses, and differences were also detected within the BECV isolates. Interestingly HECV were found to be more closely related to BECV than to human OC43. These results show that monoclonal antibodies are of valuable help for biochemical and antigenic studies as well as for diagnostic procedures.


title: Efficacy of an accelerated hydrogen peroxide disinfectant to inactivate porcine epidemic diarrhea virus in swine feces on metal surfaces.

text: In May of 2013, porcine epidemic diarrhea virus (PEDV) was detected in swine for the first time in North America. It spread rapidly, in part due to contaminated livestock trailers. The objective of this study was to test the efficacy of an accelerated hydrogen peroxide disinfectant for inactivating PEDV in the presence of feces on metal surfaces, such as those found in livestock trailers. Three-week-old barrows were inoculated intragastrically with 5 mL of PEDV-negative feces for the negative control, 5 mL of untreated PEDV-positive feces for the positive control, and 5 mL or 10 mL of PEDV-positive feces that was subjected to treatment with a 1:16 or 1:32 concentrations of accelerated hydrogen peroxide disinfectant for a contact time of 30 min at 20°C. These pigs served as a bioassay to determine the infectivity of virus following treatment. Rectal swabs collected from the inoculated pigs on days 3 and 7 post-inoculation were tested by using PEDV-specific real-time reverse transcription polymerase chain reaction and the proportion of pigs in each group that became infected with PEDV was assessed. None of the pigs used for the bioassay in the 4 treatment groups and the negative control group became infected with PEDV, which was significantly different from the positive control group (P < 0.05) in which all pigs were infected. The results suggest that the application of the accelerated hydrogen peroxide under these conditions was sufficient to inactivate the virus in feces found on metal surfaces.


title: The aetiology of SARS: Koch's postulates fulfilled.

text: Proof that a newly identified coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV) is the primary cause of severe acute respiratory syndrome (SARS) came from a series of studies on experimentally infected cynomolgus macaques (Macaca fascicularis). SARS-CoV-infected macaques developed a disease comparable to SARS in humans; the virus was re-isolated from these animals and they developed SARS-CoV-specific antibodies. This completed the fulfilment of Koch's postulates, as modified by Rivers for viral diseases, for SARS-CoV as the aetiological agent of SARS. Besides the macaque model, a ferret and a cat model for SARS-CoV were also developed. These animal models allow comparative pathogenesis studies for SARS-CoV infections and testing of different intervention strategies. The first of these studies has shown that pegylated interferon-alpha, a drug approved for human use, limits SARS-CoV replication and lung damage in experimentally infected macaques. Finally, we argue that, given the worldwide nature of the socio-economic changes that have predisposed for the emergence of SARS and avian influenza in Southeast Asia, such changes herald the beginning of a global trend for which we are ill prepared.


title: Middle East Respiratory Syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013.

text: Between June and September 2013, sera from 11 dromedary camels, 150 goats, 126 sheep and 91 cows were collected in Jordan, where the first human Middle-East respiratory syndrome (MERS) cluster appeared in 2012. All sera were tested for MERS-coronavirus (MERS-CoV) specific antibodies by protein microarray with confirmation by virus neutralisation. Neutralising antibodies were found in all camel sera while sera from goats and cattle tested negative. Although six sheep sera reacted with MERS-CoV antigen, neutralising antibodies were not detected.


title: Infectious bronchitis virus E protein is targeted to the Golgi complex and directs release of virus-like particles.

text: The coronavirus E protein is a poorly characterized small envelope protein present in low levels in virions. We are interested in the role of E in the intracellular targeting of infectious bronchitis virus (IBV) membrane proteins. We generated a cDNA clone of IBV E and antibodies to the E protein to study its cell biological properties in the absence of virus infection. We show that IBV E is an integral membrane protein when expressed in cells from cDNA. Epitope-specific antibodies revealed that the C terminus of IBV E is cytoplasmic and the N terminus is translocated. The short luminal N terminus of IBV E contains a consensus site for N-linked glycosylation, but the site is not used. When expressed using recombinant vaccinia virus, the IBV E protein is released from cells at low levels in sedimentable particles that have a density similar to that of coronavirus virions. The IBV M protein is incorporated into these particles when present. Indirect immunofluorescence microscopy showed that E is localized to the Golgi complex in cells transiently expressing IBV E. When coexpressed with IBV M, both from cDNA and in IBV infection, the two proteins are colocalized in Golgi membranes, near the coronavirus budding site. Thus, even though IBV E is present at low levels in virions, it is apparently expressed at high levels in infected cells near the site of virus assembly.


title: [Severe acute respiratory syndrome: a global overview of the epidemic].

text: In early February 2003, the World Health Organization (WHO) began receiving reports of patients with a syndrome characterized by an atypical pneumonia with rapid progression to respiratory failure without an identified cause despite extensive diagnostic workups. Most of these reports pointed out that the outbreak started in Southern China, specifically in the Guandong Province. The initial outbreak in South East Asia has already spread to other Regions in Asia, Europe, North and South America, and South Africa. Many of these cases can be linked through chains of transmission to an index case from the Guandong Province who visited Hong Kong. Although the exact mode of transmission has not been clearly established, the etiology of this syndrome has already been identified. A novel Coronavirus has been identified by electron microscopy and molecular assays in multiple laboratories from respiratory specimens throughout the world. The syndrome has been defined as SARS (Severe Acute Respiratory Syndrome) by WHO, and is characterized by an incubation period between 1 and 10 days (average 5 days) and by a febrile phase that usually lasts approximately 3 days. During the respiratory phase that begins around day 3, patients start developing a dry cough, shortness of breath and hypoxemia. Mechanical ventilatory support is required in about 10 to 40% of cases and the case-fatality rate ranges between 3 and 16%. The laboratory findings in SARS cases include leukopenia, thrombocytopenia, and a rise in transaminases and lactic dehydrogenase levels. Treatment of SARS includes supportive measures and the empiric use of ribavirin. Respiratory isolation, use of respiratory masks, and compulsory hand hygiene constitute the principal preventive measures. The confirmation of a case can be performed at reference laboratories by serologic and molecular assays. From the onset of this epidemic Mexico established a surveillance system as well as clinical guidelines and recommendations for the identification, prevention of secondary spread, and medical management of suspicious and probable cases by health care personnel.


title: Experimental demyelination produced by the A59 strain of mouse hepatitis virus.

text: Intracerebral inoculation of 4- to 6-week-old C57BL/6 mice with the A59 strain of mouse hepatitis virus (MHV), a murine coronavirus, produced biphasic disease. Acute hepatitis and mild meningoencephalitis were followed by subacute spastic paralysis with demyelinating lesions in the brain and spinal cord as determined by Epon-embedded toluidine-blue-stained sections and by electronmicroscopy. MHV-A59 was cultured by plaque assay from the blood, brain, spinal cord, and liver of infected mice during the acute phase, but not in the chronic stage. MHV-A59 antigen was detected by immunofluorescence (IF) until 3 months postinfection (PI). Serum anti-MHV-A59 antibodies were detected from 7 days to 5 months PI. The induction of demyelination by MHV-A59 provides a suitable system to study virus-induced demyelination further.


title: Gill-associated nidovirus of Penaeus monodon prawns transcribes 3'-coterminal subgenomic mRNAs that do not possess 5'-leader sequences.

text: Sequence analysis of the approximately 20 kb 5'-terminal portion of the ssRNA genome of gill-associated virus (GAV) of Penaeus monodon prawns has previously established that it contains an ORF1a-1b replicase gene equivalent to those of the coronavirus and arterivirus members of the order Nidovirales. Sequence analysis of the remaining approximately 6.2 kb of the GAV genome downstream of ORF1a-1b to a 3'-poly(A) tail has identified two highly conserved intergenic sequences in which 29/32 nucleotides are conserved. Northern hybridization using probes to the four putative GAV ORFs and either total or poly(A)-selected RNA identified two 3'-coterminal subgenomic (sg) mRNAs of approximately 6 kb and approximately 5.5 kb. Primer extension and 5'-RACE analyses showed that the sgmRNAs initiate at the same 5'-AC positions in the central region of the two conserved intergenic sequences. Neither method provided any evidence that the GAV sgmRNAs are fused to genomic 5'-leader RNA sequences as is the case with vertebrate coronaviruses and arteriviruses. Intracellular double-stranded (ds)RNAs equivalent in size to the 26.2 kb genomic RNA and two sgRNAs were also identified by RNase/DNase digestion of total RNA from GAV-infected prawn tissue. The identification of only two sgmRNAs that initiate at the same position in conserved intergenic sequences and the absence of 5'-genomic leader sequences fused to these sgmRNAs confirms that GAV has few genes and suggests that it utilizes a transcription mechanism possibly similar to the vertebrate toroviruses but distinct from coronaviruses and arteriviruses.


title: The role of wild mammals in the maintenance of Rift Valley fever virus.

text: Rift Valley fever virus (RVFV) is a zoonotic arbovirus affecting primarily domestic ruminants and humans. Numerous vector species are known or implicated in the transmission of RVFV. The role of mammals in the maintenance of RVFV, and the existence of a wild mammal reservoir in the epidemiologic cycle of RVFV, remain largely unknown. Our objective is to present a detailed review of studies undertaken on RVFV, often associated with wild mammals, with the aim of focusing future research on potential reservoirs of the virus. Natural and experimental infections related to RVFV in several mammalian orders, including Artiodactyla, Chiroptera, Rodentia, Primata (nonhuman), Perissodactyla, Carnivora, Proboscidea, Erinaceomorpha, and Lagomorpha, are reviewed; the first four orders have received the greatest attention. The possible role of wild ruminants, especially African buffalo (Syncerus caffer), is also discussed. Conflicting results have been published concerning rodents but, based on the literature, the likely candidate species include the African genera Arvicanthis and Micaelamys and the widely introduced roof rat (Rattus rattus). Members of the orders Chiroptera and Rodentia should receive greater attention associated with new research programs. For the other orders mentioned above, few data are available. We are unaware of any investigation concerning the orders Afrosoricida and Soricomorpha, which are represented in the geographic area of RVFV and can be abundant. As a first step to resolve the question of wild mammals as a reservoir of RVFV, serologic and virologic surveys should be promoted during epizootic periods to document infected wild animals and, in the case of positive results, extended to interepidemic periods to explore the role of wild animals as possible reservoirs.


Unconventional Agents and Unclassified Viruses: Recent Advances in Biology and Epidemiology. Proceedings of the 8th Munich Symposium on Microbiology. Munich, October 21-22, 1992.


title: Impact of attending a health care conference in Toronto during the severe acute respiratory syndrome crisis: survey of delegates.

text: OBJECTIVE To describe the impact on delegates of attending the Canadian Pain Society's annual meeting in Toronto during the severe acute respiratory syndrome (SARS) crisis in May 2003. METHODS A prospective survey design was used. Surveys were sent to all delegates (n=432) who attended the conference, and 294 delegates responded (68% response rate). The survey was developed to determine the level of concern about travelling to Toronto; the adequacy of screening measures; the level of stress about attending; and the occupational consequences of attending. RESULTS Fifty per cent of the participants were not concerned about travelling to Toronto, while the other 50% expressed some concern ranging from mild to serious. Concerns included being exposed to SARS and fear of transmitting it to others upon return. Reasons for attending the conference despite concern included a desire for continuing education, decrease in the number of reported SARS cases, and perceived minimal risk. Almost one-half (n=140) felt the screening measures at the conference were adequate, while 4% felt they were inadequate and 9% somewhat adequate. Delegates (n=99) suggested that temperature-taking (32.2%), improved screening vigilance (14.4%), SARS screening forms checked daily (9.1%), strictly controlled entry (8.1%) and adopting hospital screening procedures (7.1%) should have been instituted. CONCLUSION Health care professionals planning conferences in this era of new respiratory diseases can benefit from understanding the responses of delegates who attended conferences during outbreaks. Clear communication about the potential risks and benefits, as well as instituting full screening precautions, will help to allay concerns.


title: Cyclophilin A: A Key Factor in Virus Replication and Potential Target for Anti-viral Therapy.

text: Cyclophilin A (CypA) is a key member of immunophilins that has peptidyl-prolyl cis/trans isomerase (PPIase) activity. Besides acting as a cellular receptor for immunosuppressive drug cyclosporine A (CsA), CypA is involved in various cellular activities. CypA has an important role in viral infection which either facilitates or inhibits their replication. Inhibition of CypA via inhibitors is useful for overcoming several viral infections, indicating that CypA is an attractive target for anti-viral therapy. Collectively, these facts demonstrate the critical roles of CypA in mediating or inhibiting viral infections, suggesting that CypA can be an attractive cellular target for the development of anti-viral therapy.


title: Differential in vitro inhibition of feline enteric coronavirus and feline infectious peritonitis virus by actinomycin D.

text: The growth of feline enteric coronavirus strain 79-1683 in whole feline embryo cells was inhibited by the presence of 1 microgram/ml of actinomycin D in the culture fluid. No virus-specific mRNAs could be detected in such cultures and yields of infectious virus were depressed by > 99%. By contrast, the antigenically related feline infectious peritonitis virus strain 79-1146 was unaffected by the presence of actinomycin D, indicating a fundamental difference between the two feline coronavirus strains in their requirements for host-encoded function(s).


docid: osqcciae

title: Influence of viral infections on body weight, survival, and tumor prevalence in Fischer 344/NCr rats on two-year studies.

text: Sendai virus (SV), pneumonia virus of mice (PVM), and rat coronavirus/sialodacryoadenitis virus (RCV/SDAV) were common viral infections of rats in the National Cancer Institute-National Toxicology Program (NCI-NTP) studies from 1977 to 1983. Influence of these viral infections on body weight, survival, and prevalences of spontaneous tumors in the F344/NCr rats of 28 diet control groups at five different laboratories were evaluated. Tumor prevalences evaluated in this investigation included the following: leukemia and tumors of the anterior pituitary, lungs, salivary glands and Harderian glands in both sexes; adrenal pheochromocytomas in male rats; and mammary tumors in female rats. SV and PVM but not RCV/SDAV infections were associated with significant (P less than 0.05) decreases in body weights of male and female rats. Male rat groups with PVM infection had a lower prevalence of leukemia and male rat groups with RCV/SDAV infection had a higher prevalence of anterior pituitary tumors than the corresponding uninfected groups. Female rat groups with SV infection had greater survival and a higher prevalence of lung tumors than groups without SV infection. However, none of the tumor prevalence and survival differences were statistically significant when interlaboratory variability and time-related effects were taken into account.


Australia antigen and hepatitis.


title: Assessment of febrile illness in the returned traveller.

text: BACKGROUND Fever is among the most frequently reported problems in returning travellers. OBJECTIVE This article provides an overview of the general approach to fever in the returned traveller, including identification of common causes and management. DISCUSSION The returned traveller may present with fever and it is important to exclude life threatening conditions such as malaria that may be related to the travel. A complete risk assessment should be undertaken, including a complete travel history, examination and further investigations, to help to narrow the differential diagnosis. Common tropical diseases found include malaria, dengue, enteric fever, rickettsial infections and respiratory infections. General practitioners should be alert to the public health implications of travel related diseases.


title: Microbial agents associated with waterborne diseases.

text: Many classes of pathogens excreted in feces are able to initiate waterborne infections. There are bacterial pathogens, including enteric and aquatic bacteria, enteric viruses, and enteric protozoa, which are strongly resistant in the water environment and to most disinfectants. The infection dose of viral and protozoan agents is lower than bacteria, in the range of one to ten infectious units or oocysts. Waterborne outbreaks of bacterial origin (particularly typhoid fever) in the developing countries have declined dramatically from 1900s. Therefore, some early bacterial agents such as Shigella sonnei remains prevalent and new pathogens of fecal origin such as zoonotic C. jejuni and E. coli O157:H7 may contaminate pristine waters through wildlife or domestic animal feces. The common feature of these bacteria is the low inoculum (a few hundred cells) that may trigger disease. The emergence in early 1992 of serotype O139 of V. cholerae with epidemic potential in Southeast Asia suggests that other serotypes than V. cholerae O1 could also getting on epidemic. Some new pathogens include environmental bacteria that are capable of surviving and proliferating in water distribution systems. Other than specific hosts at risk, the general population is refractory to infection with ingested P. aeruginosa. The significance of Aeromonas spp. in drinking water to the occurrence of acute gastroenteritis remains a debatable point and has to be evaluated in further epidemiological studies. Legionella and Mycobacterium avium complex (MAC) are environmental pathogens that have found an ecologic niche in drinking and hot water supplies. Numerous studies have reported Legionnaires' disease caused by L. pneumophila occurring in residential and hospital water supplies. M. avium complex frequently causes disseminated infections in AIDS patients and drinking water has been suggested as a source of infection; in some cases the relationship has been proven. More and more numerous reports show that Helicobacter pylori DNA can be amplified from feces samples of infected patients, which strongly suggests fecal-to-oral transmission. Therefore, it is possible that H. pylori infection is waterbome, but these assumptions need to be substantiated. Giardiasis has become the most common cause of human waterborne disease in the U.S. over the last 30 years. However, as a result of the massive outbreak of waterborne cryptosporidiosis in Milwaukee, Wisconsin, affecting an estimated 403,000 persons, there is increasing interest in the epidemiology and prevention of new infection disease caused by Cryptosporidium spp. as well as monitoring water quality. The transmission of Cryptosporidium and Giardia through treated water supplies that meet water quality standards demonstrates that water treatment technologies have become inadequate, and that a negative coliform no longer guarantees that water is free from all pathogens, especially from protozoan agents. Substantial concern persists that low levels of pathogen occurrence may be responsible for the endemic transmission of enteric disease. In addition to Giardia and Cryptosporidium, some species of genera Cyclospora, Isospora, and of family Microsporidia are emerging as opportunistic pathogens and may have waterborne routes of transmission. More than 15 different groups of viruses, encompassing more than 140 distinct types can be found in the human gut. Some cause illness unrelated with the gut epithelium, such as Hepatitis A virus (HAV) and Hepatitis E virus (HEV). Numerous large outbreaks have been documented in the U.S. between 1950 and 1970, and the incidence rate has strongly declined in developing countries since the 1970s. Hepatitis E is mostly confined to tropical and subtropical areas, but recent reports indicate that it can occur at a low level in Europe. A relatively small group of viruses have been incriminated as causes of acute gastroenteritis in humans and fewer have proven to be true etiologic agents, including rotavirus, calicivirus, astrovirus, and some enteric adenovirus. These enteric viruses have infrequently been identified as the etiologic agents of waterborne disease outbreaks, because of inadequate diagnostic technology, but many outbreaks of unknown etiology currently reported are likely due to viral agents. Actually, Norwalk virus and Norwalk-like viruses are recognized as the major causes of waterborne illnesses world-wide. The global burden of infectious waterborne disease is considerable. Reported numbers highly underestimate the real incidence of waterborne diseases. The most striking concern is that enteric viruses such as caliciviruses and some protozoan agents, such as Cryptosporidium, are the best candidates to reach the highest levels of endemic transmission, because they are ubiquitous in water intended for drinking, being highly resistant to relevant environmental factors, including chemical disinfecting procedures. Other concluding concerns are the enhanced risks for the classic group of debilitated subjects (very young, old, pregnant, and immunocompromised individuals) and the basic requirement of to take specific measures aimed at reducing the risk of waterborne infection diseases in this growing, weaker population.


docid: xdjlpjva

title: Hajj pilgrims knowledge about Middle East respiratory syndrome coronavirus, August to September 2013.

text: In preparation for Hajj 2013, 360 French pilgrims were interviewed regarding their knowledge about Middle East respiratory syndrome (MERS). Respondents were aged 20–85 years, male-female ratio was 1.05:1;64.7% were aware of the MERS situation in Saudi Arabia; 35.3% knew about the Saudi Ministry of Health recommendations for at-risk pilgrims to postpone participation in the 2013 Hajj. None of 179 at-risk individuals(49.9%) decided to cancel their Hajj participation even after advice during consultation.


title: Requirement of proteolytic cleavage of the murine coronavirus MHV-2 spike protein for fusion activity.

text: The spike (S) protein of a non-fusogenic murine coronavirus, MHV-2, was compared to that of a variant, MHV-2f, with fusion activity. Two amino acids differed between The S proteins of these viruses; one was located in the signal sequence (amino acid 12) and the other in the putative cleavage site (amino acid 757). To determine which one of these amino acid changes is important for the alteration of fusogenicity, chimeric S proteins between MHV-2 and -2f were constructed and expressed in DBT cells by a vaccinia virus expression system. The results revealed that one amino acid change (Ser to Arg) at position 757 is responsible for the acquisition of fusogenicity of the MHV-2f S protein. This change also altered the susceptibility to proteolytic cleavage of the MHV-2 S protein which was originally uncleavable. We concluded that the non-fusogenic activity of MHV-2 results from the lack of cleavage of its S protein.


title: [Impact of COVID-19 during de-escalation in pediatric urology.]

text: Medical and surgical priorities have changed dramatically following the COVID-19 pandemic declaration. The rapid spread of the virus and the high number of cases has saturated the health system in our country and has forced many hospitals to redistribute resources to care for infected patients. This has led to asignificant reduction in surgical activity, in some cases reaching the point of delaying all elective interventions by performing only urgent interventions. The decrease in the number of infections with the progressive desaturation of hospitals has currently allowed us to enter a new phase of "de-escalation" or transition in order to recover our surgical activity in pediatric urology, which was practically canceled. It is proposed how surgical care activities such as outpatient care should be deal twith, in addition to the different circuits that patients must maintain and, above all, their and professional safety.


title: Duration of protection from reinfection following exposure to sialodacryoadenitis virus in Wistar rats.

text: Wistar rats [Cr1:(WI)BR] were inoculated intranasally with approximately 10(3) median mouse lethal infective doses of sialodacryoadenitis (SDA) virus. Animals were subsequently selected at random, removed to a separate isolation room, and reinfected with SDA virus at 3, 6, 9, 12 or 15 months. Pre- and postinoculation serum samples were collected from all animals during the course of the study and evaluated for antibody titers to SDA virus. All experimental, control and sentinel animals, following inoculation with SDA virus, were necropsied and examined for lesions consistent with SDA. Salivary gland lesions were minimal to absent in rats reinfected with SDA virus for up to 12 to 15 months after the initial exposure and minimal to moderate in the respiratory tract at 12 or 15 months. SDA-associated lesions were extensive in age matched control animals examined at each time period of reinfection with SDA virus. Thus, prior exposure to SDA virus did protect against the development of typical salivary gland lesions for up to 15 months. Recovered animals were evaluated for their ability to transmit the virus following reinfection. Rats reinfected at 6 or 9 months were infectious to their naive cage mates. The results indicate that reinfection with homologous rat coronavirus can occur as early as 6 months after the initial infection, and such rats can transmit the infection to contact controls.


docid: gcrtmzsw

title: Integrating occupational health with mainstream public health in Massachusetts: an approach to intervention.

text: In the late 19th century, workers' health was among the central concerns of the social reform movement to improve public health. Today, few state health agencies have comprehensive occupational health programs. Yet, state public health agencies have critical roles to play in occupational health and may be particularly instrumental in addressing the occupational health needs of underserved worker populations. Since the mid-1980s, with support from the National Institute for Occupational Safety and Health, the Massachusetts Department of Public Health has been working to build an occupational health program and promote the integration of occupational health concerns with ongoing public health activities in the state. This article provides a framework for considering the range of integration activities and presents examples of successful occupational health integration efforts in Massachusetts.


title: Brain natriuretic peptide and NT-proBNP levels reflect pulmonary artery systolic pressure in trekkers at high altitude.

text: Our objective was to evaluate the utility of the natriuretic peptides BNP (brain natriuretic peptide) and NT-proBNP as markers of pulmonary artery systolic pressure (PASP) in trekkers ascending to high altitude (HA). 20 participants had BNP and NT-proBNP assayed and simultaneous echocardiographic assessment of PASP performed during a trek to 5150 m. PASP increased significantly (p=0.006) with ascent from 24+/-4 to 39+/-11 mm Hg at 5150 m. At 5150 m those with a PASP>/=40 mm Hg (n=8) (versus those with PASP<40 mm Hg) had higher post-exercise BNP (pg/ml): 54.5+/-36 vs. 13.4+/-17 (p=0.012). Their resting BNP at 5150 m was also higher: 57.3+/-43.4 vs. 12.6+/-13 (p=0.017). In those with a pathological (>/=400 pg/ml) rise in NT-proBNP at 5150 m (n=4) PASP was significantly higher: 45.9+/-7.5 vs. 32.2+/-6.2 mm Hg (p=0.015). BNP and NT-proBNP may reflect elevated PASP, a central feature of high altitude pulmonary oedema, at HA.


title: Expression of bacteriophage T7 RNA polymerase in avian and mammalian cells by a recombinant fowlpox virus.

text: The bacteriophage T7 RNA polymerase gene was integrated into the fowlpox virus genome under the control of the vaccinia virus early/late promoter, P7.5. The recombinant fowlpox virus, fpEFLT7pol, stably expressed T7 RNA polymerase in avian and mammalian cells, allowing transient expression of transfected genes under the control of the T7 promoter. The recombinant fowlpox virus expressing T7 RNA polymerase offers an alternative to the widely used vaccinia virus vTF7-3, or the recently developed modified vaccinia virus Ankara (MVA) T7 RNA polymerase recombinant, a highly attenuated strain with restricted host-range. Recombinant fowlpox viruses have the advantage that as no infectious virus are produced from mammalian cells they do not have to be used under stringent microbiological safety conditions.


title: Efficacy of a paracetamol-pseudoephedrine combination for treatment of nasal congestion and pain-related symptoms in upper respiratory tract infection.

text: OBJECTIVE This study compared the efficacy of 1000 mg of paracetamol combined with 60 mg of pseudoephedrine, with that of either paracetamol or pseudoephedrine alone and placebo for the treatment of symptomatic URTI. RESEARCH DESIGN AND METHODS A double-blind, parallel group study was performed on 305 patients with URTI (nasal airflow resistance [NAR] of > 0.25 Pa cm3 s and a global pain score of at least moderate intensity). NAR and pain relief/intensity scores were measured over 4 h after initial dose. Patients then dosed up to three times daily for 3 days and recorded nasal congestion and pain intensity scores. MAIN OUTCOME MEASURES Nasal airflow conductance (NAC) and pain relief after the initial dose were primary objectives. NAC was calculated from NAR. Pain relief was measured on a 5-point verbal rating scale (VRS) and pain intensity and nasal congestion on a 4-point VRS. Data were analysed using analysis of covariance. Safety was assessed by adverse events. RESULTS A single dose of the combination was superior to paracetamol and placebo for NAC (p = 0.0001) and was superior to pseudoephedrine and placebo for pain relief (p < or = 0.048). Multiple doses of the combination were also superior to paracetamol and placebo for decongestion (p < or = 0.021) and were superior to pseudoephedrine and placebo for pain reduction (p < or = 0.0057). All treatments were well tolerated. CONCLUSIONS The combination treatment provided a greater decongestant effect than either paracetamol or placebo and better pain relief than either pseudoephedrine or placebo. The additive effect of the combination was apparent for both single and multiple doses.


title: Serosurvey of leptospirosis in feral hogs (Sus scrofa) in Florida.

text: Leptospira is a global pathogen of emerging public health importance in both developing and industrialized nations and can infect almost all mammalian species, including humans. As suburbanization and the popularity of outdoor recreational activities increases, so do human-wildlife and companion animal-wildlife interfaces. Florida offers a tropical climate favorable for outdoor activities and a semirural landscape that sustains an abundant feral hog population. Because no survey ofleptospirosis in feral hogs (Sus scrofa) in Florida has been published to our knowledge, we sought to establish preliminary seroprevalence ofleptospirosis exposure in feral hogs in Florida. Blood samples were collected opportunistically from 158 male and 166 female feral hogs taken at managed hunts and by permitted trappers in the northern, central, and southern regions of Florida. Samples were then analyzed using the microscopic agglutination test (MAT) for antibody titers to 20 Leptospira serovars representing 17 serogroups. A titer of > 1:100 was considered positive; 33% (107/324 total samples) were positive to at least one serovar, and 46% of those were positive to multiple serovars. Antibodies to L. interrogans serovar Bratislava strain Jez Bratislava (serogroup Australis) was the most common, with 18% (58/324) testing positive for antibodies. These initial data indicate that there is a significant possibility of feral hogs having a larger role in the complex etiology of leptospirosis in Florida than historically estimated and that further investigation is warranted.